Assignment

 

The interpretation of research in health care is essential to decision making. By understanding research, health care providers can identify risk factors, trends, outcomes for treatment, health care costs and best practices. To be effective in evaluating and interpreting research, the reader must first understand how to interpret the findings. 

 find three different health care articles that use quantitative research. Do not use articles that appear in the topic Resources or textbook. Complete an article analysis for each using the “Article Analysis 1” template.

Article Analysis 1

Article Citation and Permalink (APA format)

Article 1

Article 2

Article 3

Point

Description

Description

Description

Broad Topic Area/Title


Identify Independent and Dependent Variables and Type of Data for the Variables


Population of Interest for the Study

Sample

Sampling Method

Descriptive Statistics (Mean, Median, Mode; Standard Deviation)

Identify examples of descriptive statistics in the article.

Inferential Statistics

Identify examples of inferential statistics in the article.

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Physical environmental designs in residential care to improve
quality of life of older people (Review)

 

  Harrison SL, Dyer SM, Laver KE, Milte RK, Fleming R, Crotty M  

  Harrison SL, Dyer SM, Laver KE, Milte RK, Fleming R, Crotty M.
Physical environmental designs in residential care to improve quality of life of older people.
Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.: CD012892.
DOI: 10.1002/14651858.CD012892.pub2.

 

  www.cochranelibrary.com  

Physical environmental designs in residential care to improve quality of life of older people (Review)
 

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T A B L E   O F   C O N T E N T S

ABSTRACT…………………………………………………………………………………………………………………………………………………………………………….. 1

PLAIN LANGUAGE SUMMARY………………………………………………………………………………………………………………………………………………….. 2

SUMMARY OF FINDINGS………………………………………………………………………………………………………………………………………………………… 4

BACKGROUND………………………………………………………………………………………………………………………………………………………………………. 7

OBJECTIVES………………………………………………………………………………………………………………………………………………………………………….. 8

METHODS…………………………………………………………………………………………………………………………………………………………………………….. 9

RESULTS……………………………………………………………………………………………………………………………………………………………………………….. 13

Figure 1………………………………………………………………………………………………………………………………………………………………………….. 14

Figure 2………………………………………………………………………………………………………………………………………………………………………….. 19

Figure 3………………………………………………………………………………………………………………………………………………………………………….. 20

DISCUSSION………………………………………………………………………………………………………………………………………………………………………….. 29

AUTHORS’ CONCLUSIONS……………………………………………………………………………………………………………………………………………………… 33

ACKNOWLEDGEMENTS………………………………………………………………………………………………………………………………………………………….. 34

REFERENCES………………………………………………………………………………………………………………………………………………………………………… 36

CHARACTERISTICS OF STUDIES……………………………………………………………………………………………………………………………………………… 43

DATA AND ANALYSES……………………………………………………………………………………………………………………………………………………………… 79

Analysis 1.1. Comparison 1: Home-like vs. traditional environment, Outcome 1: Quality of life…………………………………………….. 79

Analysis 1.2. Comparison 1: Home-like vs. traditional environment, Outcome 2: Behaviour, mood and depression………………… 80

Analysis 1.3. Comparison 1: Home-like vs. traditional environment, Outcome 3: Function…………………………………………………… 83

Analysis 1.4. Comparison 1: Home-like vs. traditional environment, Outcome 4: Global cognitive function……………………………. 84

Analysis 1.5. Comparison 1: Home-like vs. traditional environment, Outcome 5: Quality of care ………………………………………….. 84

Analysis 1.6. Comparison 1: Home-like vs. traditional environment, Outcome 6: Serious adverse eCects………………………………. 85

Analysis 2.1. Comparison 2: Refurbishment vs. traditional environment, Outcome 1: Quality of life……………………………………… 85

Analysis 2.2. Comparison 2: Refurbishment vs. traditional environment, Outcome 2: Behaviour, mood and depression…………. 86

Analysis 2.3. Comparison 2: Refurbishment vs. traditional environment, Outcome 3: Function…………………………………………….. 87

Analysis 2.4. Comparison 2: Refurbishment vs. traditional environment, Outcome 4: Quality of care……………………………………. 87

Analysis 3.1. Comparison 3: Special-care units for dementia vs. traditional environment, Outcome 1: Behaviour, mood and
depression………………………………………………………………………………………………………………………………………………………………………

87

Analysis 3.2. Comparison 3: Special-care units for dementia vs. traditional environment, Outcome 2: Function…………………….. 89

Analysis 3.3. Comparison 3: Special-care units for dementia vs. traditional environment, Outcome 3: Global cognitive function… 89

Analysis 4.1. Comparison 4: Group living corridor vs. group living non-corridor design, Outcome 1: Behaviour, mood and
depression………………………………………………………………………………………………………………………………………………………………………

89

Analysis 5.1. Comparison 5: Lighting intervention  vs. control lighting, Outcome 1: Behaviour, mood and depression……………. 91

Analysis 5.2. Comparison 5: Lighting intervention  vs. control lighting, Outcome 2: Behaviour, mood and depression: depression
4-6 weeks………………………………………………………………………………………………………………………………………………………………………..

92

Analysis 5.3. Comparison 5: Lighting intervention  vs. control lighting, Outcome 3: Behaviour, mood and depression: agitation
4-6 weeks………………………………………………………………………………………………………………………………………………………………………..

93

Analysis 5.4. Comparison 5: Lighting intervention  vs. control lighting, Outcome 4: Function 4-6 weeks………………………………… 93

Analysis 5.5. Comparison 5: Lighting intervention  vs. control lighting, Outcome 5: Function……………………………………………….. 93

Analysis 5.6. Comparison 5: Lighting intervention  vs. control lighting, Outcome 6: Global cognitive function……………………….. 93

Analysis 6.1. Comparison 6: Dining space redesign vs. traditional environment, Outcome 1: Quality of life……………………………. 94

Analysis 6.2. Comparison 6: Dining space redesign vs. traditional environment, Outcome 2: Behaviour, mood and depression…. 94

Analysis 6.3. Comparison 6: Dining space redesign vs. traditional environment, Outcome 3: Function………………………………….. 94

Analysis 6.4. Comparison 6: Dining space redesign vs. traditional environment, Outcome 4: Global cognitive function…………… 95

Analysis 6.5. Comparison 6: Dining space redesign vs. traditional environment, Outcome 5: Serious adverse eCects……………… 95

Analysis 7.1. Comparison 7: Garden vignette vs. traditional environment, Outcome 1: Behaviour, mood and depression……….. 95

APPENDICES…………………………………………………………………………………………………………………………………………………………………………. 95

HISTORY……………………………………………………………………………………………………………………………………………………………………………….. 109

CONTRIBUTIONS OF AUTHORS………………………………………………………………………………………………………………………………………………. 110

DECLARATIONS OF INTEREST………………………………………………………………………………………………………………………………………………… 110

SOURCES OF SUPPORT…………………………………………………………………………………………………………………………………………………………. 110

DIFFERENCES BETWEEN PROTOCOL AND REVIEW…………………………………………………………………………………………………………………… 110

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NOTES………………………………………………………………………………………………………………………………………………………………………………….. 111

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[Intervention Review]

Physical environmental designs in residential care to improve quality of
life of older people

Stephanie L Harrison1,2,3, Suzanne M Dyer1, Kate E Laver1, Rachel K Milte4, Richard Fleming5, Maria Crotty1

1Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, Australia. 2Registry

of Senior Australians, South Australian Health and Medical Research Institute, Adelaide, Australia. 3Liverpool Centre for Cardiovascular

Science, University of Liverpool, Liverpool, UK. 4Caring futures institute, Flinders University, Adelaide, Australia. 5School of Science
Medicine and Health, University of Wollongong, Wollongong, Australia

Contact: Stephanie L Harrison, [email protected]

Editorial group: Cochrane ECective Practice and Organisation of Care Group.
Publication status and date: New, published in Issue 3, 2022.

Citation: Harrison SL, Dyer SM, Laver KE, Milte RK, Fleming R, Crotty M.Physical environmental designs in residential care
to improve quality of life of older people. Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.: CD012892. DOI:
10.1002/14651858.CD012892.pub2.

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

A B S T R A C T

Background

The demand for residential aged care is increasing due to the ageing population. Optimising the design or adapting the physical
environment of residential aged care facilities has the potential to influence quality of life, mood and function.

Objectives

To assess the eCects of changes to the physical environment, which include alternative models of residential aged care such as a ‘home-
like’ model of care (where residents live in small living units) on quality of life, behaviour, mood and depression and function in older
people living in residential aged care.

Search methods

CENTRAL, MEDLINE, Embase, six other databases and two trial registries were searched on 11 February 2021. Reference lists and grey
literature sources were also searched.

Selection criteria

Non-randomised trials, repeated measures or interrupted time series studies and controlled before-aJer studies with a comparison group
were included. Interventions which had modified the physical design of a care home or built a care home with an alternative model of
residential aged care (including design alterations) in order to enhance the environment to promote independence and well-being were
included. Studies which examined quality of life or outcomes related to quality of life were included. Two reviewers independently assessed
the abstracts identified in the search and the full texts of all retrieved studies.

Data collection and analysis

Two reviewers independently extracted data, assessed the risk of bias in each included study and evaluated the certainty of evidence
according to GRADE criteria. Where possible, data were represented in forest plots and pooled.

Main results

Twenty studies were included with 77,265 participants, although one large study included the majority of participants (n = 74,449). The
main comparison was home-like models of care incorporating changes to the scale of the building which limit the capacity of the living units
to smaller numbers of residents and encourage the participation of residents with domestic activities and a person-centred care approach,

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compared to traditional designs which may include larger-scale buildings with a larger number of residents, hospital-like features such as
nurses’ stations, traditional hierarchical organisational structures and design which prioritises safety.

Six controlled before-aJer studies compared the home-like model and the traditional environment (75,074 participants), but one
controlled before-aJer study included 74,449 of the participants (estimated on weighting).  It is uncertain whether home-like models
improve health-related quality of life, behaviour, mood and depression, function or serious adverse eCects compared to traditional designs
because the certainty of the evidence is very low. The certainty of the evidence was downgraded from low-certainty to very low-certainty
for all outcomes due to very serious concerns due to risk of bias, and also serious concerns due to imprecision for outcomes with more
than 400 participants. One controlled before-aJer study examined the eCect of home-like models on quality of life. The author stated
“No statistically significant diCerences were observed between the intervention and control groups.” Three studies reported on global
behaviour (N = 257). One study found little or no diCerence in global behaviour change at six months using the Neuropsychiatric Inventory
where lower scores indicate fewer behavioural symptoms (mean diCerence (MD) -0.04 (95% confidence interval (CI) -0.13 to 0.04, n = 164)),
and two additional studies (N = 93) examined global behaviour, but these were unsuitable for determining a summary eCect estimate. Two
controlled before-aJer studies examined the eCect of home-like models of care compared to traditional design on depression. AJer 18
months, one study (n = 242) reported an increase in the rate of depressive symptoms (rate ratio 1.15 (95% CI 1.02 to 1.29)), but the eCect of
home-like models of care on the probability of no depressive symptoms was uncertain (odds ratio 0.36 (95% CI 0.12 to 1.07)). One study (n
= 164) reported little or no diCerence in depressive symptoms at six months using the Revised Memory and Behaviour Problems Checklist
where lower scores indicate fewer depressive symptoms (MD 0.01 (95% CI -0.12 to 0.14)). Four controlled before-aJer studies examined
function. One study (n = 242) reported little or no diCerence in function over 18 months using the Activities of Daily Living long-form scale
where lower scores indicate better function (MD -0.09 (95% CI -0.46 to 0.28)), and one study (n = 164) reported better function scores at
six months using the Interview for the Deterioration of Daily Living activities in Dementia where lower scores indicate better function (MD
-4.37 (95% CI -7.06 to -1.69)). Two additional studies measured function but could not be included in the quantitative analysis. One study
examined serious adverse eCects (physical restraints), and reported a slight reduction in the important outcome of physical restraint use
in a home-like model of care compared to a traditional design (MD between the home-like model of care and traditional design -0.3% (95%
CI -0.5% to -0.1%), estimate weighted n = 74,449 participants at enrolment).

The remaining studies examined smaller design interventions including refurbishment without changes to the scale of the building, special
care units for people with dementia, group living corridors compared to a non-corridor design, lighting interventions, dining area redesign
and a garden vignette.

Authors’ conclusions

There is currently insuCicient evidence on which to draw conclusions about the impact of physical environment design changes for older
people living in residential aged care. Outcomes directly associated with the design of the built environment in a supported setting are
diCicult to isolate from other influences such as health changes of the residents, changes to care practices over time or diCerent staC
providing care across shiJs. Cluster-randomised trials may be feasible for studies of refurbishment or specific design components within
residential aged care. Studies which use a non-randomised design or cluster-randomised trials should consider approaches to reduce risk
of bias to improve the certainty of evidence.

P L A I N   L A N G U A G E   S U M M A R Y

Physical environmental designs in residential care to improve quality of life of older people

What is the aim of the review?

There is an increasing older population worldwide and an increase in the numbers of people living with dementia. It has been suggested
that improving lived area designs may improve quality of life, mood, and ability to perform daily living activities of aged care residents.
The aim of this Cochrane review was to examine the eCects of diCerent physical environmental design changes in residential aged care
to determine the eCect on quality of life for the residents. The review authors collected and analysed all relevant studies to answer this
question and found 20 studies.

Key messages

We are uncertain of the eCects of design changes in residential aged care to improve quality of life for residents because more high-quality
studies are needed.

What was studied in the review?

The review studied changes to physical environmental design in residential aged care, referring to any changes to the environment in
which residents live, in an aim to improve their quality of life. These may be large-scale or small-scale changes. Large-scale changes can
be changes to the design of residential care such as changing from the currently used lived-area designs to home-like designs with smaller
numbers of residents living together. Small-scale changes may involve refurbishing the lived area or changing a single part of the lived area
such as lighting. We included studies which compared diCerent large-scale or small design changes in residential aged care, or compared
design changes to currently used lived-area designs and examined the eCect of design changes on quality of life, behaviour and daily living

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activities for the residents. There is no one definition of quality of life agreed upon, but most definitions include multiple aspects of a
person’s expectations for their life, such as physical, mental, and emotional health, social activity and life situation.

What are the main results of the review?

The review authors found 20 relevant studies that took place in nine diCerent countries (Australia, Canada, Germany, Italy, the Netherlands,
Spain, Sweden, the UK and the USA). The main design change which was investigated was the eCect of creating a ‘home-like’ model of care
which usually involved creating small-scale living units for residents and changes to care practices such as changes to staCing or choices
residents had on daily routines. 

Six studies examined changes to the size of the building to limit the number of residents per living unit ranging between six and fiJeen
residents per living unit, in addition to changing care practices, for example, changes to staCing, or changes to the choices residents had
for their daily routines. One study examined quality of life, but there was insuCicient information presented to draw conclusions. Three
studies examined behaviour; one study found little or no diCerence in behaviour and two studies provided insuCicient information to draw
conclusions. Two studies examined depression and reported little or no diCerence in depressive symptoms or the eCect was uncertain. Four
studies examined daily living activities; one study reported improvement in daily living activities, one study reported little or no diCerence
in daily living activities, and two studies provided insuCicient information to draw conclusions. One study reported a reduction in serious
adverse eCects (the use of physical restraints).  We are uncertain of the eCects of home-like models of care on quality of life, behaviour,
depression, daily living activities or serious adverse eCects because the certainty (confidence) of the studies was determined to be very
low due to issues with study design.

The other fourteen studies examined smaller design interventions such as refurbishment without changes to the scale of the building,
special care units for people with dementia, diCerent corridor designs, bright lighting, redesign of the dining room and an indoor garden.

How up-to-date is this review?

The review authors searched for studies up to February 2021.

Physical environmental designs in residential care to improve quality of life of older people (Review)

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S U M M A R Y   O F   F I N D I N G S

 

Summary of findings 1.   Whole-facility changes: Home-like models compared to traditional environment for older people living in long-term
residential care

Whole-facility changes: Home-like models compared to traditional environment for older people living in long-term residential care

Patient or population: older adults living in long-term residential care including, but not limited to, dementia-specific care settings
Settings: long-term residential care
Intervention: home-like models (features of home-like models may include buildings which limit the capacity of the living units to small numbers of residents, designs to
encourage the participation of residents with domestic activities and a person-centred care approach)
Comparison: traditional design (traditional design may include larger-scale buildings with a larger number of residents, hospital-like features such as nurses’ stations, tra-
ditional hierarchical organisational structures and design which prioritises safety)

Illustrative comparative risks
(95% CI)

Outcomes

 

Assumed risk

Traditional de-
sign

Corresponding
risk 

Home-like
model

Relative effect
(95% CI)

Follow-up time

No of Partici-
pants
(studies)

 

Certainty of
the evidence
(GRADE)

Comments

Health-related quality
of life 

Dementia-specific
quality of life measure
(QUALIDEM) 

(higher scores = better)

 

N/a N/a Not estimable

6 months and
12 months

 

 

 

 

 

 

 

 

33 (1 controlled
before-after-
 study)

⊕⊝⊝⊝

very low1
2 domains (feeling at home and care relation-
ship) were examined in an analysis adjusted for
baseline differences between the groups; 7 oth-
er domains were unadjusted. The author stat-
ed “No statistically significant differences were
observed between the intervention and control
groups.”

Global behaviour N/a N/a Not estimable

6 months

257 ⊕⊝⊝⊝

very low2
One study found little or no difference in glob-
al behaviour change at 6 months using the NPI
(N = 164; MD -0.04 (95% CI -0.13 to 0.04)); two

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Neuropsychiatric Inven-
tory (NPI),

Neuropsychiatric Inven-
tory-Nursing Home ver-
sion (NPI-NH) and

Nurses Observations
Scale for Geriatric Pa-
tients (NOSGER)

(lower scores = better)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(3 controlled
before-after
studies)

  additional studies (N = 93) reported global be-
haviour endpoint data, but the data were un-
suitable for determining a summary effect esti-
mate. 

 

 

 

 

 

 

 

Depression

Revised Memory and
Behaviour Problems
Checklist (RMBPC) and

Mood Scale Score (MSS)

(lower scores = better)

 

N/a N/a Not estimable

6 months and
18 months

 

406 (2 con-
trolled be-
fore-after stud-
ies)
 

⊕⊝⊝⊝

very low3
Depressive symptoms 18-month change using
the MSS (1 study, N = 242; RR 1.15 (95% CI 1.02
to 1.29))

Probability no depressive symptoms 18 months
using the MSS (1 study, N = 242; OR 0.36 (95% CI
0.12 to 1.07))

Depressive symptoms 6-month endpoint using
the RMBPC (1 study, N = 164; MD 0.01 (95% CI
-0.12 to 0.14))

Function

Activities of daily living
(ADL) long-form scale
(lower scores = better),
Interview for the Dete-
rioration of Daily Living
activities in Dementia
(IDDD) (lower scores =
better)

N/a N/a Not estimable

6 months and
18 months

499
(4 controlled
before-after
studies)

⊕⊝⊝⊝

very low4
Function 18-month change using the ADL long-
form scale (1 study, N = 242; MD -0.09 (95% CI
-0.46 to 0.28))

Function 6-month endpoint using the IDDD (1
study, N = 164; MD -4.37 (95% CI -7.06 to -1.69))

Two additional studies: measured function
with the Barthel Index but were not included in
the quantitative analysis:

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Or Barthel Index (higher
scores = better)

 

 

• One study (data were insufficient): authors
stated: “interactions between settings and
development over time could not be proved”.

• One study (results were not adjusted for dif-
ferences in baseline characteristics): authors
stated function declined in both the interven-
tion and control groups but “more sharply” in
control group.

Serious adverse effects

Physical restraints, re-
ported as percentage
points (lower = better)

 

23 per 1000* 20 per 1000** MD -0.3%
(-0.5% to -0.1%)

Follow-up: Un-
clear

 

Unclear
(weighted es-
timate 74,449
participants at
enrolment)
(1 study)

 

⊕⊝⊝⊝

very low5
 

No further adverse effects were examined.

Unclear length of follow-up (reported as up to 5
years)

 

CI: Confidence interval; MD: Mean difference;OR: Odds Ratio; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 The certainty of evidence was downgraded two levels for risk of bias (high risk of bias on six items including high risk of selection bias, performance bias, detection bias, attrition
bias, and other (diCerences in baseline characteristics and potential residual confounding)) and two levels for imprecision (only 33 participants).
2The certainty of evidence was downgraded two levels for risk of bias (all studies at high risk of bias on at least six items) and one level for imprecision (< 400 participants).
3The certainty of evidence was downgraded two levels for risk of bias (all studies at high risk of bias on six items).
4The certainty of evidence was downgraded two levels for risk of bias (high risk of bias on at least six items) and one level for imprecision (499 participants in total across outcomes
but reported across diCerent measures).
5The certainty of evidence was downgraded two levels for risk of bias (high risk of bias on five items including high risk of selection bias, performance bias, detection bias and
other (method of selection of facilities unclear, potential residual confounding, significant diCerences in baseline characteristics and significant diCerences for many baseline
outcome measures)).
*Assumed risk for the control group was derived from the study reporting this outcome (2.3%).
**Corresponding risk based on a diCerence of 0.3%.
 

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B A C K G R O U N D

Description of the condition

The population is ageing worldwide. Life expectancy has increased
and people are living longer in older age, particularly in high-
income countries (WHO 2015). There were 901 million people
aged 60 years and older worldwide in 2015 and, by 2050. this
figure is projected to more than double to nearly 2.1 billion (UN
2015). Although information regarding population ageing is well
established, the patterns of health and quality of life for older
people remain unclear (WHO 2015).

Many older adults experience physical and/or cognitive impairment
as they age which may result in the need for care and support from
others in order to manage activities of daily living. A significant
decline in function may result in the need for long-term care.
With an increasing number of people living to an older age, there
will be an increase in the proportion of the population who will
require accommodation in residential aged care (WHO 2015). A
large proportion of those who reside in residential aged care
(also called care facilities, care homes, nursing homes, residential
homes, skilled-nursing facilities or assisted-living facilities) are
living with dementia, and the number of people living with
dementia globally is expected to increase. There are currently 46.8
million people living with dementia and this figure is expected to
double every 20 years, to 131.5 million people by 2050 (ADI 2015).
An ageing population and an increasing number of people living
with dementia is likely to increase demand for residential aged
care. Therefore, it will be increasingly important to ensure that
these facilities provide an environment which ensures that quality
of life is optimised in advancing age.

Quality of life for residents in  residential aged care has been
referred to as the degree to which the well-being of an individual is
maintained, including social activity, physical activity and health,
and whether or not this meets their expectations (Post 2014).
Maintaining quality of life in advancing age is important, both for
those living in the community and those living in residential aged
care. However, people who live in residential aged care are more
likely to experience a reduced quality of life compared to those
living in the community (Kane 2003). Moving from the community
to living in residential aged care is oJen associated with a decline
in quality of life that may be due to loss of independence and
purpose (Bradshaw 2012; Olsen 2016). Interventions to maximise
quality of life for people who live in residential aged care should
be prioritised. Implementing interventions which may improve
quality of life for people living in care facilities also has the
potential to positively impact the residents, staC and families of
the resident. Many factors may impact quality of life for people
living in residential aged care and people with dementia, including
health status, availability of activities, social participation, standard
of care provided and the physical environment. The impact of
therapies such as music therapy, art therapy and functional
analysis-based interventions for people living with dementia
on factors related to quality of life, such as behaviour, have
been examined in previous Cochrane reviews (Deshmukh 2018;
Moniz Cook 2012; Van der Steen 2018).

Description of the intervention

Maximising quality of life for people living in residential aged care
includes providing models of care that encourage engagement in

meaningful activities and care which fosters ongoing independence
(Tolson 2011). Changing the physical environment refers to
changing features of the care facility which are constantly available
to the resident, rather than temporary approaches. The physical
environment of care facilities can be altered in an attempt
to improve the quality of life of the residents. Deciding how
the physical environment of residential  aged care may be best
enhanced to benefit the residents is an emerging area of research
(Fleming 2010).

Traditionally, care facilities adopted a medicalised model of care,
meaning that facilities were designed and operated similarly
to hospitals, rather than homes for the residents (WHO 2015).
More recently, care facilities are being encouraged to oCer
diCerent models of care, which are designed to improve quality
of life for the residents by adapting the facilities to create a
more stimulating environment, which encourages individuals to
maintain independence for longer (Ausserhofer 2016). However,
the ability to oCer diCerent models of care may be impacted by
factors such as the varied funding models for residential aged care
in diCerent countries.

This ‘person-centred’ approach may involve redesigning or
building new facilities to create a more home-like environment
where residents live in small groups and which have been
specifically designed to look and feel more like a domestic
home (Chenoweth 2014). These home-like models of care have
been developed in diCerent countries including Australia (Dyer
2018), Germany (Wolf-Ostermann 2012), Japan (Funaki 2005),
the Netherlands (Te Boekhorst 2009) and the USA (Afendulis
2016,  Zimmerman 2016). These models may oCer diCerent
components regarding how they are designed and operated, but
the underlying concept of providing a home-like environment to
improve quality of life is consistent.

In the USA, the Green House model is gaining popularity. These
facilities promote person-centred care for older people by oCering
small houses where a home-like environment is maintained,
meaningful activities are accessible and teams of certified nursing
assistants are available (Zimmerman 2016). The Eden Alternative
was also originally established in the USA and has since been
implemented in Europe, Asia and Australia (Brownie 2011). The
Eden Alternative has some similarities to the Green House model of
care as it also aims to create a home-like environment to enrich the
lives of the residents, but rather than purpose-built small houses,
the Eden Alternative aims to improve the existing environment,
using methods such as the introduction of animals and plants
(Coleman 2002).

Other small-scale home-like environments specifically designed for
people with dementia have been adopted in various countries in
Europe, North America and Australia, but are oJen implemented in
diCerent ways (Verbeek 2014).

Changes to the physical environment do not always involve
large-scale changes. Instead, the environmental changes may
be small, such as tailored lighting designed to improve sleep
quality and behaviour (Figueiro 2014), or improved access to
outdoor spaces and gardens to improve well-being (Whear 2014).
Previous studies have suggested that techniques to enhance the
physical environment of care facilities may improve activities
of daily living function, quality of life, and mood, as well as
lowering hospital admissions (Ausserhofer 2016; Chenoweth 2014;

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Zimmerman 2016). However, the evidence for the impact of small-
scale or large-scale whole-facility changes to the model of care on
the quality of life of residents remains unclear.

How the intervention might work

Studies have shown that staC of care facilities are responsive to
the idea of enhancing the physical environment of their facilities.
Many facilities have reported implementing small environmental
changes (Tesh 2002), but fewer residential aged care facilities have
adopted large-scale environmental interventions such as changing
from more traditional models of residential aged care to smaller
home-like environments (Doty 2007).

As there are a wide range of interventions that can be implemented
to improve the physical environment, there will be diCerent ways
in which the interventions might work. For example, increased
access to outdoor spaces may improve mood and levels of physical
activity. Increased lighting during the day may help to improve
circadian rhythm, improve sleep patterns for residents and aCect
mood (Joseph 2015). Improvements in these types of outcomes
have been associated with improved quality of life amongst older
adults (Livingston 2014). Interventions such as ‘dementia-enabling
environments’ have been designed to encourage residents with
dementia to maintain independence for longer and increase
opportunity for engagement in meaningful activities, with the aim
of improving quality of life for the residents by helping them to feel
valued and purposeful (DEEP 2015).

Older adults prefer greater choice of living accommodation and
higher quality of services (Brownie 2013). Moving to  residential
aged care can be daunting, as it is a major change from the family
home, and can result in declines in psychological health (Ellis 2010).
Improving the physical environment could help the residents to
maintain normality and establish routine. As a large proportion
of people moving to residential aged care have dementia, it is
important to recognise that the unmet needs of these individuals
can lead to changed behaviours, or behavioural and psychological
symptoms of dementia (BPSD) (Lyketsos 2000). Although most
previous research has focused on therapies for the individual
experiencing changed behaviours or the staC caring for them,
environmental interventions may also have positive eCects on
behaviour.

Why it is important to do this review

Previous reviews have been conducted in relation to the physical
environment of care facilities and various outcomes. However,
these reviews generally do not evaluate the quality of the included
studies and do not undertake a quantitative analysis of the
study findings. Current available reviews suggest that certain
environmental changes can improve outcomes for residents and
staC of facilities (Ausserhofer 2016; Joseph 2015; Marquardt 2014;
Soril 2014).

The majority of the research summarised in previous reviews
suggests that studies which have examined environmental changes
to residential aged care facilities have focused on specific
component interventions, such as outdoor gardens, reduced
facility size and changes to lighting (Joseph 2015). Other reviews,
including only studies of people with dementia, have found a
broad range of interventions to improve the built environment,
but provide inconsistent evidence to suggest which interventions

are more favourable for certain outcomes, such as behaviour (Soril
2014).

Similarly, a recent scoping review of home-like environments
in care facilities concluded that although some studies showed
positive improvements in certain outcomes, further evidence is
needed in order to determine the eCectiveness of home-like models
of residential aged care compared to traditional models on quality
of life (Ausserhofer 2016). However, a diCerent review examining
the built environment for people with dementia concluded that
design interventions are largely beneficial for many outcomes
for people with dementia including behaviour, activities of daily
living function, well-being, social abilities, orientation and care
outcomes, but the evidence for cognitive function was inconsistent
(Marquardt 2014).

It is important to consider risk management of the environmental
interventions, as there may also be adverse eCects from some
environmental modifications, in particular falls. Falls in residential
aged care for older adults are common and can have serious
consequences, including fractures, reduced independence and
death (Cameron 2018). Changes to the physical environment,
particularly with regard to floor surfaces, furnishings or accessibility
to spaces, may increase falls. Therefore, consideration of the
evidence for both the benefits and harms of physical environmental
changes are important in order to establish recommendations.
Redesign of the built environment may also specifically be
introduced to reduce the risk of falls in residential aged care, and
these have been examined in a previous Cochrane review (Cameron
2018).

We are unaware of any high-quality systematic review that has
examined the eCectiveness of both small-scale and large-scale
environmental changes to care facilities to improve quality of life
of all residents (i.e. not limited to a subgroup). There are a wide-
range of interventions that could come under the umbrella term
of the ‘physical environment’, but largely this review refers to
features of a care facility which have been specifically altered to
improve quality of life for the residents. Furthermore, previous
reviews have included uncontrolled before-aJer studies and cross-
sectional studies which is discouraged by the Cochrane EPOC group
because ‘it is diCicult, if not impossible to attribute causation
from such studies’ (EPOC 2016b). Similarly, many prior reviews
include controlled before-aJer and cluster-randomised studies
which have only a single site enrolled in one or more arms of
the study, where outcomes are inherently confounded by site
eCects. A more detailed discussion of existing reviews is included
in the Discussion. Investigating ways to improve the quality of life
of residents not only benefits the residents themselves, but also
benefits the staC in the facilities in which they reside and family
members of the resident.

O B J E C T I V E S

The primary objective was to assess the eCects of changes to
the physical environment or alternative models of residential
aged care that enhance the environment on the quality of life
of the residents. The secondary objective was to assess whether
the eCects of changes to the physical environment or alternative
models of residential aged care that enhance the environment have
a diCerent impact on quality of life according to whether the
population are living with dementia.

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M E T H O D S

Criteria for considering studies for this review

Types of studies

We included randomised trials and cluster-randomised trials, as
these are considered the ‘gold standard’ study design to assess
the eCectiveness of an intervention. However, due to the limited
feasibility of implementing environmental design interventions
in care facilities in randomised trials, we also included other
study designs. We included non-randomised trials, controlled
before-aJer studies, interrupted time series studies and repeated-
measures studies that met the EPOC Group study design criteria
(EPOC 2016b) and provided a comparison to traditional care
facilities or alternative physical designs. Interrupted time series
were required to measure observations at a minimum of  three
data points before and three data points aJer the intervention.
Only controlled before-aJer and cluster-randomised studies which
had more than one control and intervention site were included.
Within the context of whole models of care, studies were
considered as before-aJer studies if outcomes were reported
on or before  admission and at a minimum of one follow-up
time point. We included full-text studies, conference abstracts
and unpublished data obtained via correspondence with authors.
We included studies irrespective of their publication status and
language of publication.

Types of participants

We included studies of older adults residing in care facilities,
requiring some level of nursing care beyond room and board. We
included studies where ≥ 80% of the participants are aged 65 years
and over (mean age ≥ 65 years).

Types of interventions

We included studies examining interventions which have modified
the physical design of a residential aged care facility or built a
facility with an alternative model of residential aged care in order
to enhance the environment to promote independence and well-
being. The included interventions were design features that have
been specifically implemented to improve the quality of life of the
residents. The list of included interventions below indicates many,
but not all, possible interventions that were eligible for inclusion.
We have generated this list from an examination of previous reviews
and a review of a website which has been designed to show
enabling environments in residential aged care facilities (DEEP
2015).

Cochrane EPOC recommendations for grouping interventions are
based on four main themes (delivery arrangements, financial
arrangements, governance arrangements, and implementation
strategies) (EPOC 2016a). Within these groups are categories
and subcategories; due to the nature of the review, all of
the interventions fit within the ‘delivery arrangements’ group
as described below. We have further categorised the potential
interventions according to a previous review (Joseph 2015). They
include structural and non-structural interventions as follows.

Delivery arrangements

Category: Where care is provided and changes to the healthcare
environment.

Subcategory: environment (changes to the physical or sensory
healthcare environment, by adding or altering equipment or
layout, providing music, art).

• Whole-facility model
◦ Home-like models of residential  aged care, such as the

Green House model (Zimmerman 2016). These interventions
are multi-component and will include both changes to the
physical environmental design and changes to the model of
care provided. It is not possible to distinguish the influence
of the design component of the intervention from other
components of the intervention. Studies will be further
categorised by whether the intervention is a facility built
specifically to facilitate the proposed model of care, or
refurbishment of existing facilities.

• Outdoor modifications
◦ Access to and design of outdoor spaces (e.g. outdoor dining

spaces, easy access to a safe enclosed environment, sensory
gardens, Men’s Shed).

• Building layout
◦ Design of dining spaces.

◦ Increase in helpful stimuli (way-finding cues, natural light,
visibility of key amenities such as the toilet, use of contrast to
highlight helpful features and fixtures).

• Furniture, fixtures and equipment
◦ Home-like environments (e.g. variety of furniture to produce

a non-institutionalised feel).

◦ Inclusion of unobtrusive safety measures.

◦ Paint colours.

◦ Colour contrast of furniture.

◦ Changes to lighting (e.g. flexible lighting, buildings designed
to optimise natural light).

◦ Improvements in visual access (legibility) of the internal
spaces to enable residents to see their destination.

◦ Reduction in unhelpful stimuli (e.g. noise, clutter, glare).

◦ Introduction of familiar furniture, fittings, memorabilia.

• Indoor privacy/social interaction modifications
◦ Non-shared rooms (single-resident rooms).

◦ Designated quiet rooms.

◦ Smaller intimate seating areas to promote socialisation.

◦ Kitchen designs which promote opportunities for
engagement.

◦ Reminiscence rooms.

◦ Improving facilities that encourage links with the community
(better facilities for visitors, volunteers or children).

◦ Increasing number of social rooms.

Subcategory: size of organisations (increasing or decreasing the
size of health service provider units)

• Changes in scale of the building.

• Reduction in number of residents living together.

Exclusions: Studies which examined temporary interventions
applied as a management/treatment tool at an individual resident
level, such as light therapy, music therapy or sensory therapy (e.g.
Snoezelen) were excluded.

The comparison for this review was:

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• usual care (any residential aged care facility design which meets
the national accreditation standards for residential aged care,
but without specific enhancements, as described above); or

• alternative physical environmental designs.

Types of outcome measures

Studies were only included if they reported the primary or
secondary outcomes of interest, including quality of life and other
outcomes considered likely to impact quality of life for residents.
This is because this review was focused on interventions aimed at
improving quality of life and outcomes related to quality of life, not
interventions aimed at improving safety. Only outcomes measured
at the same time points were synthesised in meta-analyses;
outcomes measured at diCerent time points were synthesised
separately. Outcomes measured using diCerent scales or with
diCerent assessors could be included in the same data synthesis if
the outcome of interest was the same.

Primary outcomes

• Health-related quality of life (as measured on internationally
recognised scales such as the EuroQol (EQ5D); 36-Item Short
Form Health Survey (SF-36); Health Utilities Index (HUI); and
Adult Social Care Outcomes Toolkit (ASCOT) instruments).

• Behaviour, mood and depression (as measured on recognised
quantitative scales, e.g. global measures with the Challenging
Behaviour Scale, agitation measured with Cohen-Mansfield
Agitation Inventory (CMAI)). DiCerent sub-domains of behaviour,
mood and depression were assessed separately.

• Function
◦ Basic function (as measured by activities of daily living

(ADL) as measured on recognised scales such as the Barthel
Index, or individual quantitative measures of basic self-care
activities (i.e. ability to dress independently)).

◦ Instrumental function (as measured by ADL-recognised
scales such as the Lawton’s instrumental ADL scale,
or individual measures of instrumental function (e.g.
independence in shopping, using the telephone)).

Secondary outcomes

• Global cognitive functioning
◦ Measured with any validated measure, e.g. Alzheimer’s

Disease Assessment Scale cognitive subscale (ADAS-cog);
Mini Mental State Examination (MMSE); Repeatable Battery
for the Assessment of Neuropsychological Status (RBANS);
Cambridge Cognition Examination (CAMCOG).

• Quality of care
◦ Number of bedfast residents, catheter use, pressure ulcers

and hospital readmissions.

• Serious adverse eCects
◦ Including falls and the use of physical restraints.

• Outcomes for carers including mood/depression, quality of life
and burden
◦ Measured with any established tool, e.g. carer mood

or depression measured with Geriatric Depression
Scale; Hospital Anxiety and Depression Scale; Centre
Epidemiological Studies-Depression Scale; Montgomery‒
Åsberg Depression Rating Scale; General Well-Being Scale;
carer quality of life measured with SF-36; EQ5D; World Health
Organization Quality of Life Questionnaire (WHOQOL-BREF);

and carer burden measured with Zarit Burden Inventory;
Perceived Stress Scale; Family Caregiving Burden Inventory.

• Outcomes for staC including staC knowledge, attitude, self-
eCicacy, quality of life, stress (or burnout), and work satisfaction
◦ Measured with any established tool, e.g. Satisfaction in

Nursing Care and Work Scale, Caregiver Stress Scale (CSS),
Strains in Nursing Care Scale, Maslach Burnout Inventory
(MBI), StaC Attitude Questionnaire (SAQ), and the Quality of
Work Life Questionnaire

In the protocol, we reported that secondary outcomes would
include “dementia-specific measures (e.g. global behaviour
measures with the Neuropsychiatric Inventory, depression as
measured with the Cornell Scale for Depression in Dementia)”.
However, it is considered that these measures should not be
examined separately to behaviour as some measures including
the Neuropsychiatric Inventory may be used for people not
living with dementia and all depression measures should also be
considered as one outcome. Therefore, we removed “dementia-
specific measures” as a secondary outcome. As ‘behaviour,
mood and depression’ is a broad category, we did not think it
was appropriate to combine measures of diCerent behavioural
outcomes, therefore, these were analysed separately. Only the two
behavioural outcomes considered most informative are included in
the Summary of findings tables. These included global behaviour
measures, as global behaviour scales incorporate questions about
a range of behaviours and depression, as this is a common and
important negative mood symptom in residents of aged care
homes. In the Summary of findings tables, we also grouped
the outcomes ‘measures of basic function’ and ‘measures of
instrumental function’ under one outcome ‘function’.

Search methods for identification of studies

The authors of this review developed a search strategy
in collaboration with the Cochrane ECective Practice and
Organisation of Care (EPOC) Information Specialist.

Electronic searches

We undertook a comprehensive search of the Cochrane Database
of Systematic Reviews for related systematic reviews.

We searched the following databases for primary studies, from
inception to 11 February 2021.

• MEDLINE Ovid (1946 onwards);

• Embase Ovid (1974 onwards);

• Cochrane Central Register of Controlled Trials, (CENTRAL; 2021,
Issue 2) in the Cochrane Library;

• CINAHL PLUS (Cumulative Index to Nursing and Allied Health
Literature), EbscoHost (1982 onwards);

• PsycINFO EBSCO (1967 onwards);

• Dissertations and Theses, ProQuest;

• Science Citation Index Expanded, Web of Science, Clarivate
(1945 onwards);

• Conference Proceedings Citation Index ‒ Science, Web of
Science, Clarivate (1990 onwards);

• Social Care Online (www.scie-socialcareonline.org.uk).

Search strategies are comprised of synonyms for diCerent potential
environmental design interventions and diCerent terms for care

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facilities in both natural language and controlled vocabulary terms.
We did not apply any limits on language. All search strategies are
available in Appendix 1.

We used filters to limit retrieval to appropriate study designs.

Searching other resources

Trial registries

• WHO ICTRP (World Health Organisation International Clinical
Trials Registry Platform; www.who.int/ictrp; to 30 November
2017). This was not available at the time of the updated search
on 11 February 2021 and therefore, was not included.

• US National Institutes of Health Ongoing Trials Register
(www.ClinicalTrials.gov; to 11 February 2021).

• ANZCTR (www.anzctr.org.au; to 11 February 2021).

The search strategies for the trial registers are also provided
in Appendix 1.

Grey literature

We conducted a grey literature search to identify studies not
indexed in the databases listed above. We searched the following
websites on 11 February 2021 for terms including nursing home
OR residential OR long term care AND architecture OR design OR
environment:

• OpenGrey (www.opengrey.eu);

• Agency for Healthcare Research and Quality (AHRQ;
www.ahrq.gov), first ten pages returned;

• National Institute for Health and Clinical Excellence (NICE;
www.nice.org.uk);

• NHS Evidence (www.evidence.nhs.uk).

Although not originally planned, we also decided to search the
following websites because we identified them as potentially
relevant for this review aJer publication of the protocol. The
following websites were also searched on 11 February 2021:

• Housing Learning and Improvement Network (Housing LIN;
www.housinglin.org.uk);

• Dementia Training Australia (www.dta.com.au);

• Google Advanced Search (www.google.co.uk/
advanced_search), first ten pages returned.

We also reviewed reference lists of all included studies and
relevant systematic reviews of alternative models of residential
care to identify additional potentially eligible primary studies. We
conducted cited reference searches for included studies which
examined whole-facility models in Science Citation Index, Web of
Science, Clarivate on 22 June 2018.

Data collection and analysis

Selection of studies

We downloaded all titles and abstracts retrieved by electronic
searching to a reference management database (Endnote) and
removed duplicates. SLH screened all titles and abstracts for
inclusion and a second reviewer (SMD, RKM, KEL or staC listed
in the acknowledgements section) also independently screened
titles and abstracts for inclusion. We retrieved the full-text study
reports/publications and two review authors (SLH and SMD, RKM

or KEL) independently screened the full texts, identified studies for
inclusion and identified and recorded reasons for exclusion of the
ineligible studies using Covidence. We resolved any disagreement
through discussion. We collated multiple reports of the same study
so that each study, rather than each report, was the unit of interest
in the review. We recorded the selection process in suCicient detail
to complete a PRISMA flow diagram (Liberati 2009).

Data extraction and management

We used  Covidence  soJware to complete data collection. Two
review authors (SLH and SMD, KEL or RKM) independently
extracted the following study characteristics from the included
studies.

• Methods: study design, number of study centres and location,
study setting, withdrawals, date of study, follow-up;

• Participants: number, mean age, age range, gender, severity
of condition, diagnostic criteria, ethnicity, country, inclusion
criteria, exclusion criteria, other relevant characteristics;

• Interventions: intervention components, comparison, fidelity
assessment;

• Outcomes: main and other outcomes specified and collected,
time points reported;

• Notes: funding for trial, conflicts of interest, ethical approval.

We resolved disagreements by consensus. We contacted authors
of included studies/reviews to seek unpublished results/data or
clarify study reports. We entered the extracted data into Review
Manager 5 (Review Manager 2014). The most important time points
for outcomes were considered to be in the range 3 to 6 months
as this allows adequate time for an intervention to have an eCect,
but is not such an extended follow-up that it will be against a
background of large functional or cognitive decline or increased
mortality in residents.

Assessment of risk of bias in included studies

Two review authors (SLH and KEL, RKM or SMD) independently
assessed risk of bias for each study using the criteria outlined in the
Cochrane Handbook for Systematic Reviews of Interventions (Higgins
2011), and the guidance from the EPOC group (EPOC 2017a). Any
disagreement was resolved by discussion. We assessed the risk of
bias according to the following domains.

• Random sequence generation

• Allocation concealment

• Blinding of participants and personnel

• Blinding of outcome assessment

• Incomplete outcome data

• Selective outcome reporting

• Other bias: baseline outcome measurements similar, baseline
characteristics similar, protection against contamination

For interrupted time series studies, we assessed the risk of bias
according to the following domains.

• Allocation concealment

• Incomplete outcome data

• Selective outcome reporting

• Intervention independent of other events

• Shape of the intervention eCect prespecified

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• ACect/influence of intervention on data collection

• Other bias: any additional potential sources of bias identified

We judged each potential source of bias as ‘high’, ‘low’, or ‘unclear’
and provided a justification for our judgement in the risk of bias
tables including a quote from the study where appropriate. We
assigned an overall low risk of bias if we judged all domains to have
a low risk of bias, an overall high risk of bias if we judged one or
more domains to have a high risk of bias, and an overall unclear risk
of bias if we judged one or more domains to have an unclear risk
of bias (i.e. not clearly reported). We summarised the risk of bias
judgements across diCerent studies for each of the domains listed.
We did not exclude studies on the grounds of their risk of bias. We
contacted study authors to clarify risk of bias for ‘unclear’ items for
studies providing quantitative outcomes suitable for pooling.

When considering treatment eCects, we took the risk of bias into
account for the studies that contributed to that outcome and
incorporated it into our grading of the certainty of the evidence.

We conducted the review according to the published protocol and
reported any deviations from it in the DiCerences between protocol
and review.

Measures of treatment e?ect

We estimated the eCect of the intervention using risk ratio/risk
diCerence, rate ratio or odds ratio (as appropriate) for dichotomous
data, and mean diCerence or standardised mean diCerence for
continuous data, together with the 95% confidence interval. We
ensured that an increase in scores for continuous outcomes could
be interpreted in the same way for each outcome, explained the
direction to the reader, and reported where the directions were
reversed, if this was necessary.

For randomised trials, we used study endpoints in preference to
change from baseline data, if possible, as recommended in Chapter
7 of the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2011). For interrupted time series studies, we planned to
abstract the diCerence in slope and the diCerence in level pre-
to post-intervention. We planned to report the post- versus pre-
intervention diCerence (adjusted for trends) at specific time points.
If the diCerences were not available in the primary reports, we
planned to attempt re-analysis using data from graphs or tables
based on the EPOC-specific guidance for analysis of interrupted
time series studies.

Unit of analysis issues

For cluster-randomised trials, where possible, we extracted data
which took the eCect of clustering into account. When clustering
was not taken into account, we planned to attempt to account
for the eCect of clustering by dividing the original sample size by
the design eCect, as described in Chapter 16.3 of the Cochrane
Handbook for Systematic Reviews of Interventions (Higgins 2011).

Dealing with missing data

We contacted investigators in order to obtain missing outcome
data. If a standard deviation needed to determine a mean
diCerence was not available, the standard deviation was obtained
from other available data such as a standard error, confidence
intervals, t statistic or P value that related to a diCerence between
means in two groups, in line with the Cochrane Handbook for

Systematic Reviews of Interventions (Higgins 2011). However, if
the studies were non-randomised and the reported means were
unadjusted for potential confounding factors, we did not attempt
to produce an eCect estimate. If the study was a repeated measures
study or interrupted time series and a statistical comparison of time
trends before and aJer the intervention were not provided; we re-
analysed the results as recommended in EPOC 2017c.

Assessment of heterogeneity

We examined heterogeneity using the I2 statistic which quantifies
the percentage of the total variation across studies that is
due to heterogeneity rather than chance (Higgins 2003). We
used Cochrane guidance to interpret the I2 statistic (0% to
40% might not be important; 30% to 60% may represent
moderate heterogeneity; 50% to 90% may represent substantial
heterogeneity; and 75% to 100% may represent very substantial
(‘considerable’) heterogeneity) (Higgins 2011).

Assessment of reporting biases

We attempted to contact study authors, asking them to provide
missing outcome data where applicable. If no response was
received, and the missing data were thought to introduce serious
bias, we planned to explore the impact of including such studies in
the overall assessment of results. If we were able to pool more than
10 trials, we planned to create and examine a funnel plot to explore
possible publication biases, interpreting the results with caution
(Sterne 2011). We did not assess reporting biases using a funnel plot
as there were too few studies for each comparison and outcome.

Data synthesis

We undertook meta-analyses only where this was meaningful, i.e.
if the treatments, participants, and the underlying clinical question
were similar enough for pooling to make clinical sense. Fixed-
eCects models were used, but random eCects would be considered
if we were concerned about the influence of small-study eCects
on the results of a meta-analysis in which there was evidence of

between-study heterogeneity (I2 > 0) as described in Chapter 10
of the Cochrane Handbook for Systematic Reviews of Interventions
(Higgins 2011). Where multiple trial arms were reported in a single
trial, we included only the relevant arms. For non-randomised
studies, only studies which reported results adjusted for potential
confounding factors were planned to be reported in forest plots
using the “estimate from the model that adjusted for the maximum
number of covariates” as recommended in Chapter 13 of the
Cochrane Handbook for Systematic Reviews of Interventions (Higgins
2011). For repeated measures studies, if the authors did not
conduct a statistical comparison of time trends before and aJer the
intervention, we re-analysed the results as recommended in EPOC
2017c. We statistically compared time trends using a segmented
regression model which included the time elapsed since the start of
the study, a dummy variable indicating the pre-intervention period
or the post-intervention period, and an interaction term between
the time elapsed and the dummy variable as predictors and the
mean scores as the outcome variable.

Where pooling of outcomes was not appropriate, we completed
a structured synthesis of the results. We provided structured
tabulations of results across studies grouped by the intervention
examined (e.g. all studies which examined a whole-facility ‘home-
like’ model of care were grouped together) and further grouped
by the outcome category (e.g. health-related quality of life). Forest

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plots were included when more than one study examined the
same intervention and outcome, and data were available for
presentation in a forest plot.

Subgroup analysis and investigation of heterogeneity

We planned to carry out the following subgroup analyses, but there
were insuCicient data to perform these.

• Level of nursing care provided by the facility (high/intermediate/
mixed). The levels of care of the facilities reflect the levels of
dependence of the participants. (Cameron 2018).

• Cognitive status (i.e. dementia versus no dementia/mixed
population)

Sensitivity analysis

We planned to perform sensitivity analyses defined a priori to
assess the robustness of our conclusions and explore their impact
on eCect sizes, but there were insuCicient data to perform these.

• restricting the analysis to published studies; and

• restricting the analysis to studies with a low risk of bias.

Summary of findings and assessment of the certainty of the
evidence

We created a Summary of findings table for the main intervention
comparison (whole-facility ‘home-like’ model compared to usual
care or alternative designs) and included main outcomes — primary
eCectiveness outcomes of health-related quality of life; measures
of behaviour, mood and depression; measures of function; plus
serious adverse eCects.  Only the main intervention comparison
was included in a Summary of findings table as this is the largest
scale design change which captures a variety of diCerent design
alterations and is considered the most important comparison.
“Behaviour, mood and depression” is a primary outcome. As this
outcome encompasses a large range of possible outcomes and
measures, only the two considered most informative were included
in the Summary of findings table. These are: global behaviour
measures (as these capture a range of these outcomes) and
depression as this is a common and important negative mood
symptom in residents of aged care homes. As described in the Data
extraction and management  section, the most important time

points for outcomes were considered to be in the range 3 to 6
months. Therefore, outcomes within this range were reported in the
Summary of findings table, where available.

Two review authors (SLH and SMD or KEL) independently assessed
the certainty of the evidence (high, moderate, low, and very low)
using the five GRADE considerations (risk of bias, consistency
of eCect, imprecision, indirectness, and publication bias) (Guyatt
2008). We used methods and recommendations described in
Section 8.5 and Chapter 12 of the Cochrane Handbook for
Systematic Reviews of Interventions (Higgins 2011), and the EPOC
worksheets (EPOC 2017b), and used GRADEpro GDT soJware
(GRADEpro GDT 2015). Randomised trials start at high certainty
of evidence and non-randomised trials start at low certainty
of evidence before the five GRADE considerations are assessed.
We resolved disagreements on certainty ratings by discussion
and provided justification for decisions to down or upgrade the
ratings using footnotes to the table with comments to aid readers’
understanding of the review, where necessary.

R E S U L T S

Description of studies

Twenty randomised controlled, before-aJer or repeated measures
studies of large- or small-scale changes to the environmental
design of aged care facilities were included in this review.
The comparison groups varied, but included comparison
to  any  alternative environmental design. Details of the
interventions and comparisons are provided in the  Included
studies section.

Results of the search

The electronic search returned 19,393 records, and 157 records
(grey literature or reference lists of studies)  were identified from
other sources. AJer removal of duplicates, 11,117 unique records
were screened, and 10,670 citations were excluded based on
titles and abstracts. We assessed the full-text for 447 records
and identified 20 completed studies eligible for inclusion in this
review (reported in 34 records). One ongoing study was identified
and one study awaiting classification.  Figure 1  shows the study
selection process.

 

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Figure 1.

 

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Included studies

See Characteristics of included studies.

Study design and country

Of the 20 included studies, five were randomised trials (Chenoweth
2014; Galik 2021; Mathey 2001; Nijs 2006; Riemersma-vanDerLek
2008), two were randomised cross-over trials (Figueiro 2019;
Hopkins 2017), 12 were controlled before-aJer studies (Afendulis
2016; Annerstedt 1993; Burack 2012; Dettbarn-Reggentin 2005;
Diaz-Veiga 2014; Elmstahl 1997; Frisoni 1998; Kenkmann 2010; Te
Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001; Yoon 2015),
and one was a repeated measures study (Marcy-Edwards 2011).
All of the randomised trials were cluster-randomised as the
facilities were randomised to receive the intervention (Chenoweth
2014; Galik 2021; Mathey 2001; Nijs 2006; Riemersma-vanDerLek
2008).  Hopkins 2017  and  Figueiro 2019  did not specifically state
the studies were cluster randomised, but as the intervention
(lighting) was installed in communal living areas in both of these
studies, it is assumed these studies are also cluster randomised.
The studies were conducted in nine diCerent countries including
the USA (n = 6,  Afendulis 2016; Burack 2012; Figueiro 2019;
Galik 2021; Wylie 2001; Yoon 2015), The Netherlands (n=4 Mathey
2001; Nijs 2006; Riemersma-vanDerLek 2008; Te Boekhorst 2009),
the UK (n=2  Hopkins 2017; Kenkmann 2010), Sweden (n =
2,  Annerstedt 1993; Elmstahl 1997), Germany (n = 2,  Dettbarn-
Reggentin 2005; Wolf-Ostermann 2012) and single studies from
Australia (Chenoweth 2014), Spain (Diaz-Veiga 2014), Italy (Frisoni
1998) and Canada (Marcy-Edwards 2011).

All studies except five reported sources of funding (Burack 2012;
Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Mathey 2001; Wylie
2001). The funding sources for the majority of studies were
research or city councils, charitable organisations, government
health organisations, universities or a mixture of these. Riemersma-
vanDerLek 2008  reported that Philips Lighting BV, Braun, and
Cambridge Neurotechnology supplied material for the study
at reduced cost.  Figueiro 2019  reported that the following
manufacturers provided in-kind lighting products: GE Current, a
Daintree company; OSRAM Sylvania; Ketra; and Sharp Corporation.
Ten studies reported no conflicts of interest and eight studies did
not report conflicts of interest. One study (Hopkins 2017) stated no
financial, personal, potential conflicts of interest in the conduct of
the study or in the manuscript development. The authors stated
that although Philips Lighting supplied the light fitments, they had
no part in the design of the protocol nor in the analysis of the data.
They stated two co-authors were co-directors of Stockgrand Ltd
and one co-author had in the past received research grant support
from Philips. One co-author was an employee of Philips Research.
Nine studies did not report ethical approval and eleven studies
reported ethical approval details. One further study (Figueiro 2019)
stated neither the funding agency nor the in-kind contributors had
any role in the design, methods, data analysis, or preparation of
the manuscript. Four co-authors received research grant support
from the National Institutes of Health, OCice of Naval Research, the
United States General Services Administration, and industry (Acuity
Brands; Axis Lighting; GE Current, a Daintree company; OSRAM
Sylvania; Ketra; USAI Lighting; Armstrong Ceilings and Walls; Philips
Lighting; Cree; View Glass; Marriott International).

Participants

The 20 studies included 77,265 participants. There was one very
large study which was unclear on the number of participants
included in the analyses used in this review, but weighted
sample percentages indicate an estimated 74,449 participants at
enrolment (Afendulis 2016). The remaining 18 studies included
2816 participants and sample sizes ranged from 34 (Marcy-Edwards
2011) to 601 (Chenoweth 2014). Two studies did not report mean
participant age (Afendulis 2016; Wylie 2001) and most studies
reported mean age by group allocation (intervention and control).
Reported mean participant age in studies which did report this
ranged from 75 (Nijs 2006) to 87.7 years (Kenkmann 2010) in
the intervention or control groups. Thirteen studies reported the
proportion of participants with dementia (range 0% to 100%).
One study included only participants without dementia (Nijs
2006) and nine studies included only participants with dementia
(Chenoweth 2014; Diaz-Veiga 2014; Elmstahl 1997; Figueiro 2019;
Mathey 2001; Riemersma-vanDerLek 2008; Te Boekhorst 2009;
Wolf-Ostermann 2012; Wylie 2001). Overall, 68% of participants
were women and 32% were men, in the 14 studies for which
this information was available (Annerstedt 1993; Chenoweth 2014;
Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Figueiro 2019; Frisoni
1998; Galik 2021; Marcy-Edwards 2011; Mathey 2001; Nijs 2006;
Riemersma-vanDerLek 2008; Te Boekhorst 2009; Wolf-Ostermann
2012; Yoon 2015).

Description of the interventions

Whole-facility model

Home-like models of care

Eleven studies (two randomised trials, nine controlled before-
aJer studies) reported on changes to the physical environment
in conjunction with changes to the whole model of care
(e.g. changes to staCing such as more consistent staCing and
residents having more choice and control over daily routines
and activities) in comparison to traditional design and care
(Afendulis 2016; Annerstedt 1993; Burack 2012; Chenoweth
2014; Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Galik 2021; Te
Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001; Yoon 2015).
The ‘traditional design’ comparators included: settings which had
not adopted a ‘small house model’ (Afendulis 2016), large long-
term care hospitals (Annerstedt 1993), settings with a ‘typical
nursing home organisational structure and standard administrative
and departmental hierarchy of care’ (Burack 2012), ‘nursing
home typical organisational structures’ (Dettbarn-Reggentin 2005),
settings which has ‘provision of public health services in
accordance with the health needs of the residents, the formal
registration of care tasks and activities, and the prioritisation of
safety both in the design of the spaces and the organisation’ (Diaz-
Veiga 2014), larger-scale settings (Te Boekhorst 2009), special care
units for people with dementia (Wolf-Ostermann 2012), ‘traditional
nursing homes’ (Wylie 2001), traditional large scale nursing
homes, with hospital-like features and traditional hierarchical
organisational structures (Yoon 2015), or residential aged care
settings which did not receive a refurbishment intervention
(Chenoweth 2014, Galik 2021).

Of these, six controlled before-aJer studies incorporated changes
to the scale of the building which limited the capacity of the living
units to small numbers of residents (this ranged from six to 15
residents assigned per living unit) (Afendulis 2016; Annerstedt 1993;

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Dettbarn-Reggentin 2005; Te Boekhorst 2009; Wolf-Ostermann
2012; Yoon 2015). These interventions usually involved design
changes to areas which both the residents and staC would use (e.g.
kitchen and laundry room).

Nine studies (five randomised trials, three controlled before-aJer
studies, one repeated measures study) reported interventions
which did not incorporate changes to the whole model of
care (Elmstahl 1997; Figueiro 2019; Frisoni 1998; Hopkins 2017;
Kenkmann 2010; Marcy-Edwards 2011; Mathey 2001; Nijs 2006;
Riemersma-vanDerLek 2008).

Refurbishment

Five of the studies (two randomised trials, three controlled
before-aJer studies) which examined physical design changes in
conjunction with changes to the whole model of care did not
incorporate changes to the number of residents living in a unit but
were smaller refurbishments and design changes of the existing
home (Burack 2012; Chenoweth 2014; Diaz-Veiga 2014; Galik 2021;
Wylie 2001).  Burack 2012  included changes to the bedrooms and
common living areas including encouraging the use of personal
items for the residents to individualise their bedrooms and
design changes to the common areas to create a “calm, peaceful
environment” (e.g. table cloths and centrepieces, artwork for
walls and painted murals) in conjunction with changes to person-
centred care such as consistent staCing, meaningful activities,
community structure changes and family involvement. Chenoweth
2014  examined changes to the physical environment with or
without changes to the whole model of care (person-centred care).
The authors stated that changes to the environment involved
using the Environment Audit Tool (EAT) to “identify features of the
home that could be improved” (Fleming 2011). The recommended
environmental changes included altering the safety, accessibility
and utility of outdoor spaces, a greater variety of social spaces
and changes to colour and addition of objects with an aim to
improve way finding and familiarity with a budget of AUD$10,000
per home. However, the authors have reported that there were
diCiculties in implementation of some design features at some
facilities within the time frame of the study. Facilities which also
received changes to person-centred care had experts in person-
centred care train five staC from each of the facilities over 32 hours
oC-site (Chenoweth 2014).  Diaz-Veiga 2014  examined the Etxean
Ondo model which includes design of physical-organisational
environments similar to domestic settings, favouring personal
privacy as well as opportunities for choice, participation in
daily life activities and social interaction, set apart by the
creation of domestic environments, the development of important
activities and organisational processes based on the daily life
and the resources of residents, families and professionals.  Galik
2021  examined a Function and Behavior Focused Care (FBFC)
model which included an examination of opportunities for physical
activity and engaging in functional tasks as well as barriers to these
activities. Based on these assessments, modifications in policy
and the environment were made.  Wylie 2001  examined the Eden
Alternative which incorporates pets, plants and children to daily life
and provides daily opportunities to give as well as receive care by
promoting resident participation in the daily routine of activities.

Special-care units for people with dementia

One controlled before-aJer study examined a special care unit
for people with dementia in comparison to traditional nursing
homes (Frisoni 1998). This intervention incorporated the following

components: ten two-bed rooms, a large wandering area, a dining
room, and a separate area for structured activity (physical and
occupational therapy); exit doors were secured by magnetic locks
opening with a digital code, noxious stimuli were minimised, wall
colours were made neutral, and way-finding cues were used to help
residents identify diCerent areas.

Group living corridors

One controlled before-aJer study examined a comparison between
diCerent building layouts within a group living unit (Elmstahl
1997). Group living units were built for six to eight residents with
dementia and incorporated a specifically designed community area
comprising a living room, laundry, kitchen and dining room shared
by residents and staC. A corridor design to the group living units was
compared to a non-corridor design (L-shaped, H-shaped or square
design).

Alternative physical environmental design (without whole-facility
changes)

Lighting

Three randomised trials examined lighting interventions (Figueiro
2019; Hopkins 2017; Riemersma-vanDerLek 2008). One study
compared high colour temperature (17000 K) blue-enriched white-
light in communal areas compared to low colour temperature
(4000 K) white light (Hopkins 2017); the higher the degrees Kelvin
the brighter the lights will appear. One study installed a large
number of fluorescent tubes in the common living room and lights
were on between 9 am and 6 pm and increased light intensity
between 10 am and 6 pm, whereas the control facilities had half
the number of tubes with concealed band-stop filters and were
installed at a greater distance from the eye (Riemersma-vanDerLek
2008). The third study examined lighting designed to provide high
circadian stimulus (Figueiro 2019). Custom-built floor luminaires,
light boxes and light tables were used, timers activated lights
according to wake times, and lights were placed in the person’s
bedrooms or in common area until 6 pm. The control lighting
provided low circadian stimulus with the light delivery method
varying depending on where the participant spent most of his/her
day.

Dining area redesign

Three studies (two randomised trials, one controlled before-
aJer study) examined changes to the dining room to create a
family-style, restaurant-style or improved ambiance environment
(Kenkmann 2010; Mathey 2001; Nijs 2006).  Nijs 2006  examined
a family-style dining intervention which included changes to the
design components of the dining room (table cloths, plates and
glasses, full cutlery, flower arrangements) and changes to the
dining service (cooked meals served on tables, greater choice
of meals, resident choice for timing of meals compared to
meals served on a pre-plated tray with none of the design
features described in the intervention). The second study which
examined a restaurant-style dining intervention also included table
cloths and flower arrangements in addition to food displayed
for residents to see, fewer tables in the dining room, white
crockery with side plates, drinks machine available at all times
and snacks available anytime (Kenkmann 2010). This intervention
also included increased choice of meals and increased choice
in timing of meals by opening the dining area for 90 minutes
with several sittings.  Mathey 2001  examined an ‘improved meal
ambiance’ intervention which included changes to the design of

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the environment: plant or flowers placed on every table, suCicient
lighting, background music chosen by the residents, table cloths
and trays and covers removed from the table. Further changes were
also employed including increasing the number of nurses during
meal times and distinguishing meal times from other activities,
e.g. medications handed out before the start of the meal and no
cleaning activities in the dining room during meal consumption.

Garden vignette

One repeated measures study  with no control group examined a
garden vignette (Marcy-Edwards 2011) which involved the creation
of a designated area that contained clusters of gardening and
nature-related objects, positioned in a highly visible, high traCic
space. The vignette included all objects required to accomplish
the activity of gardening: a garden centre table; soil, plastic pots,
garden seeds, light plastic garden tools, and a plastic watering can;
scented, colourful and edible plants, glossy gardening magazines
with engaging pictures; and large artificial flowers to attract
attention. When the garden vignette was in place, all residents had
unobstructed exposure and access, 24 hours per day.

Comparators

For changes to the whole model of care, the comparators
were ‘traditional nursing homes’ (Wylie 2001,  Yoon
2015), ‘psychogeriatric nursing homes’ (Te Boekhorst 2009),
nursing homes with ‘typical organisational structure’ (Burack
2012,  Dettbarn-Reggentin 2005) long-term care hospitals
(Annerstedt 1993), special care units for people with dementia
(Wolf-Ostermann 2012), facilities which have ‘prioritisation of
safety in design and organisation’ (Diaz-Veiga 2014) or matched
non Green House model facilities (Afendulis 2016).  Chenoweth
2014  compared the adoption of the person-centred environment
to regular monitoring of any unplanned changes to the
environment.  Elmstahl 1997  compared a corridor design to a
non-corridor design. The studies of lighting comparators were
low colour temperature white light (Hopkins 2017)  or  half the
number of fluorescent tubes installed in the intervention group
with concealed band-stop filters that were installed at a greater
distance from the eye (Riemersma-vanDerLek 2008). For the
dining interventions,  the comparator was usual care (Kenkmann
2010; Mathey 2001; Nijs 2006). The special care units were
compared to traditional environments (Frisoni 1998).  The garden
vignette intervention did not have a comparator group as this was
a repeated measures study (Marcy-Edwards 2011).

Fidelity assessment

One of the studies carried out a fidelity assessment (Galik
2021). Galik 2021 reported evidence of fidelity in terms of delivery
of the intervention (583 staC educated, completion of environment
and policy assessments, development of care-plans and ongoing
mentoring and motivating of the staC). There was also evidence
of knowledge of the intervention (98% correct on the Knowledge
Test for the intervention). There was evidence of adoption of
the intervention in the intervention facilities. This was based on
improvements in environments and policies to improve function
and physical activity (environment assessment increased from 13.5
(SD 2.07) to 15.12 (SD 0.99), and policy changes increased from 8.50
(SD 3.85) to 10.87 (SD 2.41)). There was also an increase reported in
the number of care activities. Chenoweth 2014 reported diCiculties
in implementing changes to the physical environment within the
time frame of the study (Chenoweth 2014). Of the facilities that

were randomised to receive the environment intervention, the
authors reported that only 47% at post-intervention and 54%
at eight months follow-up had implemented the environment
intervention, and of the facilities that had been randomised to
receive the environment intervention with person-centred care
training, only 14% and 27% had implemented the environment
intervention, respectively. Reported diCiculties in implementing
the environment intervention included: a) delays in finding
contractors to complete the design changes within the study
timeframe, b) management at facilities  implementing changes
which diCered from the recommended changes or management
at facilities not happy to implement the suggested changes (e.g. a
plan to make the outside area more accessible involved losing a
bedroom which the home was not prepared to do), c) quotations
for the interventions being beyond the budget of the project or the
home, d)  changes to management in the home during the study
period, e) safety issues for residents with the proposed changes
or f) feasibility of the intervention in relation to complying with
building codes. In some instances, where the management of the
home were not happy with the proposed changes or the cost of
the changes was above budget, the project team were able to
work with the home to adapt the proposed changes to fit within
budget and the study time frame, but this was not always feasible.
Furthermore, facilities that were not randomised to receive the
intervention may have initiated design improvements during the
study period which could not be controlled for. One other study
examining implementation of the Eden Alternative reported one
of the facilities  which received the intervention discontinued its
implementation and was then evaluated as part of the control
group, but reasons for discontinuation of the intervention were not
detailed in the study (Wylie 2001).

Outcomes

Primary outcomes

Health-related quality of life

Seven studies were included that reported health-related quality of
life (Chenoweth 2014; Diaz-Veiga 2014; Mathey 2001; Nijs 2006; Te
Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001). Twelve studies
were included that did not report health-related quality of life,
but reported other, related, secondary outcomes (Afendulis 2016;
Annerstedt 1993; Burack 2012; Dettbarn-Reggentin 2005; Elmstahl
1997; Frisoni 1998; Galik 2021; Hopkins 2017; Kenkmann 2010;
Marcy-Edwards 2011; Riemersma-vanDerLek 2008; Yoon 2015).
Health-related quality of life was measured using the following
assessments in single studies: Dementia Quality of Life (DEMQOL)
Proxy  (Chenoweth 2014), QUALIDEM: a dementia-specific quality
of life measure  (Wolf-Ostermann 2012), Life Satisfaction Index
(LSI)  (Wylie 2001) and Dutch Quality of Life of Somatic Nursing
Home Residents questionnaire  (Nijs 2006). The quality of life
in late-stage dementia (QUALID) and FUMAT  were used in  Diaz-
Veiga 2014 and the Sickness Impact Profile (SIP) and Philadelphia
Geriatric Centre Morale Scale (PGCMS) were used in Mathey 2001.
Quality of life was reported at six months (Nijs 2006), eight months
(Chenoweth 2014), up to 12 months (Diaz-Veiga 2014; Mathey 2001;
Wolf-Ostermann 2012) and up to 18 months (Wylie 2001) follow-up.
Although  Te Boekhorst 2009  did include Dementia Quality of Life
(DQoL) and QUALIDEM measures in their study, these findings were
not included in the review because only results at six months were
reported without baseline results or change in quality of life over
time.

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Behaviour, mood and depression

FiJeen studies reported on behaviour, mood or depression
(Annerstedt 1993; Burack 2012; Chenoweth 2014; Dettbarn-
Reggentin 2005; Elmstahl 1997; Figueiro 2019; Frisoni 1998;
Galik 2021; Hopkins 2017; Kenkmann 2010; Marcy-Edwards 2011;
Riemersma-vanDerLek 2008; Te Boekhorst 2009; Wolf-Ostermann
2012; Yoon 2015). Behaviour,  mood or depression was measured
by the Neuropsychiatric Inventory (NPI) in five studies, where
three studies used the standard version (Frisoni 1998; Marcy-
Edwards 2011; Te Boekhorst 2009), one study used the nursing
home version (Wolf-Ostermann 2012) and one study used the
questionnaire format (Riemersma-vanDerLek 2008). The Cohen-
Mansfield Agitation Inventory (CMAI) was also used in seven
studies (Burack 2012; Chenoweth 2014; Figueiro 2019; Frisoni 1998;
Galik 2021; Riemersma-vanDerLek 2008; Wolf-Ostermann 2012),
the Organic Brain Syndrome (OBS) scale was used in two  studies
(Annerstedt 1993; Elmstahl 1997) and the Philadelphia Geriatric
Centre ACect Rating Scale (PGCARS) in one  study (Riemersma-
vanDerLek 2008). The Hospital Anxiety and Depression (HAD scale)
was used in three  studies, in two  studies (Kenkmann 2010;
Riemersma-vanDerLek 2008) specifically to measure anxiety and
in one  to measure depression (Hopkins 2017). Depression was
measured using the  Cornell Depression Scale in four  studies
(Figueiro 2019; Frisoni 1998; Galik 2021; Riemersma-vanDerLek
2008), the Revised Memory and Behaviour Checklist (RMBPC) in
one study (Te Boekhorst 2009) and the Mood Scale Score (MSS) in
one study (Yoon 2015). The Index of Social Engagement (ISE) and
Revised ISE (RISE) were used to measure social engagement in Te
Boekhorst 2009 and Yoon 2015, respectively. Resistiveness to care
was measured using the Resistiveness to Care Scale in one study
(Galik 2021).

Behaviour was reported at six months follow-up (Te Boekhorst
2009), six and 12 months follow-up (Annerstedt 1993; Wolf-
Ostermann 2012) and agitation at eight months follow-up
(Chenoweth 2014).  Burack 2012  reported on verbal agitation,
forceful behaviours and physical agitation at two years follow-
up.  Marcy-Edwards 2011  also reported behaviour in a repeated
measures study over five phases of 14 days each;  the
measurements were repeated multiple times in the 14-day
period and the mean measurements for days, evenings and
nights were presented. Six studies reported behaviour and
depression at four weeks follow-up (Figueiro 2019; Hopkins 2017),
three months follow-up (Frisoni 1998) and 12 months follow-up
(Elmstahl 1997; Galik 2021; Kenkmann 2010).  Yoon 2015  reported
depressive symptoms at 18 months follow-up.  Riemersma-
vanDerLek 2008 reported behaviour and function at multiple time
points (six weeks, six months, 12 months, 18 months and 24
months follow-up).  Yoon 2015  and  Te Boekhorst 2009  reported
social engagement at 6 months (Te Boekhorst 2009) and over
18 months (Yoon 2015).  Dettbarn-Reggentin 2005  reported social
behaviour at 12 months.

Function

Nine studies reported on function (Chenoweth 2014; Dettbarn-
Reggentin 2005; Figueiro 2019; Frisoni 1998; Nijs 2006; Te Boekhorst
2009; Wolf-Ostermann 2012; Yoon 2015). Function was measured
by the  Barthel Index in four studies (Dettbarn-Reggentin 2005;
Frisoni 1998; Galik 2021; Wolf-Ostermann 2012), the Interview for
the Deterioration of Daily Living activities in Dementia  (IDDD) in
one  study (Te Boekhorst 2009), the  Bedford Alzheimer’s nursing

severity scale in one  study (Frisoni 1998), the Nursing Home
physical performance test in one study (Dettbarn-Reggentin 2005),
and Activities of Daily Living (ADLs) in three studies; the ADL long-
form scale was used in one study (Yoon 2015); the Minimum Data
Set Activities of Daily Living Scale (MDS-ADL) was used in one study
(Figueiro 2019), and the Nurse-informant adaptation of the scale by
Katz and colleagues was used in one study (Riemersma-vanDerLek
2008).

Function was reported at three months (Frisoni 1998), six months
(Nijs 2006; Te Boekhorst 2009), eight months (Chenoweth 2014), six
and 12 months (Dettbarn-Reggentin 2005; Wolf-Ostermann 2012),
four and 12 months (Galik 2021) and 18 months (Yoon 2015) follow-
up.   Figueiro 2019  was a cross-over trial with a 14-week protocol
which comprised of two 1-week baseline measurement periods
and two 4-week lighting intervention/control periods, separated
by a 4-week washout period. Data were collected during the
baseline measurement weeks (weeks 1 and 10) prior to each 4-week
intervention/control period and once again during the final week of
each intervention/control period (weeks 5 and 14).

Secondary outcomes

Global cognitive functioning

Seven studies reported on global cognitive functioning (Dettbarn-
Reggentin 2005; Frisoni 1998; Kenkmann 2010; Riemersma-
vanDerLek 2008; Te Boekhorst 2009; Wolf-Ostermann 2012; Yoon
2015). Global cognitive functioning was measured with the
Mini Mental State Examination (MMSE) in six  studies (Dettbarn-
Reggentin 2005; Frisoni 1998; Kenkmann 2010; Riemersma-
vanDerLek 2008; Te Boekhorst 2009; Wolf-Ostermann 2012), the
Clinical Dementia Rating in one  study (Frisoni 1998) and the
Cognitive Performance Scale (CPS) in one study (Yoon 2015). Global
cognitive function was reported at three months (Frisoni 1998),
six months (Kenkmann 2010; Wolf-Ostermann 2012), 12 months
(Dettbarn-Reggentin 2005; Te Boekhorst 2009; Wolf-Ostermann
2012) and 18 months (Yoon 2015). Riemersma-vanDerLek 2008 also
reported cognitive function at multiple time points.

Quality of care

Two studies reported on quality of care (Afendulis 2016; Chenoweth
2014). Chenoweth 2014 used the Quality of Interactions Schedule
(QUIS) to measure quality of care and Afendulis 2016 used number
of bedfast residents, catheter use, low-risk and high-risk pressure
ulcers, rehospitalisations and avoidable rehospitalisations as
quality of care measures.

Afendulis 2016 reported these outcomes at up to 5-year follow-up
and  Chenoweth 2014  reported these  at post-intervention at four
months and eight months follow-up.

Serious adverse e?ects

Three studies reported on serious adverse eCects (Afendulis
2016; Frisoni 1998; Kenkmann 2010).  Afendulis 2016  and  Frisoni
1998  reported use of physical restraints over five years and three
months respectively.  Frisoni 1998  reported frequency of falls in
three months and Kenkmann 2010 reported number of falls in 12
months.

Outcomes for carers

No included studies reported outcomes for carers.

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Outcomes for sta?

No included studies reported outcomes for staC.

Ongoing studies

One ongoing study was identified (see  Characteristics of
ongoing studies for details). This ongoing national cross-sectional
monitoring study is examining quality of life, quality of care and
staC outcomes in diCerent styles of aged care facilities every two to
three years in The Netherlands. Between 47 and 144 facilities have
participated in the four cycles conducted so far (Willemse 2011).
The study aimed to compare “traditional large scale nursing homes,
nursing home wards in a home for the aged, large nursing home
where group living home care is provided, group living homes
nearby the mother facility and stand-alone group living homes
in the community” (Willemse 2011). Whilst all the potentially
relevant analyses identified from the study thus far have been
cross-sectional, future publications will be monitored for studies
that meet the inclusion criteria for this review.

Studies awaiting classification

One study was identified which is awaiting classification. Kolberg
2020 is a cluster-randomised trial examining a lighting intervention

in common living areas in eight aged care facilities. A conference
abstract and thesis have been published showing the results of the
study. There is insuCicient information in the conference abstract
and thesis to determine if the study should be included.

Excluded studies

We excluded 406 studies following full-text review; 290 were
excluded due to ineligible study design, such as the study only had
one intervention and control site or was a longitudinal study but did
not have a measure before the intervention, i.e. before admission to
a facility; 100 were excluded because the intervention was ineligible
such as temporary therapies or changes to care practices without
any changes to the environmental design of the facilities; and
16 were excluded because the care setting was ineligible such as
living in an assisted living setting with no nursing care required.
The Characteristics of excluded studies section details the reason
for exclusion of studies which might be expected to be included in
this review to explain why they are excluded.

Risk of bias in included studies

See Figure 2 and Figure 3.

 

Figure 2.   Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages
across all included studies.

Random sequence generation (selection bias)
Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias): All outcomes
Blinding of outcome assessment (detection bias): All outcomes

Incomplete outcome data (attrition bias): All outcomes
Selective reporting (reporting bias)

Other bias
Intervention independent of other changes (ITS)

Shape of the intervention effect pre-specified (ITS)
Intervention unlikely to affect data collection (ITS)

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

 
 

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Figure 3.   Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.

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Afendulis 2016 – – – – ? ? –

Annerstedt 1993 – – – – – + –
Burack 2012 – – – – ? – –

Chenoweth 2014 + ? – – ? + +
Dettbarn-Reggentin 2005 – – – – – – –

Diaz-Veiga 2014 – – – – ? + –
Elmstahl 1997 – – – – + – ?
Figueiro 2019 ? ? ? ? ? + +

Frisoni 1998 – – – – + + –
Galik 2021 + ? – – ? + ?

Hopkins 2017 ? ? – – – ? ?
Kenkmann 2010 – – – – – + –

Marcy-Edwards 2011 – + + + ? – +
Mathey 2001 ? ? – ? – ? –

Nijs 2006 – + – ? – + –
Riemersma-vanDerLek 2008 + + + + – + +

Te Boekhorst 2009 – – – – – + –
Wolf-Ostermann 2012 – – – – – + –

Wylie 2001 – – – – – + –
Yoon 2015 – – – – – ? –

 

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Allocation

Random sequence generation

Thirteen studies were rated as having high risk of bias because
randomisation was not applied (Afendulis 2016; Annerstedt 1993;
Burack 2012; Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Elmstahl
1997; Frisoni 1998; Kenkmann 2010; Te Boekhorst 2009; Wolf-
Ostermann 2012; Wylie 2001; Yoon 2015) or a non-random
component to sequence generation (including the first letter of
the ward name) was used (Nijs 2006). Three studies (Chenoweth
2014; Galik 2021; Riemersma-vanDerLek 2008)  were rated as
having low risk of bias as they described an appropriate
method of randomisation. Three studies (Figueiro 2019; Hopkins
2017; Mathey 2001) were rated as having unclear risk of bias
because randomisation was stated, but no  specific details were
reported. Marcy-Edwards 2011 was a repeated measures study and
therefore this was not applicable.

Allocation concealment

Thirteen studies were rated as having high risk of bias because
randomisation was not applied (Afendulis 2016; Annerstedt 1993;
Burack 2012; Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Elmstahl
1997; Frisoni 1998; Kenkmann 2010; Marcy-Edwards 2011; Te
Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001; Yoon 2015). Two
studies were rated as having low risk of bias because adequate
allocation concealment was reported (Nijs 2006; Riemersma-
vanDerLek 2008). Five studies was rated at unclear risk of
bias because allocation concealment details were not specified
(Figueiro 2019; Galik 2021; Hopkins 2017; Mathey 2001) or  it was
unclear where the randomisation sequence was stored (Chenoweth
2014).

Blinding

Blinding of participants and personnel

One study was rated as having low risk of bias as blinding of
outcome assessment and blinding of participants and personnel
were both adequately described (Riemersma-vanDerLek 2008).
Seventeen studies were rated at high risk of bias for blinding of
participants and personnel as this was not feasible (e.g. where
residents or staC who are aware of group allocation provided the
data) (Afendulis 2016; Annerstedt 1993; Burack 2012; Chenoweth
2014; Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Elmstahl 1997;
Frisoni 1998; Galik 2021; Hopkins 2017; Kenkmann 2010; Mathey
2001; Nijs 2006; Te Boekhorst 2009; Wolf-Ostermann 2012; Wylie
2001; Yoon 2015).  One study was rated as having unclear risk of
bias as the study stated “facility staC were not informed of any
diCerences between the lighting interventions”, but it was unclear if
any diCerences had been observed (Figueiro 2019). Marcy-Edwards
2011  was a repeated measures study and therefore this was not
applicable.

Blinding of outcome assessment

Three studies were rated as having unclear risk of bias as none
reported specific details of blinding (Figueiro 2019; Mathey 2001;
Nijs 2006). One study was rated as having low risk of bias as
adequate descriptions of blinding of the outcome assessment
was provided (Riemersma-vanDerLek 2008). FiJeen studies used
outcomes where blinding was not feasible (e.g. residents or
staC who were aware of group allocation provided the data)
(Afendulis 2016; Annerstedt 1993; Burack 2012; Chenoweth 2014;

Dettbarn-Reggentin 2005; Diaz-Veiga 2014; Galik 2021; Te Boekhorst
2009; Wolf-Ostermann 2012; Wylie 2001; Yoon 2015) or outcome
assessment was not blinded (Elmstahl 1997; Frisoni 1998; Hopkins
2017; Kenkmann 2010).  Marcy-Edwards 2011  was a repeated
measures study and therefore this was not applicable.

Incomplete outcome data

Eleven studies were rated as having high risk of bias as there
was high loss to follow-up (> 20%) (Annerstedt 1993; Dettbarn-
Reggentin 2005; Hopkins 2017; Kenkmann 2010; Mathey 2001;
Nijs 2006; Riemersma-vanDerLek 2008; Te Boekhorst 2009; Wolf-
Ostermann 2012; Wylie 2001; Yoon 2015). Eight studies were rated
at unclear risk of bias due to  information not being provided
by group allocation (Burack 2012), or the reasons for dropout
(Chenoweth 2014), did not report loss to follow-up over time
(Afendulis 2016; Diaz-Veiga 2014; Figueiro 2019) or reported large
loss to follow-up, 30% aJer randomisation, but it was unclear which
randomised group the participants belonged to (Galik 2021). Three
studies were rated at low risk of bias due to adequate (> 85%, Marcy-
Edwards 2011  and > 90%,  Elmstahl 1997) or no loss to follow-up
(Frisoni 1998).

Selective reporting

Thirteen studies were rated as having low risk of bias as their
results matched what was reported in a protocol, trial registration
or methods section for non-randomised studies which did not have
a protocol  (Annerstedt 1993; Chenoweth 2014; Diaz-Veiga 2014;
Figueiro 2019; Frisoni 1998; Galik 2021; Kenkmann 2010; Marcy-
Edwards 2011; Nijs 2006; Riemersma-vanDerLek 2008; Te Boekhorst
2009; Wolf-Ostermann 2012; Wylie 2001). Three studies were rated
at high risk of bias due to not reporting outcomes which were
described in the methods (Burack 2012; Dettbarn-Reggentin 2005;
Elmstahl 1997). Four studies were rated at unclear risk of bias
because they did not have published protocols and were based on
data from the Minimum DataSet (MDS) which included many fields
from the MDS which were not reported; (Afendulis 2016; Yoon 2015)
or were randomised trials that did not report details of a study
protocol or trial registration (Hopkins 2017; Mathey 2001).

Other potential sources of bias

Thirteen studies were rated at high risk of bias (Afendulis 2016;
Annerstedt 1993; Burack 2012; Dettbarn-Reggentin 2005; Diaz-
Veiga 2014; Frisoni 1998; Kenkmann 2010; Mathey 2001; Nijs
2006; Te Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001; Yoon
2015). Reasons for being rated at high risk of bias included
diCerences in baseline characteristics (Afendulis 2016, Annerstedt
1993, Burack 2012, Frisoni 1998, Kenkmann 2010, Mathey 2001, Nijs
2006, Te Boekhorst 2009; Wylie 2001, Wolf-Ostermann 2012, Yoon
2015), diCerences in baseline outcome measures (Afendulis 2016;
Annerstedt 1993; Burack 2012; Dettbarn-Reggentin 2005; Diaz-
Veiga 2014; Frisoni 1998) and potential for contamination (Mathey
2001; Wylie 2001). Twelve studies were non-randomised studies,
therefore residual confounding was a potential source of bias
(Afendulis 2016; Annerstedt 1993; Burack 2012; Dettbarn-Reggentin
2005; Diaz-Veiga 2014; Elmstahl 1997; Frisoni 1998; Kenkmann 2010;
Te Boekhorst 2009; Wolf-Ostermann 2012; Wylie 2001; Yoon 2015).
Three studies were rated at unclear risk of bias (Elmstahl 1997;
Galik 2021; Hopkins 2017); two studies did not report baseline
characteristics by group allocation (Elmstahl 1997; Hopkins 2017);
one study reported outcome measures in little detail (Hopkins
2017); and in one study there appeared to be diCerences in one

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of the outcomes but no statistical analysis was performed (Galik
2021). Four studies were rated at low risk of bias for having no
statistically significant diCerences between groups at baseline,
no statistically significant diCerences in outcome measures at
baseline, having the intervention assigned at the level of the
care facility and no other potential sources of bias identified
(Chenoweth 2014; Figueiro 2019; Marcy-Edwards 2011; Riemersma-
vanDerLek 2008).

Intervention independent of other changes

Marcy-Edwards 2011 was a repeated measures study and therefore
the criteria for risk of bias also included ‘intervention independent
of other changes’, and was rated as having unclear risk of bias as
it was not reported that the intervention was not independent of
other changes in time nor was there compelling evidence that the
intervention was independent.

Shape of the intervention e”ect prespecified

Marcy-Edwards 2011 was also rated at high risk of bias for ‘shape
of the intervention eCect prespecified’ because the baseline data
collection was spread over four weeks.

Intervention unlikely to a”ect data collection

Marcy-Edwards 2011 was rated at low risk of bias for ‘intervention
unlikely to aCect data collection’ as the sources and methods of
data collection were the same before and aJer the intervention.

E?ects of interventions

See: Summary of findings 1 Whole-facility changes: Home-like
models compared to traditional environment for older people
living in long-term residential care

Whole-facility model

A summary of the evidence for home-like in comparison to
traditional models of care is provided in Summary of findings 1.

Home-like model versus traditional environment

Six controlled before-aJer studies compared the home-like model
and the traditional environment (136,419 participants) (Afendulis
2016; Annerstedt 1993; Dettbarn-Reggentin 2005; Te Boekhorst
2009; Wolf-Ostermann 2012; Yoon 2015). One controlled before-
aJer study did not report participant numbers according to their
exposure (Afendulis 2016).

Health-related quality of life

It is uncertain whether home-like models improved health-related
quality of life because the certainty of the evidence is very low
(1 study; 33 participants; very low-certainty evidence). No eCect
estimate could be derived because of the unavailability of the data.
The certainty of the evidence was downgraded from low-certainty
to very low-certainty because of very serious concerns due to risk
of bias and imprecision.

One controlled-before aJer study examined quality of life (Wolf-
Ostermann 2012). Outcomes were measured at baseline, six
months and 12 months by examining multiple domains from
the QUALIDEM, where high scores indicate better quality of
life.  Although 56 participants were included in the study, only
33 participants completed the follow-up and were included
in the analysis. The authors examined nine domains of the

QUALIDEM including care relationship, feeling at home, social
relations, positive self-image, restless tense behaviour, having
something to do, positive aCect, negative aCect and social
isolation. Two  domains (feeling at home and care relationship)
were examined in analyses adjusted for baseline diCerences
between the groups and the seven other domains were examined in
unadjusted analyses. The author stated “no statistically significant
diCerences were observed between the intervention and control
groups.” (Analysis 1.1).

Behaviour, mood and depression

It is uncertain whether home-like models improved behaviour,
mood and depression because the certainty of the evidence
is very low (3 studies for global behaviour; 257 participants;
very low-certainty evidence, and two studies for depression; 406
participants; very low-certainty evidence).  The certainty of the
evidence was downgraded from low-certainty to very low-certainty
because of very serious concerns due to risk of bias, and also
serious concerns due to imprecision for global behaviour. Meta-
analyses could not be completed because of diCerences in the
outcomes reported.

Five controlled before-aJer studies compared the home-like model
to a traditional environment (625 participants) and reported
data for a home-like model versus traditional environment on
behaviour, mood and depression outcomes (Annerstedt 1993;
Dettbarn-Reggentin 2005; Wolf-Ostermann 2012; Yoon 2015; Te
Boekhorst 2009). Two studies (Annerstedt 1993; Wolf-Ostermann
2012) reported results for sub-domains of behaviour, three studies
(Dettbarn-Reggentin 2005,  Te Boekhorst 2009    Wolf-Ostermann
2012) examined global behaviour, two studies (Yoon 2015; Te
Boekhorst 2009) examined social engagement and two studies
(Yoon 2015; Te Boekhorst 2009) examined depression.

For global behaviour, Te Boekhorst 2009 used the Neuropsychiatric
Inventory (NPI), Wolf-Ostermann 2012 used the NPI-Nursing Home
version (NPI-NH) and  Dettbarn-Reggentin 2005  examined global
behaviour using the Nurses Observation Scale for Geriatric Patients
(NOSGER). For depression,  Te Boekhorst 2009  used the Revised
Memory and Behaviour Problems Checklist (RMBPC) and  Yoon
2015  used the Mood Scale Score (MSS). For subdomains of
behaviour,  Annerstedt 1993  used the Organic Brain Syndromes
(OBS) scale to report outcomes for dyspraxia, hallucinations,
lack of vitality, dysphasia, paranoia, aggressiveness, depression,
clinical variations, restlessness, and Wolf-Ostermann 2012 used the
Cohen-Mansfield Agitation Inventory (CMAI) to report changes in
verbal agitation, physical non-aggressive and physical aggressive
behaviour. For all of these measures, lower scores indicate fewer
behavioural symptoms. For social engagement,  Yoon 2015  used
the Index of Social Engagement (ISE) and Te Boekhorst 2009 used
Revised Index of Social Engagement (RISE), and higher scores
indicate better social engagement.

Behaviour, mood and/or depression outcomes were examined at
baseline (Annerstedt 1993; Dettbarn-Reggentin 2005; Te Boekhorst
2009; Wolf-Ostermann 2012; Yoon 2015), three months (Yoon
2015), six months (Annerstedt 1993,  Dettbarn-Reggentin 2005,Te
Boekhorst 2009,  Wolf-Ostermann 2012,  Yoon 2015), nine months
(Yoon 2015), 12 months (Annerstedt 1993,  Dettbarn-Reggentin
2005,  Wolf-Ostermann 2012,  Yoon 2015), 15 months (Yoon 2015),
and 18 months (Yoon 2015).

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Dettbarn-Reggentin 2005  did not adjust results for baseline
diCerences between the groups, but the authors stated there was
a “significant influence of the residential group environment on
the social behaviour and state of mind of the residents”. The
results from  Wolf-Ostermann 2012  stated for global behaviour:
“interactions between settings and development over time could
not be proved”. No eCect estimate for Wolf-Ostermann 2012 could
be derived because of the reporting of the data.  Results from  Te
Boekhorst 2009 suggested little or no diCerence in global behaviour
(mean diCerence (MD): -0.04, 95% Confidence Interval (CI) -0.13 to
0.04; Analysis 1.2.1; 1 study).

Results on depression outcomes could not be combined in a meta-
analysis because  Yoon 2015  examined the change of depression
and probability of having zero depressive symptoms whereas  Te
Boekhorst 2009  reported the endpoint depression results.  Yoon
2015  indicated an increase in depressive symptoms over 18
months with a home-like model of care (rate ratio 1.15, 95% CI
1.02 to 1.29;  Analysis 1.2.2; 1 study with 242 participants), but
the eCect on the probability of zero depressive symptoms was
uncertain (odds ratio (OR) 0.36, 95% CI 0.12 to 1.07;  Analysis
1.2.2; 1 study).  Te Boekhorst 2009  found little or no diCerence
in depressive symptoms at six months (MD 0.01, 95% CI -0.12
to 0.14;  Analysis 1.2.2; 1 study). It is uncertain whether home-
like models of care improve depressive symptoms because the
certainty of this evidence is very low.

Annerstedt 1993 reported that “a diCerence in clinical changes was
significant” between the intervention and control groups aJer six
months in dyspraxia (spatial disorientation) and depression, but
aggressiveness increased among the intervention group (Analysis
1.2.3).  Wolf-Ostermann 2012  found little or no eCect on verbal
agitation, physical non-aggressive or physical aggressive behaviour
with the home-like model.

Results for social engagement could not be combined in a
meta-analysis because  Yoon 2015  examined the change of social
engagement and probability of not being socially engaged over 18
months, whereas  Te Boekhorst 2009  reported social engagement
over six months.  Yoon 2015  had contradictory findings with little
or no diCerence in change in the level of social engagement over
18 months (rate ratio 0.99, 95% CI 0.82 to 1.19;  Analysis 1.2.4; 1
study with 242 participants), but an increase in probability of social
engagement (a decrease in the probability of not being socially
engaged) for those in a home-like model of care (OR 0.76, 95% CI
0.62 to 0.94;  Analysis 1.2.4; 1 study).  Te Boekhorst 2009  found an
increase in social engagement at six months (MD 0.79, 95% CI 0.11
to 1.50; Analysis 1.2.4; 1 study with 164 participants). It is uncertain
whether home-like models of care improve social engagement
because the certainty of this evidence is very low.

Function

It is uncertain whether home-like models improved function
because the certainty of the evidence is very low (4 studies;
499 participants; very low-certainty evidence).  The certainty of
evidence was downgraded from low-certainty to very low-certainty
because of very serious concerns due to risk of bias and serious
concerns due to imprecision (499 participants in total across
outcomes but reported across diCerent measures and at diCerent
time points). Meta-analyses could not be completed because of
diCerences in follow-up times and availability of data.

Four controlled before-aJer studies (499 participants) assessed
function (Dettbarn-Reggentin 2005; Te Boekhorst 2009; Wolf-
Ostermann 2012; Yoon 2015). To measure function,  Yoon
2015  used the Activities of Daily Living (ADL)-long form scale,  Te
Boekhorst 2009  used the Interview for the Deterioration of Daily
Living activities in Dementia (IDDD) and both  Wolf-Ostermann
2012 and Dettbarn-Reggentin 2005 used the Barthel Index. Lower
scores indicate better function for the ADL-long-form scale and
IDDD, whereas higher scores indicate better function for the Barthel
Index.

Function was measured at three months (Yoon 2015), six months
(Te Boekhorst 2009,  Yoon 2015,  Wolf-Ostermann 2012), nine
months (Yoon 2015), 12 months (Yoon 2015  ,  Wolf-Ostermann
2012, Dettbarn-Reggentin 2005) and 18 months (Yoon 2015).

Wolf-Ostermann 2012  stated for functional status: “interactions
between settings and development over time could not be
proved”. Dettbarn-Reggentin 2005 stated that function declined in
both the intervention and control groups, but function declined
“more sharply” in the control group (Analysis 1.3).

Yoon 2015 reported little or no diCerence in change in function over
18 months aJer admission (MD -0.09, 95% CI -0.46 to 0.28; Analysis
1.3; 1 study).  Te Boekhorst 2009  reported an increase in function
(decreased IDDD score) for those in a home-like model of care six
months aJer admission (MD -4.37, 95%CI -7.06 to -1.69; Analysis 1.3;
1 study).

Global cognitive function

It is uncertain whether home-like models improved global cognitive
function because the certainty of the evidence is very low (4 studies;
569 participants; very low-certainty evidence).  The certainty of
evidence was downgraded from low-certainty to very low-certainty
because of very serious concerns due to risk of bias and imprecision
(569 participants in total across outcomes but reported across
diCerent measures and at diCerent time points).  Meta-analyses
could not be completed because of diCerences in follow-up times
and availability of data.

Four controlled before-aJer studies (569 participants) reported
global cognitive function as an outcome (Dettbarn-Reggentin
2005; Te Boekhorst 2009; Wolf-Ostermann 2012; Yoon 2015).
Two studies used the Mini-Mental State Examination (MMSE)
(Dettbarn-Reggentin 2005; Wolf-Ostermann 2012), one study used
the standardised MMSE (Te Boekhorst 2009) and one study used
the Cognitive Performance Scale (CPS) (Yoon 2015). Higher scores
indicate better global cognitive function, except for the CPS where
lower scores indicate better global cognitive function.

Global cognitive function was measured at three months (Yoon
2015), six months (Te Boekhorst 2009, Yoon 2015, Wolf-Ostermann
2012), nine months (Yoon 2015), 12 months (Yoon 2015  ,  Wolf-
Ostermann 2012,  Dettbarn-Reggentin 2005) and 18 months (Yoon
2015).

Yoon 2015  did not conduct any analysis to examine the evidence
of an eCect, and the means reported were unadjusted for potential
confounding factors. Dettbarn-Reggentin 2005 suggested a sharper
decline in MMSE scores over time for the control group compared
to the intervention group, but the results were not adjusted for
potential confounding factors.  Wolf-Ostermann 2012  suggested
better MMSE scores for those in a home-like model of care at

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baseline to six months and little or no diCerence at 12 months,
but the results were also not adjusted for potential confounding
factors (Analysis 1.4).  The results from the study by  Te Boekhorst
2009 showed that home-like models of care made no diCerence to
global cognitive function   (MD 0.54, 95% CI -1.43 to 2.50;  Analysis
1.4; 1 study).

Quality of care

It is uncertain whether home-like models of care improved quality
of care because the certainty of the evidence is very low (1
study; weighted estimate 74,449 participants; very low-certainty
evidence). The certainty of evidence was downgraded from low-
certainty to very low-certainty because of very serious concerns due
to risk of bias.

One controlled before-aJer study (weighted estimate 74,449
participants at enrolment) examined quality of care by reporting
the number of bedfast residents, catheter use, high-risk pressure
ulcers, low-risk pressure ulcers, hospital readmissions and
avoidable hospital readmissions as proxy measures for quality
of care (Afendulis 2016).  Afendulis 2016  comprised the majority
of the participants in this review, but did not examine any of
the primary outcomes.  Quality of care outcomes were assessed
between January 1, 2005 and September 30, 2010 to determine
the frequency of occurrence. The study estimated diCerence-
in-diCerence regression coeCicients for the pre-post diCerence
in the home-like model homes minus the pre-post diCerence
in traditional homes. The coeCicients suggested the diCerence
in percentage points (e.g. percentage of hospital readmissions)
between the home-like model of care and traditional model, with
lower scores indicating better quality of care according to the proxy
measures. The follow-up time in this study was unclear.

For those in a home-like model of care,  Afendulis 2016  reported
a reduction in the number of bedfast residents (MD -0.3%, 95%
CI -0.4% to -0.2%;  Analysis 1.5; 1 study), catheter use (MD -4.1%,
95% CI -6.1% to -2.1%;  Analysis 1.5; 1 study), low-risk pressure
ulcers (MD -1.9%, 95%CI -2.5% to -1.3%;  Analysis 1.5; 1 study),
hospital readmissions (MD -5.5%, 95% CI -10.2% to -0.8%; Analysis
1.5; 1 study) and avoidable hospital readmissions (MD -3.9%, 95%
CI -7.6% to -0.2%;  Analysis 1.5;  1 study).  AJer accounting for
multiple comparisons, the authors indicated that these diCerences
were statistically significant. Whilst these diCerences may be small
in percentage terms (representing a range of 0.3% for bedfast
residents, to 5.5% for hospital readmissions), given the large
numbers of residents living in aged care homes, these values
could translate to large numbers of individuals at a regional or
national level. Any improvement in such critical outcomes that
are likely to impact on quality life may be considered clinically
meaningful.  Afendulis 2016  reported that a home-like model of
care may have little to no eCect on high-risk pressure ulcers (MD
-1.2%, -3.8% to 1.4%; Analysis 1.5; 1 study), but the evidence is very
uncertain.

Serious adverse e”ects

It is uncertain whether  home-like models of care reduce physical
restraint use as the certainty of the evidence is very low (one study;
weighted estimate 74,449 participants). The certainty of evidence
was downgraded from low to very low due to very serious concerns
about the risk of bias.

One controlled before-aJer study (Afendulis 2016)  examined
serious adverse eCects. This study reported a slight reduction in
the use of physical restraints for those in a home-like model of care
(MD -0.3%, 95%CI -0.5% to -0.1%;  Analysis 1.5; 1 study) between
January 1, 2005 and September 30, 2010 (Afendulis 2016). The
authors conducted analyses accounting for multiple comparisons
and reported that this finding was not statistically significant. As
discussed above, although the diCerence observed represented
0.3% of residents, any improvement observed in such a critical
outcome is potentially clinically meaningful. No other serious
adverse eCects were examined or reported in any of the included
studies. However, as the certainty of the evidence is considered very
low, there is uncertainty in this finding.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Refurbishment versus traditional environment

Five studies examined refurbishment of care homes in conjunction
with measures to develop person-centred care compared to
a traditional environment (1357 participants). Three studies
were controlled before-aJer studies (Burack 2012; Diaz-Veiga
2014; Wylie 2001) and two studies were cluster-randomised
trials (Chenoweth 2014; Galik 2021).  Burack 2012  examined
refurbishment in conjunction with person-centred care referred to
as ‘culture change’ compared to a traditional environment and
traditional care.  Diaz-Veiga 2014  examined refurbishment using
the Etxean Ondo model which aims to develop a domestic setting
in conjunction with person-centred care.  Wylie 2001  examined
refurbishment using the Eden Alternative which introduces pets,
plants and children in addition to person-centred care. One
cluster-randomised trial (Chenoweth 2014) studied the eCect of
a person-centred environment (with or without person-centred
care) compared to a traditional environment and traditional
care, and the development of the person-centred environment
and person-centred care involved the use of the Person-Centred
Environment and Care Assessment Tool (PCECAT). A diCerent
cluster-randomised trial (Galik 2021) examined an intervention
called Function and Behavior Focused Care for the Cognitively
Impaired (FBFC) compared to an education-only control group.
Within the FBFC intervention, FBFC research nurses examined the
environment to identify opportunities for physical activity and
engaging in functional tasks as well as barriers to these activities
and based on these assessments, modifications in policy and the
environment were made.

Health-related quality of life

It is uncertain whether refurbishment comprising of a person-
centred environment improved health-related quality of life
because the certainty of the evidence is very low (MD 3.00, 95%
CI -1.91 to 7.91; 1 study; 143 participants; very low-certainty
evidence; Analysis 2.1). The certainty of evidence was downgraded
from high-certainty to very low-certainty  due  to very serious
concerns because of risk of bias and serious concerns due
to imprecision. A further two studies examined the impact of
refurbishment on quality of life, but these were not randomised
trials and due to heterogeneity in the interventions, a meta-analysis
was not performed.

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Three studies (820 participants) examined quality of life
(Chenoweth 2014; Diaz-Veiga 2014; Wylie 2001) comparing
refurbishment with the traditional environment. One study was
a randomised trial (Chenoweth 2014) and two were controlled
before-aJer studies (Diaz-Veiga 2014; Wylie 2001).

Quality of life was measured using DEMQOL Proxy (Chenoweth
2014), FUMAT scale (Diaz-Veiga 2014), QUALID scale (Diaz-Veiga
2014) or Life Satisfaction Index (LSI) (Wylie 2001). For all of these
measures, higher scores indicate better quality of life, except the
Qualid where lower scores indicate better quality of life. Quality
of life was measured at baseline (Chenoweth 2014; Diaz-Veiga
2014; Wylie 2001), six months (Diaz-Veiga 2014; Wylie 2001), four
months  (Chenoweth 2014),  eight months (Chenoweth 2014), 12
months (Wylie 2001), and 18 months (Wylie 2001).

A mean diCerence in  quality of life with refurbishment, with and
without person-centred care (PCC), compared with a traditional
environment was estimated post-intervention (with PCC: MD 3.00,
95% CI -1.20 to 7.20; without PCC: MD 2.00, 95% CI -2.19 to 6.19) and
at eight months (with PCC: MD 2.00, 95% CI -2.91 to 6.91; without
PCC: MD 3.00, 95% CI -1.91 to 7.91) (Chenoweth 2014). It is uncertain
whether a person-centred environment, with or without person-
centred care improves quality of life because the certainty of this
evidence is very low.

Findings from the two controlled before-aJer studies were
uncertain (Analysis 2.1). Diaz-Veiga 2014 reported that “in the post-
study phase, the experimental group showed much  better  levels
in quality of life (QUALID) in comparison to the control group”, but
the authors did not adjust the results for the baseline diCerences
between the groups.

For individuals  with mild levels of cognitive impairment, the
authors stated no “significant diCerences” between the groups
were recorded at the post-evaluation stage. Wylie 2001 also did not
adjust for baseline diCerences between the groups.

Behaviour, mood and depression

It is uncertain whether refurbishment comprising of a person-
centred environment improved agitation because the certainty
of the evidence is very low (1 study; 143 participants; MD 4.00,
95% CI -9.21 to 17.21; very low-certainty evidence). The certainty
of evidence was downgraded from high-certainty to very low-
certainty due to very serious concerns because of risk of bias and
serious concerns due to imprecision. Refurbishment comprising
the FBFC intervention may make little or no diCerence to agitation
or depression (agitation: MD -0.72, 95% CI -2.63 to 1.20, 1 study,
  low-certainty evidence; depression: MD -0.73, 95% CI -1.93 to
0.47,1 study ; low-certainty evidence).  The certainty of evidence
was downgraded from high-certainty to low-certainty because of
serious concerns due to risk of bias and serious concerns due
to imprecision. One further non-randomised study examined the
impact of refurbishment on behaviour, mood and depression, but
due to heterogeneity in the interventions and follow-up times, a
meta-analysis was not performed.

Three studies (1138 participants) examined behaviour (Burack
2012  ;  Chenoweth 2014; Galik 2021).  Chenoweth 2014  and  Galik
2021 are randomised trials while Burack 2012 is a controlled before-
aJer study. All three studies used the Cohen-Mansfield Agitation
Inventory (CMAI) for outcome measurement, where lower scores
indicate fewer behavioural symptoms. Behaviour was measured

at baseline (Burack 2012; Chenoweth 2014; Galik 2021), four
months  (Chenoweth 2014; Galik 2021),  eight months (Chenoweth
2014),  12 months (Galik 2021) and 24 months (Burack 2012). One
study (Galik 2021) also examined resistiveness to care using the
Resistiveness to Care Scale where lower scores indicate lower
resistive behaviours, and depression using the Cornell Scale for
Depression in Dementia (CSDD) where lower scores indicate fewer
depressive symptoms.

The FBFC intervention may make little or no diCerence to
depression compared to an education control (low-certainty
evidence) aJer four months (MD -0.73, 95% CI -1.93 to 0.47; Analysis
2.2.1; 1 study) or 12 months follow-up (MD -0.04, 95% CI -1.35
to 1.26;  Analysis 4.1; 1 study). This intervention may also make
little or no diCerence to agitation (low-certainty evidence) at four
months (MD -0.72, 95% CI -2.63 to 1.20; Analysis 2.2.2; 1 study) or
12 months follow-up (MD -0.36, 95% CI -2.41 to 1.69; Analysis 2.2.2;
1 study). The FBFC intervention may make little or no diCerence
to resistiveness to care (4 months, MD -1.56, 95% CI -2.71 to
-0.40; Analysis 2.2.2; 1 study; 12 months, MD 0.32, 95% CI -0.29 to
0.94; Analysis 2.2.2; 1 study).

Burack 2012 examined refurbishment in combination with ‘culture
change’ and reported a slight reduction in forceful behaviours
(MD -0.06, 95% CI -0.10, -0.02;  Analysis 2.2.2;  1 study with 101
participants) and physical agitation (MD -0.070, 95% CI -0.136 to
-0.004; Analysis 2.2.2; 1 study), but little or no diCerence in verbal
agitation (MD 0.110, 95% CI -0.004 to 0.224; Analysis 2.2.2; 1 study).
However, the impact of the intervention on behaviour is uncertain
because the certainty of this evidence is considered very low.

The eCect of a person-centred environment on agitation, with or
without PCC, was uncertain (without PCC: MD 2.00, 95% CI -11.29
to 15.29; Analysis 2.2.2; 1 study; with PCC: MD 7.00, 95% CI -5.66 to
19.66; Analysis 2.2.2; 1 study post-intervention; 8 months follow-up
without PCC: MD 4.00, 95% CI -9.21 to 17.21; Analysis 2.2.2; 1 study;
with PCC: MD 13.00, 95% CI -0.22 to 26.22; Analysis 2.2.2; 1 study;
very low-certainty evidence).

Function

Refurbishment may make little or no diCerence to function (low-
certainty evidence). The certainty of evidence was downgraded
from high to low due to serious concerns about risk of bias and
imprecision. One randomised controlled trial examined the FBFC
intervention with the Barthel index, where higher scores indicate
better function (Analysis 2.3; 4 months: MD 1.24, 95% CI -3.34
to 5.81; 12 months: MD 1.49, 95% CI -3.53 to 6.50; 1 study, 336
participants).

Global cognitive function

No included studies reported on outcomes for global cognitive
function.

Quality of care

It is uncertain whether refurbishment comprising of a person-
centred environment improves quality of care because the
certainty of this evidence is very low (1 study; 143 participants;
MD 0.00, 95% CI -8.34 to 8.34; very low-certainty evidence). The
certainty of evidence was downgraded from high-certainty to very
low-certainty because of very serious concerns due to risk of bias
and serious concerns due to imprecision.

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One randomised controlled trial examined quality of care (601
participants) from refurbishment compared to the traditional
environment (Chenoweth 2014) using the Quality of Interactions
Schedule (QUIS), where higher scores indicate better quality of
care. The outcome was measured at baseline, four months (post-
intervention) and eight months. The findings suggested an increase
in quality of care at post-intervention for the intervention group
both with or without PCC (without PCC: MD 8.00, 95% CI 1.03 to
14.97;  Analysis 2.4; 1 study; with PCC: MD 13.00, 95% CI 6.02 to
19.98;  Analysis 2.4; 1 study; post-intervention). At eight months
(four months aJer the intervention), the eCect on quality of care
was uncertain (without PCC: MD 0.00, 95% CI -8.34 to 8.34; Analysis
2.4; 1 study; with PCC: MD -2.00, 95% CI -9.67 to 5.67; Analysis 2.4;
1 study).

Serious adverse e”ects

No included studies reported on outcomes for serious adverse
eCects.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Special care units versus traditional environment

One controlled before-aJer study (66 participants) examined
a special care unit for people with dementia compared with
a traditional environment (Frisoni 1998). The results were not
considered suitable to contribute to the quantitative analysis as
they were unadjusted for diCerences in baseline characteristics of
the participants.

Health-related quality of life

No included studies reported quality of life.

Behaviour, mood and depression

It is uncertain whether special care units for people with
dementia improved behaviour because the certainty of the
evidence is very low. Frisoni 1998 examined global behaviour and
subdomains including delusions, hallucinations, agitation, anxiety,
euphoria/elation, disinhibition, irritability/lability, abnormal motor
behaviour and sleep using the Neuropsychiatric Inventory (NPI),
agitation using the CMAI and depression using the Cornell
Depression Scale. For all measures, lower scores indicate fewer
behavioural symptoms and these were measured at baseline and
three months.

In this study, the unadjusted results suggested special care units
were associated with a reduction in global behaviour (Analysis
3.1.1), depressive symptoms (Analysis 3.1.2) and in delusions,
hallucinations, agitation and sleep (Analysis 3.1.3). The traditional
environment was also associated with  a reduction in global
behaviour (Analysis 3.1.1), reduction in anxiety and euphoria/
elation (Analysis 3.1.3), but conversely was associated with an
increase in depressive symptoms (Analysis 3.1.2); however, the
certainty of evidence is very low. The eCect of special care units
on agitation measured by CMAI demonstrated at three months was
uncertain (Analysis 3.1.3).

Function

It is uncertain whether special care units for people with dementia
improved function because the certainty of the evidence is very
low.  Frisoni 1998  examined function using two measures: the
Bedford Alzheimer’s nursing severity scale and the Barthel Index;
for both measures, higher scores indicate better function. Function
was measured at baseline and three months. The eCect of special
care units on function using either of the measures was uncertain
(Analysis 3.2).

Global cognitive function

Cognitive function was assessed in  Frisoni 1998  using the MMSE
(higher scores indicate better cognitive function) and Extended
Clinical Dementia Rating (higher scores indicate more severe
cognitive impairment). Global cognitive function was measured
at baseline and three months. The eCect of special care units
on cognitive function was uncertain using either of the measures
investigated (Analysis 3.3).

Quality of care

No included studies reported on outcomes for quality of care.

Serious adverse e”ects

Frisoni 1998 investigated serious adverse eCects by the frequency
of falls and use of physical restraints at baseline and three months,
but it was unclear if the numbers were referring to the overall
number of falls and use of physical restraints or the number of
people who fell or were exposed to physical restraints; therefore,
these data were not included in this review. It was uncertain if there
was a diCerence in falls at three months between the intervention
and control groups, but for physical restraints the authors reported
that “while their use in cases did not increase aJer 3 months, a
significant increase was apparent in controls”.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Corridor versus non-corridor design

One controlled before-aJer study (105 participants) examined a
corridor design compared with a non-corridor design in group living
units (Elmstahl 1997).

Health-related quality of life

No included studies reported on outcomes for quality of life.

Behaviour, mood and depression

It is uncertain whether a corridor design or non-corridor design
improves behaviour, mood and depression because the certainty
of evidence was very low (OR 8.82, 95% CI 1.14 to 68.22 for
depression, 1 study; 105 participants; very low-certainty evidence).
The certainty of evidence was downgraded from low-certainty to
very low-certainty because of very serious concerns due to risk of
bias and serious concerns due to imprecision.

Elmstahl 1997  examined 11 sub-domains of behaviour using the
Organic Brain Syndrome (OBS) scale including aggressiveness,
depression, dyspraxia, hallucinations, lack of vitality, dysphasia,

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paranoia, restlessness, disorientation (recent memory, time and
identity), and lower scores indicate better behaviour. Behaviour
was measured at baseline and 12 months. Results were analysed as
the proportion of participants who experienced the behaviours and
odds ratios < 1 favoured the corridor design.

Elmstahl 1997  reported a decrease in depression for those in the
non-corridor design compared to the corridor design (OR 8.82,
95% CI 1.14 to 68.22;  Analysis 4.1.1; 1 study). The eCect of a non-
corridor design compared to a corridor design on other behavioural
measures was uncertain (aggressiveness: OR 2.02, 95% CI 0.56 to
7.27; dyspraxia: OR 4.57, 95% CI 0.76 to 27.35; hallucinations: OR
1.06, 95% CI 0.05 to 22.09; lack of vitality: OR 0.23, 95% CI 0.04 to
1.47; dysphasia: OR 0.87, 95% CI 0.08 to 9.73; paranoia: OR 0.12,
95% CI 0.01 to 1.24; restlessness: OR 0.21, 95% CI 0.04 to 1.00; recent
memory: OR 0.87, 95% CI 0.31 to 2.42; time: OR 0.66, 95% CI 0.22 to
2.01; identity: OR 1.23, 95% CI 0.56 to 2.68 (Analysis 4.1.2, 1 study).

No included studies reported on outcomes for global behaviour.

Function

No included studies reported on outcomes for function.

Global cognitive function

No included studies reported on outcomes for global cognitive
function.

Quality of care

No included studies reported on outcomes for quality of care.

Serious adverse e”ects

No included studies reported on outcomes for serious adverse
eCects.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Alternative physical environmental design without whole-
facility changes

Lighting intervention versus control lighting

Three cluster-randomised trials (291 participants) studied the eCect
of lighting interventions on long-term residential care compared
to control lighting (Figueiro 2019; Hopkins 2017; Riemersma-
vanDerLek 2008). The studies did not take clustering in to account
in their estimates and provided insuCicient data to correct
analyses for cluster-randomised trials as described in the Cochrane
Handbook (Higgins 2011).

Health-related quality of life

No studies examined quality of life.

Behaviour, mood and depression

It is uncertain whether bright lighting improves global behaviour
because the certainty of this evidence is low (MD 0.50, 95% CI
-1.80 to 2.80; 1 study, 74 participants; low-certainty evidence).
The certainty of evidence was downgraded from high-certainty to
low-certainty because of serious concerns due to risk of bias and

serious concerns due to imprecision. It is uncertain whether bright
lighting improves depression because the certainty of evidence
is very low (SMD -0.22, 95% CI -0.45 to 0.01; 3 studies; very

low-certainty evidence; I2 = 64%). The certainty of evidence was
downgraded from high-certainty to very low-certainty because of
very serious concerns due to risk of bias and serious concerns due
to imprecision.

Riemersma-vanDerLek 2008  examined global behaviour in  94
participants in a randomised trial using the questionnaire format
of the NPI (NPI-Q) and withdrawn behaviour using the Multi
Observational Scale for Elderly Subjects (MOSES) and mood using
the Philadelphia Geriatric Centre ACect Rating Scale (PGCARS).
For all measures, lower scores indicate better behaviour except
for the PGCARS (for positive mood higher scores indicate better
positive mood). Behaviour, mood and depression were measured
at baseline, six weeks, six months, one year, 1.5 years and two years.

Riemersma-vanDerLek 2008  reported little to no eCect on global
behaviour (MD 0.50 (95% CI -1.80 to 2.80) at six months;  Analysis
5.1.1; 1 study; low-certainty evidence).

The eCect of bright lighting on depression was examined
by Riemersma-vanDerLek 2008 and Figueiro 2019 using the Cornell
Scale for Depression in Dementia (CSDD) and Hopkins 2017 using
the depression subset of the hospital anxiety and depression
(HADD) scale. There was little or no diCerence in depression at four
to six weeks (SMD -0.22, 95% CI -0.45 to 0.01; Analysis 5.2; 3 studies,

very low-certainty evidence, I2 = 64%).  Depression was further
examined at longer time points by Riemersma-vanDerLek 2008, but
little to no eCect on depression was reported at six months, 12
months, 18 months or 24 months (Analysis 5.1.2).

Hopkins 2017  assessed anxiety as a behaviour outcome using
the anxiety subset of the Hospital Anxiety and Depression (HADA)
scale and lower scores indicate lower anxiety levels. Anxiety was
assessed at four weeks. and  Hopkins 2017  reported little or no
diCerence in anxiety at four weeks (MD -0.10, 95% CI -1.67 to
1.47; Analysis 5.1.3; 1 study). Riemersma-vanDerLek 2008 reported
little or no eCect on distress, withdrawn behaviour, positive
mood and  negative mood (Analysis 5.1.3). This study did report
a reduction for those in the bright lighting intervention group in
withdrawn behaviour at 18 months only (MD -4.30, 95% CI -7.45
to -1.15; Analysis 5.1.3; 1 study) and a reduction in negative mood
only at 24 months (MD -2.70, 95% CI -4.80 to -0.60; Analysis 5.1.3;
1 study). Two studies (Figueiro 2019; Riemersma-vanDerLek 2008)
examined the impact of increased lighting on agitation using the
CMAI, and lower scores indicate better behaviour. There was little
or no diCerence in agitation at four to six weeks (SMD -0.16, 95%

CI -0.45 to 0.14;  Analysis 5.3; 2 studies, low-certainty evidence, I2

= 17%). It is uncertain whether bright lighting improves agitation
because the certainty of this evidence is low.

Function

It is uncertain whether bright lighting improves function because
the certainty of this evidence is low (SMD -0.29, 95% CI -0.69 to 0.00;
2 studies, 179 participants; low-certainty evidence). The certainty
of evidence was downgraded from high-certainty to low-certainty
because of serious concerns due to risk of bias and serious concerns
due to imprecision.

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Two cluster-randomised trials (94 participants) assessed the eCect
of bright lighting on function (Figueiro 2019; Riemersma-vanDerLek
2008).  Function was assessed by the nurse-informant adaptation
(NI-ADL) of the scale by Katz and colleagues (Riemersma-vanDerLek
2008) and the Minimum Data Set Activities of Daily Living
Scale (MDS-ADL) (Figueiro 2019), and higher scores indicate
more functional limitations. Riemersma-vanDerLek 2008 measured
function at baseline, six weeks, six months, one year, 1.5 years
and two years and Figueiro 2019 measured function at four weeks.
There was little or no diCerence in function at four to six weeks
(SMD -0.29, 95% CI -0.69 to 0.00;  Analysis 5.4;  2 studies, low-

certainty evidence, I2 = 0%). Riemersma-vanDerLek 2008 reported
an increase in function (decrease in NI-ADL scores) at 18 months
and 24 months (Analysis 5.5; 1 study), but there was little to no
eCect at six months or 12 months.

Global cognitive function

It is uncertain whether bright lighting improves global cognitive
function because the certainty of this evidence is low (MD 1.20, 95%
CI -1.56, 3.96; 1 study; 74 participants; low-certainty evidence). The
certainty of evidence was downgraded from high-certainty to low-
certainty because of serious concerns due to risk of bias and serious
concerns due to imprecision.

One cluster-randomised trial (87 participants at six weeks) assessed
the eCect of bright lighting in communal living spaces during the
day on global cognitive function  (Riemersma-vanDerLek 2008).
Cognitive function was assessed using the MMSE and higher scores
indicate better global cognitive function. Global cognitive function
was measured at baseline, six weeks, six months, one year, 1.5 years
and two years. There was little to no eCect on global cognitive
function at the five follow-up times between six weeks and 24
months (Analysis 5.6).

Quality of care

No included studies reported on outcomes for quality of care.

Serious adverse e”ects

No included studies reported on outcomes for serious adverse
eCects.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Dining space redesign versus usual environment

Three studies examined the eCect of dining interventions (403
participants) in long-term residential care compared to the usual
dining environment (Kenkmann 2010, Mathey 2001 and Nijs 2006).
Two studies were cluster-randomised trials (Mathey 2001; Nijs
2006) and one study was a controlled before-aJer study (Kenkmann
2010).

Health-related quality of life

It  is uncertain whether dining space redesign improves health-
related quality of life because the certainty of this evidence is very
low (2 studies; 283 participants; very low-certainty evidence).
This certainty of the evidence was downgraded from high to

very low because of very serious concerns due to risk of bias
and serious concerns due to imprecision. Meta-analysis was not
possible because one of the studies reported results as percentage
changes over time without adjustment for clustering.

Two studies (283 participants) measured the eCect of dining space
redesign on quality of life (Mathey 2001; Nijs 2006). Quality of life
was measured by the Dutch Quality of Life of Somatic Nursing Home
Residents questionnaire (Nijs 2006 ) or the Sickness Impact Profile
(SIP) and the Dutch version of the Philadelphia Geriatric Center
Moral Scale (PGCMS) (Mathey 2001). Higher scores in the tools
used indicate better quality of life. Quality of life was measured at
baseline (Mathey 2001; Nijs 2006), six months (Nijs 2006) and 12
months (Mathey 2001).

Nijs 2006 reported a higher quality of life for those with the family-
style dining intervention; there was less decline in quality of life
in the intervention group (MD 6.10, 95% CI 2.10 to 10.10; Analysis
6.1; 1 study) and results were adjusted for clustering and baseline
characteristics of the residents.  Mathey 2001  reported results
as percentage changes over time and a summary is provided
in  Analysis 6.1.  Mathey 2001  did not adjust for clustering and did
not provide suCicient data to perform correct analyses for cluster-
randomised trials as described in the Cochrane Handbook (Higgins
2011). The authors reported SIP scores had “significantly declined”
in the control group, “stayed stable” in the intervention group, and
PGCMS scores remained “relatively stable” in both the intervention
and control groups.

Behaviour, mood and depression

One study (120 participants) examined the eCect of dining space
redesign on anxiety using the HAD scale (Kenkmann 2010). Anxiety
was measured at baseline and 12 months. The results were not
considered suitable to contribute to the quantitative analysis as
they were unadjusted for diCerences in baseline characteristics
of the participants; a summary is presented  in  Analysis 6.2. The
authors did not comment on the statistical significance of the
results.

No included studies reported on any further outcomes for
behaviour and depression.

Function

It is uncertain whether dining space redesign improves function
because the certainty of evidence is very low (MD 3.20, 95% CI 0.90
to 5.50; 1 study; 178 participants; very low-certainty evidence). This
certainty of the evidence was downgraded from high to very low
due to very serious concerns due to risk of bias and serious concerns
due to imprecision.

One study (178 participants) examined change in function using the
Nursing Home Physical Performance test and higher scores indicate
better function (Nijs 2006). Function was measured at baseline and
six months.  Nijs 2006  reported better function for those with the
family-style dining intervention, as there was less decline over time
(MD 3.20, 95% CI 0.90 to 5.50; Analysis 6.3; 1 study).

Global cognitive function

One study examined the eCect of dining space redesign on global
cognitive function using the MMSE (Kenkmann 2010). Global
cognitive function was measured at baseline and 12 months.
The results were not considered suitable to contribute to the

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quantitative analysis as they were unadjusted and are presented
in  Analysis 6.4. The authors commented that “there was no
evidence that the food and drink intervention had an impact on
residents cognitive functioning”.

Quality of care

No included studies reported on outcomes for quality of care.

Serious adverse e”ects

It is uncertain whether dining space redesign impacts the rate or
risk of falls because the certainty of this evidence is very low (rate
ratio 0.76, 95% CI 0.57 to 1.01; 1 study; 120 participants; very low-
certainty evidence). The certainty of evidence was downgraded
from low to very low because of very serious concerns due to risk of
bias and serious concerns due to imprecision.

One study examined serious adverse eCects through an adjusted
rate of falls and proportion of people falling at baseline and 12
months (Kenkmann 2010).  Kenkmann 2010  reported little to no
eCect on the rate of falls (rate ratio 0.76, 95% CI 0.57 to 1.01; Analysis
6.5, 1 study). The risk of falling (i.e. the proportion of people falling)
in 12 months is also presented in Analysis 6.5 but the results were
unadjusted, and the authors commented that diCerences between
the groups “were not statistically significant”.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

Garden vignette versus traditional environment

One repeated measures study (33 participants) examined the
eCect of a garden vignette in long-term residential care using five
phases: two intervention phases and three washout phases (Marcy-
Edwards 2011).

Health-related quality of life

No included studies reported on outcomes for quality of life.

Behaviour, mood and depression

It is uncertain whether a garden vignette improves global behaviour
because the certainty of this evidence is very low (MD 12.8, 95% CI
-10.7 to 36.3; 1 study; 33 participants; very low-certainty evidence).
The certainty of evidence was downgraded because of very serious
concerns due to risk of bias and very serious concerns due to
imprecision.

The authors had not conducted a statistical comparison of time
trends before and aJer the intervention; we re-analysed the results
as recommended in EPOC 2017c. Global behaviour was measured
with the NPI-NH and lower scores indicate fewer behavioural
symptoms. The eCect of a garden vignette on global behaviour was
uncertain (MD 12.8, 95% CI -10.7 to 36.3; Analysis 7.1; 1 study).

Function

No included studies reported on outcomes for function.

Global cognitive function

No included studies reported on outcomes for global cognitive
function.

Quality of care

No included studies reported on outcomes for quality of care.

Serious adverse e”ects

No included studies reported on outcomes for serious adverse
eCects.

Outcomes for carers

No included studies reported on outcomes for carers.

Outcomes for sta”

No included studies reported on outcomes for staC.

D I S C U S S I O N

Summary of main results

The main objective of this review was to determine the eCects of
changes to the physical environment of residential aged care or
alternative models of residential aged care on the quality of life of
older residents. The included studies compared home-like small-
scale models of care to more traditional large-scale models of care.
We also included studies which examined interventions which were
not changes to the whole building, but refurbishment or changes to
one or more design components. These changes included changes
to lighting, design of the dining room or addition of a garden
vignette. There were too few studies included to examine whether
dementia alters the eCects of changes to the physical environment
or alternative models of residential aged care on quality of life.

The literature search identified six studies for the main comparison
(Afendulis 2016; Annerstedt 1993; Dettbarn-Reggentin 2005; Te
Boekhorst 2009; Wolf-Ostermann 2012; Yoon 2015), but the
certainty of evidence was very low with all the studies being
non-randomised and usually of small sample size. A large study
by Afendulis 2016 included the majority of the participants in the
review.  Afendulis 2016  examined a home-like model of care (the
Green House model) compared to traditional care, but the study
was non-randomised and rated at high risk of bias. The study also
only  reported on quality of care measures rather than any of the
prespecified primary outcomes of interest in this review.

Clinical heterogeneity involving diCerences in interventions,
comparisons and outcome measures precluded pooling of study
results on most occasions. In addition, there was variation in
the methods of statistical analyses including whether the study
reported results unadjusted or adjusted for diCerences in baseline
characteristics of the participants. For the main comparison, we
were not able to pool any studies. There were also insuCicient data
to  explore  whether changes to the physical environment have a
diCerent impact depending on whether the population is living with
dementia.

For the primary outcomes, one study examined the eCect of home-
like models on quality of life and stated “no statistically significant
diCerences were observed between the intervention and control
groups” (Wolf-Ostermann 2012). Three studies examined global
behaviour for a home-like compared to traditional model of care

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(Dettbarn-Reggentin 2005; Te Boekhorst 2009; Wolf-Ostermann
2012). One study found little or no diCerence in global behaviour
change at six months and two additional studies examined global
behaviour, but these were unsuitable for determining a summary
eCect estimate. Two studies examined depression for the main
comparison (Te Boekhorst 2009; Yoon 2015). AJer 18 months, one
study reported an increase in the rate of depressive symptoms,
but the eCect of home-like models of care on the probability of
no depressive symptoms was uncertain (Yoon 2015). One study
reported little or no diCerence in depressive symptoms at six
months (Te Boekhorst 2009). Four studies examined function as
an outcome for the main comparison (Dettbarn-Reggentin 2005; Te
Boekhorst 2009; Wolf-Ostermann 2012; Yoon 2015). DiCerences in
the study design and reporting made interpretation diCicult. One
study reported evidence of a positive eCect of a home-like model
compared to a more traditional model on function and one
study reported little or no diCerence in function. Two additional
studies measured function but could not be included in the
quantitative analysis. One study examined quality of care and
reported a reduction in the number of bedfast residents, catheter
use, low-risk pressure ulcers and avoidable hospital readmission,
but reported little or no diCerence in high-risk pressure ulcers
(Afendulis 2016). One study reported a slight reduction in the use
of physical restraints, but no other serious adverse eCects were
examined (Afendulis 2016). The certainty of evidence was rated
as very low on GRADE for all outcomes for the main comparison;
therefore, it is uncertain whether a home-like model of care
aCects outcomes including  quality of life, behaviour, mood and
depression, function or serious adverse eCects.

In addition to the main comparison, included studies also
compared interventions which focused on one or more design
components within residential aged care. Five studies examined
the eCect of refurbishment of residential aged care facilities in
conjunction with measures to improve person-centred care (Burack
2012; Chenoweth 2014; Diaz-Veiga 2014; Galik 2021; Wylie 2001).
Three studies (one randomised trial) assessed quality of life but
it is uncertain whether refurbishment compared to traditional
environments improved quality of life because the certainty of
evidence was very low.

Three studies examined the impact of refurbishment on behaviour
(Burack 2012; Chenoweth 2014; Galik 2021). Two randomised trials
examined the impact of refurbishment on behaviour; one found
little or no diCerence in behaviour with the intervention (Galik
2021), and the eCects in the other trial were uncertain (Chenoweth
2014).  One further non-randomised study examined the eCect of
refurbishment in combination with ‘culture change’ (Burack 2012).
Three sub-domains of behaviour were examined in relation to this
intervention and a reduction in forceful behaviours and physical
agitation was found, but there was little or no diCerence in verbal
agitation. However, it is uncertain if refurbishment with culture
change improves behaviour as the certainty of evidence was very
low.

One randomised trial examined the impact of refurbishment on
function. Refurbishment comprising the FBFC intervention may
make little or no diCerence to function (low-certainty evidence). No
studies examined the eCect of refurbishment on serious adverse
eCects.

One non-randomised study examined the eCect of a special care
unit for people with dementia (Frisoni 1998). This study did

not adjust results for potential baseline diCerences between the
groups; therefore, the results should be interpreted with caution
and the eCects on behaviour, function, physical restraints and falls
are considered uncertain. No studies examined the eCect of special
care units on quality of life or quality of care.

One non-randomised study (Elmstahl 1997) examined the eCect
of a corridor vs non-corridor design and reported a decrease
in depression associated with the non-corridor design, but the
certainty of evidence was very low. The eCect of a corridor design
on 10 other measures of behaviour was uncertain. Therefore,
whether a corridor vs non-corridor design within group living units
is preferable for behaviour is uncertain. No studies examined the
eCect of a corridor versus non-corridor design on quality of life,
quality of care, function or serious adverse eCects.

Three cluster-randomised trials examined the eCect of lighting
interventions (Figueiro 2019; Hopkins 2017; Riemersma-vanDerLek
2008). All of the studies reported results at short-term follow-
up (four to six weeks) and one study also reported results
at longer follow-up (Riemersma-vanDerLek 2008, up to 24
months).  However, there was  large loss to follow-up in the study
by Riemersma-vanDerLek 2008 and little or no eCect was reported
for global behaviour. Pooled data from the three studies showed
little or no diCerence in depression at short-term follow-up. Two
cluster-randomised trials assessed the eCect of bright lighting on
function (Figueiro 2019; Riemersma-vanDerLek 2008). There was
little or no diCerence in function at four to six weeks. The certainty
of evidence was low, therefore, the eCects of lighting for behaviour
or function are uncertain. No studies examined the eCect of lighting
interventions on quality of life, quality of care or serious adverse
eCects.

Two cluster-randomised trials and one non-randomised trial
examined the eCect of dining space redesign  (Kenkmann 2010;
Mathey 2001; Nijs 2006). One randomised trial (Nijs 2006) found
better quality of life and function for participants receiving a family-
style dining intervention over six months. The other two studies
did not conduct appropriate adjustments for potential confounding
or clustering. One study reported better function with a family-
style dining intervention, as there was less decline over time (Nijs
2006). Another reported little to no eCect on the rate of falls
(Kenkmann 2010). However, it is uncertain whether dining space
design eCects quality of life, function or rate of falls because
the certainty of evidence was very low. One study examined the
eCect of dining space redesign on anxiety, but the results were
not suitable to contribute to the quantitative analysis as they
were unadjusted for diCerences in baseline characteristics of the
participants (Kenkmann 2010). No studies examined the eCect of
dining space redesign on quality of care.

One repeated measures study examined the eCect of a
garden vignette intervention using 14-day phases incorporating
intervention and washout phases (Marcy-Edwards 2011). The eCect
of a garden vignette on global behaviour was uncertain, and the
eCects of a garden vignette on other outcomes were not examined.

Overall completeness and applicability of evidence

We used a comprehensive search strategy, and therefore we are
likely to have identified all studies that meet the inclusion criteria
for this review, but we cannot be certain. Whilst a number of grey
literature sites were searched, it is possible that some studies that

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have not been published in mainstream literature databases were
not identified. The studies included were from many countries
including the USA, the Netherlands, the UK, Sweden, Germany,
Spain, Italy, Canada and Australia and some included studies
were published in non-English languages (one German and one
Spanish). Included studies were published over a prolonged period
(24 years) and, over this time, residential aged care  policies
and practices have changed. Therefore, the  applicability of some
older studies to current practice, in particular, where there is
a comparison to ‘standard care’ may be reduced; the earliest
included study was published in 1993 (Annerstedt 1993).

We could not make robust conclusions from the evidence due to
the limited number of eligible studies identified and variability
in design, interventions, outcomes, instruments used to assess
outcomes, and statistical analysis approaches. The wide variability
in outcomes assessed and measures used generally prevented
pooling of the data. The majority of the evidence for large-
scale design interventions was from non-randomised studies.
For the  lighting and dining interventions, four of five studies
were randomised, most likely due to the increased feasibility of
conducting this type of study. Studies also varied by which type
of statistical analyses were performed, whether endpoint data or
change over time data were analysed, whether the studies adjusted
for potential confounding factors and which potential confounding
factors were adjusted for in analyses. Five cluster-randomised
studies were included in the review. Two of these studies took the
eCect of clustering in to account in their analyses (Chenoweth 2014;
Nijs 2006). The other studies did not adjust for clustering and did not
provide suCicient data to perform adjusted analyses for clustering
as described in the Cochrane Handbook (Higgins 2011).

In accordance with Cochrane EPOC review guidance, only
controlled before-aJer and cluster-randomised studies which had
more than one control and intervention site were included.
Therefore, many studies which only reported results for one
intervention and/or one control site were excluded from the review
(including Kane 2007; Reimer 2004).

In addition, observational study designs were required to
include  pre- and post-intervention measures (i.e. controlled
before-aJer studies or repeated measures). This excluded a
number of studies which did not include pre-intervention baseline
measures  (i.e. a measure of participant outcomes on admission
to care), including  De Boer 2017; De Rooij 2012; Verbeek 2014.
For example,  Verbeek 2014  investigated small-scale home-like
environments in comparison to traditional environments for  259
residents with dementia. The study  suggested positive eCects on
outcomes including fewer physical restraints and psychotropic
medicines, but little or no diCerence in behaviour and quality
of life. However, by not including pre-intervention measures,
determining the eCect of the intervention is limited. Similarly, De
Boer 2017 has reported increased social interaction in residents of
green care farms in comparison to traditional facilities, but no pre-
intervention measures were reported.

A total of 77,265 participants were included in 20 studies, but
most (n = 74,449) of these participants were from a single
study. Therefore, most of the studies included small numbers
of participants (range 34 to 601). Most of the included studies
for large-scale design interventions were non-randomised which
means that even well-designed studies are only likely to provide
low level evidence. However, for whole models of care, conducting

randomised trials is rarely feasible. While a clustered design of
refurbishment is possible, this is unlikely to be able to capture
large-scale changes to the physical size and design of the buildings.
In contrast, randomised trials for smaller scale interventions such
as lighting or dining changes are more feasible, and several
randomised trials were identified.

Identified evidence was only suCicient to allow for the pooling
of data from two randomised studies for one outcome for
one comparison (depression with lighting interventions) and
heterogeneity for this outcome was substantial. Most of the
evidence was from individual studies which were usually modest
in size and likely to be underpowered. For all outcomes and
comparisons, the certainty of evidence was very low.

Studies generally did not report fidelity assessments. One
randomised study examined the eCects of an intervention which
involved assessing the environment with the Environmental
Audit Tool and identifying areas for improvement. This study
reported diCiculties in implementing the proposed design changes
(Chenoweth 2014). Similarly,  Wylie 2001  reported that one of
the facilities  which received the Eden Alternative  intervention
discontinued its implementation, but did not state the reasons for
this.

Some included studies did not measure quality of life as an
outcome which is a limitation of the review. We included
studies which examined other primary outcomes and secondary
outcomes,  because these included outcomes are likely to impact
quality of life for residents. Care home residents are oJen
unable to complete health-related quality of life questionnaires for
themselves and the validity of quality of life measures for care home
residents has been questioned (Usman 2019). Therefore, we think
it is important to consider multiple outcomes which impact quality
of life for residents, not only self- and proxy-reported quality of life
measures.

The searches for this review were completed during the coronavirus
2019 (COVID-19) pandemic, but all the included studies were
conducted prior to the start of the COVID-19 pandemic. This review
focuses on quality of life, thus infection-related outcomes were not
included in the protocol. Since this time, questions have arisen
regarding the role of the design of residential aged care facilities in
infection control (Werner 2020). Older people living in residential
aged care have been disproportionately impacted by the COVID-19
pandemic in many countries including the UK and the US. Based on
data from 22 countries to January 2021, 41% of all COVID-19-related
deaths were of people living in aged care (Comas-Herrera 2021). It
has been suggested that alternative architectural designs of aged
care facilities may benefit both resident quality of life and infection
control (Anderson 2020). However, others have questioned whether
home-like designs contain the necessary infrastructure for tight
infection control (Ibrahim 2020). Other characteristics which may
have impacted rates of COVID-19 infections in residential aged
care settings include ownership, staCing, provider size and resident
characteristics (Bach-Mortensen 2021). Further research on the
impact of design of residential aged care and the impact on
infection rates and outbreak control is needed. This should be in
conjunction with addressing issues regarding funding, staCing and
support for residential aged care facilities which will impact quality
of life for residents (Oliver 2020).

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Quality of the evidence

For the main comparison of home-like models  compared
to traditional models of care, attrition was oJen high. OJen studies
did not adequately report the numbers lost to follow-up, the
reasons for loss to follow-up or diCerences between those lost to
follow-up and those not lost to follow-up. If reasons for loss to
follow-up are imbalanced across the groups, this is likely to impact
on the estimate of eCect and introduce bias to the study findings.

For all controlled before-aJer studies, random sequence
generation and allocation concealment is rated at high risk of
bias as these criteria cannot be met for this  study design.
There was also a lack of adjustment for diCerences in baseline
characteristics of participants in many studies. By not adequately
adjusting for diCerences in baseline characteristics, the potential
for confounding factors influencing the results is high. In addition,
it is possible that not all likely confounding factors (e.g. public
versus private ownership, resident access to healthcare) were taken
into account in the included studies, and the design of many of
the included studies means that they are particularly prone to
bias from lack of adjustment for confounding factors. Four studies
were rated at high risk of bias and four studies were rated at
unclear risk of bias for selective outcome reporting as they listed
outcomes in their methods and did not report results. However,
56% of studies reported results as indicated in the methods or
protocol and were rated at low risk of bias for selective reporting.
Only two studies were considered to be at risk of contamination
of the intervention in the control group, as for most studies the
participants of the intervention and control groups were living in
diCerent facilities or living units. However, one study reported one
of the control sites had previously implemented and discontinued
the intervention,  and one study randomised wards within one
home; therefore, contamination was likely. Of the included studies,
67% were rated at high risk of bias for other bias, mainly due to the
potential for residual confounding associated with the use of non-
randomised study designs.

Few studies examined serious adverse eCects as an outcome.
Falls risk is an important factor to include in the consideration of
any environmental design changes, however, falls outcomes were
frequently not reported.

There are feasibility and ethical considerations when considering
the design of a study to assess whole-facility changes to the model
of care and design of the built environment. For instance, oCering
improved environments to only some residents on a site may be
perceived as inappropriate to both residents and family members.
Furthermore, when examining the impact of changes to the whole
facility it is diCicult to eCectively isolate the impact of the built
environment from the impact of other changes to the model of care
such as care practice changes or staCing changes. It is also diCicult
to adequately account for changes to the health of residents
with progressive diseases over time. This review highlights the
complexities of care and quality of life in residential aged care
settings. Design elements may be important factors in decision-
making for families, but other elements including model of care
should also be considered.

Potential biases in the review process

As the list of included interventions was broad, identifying relevant
studies was challenging. We minimised publication bias by using

a comprehensive search strategy of multiple databases, including
trial registers and grey literature. Authors of completed studies
identified in trials registers for which study publications were
not been identified were contacted, as were authors of studies
identified only as conference abstracts. We did not restrict the
search strategy by language and non-English language studies
were included in the review (Dettbarn-Reggentin 2005; Diaz-
Veiga 2014).  Correspondence with authors provided additional
information on study methods and results. However, we cannot be
certain that there was no publication bias in the included studies.
Each study was assessed by two reviewers working independently
at all stages of the study selection process, and we were careful
not to exclude relevant studies. Yet,  it is still possible that there
are additional relevant studies which were not identified  that
would have met the inclusion criteria. The data extraction, risk of
bias assessment and GRADE assessment for each study was also
conducted in duplicate by two reviewers working independently.

Agreements and disagreements with other studies or
reviews

Marquardt 2014  conducted a review with a systematic search
of the design of the physical environment for people with
dementia living in residential aged care. The review included 169
studies with a broad range of study designs and the review also
included temporary therapies; six of the studies were eligible
for inclusion in the current review. The review included 30
studies of small-scale home-like environments and the review
suggested that there was a potential improvement in function and
social abilities,  no evidence for a beneficial eCect on cognition
and  conflicting results for behaviour. The review assessed the
quality of the studies by focusing on the study design and did not
assess other methodological issues or risk of bias. In a scoping
review, Ausserhofer 2016 examined the eCect of home-like models
of care in comparison to usual care in residential aged care for
older people. The review completed a broad but comprehensive
literature search and included 14 studies, three of which met the
inclusion criteria for the current review. The review authors did
not critically appraise the risk of bias of included studies. The
review authors concluded that there was evidence of “benefit
related to physical functioning of residents living in dementia-
specific small houses and satisfaction with care of residents living
in non-dementia-specific small houses compared with those living
in traditional nursing homes”. However, no benefit was found
for other outcomes for residents, family or staC. Overall, the
authors stated there was limited evidence on home-like models of
residential aged care and a stronger evidence base was needed,
which accorded with the conclusions of this review.  Ausserhofer
2016 did not rate the certainty of the evidence.

A 2009 Cochrane review of special care units for people with
dementia experiencing behavioural problems included eight
studies, of which four provided data suitable for analysis (Lai
2009).  The review included studies reporting on the outcomes of
behaviour and physical restraint use. One of these studies (Frisoni
1998) was also included in the current review. Outcome data
came from single studies and no eligible RCTs were identified.
The authors commented that almost all the positive outcomes of
special care units  in the review came from a single study (Nobili
2006). The authors concluded that there was no strong evidence
for benefit of special care units, however the design features of

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special care units are oJen focused on increased safety rather than
improving resident quality of life.

Joseph 2015  included 66 studies in a systematic review of the
physical environment of residential health, care and support
facilities. The review had much broader inclusion criteria than the
current review in terms of setting (e.g. including assisted living
and rehabilitation facilities), study design (e.g. including cross-
sectional studies) and outcomes (e.g. including physical activity
engagement and medication errors). The authors stated that the
quality of the studies varied, with some studies with stronger
designs having data from very few participants and that additional
research was needed. Nevertheless, the authors stated that the
review indicated that “the built environment is an important
component of the care provided in residential care settings”.

A systematic review of use of the physical environment to support
people with dementia included 72 studies conducted in any
setting including the home (Woodbridge 2018), although most were
from residential settings. The review focused on the outcome of
function, i.e. everyday tasks. No specific inclusion/exclusion criteria
by study design were applied, nor were any quality appraisal
tools applied to the included studies. The authors concluded that
“more work is needed to extend theoretical understandings of how
people with dementia interact with their environments so that
these spaces can be designed to further support activities of daily
living performance”.

A healthy technology assessment by the Canadian Agency for
Drugs and Technologies in Health (CADTH) included a “limited
literature search” in 2010 of the eCects of the Eden Alternative
and Green House designs (CADTH 2010). Three non-randomised
studies were included in this assessment which we identified in
our search, but the studies did not meet the inclusion criteria. The
authors also concluded that evidence was limited and noted issues
in attrition bias and adoption of design principles by residential
aged care facilities.  Brownie 2013  reviewed person-centred care
interventions which included eight studies which examined the
Eden Alternative, Green House model or facility-specific person-
centred care; one of the included studies  was included in the
current review. The review concluded that the Eden Alternative
was associated with significant improvements in boredom and
helplessness, but also noted limitations in study designs and
potential for confounding bias. Our review only identified one
study which examined the Eden Alternative that met the inclusion
criteria; in that study, the authors found little or no diCerence in
quality of life.

There have been many studies conducted examining  non-
environmental design interventions  to improve quality of life
for older adults living in residential aged care. A systematic
review of organisational level person-centred care for people
with dementia found a significant eCect for quality of life post-
intervention, but this review included hospital care and extra-
care community housing in addition to residential aged care
(Chenoweth 2019).  Non-pharmacological interventions such as
music therapy and function-analysis based interventions can be
eCective in improving behavioural symptoms for people with
dementia without associated serious adverse eCects (Dyer 2017).
A Cochrane review of music therapy for people with dementia
found that at least five sessions of a music-based therapeutic
intervention probably reduced depressive symptoms, improves
behavioural problems and may also improve quality of life and

emotional well-being (Van der Steen 2018). Another systematic
review has concluded that receptive music therapy could reduce
agitation, behavioural symptoms, and anxiety in older people with
dementia, and appears to be more eCective than interactive music
therapy (Tsoi 2018). A  Cochrane review of functional-analysis-
(FA)-based interventions for people with dementia included 18
RCTs and found  positive eCects for certain outcomes at post-
intervention, but not follow-up, including the frequency of reported
challenging behaviour  and for caregiver reaction (Moniz  Cook
2012). In people with dementia, animal-assisted therapy may have
a slight reduction in depressive symptoms (Lai 2019). While several
of these reviews did not focus specifically on residential aged
care settings, there is a high prevalence of cognitive impairment
and dementia in people living in these settings (Lang 2017), so
interventions with demonstrated benefit may be of value.

A 2016 Cochrane review of interventions to optimise prescribing
for older people in residential aged care included 12 studies.
Many of the included interventions had multiple components
and  oJen involved  a  review  of medicines with a pharmacist
and doctor (Alldred 2016).  The authors found  no evidence
of benefit of the interventions with respect to reducing
adverse drug events or death, but one of two included
studies which investigated quality of life  reported a  slower
decline in health-related quality of life with low-certainty
evidence.  Selected studies also indicated that multicomponent
interventions may provide benefits. A randomised controlled trial
of a multicomponent intervention  combining communication,
systematic pain management, medication review, and activities
in 33 nursing homes found, although quality of life worsened
significantly during the intervention, quality of life was improved
at 4 to 9-month follow-up (Husebø  2019). Another  randomised
trial examined a multicomponent intervention combining person-
centred  training for staC  and a system for triggering appropriate
review of antipsychotic medicines in 69 residential aged care
facilities. The study reported improvements in agitation and quality
of life for the residents and deemed the intervention to be cost-
eCective when compared with usual care (Romeo 2018).

Overall, previous reviews have indicated that the physical
environment is an important consideration when determining
interventions to improve quality of life for residents in aged care
facilities, but the quality of evidence is mixed and there is a lack
of definitive high-quality evidence. There is also some evidence to
suggest  non-pharmacological interventions  or approaches  which
do not alter the physical environment may positively impact quality
of life.

A U T H O R S ‘   C O N C L U S I O N S

Implications for practice

While 20 studies were included in this review, there was variation
in the interventions and outcomes assessed and the certainty
of evidence was low or very low for all outcomes investigated.
Thus, there is currently insuCicient evidence on which to draw
conclusions about the impact of physical environment design
changes for older people living in residential aged care. Additional
studies that examine the eCects of physical environmental designs
of residential aged care facilities are required to improve the quality
of evidence available.

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Implications for research

Individually randomised trials for larger-scale interventions of the
physical environment for older people living in residential aged
care such as changing the scale of the building and whole model
of care are unlikely to be feasible. A planned randomised trial of
people living with dementia on admission to special care facilities
or traditional care had to modify the design due to too few people
being wait-listed for admission during the time period of the
study (Reimer 2004). Nevertheless, to improve the quality of the
evidence available, careful consideration of alternative methods
for design should be made by study authors  such as cluster-
randomised,  stepped-wedge randomised trials and interrupted
time series with three data points before and aJer changes.
Although non-randomised studies will have potential for risk of bias
which cannot be altered due to the lack of randomisation, non-
randomised studies can be optimised to reduce the risk of bias and
improve the certainty of evidence from these studies. For example,
many non-randomised studies were excluded from this review for
having only one intervention and/or control site which cannot be
considered for inclusion in Cochrane EPOC reviews because “the
intervention is completely confounded by study site making it
diCicult to attribute any observed diCerences to the intervention
rather than to other site-specific variables”. Many studies were also
excluded because they did not include a control group, or they
did not include measurements before the intervention (e.g. on
admission to residential aged care) which also limits the usability of
the results from such studies and the evidence cannot be included
in Cochrane EPOC reviews to inform current evidence. The certainty
of evidence was oJen downgraded due to the imprecision of results
and, therefore, studies with larger sample sizes of participants
across multiple sites are warranted. Other items of risk of bias that
were oJen deemed high risk were due to inadequate reporting of
and adjustment for baseline characteristics and baseline outcome
measures of the population being studied, or inadequate reporting
of outcomes to be assessed in the methods or study protocol (or
not stating reason for choice of outcomes assessed if using a data
source with many potential fields). Whilst some prospective cohort
studies address these criteria, the lack of reporting participant
measures before the intervention (e.g. on admission for whole
models of residential aged care) meant that they did not meet the
inclusion criteria for this review.

When conducting studies on older people living in residential
aged  care, attrition due to mortality or ill-health will be an issue
in most populations. Adequately reporting loss to follow-up and
reasons for diCerences between those lost to follow-up by group
allocation is critical to the interpretation of results. When planning
the study, the expected attrition should be considered when
determining an appropriate sample size.

Studies should investigate outcomes which are important to both
residents and carers including, but not limited to, quality of life,
behaviour, function, cognitive function, quality of care, serious
adverse eCects, outcomes for carers (including quality of life,
mood and carer burden) and outcomes for staC (including staC
knowledge, attitude, self-eCicacy, quality of life and burnout).
Outcomes should be measured using instruments which have
been validated in older people living in residential aged care.
Although residual confounding factors will always be a risk of bias
in non-randomised studies, statistical analyses in non-randomised
studies should plan analyses during the study design stage,

including adequate data collection to allow for adjustment for
many potential confounding factors. Cluster-randomised trials
should statistically adjust for the eCect of clustering as those
which do not take clustering into account create a unit of
analysis error and produce over-precise results (Higgins 2011).
Guidelines and a checklist for reporting interventions are available
such as the template for intervention description and replication
(TIDieR) checklist and guide (HoCmann 2014) and study authors
should follow these guidelines to ensure they clearly describe
the intervention and control arms of studies. Any diCiculties in
implementing the intervention should also be fully reported, either
in the main paper or as supplementary material. As shown in this
review, isolating eCects of the built environment in a controlled
setting whilst minimising bias can be diCicult to achieve in a
residential aged care setting due to other changes which may
occur, such as changes in care practices and changes to the health
of the residents. Future studies should be aware of any changes
which are likely to occur to the staCing structure or health of
the residents during the study period and plan for appropriate
statistical analyses to account for these changes.

Cluster-randomised trials are feasible for studies of refurbishment
of  residential aged care or interventions focusing on a specific
design component within a care home (e.g. dining room redesign or
lighting). When considering refurbishment in long-term residential
aged care, issues in implementing design changes for a specific
budget and time frame, as described in the study by  Chenoweth
2014,  should be considered during the development of the
study protocol. Blinding should be carried out on all personnel,
where feasible, including those conducting all analyses and those
assessing the outcomes, where possible (e.g. patient-reported
outcomes, such as quality of life, would be collected in the
knowledge of the intervention received whereas others, such as
functional ability measures, can be collected by an independent
clinician who is blinded) (EPOC 2016a).

A C K N O W L E D G E M E N T S

We acknowledge the help and support of Cochrane ECective
Practice and Organisation of Care (EPOC). The authors would also
like to thank the following editors and peer referees who provided
comments to improve the protocol: Signe Flottorp (EPOC Editor),
Paul Miller (EPOC Information Specialist), Julie Udell (external Peer
Referee), and Jemma Hudson (EPOC Statistician); also Elizabeth
Royle and Copy Edit Support for copy editing the protocol. We
would also like to thank the following editors and peer referees
who provided comments to improve the full review: Phillippa
Carnemolla (Content expert, external), Nick Seemann (Content
expert, external), Brian Duncan (Consumer, external), Harrison
Davies (Consumer, external), JC Han (Assistant Managing Editor,
EPOC), Denise O’Connor (Contact Editor, EPOC), Cristián Mansilla
(Associate Editor, EPOC), Noah Ivers  (Associate Editor, EPOC),
Paul Miller (Information Specialist, EPOC) and Jennifer Hilgart
(Statistical Editor, Public Health and Health Systems’ Network
Editorial & Methods Department). We would also like to thank Anne
Lethaby for copy-editing the review.

National Institute for Health Research (NIHR), via Cochrane
Infrastructure, gave funding to the ECective Practice and
Organisation of Care (EPOC) Group. We also acknowledge Ms
Natalie May, Ms Megan Winsall, Dr Wendy Shulver, Dr Justine Irving

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and Dr Helena Kopunic for assistance in initial abstract and title
screening of some citations for full-text review (in duplicate with
study authors) and assistance with grey literature searching. We
thank Jenni Suen for research assistance. The views and opinions
expressed herein are those of the authors and do not necessarily
reflect those of the Systematic Reviews Programme, NIHR, National
Health Service (NHS), or the Department of Health.

The Australasian Satellite of the Cochrane EPOC Group is funded by
Cochrane.

The contents of the published materials are solely the responsibility
of the administering institution — Flinders University and The
University of Woollongong — and the individual authors identified,
and do not reflect the views of the NHMRC or any other funding
bodies or the funding partners.

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R E F E R E N C E S
 

References to studies included in this review

Afendulis 2016 {published data only}

Afendulis CC, Caudry DJ, O’Malley AJ, Kemper P, Grabowski DC,
Thrive Research Collaborative.Green house adoption and
nursing home quality. Health Services Research 2016;51 Suppl
1:454-74.

Annerstedt 1993 {published data only}

*  Annerstedt L, Gustafson L, Nilsson K.Medical outcome of
psychosocial intervention in demented patients: one-year
clinical follow-up aJer relocation into group living units.
International Journal of Geriatric Psychiatry 1993;8(10):833-41.

Annerstedt L.An attempt to determine the impact of group
living care in comparison to traditional long-term care on
demented elderly patients. Aging Clinical and Experimental
Research 1994;6(5):372-80.

Annerstedt L.Group-living care: an alternative for the
demented elderly. Dementia & Geriatric Cognitive Disorders
1997;8(2):136-42.

Annerstedt L.On group-living care for the demented elderly:
experiences from the Malmo model. Ann Arbor Lunds
Universitet 1995;C405957:69.

Burack 2012 {published data only}

Burack OR, Reinhardt JP, Weiner AS.Person-centered care and
elder choice: a look at implementation and sustainability.
Clinical Gerontologist 2012;35(5):390-403.

*  Burack OR, Weiner AS, Reinhardt JP.The impact of culture
change on elders’ behavioral symptoms: a longitudinal
study. Journal of the American Medical Directors Association
2012;13(6):522-8.

Chenoweth 2014 {published data only}

Chenoweth L,  Jeon YH,  Stein-Parbury J, Forbes I, Fleming R,
Cook J,  et al.PerCEN trial participant perspectives on the
implementation and outcomes of person-centered dementia
care and environments. International Psychogeriatrics
2015;27(12):2045-57.

*  Chenoweth L, Forbes I, Fleming R, King MT, Stein-Parbury J,
Luscombe G, et al.PerCEN: a cluster randomized controlled
trial of person-centered residential care and environment
for people with dementia. International Psychogeriatrics
2014;26(7):1147-60.

Chenoweth L, King M, Luscombe G, Forbes I, Jeon YH,
Parbury JS, et al.Study protocol of a randomised controlled
group trial of client and care outcomes in the residential
dementia care setting. Worldviews on Evidence-Based Nursing
2011;8(3):153-65.

Chenoweth L.The Percen study: supporting client and care
outcomes in the residential dementia care setting. Alzheimer’s
and Dementia 2011;7(4 Suppl 1):S292.

Dettbarn-Reggentin 2005 {published data only}

Dettbarn-Reggentin J.Study on the influence of environmental
residential groups on demented old people in nursing home
residents [Studie zum einfluss von wohngruppenmilieus auf
demenziell erkrankte in stationären einrichtungen]. Zeitschri/
Fur Gerontologie Und Geriatrie 2005;38(2):95-100.

Diaz-Veiga 2014 {published data only}

Diaz-Veiga P, Sancho M, Garcia A, Rivas E, Abad E, Suarez N, et
al.ECects from the Person Centered-Care model on quality of
life of cognitive impaired persons from gerontological centers
[Efectos del Modelo de Atención Centrado en la Persona en la
calidadde vida de personas con deterioro cognitivo de centros
gerontológicos]. Revista Espanola de Geriatria y Gerontologia
2014;49(6):266-71.

Elmstahl 1997 {published data only}

Elmstahl S, Annerstedt L, Ahlund O.How should a group living
unit for demented elderly be designed to decrease psychiatric
symptoms? Alzheimer Disease and Associated Disorders
1997;11(1):47-52.

Figueiro 2019 {published data only}

Figueiro M, Rea M.Tailored lighting intervention to improve
sleep in patients with dementia. Sleep Medicine  2019;64:S115.

Figueiro MG, Kalsher M, Plitnick B, Rohan C, Rea MS.Tailored
lighting intervention for Alzheimer’s patients and its eCects on
sleep, mood and agitation. Sleep 2018;41:A113-A114.

*  Figueiro MG, Plitnick B, Roohan C,  Sahin L, Kalsher M,
Rea MS.ECects of a tailored lighting intervention on sleep
quality, rest-activity, mood, and behavior in older adults with
Alzheimer disease and related dementias: a randomized clinical
trial. Journal of Clinical Sleep Medicine 2019;15(12):1757-67.

Frisoni 1998 {published data only}

Bellelli G, Giovanni GB, Bianchetti A, BoCelli S, Guerrini GB,
Scotuzzi A, et al.Special care units for demented patients: a
multicenter study. Gerontologist 1998;38(4):456-62.

Bianchetti A, Benvenuti P, Ghisla KM, Frisoni GB, Trabucchi M.An
Italian model of dementia special care unit: results of a
pilot study. Alzheimer Disease and Associated Disorders
1997;11(1):53-6.

*  Frisoni GB, Gozzetti A, Bignamini V, Vellas BJ, Berger AK,
Bianchetti A, et al.Special care units for dementia in nursing
homes: a controlled study of eCectiveness. Archives of
Gerontology and Geriatrics 1998;26:215-24.

Galik 2021 {published data only}

Galik EM, Resnick B, Holmes SD, Vigne E, Lynch K, Ellis J, et
al.A cluster randomized controlled trial testing the impact of
function and behavior focused care for nursing home residents
with dementia. Journal of the American Medical Directors
Association 2021;22(7):1421-8.

Physical environmental designs in residential care to improve quality of life of older people (Review)

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Informed decisions.
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Hopkins 2017 {published data only}

*  Hopkins S, Morgan PL, Schlangen LJM, Williams P, Skene DJ,
Middleton B.Blue-enriched lighting for older people living in
care homes: eCect on activity, actigraphic sleep, mood and
alertness. Current Alzheimer Research 2017;14:1053-62.

Middleton B, Hopkins S, Morgan PL, Barrett D, Schlangen LJ,
Skene DJ.ECects of blue-enriched and control white light on
activity levels and timing in older people living in care homes.
Journal of Sleep Research 2010;19:188.

Kenkmann 2010 {published data only}

Kenkmann A, Hooper L.The restaurant within the home:
experiences of a restaurant-style dining provision in residential
homes for older people. Quality in Ageing & Older Adults
2012;13(2):98-110.

*  Kenkmann A, Price GM, Bolton J, Hooper L.Health, wellbeing
and nutritional status of older people living in UK care homes:
an exploratory evaluation of changes in food and drink
provision. BMC Geriatrics 2010;10:28.

Marcy-Edwards 2011 {published data only}

*  Marcy-Edwards D, Wardell R, Simon J, Hansen J, Baden L,
Grant N.The eCect of vignette activity on the neuropsychiatric
behaviours expressed by individuals with dementia, living
in long-term care. Alzheimer’s and Dementia 2011;7(4 Suppl
1):S644-S645.

Marcy-Edwards D.Engaging at a Garden Vignette: the ECect on
Neuropsychiatric Behaviour in Moderate to Severe Dementia
(thesis). Calgary, Canada: University of Calgary, 2014.

Mathey 2001 {published data only}

Mathey MF, Vanneste VG, De Graaf C, De Groot LC, Van
Staveren WA.Health eCect of improved meal ambience in a
Dutch nursing home: a 1-year intervention study. Preventive
Medicine 2001;32(5):416-23.

Nijs 2006 {published data only}

Nijs KA, De Graaf C, Kok FJ, Van Staveren WA.ECect of family
style mealtimes on quality of life, physical performance, and
body weight of nursing home residents: cluster randomised
controlled trial. BMJ 2006;332(7551):1180-4.

Riemersma-vanDerLek 2008 {published data only}

Riemersma-van Der Lek RF, Swaab DF, Twisk J, Hol EM,
Hoogendijk WJG, Van Someren EJW.ECect of bright light and
melatonin on cognitive and noncognitive function in elderly
residents of group care facilities – a randomized controlled trial.
JAMA 2008;299:2642-55.

Te Boekhorst 2009 {published data only}

Te Boekhorst S, Depla MF, De Lange J, Pot AM, Eefsting JA.The
eCects of group living homes on older people with dementia: a
comparison with traditional nursing home care. International
Journal of Geriatric Psychiatry 2009;24(9):970-8.

Wolf-Ostermann 2012 {published data only}

Fischer T, Wolf-Ostermann K.The Berlin study on structures
and outcomes of <<WohngemeinschaJen>> for people
with dementia (DeWeGE), a small-scale living arrangement

[Die Berliner studie zu versorgungsstrukturen and
versorgunsergebnissen von Wohngemeinschafrern
fur menschen mit demenz (DeWeGe)]. Zeitschri/ fur
Gerontopsychologie & Psychiatrie 2008;21(3):179-83.

*  Wolf-Ostermann K, Worch A, Fischer T, WulC I, Graske J.Health
outcomes and quality of life of residents of shared-housing
arrangements compared to residents of special care units –
results of the Berlin DeWeGE-study. Journal of Clinical Nursing
2012;21(21-22):3047-60.

Wylie 2001 {published data only}

Wylie R.Impact of the Eden Alternative™ on Texas Nursing
Homes Residents’ Quality of Life: a Psychosocial Perspective
(thesis). Texas, United States: Texas State University, 2001.

Yoon 2015 {published data only}

*  Yoon JY, Brown RL, Bowers BJ, Sharkey SS,
Horn SD.Longitudinal psychological outcomes of the small-
scale nursing home model: a latent growth curve zero-
inflated Poisson model. International Psychogeriatrics
2015;27(6):1009-16.

Yoon JY, Brown RL, Bowers BJ, Sharkey SS, Horn SD.The eCects
of the Green House nursing home model on ADL function
trajectory: a retrospective longitudinal study. International
Journal of Nursing Studies 2016;53:238-47.

Yoon JY.The eCect of Green House nursing home model on the
health outcome trajectories. University of Wisconsin Madison
2013.

 

References to studies excluded from this review

Auer 2017 {published data only}

Auer S,  Kienberger U, Pascher P, Geck M, Hofmann B,
Viereckl C.Small-scale group living versus traditional nursing
home for persons with dementia [WohngemeinschaJ versus
traditionelles pflegeheim für personen mit demenz. Eine
vergleichende beobachtungsstudie.]. Pflegewissenscha/
2017;3/4:156–65.

Barrick 2010 {published data only}

Barrick AL, Sloane PD, Williams CS, Mitchell CM, Connell BR,
Wood W, et al.Impact of ambient bright light on agitation
in dementia. International Journal of Geriatric Psychiatry
2010;25(10):1013-21.

Bergman-Evans 2004 {published data only}

Bergman-Evans B.Beyond the basics. ECects of the Eden
Alternative model on quality of life issues. Journal of
Gerontological Nursing 2004;30(6):27-34.

Bonardi 1989 {published data only}

Bonardi E, Pencer I, Tourigny-Rivard MF.Observed changes in
the functioning of nursing home residents aJer relocation.
International Journal of Ageing and Human Development
1989;28(4):295-304.

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Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

Bond 1999 {published data only}

Bond GE, Fiedler FE.A comparison of leadership vs. renovation
in changing staC values. Nursing Economics 1999;17(1):37-43.

Chafetz 1991 {published data only}

Chafetz PK.Behavioral and cognitive outcomes of SCU care.
Clinical Gerontologist: Journal of Aging and Mental Health
1991;11(1):19-38.

Chang 2013 {published data only}

Chang YP, Li J, Porock D.The eCect on nursing home resident
outcomes of creating a household within a traditional
structure. Journal of the American Medical Directors Association
2013;14(4):293-9.

Cohen-Mansfield 1998 {published data only}

Cohen-Mansfield J, Werner P.The eCects of an enhanced
environment on nursing home residents who pace.
Gerontologist 1998;38(2):199-208.

Coleman 2002 {published data only}

Coleman MT, Looney S, O’Brien J, Ziegler C, Pastorino CA,
Turner C.The Eden Alternative: findings aJer 1 year of
implementation. Journals of Gerontology. Series A, Biological
Sciences and Medical Sciences 2002;57(7):422-7.

De Boer 2017 {published data only}

De Boer B, Bozdemir B, Jansen J, Hermans M, Hamers JPH,
Verbeek H.The Homestead: developing a conceptual framework
through co-creation for innovating long-term dementia care
environments. International Journal of Environmental Research
and Public Health 2021;18(1):57.

De Boer B, Hamers JP, Beerens HC, Zwakhalen SM, Tan FE,
Verbeek H.Living at the farm, innovative nursing home care
for people with dementia – study protocol of an observational
longitudinal study. BMC Geriatrics 2015;15:144.

De Boer B, Hamers JP, Zwakhalen SM, Tan FE, Beerens HC,
Verbeek H.Green Care Farms as innovative nursing homes,
promoting activities and social interaction for people With
dementia. Journal of the American Directors Association
2017;18(1):40-6.

De Rooij 2012 {published data only}

De Rooij AH, Luijkx KG, Declercq AG, Emmerink PM,
Schols JM.Professional caregivers’ mental health problems and
burnout in small-scale and traditional long term care settings
for elderly people with dementia in the Netherlands and
Belgium. Journal of the American Medical Directors Association
2012;13(5):486.e7-11.

De Rooij AH, Luijkx KG, Schaafsma J, Declercq AG,
Emmerink PM, Schols JM.Quality of life of residents with
dementia in traditional versus small-scale long-term care
settings: a quasi-experimental study. International Journal of
Nursing Studies 2012;49(8):931-40.

De Rooij I, Luijkx K, Declercq A, Schols J.Small-scale living
facilities in the Netherlands and Belgium: a longitudinal study
on patient outcome; Fourth European Nursing Congress.
Journal of Clinical Nursing 2010;19:139.

Falk 2009 {published data only}

Falk H, Wijk H, Persson LO.The eCects of refurbishment
on residents’ quality of life and wellbeing in two Swedish
residential care facilities. Health and Place 2009;15(3):687-94.

Giggins {published data only}

Giggins OM, Doyle J, Hogan K, George M.The impact of a cycled
lighting intervention on nursing home residents: a pilot study.
Gerontology & Geriatric Medicine 2019;5:2333721419897453.

Hermer 2017 {published data only}

Hermer L, Bryant NS, Pucciarello M, Mlynarczyk C,
Zhong B.Does comprehensive culture change adoption via
the Household model enhance nursing home residents’
psychosocial well-being? Innovation in Aging  2017;1(2):igx033.

Holmes 1990 {published data only}

Holmes D, Teresi J, Weiner A, Monaco C, Ronch J,
Vickers R.Impacts associated with special care units in long-
term care facilities. Gerontologist 1990;30(2):178-83.

Inventor 2018 {published data only}

Inventor 2018.Longitudinal eCects of activities, social
environment, and psychotropic medication use on behavioral
symptoms of individuals with Alzheimer’s disease in nursing
homes. Journal of Psychosocial Nursing & Mental Health Services
2018;56(11):18-26.

Kane 2007 {published data only}

Kane RA, Lum TY, Cutler LJ, Degenholtz HB, Yu TC.Resident
outcomes in small-house nursing homes: a longitudinal
evaluation of the initial green house program. Journal of the
American Geriatrics Society 2007;55(6):832-9.

Klosinska {published data only}

Kłosińska U, Derejczyk J, Benek I, Szczepanek A,
Derejczyk G.Look around-architectural interventions in LTC
home and professional stress of formal caregivers. European
Geriatric Medicine  2019;10:S179.

Kok 2017 {published data only}

*  Kok JS, Berg IJ, Blankevoort GCG, Scherder EJA.Rest-activity
rhythms in small scale homelike care and traditional care for
residents with dementia. BMC Geriatrics 2017;17(1):137.

Kok JS, Van Heuvelen MJ, Berg IJ, Scherder EJ.Small scale
homelike special care units and traditional special care units:
eCects on cognition in dementia; a longitudinal controlled
intervention study. BMC Geriatrics 2016;16:47.

Kok 2018 {published data only}

Kok JS, Nielen MMA, Scherder EJA.Quality of life in small-scaled
homelike nursing homes: an 8-month controlled trial. Health &
Quality of Life Outcomes 2018;16(1):38.

Kubsch 2018 {published data only}

Kubsch SM, Tyczkowski BL, Passel C.The impact of the Eden
Alternative on hope. Nursing & Residential Care 2018;20(2):91-4.

Physical environmental designs in residential care to improve quality of life of older people (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

38

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Library

Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

Lee 2016 {published data only}

Lee SY, Chaudhury H, Hung L.ECects of physical environment on
health and behaviors of residents with dementia in long-term
care facilities: a longitudinal study. Research in Gerontological
Nursing 2016;9(2):81-91.

Lum 2008 {published data only}

Lum TY, Kane RA, Cutler LJ, Yu TC.ECects of Green House
nursing homes on residents’ families. Health Care Financing
Review 2008;30(2):35-51.

Molony 2011 {published data only}

Molony SL, Evans LK, Jeon S, Rabig J, Straka LA.Trajectories of
at-homeness and health in usual care and small house nursing
homes. Gerontologist 2011;51(4):504-15.

O’Connor 1991 {published data only}

O’Connor BP, Davidson H, GiCord R.Window view, social
exposure and nursing home adaptation. Canadian Journal on
Aging 1991;10(3):216-23.

Palm 2019 {published data only}

Palm R, Trutschel D, Sorg CG, Dichter MN, Haastert B,
Holle B.Quality of life in people with severe dementia and
its association with the environment in nursing homes: an
observational study. Gerontologist 2019;59(4):665-74.

Pomeroy 2011 {published data only}

Pomeroy SH, Scherer Y, Runkawatt V, Iamsumang W,
Lindemann J, Resnick B.Person-environment fit and functioning
among older adults in a long-term care setting. Geriatric Nursing
2011;32:368-78.

Potter 2018 {published data only}

Potter R, Sheehan B, Cain R, GriCin J, Jennings PA.The impact
of the physical environment on depressive symptoms of
older residents living in care homes: a mixed methods study.
Gerontologist 2018;58(3):438-47.

Reimer 2004 {published data only}

Reimer MA, Slaughter S, Donaldson C, Currie G,
Eliasziw M.Special care facility compared with traditional
environments for dementia care: a longitudinal study of
quality of life. Journal of the American Geriatrics Society
2004;52(7):1085-92.

Scott 2014 {published data only}

Scott TL, Masser BM, Pachana NA.Multisensory installations
in residential aged-care facilities: increasing novelty and
encouraging social engagement through modest environmental
changes. Journal of Gerontological Nursing 2014;40(9):20-31.

Steiner 2020 {published data only}

Steiner B.Assisted living facilities in inpatient and outpatient
settings [Wohn- und hausgemeinschaJen in stationären und
ambulanten settings]. Zeitschri/ Fur Gerontologie Und Geriatrie
2020;53(6):505-12.

Varshawsky {published data only}

Varshawsky A, Traynor V.Live behind the orange door –
the eCects of changing suite doors for individuals living

with dementia. Australian Nursing & Midwifery Journal 
2018;25(7):38-9.

*  Varshawsky AL, Traynor V.Graphic designed bedroom doors
to support dementia wandering in residential care homes:
innovative practice. Dementia – International Journal of Social
Research and Practice 2021;20(1):348–54.

Verbeek 2014 {published data only}

Verbeek H, Van Rossum E, Zwakhalen SM, Kempen GI,
Hamers JP.Small, homelike care environments for older
people with dementia: a literature review. International
Psychogeriatrics 2009;21(2):252-64.

Verbeek H, Zwakhalen SM, Van Rossum E, Ambergen T,
Kempen GI, Hamers JP.Dementia care redesigned: eCects of
small-scale living facilities on residents, their family caregivers,
and staC. Journal of the American Medical Directors Association
2010;11(9):662-70.

*  Verbeek H, Zwakhalen SM, Van Rossum E, Ambergen T,
Kempen GI, Hamers JP.ECects of small-scale, home-
like facilities in dementia care on residents’ behavior,
and use of physical restraints and psychotropic drugs: a
quasi-experimental study. International Psychogeriatrics
2014;26(4):657-68.

Verbeek H, Zwakhalen SM, Van Rossum E, Kempen GI,
Hamers JP.Small-scale, homelike facilities in dementia care:
a process evaluation into the experiences of family caregivers
and nursing staC. International Journal of Nursing Studies
2012;49(1):21-9.

Zwakhalen SM, Hamers JP, Van Rossum E, Ambergen T,
Kempen GI, Verbeek H.Working in small-scale, homelike
dementia care: eCects on staC burnout symptoms and job
characteristics. A quasi-experimental, longitudinal study.
Journal of Research in Nursing 2018;23(2-3):109-22.

 

References to studies awaiting assessment

Kolberg 2020 {published and unpublished data}

Johnsen Hjetland G.The ECect of Bright Light on Sleep in
Nursing Home Patients with Dementia (PhD thesis). Norway:
University of Bergen, 2021.

*  Kolberg E, Pallesen S, Johnsen Hjetland G, Nordhus IH,
Thun E, Flo-Groeneboom E.The potential of bright light
treatment in the management of depression and anxiety
in dementia during winter. Journal of Sleep Research
2020;29(Suppl 1):P309.

 

References to ongoing studies

Willemse 2011 {published data only}

Prins M, Willemse BM, Heijkants CH, Pot AM.Nursing home care
for people with dementia: update of the design of the Living
Arrangements for people with Dementia (LAD) study. Journal of
Advanced Nursing 2019;75(12):3792-804.

Physical environmental designs in residential care to improve quality of life of older people (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

39

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Library

Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

Smit D, De Lange J, Willemse B, Pot AM.Predictors of activity
involvement in dementia care homes: a cross-sectional study.
BMC Geriatrics 2017;17:175.

Smit D, Willemse B, De Lange J, Pot AM.Wellbeing-enhancing
occupation and organizational and environmental contributors
in long-term dementia care facilities: an explorative study.
International Psychogeriatrics 2014;26(1):69-80.

*  Willemse BM, Smit D, De Lange J, Pot A.Nursing home care for
people with dementia and residents’ quality of life, quality of
care and staC well-being: design of the Living Arrangements for
people with Dementia (LAD) study. BMC Geriatrics 2011;11:11.

Willemse BM.Working conditions and person-centredness of the
dementia care workforce: impact on quality of care, staC and
resident well-being. Vrije Universiteit Amsterdam: Amsterdam,
the Netherlands (accessed prior to 12 Feb 2022).

 

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Anderson RM, Grey T, Kennelly S, O’Neill D.Nursing home design
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Physical environmental designs in residential care to improve quality of life of older people (Review)

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Better health.

 
 

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HoCmann TC, Glasziou PP, Bourton I, Milne R, Perera R,
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Husebø BS, Ballard C,  Aarsland D,  Selbaek G,  Slettebo DD,
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Informed decisions.
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UN 2015

United Nations.World Population Ageing. www.un.org/en/
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Usman 2019

Usman A, Lewis S, HinsliC-Smith K, Long A, Housley G, Jordan J,
et al.Measuring health-related quality of life of care home
residents: comparison of self-report with staC proxy responses.
Age and Ageing 2019;48(3):407–13.

Van der Steen 2018

Van der Steen JT, Smaling HJA, Van der Wouden JC,
Bruinsma MS, Scholten RJPM, Vink AC.Music-based therapeutic
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of Systematic Reviews 2018, Issue 7. Art. No: CD003477. [DOI:
10.1002/14651858.CD003477.pub4]

Werner 2020

Werner RM, HoCman AK, Coe NB.Long-Term Care Policy aJer
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NEJMp2014811]

Whear 2014

Whear R, Coon JT, Bethel A, Abbott R, Stein K, Garside R.What
is the impact of using outdoor spaces such as gardens on the
physical and mental well-being of those with dementia? A
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Willemse BM, Depla MFIA, Smit D, Pot AM.The relationship
between small-scale nursing home care for people with

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Willemse BM, De Jonge J, Smit D, Visser Q, Depla MFIA,
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Willemse 2016

Willemse BM.Working Conditions and Person-Centredness of
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Vrije Universiteit Amsterdam, 2016.

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Woodbridge R, Sullivan MP, Harding E, Crutch S, Gilhooly KJ,
Gilhooly MLM, et al.Use of the physical environment to support
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References to other published versions of this review

Harrison 2017

Harrison SL, Dyer SM, Laver KE, Milte RK, Fleming R,
Crotty M.Physical environmental designs in residential care
to improve quality of life of older people. Cochrane Database
of Systematic Reviews 2017, Issue 12. Art. No: CD012892. [DOI:
10.1002/14651858.CD012892]

 
* Indicates the major publication for the study

 

C H A R A C T E R I S T I C S   O F   S T U D I E S

Characteristics of included studies [ordered by study ID]

 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: unclear (total of GreenHouse, control and excluded GreenHouse owned “legacy”
homes: 190; 12 intervention and 178 control)

Participants N = 74,449 (weighted sample)

Mean age: not reported.

% Female: not reported.

% Dementia: 33.9

Afendulis 2016 

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Mean number of comorbidities: not reported
Country: USA

Inclusion criteria:

Nursing homes:

• that adopted the GreenHouse (GH) model over the period 2005 to 2010 (from list provided by The
Green House Project)

• were in operation in the period prior to adoption – non-GH nursing home organisations matched at
facility-level by OSCAR (Online Survey, Certification, and Reporting)

• nursing home level data for each GH nursing home plus matched on state and year of adoption, using
nearest neighbour matching

• matched on these covariates: nonprofit ownership, for-profit ownership, government ownership,
chain status, small size (75 beds or fewer), medium size (76–125 beds), large size (126 or more
beds), rural location, above median Medicaid share, above median Medicare share, above median pri-
vate-pay share, and a nursing home-level aggregate activities of daily living (ADL) score (0 if less than
4 on a scale of 0–5, 1 otherwise), with propensity score weighting

Exclusion criteria:

• Residents who were not entitled to Medicare Part A in the month of admission

• Residents who died during the month of admission

• Residents who were enrolled in the Medicare Advantage program during the month of admission

Interventions Type of intervention: Home-like model

Name of intervention: Green House model.

Design features: Small buildings (maximum 12 residents) and fit the style of surrounding neighbour-
hood

Other features that differed: Residents have more control over daily activities.

Control: Matched by multiple facility characteristics, state and year that did not adopt the Green House
model, not a “small house” model

Outcomes The following outcomes were reported:

Rehospitalisations, avoidable rehospitalisations, bedfast residents, catheter use, pressure ulcers (low
risk and high risk) and use of physical restraints

Follow-up: Up to five years

Notes Study supported by the Robert Wood Johnson Foundation. Conflicts of interest: None. Ethical ap-
proval: not stated.

Data reported on “Legacy” units within the GreenHouse organisation (that were not GreenHouse model
of care homes) were excluded.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Afendulis 2016  (Continued)

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Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

Unclear risk Loss to follow-up not stated

Selective reporting (re-
porting bias)

Unclear risk No protocol; likely to be many fields in MDS not reported

Other bias High risk Method of selection of facilities unclear and potential residual confounding.
Significant differences in baseline characteristics. Significant differences for
many baseline outcome measures

Afendulis 2016  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 6 (3 intervention and 3 control)

Participants N = 56 (intervention: N = 28; control: N = 28)

Mean age (SD): Intervention: 82.8 (5.0), control: 81.6 (5.0)

% Female: Intervention: 89.3, control: 82.1

% Dementia: not reported

Mean number of comorbidities: not reported

Country: Sweden

Inclusion criteria:

• Intervention residents: Alzheimer’s, vascular dementia or mixed according to DSM-III criteria (severity
of dementia II to IV on Berger’s scale)

• Control residents: matched by age, gender, diagnosis and level of dementia to the intervention resi-
dents

Exclusion criteria:

• Patients suffering from physical illness, clinically estimated to become terminal within 1 year

Interventions Type of intervention: Home-like model

Design features: 8-10 residents, situated in ordinary blocks of flats in suburbs, specially adapted for
people living with dementia. Flats had private areas with 1 or 2 rooms with toilet and shower, kitchen,
living room, dining room and laundry room available to staC and residents. StaC/patient ratios were
similar in the two types of care (0.69 in group living; 0.71 in traditional). However, the intervention staC
were responsible not only for patient care but also for cooking, cleaning, washing, transportation and
activating therapies.

Annerstedt 1993 

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Other features that differed: StaC familiar with resident biographies. A group living project was con-
nected to a clinic, responsible for the geriatric care in a certain area corresponding to 20% of the per-
sons 65 years old or older of the population in the community.

Control: Offered in three big long-term care hospitals, mostly with wards of 50 patients and original-
ly designed for acute medical care or rehabilitation. The care was usually organised in four separate
groups in order to break the large-scale design of the physical environment. Each of these groups in-
cluded both somatic long-term care patients with and without dementia. StaC training was seldom reg-
ularly scheduled and surveyed most aspects of geriatric care, favouring physical items.

Outcomes The following outcomes (measurement scale) were reported:

Dyspraxia, hallucinations, lack of vitality, dysphasia, paranoia, aggressiveness, depression, clinical vari-
ations, restlessness, recent memory and identity (Organic Brain Syndrome Scale: OBS Scale)

Follow-up: 6 months and 12 months

Notes Sponsorship source: Swedish Medical Research Council, the Swedish Council for Social Research,
Alzheimer Foundation and Medical Foundation at Lund University. Conflicts of interest: Not stated. Eth-
ical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk 21% loss to follow-up

Selective reporting (re-
porting bias)

Low risk All outcomes discussed were reported.

Other bias High risk Possible confounding, unadjusted results. Significant baseline differences in
the time the participants had been institutionalised prior to relocation; partici-
pants in traditional facilities received more neuroleptic treatment. Differences
in baseline outcomes e.g. dyspraxia and identity not controlled for.

Annerstedt 1993  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Burack 2012 

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Number of facilities: 13 (7 intervention and 6 control)

Participants N = 201 enrolled, 101 analysed (intervention: N = 50; control: N = 51)

Mean age (SD): Intervention: 83.8 (8.8), control: 83.5 (9.8)

% Female: Intervention: 62, control: 67

% Dementia: 59 (not reported by intervention and control groups)

Mean (SD) number of comorbidities: 4.3 (1.9) (intervention: 4.2 (1.9) and control: 4.4 (2.0))

Country: USA

Inclusion criteria:

Facilities

• Intervention: 2 to 3 pilot communities at each of 3 nursing home campuses for a total of 7 communities
operated by one provider. Nursing and administrative staC chose communities with well-functioning
teams (2 communities each at 2 of the campuses, and 3 communities at the third campus) to pilot the
culture change intervention to optimise the potential for a successful culture change transformation.

• Comparison: 2 communities at each campus were identified to serve as a comparison group (for a total
of 6 comparison communities), selected by administrative and nursing leaderships’ clinical expertise
to best match the culture change group by the level of care needed by elders, staC team functioning,
number of elders in the community, and the environmental community structure.

Residents

• Living in community for at least 3 months, 60 years or older

Exclusion criteria:

• Not reported

Interventions Name of intervention: Culture change model

Design features: Environmental changes were implemented in elder rooms and common areas, with a
focus on person-centred care. Elders and their family members were encouraged to individualise elder
rooms with personal items, decoration, and pictures. Within the common areas, attention was given to
creating a calm, peaceful environment. In the dining areas, new table cloths were purchased, centre-
pieces were placed on tables, art work decorated the walls, and water and juice were easily accessible
to elders at all times. Hallways were decorated with painted murals and new wallpaper. The outsides
of the elders’ rooms were individualised to facilitate easy room recognition for the elders. Additionally,
homey nooks were created at the end of hallways with comfortable seating. Noise level was addressed
by discontinuing the overhead paging system and turning oC TVs and radios when they were not being
actively used.

Other features that differed: Community co-ordinators, education, organisational and community
structure changes, meaningful activities and resident choice, family involvement, reduced floating and
consistent staCing

Control: Continued to function along the nursing home’s pre-culture change model, following the typi-
cal nursing home organisational structure and standard administrative and departmental hierarchy of
care

Outcomes The following outcomes (measurement scale) were reported:

Behaviour: forceful behaviours, physical agitation and verbal agitation (Cohen-Mansfield Agitation In-
ventory: CMAI)

Follow-up: 2 years

Burack 2012  (Continued)

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Notes Sponsorship source not reported. Conflicts of interest: None. Ethical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

Unclear risk Large loss to follow-up; no differences between those lost and those with fol-
low-up, but this not reported by group allocation

Selective reporting (re-
porting bias)

High risk Only reported behavioural outcomes, not changes in ADLs or cognition. CMAI
overall score not reported and reported according to specific groupings

Other bias High risk Culture change communities selected based on “well-functioning teams” to
optimise potential for successful transformation. Significant baseline differ-
ences in ADLs and race reported. Significant differences in baseline outcome
measurements

Burack 2012  (Continued)

 
 

Study characteristics

Methods Study design: Cluster-randomised controlled trial.

Number of facilities: 38 (8 control, 10 PCE, 10 PCC, 10 PCE + PCC)

Participants N = 601 (person-centred environment (PCE): 154, person-centred care (PCC): 155, PCE + PCC: 150, usual
environment (UE, control): 142)

Mean age (SD): PCE: 84 (8), PCC: 84 (8), PCE + PCC: 84 (7), control: 86 (7)

% Female: PCE: 66, PCC: 67, PCE + PCC: 70, control: 77

% Dementia: 100

Mean (SD) number of comorbidities: not reported. % > 3 comorbidities: PCE: 35, PCC: 51, PCE + PCC: 55,
control: 68

Country: Australia

Inclusion criteria:

Residential aged care home

Chenoweth 2014 

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• Government accreditation and building certification; high-level care homes; accessible by sealed
road, located within a 500 km radius of Sydney, Australia; with room for improvement in both PCE and
PCC according to the Person-Centred Environment and Care Assessment Tool (PCECAT), a validated
44-item rating instrument with three domains designed for evaluation of residential aged care. The
PCECAT 4-point scale was rescored 0 (the best possible rating) and 1, 2, 3 (the worst possible ratings,
ranked).

• A total “room for improvement score” (RFI) was calculated by summing across items (20 items in do-
main 2 (care services), and 19 in domain 3 (environment)). Homes that scored 1–3 for both care ser-
vices and environment RFI were considered eligible.

Participants

• Self-consent, proxy consent or Guardianship Tribunal consent

• Recorded dementia diagnosis

• Permanent stay

• Admission at least 3 months prior to baseline

• Assessed high care needs and presence of agitation

• Ability to participate over the life of the study (e.g. no florid mental illness or end-stage dementia)

Exclusion criteria:

• Did not meet inclusion criteria

Interventions Type of intervention: PCE or PCE + PCC

PCE: Two chief investigators with expertise in Person-Centre Environment design and a Master of De-
sign research student took responsibility for implementing the PCE interventions at each of the 10 PCE
and 10 PCE + PCC sites. The Environment Audit Tool (EAT) was employed to evaluate the relationships
between operations and space in terms of effectiveness and ideal resident care, and determining re-
quired environmental changes to meet PCE principles at the sites. Discussions of EAT findings were
held with the home’s executive staC and managers to initially determine their understanding of the
dysfunction generated for residents through the poor physical environment features identified. Plan-
ning then occurred with these senior staC to determine the best ways to undertake the most essential
and inexpensive environmental changes required. Planned modifications to the environment were un-
dertaken in some homes where feasible by a contracted building company. The environment interven-
tions, agreed to by the managers and priced by the contractor, were as follows: (1) two facilities need-
ed extensions of activity space made by covering balconies or areas that were previously open; (2) two
facilities had changes made to internal walls that would allow better visual access to activity and bed-
room spaces; (3) one facility was to be altered to provide access to a courtyard from a dining area need-
ed for activity and group activities; (4) two facilities needed internal divisions with added partitions to
reduce the overstimulation in larger group spaces; (5) two facilities had walls removed to make sitting
areas visible to residents passing in the corridor; (6) one facility had fire doors relocated to improve ac-
cess to the garden and (7) the remaining facilities all had some variation of external paving, new sitting
areas in gardens or covered spaces in a landscaped exterior. All these changes were considered to pro-
vide maximum benefit in achieving improved support or staC undertaking PCC-focused activities while
engaging with residents.

PCC: Kitwood’s (1997) PCC principles, using experiential and adult learning approaches, were facil-
itated by two chief investigators with expertise in PCC approaches and one expert PCC trainer from
Alzheimer’s Australia, employing train-the-trainer processes. Five staC (one Care Manager, one Regis-
tered Nurse, two Enrolled Nurses or Assistants in Nursing, one Diversion/Recreation Therapist) from
each of the 10 PCC and 10 PCC + PCE homes were involved in the PCC training. The 32-hour oC-site
training occurred over 1 week, complemented by a further 32 hours of on-site education and support
to implement PCC in daily care practices and recreation activities. Prior experiences, case studies, role
plays and simulations were utilised to develop awareness and insight of the relationship between care
and the resident’s quality of life. The PCC trainer guided and supported PCC-trained staC to employ
PCC learning resources, mentoring and role modelling in educating all care and therapy staC in PCC.
With the support of their managers and the PCC trainer, direct-care staC members were assisted to de-
velop person-centred resident care and recreation activity plans, and to implement changes in care
routines and procedures, with the focus on improving residents’ quality of life and reducing changed

Chenoweth 2014  (Continued)

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behaviours. Ongoing telephone support continued for PCC-trained staC by the PCC trainer until post-
test.

Control: Regular monitoring of any unplanned changes to the environment

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Dementia Quality of Life: DEMQOL), agitation (Cohen-Mansfield Agitation Inventory:
CMAI), quality of care (Quality of Interactions Schedule: QUIS)

Follow-up: 8 months

Notes Sponsorship source: National Health and Medical Research Council, Australia (funding source category
1), University of Technology Sydney, Australia (primary sponsor) and Australian Health Ministers-States
& Territories, Australia (secondary sponsor). Conflicts of interest: None. Ethical approval: Research
ethics approval was granted by the University of Technology Sydney Human Research Ethics commit-
tee approval number: UTS-HREC 2006-269A in November 2007, and also by the participating residen-
tial care homes. Proxy consent was obtained for all participating residents and both written and verbal
consent were obtained from a small number of residents who were able to understand and remember
the study’s purpose and procedures prior to administering the measures that required their direct in-
volvement.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Low risk Generated using a SAS program

Allocation concealment
(selection bias)

Unclear risk Unclear where the randomisation sequence was stored

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not possible on outcomes collected involving residents, family or staC

Incomplete outcome data
(attrition bias)
All outcomes

Unclear risk 31% loss to follow-up and reasons not described. Analysis compared com-
pleters and non-completers.

Selective reporting (re-
porting bias)

Low risk Published protocol and outcomes reported in protocol were the same as in the
main paper.

Other bias Low risk No other instances for bias obvious from the study

Chenoweth 2014  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Dettbarn-Reggentin 2005 

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Number of facilities: 6 (3 intervention and number of control facilities unclear, but stated there was a
control group “for each of the three residential groups”)

Participants N = 60 (Intervention: N = 27; control N = 33)

Mean age: Intervention: 82.9, control: 83.1

% Female: Intervention: 81.5, control: 78.5

% Dementia: 100

Mean (SD) number of comorbidities: not reported

Country: Germany

Inclusion criteria:

Intervention participants

• Residents from 3 dementia-specific facilities

• Moderate or severe dementia (MMSE < 18)

• Barthel 25-50

• Not excluded based on behaviour

Control participants

• Residents from home operated by same provider

• Matched by age

• Progression of dementia and mobility (Barthel) Cognition: MMSE; function: Barthel; length of stay in
months

Exclusion criteria:

• Not reported

Interventions Name of intervention: Residential group environment

Design features: This was the focus of residential groups for people with dementia. A residential living
environment was created in small residential units that followed family structures. The size was be-
tween 6 and 12 and, exceptionally, up to 15 residents. A home-like living environment, adapted to the
residents, was created for all three segregated residential groups (13, 15, 15 residents). All three resi-
dential groups operated under the live-in kitchen model, aimed at addressing the residents’ multiple
facets (activation, communication, emotion, chronological structuring).

Other features that differed: Nursing home typical organisational structures were replaced by small-
scale design, familiarity, communication, needs-based activity and close human interaction (staC con-
sistency and staC on duty). The daily routine was not dominated by the care activity, but relied on fa-
miliar day-to-day household tasks. StaC members interacted with the residents in a trusting respectful
manner. The events of the day were aligned to the residents’ mobility, cognitive abilities as well as their
habits. The staC assigned to the participating residential groups and the control groups had compara-
ble qualifications and rosters.

Control: Nursing home typical organisational structures.

Outcomes The following outcomes (measurement scale) were reported:

Social behaviour (Nurses Observations Scale for Geriatric Patients: NOSGER), function (Barthel Index)
and cognitive function (Mini Mental State Examination: MMSE)

Follow-up: 12 months

Notes Sponsorship source not reported. Conflicts of interest: Not stated

Dettbarn-Reggentin 2005  (Continued)

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Ethical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk No randomisation

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk Stated 158 residents participated and 111 available for all three surveys but re-
sults for 60 presented

Selective reporting (re-
porting bias)

High risk Stated Cohen-Mansfield Agitation Inventory measured but results not shown

Other bias High risk No adjustments made so potential for confounding. For baseline characteris-
tics: no statistical tests completed, appeared to be some differences but un-
clear if statistically or clinically significant. Baseline differences in social be-
haviour

Dettbarn-Reggentin 2005  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 8 (3 intervention and 5 control)

Participants N = 119 enrolled (Intervention: N = 60, control: N = 59)

Mean age (SD): Intervention: 82.3 (5.7, mild cognitive impairment) 81.5 (7.4, severe cognitive impair-
ment), control: 82.7 (8.0, mild cognitive impairment) 82.2 (8.0, severe cognitive impairment)

% Female: Intervention: 79.8 (mild cognitive impairment) 82.1 (severe cognitive impairment), control:
78.1 (mild cognitive impairment) 82.1 (severe cognitive impairment)

% Dementia: not reported

Mean (SD) number of comorbidities: not reported

Country: Spain

Inclusion criteria:

• Cognitive impairment

Diaz-Veiga 2014 

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• Experimental group: resided in one of the 8 day or permanent cohabitation units, where the interven-
tions relating to “Etxean Ondo” were incorporated

• Control group: The members of the control group were identified from five distinct centres, three of
which coincided with the location of the cohabitation units.

Exclusion criteria:

• Absence of cognitive impairment, measured by Lobo’s Cognitive Mini Examination (MEC > 29)

Interventions Name of intervention: Etxean Ondo

Design features: Creation of domestic environments. “Comfortable, safe and accessible homelike envi-
ronments, which expedite the daily life of the residents by integrating their important preferences, cus-
toms and activities” and “physical spaces were selected that were susceptible to be adapted to the fea-
tures of domestic environments, favouring the incorporation of their own furniture and other decora-
tive and important items both in public and private spaces”.

Other features that differed: The development of important activities and organisational processes
based on the daily life and the resources of residents, families and professionals. Support staC who vol-
unteered to work in the units. Increased staC ratio “support staC ratio was increased, reducing the staC
rotation between the different areas in the centres, and providing them with continuous professional
development” and “periodical meetings of the technical staC (doctor, nurse, psychologist, etc.) with
the support teams were set up, changing the decision-making in relation to the care, with adaptations
based on the information provided by the support staC, who act as “reference professionals” for the
residents.”

Control: Provision of public health services in accordance with the health needs of the residents, the
formal registration of care tasks and activities, and the prioritisation of safety both in the design of the
spaces and the organisation.

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Quality of Life in Late-Stage Dementia: QUALID for severe cognitive impairment or Fumat
for mild cognitive impairment)

Follow-up: 6 months

Notes Sponsorship source not reported. Conflicts of interest: None
Ethical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk No randomisation

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)

Unclear risk Did not report loss to follow-up

Diaz-Veiga 2014  (Continued)

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All outcomes

Selective reporting (re-
porting bias)

Low risk Outcomes reported as per methods

Other bias High risk No adjustments made so potential confounding. Stated statistically different
quality of life measurements between groups at baseline. Possible contamina-
tion through professional staC “reduced staC rotation” mentioned which indi-
cates there may have still been some rotation, plus technical staC meetings

Diaz-Veiga 2014  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 18 (14 corridor design and 4 non-corridor design)

Participants N = 105 (Corridor design: N = 66; non-corridor design: N = 39)

Mean age (SD): Corridor design: 82.9 (5.3), non-corridor design: not reported

% Female: Corridor design: 89, non-corridor design: 87

% Dementia: 100

Mean (SD) number of comorbidities: not reported

Country: Sweden

Inclusion criteria:

• Living with dementia and admitted to group living units in Malmo, Sweden during study period

• Group living eligibility: dementia of Alzheimer’s type or vascular dementia, care planning team judged
home care situation as insufficient

Exclusion criteria:

• Not reported

Interventions Type of intervention: building layout (comparison of group living units with a corridor design versus
non-corridor design (L-shaped, square or H-shaped))

Design features: Built for 6-8 residents, with specially designed community area comprising living
room, laundry, kitchen and dining room shared by the residents and staC. Each resident has a private

area of approximately 25 m2, furnished by the resident and included a toilet and shower. Located in or-
dinary blocks of flats outside institutions. Physical environment assessed by architect in standardised
manner using Therapeutic Environment Screening Scale (TESS-2)

Outcomes The following outcomes (measurement scale) were reported:

Dyspraxia, hallucinations, lack of vitality, dysphasia, paranoia, aggressiveness, depression, clinical vari-
ations, restlessness, recent memory and identity (Organic Brain Syndrome Scale: OBS Scale)

Follow-up: 12 months

Notes Supported by the Swedish Council for Social Research. Conflicts of interest: Not stated. Ethical ap-
proval: Not stated

Elmstahl 1997 

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Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk No blinding

Incomplete outcome data
(attrition bias)
All outcomes

Low risk > 90% follow-up; unlikely to bias results

Selective reporting (re-
porting bias)

High risk In the methods, there was mention of measuring ADLs and MMSE but results
for these have not been reported. Also 6-month data were not reported.

Other bias Unclear risk Potential residual confounding and baseline characteristics not shown by
group. Significant differences in lack of vitality and restlessness at baseline.
Adjusted analysis accounted for other symptoms.

Elmstahl 1997  (Continued)

 
 

Study characteristics

Methods Study design: cluster-randomised trial (participants served as own controls)

Number of facilities: 8

Participants N = 52 

Mean age (SD): 85.1 (7.1)

% Female: 65.2%

% Dementia: 100

Number of comorbidities: not reported

Country: USA

Inclusion criteria: diagnosis of dementia according to Diagnostic and Statistical Manual of Mental Dis-
orders, Fourth Edition; a Mini Mental State Examination (MMSE) score between 4 and 24 points (indicat-
ing severe [≤ 10] to mild [< 25] dementia) or a Brief Interview for Mental Status (BIMS) score between 3
and 12 points (indicating severe [≤ 7] to moderate [8–12] cognitive impairment), depending on the par-
ticular facility’s evaluation procedures; and a score > 5 (indicating sleep disturbance) on the Pittsburgh
Sleep Quality Index (PSQI) questionnaire

Figueiro 2019 

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Exclusion criteria: Major organ failure, a major illness, a history of head injury, uncontrolled generalised
disorders (e.g. diabetes), obstructing cataracts, macular degeneration, blindness, or used psychotropic
medicine. Those with severe sleep apnoea or restless legs syndrome were also excluded

Interventions Lighting designed to provide high circadian stimulus. Custom-built floor luminaires, light boxes and
light tables were used. Timers activated lights according to wake times and lights were placed in the
person’s bedroom or in the common area until 6 pm.

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Minimum Data Set Activities of Daily Living Scale (MDS-ADL)), behaviour (Cohen-Mans-
field Agitation Inventory (CMAI)) and depression (Cornell Scale for Depression in Dementia (CSDD))

Notes Sponsorship source: This research was funded by the National Institute on Aging (grant
#R01AG034157); the following manufacturers are acknowledged for their provision of in-kind lighting
products: GE Current, a Daintree company; OSRAM Sylvania; Ketra; and Sharp Corporation. Conflicts of
interest: Neither the funding agency nor the in-kind contributors had
any role in the design, methods, data analysis, or preparation of the manuscript.
Figueiro, Plitnick, Roohan, Sahin, and Rea received research grant support from the National Institutes
of Health, Office of Naval Research, The United States General Services Administration, and industry
(Acuity Brands; Axis Lighting; GE Current, a Daintree company; OSRAM Sylvania; Ketra; USAI Lighting;
Armstrong Ceilings and Walls; Philips Lighting; Cree; View Glass; Marriott International). Kalsher re-
ceived research grant support from the National Institutes of Health. Ethical approval: Approved by the
Rensselaer Polytechnic Institute Institutional Review Board

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Unclear risk Unclear as to method of sequence generation

Allocation concealment
(selection bias)

Unclear risk Did not specify details

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

Unclear risk Details of blinding not reported

Blinding of outcome as-
sessment (detection bias)
All outcomes

Unclear risk Details of blinding not reported

Incomplete outcome data
(attrition bias)
All outcomes

Unclear risk No flow of participants reported. Reported data not available for 4 participants
due to nonadherence and some data were not usable

Selective reporting (re-
porting bias)

Low risk Trial registered

Other bias Low risk Participants served as own controls.

Figueiro 2019  (Continued)

 
 

Study characteristics

Frisoni 1998 

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Methods Study design: Controlled before-after study

Number of facilities: 43 (25 SCU and 18 control)

Participants N = 66 (Special care unit (SCU): N = 31; control: N = 35)

Mean age (SD): SCU: 81 (8), control: 81 (6)

% Female: SCU: 71, control: 80

% Dementia: 100

Mean (SD) number of comorbidities: SCU: 18 (4), control: 19 (3)

Country: Italy

Inclusion criteria:

Facilities

• NHs of East Lombardia region and Milano area that admitted residents with dementia with some de-
gree of behavioural disturbance expected to stay at least 3 months

Patients

• Newly admitted

• Diagnosis of degenerative or vascular dementia according to accepted criteria, MMSE 21 or lower plus
CDR 4 or lower plus at least one behavioural disturbance of mild to moderate severity

• MMSW 16 or lower, CDR score 2-4, NPI total 24 or higher or score of 12 or more in at least one subscale

Exclusion criteria:

• MMSE 22 or higher, extended CDR scale 5 or higher (bed-bound)

• 15 days or more between admission and communication

• Incomplete data provided by NH physician in first screening form

• History of mental insufficiency, psychosis or major depression

Interventions Type of intervention: 10 two-bed rooms, a large wandering area, a dining room, and a separate area
for structured activity (physical and occupational therapy). Exit doors were secured by magnetic locks
opening with a digital code. Noxious stimuli were minimised, and wall colours were made neutral. Way-
finding cues were used to help residents identify different areas.

Outcomes The following outcomes (measurement scale) were reported:

Delusions, hallucinations, agitation, anxiety, euphoria/elation, disinhibition, irritability/lability, abnor-
mal motor behaviour, sleep and global behaviour (NPI), agitation (CMAI), depression, cognitive func-
tion (MMSE and Clinical Dementia Rating), function (Bedford Alzheimer’s Nursing Severity Scale), func-
tion (Barthel Index), falls in 3 months, physical restraints

Follow-up: 3 months

Notes Supported by European Commission (DGV). Conflicts of interest: Not stated. Ethical approval: Not stat-
ed

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Frisoni 1998  (Continued)

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Allocation concealment
(selection bias)

High risk Allocation not concealed

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Not blinded. Follow-up assessment carried out by same interviewer who car-
ried out baseline assessment whenever possible.

Incomplete outcome data
(attrition bias)
All outcomes

Low risk Appeared to be no loss to follow-up over 3 months

Selective reporting (re-
porting bias)

Low risk All relevant outcomes in the methods section were reported in the results sec-
tion.

Other bias High risk Possibility of residual confounding. High risk of falls outcome only; low risk for
other outcomes. Higher risk of falls (Tinetti balance and gait scale) in tradition-
al arm. Differences in behavioural disturbances at baseline (although not sta-
tistically significant) and no adjustments made

Frisoni 1998  (Continued)

 
 

Study characteristics

Methods Study design: cluster-randomised controlled trial

Number of facilities: 12 (6 intervention and 6 control)

Participants N = 336 (173 intervention, 163 control)

Mean age (SD): 82.6 (10.1). Intervention: 82.7 (9.8), control: 82.5 (10.4)

% Female: 72.0%. Intervention: 72.3%, control: 71.8%

% Dementia: not reported

Mean comorbidities (SD): 2.9 (1.6). Intervention: 2.8 (1.5), control: 3.1 (1.7)

Country: USA

Inclusion criteria: 55 years of age or older, able to speak English, currently living in the nursing home,
and scored ≤ 15 on the Mini-Mental State Examination (MMSE)

Exclusion criteria: receiving hospice or sub-acute rehabilitation

 

Interventions Function and Behavior Focused Care for the Cognitively Impaired (FBFC). The FBFC Research Nurse
worked with the facility Champion to assess the facility’s policies and the environment to identify op-
portunities for physical activity and engaging in functional tasks as well as barriers to these activities.
For example, corridors were evaluated for wide, clear areas for walking and outdoor access was as-
sessed. In addition, the FBFC Nurse and Champion collaborated with the activities director and reha-
bilitation staC (as available) to determine opportunities for exercise classes within the facility. Barriers
to physical activity, such as policies that unnecessarily restrict movement for fear of falls, and environ-
ments that lack rest areas and age-appropriate exercise materials also were assessed. Based on these

Galik 2021 

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assessments, modifications in policy and the environment were made, such as increasing availability
of recreational activities that included physical activity (i.e. horseshoes, resistance bands, physical ac-
tivity, BINGO), having adequate supply of chairs in dining rooms to allow for transfer out of wheelchairs
for meals, having safe access to the outdoors, placing a bench in a hallway to have a resting place when
walking, providing long-handle sponges, no spill cups, adaptive utensils as appropriate, and changing
the height of a toilet or bed to facilitate function.

Outcomes The following outcomes (measurement scale) were reported:

Depression (Cornell Scale for Depression in Dementia (CSDD)), behaviour (Cohen-Mansfield Agitation
Inventory (CMAI)), resistiveness to care (Resistiveness to Care Scale) and function (Barthel Index)

Notes Sponsorship source: National Institute on Aging grant R01 AG046217. Conflicts of interest: None. Ethical
approval: Approved by a university-based institutional review board

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Low risk Coin toss within matched pairs

Allocation concealment
(selection bias)

Unclear risk Not specified

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk High for staC reported, functional ability, behaviour and mood

Incomplete outcome data
(attrition bias)
All outcomes

Unclear risk Large loss to follow-up, 146 (30%) after randomisation due to MMSE but un-
clear which randomised group they belonged to. Other reasons: very roughly
balanced follow-up 61% intervention group, 73% control group (119/163)

Selective reporting (re-
porting bias)

Low risk All reported as per methods

Other bias Unclear risk Differences in baseline outcome measures but no statistical significance re-
ported

Galik 2021  (Continued)

 
 

Study characteristics

Methods Study design: Randomised trial (cross-over)

Number of facilities: 8 (cross-over trial)

Participants N = 80 enrolled; N = 69 post-intervention

Mean age (SD): 85.8 (7.5)

% Female: 86.3

Hopkins 2017 

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% Dementia: not reported

Mean (SD) number of comorbidities: not reported

Country: England

Inclusion criteria:

• Resident of one of seven included care homes over 60 years of age

• Willing and able to give written informed consent or their family spend time each day in communal
rooms where lights were installed

Exclusion criteria:

• Did not meet inclusion criteria

Interventions Type of intervention: lighting (blue-enriched lighting)

Design features: High colour temperature (17000 K) blue-enriched white light in communal areas

Control: Low colour temperature (4000 K) white light

Outcomes The following outcomes (measurement scale) were reported:

Behaviour and depression (Hospital Anxiety and Depression: HAD scale and Geriatric Depression Scale:
GDS)

Follow-up: 4 weeks

Notes Sponsorship source: Cross-Council New Dynamics of Ageing (NDA) Initiative

Conflicts of interest: There were no financial, personal, potential conflicts of interest in the conduct of
the study or in the manuscript development. Although Philips Lighting supplied the light fitments, they
had no part in the design of the protocol nor in the analysis of the data. Prof. Skene and Dr Middleton
are co-directors of Stockgrand Ltd and Prof. Skene has in the past received research grant support from
Philips. Dr. Luc Schlangen is an employee of Philips Research.
Ethical approval: A favourable ethical opinion was obtained from the University of Surrey Ethics Com-
mittee and the care homes, whilst all research was carried out according to the Declaration of Helsin-
ki 2008. Informed written consent was obtained from participants or their families where participants
were unable to give consent themselves.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Unclear risk Described as randomised but did not specify randomisation

Allocation concealment
(selection bias)

Unclear risk Did not specify details

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk No blinding reported

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk No blinding reported

Incomplete outcome data
(attrition bias)

High risk 69 completed study but 56 at most were analysed for included outcomes.

Hopkins 2017  (Continued)

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All outcomes

Selective reporting (re-
porting bias)

Unclear risk Paper did not report details of published study protocol or trial registration.

Other bias Unclear risk Age and sex reported for each care home at baseline appeared to be different,
but no statistical tests performed and no other characteristics reported. Base-
line outcomes measures reported in little detail

Hopkins 2017  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 6 (3 intervention and 3 control)

Participants N = 120 (Intervention: N = 57; control: N = 48)

Mean age (SD): Intervention: 86.1 (6.7), control: 87.7 (6.8)

% Female: Intervention: 67, control: 75

% Dementia: not reported

Mean (SD) number of comorbidities: not reported

Country: UK

Inclusion criteria:

• If informed assent provided (where the resident could not self-consent), the interview only went ahead
if the resident appeared happy and relaxed during the process.

Exclusion criteria:

• Living in the care home less than two months

Interventions Type of intervention: dining

Design features: Food displayed for residents to see, fewer tables in dining room, tablecloths, flowers
on table, white crockery with side plates for vegetables, drinks machine available at all times, biscuits,
fruit, sandwiches and yoghurts on display available any time

Other features that differed: Increased choice at meals, increased number of hot meal options at break-
fast and evening meal, choice of meal at mealtime with change of mind accommodated, use of buffet
and Bain-Marie to display options to residents, dining open for 90 minutes with several sittings of resi-
dents, visitors welcome, large variety of self-service snacks available

Control: Limited choice at meals, only cold meal options available at breakfast and evening meal, res-
idents make their meal selection in advance, meals at set times with single sitting, visitors rarely eat
with residents, limited drinks and snacks available only on drinks trolley

Outcomes The following outcomes (measurement scale) were reported:

Cognitive function (Mini Mental State Examination: MMSE), behaviour and depression (Hospital Anxiety
and Depression: HAD scale) and adverse events (number of falls)

Follow-up: 12 months

Kenkmann 2010 

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Notes Funded by Norfolk City Council

Conflicts of interest: The research was funded by Norfolk County Council, and JB works for Norfolk
County Council. These links did not affect the way that the data are presented. Ethical approval:
Ethical approval for the study was obtained from the University of East Anglia, Faculty of Health,
Ethics Committee. The trial was registered as ISRCTN86057119 (see http://www.controlled-tri- al-
s.com/ISRCTN86057119).

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Non-randomised trial

Allocation concealment
(selection bias)

High risk Non-randomised trial

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Primary outcome (falls) measured from the notes as reported by staC (who
knew the allocation)

Incomplete outcome data
(attrition bias)
All outcomes

High risk Significant incomplete outcome data (which authors themselves noted)

Selective reporting (re-
porting bias)

Low risk No evidence of selective reporting as all outcomes described in methods were
in results

Other bias High risk Potential residual confounding. Significant differences in baseline characteris-
tics between groups at baseline

Kenkmann 2010  (Continued)

 
 

Study characteristics

Methods Study design: Repeated measures study with no control group

Number of facilities: 2 (repeated measures study)

Participants N = 34

Mean age: 77.8

% Female: 33

% Dementia: 100

Mean (SD) number of comorbidities: not reported

Country: Canada

Inclusion criteria:

Marcy-Edwards 2011 

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• A diagnosis of dementia

• Presence of one or more difficult to manage behaviours

• Living in a long-term care setting

• Consent from their legal guardian to participate

• Moderate to severe dementia as indicated by Global Deterioration Scale/Functional Assessment Stag-
ing (GDS/FAST) (138, 139) scores of 5 to 7 and Mini Mental State Exam (MMSE) (139, 140) score of less
than 20

• Residence on the unit for a minimum of four weeks

• A minimum of one difficult-to-manage behaviour such as delusions, hallucinations, agitation/aggres-
sion, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritabili-
ty/lability, aberrant motor behaviour, sleep and night-time behaviour disorders, and appetite and
eating disorders

Exclusion criteria:

• Presence of intractable pain

Interventions Type of intervention: Garden vignette

Design features: Designated area that contained clusters of gardening and nature-related objects de-
signed to both attract attention and encourage self-determined interaction and exploration. Identi-
cal vignettes were established on each unit directly opposite each other but separated by a five-foot
high wall. Positioned in a highly visible, high traffic space. The vignette included all objects required
to accomplish the activity of gardening: a sturdy garden centre table; soil, plastic pots, garden seeds,
light plastic garden tools, and a plastic watering can; scented, colourful, edible plants; glossy garden-
ing magazines with engaging pictures; and large artificial flowers to attract attention. When the garden
vignette was in place, all residents had unobstructed exposure and access, 24 hours per day.

Outcomes The following outcomes (measurement scale) were reported:

Behaviour (Neuropsychiatric Inventory for Nursing Homes: NPI-NH and NPI-NH-Occupational Distress:
NPI-NH-OD)

Follow-up: Placed for 14 days then removed for 14 days and process repeated once

Notes Sponsorship source: Canadian Nurses Foundation, Dr. Ann Beckingham Scholarship and the Alberta
Registered Nurses Educational Trust Scholarship.

Conflicts of interest: Not stated.
Ethical approval: The Institutional Ethics Review Board of the University of Calgary granted ethics ap-
proval

Risk of bias

Bias Authors’ judgement Support for judgement

Allocation concealment
(selection bias)

High risk Repeated measures study, no control group

Incomplete outcome data
(attrition bias)
All outcomes

Low risk Lowest follow-up for one outcome was 29/34 = 85%.

Selective reporting (re-
porting bias)

Low risk All outcomes reported as stated in methods

Other bias Low risk Same study participants used as repeated measures study. Intervention re-
moved during washout phases

Marcy-Edwards 2011  (Continued)

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Intervention independent
of other changes (ITS)

Unclear risk No reported compelling evidence that intervention was independent, nor
that that intervention was not independent of other changes in time

Shape of the intervention
effect pre-specified (ITS)

High risk Baseline measurement spread over 4 weeks, performed at time of admission,
then intervention effect in second week of vignette rather than at the time of
intervention

Intervention unlikely to af-
fect data collection (ITS)

Low risk Sources and methods of data collection were the same before and after the in-
tervention.

Marcy-Edwards 2011  (Continued)

 
 

Study characteristics

Methods Study design: Cluster-randomised controlled trial

Number of facilities: 4 wards in one nursing home randomised (2 Intervention wards and 2 control
wards)

Participants N enrolled: Intervention: 21, control: 17. N analysed: Intervention: 20, control: 14

Mean age (SD): Intervention: 82.6 (7.5), control: 78.2 (7)

% Female: Intervention: 66.6, control: 70

% Dementia: Not reported

Mean (SD) number of comorbidities: Intervention: 3 (1.2), control: 2.3 (1.3)

Country: The Netherlands.

Inclusion criteria:

• Resident in a nursing home from one of the four wards invited to join the study

• Older than 65 years

• Resident for more than 3 months at the start of the study

Exclusion criteria:

• Parenteral nutrition

• Terminal phase of a disease

• A specific exclusion criterion for the analyses of biochemical indicators of health was applied for the
patients with severe anaemia.

Interventions Type of intervention: Dining

Design features: Plant or flowers placed on every table and sufficient lighting. Background music cho-
sen by the patients. Just before meals, tables were dressed up in the dining room with appropriate
tablecloths and dinner plates, trays and covers removed from the table, carers out of patients’ sight.
Other features that differed: Dishes served on dinner plate per course and per table, simultaneous start
of the meal per table, and possibility of receiving help when necessary. Breakfast and supper served
per table and at patients’ discretion: no ready-to-eat sandwiches. Continuous availability of coffee, tea,
and soJ drinks such as fruit juices outside meal periods. Rescheduling nursing staC timetable to have
enough nurses at mealtime (one nurse for two patients). No walking around of the nursing staC in the
dining room during meals. Medications handed out before the start of the meal to distinguish med-
ical care and meals. No interference with patients’ meal: no questions or wishes for the next meal. Pro-
gramme monitoring every trimester by both nursing staC and researchers. No cleaning activities in the

Mathey 2001 

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dining room during meal consumption. Immediately after meals, tidying up the dining-room for the so-
cial activities

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Sickness Impact Profile: SIP and Dutch version of the Philadelphia Geriatric Center Moral
Scale: PGCMS)

Follow-up: 4 months, 8 months and 12 months

Notes Sponsorship source: Not reported.

Conflicts of interest: Not stated. Ethical approval: The study protocol was approved by the ethical com-
mittee of the nursing home.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Unclear risk Randomisation method not stated

Allocation concealment
(selection bias)

Unclear risk No details reported

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

Unclear risk Not reported

Incomplete outcome data
(attrition bias)
All outcomes

High risk 58% loss to follow-up for quality of life outcomes

Selective reporting (re-
porting bias)

Unclear risk Protocol or trial registration not mentioned

Other bias High risk Some clinical differences between groups in baseline characteristics. Statis-
tical significance of differences not reported. Likely some contamination as
wards randomised but within one nursing home

Mathey 2001  (Continued)

 
 

Study characteristics

Methods Study design: Cluster-randomised controlled trial

Number of facilities: 6 (3 intervention and 3 control)

Participants N enrolled: Intervention: 133, control: 112. N analysed: Intervention: 95, control: 83

Mean age (SD): Intervention: 78 (11.1), control: 75 (9.9)

% Female: Intervention: 70, control: 55

Nijs 2006 

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% Dementia: 0

Mean (SD) number of comorbidities: Intervention: 3 (1.4), control: 3 (1.6)

 

Country: The Netherlands

Inclusion criteria:

• Residing in an eligible nursing home ward (medium-sized, general population, two wards for chronic
somatic disease, long-term care, cover different parts of country, similar in organisational character-
istics)

Exclusion criteria:

• Terminal phase of disease

• Needing total parenteral feeding

• Unable to give informed consent owing to a physical or mental condition

Interventions Type of intervention: Dining

Design features: Tablecloths, normal plates and glasses, full cutlery, and flower arrangements

Other features that differed: Cooked meals served on table, greater choice at meals, residents decide
when meal begins, staC sit down with residents

Control: No tablecloth, plastic cups, pre-designed plate, divided into 3 sections, residents wear bibs.
Cooked meals served individually on pre-plated tray, residents choose meals two weeks before, staC do
not sit down, no choice in meal times

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Dutch Quality of Life of Somatic Nursing Home Residents questionnaire) and function
(Nursing Home Physical Performance test)

Follow-up: 6 months

Notes Sponsorship source: Netherlands Organisation for Health Research and Development. Conflicts of
interest: None. Ethical approval: This study was approved by the Ethical Committees of the nursing
homes and the Medical Ethical Committee of Wageningen University.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Non-random component in the sequence generation (e.g. using first letter of
ward name)

Allocation concealment
(selection bias)

Low risk Randomisation at start of study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

Unclear risk Allocation was blinded but did not describe details of whether the analyses
were blinded

Nijs 2006  (Continued)

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Incomplete outcome data
(attrition bias)
All outcomes

High risk Follow-up < 80%

Selective reporting (re-
porting bias)

Low risk All outcomes in methods reported in results

Other bias High risk Baseline differences between groups in age, gender and length of stay

Nijs 2006  (Continued)

 
 

Study characteristics

Methods Study design: 2 x 2 factorial randomised trial

Number of facilities: 12 (6 intervention and 6 control)

Participants N enrolled: intervention: 49, control: 45. N analysed: Intervention: 47, control: 40

Mean age (SD): Intervention: 85 (6), control: 85 (5)

% Female: Intervention: 91.8, control: 88.9

% Dementia: 100

Mean (SD) number of comorbidities: not reported

 

Country: The Netherlands

Inclusion criteria:

• Resident at one of 12 facilities who agreed to participate (assisted-care facilities in which residents
have their own apartment where they sleep and retreat, but spend most of the daytime in a common
living room supervised by caregivers)

Exclusion criteria:

• Nil other

Interventions Type of intervention: Lighting (bright light)

Design features: Light exposure was manipulated by installing a large number of ceiling-mounted fix-
tures with Plexiglas diffusers containing an equal amount of Philips TLD 840 and 940 fluorescent tubes
in the common living room. Lights were on daily between approximately 9 am and 6 pm. Light intensity
was increased to ± 1000 lux between 10 am and 6 pm at the 6 light facilities (active condition)

Control: An equal number of fixtures were installed, but these contained only half of the tubes, accom-
modated concealed band-stop filters, and were installed at a greater distance from the eyes.

Outcomes The following outcomes (measurement scale) were reported:

Behaviour (Neuropsychiatric Inventory: NPI), depression (Cornell Scale for Depression in Dementia:
CSDD), withdrawn behaviour (sub-scale of the Multi Observational Scale for Elderly Subjects: MOSES),
agitation (Cohen-Mansfield Agitation Inventory: CMAI), positive and negative mood (Philadelphia Geri-
atric Centre Affect Rating Scale: PGCARS), cognitive function (Mini Mental State Examination: MMSE),
and function (Nurse-informant adaptation of the scale by Katz and colleagues)

Riemersma-vanDerLek 2008 

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Follow-up: 6 weeks, 6 months, 12 months, 18 months and 24 months

Notes Sponsorship source: Financial and material support were provided by the Netherlands Organisation
for Health Research, The Hague, by grants 0028-300-30 and 907-00-012; the Netherlands Organisation
for Scientific Research, The Hague, by grants 016.025.041 and 051.04.010; the Stichting De Drie Lichten,
Leiden;Stichting RVVZ; Zeist by grant 01-220; Japan Foundation for Aging and Health; Hersenstichting
Nederland by grant 11F04-2.47; Internationale Stichting Alzheimer Onderzoek by grant 05511. Philips
Lighting BV, Braun, and Cambridge Neurotechnology supplied material for this study at reduced cost.

Conflicts of interest: Reported no financial disclosures
Ethical approval: The Medical Ethics Committees of Hospital De GelderseVallei, Ede, and the VU Univer-
sity Medical Center, Amsterdam, the Netherlands, approved the study.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

Low risk Random number generator

Allocation concealment
(selection bias)

Low risk Managed by a research assistant external to the study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

Low risk Stated caregivers blinded and no significant difference when they asked care-
givers to guess their facilities light status

Blinding of outcome as-
sessment (detection bias)
All outcomes

Low risk Assessors were blinded to allocation.

Incomplete outcome data
(attrition bias)
All outcomes

High risk High loss to follow-up

Selective reporting (re-
porting bias)

Low risk Registered on clinical trial registry – all outcomes reported

Other bias Low risk No significant differences in baseline characteristics between groups. No dif-
ferences in baseline outcome variables. Light exposure randomised by facility
protecting against contamination

Riemersma-vanDerLek 2008  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 26 (19 intervention and 7 control)

Participants N enrolled: Intervention: 79, control: 132. N analysed: Intervention: 67, control: 97

Mean age (95% confidence interval): Intervention: 81.2 (79.7, 82.7), control: 83.6 (81.1, 86.1)

% Female: Intervention: 91.0, control: 73.2

% Dementia: 100

Te Boekhorst 2009 

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Mean (SD) number of comorbidities: not reported

Country: The Netherlands

Inclusion criteria:

• Psychogeriatric group living homes and psychogeriatric nursing homes or nursing homes with psy-
chogeriatric units were selected.

Group living homes

• Maximum 6 residents

• Maximum 6 units

• Situated more than 200 m from the nursing home to which they belonged

• Prepared their own meals

• Built more than 2 years prior to the start of the study

Traditional nursing homes

• Built according to the Dutch 1997 Building Regulation for Nursing Homes

• 20 residents per unit

Exclusion criteria:

• Residents not surviving to 6 months

Interventions Type of intervention: home-like model

Design features: Psychogeriatric group living homes. Criteria based on Concept Map that defined group
living care (a) had a maximum of six residents; (b) had a maximum of six units; (c) were situated more
than 200 meters from the nursing home to which they belonged; (d) prepared their own meals and (e)
were built more than 2 years prior to the start of the study.

Control: Psychogeriatric nursing homes or nursing homes with psychogeriatric units. Built according to
the Dutch 1997 Building Regulation for Nursing Homes, as these facilities offer, among other structural
improvements, only single bedrooms. Large-scale: more than 20 residents per unit were included in the
study.

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Dementia Quality of Life: DQoL), behaviour (Revised Memory and Behavior Problems
Checklist: RMBPC and the Neuropsychiatric Inventory-Questionnaire: NPI-Q), cognitive function (Stan-
dardised Mini Mental State Examination: S-MMSE), function (Interview for the Deterioration of Daily Liv-
ing activities in Dementia: IDDD), social engagement (Revised Index of Social Engagement: RISE from
the Resident Assessment Instrument: RAI) and physical restraints (nursing home physician or psycholo-
gist asked whether residents were prescribed one or more physical restraints)

Follow-up: 6 months

Notes Sponsorship source: Dutch ministry of Health Welfare and Sport, Foundation Het Zonnehuis, ActiZ or-
ganisation of care entrepreneurs

The authors had no conflicts of interests during any part of the study. Sponsors had no role in the de-
sign, collection, analysis and interpretation of the data, nor in writing the report and the decision to
submit it for publication.
Ethical approval: The study was approved by the Medical Ethics Committee of the National Institute of
Mental Health and Addiction.

Risk of bias

Bias Authors’ judgement Support for judgement

Te Boekhorst 2009  (Continued)

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Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk < 80% follow-up

Selective reporting (re-
porting bias)

Low risk All outcomes reported as stated in methods

Other bias High risk Potential residual confounding. Significant differences in cognition (MMSE)
and depression scores at baseline

Te Boekhorst 2009  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 112 (89 intervention and 23 control)

Participants N enrolled: Intervention: 34, control: 22. N analysed: Intervention: 20, control: 13

Mean age (SD): Intervention: 83.4 (8.1), control: 81.2 (10.4)

% Female: Intervention: 76.9, control: 23.1

% Dementia: 100

Mean (SD) number of comorbidities: not reported

Country: Germany

Inclusion criteria:

• New residents of SHA and SCU with dementia in Berlin 1 July-31 Dec 2008

• Established diagnosis dementia – MMSE 24 or below

• Moving into SHA or SCU within 14 days

• Control (SCU): Admission criteria were eligibility to benefits under the long-term care insurance
scheme, a medical diagnosis of irreversible dementia and a score of less than 18 points according to
the MMSE, severe behavioural problems according to the modified Cohen-Mansfield Agitation Inven-
tory and being able to participate in group activities and general group social life.

Exclusion criteria:

• Not reported

Wolf-Ostermann 2012 

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Interventions Type of intervention: home-like model

Design features: Small-scale living shared housing arrangements were completely disconnected from
traditional nursing homes. Often situated in large apartments in mostly urban settings, mostly 6-8 peo-
ple, which had typical structures of a flat with a kitchen, a living room and private bedrooms

Control: Special-care unit for people with dementia. Admission criteria for special-care unit for people
with dementia in Berlin were eligibility to benefits under the long-term care insurance scheme, a med-
ical diagnosis of irreversible dementia and a score of less than 18 points according to the MMSE, severe
behavioural problems according to the modified Cohen-Mansfield Agitation Inventory and being able
to participate in group activities and general group social life.

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Dementia-specific QUALIDEM), behaviour (Neuropsychiatric Inventory for Nursing
Homes: NPI-NH), cognitive function (Mini Mental State Examination: MMSE and Global Deterioration
Scale: GDS to assess severity of dementia) and function (Barthel ADL Index)

Follow-up: 6 months and 12 months

Notes Sponsorship source: Grant of the German Federal Ministry of Health ‘Leuchtturmprojekt Demenz’

Conflicts of interest: Not stated
Ethical approval: The study was approved by the Medical Ethics Committee of Charite ́–Universi-
tätsmedizin Berlin (application number EA1/109/08).

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk Large loss to follow-up; not balanced between groups

Selective reporting (re-
porting bias)

Low risk Outcomes reported as per methods

Other bias High risk Potential residual confounding. Significant differences in gender at baseline

Wolf-Ostermann 2012  (Continued)

 
 

Study characteristics

Wylie 2001 

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Methods Study design: Controlled before-after study

Number of facilities: 5 (3 intervention and 2 control)

Participants N enrolled: Intervention: 41, control: 59. N analysed: Intervention: 25, control: 45

Mean age: Not reported

% Female: Not reported

% Dementia: Not reported

Mean (SD) number of comorbidities: not reported

Country: USA

Inclusion criteria:

Facilities

• Experimental: Texas nursing homes initiating the implementation process of the Eden Alternative™
model in their respective facilities

• Control: Texas nursing homes not initiating the Eden Alternative™ model agreed to participate.

Residents

• Facility social workers’ assessment of the residents’ cognitive ability to understand and complete
questionnaires

• Agree to participate

Interventions Name of intervention: Eden alternative

Design features: Human habitat model – pets, plants and children. Imbued daily life with variety and
spontaneity by creating an environment in which unexpected and unpredictable interactions and hap-
penings can take place. Other features: Provided daily opportunities to give as well as receive care by
promoting resident participation in the daily round of activities that are necessary to maintain the Hu-
man Habitat. De-emphasised the role of prescription drugs in the residents’ daily lives and commit-
ted those resources to the maintenance and growth of the Human Habitat. Leadership that placed the
need to improve resident quality of life over and above the inevitable objections to change

Control: Traditional nursing home

Outcomes The following outcomes (measurement scale) were reported:

Quality of life (Life Satisfaction Index: LSI)

Follow-up: 6 months, 12 months and 18 months

Notes Sponsorship source: Unclear

Conflicts of interest: Not stated
Ethical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Not randomised

Allocation concealment
(selection bias)

High risk Controlled before-after study

Wylie 2001  (Continued)

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Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk Loss to follow-up 30% by second data collection point

Selective reporting (re-
porting bias)

Low risk Outcomes reported as in methods

Other bias High risk Potential residual confounding. Some resident and staC baseline character-
istics reported in Table 1, p. 15, no statistical comparisons performed. Differ-
ences in staC turnover between facilities. Difference in payer type and racial
mix for Eden model. Significant difference in proportion of payers for Eden
vs control (reviewer calc: Eden 301/410 vs 25/313 control; P < 0.0000001 Chi-
square Epionline). Some contamination; one control facility commenced im-
plementing the Eden alternative and then abandoned.

Wylie 2001  (Continued)

 
 

Study characteristics

Methods Study design: Controlled before-after study

Number of facilities: 13 (9 intervention and 4 control)

Participants N = 242 (Intervention: N = 93; control: N = 149)

Mean age (SD): Intervention: 87.2 (7.2), control: 85.8 (9.7)

% Female: Intervention: 73.1, control: 73.9

% Dementia: Intervention: 55.9, control: 50.0

Mean (SD) number of comorbidities: Intervention: 1.9 (1.2), control: 2.3 (1.4)

Country: USA

Inclusion criteria:

• Residing in included nursing home for at least six months

Exclusion criteria:

• Admitted for short-term rehab or hospice at the start of their stay

Interventions Type of intervention: home-like model

Name of intervention: Green House model

Design features: Home-like environment, Cluster of 2 or 3 homes with 10 residents each, private bed-
room and bathroom, large common living and dining room, no nurses stations, medication carts, pag-
ing systems

Yoon 2015 

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Other features that differed: Organisational changes to support resident quality of life, care staC have
diverse roles and greater autonomy and responsibility in daily care.

Control: Traditional large scale nursing homes, hospital-like features such as nurses stations, medica-
tion charts, paging systems. Traditional hierarchical organisational structure and traditional care staC
roles

Outcomes The following outcomes (measurement scale) were reported:

Social engagement (Index of Social Engagement: ISE), depressive symptoms (Mood Scale Score: MSS),
function (ADL long-form scale) and cognitive function (Cognitive Performance Scale: CPS)

Follow-up: Up to 18 months

Notes Study partially supported by a grant from the Robert Wood Johnson Foundation (Grant 66360; PI: SDH)
and the Clinical and Translational Science Award Program, through the NIH National Center for Ad-
vancing Translational Sciences (grant UL1TR000427; BJB)

Conflicts of interest: None

Ethical approval: Not stated

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence genera-
tion (selection bias)

High risk Controlled before-after study

Allocation concealment
(selection bias)

High risk Controlled before-after study

Blinding of participants
and personnel (perfor-
mance bias)
All outcomes

High risk Blinding not feasible

Blinding of outcome as-
sessment (detection bias)
All outcomes

High risk Blinding not feasible

Incomplete outcome data
(attrition bias)
All outcomes

High risk High loss to follow-up (62%)

Selective reporting (re-
porting bias)

Unclear risk Many outcomes on MDS so unclear how outcomes were decided

Other bias High risk Potential residual confounding. Significant difference in comorbidities at
baseline

Yoon 2015  (Continued)

ADLs: Activities of Daily Living
BIMS: Brief Interview for Mental Status
CDR: Clinical Dementia Rating
CMAI: Cohen-Mansfield Agitation Inventory
CPS: Cognitive Performance Scale
CSDD: Cornell Scale for Depression in Dementia
DEMQOL: Dementia Quality of Life questionnaire
DQoL: Dementia Quality of Life

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DSM-III: Diagnostic and Statistical Manual of Mental Disorders Third Edition
EAT: Environment Audit Tool
FAST: Fuctional Assessment Staging
FBFC: Function and Behavior Focused Care
GDS: Geriatric Depression Scale
GH: GreenHouse
HAD: Hospital Anxiety and Depression Scale
IDDD: Interview for the Deterioration of Daily Living activities in Dementia
ISE: Index of Social Engagement
MDS: Minimum Data Set
MEC: Mini-Examination Cognitive
MMSE: Mini Mental State Examination
MOSES: Multi Observational Scale for Elderly Subjects
MSS: Mood Scale Score
NDA: New Dynamics of Aging
NH: Nursing Home
NOSGER: Nurses Observation Scale for Geriatric Patients
NPI-(Q): Neuropsychiatric Inventory Questionnaire
OBS: Organic Brain Syndrome
OD: Occupational Distress
OSCAR: Online Survey, Certification, and Reporting
PCC: Person-Centred Care
PCE(CAT): Person-Centred Environment (Care Assessment Tool)
PGCARS: Philadelphia Geriatric Centre ACect Rating Scale
PGCMS: Philadelphia Geriatric Center Moral Scale
PSQI: Pittsburgh Sleep Quality Index
QUALID: Quality of Life in Late-Stage Dementia
QUALIDEM: A Dementia-Specific Quality of Life measure
QUIS: Quality of Interactions Schedule
RAI: Resident Assessment Instrument
RFI: Room for Improvement
RISE: Revised Index of Social Engagement
RMBPC: Revised Memory and Behavior Problems Checklist
SAS: Statistial Analytics System
SCU: Special Care Unit
SD: Standard Deviation
SHA: Shared Housing Arrangement
SIP: Sickness Impact Profile
TESS-2: Therapeutic Environment Screening Scale-2
UE: Usual Environment
vs.: versus
 

Characteristics of excluded studies [ordered by study ID]

 

Study Reason for exclusion

Auer 2017 Longitudinal study but not before-after (no measure on admission to facility) and only one inter-
vention site

Barrick 2010 Majority of participants were from a hospital setting and could not separate out those who were
from a residential care environment.

Bergman-Evans 2004 One intervention and one control site

Bonardi 1989 One intervention and one control site

Bond 1999 One intervention and one control site

Chafetz 1991 One intervention and one control site

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Study Reason for exclusion

Chang 2013 One intervention and one control site

Cohen-Mansfield 1998 One intervention and one control site

Coleman 2002 One intervention and one control site

De Boer 2017 Longitudinal study but not before-after (no measure on admission to facility)

De Rooij 2012 Longitudinal study but not before-after (no measure on admission to facility)

Falk 2009 Longitudinal study but not before-after (no measure on admission to facility)

Giggins Before-after study with one nursing home and no comparator group

Hermer 2017 Only one intervention site.

Holmes 1990 Longitudinal study but not before-after (no measure on admission to facility)

Inventor 2018 Only one control and one intervention site

Kane 2007 Only one intervention site

Klosinska Before-after study with one nursing home and no comparator group

Kok 2017 One intervention and one control site

Kok 2018 Only one intervention and one control site

Kubsch 2018 Only one intervention and one control site

Lee 2016 One intervention and one control site

Lum 2008 Only one intervention site

Molony 2011 One intervention and one control site

O’Connor 1991 One intervention and one control site

Palm 2019 Longitudinal study but not before-after (no measure on admission to facility)

Pomeroy 2011 Repeated measures without measures before the intervention

Potter 2018 Longitudinal study but not before-after (no measure on admission to facility)

Reimer 2004 Only one intervention site

Scott 2014 Only one control site

Steiner 2020 Only one control site

Varshawsky  Before-after study with one nursing home and no comparator group

Verbeek 2014 Longitudinal study but not before-after (no measure on admission to facility)

 

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Characteristics of studies awaiting classification [ordered by study ID]

 

Methods Cluster-randomised controlled trial

Participants 69 participants

Inclusion criteria:

• ≥ 60 years and in long-term care (> 4 weeks)

• had dementia in accordance with DSM-5

• had either sleep/circadian rhythm disturbances, BPSD as identified by NPI-NH, or severely re-
duced ADL function

• provided written informed consent if the participant had capacity or, if not, a written proxy in-
formed consent from a legally authorised representative

Exclusion criteria:

• blind or might otherwise not benefit from light

• took part in another trial

• had a condition contra-indicated to the intervention

• had an advanced, severe medical disease/disorder and/or expected survival less of than 6 months
or other aspects that could interfere with participation

• were psychotic or had a severe mental disorder

Interventions Light-emitting diode (LED) ceiling-mounted bright light solution that was installed in the com-
mon rooms of four intervention units. The light setup was delivered by Glamox, using a number of
square LED units (Glamox, 1 x C95 48 CCT 6,500 K MP 47 W/4,702 lm). Glamox engineers calculated
the number of LED units needed to provide the target light levels in each common room, account-
ing for the number and direction of windows. The LED units were programmed to provide 400 lux
and 3,000 K (measured vertically) from 07:00-10:00, 1,000 lux and 6,000 K from 10:00 to 15:00, 400
lux and 3,000 K from 15:00-18:00, and 100 lux and 2,500 K from 18:00-21:00. Light values gradually
changed across 30 minutes.

Outcomes Depression: Cornell Scale for Depression in Dementia (CSDD)

Global behaviour: Neuropsychiatric Inventory Nursing Home Version (NPI-NH)

Notes Sponsorship source: The dissertation was part of the public sector Ph.D. scheme by the Research
Council of Norway (Sponsor’s Protocol Code 259987/H40), where the Department of Health and
Care, City of Bergen, has been the candidate’s employer. The candidate also received funding from
Thordis and Johannes Gahrs Fund for Promoting Gerontopsychiatric Research. The trial received
funding for the light fittings used in the trial from the Rebekka Ege Hegermanns Grant and the GC
Rieber Foundations.

Conflicts of interest: None

Ethical approval: The trial was approved by the Regional Committee for Medical and Health Re-
search Ethics, Health Region South East (project no. 2016/2246).

Kolberg 2020 

ADL: Activities of Daily Living
BPSD: Behavioural and Psychological Symptoms of Dementia
CSDD: Cornell Scale for Depression in Dementia
DSM-5: Diagnostic and Statistical Manual of Mental Disorders FiJh Edition
LED: Light-emitting Diode
NH: Nursing Home
NPI: Neuropsychiatric Inventory
 

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Characteristics of ongoing studies [ordered by study ID]

 

Study name Nursing home care for people with dementia and residents’ quality of life, quality of care and staC
well-being: design of the Living Arrangements for people with Dementia (LAD)-study

Methods Non-randomised study with a control group; follow-up every two years

Participants 12 residents and 15 healthcare staC randomly selected from each of the 150 living arrangements
(30 living arrangements from five different living arrangements: traditional large-scale nursing
homes, nursing home wards in a home for the aged, large nursing home where group living home
care was provided, group living homes nearby the mother facility and stand-alone group living
homes in the community). Healthcare staC were excluded if they were not working on a permanent
basis (temporary staC and student-nurses).

Inclusion criteria:

• People with a primary diagnosis of dementia

• Healthcare staC were randomly selected from 30 living arrangements for each of five categories
of living arrangements as per Interventions.

Exclusion criteria:

• Not reported

Interventions Traditional large-scale nursing homes, nursing home wards in a home for the aged, large nursing
home where group living home care was provided, group living homes nearby the mother facility
and stand-alone group living homes in the community

Outcomes Resident outcomes:

Quality of life:

Quality of life (QUALIDEM)

Pain (subscale from Minimum Data Set of the Resident Assessment Instrument: MDS:RAI)

Quality of care:

Physical restraints (type and number of times used per resident)

Psychotropic drugs (type and number of times used per resident)

Client satisfaction (Consumer Quality Index: CQ-Index)

Approach to dementia (Approach to Dementia Questionnaire ADQ)

Involvement in activities (subscale from MDS:RAI)

Sta? outcomes:

Job satisfaction (subscale job satisfaction from The Leiden Quality of Work Questionnaire: LQWQ)

Burnout complaints (Utrecht Burnout Scale: UBOS)

Workload (subscale from LQWQ)

Autonomy (subscale from LQWQ)

Social support (subscale from LQWQ)

Starting date Unclear

Contact information [email protected]

Willemse 2011 

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Netherlands Institute of Mental Health and Addiction (Trimbos-Institute), Utrecht, The Netherlands

Notes Sponsorship source: Ministry of Health, Welfare and Sports

The study is a national monitoring study in the Netherlands which will collect data every two years.
A number of cross-sectional analyses from the study have been published that are not eligible for
inclusion in this review (Willemse 2014; Willemse 2015; Willemse 2016)

Conflicts of interest: None
Ethical approval: data of people with dementia were collected via observation by the healthcare
staC. For these reasons, this study did not come within the scope of the Medical Research Involving
Human Subjects Act (WMO) and therefore it did not need approval. We came to this decision after
consultation of a representative of the Medical Ethics committee METiGG.

Willemse 2011  (Continued)

ADQ: Approach to Dementia Questionnaire
CQ-Index: Consumer Quality Index
LAD: Living Arrangements for people with Dementia
LQWQ: The Leiden Quality of Work Questionnaire
MDS:RAI: Minimum Data Set of the Resident Assessment Instrument
QUALIDEM: Dementia-specific Quality of Life measure
UBOS: Utrecht Burnout Scale
 

 

D A T A   A N D   A N A L Y S E S

 

Comparison 1.   Home-like vs. traditional environment

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

1.1 Quality of life 1   Other data No numeric data

1.2 Behaviour, mood and depression 5   Other data No numeric data

1.2.1 Global behaviour 3   Other data No numeric data

1.2.2 Depression 2   Other data No numeric data

1.2.3 Behaviour subdomains 2   Other data No numeric data

1.2.4 Social engagement 2   Other data No numeric data

1.3 Function 4   Other data No numeric data

1.4 Global cognitive function 4   Other data No numeric data

1.5 Quality of care  1   Other data No numeric data

1.6 Serious adverse effects 1   Other data No numeric data

 
 

Analysis 1.1.   Comparison 1: Home-like vs. traditional environment, Outcome 1: Quality of life

Quality of life

Study Measure Home-like Traditional Sample size Reported significance

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QUALIDEM 
-Feeling at home (adjust-
ed, mean)
(higher scores = better)

Baseline: 55.1
6 months: 65.5
12 months: 77.4

Baseline: 58.7
6 months: 65.5
12 months: 83.2

33 Group differences in
trends over time adjust-
ed for gender and stage
of dementia:
P = 0.674
 

QUALIDEM
-Care relationship (ad-
justed, mean)
(higher scores = better)

Baseline: 68.2
6 months: 74.2
12 months: 90.5

Baseline: 69.5
6 months: 58.0
12 months: 58.9

33 P = 0.065

QUALIDEM
-Positive affect (unad-
justed mean (SD))
(higher scores = better)

Baseline: 64.3 (24.7)
6 months: 75.0 (23.2)
12 months: 79.2 (20.0)

Baseline: 68.8 (21.7)
6 months: 76.5 (23.3)
12 months: 81.2 (23.5)

33 P = 0.683

QUALIDEM
-Negative affect (unad-
justed mean (SD))
(higher scores = better)

Baseline: 49.4 (28.7)
6 months: 53.6 (25.7)
12 months: 61.7 (23.0)

Baseline: 57.7 (30.6)
6 months: 59.8 (22.2)
12 months: 58.5 (30.0)

33 P = 0.373

QUALIDEM
-Social isolation (unad-
justed, mean (SD))
(higher scores = better)

Baseline: 77.8 (20.7)
6 months: 70.6 (24.3)
12 months: 67.8 (22.2)

Baseline: 61.5 (25.9)
6 months: 63.2 (26.6)
12 months: 59.8 (28.8)

33 P = 0.456

QUALIDEM
-Social relations (unad-
justed, mean (SD))
(higher scores = better)

Baseline: 61.1 (22.1)
6 months: 67.5 (22.9)
12 months: 68.1 (18.8)

Baseline: 47.9 (17.5)
6 months: 66.2 (20.7)
12 months: 59.8 (14.9)

33 P = 0.947

QUALIDEM
-Positive self-image (un-
adjusted, mean (SD))
(higher scores = better)

Baseline: 67.8 (28.9)
6 months: 62.0 (23.5)
12 months: 68.6 (25.5)

Baseline: 69.7 (26.3)
6 months: 65.3 (33.8)
12 months: 68.5 (33.8)

33 P = 0.990

QUALIDEM
-Restless tense behav-
iour (unadjusted, mean
(SD))
(higher scores = better)

Baseline: 46.7 (34.3)
6 months: 53.9 (32.1)
12 months: 53.9 (36.3)

Baseline: 45.3 (32.9)
6 months: 54.7 (35.0)
12 months: 54.7 (32.9)

33 P = 0.226

Wolf-Ostermann 2012

QUALIDEM
-Having something to do
(unadjusted, mean (SD)),
(higher scores = better)

Baseline: 52.6 (32.5)
6 months: 51.8 (64.6)
12 months: 53.9 (33.1)

Baseline: 29.2 (28.8)
6 months: 62.5 (24.8)
12 months: 55.6 (33.6)

33 P = 0.878

 
 

Analysis 1.2.   Comparison 1: Home-like vs. traditional environment, Outcome 2: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Home-like Traditional Sample size Effect estimate or re-
ported significance

Global behaviour

Nurses Observation
Scale for Geriatric Pa-
tients (NOSGER) (unad-
justed mean)
(lower scores = better)

Baseline 15.9
6 months 16.0
12 months 15.3

Baseline 18.0
6 months 18.8
12 months 19.6

60 P < 0.01 at baseline
P < 0.001 at 6 months
P < 0.0001 at 12 months

         

         

         

         

         

         

         

Dettbarn-Reggentin
2005

         

Neuropsychiatric Inven-
tory (NPI) (unadjusted
mean (95% confidence
interval))
(lower scores = better)

Baseline: 12.1 (10.5 to
13.8)
6 months: 7.5 (6.2 to 6.7)

Baseline: 11.7 (10.9 to
12.8)
6 months 8.8 (7.5 to 10.1)

164 Adjusted MD for global
behaviour change over 6
months:
-0.04 (95% CI -0.13 to
0.04) 

         

Te Boekhorst 2009

         

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Neuropsychiatric Inven-
tory-Nursing Home ver-
sion (NPI-NH) (adjusted
mean)
(lower scores = better)

Baseline 47.3
6 months 26.7
12 months 17.4

Baseline 34.1
6 months 36.6
12 months 20.5

Baseline: 56
12 months: 33

P > 0.05

         

         

         

         

         

         

         

Wolf-Ostermann 2012

         

Depression

Revised Memory and Be-
haviour Problems Check-
list (RMBPC) (unadjusted
mean (95% confidence
interval))
(lower scores = better)

Baseline 14.9 (12.8 to
17.0)
6 months 8.9 (7.4 to 10.5)

Baseline 13.1 (12.3 to
13.8)
6 months 8.0 (7.4 to 8.6)

164 Adjusted MD (95% confi-
dence interval) for global
behaviour change over 6
months:
0.01 (-0.12 to 0.14)

         

         

         

         

         

         

         

Te Boekhorst 2009

         

Mood Scale Score (MSS)
(lower scores = better)

N/R N/R 242 Adjusted RR (95% con-
fidence interval) for lev-
el of social engagement
over 18 months: 
1.15 (1.02 to 1.29)
Adjusted OR (95% confi-
dence interval) for prob-
ability of not being so-
cially engaged over 18
months:
0.36 (0.12 to 1.07)

         

         

         

         

         

         

         

Yoon 2015

         

Behaviour subdomains

Organic Brain Syndrome
(OBS) scale
-Dyspraxia (unadjusted
mean (SD))
(lower scores = better)

0-6 months:
0.95 (0.49)
0-12 months:
0.57 (0.49)

0-6 months:
0.54 (0.54)
0-12 months:
0.69 (0.69)

0-6 months:
53
0-12 months:
44

0-6 months: P < 0.001
0-12 months: P > 0.05

 OBS scale
-Hallucinations (unad-
justed mean (SD))
(lower scores = better)

0-6 months:
0.02 (0.29)
0-12 months:
0.14 (0.47)

0-6 months:
0.03 (0.36)
0-12 months:
0.14 (0.41)

0-6 months:
53
0-12 months:
44

0-6 months: P > 0.05
0-12 months: P > 0.05

Annerstedt 1993

OBS scale 0-6 months: 0-6 months: 0-6 months: 0-6 months: P > 0.05

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-Lack of vitality (unad-
justed mean (SD))
(lower scores = better)

0.05 (0.49)
0-12 months:
0.63 (0.52)

0.24 (0.47)
0-12 months:
0.31 (0.55)

53
0-12 months:
44

0-12 months: P < 0.05

OBS scale
-Dysphasia (unadjusted
mean (SD))
(lower scores = better)

0-6 months:
0.04 (0.56)
0-12 months:
0.63 (0.52)

0-6 months:
0.36 (0.48)
0-12 months:
0.42 (0.70)

0-6 months:
53
0-12 months:
44

0-6 months: P < 0.05
0-12 months: P > 0.05

OBS scale
-Paranoia (unadjusted
mean (SD))
(lower scores = better)

0-6 months:
-0.05 (0.32)
0-12 months:
0.44 (0.40)

0-6 months:
0.17 (0.37)
0-12 months:
0.28 (0.41)

0-6 months:
53
0-12 months:
44

0-6 months: P < 0.05
0-12 months: P > 0.05

OBS scale
-Aggressiveness (unad-
justed mean (SD))
(lower scores = better)

0-6 months:
0.22 (0.51)
0-12 months:
0.45 (0.45)

0-6 months:
0.09 (0.58)
0-12 months:
0.07 (0.41)

0-6 months:
53
0-12 months:
44

0-6 months: P > 0.05
0-12 months: P < 0.01

OBS scale
-Depression, anxious-
ness (unadjusted mean
(SD))
(lower scores = better)

0-6 months:
-0.19 (0.23)
0-12 months:
0.32 (0.50)

0-6 months:
0.28 (0.60)
0-12 months:
0.30 (0.49)

0-6 months:
53
0-12 months:
44

0-6 months: P < 0.01
0-12 months: P > 0.05

OBS scale
-Clinical variations (un-
adjusted mean (SD))
(lower scores = better)

0-6 months:
0.06 (0.54)
0-12 months:
0.65 (0.65)

0-6 months:
0.29 (0.75)
0-12 months:
0.16 (0.68)

0-6 months:
53
0-12 months:
44

0-6 months: P > 0.05
0-12 months: P < 0.05

OBS scale
-Restlessness (unadjust-
ed mean (SD))
(lower scores = better)

0-6 months:
-0.11 (0.28)
0-12 months:
0.22 (0.53)

0-6 months:
0.09 (0.38)
0-12 months:
0.26 (0.58)

0-6 months:
53
0-12 months:
44

0-6 months: P < 0.05
0-12 months: P > 0.05

Cohen-Mansfield Agita-
tion Inventory (CMAI),
proportion with physical
non-aggressive behav-
iour
(lower scores = better)

Baseline: 35.0%
6 months: 40.0%
12 months: 30.0%

Baseline: 46.2%
6 months: 46.2%
12 months: 53.8%

33 P > 0.05

CMAI, proportion with
verbal agitation
(lower scores = better)

Baseline: 50.0%
6 months: 50.0%
12 months: 40.0%

Baseline: 30.8%
6 months: 53.8%
12 months: 61.5%

33 P > 0.05

CMAI, proportion with
physical aggressive be-
haviour
(lower scores = better)

Baseline: 0%
6 months: 5.0%
12 months: 25.0%

Baseline: 30.8%
6 months: 30.8%
12 months: 30.8%

33 P = 0.066 for baseline to
6 months 
P > 0.05 for baseline to
12 months

         

         

         

         

         

Wolf-Ostermann 2012

         

Social engagement

Revised Index of Social
Engagement (RISE) 
(unadjusted mean (95%
confidence interval))
(higher scores = better)
 

Baseline 3.2 (2.7 to 3.7)
6 months 4.5 (4.0 to 5.0)

Baseline 2.9 (2.5 to 3.2)
6 months 3.2 (2.6 t0 3.7)

164 Adjusted MD (95% confi-
dence interval) for global
behaviour change over 6
months:
0.79 (0.11 to 1.50)

         

         

         

         

         

         

         

Te Boekhorst 2009

         

Yoon 2015 Index of Social Engage-
ment (ISE) 
(higher scores = better)

N/R N/R 242 Adjusted RR (95% con-
fiedence interval) for lev-
el of social engagement
over 18 months:
0.99 (0.82 to 1.19)
Adjusted OR (95% confi-
dence interval) for prob-

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ability of not being so-
cially engaged over 18
months:
0.76 (0.62 to 0.94)

         

         

         

         

         

         

         

         

 
 

Analysis 1.3.   Comparison 1: Home-like vs. traditional environment, Outcome 3: Function

Function

Study Measure Home-like Traditional Sample size Effect estimate or re-
ported significance

Barthel Index (unadjust-
ed mean)
(higher scores = better)

Baseline: 40.9
12 months: 35.9

Baseline: 35.9
12 months: 23.9

60 P = 0.039

         

         

         

         

         

         

         

Dettbarn-Reggentin
2005

         

The Interview for the De-
terioration of Daily Liv-
ing activities in Demen-
tia (IDDD) (unadjusted
mean (95% confidence
interval)) 
(lower scores = better)

Baseline 25.9 
(22.9 to 28.8)
6 months 28.3 
(26.3 to 30.3)

Baseline 33.0 
(30.5 to 35.6)
6 months 34.6 
(31.9 to 37.2)

164 Adjusted MD (95% confi-
dence interval) over six
months:
-4.37 (-7.06 to -1.69)

         

         

         

         

         

         

         

Te Boekhorst 2009

         

Barthel Index  (adjusted
mean)
(higher scores = better)

Baseline: 58.6
6 months: 43.7
12 months: 36.2

Baseline: 64.8
6 months: 46.3
12 months: 49.8

Baseline: 56
Follow-up: 33

Interactions between
setting and development
over time, P > 0.05

Bathing-decrease in pro-
portion independent 12
months (%, N)

10.0% 7.7% 33 –

Toilet use-decrease in
proportion independent
12 months (%, N)

30.0% 23.1% 33 –

Grooming-decrease in
proportion independent
12 months (%, N)

15.0% 15.4% 33 –

Bladder-decrease in pro-
portion independent 12
months (%, N)

15.0% 15.4% 33 –

Wolf-Ostermann 2012

Stairs-decrease in pro-
portion independent 12
months(%, N)

20.0% 0% 33 –

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Feeding-decrease in pro-
portion independent 12
months (%, N)

20.0% 15.4% 33 –

Dressing-decrease in
proportion independent
12 months (%, N)

15.0% 7.7% 33 –

Transferring-decrease in
proportion independent
12 months (%, N)

15.0% 7.7% 33 –

Activities of daily living
(ADL) long-form scale
(unadjusted mean (SD))
(lower scores = better)

Baseline: 14.5 (6.7)
6 months: 15.6 (6.9)
18 months: 18.5 (4.4)

Baseline: 14.5 (7.4)
 6 months: 15.1 (7.3)
18 months: 16.9 (7.0)

Baseline n = 242
6 months
n = 238
18 months
n = 92

Adjusted MD (95% confi-
dence interval) over 18
months: -0.09 (-0.46 to
0.28)
 

         

         

         

         

         

         

         

Yoon 2015

         

 
 

Analysis 1.4.   Comparison 1: Home-like vs. traditional environment, Outcome 4: Global cognitive function

Global cognitive function

Study Measure Home-like Traditional Sample size Effect estimate or re-
ported significance

Dettbarn-Reggentin
2005

Mini-Mental State Exam-
ination (MMSE) (unad-
justed mean)
(higher scores = better)

Baseline: 10.3
12 months: 9.9

Baseline: 9.1
12 months: 7.6

60 P = 0.0082

Te Boekhorst 2009 Standardised Mini-Men-
tal State Examination
(MMSE) (unadjusted
mean (95% confidence
interval))
(higher scores = better)

Baseline 15.4 (13.5 to
17.3)
6 months 13.0 (10.4 to
15.6)

Baseline 10.3 (8.3 to
12.3)
6 months 8.9 (6.2 to 11.6)

164 Adjusted MD (95% con-
fidence interval) over 6
months:
0.54 (-1.43 to 2.50)

Wolf-Ostermann 2012 Mini-Mental State Exam-
ination (MMSE) (unad-
justed mean (SD))
(higher scores = better)

Baseline: 15.7 (6.9)
6 months: 13.8 (6.8)
12 months: 10.8 (10.0)

Baseline: 12.4 (6.5)
6 months: 8.4 (7.4)
12 months: 8.7 (7.7)

33 P = 0.004 for baseline to
6 months
P > 0.05 for baseline to
12 months

Yoon 2015 Cognitive Performance
Scale (CPS) (unadjusted
mean (SD))
(lower scores = better)

Baseline: 2.5 (1.0)
6 months: 2.6 (1.1)
18 months: 2.9 (1.3)

Baseline: 2.2 (1.2)
6 months: 2.3 (1.3)
18 months: 2.3 (1.5)

Baseline 
n = 242
6 months
n=238
18 months
n=92

N/R

 
 

Analysis 1.5.   Comparison 1: Home-like vs. traditional environment, Outcome 5: Quality of care 

Quality of care 

Study Measure Sample size Effect estimate (unclear follow-up
time, reported as up to 5 years)

Number of bedfast residents Estimated weighted sample 74,449  Adjusted MD (95% confidence interval)
-0.3% (-0.4% to -0.2%)

Catheter use Estimated weighted sample 74,449  Adjusted MD (95% confidence interval)
-4.1% (-6.1% to -2.1%)

High-risk pressure ulcers Estimated weighted sample 74,449 Adjusted MD (95% confidence interval)
-1.2% (-3.8% to 1.4%)

Low-risk pressure ulcers Estimated weighted sample 74,449 Adjusted MD (95% confidence interval)
-1.9% (-2.5% to -1.3%)

Afendulis 2016

Hospital readmissions Estimated weighted sample 74,449 MD (95% confidence interval)

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-5.5% (-10.2% to -0.8%)

Avoidable hospital readmissions Estimated weighted sample 74,449 MD (95% confidence interval)
-3.9% (-7.6% to -0.2%)

 
 

Analysis 1.6.   Comparison 1: Home-like vs. traditional environment, Outcome 6: Serious adverse e?ects

Serious adverse effects

Study Measure Sample size Effect estimate (unclear follow-up,
reported as up to 5 years)

Afendulis 2016 Physical restraints Estimated weighted sample 74,449 Adjusted MD (95% confidence interval):
-0.3% (-0.5% to -0.1%)

 
 

Comparison 2.   Refurbishment vs. traditional environment

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

2.1 Quality of life 3   Other data No numeric data

2.2 Behaviour, mood and depression 3   Other data No numeric data

2.2.1 Depression 1   Other data No numeric data

2.2.2 Behaviour subdomains 3   Other data No numeric data

2.3 Function 1   Other data No numeric data

2.4 Quality of care 1   Other data No numeric data

 
 

Analysis 2.1.   Comparison 2: Refurbishment vs. traditional environment, Outcome 1: Quality of life

Quality of life

Study Measure Refurbishment Traditional Sample size Effect estimate or re-
ported significance

Dementia quality of life
(DEMQOL) Proxy (ad-
justed mean (95% confi-
dence interval))
(higher scores = better)

Person-centred envi-
ronment (PCE)
Baseline: 101 (99 to 104)
Post-intervention: 102
(99 to 105)
8 months: 106 (103 to
110)
PCE + person-centred
care (PCC)
Baseline: 101 (99 to 104)
Post-intervention: 103
(100 to 106)
8 months: 105 (102 to
108)

Baseline: 101 (98 to 104)
Post-intervention: 100
(97 to 104)
8 months: 103 (99 to 106)

Baseline: 601
Post-intervention: 416
8 months: 296

Adjusted MD (95% confi-
dence interval)
PCE vs. traditional: 
Post-intervention: 2.00
(-2.19 to 6.19)
8 months: 3.00 (-1.91 to
7.91)
PCE + PCC vs tradition-
al:
Post-intervention: 3.00
(-1.20 to 7.20)
8 months: 2.00 (-2.91 to
6.91)

Chenoweth 2014

         

Fumat for mild cognitive
impairment (unadjusted
mean (SD))
(higher scores = better)

Baseline: 100.6 (8.0)
6 months: 104.5 (8.0)

Baseline: 107.1 (11.1)
6 months: not reported

Unclear P = 0.850Diaz-Veiga 2014

Qualid for severe cogni-
tive impairment (unad-
justed mean (SD))
(lower scores = better)

Baseline: 27.4 (12.1)
6 months: 23.8 (12.4)

Baseline: not reported
6 months: 30.8 (11.1)

Unclear P = 0.33

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Life Satisfaction Index
(unadjusted mean (SD))
(higher scores = better)

Baseline: 12.0 (4.1)
6 months: 11.2 (3.4)
12 months: 12.1 (3.3)
18 months: 12.6 (3.3)

Baseline: 12.0 (3.9)
6 months: 11.1 (3.6)
12 months: 11.3 (3.3)
18 months: 11.1 (3.4)

Baseline: 100
6 months: 70
12 months: 43
18 months: 33

‘Not significant’Wylie 2001

         

 
 

Analysis 2.2.   Comparison 2: Refurbishment vs. traditional
environment, Outcome 2: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Refurbishment Traditional Sample size Effect measure or re-
ported significance

Depression

Cornell Scale for Depres-
sion in Dementia (CSDD)
(unadjusted mean (SD))
(lower scores = better)

Baseline: 4.5 (4.2)
4 months: 4.4 (4.6)
12 months: 3.9 (4.5)

Baseline: 3.9 (3.8)
4 months: 4.2 (4.3)
12 months: 3.2 (3.5)

336 Adjusted MD (95% confi-
dence interval) baseline
to 4 months:
-0.73 (-1.93 to 0.47)
Adjusted MD (95% confi-
dence interval) baseline
to 12 months:
-0.04 (-1.35 to 1.26)

         

Galik 2021

         

Behaviour subdomains

Cohen Mansfield Agita-
tion Inventory (CMAI)
(adjusted mean)
Physical agitation
(lower scores = better)

Baseline: 1.68
Two years: 1.44

Baseline: 1.24
Two years: 1.51

101 Adjusted MD (95% confi-
dence interval):
-0.07 (-0.14 to -0.00)

Cohen Mansfield Agita-
tion Inventory (CMAI)
(adjusted mean)
Forceful behaviours
(lower scores = better)

Baseline: 1.50
Two years: 1.35

Baseline: 1.21
Two years: 1.41

101 Adjusted MD (95% confi-
dence interval):
-0.06 (-0.10 to -0.02)

Burack 2012

Cohen Mansfield Agita-
tion Inventory (CMAI)
(adjusted mean)
Verbal agitation
(lower scores = better)

Baseline: 2.13
Two years: 1.95

Baseline: 1.48
Two years: 2.06

101 Adjusted MD (95% confi-
dence interval):
0.11 (-0.00 to 0.22)

Cohen Mansfield Agita-
tion Inventory (CMAI)
(adjusted mean (95%
confidence interval))
(lower scores = better)

Person-centred envi-
ronment (PCE)
Baseline: 65 (57 to 73)
Post-intervention: 55 (46
to 64)
8 months: 55 (46 to 64)
PCE + person-centred
care (PCC)
Baseline: 57 (49 to 65)
Post-intervention: 60 (52
to 69)
8 months: 64 (55 to 73)

Baseline: 52 (43 to 61)
Post-intervention: 53 (43
to 63)
8 months: 51 (41 to 62)

Baseline: 601
Post-intervention: 416
8 months: 296

Adjusted MD (95% confi-
dence interval)
PCE vs. traditional: 
Post-intervention: 2.00
(-11.29 to 15.29)
8 months: 4.00 (-9.21 to
17.21)
PCE + PCC vs tradition-
al:
Post-intervention: 7.00
(-5.66 to 19.66)
8 months: 13.00 (-0.22 to
26.22)

         

Chenoweth 2014

         

Cohen Mansfield Agita-
tion Inventory (CMAI)
(unadjusted mean (SD))
(lower scores = better)

Baseline: 19.8 (6.1)
4 months: 19.2 (5.9)
12 months: 19.2 (7.8)

Baseline: 20.2 (6.6)
4 months: 19.7 (6.8)
12 months: 18.9 (5.6)

336 Adjusted MD (95% confi-
dence interval) baseline
to 4 months:
-0.72 (-2.63 to 1.20)
Adjusted MD (95% confi-
dence interval) baseline
to 12 months:
-0.36 (-2.41 to 1.69)

Galik 2021

Resistiveness to Care
scale (unadjusted mean
(SD))
(lower scores = better)

Baseline: 0.83 (2.15)
4 months: 0.10 (0.48)
12 months: 0.81 (2.40)

Baseline: 0.65 (1.62)
4 months: 0.46 (1.34)
12 months: 0.59 (1.85)

336 Adjusted MD (95% confi-
dence interval) baseline
to 4 months:
-1.56 (-2.71 to -0.40)
Adjusted MD (95% confi-
dence interval) baseline
to 12 months:

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0.32 (-0.29 to 0.94)

         

 
 

Analysis 2.3.   Comparison 2: Refurbishment vs. traditional environment, Outcome 3: Function

Function

Study Measure Refurbishment, mean Traditional, mean Sample size Effect size

Galik 2021 Barthel Index (unadjust-
ed mean (SD))
(higher scores = better)

Baseline: 45.2 (27.8)
4 months: 44.0 (28.4)
12 months: 42.2 (25.7)

Baseline: 47.6 (27.0)
4 months: 47.9 (28.1)
12 months: 42.2 (25.4)

336 Adjusted MD (95% confi-
dence interval) baseline
to 4 months:
1.24 (-3.34 to 5.81)
Adjusted MD (95% confi-
dence interval) baseline
to 12 months:
1.49 (-3.53 to 6.50)

 
 

Analysis 2.4.   Comparison 2: Refurbishment vs. traditional environment, Outcome 4: Quality of care

Quality of care

Study Measure Refurbishment Traditional Sample size Effect estimate

Chenoweth 2014 Quality of Interactions
Schedule (QUIS) (ad-
justed mean (95% confi-
dence interval))
(higher scores = better)

Person-centred envi-
ronment (PCE)
Baseline: 78 (74 to 83)
Post-intervention: 81 (76
to 85)
8 months: 82 (76 to 87)
PCE + person-centred
care (PCC)
Baseline: 76 (72 to 81)
Post-intervention: 86 (81
to 91)
8 months: 80 (75 to 85)

Baseline: 78 (73 to 83)
Post-intervention: 73 (68
to 79)
8 months: 82 (76 to 88)

Baseline: 601
Post-intervention: 416
8 months: 296

Adjusted MD (95% confi-
dence interval)
PCE vs. traditional: 
Post-intervention: 8.00
(1.03 to 14.97)
8 months: MD 0.00 (-8.34
to 8.34)
PCE + PCC vs tradition-
al:
Post-intervention: 13.00
(6.02 to 19.98)
8 months: -2.00 (-9.67 to
5.67)

 
 

Comparison 3.   Special-care units for dementia vs. traditional environment

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

3.1 Behaviour, mood and depression 1   Other data No numeric data

3.1.1 Global behaviour 1   Other data No numeric data

3.1.2 Depression 1   Other data No numeric data

3.1.3 Behaviour subdomains 1   Other data No numeric data

3.2 Function 1   Other data No numeric data

3.3 Global cognitive function 1   Other data No numeric data

 
 

Analysis 3.1.   Comparison 3: Special-care units for dementia vs.
traditional environment, Outcome 1: Behaviour, mood and depression

Behaviour, mood and depression

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Study Measure Special care units Traditional Sample size Reported significance

Global behaviour

Neuropsychiatric Inven-
tory (NPI) (unadjusted
mean (SD))
(lower scores = better)

Baseline: 39.2 (18.1)
3 months: 29.0 (15.0)

Baseline: 29.2 (13.8)
3 months: 20.5 (11.1)

66 P = 0.007 for intervention
P = 0.006 for comparator

         

         

         

         

         

         

         

         

Frisoni 1998

         

Depression

Cornell Depression Scale
(unadjusted mean (SD))
(lower scores = better)

Baseline: 10.7 (4.6)
3 months: 8.4 (3.4)

Baseline: 6.5 (3.5)
3 months: 10.5 (5.9)

66 P = 0.03 for intervention
P = 0.004 for comparator

         

         

         

         

         

         

         

         

Frisoni 1998

         

Behaviour subdomains

Neuropsychiatric Inven-
tory (NPI)
-delusions (unadjusted
mean (SD))
(lower scores = better)

Baseline: 4.4 (4.6)
3 months: 2.8 (3.7)

Baseline: 3.0 (4.1)
3 months: 2.2 (3.4)

66 P = 0.06 for intervention
P > 0.05 for comparator

NPI
-hallucinations (unad-
justed mean (SD))
(lower scores = better)

Baseline: 2.9 (4.5)
3 months: 1.2 (2.6)

Baseline: 1.3 (2.7)
3 months: 0.8 (1.8)

66 p=0.004 for intervention
p>0.05 for comparator

NPI
-agitation (unadjusted
mean (SD))
(lower scores = better)

Baseline: 5.4 (4.4)
3 months: 3.8 (3.5)

Baseline: 3.5 (4.0)
3 months: 2.5 (2.9)

66 p=0.02 for intervention
p>0.05 for comparator

NPI
-anxiety (unadjusted
mean (SD))
(lower scores = better)

Baseline: 4.8 (4.5)
3 months: 4.0 (4.0)

Baseline: 3.7 (3.9)
3 months: 2.6 (4.1)

66 p>0.05 for intervention
p=0.04 for comparator

NPI
-euphoria/elation (unad-
justed mean (SD))
(lower scores = better)

Baseline: 1.2 (2.6)
3 months: 1.2 (2.7)

Baseline: 1.4 (3.1)
3 months: 0.6 (1.7)

66 p>0.05 for intervention
p=0.04 for comparator

NPI
-disinhibition (unadjust-
ed mean (SD))
(lower scores = better)

Baseline: 2.0 (3.5)
3 months: 2.0 (3.0)

Baseline: 1.6 (3.5)
3 months: 1.4 (2.5)

66 p>0.05 for intervention
p>0.05 for comparator

NPI
-irritability/lability (un-
adjusted mean (SD))
(lower scores = better)

Baseline: 4.7 (4.6)
3 months: 4.7 (3.7)

Baseline: 2.9 (4.0)
3 months: 1.9 (2.8)

66 p>0.05 for intervention
p=0.05 for comparator

NPI
-abnormal motor behav-
iour (unadjusted mean
(SD))
(lower scores = better)

Baseline: 9.0 (4.3)
3 months: 7.5 (5.0)

Baseline: 8.2 (4.7)
3 months: 6.9 (4.7)

66 p>0.05 for intervention
p>0.05 for comparator

Frisoni 1998

NPI
-sleep (unadjusted mean
(SD))

Baseline: 4.8 (4.9)
3 months: 2.3 (3.1)

Baseline: 3.9 (4.2)
3 months: 1.7 (3.3)

66 p=0.01 for intervention
p=0.02 for comparator

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(lower scores = better)

Cohen Mansfield Inven-
tory (CMAI) (unadjusted
mean, SD)
(lower scores = better)

Baseline: 40.7 (24.6)
3 months: 36.4 (17.8)

Baseline: 31.2 (14.3)
3 months: 26.7 (11.8)

66 p>0.05 for intervention
p>0.05 for comparator

 
 

Analysis 3.2.   Comparison 3: Special-care units for dementia vs. traditional environment, Outcome 2: Function

Function

Study Measure Special care units Traditional Sample size Reported significance

Bedford Alzheimer’s
nursing severity scale
(unadjusted mean (SD))
(higher scores = better)

Baseline: 13.5 (3.5)
3 months: 14.0 (4.3)

Baseline: 13.8 (3.9)
3 months: 14.1 (4.7)

66 P > 0.05 for intervention
P > 0.05 for comparator

Frisoni 1998

Barthel Index (unadjust-
ed mean (SD))
(higher scores = better)

Baseline: 60.7 (23.5)
3 months: 57.5 (26.3)

Baseline: 52.7 (28.1)
3 months: 45.9 (30.2)

66 P > 0.05 for intervention
P > 0.05 for comparator

 
 

Analysis 3.3.   Comparison 3: Special-care units for dementia vs.
traditional environment, Outcome 3: Global cognitive function

Global cognitive function

Study Measure Special care units Traditional Sample size Reported significance

MMSE (unadjusted mean
(SD))
(higher scores = better)

Baseline: 7.0 (5.2)3
months: 7.4 (5.8)

Baseline: 8.3 (5.1)3
months: 8.9 (6.2)

66 P > 0.05 for intervention
P > 0.05 for comparator

Frisoni 1998

Clinical Dementia Rating
(unadjusted mean (SD))
(lower scores = better)

Baseline: 2.8 (0.5)
3 months: 2.9 (0.5)

Baseline: 2.9 (0.5)
3 months: 3.0 (0.5)

66 P > 0.05 for intervention
P > 0.05 for comparator

 
 

Comparison 4.   Group living corridor vs. group living non-corridor design

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

4.1 Behaviour, mood and depression 1   Other data No numeric data

4.1.1 Depression 1   Other data No numeric data

4.1.2 Behaviour subdomains 1   Other data No numeric data

 
 

Analysis 4.1.   Comparison 4: Group living corridor vs. group living
non-corridor design, Outcome 1: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Sample size Adjusted OR (95% confidence inter-
val)

Depression

Organic Brain Syndrome (OBS) scale
(lower scores = better)

105 8.82 (1.14 to 68.22)

     

     

     

Elmstahl 1997

     

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Behaviour subdomains

Organic Brain Syndrome (OBS) scale
Aggressiveness
(lower scores = better)

105 2.02 (0.56 to 7.27)

Organic Brain Syndrome (OBS) scale
Dyspraxia
(lower scores = better)

105 4.57 (0.76 to 27.35)

Organic Brain Syndrome (OBS) scale
Hallucinations
(lower scores = better)

105 1.06 (0.05 to 22.09)

Organic Brain Syndrome (OBS) scale
Lack of vitality
(lower scores = better)

105 0.23 (0.04 to 1.47)

Organic Brain Syndrome (OBS) scale
Dysphasia
(lower scores = better)

105 0.87 (0.08 to 9.73)

Organic Brain Syndrome (OBS) scale
Paranoia
(lower scores = better)

105 0.12 (0.01 to 1.24)

Organic Brain Syndrome (OBS) scale
Restlessness
(lower scores = better)

105 0.21 (0.04 to 1.00)

Organic Brain Syndrome (OBS) scale
Disorientation, recent memory
(lower scores = better)

105 0.87 (0.31 to 2.42)

Organic Brain Syndrome (OBS) scale
Disorientation, time
(lower scores = better)

105 0.66 (0.22 to 2.01)

Elmstahl 1997

Organic Brain Syndrome (OBS) scale
Disorientation, identity
(lower scores = better)

105 1.23 (0.56 to 2.68)

 
 

Comparison 5.   Lighting intervention  vs. control lighting

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

5.1 Behaviour, mood and depression 2   Other data No numeric data

5.1.1 Global behaviour 1   Other data No numeric data

5.1.2 Depression 1   Other data No numeric data

5.1.3 Behaviour subdomains 2   Other data No numeric data

5.2 Behaviour, mood and depression:
depression 4-6 weeks

3 291 Std. Mean Difference (IV,
Fixed, 95% CI)

-0.22 [-0.45, 0.01]

5.3 Behaviour, mood and depression:
agitation 4-6 weeks

2 179 Std. Mean Difference (IV,
Fixed, 95% CI)

-0.16 [-0.45, 0.14]

5.4 Function 4-6 weeks 2 179 Std. Mean Difference (IV,
Fixed, 95% CI)

-0.29 [-0.59, 0.00]

5.5 Function 1   Other data No numeric data

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Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

5.6 Global cognitive function 1   Other data No numeric data

 
 

Analysis 5.1.   Comparison 5: Lighting intervention  vs. control lighting, Outcome 1: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Lighting intervention Control lighting Sample size Effect estimate

Global behaviour

Questionnaire format of
the NPI (NPI-Q) (mean
(SD))
(lower scores = better)

6 weeks: 4.7 (5.0)
6 months: 5.7 (5.7)
12 months: 5.8 (5.7)
18 months: 4.0 (4.6)
24 months: 4.9 (5.8)

6 weeks: 6.4 (5.3)
6 months: 5.2 (4.4)
12 months: 6.1 (3.5)
18 months: 6.8 (5.0)
24 months: 8.2 (3.9)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: -1.70 (-3.88 to
0.48)
6 months: 0.50 (-1.80 to
2.80)
12 months: -0.30 (-2.73
to 2.13)
18 months: -2.80 (-5.78
to 0.18)
24 months: -3.30 (-7.27
to 0.67)

         

         

         

Riemersma-vanDerLek
2008

         

Depression

 Cornell Scale for De-
pression in Dementia
(CSDD) , (mean, SD)
(lower scores = better)

6 months: 7.9 (5.6)
12 months: 11.0 (7.7)
18 months: 9.9 (5.9)
24 months: 10.7 (7.3)

6 months: 9.3 (6.1)
12 months: 11.3 (7.4)
18 months: 12.0 (7.5)
24 months: 15.1 (8.6)

6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 months: -0.24 (-0.70 to
0.23)
12 months: -0.04 (-0.58
to 0.50)
18 months: 0.31 (-0.93 to
0.31)
24 months: -0.55 (-1.35
to 0.26)

         

         

         

Riemersma-vanDerLek
2008

         

Behaviour subdomains

Anxiety
Anxiety subset of the
hospital anxiety and de-
pression (HADA) scale
(mean (SD))
(lower scores = better)

4 weeks: 4.5 (2.5) 4 weeks: 4.7 (2.7) 42 MD (95% confidence in-
terval):
-0.10 (-1.67 to 1.47)

         

         

         

Hopkins 2017

         

Riemersma-vanDerLek
2008

Distress
Questionnaire format of
the NPI (NPI-Q) distress
subdomain (mean (SD))
(lower scores = better)

6 weeks: 5.1 (6.0)
6 months: 6.1 (7.4)
12 months: 6.0 (7.2)
18 months: 4.2 (5.3)
24 months: 5.4 (6.8)

6 weeks: 6.0 (5.9)
6 months: 3.6 (4.6)
12 months: 3.2 (3.5)
18 months: 4.2 (4.6)
24 months: 7.4 (4.5)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: -0.90 (-3.41 to
1.61)
6 months: 2.50 (-0.24 to
5.24)
12 months: 2.80 (-0.06 to
5.66)
18 months: -0.00 (-3.03
to 3.03)
24 months: -2.00 (-6.35
to 2.35)

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Withdrawn behaviour 
Multi Observational
Scale for Elderly Subjects
(MOSES) (mean (SD))
(lower scores = better)

6 weeks: 17.5 (5.9)
6 months: 19.0 (6.1)
12 months: 17.6 (6.2)
18 months: 15.5 (4.7)
24 months: 16.4 (6.2)

6 weeks: 16.6 (6.1)
6 months: 17.9 (6.0)
12 months: 17.0 (4.1)
18 months: 19.8 (5.4)
24 months: 19.9 (5.0)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: 0.90 (-1.63 to
3.43)
6 months: 1.10 (-1.69 to
3.89)
12 months: 0.60 (-2.12 to
3.32)
18 months: -4.30 (-7.45
to -1.15)
24 months: -3.50 (-7.84
to 0.84)

Positive mood
Philadelphia Geriatric
Centre Affect Rating
Scale (PGCARS) (mean
(SD))
(higher scores = better)

6 weeks: 10.7 (3.5)
6 months: 10.9 (3.2)
12 months: 11.6 (3.1)
18 months: 11.5 (2.2)
24 months: 11.5 (2.4)

6 weeks: 11.3 (2.4)
6 months: 10.5 (2.6)
12 months: 11.9 (2.6)
18 months: 10.6 (2.9)
24 months: 11.0 (1.0)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: -0.60 (-1.85 to
0.65)
6 months: 0.40 (-0.92 to
1.72)
12 months: 0.30 (-1.82 to
1.22)
18 months: 0.90 (-0.71 to
2.51)
24 months: 0.50 (-0.83 to
1.83)

Negative mood
Philadelphia Geriatric
Centre Affect Rating
Scale (PGCARS) (mean
(SD))
(lower scores = better)

6 weeks: 5.8 (2.3)
6 months: 6.1 (2.6)
12 months: 7.3 (3.2)
18 months: 6.3 (3.1)
24 months: 6.4 (2.9)

6 weeks: 7.0 (2.9)
6 months: 6.7 (2.6)
12 months: 6.2 (2.0)
18 months: 6.6 (2.2)
24 months: 9.1 (2.5)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: -1.20 (-2.31 to
-0.09)
6 months: -0.60 (-1.80 to
0.60)
12 months: 1.10 (-0.27 to
2.47)
18 months: -0.30 (-1.92
to 0.32)
24 months: -2.70 (-4.80
to -0.60)

Agitation
Cohen-Mansfield Agita-
tion Inventory (CMAI)
(mean (SD))
(lower scores = better)

6 weeks: 37.1 (11.1)
6 months: 44.0 (18.0)
12 months: 46.0 (18.0)
18 months: 42.0 (14.0)
24 months: 49.0 (15.0)

6 weeks:37.1 (10.9)
6 months: 47.0 (19.0)
12 months: 48.0 (18.0)
18 months: 47.0 (15.0)
24 months: 58.0 (16.0)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: -0.16 (-0.45 to
0.14)
6 months: -0.16 (-0.62 to
0.30)
12 months: -0.11 (-0.65
to 0.43)
18 months:-0.34 (-0.96,
0.28)
24 months: -0.57 (-1.37,
0.24)

 
 

Analysis 5.2.   Comparison 5: Lighting intervention  vs. control lighting,
Outcome 2: Behaviour, mood and depression: depression 4-6 weeks

Study or Subgroup

Figueiro 2019
Hopkins 2017
Riemersma-vanDerLek 2008

Total (95% CI)
Heterogeneity: Chi² = 5.56, df = 2 (P = 0.06); I² = 64%
Test for overall effect: Z = 1.84 (P = 0.07)
Test for subgroup differences: Not applicable

Lighting 
Mean

7.1
4.4
5.8

SD

4.5
2.9
4.9

Total

46
56
47

149

Control
Mean

9.6
4

7.8

SD

5.7
3.3
5.2

Total

46
56
40

142

Weight

31.2%
39.1%
29.6%

100.0%

Std. Mean Difference
IV, Fixed, 95% CI

-0.48 [-0.90 , -0.07]
0.13 [-0.24 , 0.50]

-0.39 [-0.82 , 0.03]

-0.22 [-0.45 , 0.01]

Std. Mean Difference
IV, Fixed, 95% CI

-1 -0.5 0 0.5 1
Favours lighting Favours control

 
 

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Analysis 5.3.   Comparison 5: Lighting intervention  vs. control lighting,
Outcome 3: Behaviour, mood and depression: agitation 4-6 weeks

Study or Subgroup

Figueiro 2019
Riemersma-vanDerLek 2008

Total (95% CI)
Heterogeneity: Chi² = 1.20, df = 1 (P = 0.27); I² = 17%
Test for overall effect: Z = 1.05 (P = 0.29)
Test for subgroup differences: Not applicable

Lighting 
Mean

37.1
41

SD

11.1
12

Total

46
47

93

Control
Mean

37.1
46

SD

10.9
18

Total

46
40

86

Weight

51.9%
48.1%

100.0%

Std. Mean Difference
IV, Fixed, 95% CI

0.00 [-0.41 , 0.41]
-0.33 [-0.75 , 0.10]

-0.16 [-0.45 , 0.14]

Std. Mean Difference
IV, Fixed, 95% CI

-1 -0.5 0 0.5 1
Favours intervention Favours control

 
 

Analysis 5.4.   Comparison 5: Lighting intervention  vs. control lighting, Outcome 4: Function 4-6 weeks

Study or Subgroup

Figueiro 2019
Riemersma-vanDerLek 2008

Total (95% CI)
Heterogeneity: Chi² = 0.78, df = 1 (P = 0.38); I² = 0%
Test for overall effect: Z = 1.94 (P = 0.05)
Test for subgroup differences: Not applicable

Lighting 
Mean

10.1
15

SD

7.5
11

Total

46
47

93

Control
Mean

11.4
20

SD

8.1
12

Total

46
40

86

Weight

52.1%
47.9%

100.0%

Std. Mean Difference
IV, Fixed, 95% CI

-0.17 [-0.57 , 0.24]
-0.43 [-0.86 , -0.01]

-0.29 [-0.59 , 0.00]

Std. Mean Difference
IV, Fixed, 95% CI

-1 -0.5 0 0.5 1
Favours lighting Favours control

 
 

Analysis 5.5.   Comparison 5: Lighting intervention  vs. control lighting, Outcome 5: Function

Function

Study Measure Lighting intervention Control Sample size Effect estimate

Riemersma-vanDerLek
2008

Nurse-informant adapta-
tion (NI-ADL) of the scale
by Katz et al (mean (SD))
(lower scores = better)

6 months: 20.0 (14.0)
12 months: 17.0 (12.0)
18 months: 17.0 (14.0)
24 months: 13.0 (11.0)

6 months: 22.0 (12.0)
12 months: 22.0 (11.0)
18 months: 27.0 (14.0)
24 months: 29.0 (14.0)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 months: -0.15 (-0.61 to
0.31)
12 months: -0.42 [-0.97,
0.12]
18 months: -0.70 (-1.34
to -0.06)
24 months: -1.27 (-2.14
to -0.39)

 
 

Analysis 5.6.   Comparison 5: Lighting intervention  vs. control lighting, Outcome 6: Global cognitive function

Global cognitive function

Study Measure Lighting intervention Control Sample size  Effect estimate

Riemersma-vanDerLek
2008

Mini-mental state exam-
ination (MMSE) (mean
(SD))
(higher scores = better)

6 weeks: 14.5 (6.2)
6 months: 16.6 (5.5)
12 months: 15.6 (5.2)
18 months: 16.2 (4.5)
24 months: 17.4 (3.7)

6 weeks: 14.3 (7.0)
6 months: 15.4 (7.3)
12 months: 15.6 (6.4)
18 months: 14.5 (5.4)
24 months: 13.7 (7.4)

6 weeks: 87
6 months: 74
12 months: 55
18 months: 41
24 months: 26

MD (95% confidence in-
terval):
6 weeks: 0.20 (-2.48 to
2.88)
6 months: 1.20 (-1.56 to
3.96)
12 months: 0.00 (-2.74 to
2.74)
18 months: 1.70 (-1.03 to
4.43)
24 months: 3.70 (-0.04 to
7.44)

 
 

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Comparison 6.   Dining space redesign vs. traditional environment

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

6.1 Quality of life 2   Other data No numeric data

6.2 Behaviour, mood and depression 1   Other data No numeric data

6.3 Function 1   Other data No numeric data

6.4 Global cognitive function 1   Other data No numeric data

6.5 Serious adverse effects 1   Other data No numeric data

 
 

Analysis 6.1.   Comparison 6: Dining space redesign vs. traditional environment, Outcome 1: Quality of life

Quality of life

Study Measure Dining space redesign Traditional Sample size Effect estimate or re-
ported significance

Sickness Impact Profile
(SIP) (mean percentage
change (SD))
(higher scores = better)

-2% (11%) -13% (12%) 16 P < 0.05 in control group
Authors reported values
“stayed stable” in inter-
vention group

Mathey 2001

Dutch version of the
Philadelphia Geriatric
Center Moral Scale
(PGCMS) (mean percent-
age change (SD))
(higher scores = better)

-3% (20%) -2% (19%) 16 Authors reported values
remained “relatively sta-
ble”, no P values report-
ed

Dutch quality of life of
somatic nursing home
residents questionnaire 
(higher scores = better)

N/R N/R 178 MD (95% confidence in-
terval):
6.10 (2.10 to 10.10)

Nijs 2006

         

 
 

Analysis 6.2.   Comparison 6: Dining space redesign vs. traditional
environment, Outcome 2: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Dining space redesign Traditional Sample size Reported significance

Kenkmann 2010 Hospital Anxiety and De-
pression Scale (HADS),
(unadjusted mean (SD))
(lower scores = better)

Baseline: 4.07 (3)
12 months: 4.86 (4.61)

Baseline: 6.3 (4.45)
12 months: 6.78 (3.83)

120 N/R

 
 

Analysis 6.3.   Comparison 6: Dining space redesign vs. traditional environment, Outcome 3: Function

Function

Study Measure n Effect estimate

Nijs 2006 Nursing home physical performance
test
(higher scores = better)

178 MD (95% confidence interval):
3.20 (0.90 to 5.50)

 
 

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Analysis 6.4.   Comparison 6: Dining space redesign vs.
traditional environment, Outcome 4: Global cognitive function

Global cognitive function

Study Measure Dining space redesign Traditional Sample size Reported significance

Kenkmann 2010 Mini-Mental State Exam-
ination (MMSE) (unad-
justed mean (SD))
(higher scores = better)

Baseline: 19 (5.6)
12 months: 17 (6.2)

Baseline: 17 (6.2)
12 months: 15 (7.9)

56 P > 0.05

Kenkmann 2010 MMSE, cognitive impair-
ment <= 23, %

Baseline: 83.3%
12 months: 81.5%

Baseline: 87.5%
12 months: 79.2%

54 P > 0.05

 
 

Analysis 6.5.   Comparison 6: Dining space redesign vs. traditional environment, Outcome 5: Serious adverse e?ects

Serious adverse effects

Study Measure Dining space redesign Traditional Sample size Effect estimate or re-
ported significance

Fall within previous year,
%

Baseline: 60%
12 months: 60%

Baseline: 56%
12 months: 50%

105 P > 0.05Kenkmann 2010

Rate of falls N/R N/R 105 Rate ratio (95% confi-
dence interval):
0.76 (0.57 to 1.01)

 
 

Comparison 7.   Garden vignette vs. traditional environment

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

7.1 Behaviour, mood and depression 1   Other data No numeric data

 
 

Analysis 7.1.   Comparison 7: Garden vignette vs. traditional
environment, Outcome 1: Behaviour, mood and depression

Behaviour, mood and depression

Study Measure Garden vignette Traditional Sample size Effect estimate

Marcy-Edwards 2011 Neuropsychiatric Inven-
tory-Nursing Homes
(NPI, NH), (mean change
(SD))
(lower scores = better)

12.4 (66.1) -0.4 (19) 33 MD (95% confidence in-
terval):
12.8 (-10.7 to 36.3)

 

 

A P P E N D I C E S

Appendix 1. Search strategies

MEDLINE

OVID

 

1. aged/

 

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2. “aged, 80 and over”/

3. frail elderly/

4. (geriatric? or senior? or elderly or aged).ti,ab.

5. (older adult? or older person? or older people or older patient?).ti,ab.

6. geriatrics/

7. *geriatric dentistry/

8. *geriatric nursing/

9. geriatric assessment/

10. *geriatric psychiatry/

11. “health services for the aged”/

12. or/1-11

13. long-term care/

14. long-term care.ti,ab.

15. (long stay adj2 (care or healthcare or service? or treatment? or patient? or resident?)).ti,ab.

16. (function* adj2 (dependen* or independen* or limit* or decline* or status or impair*)).ti,ab.

17. (candidate? adj3 (institution* or deinstitution* or home or place*)).ti,ab.

18. (residential adj3 (care or healthcare or facilit*)).ti,ab.

19. residential facilities/

20. assisted living facilities/

21. group homes/

22. (group? adj (home? or living)).ti,ab.

23. halfway houses/

24. halfway hous*.ti,ab.

25. homes for the aged/

26. intermediate care facilities/

27. skilled nursing facilities/

28. hospice?.ti,ab.

29. hospices/

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30. or/13-29

31. nursing homes/

32. nursing home?.ti,ab.

33. 12 and 30

34. or/31-33

35. exp health facility environment/

36. exp “facility design and construction”/

37. (environment* adj2 (person-centered or person-centred or attribute* or model? or change? or built
or scale or modif* or special* or design* or physical or safe or stimul* or home* or house* or ac-
cess* or improv* or facilit* or residential* or infrastructur* or adjust* or adapt* or living)).ti,ab.

38. ((men* or communit*) adj2 shed?).ti,ab.

39. (architectur* or cottage model? or green house or home-like or homelike or person-centered or
person-centred or outdoor* or garden* or private room* or quiet room* or lighting or paint* or
colour? or color? or floor* or dining or kitchen* or reminiscen* or small-scale or large-scale or fur-
nishing*).ti,ab.

40. or/35-39

41. 34 and 40

42. randomized controlled trial.pt.

43. controlled clinical trial.pt.

44. multicenter study.pt.

45. pragmatic clinical trial.pt.

46. (randomis* or randomiz* or randomly).ti,ab.

47. groups.ab.

48. (trial or multicenter or multi center or multicentre or multi centre).ti.

49. (intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre
adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experi-
ment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or re-
peated measur*).ti,ab.

50. non-randomized controlled trials as topic/

51. interrupted time series analysis/

52. controlled before-after studies/

53. or/42-52

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54. exp animals/

55. humans/

56. 54 not (54 and 55)

57. review.pt.

58. meta analysis.pt.

59. news.pt.

60. comment.pt.

61. editorial.pt.

62. cochrane database of systematic reviews.jn.

63. comment on.cm.

64. (systematic review or literature review).ti.

65. or/56-64

66. 53 not 65

67. 41 and 66

  (Continued)

 

Embase

OVID

 

1. exp aged/

2. geriatrics/

3. exp elderly care/

4. (older adult? or older person? or older people or older patient?).ti,ab,kw.

5. (geriatric? or senior? or elderly or aged).ti,ab,kw.

6. or/1-5

7. long term care/

8. (long-term adj2 (care or healthcare or service? or treatment? or patient? or resident?)).ti,ab,kw.

9. (long stay adj2 (care or healthcare or service? or treatment? or patient? or resident?)).ti,ab,kw.

10. (function* adj2 (dependen* or independen* or limit* or decline* or status or impair*)).ti,ab,kw.

 

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11. (candidate? adj3 (institution* or deinstitution* or home or place*)).ti,ab,kw.

12. (residential adj3 (care or healthcare or facilit*)).ti,ab,kw.

13. residential home/

14. assisted living facility/

15. (assisted living facilit* or assisted care facilit*).ti,ab,kw.

16. (group? adj (home? or living)).ti,ab,kw.

17. halfway house/

18. halfway hous*.ti,ab,kw.

19. hospice/

20. hospice?.ti,ab,kw.

21. or/7-20

22. home for the aged/

23. nursing home/

24. nursing home?.ti,ab,kw.

25. 6 and 21

26. or/22-25

27. (facilit* adj2 (design or designed or designing or designs)).ti,ab,kw.

28. (single adj2 room?).ti,ab,kw.

29. built environment?.ti,ab,kw.

30. (environment* adj2 (person-centered or person-centred or attribute* or model? or change? or built
or scale or modif* or special* or design* or physical or safe or stimul* or home* or house* or ac-
cess* or improv* or facilit* or residential* or infrastructur* or adjust* or adapt* or living)).ti,ab,kw.

31. ((men* or communit*) adj2 shed?).ti,ab,kw.

32. (architectur* or cottage model? or green house or home-like or homelike or person-centered or
person-centred or outdoor* or garden* or private room* or quiet room* or lighting or paint* or
colour? or color? or floor* or dining or kitchen* or reminiscen* or small-scale or large-scale or fur-
nishing*).ti,ab,kw.

33. environmental planning/

34. or/27-33

35. 26 and 34

36. randomized controlled trial/

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37. controlled clinical trial/

38. quasi experimental study/

39. pretest posttest control group design/

40. time series analysis/

41. experimental design/

42. multicenter study/

43. (randomis* or randomiz* or randomly).ti,ab.

44. groups.ab.

45. (trial or multicentre or multicenter or multi centre or multi center).ti.

46. (intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre
adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experi-
ment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or re-
peated measur*).ti,ab.

47. or/36-46

48. (systematic review or literature review).ti.

49. “cochrane database of systematic reviews”.jn.

50. exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or ani-
mal cell/ or nonhuman/

51. human/ or normal human/ or human cell/

52. 50 not (50 and 51)

53. 48 or 49 or 52

54. 47 not 53

55. 35 and 54

  (Continued)

 

Cochrane Library

Wiley

 

#1.  [mh aged] 

#2. [mh “aged, 80 and over”] 

#3. [mh “frail elderly”] 

 

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#4. (geriatric? or senior? or elderly or aged):ti,ab 

#5. (older next adult? or older next person? or older next people or older next patient?):ti,ab 

#6. [mh geriatrics] 

#7. [mh “health services for the aged”] 

#8. {or #1-#7} 

#9. [mh “long-term care”] 

#10. (long-term near/2 (care or healthcare or service? or treatment? or patient? or resident?)):ti,ab 

#11. (long stay near/2 (care or healthcare or service? or treatment? or patient? or resident?)):ti,ab 

#12. (function* near/2 (dependen* or independen* or limit* or decline* or status or impair*)):ti,ab 

#13. (candidate? near/3 (institution* or deinstitution* or home or place*)):ti,ab 

#14. (residential near/3 (care or healthcare or facilit*)):ti,ab 

#15. [mh “residential facilities”] 

#16. [mh “assisted living facilities”] 

#17. (assisted living facilit* or assisted care facilit*):ti,ab 

#18. [mh “group homes”] 

#19. (group? next (home? or living)):ti,ab 

#20. [mh “halfway houses”] 

#21. halfway next hous*:ti,ab 

#22. [mh “intermediate care facilities”] 

#23. [mh “skilled nursing facilities”] 

#24. hospice?:ti,ab 

#25. [mh hospices] 

#26. {or #9-#25} 

#27. [mh “homes for the aged”] 

#28. [mh “nursing homes”] 

#29. nursing next home?:ti,ab 

#30. #8 and #26 

#31. {or #27-#30} 

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#32. [mh “health facility environment”] 

#33. [mh “facility design and construction”] 

#34. (facilit* near/2 (design or designed or designing or designs)):ti,ab 

#35. (single near/2 room?):ti,ab 

#36. built next environment?:ti,ab 

#37. (environment* near/2 (person-centered or person-centred or attribute* or model? or change? or
built or scale or modif* or special* or design* or physical or safe or stimul* or home* or house* or
access* or improv* or facilit* or residential* or infrastructur* or adjust* or adapt* or living)):ti,ab 

#38. ((men* or communit*) near/2 shed?):ti,ab 

#39. (architectur* or (cottage next model?) or (green next house) or home-like or homelike or per-
son-centered or person-centred or outdoor* or garden* or (private next room*) or (quiet next
room*) or lighting or paint* or colour? or color? or floor* or dining or kitchen* or reminiscen* or
small-scale or large-scale or furnishing*):ti,ab 

#40. {or #32-#39} 

#41. #31 and #40 

  (Continued)

 

CINAHL PLUS

EBSCO

 

S1. (MH “Aged+”)

S2. (MH “Geriatrics”)

S3. (MH “Health Services for the Aged”)

S4. geriatric? or senior? or elderly or aged

S5. older adult? or older person? or older people or older patient?

S6. S1 OR S2 OR S3 OR S4 OR S5

S7. (MH “Long Term Care”)

S8. (MH “Residential Facilities”)

S9. (MH “Halfway Houses”)

S10. (MH “Skilled Nursing Facilities”)

S11. long-term N2 (care or healthcare or service? or treatment? or patient? or resident?)

 

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S12. long stay N2 (care or healthcare or service? or treatment? or patient? or resident?)

S13. function* N2 (dependen* or independen* or limit* or decline* or status or impair*)

S14. candidate? N3 (institution* or deinstitution* or home or place*)

S15. residential N3 (care or healthcare or facilit*)

S16. assisted living facilit* or assisted care facilit*

S17. group? N (home? or living)

S18. halfway hous*

S19. hospice

S20. (MH “Hospices”)

S21. S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20

S22. (MH “Nursing Home Patients”)

S23. (MH “Nursing Homes”)

S24. nursing home

S25. S6 AND S21

S26. S22 OR S23 OR S24 OR S25

S27. (MH “Nursing Home Design and Construction”)

S28. (MH “Facility Design and Construction+”)

S29. (MH “Health Facility Environment”)

S30. facilit* N2 (design or designed or designing or designs)

S31. single N2 room?

S32. built environment

S33. environment* N2 (person-centered or person-centred or attribute* or model? or change? or built or
scale or modif* or special* or design* or physical or safe or stimul* or home* or house* or access*
or improv* or facilit* or residential* or infrastructur* or adjust* or adapt* or living)

S34. (men* or communit*) N2 shed?

S35. architectur* or cottage model? or green house or home-like or homelike or person-centered or per-
son-centred or outdoor* or garden* or private room* or quiet room* or lighting or paint* or colour?
or color? or floor* or dining or kitchen* or reminiscen* or small-scale or large-scale or furnishing*

S36. S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35

S37. S26 AND S36

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S38. PT randomized controlled trial

S39. PT clinical trial

S40. PT research

S41. (MH “Randomized Controlled Trials”)

S42. (MH “Clinical Trials”)

S43. (MH “Intervention Trials”)

S44. (MH “Nonrandomized Trials”)

S45. (MH “Experimental Studies”)

S46. (MH “Pretest-Posttest Design+”)

S47. (MH “Quasi-Experimental Studies+”)

S48. (MH “Multicenter Studies”)

S49. (MH “Health Services Research”)

S50. TI ( randomis* or randomiz* or randomly) OR AB ( randomis* or randomiz* or randomly)

S51. TI (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest or “pre
test”) and (posttest or “post test”)) or quasiexperiment* or quasi W0 experiment* or pseudo exper-
iment* or pseudoexperiment* or evaluat* or “time series” or time W0 point* or repeated W0 mea-
sur*) OR AB (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest
or “pre test”) and (posttest or “post test”)) or quasiexperiment* or quasi W0 experiment* or pseudo
experiment* or pseudoexperiment* or evaluat* or “time series” or time W0 point* or repeated W0
measur*)

S52. S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR
S51

S53. S37 AND S52

S54. S53 Limiters – Exclude MEDLINE records

  (Continued)

 

PsycINFO

EBSCO

 

S1.  (MH “Aged+”)

S2. (MH “Geriatrics”)

S3. (MH “Health Services for the Aged”)

 

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S4. geriatric? or senior? or elderly or aged

S5. older adult? or older person? or older people or older patient?

S6. S1 OR S2 OR S3 OR S4 OR S5

S7. (MH “Long Term Care”)

S8. (MH “Residential Facilities”)

S9. (MH “Halfway Houses”)

S10. (MH “Skilled Nursing Facilities”)

S11. long-term N2 (care or healthcare or service? or treatment? or patient? or resident?)

S12. long stay N2 (care or healthcare or service? or treatment? or patient? or resident?)

S13. function* N2 (dependen* or independen* or limit* or decline* or status or impair*)

S14. candidate? N3 (institution* or deinstitution* or home or place*)

S15. residential N3 (care or healthcare or facilit*)

S16. assisted living facilit* or assisted care facilit*

S17. group? N (home? or living)

S18. halfway hous*

S19. hospice

S20. (MH “Hospices”)

S21. S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20

S22. (MH “Nursing Home Patients”)

S23. (MH “Nursing Homes”)

S24. nursing home

S25. S6 AND S21

S26. S22 OR S23 OR S24 OR S25

S27. (MH “Nursing Home Design and Construction”)

S28. (MH “Facility Design and Construction+”)

S29. (MH “Health Facility Environment”)

S30. facilit* N2 (design or designed or designing or designs)

S31. single N2 room?

  (Continued)

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S32. built environment

S33. environment* N2 (person-centered or person-centred or attribute* or model? or change? or built or
scale or modif* or special* or design* or physical or safe or stimul* or home* or house* or access*
or improv* or facilit* or residential* or infrastructur* or adjust* or adapt* or living)

S34. (men* or communit*) N2 shed?

S35. architectur* or cottage model? or green house or home-like or homelike or person-centered or per-
son-centred or outdoor* or garden* or private room* or quiet room* or lighting or paint* or colour?
or color? or floor* or dining or kitchen* or reminiscen* or small-scale or large-scale or furnishing*

S36. S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35

S37. S26 AND S36

S38. PT randomized controlled trial

S39. PT clinical trial

S40. PT research

S41. (MH “Randomized Controlled Trials”)

S42. (MH “Clinical Trials”)

S43. (MH “Intervention Trials”)

S44. (MH “Nonrandomized Trials”)

S45. (MH “Experimental Studies”)

S46. (MH “Pretest-Posttest Design+”)

S47. (MH “Quasi-Experimental Studies+”)

S48. (MH “Multicenter Studies”)

S49. (MH “Health Services Research”)

S50. TI ( randomis* or randomiz* or randomly) OR AB ( randomis* or randomiz* or randomly)

S51. TI (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest or “pre
test”) and (posttest or “post test”)) or quasiexperiment* or quasi W0 experiment* or pseudo exper-
iment* or pseudoexperiment* or evaluat* or “time series” or time W0 point* or repeated W0 mea-
sur*) OR AB (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest
or “pre test”) and (posttest or “post test”)) or quasiexperiment* or quasi W0 experiment* or pseudo
experiment* or pseudoexperiment* or evaluat* or “time series” or time W0 point* or repeated W0
measur*)

S52. S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR
S51

S53. S37 AND S52

  (Continued)

 

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ProQuest dissertations and theses

 

TI,AB(geriatric* or senior* or elderly or frail or older) AND TI,AB(nursing home* or residential or long term care) AND TI,AB(design* or
environment*) AND (SU(health*) OR TI(effect OR effects OR impact OR influenc* OR random* OR study OR controlled OR trial OR ef-
fectiveness) OR ALL(random* OR intervention OR collaborat* OR team* OR multidisciplin* OR multi-disciplin* OR crossdisciplin* OR
cross-disciplin* OR interdisciplin* OR community OR quasi*) OR ALL(before NEAR/10 after) OR ALL(before NEAR/10 during) OR AL-
L(“time series” OR timeseries) OR ALL((control* NEAR/2 group) OR (control NEAR/2 study) OR (control NEAR/2 cohort)))

 

 

Science Citation Index and Conference Proceedings Citation Index-Science

 

#1 TS=((geriatric? OR senior? OR elderly OR older) NEAR/1 (adult? OR person? OR people OR patient?)) 

#2 TS=(long NEAR/3 (care OR healthcare OR service? OR treatment? OR patient? OR resident?)) 

#3 TS=(function* NEAR/2 (dependen* OR independen* OR limit* OR decline* OR status OR impair*)) 

#4 TS=(candidate? NEAR/3 (institution* OR deinstitution* OR home OR place*)) 

#5 TS=(residential NEAR/3 (care OR healthcare OR facilit*)) 

#6 TS=(assisted living facilit* OR assisted care facilit*) 

#7 TS=(group? NEAR/0 (home? OR living)) 

#8 TS=(halfway hous* OR hospice?) 

#9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 

#10 #9 AND #1 

#11 TS=nursing home? 

#12 #11 OR #10 

#13 TS=(facilit* NEAR/2 (design OR designed OR designing OR designs)) 

#14 TS=(single NEAR/2 room?) 

#15 TS=built environment? 

#16 TS=(environment* NEAR/2 (person-centered OR person-centred OR attribute* OR model? OR
change? OR built OR scale OR modif* OR special* OR design* OR physical OR safe OR stimul* OR
home* OR house* OR access* OR improv* OR facilit* OR residential* OR infrastructur* OR adjust*
OR adapt* OR living)) 

#17 TS=((men* OR communit*) NEAR/2 shed?) 

#18 TS=(architectur* OR cottage model? OR green house OR home-like OR homelike OR person-cen-
tered OR person-centred OR outdoor* OR garden* OR private room* OR quiet room* OR lighting

 

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OR paint* OR colour? OR color? OR floor* OR dining OR kitchen* OR reminiscen* OR small-scale OR
large-scale OR furnishing*) 

#19 #18 OR #17 OR #16 OR #15 OR #14 OR #13 

#20 #19 AND #12 

#21 TS=(randomis* OR randomiz* OR randomly OR groups) 

#22 TS=(trial OR multicenter OR “multi center” OR multicentre OR “multi centre”) 

#23 TS=(intervention* OR effect* OR impact* OR controlled OR “control group*” OR (before near/5 af-
ter) OR (pre near/5 post) OR ((pretest OR “pre test”) AND (posttest OR “post test”)) OR quasiexperi-
ment* OR “quasi experiment*” OR “pseudo experiment*” OR pseudoexperiment* OR evaluat* OR
time series OR “time point*” OR “repeated measur*”) 

#24 #23 OR #22 OR #21 

#25 #24 AND #20 

  (Continued)

 

Social Care Online (www.scie-socialcareonline.org.uk)

 

Title  nursing home

Title  OR residential

Title OR long term care

Title AND environment

Title OR design

Title OR architecture

 

 

WHO International Clinical Trials Registry Platform (ICTRP)

 

1. nursing home AND environment

2. nursing home AND design

3. nursing home AND architecture

4. residential AND environment

5. residential AND design

 

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6. residential AND architecture

7. long term care AND environment

8. long term care AND design

9. long term care AND architecture

  (Continued)

 

US National Institutes of Health Ongoing Trials Register (Clinicaltrials.gov)

 

Other terms nursing home OR long term care OR residential

Intervention / Treatment: environment OR design OR architecture

age group  older adult (65+)

study type interventional

 

 

ANZCTR (ANZCTR.org.au)

 

1. nursing home AND environment

2. nursing home AND design

3. nursing home AND architecture

4. residential AND environment

5. residential AND design

6. residential AND architecture

7. long term care AND environment

8. long term care AND design

9. long term care AND architecture

 

 

H I S T O R Y

Protocol first published: Issue 12, 2017

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C O N T R I B U T I O N S   O F   A U T H O R S

All authors contributed to design of the review protocol. SLH independently screened the abstracts and SMD, KEL and RKM screened
abstracts in duplicate. SLH screened the full texts retrieved and SMD, KEL and RKM screened full-text articles in duplicate. SLH, SMD, KEL
and RKM independently extracted data and assessed the risk of bias of included studies. SLH completed the GRADE summary tables and
duplicate GRADE analysis was completed by SMD and KEL. SLH and SMD draJed the review and all authors reviewed and commented on
draJs and approved the final version. All authors made substantial contributions to the conception and design of the work.

D E C L A R A T I O N S   O F   I N T E R E S T

• SLH reports multiple academic publications on the topic of environmental design of aged care facilities. These publications are not
included studies in the review.

• SMD reports employment managing a project examining models of residential aged care. The INSPIRED study was supported by
funding from the National Health and Medical Research Council (NHMRC) Partnership Centre on Dealing with Cognitive and Related
Functional Decline in Older People (CDPC, GNT9100000). Australian aged care service providers were partners in the NHMRC CDPC;
they provided information on organisational structures of residential care and access to their facilities. SMD reports multiple academic
publications on the topic of environmental design of aged care facilities and multiple unpaid conference presentations (oral and posters)
on environmental design in aged care. These publications are not included studies in the review. SMD reports submissions to Australian
government inquiries and research reports conducted for the Australian Aged Care Royal Commission that include information on the
topic of environmental design in aged care. SMD also reports mainstream and social media dissemination of academic publications on
environmental design of aged care facilities.

• KEL reports a fellowship from the Australian Research Council.

• RKM reports grant payments from ECH Inc., Helping Hand, Presbyterian Aged Care, Uniting and Uniting AgeWell. RKM is an author on
multiple academic publications on the topic of environmental design of aged care facilities. These publications are not included studies
in the review.

• RF reports consultancy payments from Richard Fleming and Associates which involves providing advice on environmental design for
people living with dementia. RF is an author on an included study in the review, RF did not contribute to data extraction or assessment
of risk of bias of this study.

• MC reports one grant from Amgen and a consultant role for the Royal Commission into Aged Care Quality and Safety. MC  reports two
academic publications on the topic of environmental design of aged care facilities. These publications are not included studies in the
review. MC also works as a health professional (rehabilitation physician at Flinders Medical Centre).

S O U R C E S   O F   S U P P O R T

Internal sources

• Flinders University, Australia

SLH, SMD, KEL and MC are all staC at Flinders University and Flinders University provided the infrastructure for the project.

• Dementia Training Australia, Australia

RF’s funding was covered by Dementia Training Australia, a consortium of five universities and Alzheimer’s Australia funded by the
Australian Department of Health to develop, disseminate and implement new knowledge on the care of people with dementia.

External sources

• NHMRC Cognitive Decline Partnership Centre, Australia

The salaries of SLH and SMD, and partly the salary of MC, are supported by funding provided by the National Health and Medical
Research Council (NHMRC) Cognitive Decline Partnership Centre (grant no. GNT9100000).

• NHMRC-ARC Dementia Research Development Fellowship, Australia

KEL is supported by a NHMRC-ARC Dementia Research Development Fellowship.

• NHMRC and Institute for Safety, Compensation and Recovery Research, Australia

RKM is supported by grants from the NHMRC (grant nos. 1079542 and 1121334) and the Institute for Safety, Compensation and Recovery
Research Collaborative Grant.

D I F F E R E N C E S   B E T W E E N   P R O T O C O L   A N D   R E V I E W

In the protocol, we reported that secondary outcomes would include “dementia-specific measures (e.g. global behaviour measures with
the Neuropsychiatric Inventory, depression as measured with the Cornell Scale for Depression in Dementia)”. However, it is considered
that these measures should not be examined separately to behaviour as some measures, including the Neuropsychiatric Inventory, may be

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used for people not living with dementia and all depression measures should also be considered as one outcome. Therefore, we removed
“dementia-specific measures” as a secondary outcome. We also omitted ‘protection against contamination’ as one of the EPOC criteria for
risk of bias in the protocol, so this was corrected and added in the review.

For the search strategy, we stated we would search Index to Theses, but this was no longer available, and the content was merged into
ProQuest dissertations and theses which was searched. We also stated we would search  Health Management Information Consortium
(HMIC) Ovid, but this was not available at the University of Oxford where the search was conducted.

In the protocol, we stated we would create a Summary of findings table for the main intervention: whole-facility model compared to usual
care or alternative designs. In this review, we also created Summary of findings tables for the lighting and dining room interventions
to provide a succinct summary for the smaller interventions which focused on a specific component of design that was analysed
quantitatively. In the Summary of findings table, we also grouped the outcomes ‘measures of basic function’ and ‘measures of instrumental
function’ under one outcome ‘function’.

The protocol named “behaviour, mood and depression” as a primary outcome. As this outcome encompasses a large range of possible
outcomes and measures, only the two considered most informative were included in the Summary of findings tables. These are: global
behaviour measures (as these capture a range of these outcomes) and depression, as this is a common and important negative mood
symptom in residents of aged care homes.

The protocol did not specify time points for any of the outcomes. The most important time points for outcomes are considered to be in the
range three to six months, as this allows adequate time for an intervention to have an eCect, but is not such an extended follow-up that it
will be against a background of large functional or cognitive decline or increased mortality in residents.

N O T E S

This review is based on standard text and guidance provided by Cochrane ECective Practice and Organisation of Care (EPOC).

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Inhaled corticosteroids for the treatment of COVID-19 (Review)

 

  Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf MI, Nair AA, Daniel J,
Fischer AL, Skoetz N

 

  Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf M-I, Nair AAnil, Daniel J, Fischer A-L, Skoetz N.
Inhaled corticosteroids for the treatment of COVID-19.
Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.: CD015125.
DOI: 10.1002/14651858.CD015125.

 

  www.cochranelibrary.com  

Inhaled corticosteroids for the treatment of COVID-19 (Review)
 

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T A B L E   O F   C O N T E N T S

ABSTRACT…………………………………………………………………………………………………………………………………………………………………………….. 1

PLAIN LANGUAGE SUMMARY………………………………………………………………………………………………………………………………………………….. 3

SUMMARY OF FINDINGS………………………………………………………………………………………………………………………………………………………… 5

BACKGROUND………………………………………………………………………………………………………………………………………………………………………. 7

OBJECTIVES………………………………………………………………………………………………………………………………………………………………………….. 8

METHODS…………………………………………………………………………………………………………………………………………………………………………….. 8

RESULTS……………………………………………………………………………………………………………………………………………………………………………….. 13

Figure 1………………………………………………………………………………………………………………………………………………………………………….. 14

DISCUSSION………………………………………………………………………………………………………………………………………………………………………….. 19

AUTHORS’ CONCLUSIONS……………………………………………………………………………………………………………………………………………………… 20

ACKNOWLEDGEMENTS………………………………………………………………………………………………………………………………………………………….. 21

REFERENCES………………………………………………………………………………………………………………………………………………………………………… 22

CHARACTERISTICS OF STUDIES……………………………………………………………………………………………………………………………………………… 26

RISK OF BIAS………………………………………………………………………………………………………………………………………………………………………… 50

DATA AND ANALYSES……………………………………………………………………………………………………………………………………………………………… 52

Analysis 1.1. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 1: All-cause mortality at up to day 30…………………………………………………………………………………………………………………

53

Analysis 1.2. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 2: Admission to hospital or death at up to 30 days………………………………………………………………………………………………

53

Analysis 1.3. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 3: Symptom resolution: all initial symptoms resolved (asymptomatic) at day 14……………………………………………………

54

Analysis 1.4. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 4: Symptom resolution: mean time to recovery (days)…………………………………………………………………………………………

54

Analysis 1.5. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 5: Symptom resolution: all initial symptoms resolved at up to day 30…………………………………………………………………..

54

Analysis 1.6. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 6: Quality of life at day 28: mean in well-being (WHO-5 Well-Being Questionnaire)…………………………………………………

54

Analysis 1.7. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 7: Serious adverse events………………………………………………………………………………………………………………………………….

55

Analysis 1.8. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 8: Adverse events………………………………………………………………………………………………………………………………………………

55

Analysis 1.9. Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo),
Outcome 9: Infections………………………………………………………………………………………………………………………………………………………

55

ADDITIONAL TABLES……………………………………………………………………………………………………………………………………………………………… 56

APPENDICES…………………………………………………………………………………………………………………………………………………………………………. 60

WHAT’S NEW…………………………………………………………………………………………………………………………………………………………………………. 62

HISTORY……………………………………………………………………………………………………………………………………………………………………………….. 62

CONTRIBUTIONS OF AUTHORS………………………………………………………………………………………………………………………………………………. 62

DECLARATIONS OF INTEREST………………………………………………………………………………………………………………………………………………… 63

SOURCES OF SUPPORT…………………………………………………………………………………………………………………………………………………………. 63

DIFFERENCES BETWEEN PROTOCOL AND REVIEW…………………………………………………………………………………………………………………… 64

NOTES………………………………………………………………………………………………………………………………………………………………………………….. 64

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[Intervention Review]

Inhaled corticosteroids for the treatment of COVID-19

Mirko Griesel1a, Carina Wagner2b, Agata Mikolajewska3,4, Miriam Stegemann3, Falk Fichtner1, Maria-Inti Metzendorf5, Avinash Anil Nair6,

JeGerson Daniel7, Anna-Lena Fischer1c, Nicole Skoetz2d

1Department of Anesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig, Germany. 2Cochrane Haematology,
Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University

Hospital Cologne, University of Cologne, Cologne, Germany. 3Department of Infectious Diseases and Respiratory Medicine, Charité –

Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 4Centre
for Biological Threats and Special Pathogens (ZBS), Strategy and Incident Response, Clinical Management and Infection Control, Robert

Koch Institute, Berlin, Germany. 5Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of

the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 6Department of Respiratory Medicine, Christian Medical College, Vellore,

India. 7Department of Pulmonary Medicine, Christian Medical College, Vellore, India

acontributed equally (first author). bcontributed equally (first author). ccontributed equally (last author). dcontributed equally (last
author)

Contact: Nicole Skoetz, [email protected]

Editorial group: Cochrane Airways Group.
Publication status and date: Edited (no change to conclusions), published in Issue 3, 2022.

Citation: Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf M-I, Nair AAnil, Daniel J, Fischer A-L,
Skoetz N.Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.:
CD015125. DOI: 10.1002/14651858.CD015125.

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

A B S T R A C T

Background

Inhaled corticosteroids are well established for the long-term treatment of inflammatory respiratory diseases such as asthma or
chronic obstructive pulmonary disease. They have been investigated for the treatment of coronavirus disease 2019 (COVID-19). The
anti-inflammatory action of inhaled corticosteroids might have the potential to reduce the risk of severe illness resulting from
hyperinflammation in COVID-19.

Objectives

To assess whether inhaled corticosteroids are eGective and safe in the treatment of COVID-19; and to maintain the currency of the evidence,
using a living systematic review approach.

Search methods

We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, and
medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease
to identify completed and ongoing studies to 7 October 2021.

Selection criteria

We included randomised controlled trials (RCTs) evaluating inhaled corticosteroids for COVID-19, irrespective of disease severity, age, sex,
or ethnicity.

We included the following interventions: any type or dose of inhaled corticosteroids. We included the following comparison: inhaled
corticosteroids plus standard care versus standard care (with or without placebo).

We excluded studies examining nasal or topical steroids.

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Data collection and analysis

We followed standard Cochrane methodology. For risk of bias assessment, we used the Cochrane RoB 2 tool. We rated the certainty of
evidence using the GRADE approach for the outcomes of mortality, admission to hospital or death, symptom resolution, time to symptom
resolution, serious adverse events, adverse events, and infections.

Main results

Inhaled corticosteroids plus standard care versus standard care (with/without placebo)

People with a confirmed diagnosis of moderate-to-severe COVID-19

We found no studies that included people with a confirmed diagnosis of moderate-to-severe COVID-19.

People with a confirmed diagnosis of asymptomatic SARS-CoV-2 infection or mild COVID-19

We included three RCTs allocating 3607 participants, of whom 2490 had confirmed mild COVID-19. We analysed a subset of the total
number of participants recruited to the studies (2171, 52% female) as some trials had a platform design where not all participants were
allocated to treatment groups simultaneously. The included studies were community-based, recruiting people who were able to use
inhaler devices to deliver steroids and relied on remote assessment and self-reporting of outcomes. Most people were older than 50
years and had co-morbidities such as hypertension, lung disease, or diabetes. The studies were conducted in high-income countries prior
to wide-scale vaccination programmes. A total of 1057 participants were analysed in the inhaled corticosteroid arm (budesonide: 860
participants; ciclesonide: 197 participants), and 1075 participants in the control arm. No studies included people with asymptomatic SARS-
CoV-2 infection.

With respect to the following outcomes, inhaled corticosteroids compared to standard care:

– may result in little to no diGerence in all-cause mortality (at up to day 30) (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.22 to 1.67;
2132 participants; low-certainty evidence). In absolute terms, this means that for every nine deaths per 1000 people not receiving inhaled
corticosteroids, there were six deaths per 1000 people who did receive the intervention (95% CI 2 to 16 per 1000 people);

– probably reduces admission to hospital or death (at up to 30 days) (RR 0.72, 95% CI 0.51 to 0.99; 2025 participants; moderate-certainty
evidence);

– probably increases resolution of all initial symptoms at day 14 (RR 1.19, 95% CI 1.09 to 1.30; 1986 participants; moderate-certainty
evidence);

– may reduce the duration to symptom resolution (at up to day 30) (by −4.00 days, 95% CI −6.22 to −1.78 less than control group rate of 12
days; 139 participants; low-certainty evidence);

– the evidence is very uncertain about the eGect on serious adverse events (during study period) (RR 0.51, 95% CI 0.09 to 2.76; 1586
participants; very low-certainty evidence);

– may result in little to no diGerence in adverse events (at up to day 30) (RR 0.78, 95% CI 0.47 to 1.31; 400 participants; low-certainty evidence);

– may result in little to no diGerence in infections (during study period) (RR 0.88, 95% CI 0.30 to 2.58; 400 participants; low-certainty
evidence).

As studies did not report outcomes for subgroups (e.g. age, ethnicity, sex), we did not perform subgroup analyses.

Authors’ conclusions

In people with confirmed COVID-19 and mild symptoms who are able to use inhaler devices, we found moderate-certainty evidence that
inhaled corticosteroids probably reduce the combined endpoint of admission to hospital or death and increase the resolution of all initial
symptoms at day 14. Low-certainty evidence suggests that corticosteroids make little to no diGerence in all-cause mortality up to day 30 and
may decrease the duration to symptom resolution. We do not know whether inhaled corticosteroids increase or decrease serious adverse
events due to heterogeneity in the way they were reported across the studies. There is low-certainty evidence that inhaled corticosteroids
may decrease infections.

The evidence we identified came from studies in high-income settings using budesonide and ciclesonide prior to vaccination roll-outs.

We identified a lack of evidence concerning quality of life assessments, serious adverse events, and people with asymptomatic infection
or with moderate-to-severe COVID-19. The 10 ongoing and four completed, unpublished RCTs that we identified in trial registries address
similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future
versions of this review.

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We monitor newly published results of RCTs on inhaled corticosteroids on a weekly basis and will update the review when the evidence
or our certainty in the evidence changes.

P L A I N   L A N G U A G E   S U M M A R Y

Are inhaled corticosteroids an e8ective treatment for people with mild COVID-19?

Key messages

Inhaled corticosteroids (anti-inflammatory medicines) given via the oral inhaled route are evaluated for treatment of coronavirus disease
2019 (COVID-19).

We identified three published studies for people with mild disease. Inhaled corticosteroids probably reduce the risk of people going to
hospital or death (admission to hospital or death before hospital admission). Inhaled corticosteroids may lower the number of days people
have symptoms of mild COVID-19 and probably increase resolution of COVID-19 symptoms at day 14. They may make little to no diGerence
in death from any cause, and we do not have enough evidence to know whether they cause serious harms.

There are no data for people with COVID-19 with no symptoms (asymptomatic) or people with moderate-to-severe COVID-19.

We found 10 ongoing and four completed unpublished studies. We will update this review when their results become available.

What are inhaled corticosteroids?

Inhaled corticosteroids are medicines that are breathed into the lower airways through an inhaler where they reduce inflammation in the
lungs. They are commonly used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease. Long-term use and
incorrect inhaler technique may lead to side eGects that include a mouth infection called thrush, a change in voice, and an increased risk
of lung infections. Good inhaler technique means the medicine does not stay in the mouth and throat.

Why are inhaled corticosteroids possible treatments for COVID-19?

COVID-19 mainly aGects the lungs and airways. When the immune system fights the virus, the lungs and airways become inflamed. This
inflammation causes breathing diGiculties, and the lungs cannot easily move oxygen into the blood and remove carbon dioxide from the
blood.

What did we want to find out?

People need more and better treatment options for asymptomatic SARS-CoV-2 infection (the virus that causes COVID-19) or mild, moderate,
or severe COVID-19. We wanted to know if inhaled corticosteroids are an eGective and helpful treatment option for COVID-19 in any setting
(for example, home or hospital) and whether they cause unwanted eGects.

We were interested in:

– death from any cause up to day 30, day 60, or longer if reported;

– admission to hospital or death within 30 days;

– whether symptoms resolved and how fast;

– quality of life;

– unwanted eGects.

What did we do?

We looked for studies where the investigators compared inhaled corticosteroids and usual care to usual care only, sometimes in addition
to a dummy medicine that did not contain any active ingredients (placebo) but was given in the same way. To make the comparison least
skewed and more fair, patients in the studies must all have had the same random chance (like the flip of a coin) to receive the inhaled
corticosteroids or the other treatment. The studies could include people of any age, sex, or ethnicity.

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods
and sizes.

What did we find?

Three studies compared inhaled corticosteroids plus usual care compared to usual care with or without placebo in people with a confirmed
diagnosis of mild COVID-19. These studies analysed 2171 participants mostly older than 50 years and with other medical problems, 52%

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of them were female, of whom 1057 received inhaled corticosteroids in our analyses. We found no studies that included people with
asymptomatic infection or confirmed diagnosis of moderate-to-severe COVID-19.

We also found 10 ongoing studies, and four completed studies without published results.

Main results

All studies compared inhaled corticosteroids with usual care or placebo. The studies included only people with a confirmed diagnosis
of SARS-CoV-2 infection and mild disease. No studies looked at hospitalised people or people with asymptomatic SARS-CoV-2 infection.
Inhaled corticosteroids

– may make little to no diGerence in death from any cause up to day 30;

– probably reduce the risk of admission to hospital or occurrence of death up to day 30;

– probably increase resolution of COVID-19 symptoms at day 14 and may reduce time to symptom resolution.

We are very uncertain about a possible diGerence in serious unwanted eGects. Moreover, inhaled corticosteroids may result in little to no
diGerence in the number of any unwanted eGects or additional infections.

What are the limitations of the evidence?

The studies were conducted in populations from wealthy countries, prior to the roll-out of COVID-19 vaccination programmes. We have
moderate confidence in the evidence for the outcomes of symptom resolution at day 14 and hospital admission. We have low confidence in
the evidence for the eGects on deaths from any cause for people with mild COVID-19 and time to symptom resolution. The confidence in the
unwanted or serious unwanted eGects and infections is low or very low, because of the diGerences in the way investigators recorded and
reported results. There was no evidence for people with asymptomatic infection or moderate-to-severe COVID-19 who were hospitalised.

How up to date is this evidence?

Our evidence is up-to-date to 7 October 2021.

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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Summary of findings 1.   Inhaled corticosteroids plus standard care compared to standard care (with or without placebo) for adults with a confirmed
diagnosis of mild COVID-19

Inhaled corticosteroids plus standard care compared to standard care (with or without placebo) for adults with a confirmed diagnosis of asymptomatic SARS-
CoV-2 infection or mild COVID-19

Patient or population: adults with a confirmed diagnosis of mild COVID-19, of whom only 10% (219/2132) participants had received ≥ 1 vaccination

Setting: outpatient

Intervention: inhaled corticosteroids plus standard care

Comparison: standard care (with or without placebo)

Anticipated absolute effects* (95%
CI)

Outcomes

Risk with stan-
dard care (with
or without

placebo)a

Risk with inhaled
corticosteroids
(plus standard
care)

Relative effect
(95% CI)

No of partici-
pants

(studies)

Certainty of
the evidence

(GRADE)

Comment

All-cause mortality

Follow-up: at up to 30
days

9 per 1000 6 per 1000

(2 to 16)

RR 0.61

(0.22 to 1.67)

2132

(3 studies)

⊕⊕⊖⊖

Low b

Inhaled corticosteroids may result in little
to no difference in all-cause mortality up
to day 30.

Admission to hospital or
death

Follow-up: at up to 30
days

79 per 1000 57 per 1000

(40 to 78)

RR 0.72

(0.51 to 0.99)

2025

(2 studies)

⊕⊕⊕⊖

Moderate c

Inhaled corticosteroids probably reduce
the risk of admission to hospital or death
up to day 30.

Symptom resolution: all
initial symptoms resolved

at day 14

465 per 1000 553 per 1000

(507 to 605)

RR 1.19

(1.09 to 1.30)

1986

(2 studies)

⊕⊕⊕⊖

Moderate d

Inhaled corticosteroids probably increase
the resolution of all initial symptoms at
day 14.

Symptom resolution: du-
ration to symptoms re-
solved

Follow-up: at up to day 30

The mean du-
ration to symp-
toms resolved
was 12.00 days.

The mean dura-
tion of symptoms
resolved was 8.00
days (5.78 to 10.22
days).

MD −4.00 days

(−6.22 to −1.78)

139

(1 study)

⊕⊕⊖⊖

Low d,e

Inhaled corticosteroids may decrease the
duration to symptom resolution.

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Serious adverse events

Follow-up: during study
period

5 per 1000 3 per 1000

(0 to 14)

RR 0.51

(0.09 to 2.76)

1586

(1 study)

⊕⊖⊖⊖

Very Low b,d

The evidence is very uncertain about the
effect of inhaled corticosteroids on seri-
ous adverse events.

Adverse events

Follow-up: at up to day 30

143 per 1000 111 per 1000

(67 to 187)

RR 0.78

(0.47 to 1.31)

400

(1 study)

⊕⊕⊖⊖

Low d,e

Inhaled corticosteroids may result in little
to no difference in adverse events.

Infections

Follow-up: during study
period

34 per 1000 30 per 1000

(10 to 89)

RR 0.88

(0.30 to 2.58)

400

(1 study)

⊕⊕⊖⊖

Low b

Inhaled corticosteroids may result in little
to no difference in infections.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention
group (and its 95% CI).

CI: confidence interval; MD: mean difference; RR: risk ratio.

GRADE working group grades evidence

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different.

Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.

Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aControl group risk estimated from included studies (with 10% of participants being vaccinated at least once).
bDowngraded two levels for very serious imprecision (very low number of events, wide CI).
cDowngraded one level for serious imprecision (low number of participants/events and optimal information size would be 3764 participants).
dDowngraded one level for serious risk of bias (partly measurement of the outcome aGected by unblinded design, selection of the reported result, missing outcome data as the
safety-relevant outcome was not reported) and reporting bias (the safety-relevant outcome was not reported).
eDowngraded one level for serious imprecision (low number of participants/events and wide CI).
 

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B A C K G R O U N D

This work is part of a series of Cochrane Reviews investigating
treatments and therapies for coronavirus disease 2019 (COVID-19).
Reviews in this series share information in the background
section and methodology with the first published reviews about
monoclonal antibodies (Kreuzberger 2021) and convalescent
plasma (Piechotta 2021) from the German research project
‘CEOsys’ (COVID-19 Evidence Ecosystem).

Description of the condition

COVID-19 is a rapidly spreading infectious disease caused by severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2;  WHO
2020a). On 11 March 2020, the World Health Organization (WHO)
declared the current COVID-19 outbreak a pandemic. The severity
of COVID-19 is unprecedented in comparison to that of previous
coronavirus outbreaks such as severe acute respiratory syndrome
(SARS), which caused 813 deaths, and Middle East respiratory
syndrome (MERS), which caused 858 deaths (WHO 2007; WHO
2019). Despite intensive international eGorts to contain its spread,
SARS-CoV-2 has resulted in a continuously rising number of cases
and deaths with a clearly accelerating increase in the first months of
2021 (WHO 2021a; WHO 2021b). In the meantime, the appearance
of SARS-CoV-2 variants with higher transmissibility is further
increasing infection rates (WHO 2021c).

The risk for a severe course of disease, hospitalisation, and
mortality is higher among people aged 65 years or older; smokers;
and those with certain underlying medical conditions such as
cancer, chronic kidney disease, chronic obstructive pulmonary
disease (COPD), heart conditions, immunocompromised state,
obesity, sickle cell disease, or type 2 diabetes mellitus (Huang 2020;
Liang 2020; WHO 2020a; Williamson 2020). COVID-19 case fatality
ratios vary widely between countries and reporting periods, from
0.0% to more than 25% (Johns Hopkins University 2021). However,
these numbers may be misleading as they tend to overestimate
the infection:fatality ratio due to varying testing frequency, a lack
of reporting dates, and variations in case definitions, especially in
the beginning of the pandemic when the main focus was on severe
cases (WHO 2020b).

The median incubation time is estimated to be five to six days,
and 97.5% of symptomatic cases develop symptoms within 11.5
days of exposure (Lauer 2020). Sore throat, cough, fever, headache,
fatigue, and myalgia or arthralgia are the most commonly reported
symptoms (Struyf 2020). Other symptoms include dyspnoea, chills,
nausea or vomiting, diarrhoea, and nasal congestion (WHO 2020a).
Most infected people (approximately 80%) have mild symptoms
(Wu 2020), or remain completely asymptomatic (Buitrago-Garcia
2020). A smaller proportion (approximately 14%) are aGected by
severe or critical disease which requires treatment at an intensive
care unit (ICU) due to respiratory failure, septic shock, or multiple
organ dysfunction (Wu 2020). In light of the extent of the COVID-19
pandemic and the scarcity of eGective treatments, there is an
urgent need for eGective therapies to save lives and to reduce
the high burden on healthcare systems, especially in the face
of evolving variants of the virus with the potential for increased
transmissibility and the limited global availability of vaccines.

Description of the intervention

Corticosteroids are a group of stress hormones produced from the
adrenal cortex. In addition to their stress-mediated mechanisms
for generating energy substrates, corticosteroids have anti-
inflammatory and immunosuppressive properties in higher doses
and are applied widely in almost all medical fields (Barnes
2006; Rhen 2005). The eGects are based on the binding to
intracellular receptors, which influences protein expression. In
addition, glucocorticoids also develop extragenomic eGects. All
active ingredients are lipophilic and thus easily reach the cells
via the cell membrane. Long-term systemic corticosteroid therapy,
unless in a very low dose, can be associated with many adverse
eGects (e.g. hypertension, osteoporosis, and diabetes). Inhaled
corticosteroids have a lower risk of undesirable eGects compared
with systemic administration. They can be used as dose aerosols,
inhalable powder, or inhalation capsules in diGerent dosages
(low, medium, and high dosages) depending on indication (Daley-
Yates  2015). Inhaled corticosteroids reach the lower respiratory
tract as a finely divided aerosol via the airflow and develop their
eGect directly on the bronchial mucosa. This form of administration
is particularly important for the treatment of inflammatory
respiratory diseases such as asthma or COPD (Geddes 1992).
However, many adverse eGects are dose-related and can include
local eGects such as oropharyngeal candidiasis, hoarseness, and
increased risk of pneumonia, in addition to the systemic eGects
mentioned above (Daley-Yates 2015; Price 2012).

How the intervention might work

In COVID-19, an imbalanced inflammation is thought to play a
key role in the pathophysiology of hypoxaemic respiratory failure
(Schulte-Schrepping 2020). A systemic inflammatory response with
an excessive release of cytokines and inflammatory mediators can
lead to lung injury with the development of acute respiratory
distress syndrome (ARDS).

It has been proposed that corticosteroids could be clinically
eGective against severe and critical COVID-19, due to their
anti-inflammatory and immunomodulatory properties (Villar
2020). Furthermore, in vitro studies have shown that
inhaled glucocorticoids have antiviral eGectiveness due to two
mechanisms: downregulation of the expression of ACE2 and
TMPRSS2 genes, which are critical for viral cell entry (Finney 2021;
Matsuyama 2020; Peters 2020), and reduction of the replication of
SARS-CoV-2 in airway epithelial cells (Yamaya 2020). In addition,
corticosteroids reduce the exacerbation rate in COPD and asthma,
which is very oUen caused by viral infections (Viniol 2018).
Observation from the early pandemic showed that people with
bronchial asthma and COPD were less likely to be hospitalised for
COVID-19, which is postulated to be due to the routine medication
with inhaled corticosteroids in those people (Halpin 2020).

Why it is important to do this review

Globally, the number of new COVID-19 cases and deaths continue
to increase with a substantial impact on healthcare systems.
Vaccination remains a key component of options for response
to address the ongoing circulation and reduce the impact of
the dominant variants of concern. Despite the eGorts to increase
full vaccination uptake in people who are currently insuGiciently
vaccinated, some pharmaceutical interventions remain a mainstay
in the management of COVID-19. Treatment decisions should be

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informed by high-quality, relevant, and up-to-date synthesised
research evidence provided by international networks. There are
several systematic reviews on the use of systemic corticosteroids
for the treatment of COVID-19 based on randomised controlled
trials (RCTs) and non-randomised studies (e.g. Sterne 2020; van
Paassen 2020; Wagner 2021a).

This systematic review fills current gaps by identifying, describing,
evaluating, and meta-analysing RCTs for inhaled corticosteroids on
clinical outcomes as an additional treatment option in COVID-19.
We will search for RCTs on inhaled corticosteroids for COVID-19 on
a weekly basis and update this living systematic review once new
relevant evidence becomes available to ensure the review remains
current. For the most up-to-date information about the review, the
results of the searches, and any new evidence being incorporated,
readers are encouraged to check the update status information.
The update status information will be updated whenever the
searches are rerun.

O B J E C T I V E S

To assess whether inhaled corticosteroids are eGective and safe in
the treatment of COVID-19; and to maintain the currency of the
evidence, using a living systematic review approach.

M E T H O D S

Criteria for considering studies for this review

Types of studies

The main description of methods is based on the standard
template of the Cochrane Haematology review group and is in
line with a series of Cochrane Reviews investigating treatments
and therapies against COVID-19. Specific adaptions related to the
research question were made if necessary (see DiGerences between
protocol and review). The protocol for this review was registered
with PROSPERO on 9 July 2021 (Wagner 2021b).

To assess the eGicacy and safety of inhaled corticosteroids against
COVID-19, we included RCTs, as this study design, if performed
appropriately, provides the best evidence for experimental
therapies in highly controlled therapeutic settings. We used the
methods recommended in the Cochrane Handbook for Systematic
Reviews of Interventions (Higgins 2020). We would also have
accepted cluster-randomised trials for inclusion, if we had found
any. We found no cross-over studies, but would have excluded them
because of the short duration of the disease and potential carry-
over eGects of corticosteroids.

We included the following formats, if suGicient information
was available on study design, characteristics of participants,
interventions, and outcomes:

• full-text publications;

• preprint articles.

We included preprints to have a complete overview of the ongoing
research activity, especially for tracking newly emerging studies
about systemic corticosteroids against COVID-19. We did not apply
any limitation with respect to the length of follow-up.

Types of participants

We included people with a confirmed diagnosis of COVID-19
and moderate-to-severe disease and people with a confirmed
diagnosis of asymptomatic SARS-CoV-2 infection or mild COVID-19
(as described in the study). We did not exclude any studies based
on sex, ethnicity, disease severity, or setting.

Types of interventions

We included the following intervention:

• any type or dose of inhaled corticosteroids.

We included the following comparisons:

• inhaled corticosteroid plus standard care versus standard care
(with or without placebo).

Standard care in both arms had to be similar.

We excluded the following interventions:

• topical corticosteroids.

Types of outcome measures

We evaluated core outcomes in accordance with the Core Outcome
Measures in EGectiveness Trials (COMET) Initiative for people with
COVID-19 (COMET 2020; Marshall 2020), and additional outcomes
that have been prioritised by consumer representatives and the
panel of the German “national treatment guidance for hospitalized
COVID-19 patients” (Kluge 2022).

We defined this outcome set for hospitalised people with
a confirmed diagnosis of COVID-19 and moderate-to-severe
disease, according to WHO clinical progression scale stage 4
to 9 (Marshall 2020) (i.e. all patients who were hospitalised
because of symptomatic COVID-19 treated with all diGerent
levels of respiratory support, such as no additional oxygen,
low-flow oxygen prongs or mask (‘low-flow oxygen’), high-
flow oxygen or non-invasive ventilation, invasive mechanical
ventilation inclusively extracorporeal membrane oxygenation) and
people with a confirmed diagnosis of SARS-CoV-2 infection and
asymptomatic or mild disease, according to the WHO clinical
progression scale (Marshall 2020). Of note, the reader will
encounter respiratory support both as baseline characteristic and
as outcome measure – in the latter case changes in the level of
support will be utilised.

In review updates, we will also evaluate patient-reported
experience measures (PREMS), as suggested by the consumer
editor. However, up to October 2021, the included studies did not
report PREMS.

People with a confirmed diagnosis of COVID-19: moderate or
severe disease

E8icacy of inhaled corticosteroids

Prioritised outcomes (included in the summary of findings table)

• All-cause mortality at day 30, day 60, time-to-event, and up to
longest follow-up.

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• Clinical status at day 30, day 60, and up to longest follow-up,
including:
◦ worsening of clinical status:

▪ participants with clinical deterioration (new need for
invasive mechanical ventilation) or death;

◦ improvement of clinical status:
▪ participants discharged alive. Participants should be

discharged without clinical deterioration or death.

• Quality of life, including fatigue and neurological status,
assessed with standardised scales (e.g. WHOQOL-100) at up to
seven days; up to 30 days, and longest follow-up available.

Safety of inhaled corticosteroids

• Serious adverse events during the study period, defined as
number of participants with any serious adverse event (serious
as defined according to CTCAE (Common Terminology Criteria
for Adverse Events)).

• Adverse events (any grade) during the study period, defined as
number of participants with any adverse event.

• Hospital-acquired infections during the study period.

People with a confirmed diagnosis of asymptomatic SARS-CoV-2
infection or mild COVID-19

E8icacy of inhaled corticosteroids

Prioritised outcomes (included in the summary of findings table)

• All-cause mortality at day 30, day 60, time-to-event, and up to
longest follow-up.

• Admission to hospital or death within 30 days.

• Symptom resolution:
◦ all initial symptoms resolved (asymptomatic) at day 14;

◦ duration to symptom resolution.

Prioritised outcomes (not included in the summary of findings table)

• Symptom resolution:
◦ all initial symptoms resolved (asymptomatic) at day 30.

• Quality of life, including fatigue and neurological status,
assessed with standardised scales (e.g. WHOQOL-100) at up to
seven days, up to 30 days, and longest follow-up available.

Safety of inhaled corticosteroids

• Serious adverse events during the study period, defined as
number of participants with any serious adverse event (serious
as defined according to CTCAE (Common Terminology Criteria
for Adverse Events)).

• Adverse events (any grade) during the study period, defined as
number of participants with any adverse event.

• Infections during the study period.

• PREMs (e.g. through questionnaires, including information on
satisfaction with the treatment to investigate possible reasons
for deviations from intended interventions).

Timing of outcome measurement

In case of time-to-event analysis (e.g. for time to clinical
improvement), we included the outcome measure based on the
longest follow-up time. We also collected information on outcomes
from all other time points reported in the publications.

Search methods for identification of studies

Electronic searches

Our information specialist (MIM) conducted systematic searches
in the following sources from the inception of each database to
7 October 2021 (search date for all databases) and placed no
restrictions on the language of publication.

• Cochrane COVID-19 Study Register (CCSR)
(www.covid-19.cochrane.org), comprising:
◦ Cochrane Central Register of Controlled Trials (CENTRAL),

monthly updates;

◦ MEDLINE (PubMed), daily updates;

◦ Embase.com, weekly updates;

◦ ClinicalTrials.gov (www.clinicaltrials.gov), daily updates;

◦ WHO International Clinical Trials Registry Platform (ICTRP)
(www.who.int/trialsearch), weekly updates;

◦ medRxiv (www.medrxiv.org), weekly updates.

• Web of Science Core Collection (Clarivate), from 1 January 2020
onwards:
◦ Science Citation Index Expanded (from 1945);

◦ Emerging Sources Citation Index (from 2015).

• WHO COVID-19 Global literature on coronavirus disease
(search.bvsalud.org/global-literature-on-novel-
coronavirus-2019-ncov/).

Database search results for Web of Science were restricted to
publications from 2020 to October 2021, as no treatment trials on
COVID-19 were registered prior to January 2020. For detailed search
strategies, see Appendix 1.

We did not conduct separate searches of the databases required
by the MECIR standards (Higgins 2021a), since these databases are
already regularly searched for the production of the CCSR.

Living systematic review considerations

We will use the CCSR to monitor newly published results of RCTs on
inhaled corticosteroids on a weekly basis.

Searching other resources

We identified other potentially eligible studies or ancillary
publications by searching the reference lists of included studies and
systematic reviews.

Living systematic review considerations

The signal for updating this review will stem from the weekly
monitoring of the published relevant RCTs via the CCSR, as
described under Electronic searches. Once the decision to update
the review has been made, the methods mentioned in this section
will be incorporated in the review update.

Data collection and analysis

Selection of studies

Two review authors (CW, AF) independently screened the results of
the search for eligibility by reading the titles and abstracts using
EndNote SoUware (EndNote X9). We coded the abstracts as either
‘include’ or ‘exclude’. In the case of disagreement or if it was unclear
whether we should retrieve the abstract, we obtained the full-text
publication for further discussion. Two review authors assessed the

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full-text articles of selected studies. If the two review authors were
unable to reach a consensus, they consulted the third review author
to reach a final decision.

We documented the study selection process in a PRISMA flow chart
(Moher 2009), and showed the total numbers of retrieved references
and the numbers of included and excluded studies. We listed all
studies that we excluded aUer full-text assessment and the reasons
for their exclusion in the Characteristics of excluded studies section.

Data extraction and management

We conducted data extraction according to Cochrane guidelines (Li
2020). Two of four review authors (MG, CW, AF, AM) extracted data
independently and in duplicate, using a customised data extraction
form developed in MicrosoU Excel (MicrosoU Excel). We solved
disagreements by discussion. If no agreement was obtained, a third
review author was involved to solve the disagreement.

Two of three review authors (MG, CW, AF) independently assessed
eligible studies obtained in the process of study selection (as
described above) for methodological quality and risk of bias. If the
review authors were unable to reach a consensus, a third review
author was consulted.

We extracted the following information if reported.

• General information: author, title, source, publication date,
country, language, duplicate publications.

• Study characteristics: trial design, setting and dates, source
of participants, inclusion/exclusion criteria, comparability of
groups, treatment cross-overs, compliance with assigned
treatment, length of follow-up.

• Participant characteristics: age, sex, ethnicity, number
of participants recruited/allocated/evaluated, number of
participants with positive, negative, or unknown polymerase
chain reaction (PCR) test result, additional diagnoses, severity
of disease, previous treatments, concurrent treatments,
comorbidities (e.g. diabetes, immunosuppression).

• Interventions: type of corticosteroid, dose, frequency, timing,
duration and route of administration, setting (e.g. hospitalised,
non-hospitalised), duration of follow-up.

• Control interventions: placebo, no treatment, or other
intervention; dose, frequency, timing, duration, and route of
administration; setting; duration of follow-up.

• Outcomes: as specified under Types of outcome measures.

• Risk of bias assessment: randomisation process, deviations
from the intended interventions, missing outcome data,
measurement of the outcome, selection of the reported result.

Assessment of risk of bias in included studies

We used the Risk of Bias 2 (RoB 2) tool (version of 22 August 2019) to
analyse the risk of bias of study results (Sterne 2019). Of interest for
this review was the eGect of the assignment to the intervention (the
intention-to-treat (ITT) eGect), thus, we performed all assessments
with RoB 2 on this eGect. The outcomes that we assessed were
those specified for inclusion in the summary of findings table.

Two of five review authors (MG, CW, AF, JD, AN) independently
assessed the risk of bias for each outcome. In case of discrepancies
among their judgements and inability to reach consensus, we
consulted another review author to reach a final decision. We

assessed the following types of bias for RCTs as outlined in Chapter
8 (Higgins 2021b) and for cluster-RCTs as outlined in Chapter
23 (Table 23.1.a; Higgins 2021c) of the Cochrane Handbook for
Systematic Reviews of Interventions.

For RCTs:

• bias arising from the randomisation process;

• bias due to deviations from the intended interventions;

• bias due to missing outcome data;

• bias in measurement of the outcome;

• bias in selection of the reported result.

For cluster-RCTs:

• bias arising from the randomisation process;

• bias arising from the timing of identification and recruitment of
participants;

• bias due to deviations from intended interventions;

• bias due to missing outcome data;

• bias in measurement of the outcome;

• bias in selection of the reported result.

To address these types of bias we used the signalling questions
recommended in RoB 2 and made a judgement using the following
options.

• ‘Yes’: if there was firm evidence that the question was fulfilled
in the study (i.e. the study was at low or high risk of bias for the
given the direction of the question).

• ‘Probably yes’: a judgement was made that the question was
fulfilled in the study (i.e. the study was at low or high risk of bias
given the direction of the question).

• ‘No’: if there was firm evidence that the question was unfilled in
the study (i.e. the study was at low or high risk of bias for the
given the direction of the question).

• ‘Probably no’: a judgement was made that the question was
unfilled in the study (i.e. the study was at low or high risk of bias
given the direction of the question).

• ‘No information’: if the study report did not provide suGicient
information to allow any judgement.

We used the algorithms proposed by RoB 2 to assign each domain
one of the following levels of bias.

• Low risk of bias.

• Some concerns.

• High risk of bias.

Subsequently, we derived an overall risk of bias rating for each
prespecified outcome in each study in accordance with the
following suggestions.

• ‘Low risk of bias’: we judged the trial at low risk of bias for all
domains for this result.

• ‘Some concerns’: we judged the trial to raise some concerns in
at least one domain for this result, but not at high risk of bias for
any domain.

• ‘High risk of bias’: we judged the trial at high risk of bias in at
least one domain for the result, or we judged the trial to have

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some concerns for multiple domains in a way that substantially
lowered confidence in the results.

We used the RoB 2 Excel tool to implement RoB 2 (available on the
riskofbias.info website), stored, and presented our detailed RoB 2
assessments in the analyses section and as supplementary online
material.

Measures of treatment e8ect

For continuous outcomes, we recorded the mean, standard
deviation (SD), and total number of participants in both treatment
and control groups. Where continuous outcomes used the same
scale, we performed analyses using the mean diGerence (MD) with
95% confidence intervals (CI). For continuous outcomes measured
with diGerent scales, we planned to perform analyses using the
standardised mean diGerence (SMD), but this was not needed in
this review. For interpreting SMDs, we planned to re-express SMDs
in the original units of a particular scale with the most clinical
relevance and impact (e.g. clinical symptoms with the WHO Clinical
Progression Scale (WHO 2020c)).

For dichotomous outcomes, we recorded the number of events and
total number of participants in both treatment and control groups.
We reported the pooled risk ratio (RR) with a 95% CI (Deeks 2021).

We planned to extract and report hazard ratios (HRs) for time-to-
event outcomes (e.g. time to recovery), but there were no data
available. There was also no need to estimate the HR as accurately
as possible from available data using the methods proposed by
Parmar and Tierney (Parmar 1998; Tierney 2007).

We received the advice from a statistician to not use Peto odds ratio
instead of RR when event rates were low, since we only have a few
studies in our main analysis.

Unit of analysis issues

The aim of this review was to summarise trials that analysed data
at the level of the participant. We collated multiple reports of one
study so that the study, and not the report, was the unit of analysis.

Studies with multiple treatment groups

As recommended in Chapter 6 of the Cochrane Handbook for
Systematic Reviews of Interventions (Higgins 2021d), for studies with
multiple treatment groups of the same intervention (i.e. dose, route
of administration), we planned to evaluate whether study arms
were suGiciently homogeneous to be combined. If arms could not
be pooled, we planned to compare each arm with the common
comparator separately. For pair-wise meta-analysis, we planned
to split the ‘shared’ group into two or more groups with smaller
sample size, and include two or more (reasonably independent)
comparisons. For this purpose, for dichotomous outcomes, we
planned to divide both the number of events and the total number
of participants, and for continuous outcomes, we planned to divide
the total number of participants with unchanged means and SDs.

Dealing with missing data

Missing data can occur on diGerent levels (Deeks 2021).

• Missing studies: our comprehensive search for RCTs including
registry entries aimed at providing an overview on all published,
ongoing, and planned studies. We included too few studies to
assess publication bias by a funnel plot.

• Missing outcomes: if an outcome of interest to us was
prespecified but not reported we considered that in the GRADE
process and comment in the Discussion section.

• Missing summary data: if missing summary data of an outcome
of interest necessary for meta-analysis were missing, we
contacted the authors.

• Missing participants: whenever possible, we contacted the
original investigators to request missing data. We assumed data
to be missing at random when the rate of missingness across
arms was comparable and the characteristics of participants
with missing data were comparable to the characteristics of
participants without missing data. Otherwise, we assumed data
not to be missing at random. For the primary analysis, we
conducted a complete-case analysis by excluding participants
with missing outcome data from the meta-analysis.

• We performed sensitivity analyses to assess how robust results
were to a worst-case scenario assumption.

• We addressed the potential impact of missing data under
Potential biases in the review process.

• Missing study-level characteristics: outcomes were not available
stratified by potentially important characteristics such as sex,
age, or ethnicity.

We requested data for all outcomes for one study because the
trial reported it partly for participants who received inhaled
corticosteroids plus hydroxychloroquine (Song 2021). Furthermore,
we asked the authors to specify the setting of their study, as it
was unclear from the publication whether the participants were
hospitalised and hence what their disease severity was at baseline.

Assessment of heterogeneity

We used the I2 statistic (Higgins 2003), and visual examination,
to assess possible heterogeneity (I2 > 30% to signify moderate
heterogeneity, I2 > 75% to signify considerable heterogeneity;
Deeks 2021). If heterogeneity was above 80%, we planned
to explore potential causes through sensitivity and subgroup
analyses. If we could not find a reason for heterogeneity, we did not
perform a meta-analysis but planned to comment on results from
all studies and present these in tables.

As the heterogeneity was never above 80%, we did not explore
potential causes through sensitivity and subgroup analyses.
However, we will do this for future updates.

Assessment of reporting biases

We searched trials registries to identify completed trials that
had not been published elsewhere, to minimise or determine
publication bias. We intended to explore potential publication
bias by generating a funnel plot and statistically testing this by
conducting a linear regression test for meta-analyses involving at
least 10 trials (Sterne 2019). We would have considered P < 0.1 as
significant for this test.

We planned to generate a funnel plot, but had fewer than 10 studies.
We will produce a funnel plot for future updates.

Data synthesis

If the clinical and methodological characteristics of individual
studies were suGiciently homogeneous, we pooled the data
in a meta-analysis. We performed analyses according to the

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recommendations of the Cochrane Handbook for Systematic
Reviews of Interventions (Deeks 2021). We analysed trials including
diGerent severities of disease separately grouping them with
respect to disease severity according to need for respiratory
support at randomisation (see Types of outcome measures). We
treated placebo and standard care as the same intervention, as well
as standard care at diGerent institutions and time points. For the
primary analyses, data were pooled regardless of risk of bias.

We used Review Manager Web soUware for analyses (RevMan Web
2019). One review author entered the data into the soUware, and a
second review author checked the data for accuracy. We used the
random-eGects model for all analyses as we anticipated that true
eGects were related, but were not the same for included studies.
If we deemed meta-analysis inappropriate for a certain outcome
because of heterogeneity of included studies both statistically or
conceptually or for too high risk of bias, we presented descriptive
statistics only.

If meta-analysis was possible, we assessed the eGects of potential
biases in sensitivity analyses (see Sensitivity analysis). For binary
outcomes, we based the estimation of the between-study variance
using the Mantel-Haenszel method. We planned to explore
heterogeneity above 80% with subgroup analyses. If we could not
find a cause for the heterogeneity, we did not perform a meta-
analysis, but commented on the results as a narrative with the
results from all studies presented in tables.

Subgroup analysis and investigation of heterogeneity

Because of clinical relevance, we planned subgroup analyses of
mortality for the following characteristics.

• Sociodemographic characteristics (e.g. sex, age, ethnicity).

• Comorbidities.

• DiGerent dosage.

• DiGerent timing.

• Vaccination status.

Due to insuGicient data, we were unable to perform these subgroup
analyses.

Sensitivity analysis

We planned sensitivity analysis of mortality for the following
potential confounders.

• Risk of bias assessment components (studies with a low risk of
bias or some concerns versus studies with a high risk of bias).

• High rate of missing data.

Because there were no studies with a high risk of bias or high rate
of missing data that reported mortality, we could not perform a
sensitivity analysis.

We performed sensitivity analysis for mortality for the following
potential confounders.

• Fixed-eGect versus random-eGects model.

• Preprint versus journal publication.

Summary of findings and assessment of the certainty of the
evidence

We used the GRADE approach to assess the certainty of the
evidence for the following outcomes, and prepared one summary
of findings table per population.

Summary of findings

We used GRADEpro GDT soUware to create summary of findings
tables. For time-to-event outcomes, we planned to calculate
absolute eGects at specific time points, as recommended in the
GRADE guidance (Skoetz 2020).

According to Chapter 14 of the Cochrane Handbook for Systematic
Reviews of Interventions, the “most critical and/or important health
outcomes, both desirable and undesirable, limited to seven or
fewer outcomes” should be included in the summary of findings
tables (Schünemann 2020). We included outcomes prioritised
according to the core outcome sets for studies for the treatment
of people with confirmed COVID-19 (COMET 2020), and patient
relevance. We included the following outcomes.

People with a confirmed diagnosis of COVID-19: moderate or severe
disease

• All-cause mortality at day 30, day 60, time-to-event, and at
hospital discharge.

• Clinical status at day 30, day 60, and up to longest follow-up,
including:
◦ worsening of clinical status:

▪ participants with clinical deterioration (new need for
invasive mechanical ventilation) or death;

◦ improvement of clinical status:
▪ participants discharged alive. Participants should be

discharged without clinical deterioration or death.

• Quality of life, including fatigue and neurological status,
assessed with standardised scales (e.g. WHOQOL-100) at up to 7
days; up to 30 days, and longest follow-up available.

• Serious adverse events during the study period, defined as
number of participants with any serious adverse event (serious
as defined according to CTCAE (Common Terminology Criteria
for Adverse Events)).

• Adverse events (any grade) during the study period, defined as
number of participants with any adverse event.

• Hospital-acquired infections during the study period.

People with a confirmed diagnosis of asymptomatic SARS-CoV-2
infection or mild COVID-19

• All-cause mortality at day 30, day 60, time-to-event, and up to
longest follow-up.

• Admission to hospital or death within 30 days.

• Symptom resolution:
◦ all initial symptoms resolved (asymptomatic) at day 14;

◦ duration to symptom resolution.

• Serious adverse events during the study period, defined as
number of participants with any serious adverse event (serious
as defined according to CTCAE (Common Terminology Criteria
for Adverse Events)).

• Adverse events (any grade) during the study period, defined as
number of participants with any adverse event.

• Infections during the study period.

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Assessment of the certainty of the evidence

We used the GRADE approach to assess the certainty in the evidence
for the above outcomes.

The GRADE approach uses five domains (risk of bias, consistency of
eGect, imprecision, indirectness, and publication bias) to assess the
certainty in the body of evidence for each prioritised outcome.

We downgraded our certainty of evidence for:

• serious (−1) or very serious (−2) risk of bias;

• serious (−1) or very serious (−2) inconsistency;

• serious (−1) or very serious (−2) uncertainty about directness;

• serious (−1) or very serious (−2) imprecise or sparse data;

• serious (−1) or very serious (−2) probability of reporting bias.

The GRADE system used the following criteria for assigning grade
of evidence.

• High: we are very confident that the true eGect lies close to that
of the estimate of the eGect.

• Moderate: we are moderately confident in the eGect estimate;
the true eGect is likely to be close to the estimate of eGect, but
there is a possibility that it is substantially diGerent.

• Low: our confidence in the eGect estimate is limited; the true
eGect may be substantially diGerent from the estimate of the
eGect.

• Very low: we have very little confidence in the eGect estimate;
the true eGect is likely to be substantially diGerent from the
estimate of eGect.

We followed the current GRADE guidance for these assessments
in its entirety as recommended in Chapter 14 of the Cochrane
Handbook for Systematic Reviews of Interventions (Schünemann
2020).

We used the overall risk of bias judgement, derived from the RoB 2
Excel tool, to inform our decision on downgrading for risk of bias.
We phrased the findings and certainty in the evidence as suggested
in the informative statement guidance (Santesso 2020).

Methods for future updates

Living systematic review considerations

Our information specialist (MIM) will provide us with new
search records each month, which two review authors will

screen, evaluate, extract, and integrate following the guidance for
Cochrane living systematic reviews (Living Evidence Network 2019).

We will manually check platform trials that were previously
identified and listed as ‘studies awaiting classification’ for
additional treatment arms.

We will wait until the accumulating evidence changes our
conclusions of the implications of research and practice before
republishing the review. We will consider one or more of the
following components to inform this decision.

• The findings of one or more prioritised outcomes for population
with virologically confirmed SARS-CoV-2 infection.

• The credibility (e.g. GRADE rating) of one or more prioritised
outcomes.

• New settings, populations, interventions, comparisons, or
outcomes studied.

In case of emerging policy relevance because of global
controversies around the intervention, we will consider
republishing an updated review even though our conclusions
remain unchanged. We will review the review scope and methods
approximately monthly, or more frequently if appropriate, in light
of potential changes in COVID-19 research (e.g. when additional
comparisons, interventions, subgroups, or outcomes, or new
review methods become available).

R E S U L T S

Description of studies

Results of the search

We searched all databases and screened the resulting records up
to 7 October 2021. We identified 1560 records. AUer removing
duplicates, we screened 1329 records based on their titles and
abstracts. We excluded 1305 records that did not meet the inclusion
criteria. Of the remaining 24 records, we included 23 records:

• three RCTs (in six records) for inclusion in this review;

• five RCTs (in six records) are awaiting classification;

• 10 RCTs (in 11 records) are ongoing.

The study flow diagram in Figure 1 illustrates the study selection
process according to PRISMA guidelines (Moher 2009).

 

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Figure 1.

 
 

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Figure 1.   (Continued)

 
Included studies

See Characteristics of included studies table and Table 1.

Designs of the studies and publication status

None of the studies were cluster-RCTs. We included three RCTs
with 3607 participants, of whom 1343 were allocated to inhaled
corticosteroids plus standard care and 2264 to standard care
(with or without placebo). One open-label, parallel-group, phase
2 clinical trial allocated 146 participants of whom eight (6%) were
PCR-negative at randomisation (Ramakrishnan 2021); one open-
label, multi-arm, adaptive platform RCT allocated 3061 participants
to inhaled corticosteroids plus standard care or standard care
(Yu 2021); one double-blind placebo-controlled trial allocated 400
participants eligible for inclusion if they had a positive SARS-
CoV-2 molecular or antigen diagnostic sample (no information on
percentage of PCR-positive participants) (Clemency 2021).

From the allocated 3061 participants in Yu 2021, we used data from
1625 in this review. We restricted the analysis to participants who
were randomised concurrently and were confirmed as SARS-CoV-2
positive. This was to reduce the risk of bias and indirectness arising
from analysis of outcomes in participants included only on the basis
of symptoms or who were randomised to usual care prior to the
addition of budesonide. Comparing study participants recruited
under diGerent editions of the trial protocol, were treated according
to changes in therapy or prophylaxis (e.g. vaccination) over time
or were recruited in the context of other local regulations during
the pandemic (e.g. contact restrictions, lockdown) and diagnostic
options (e.g. access to PCR testing) would limit the applicability of
evidence from this study.

The number of participants included in the analyses in this
review was 2171. The number of participants analysed for the
respective endpoints ranged between 139 and 2132 depending on
the availability of data.

The three studies were performed as remote pragmatic outpatient
trials partly relying on electronic self-assessments and telephone
calls. Ramakrishnan 2021 was performed in one centre in the
community in Oxfordshire, UK, while two studies were multicentric:
Yu 2021 with multisite and multimethods enrolment in the UK
and Clemency 2021 in 10 centres in the US. All three included
studies were performed in high-income countries. However, the
investigators of Yu 2021 undertook extensive community outreach
to increase recruitment from ethnic minority and socially deprived
communities.

All studies reported information on the responsible ethics
committee and the financial support. Ramakrishnan 2021 and Yu
2021 were funded by departmental or governmental resources as
well as non-profit organisations: the National Institute for Health
Research (NIHR) Biomedical Research Centre (Ramakrishnan 2021)
and NIHR and United Kingdom Research Innovation (Yu 2021).
Both studies also received support by AstraZeneca producing the

intervention medication (Ramakrishnan 2021; Yu 2021, including
individual authors). Clemency 2021 was funded by Covis Pharma
GmbH producing the intervention medication.

Two trials were peer-reviewed publications in indexed journals
(Ramakrishnan 2021; Yu 2021); one study was available as
a preprint at the time of the publication of this review
(Clemency 2021). All included studies registered a study protocol
prospectively.

Participants

All three studies recruited participants in the outpatient setting:
in participating general medical practices (Ramakrishnan 2021;
Yu 2021), via local COVID-19 testing sites (Ramakrishnan 2021),
as well online or by telephone (Yu 2021), and public and private
academic and non-academic centres (Clemency 2021). Positive
PCR rates among the participants diGered significantly across the
studies. In Yu 2021, the virological confirmation of the SARS-CoV-2
infection (through PCR or rapid antigen test) was not mandatory to
participate in the study and only 87% of all participants randomly
assigned to budesonide, usual care alone, or other treatments were
PCR tested. About 67% of those PCR-tested participants and 82.2%
of those concurrently randomised in the budesonide or usual care
arms had a positive PCR-test result. In this review, we analysed
only PCR-positive participants from the study Yu 2021 (SARS-CoV-2-
positive concurrent randomisation analysis population) to reduce
risk of bias and indirectness. There is no information on how many
participants who carried out a rapid antigen test. In Clemency
2021, the rate of positive PCR tests was not reported. However, all
participants had a positive PCR or an antigen test, since it was the
inclusion criterion of the study, and therefore could be defined as
confirmed virologically. In Ramakrishnan 2021, 94% of participants
were PCR-positive.

In two studies all participants were adults (Ramakrishnan 2021; Yu
2021). In Clemency 2021, the participants had to be at least 12 years
of age. In this study, the mean age of all participants was 43.3 (SD
16.89) years, 4% of all participants were aged less than 18 years.
In Yu 2021, 36% (intervention group) and 36% (control group) of
participants were between 50 and 64 years old. In Ramakrishnan
2021, the mean age of participants was 44 (range 19–71) years in the
intervention group and 46 (range 19–79) years in the control group.

In Ramakrishnan 2021, the participants in both groups had, on
average, one comorbidity, most frequently past or current history
of asthma (16% in budesonide arm versus 14% in control arm).
In Yu 2021, 80% of participants in each group (intervention group
and control group) had one or more comorbidity. The most
common comorbidity was high blood pressure requiring therapy
in 45% participants. Ten percent of study participants had lung
disease. The most common comorbidity in Clemency 2021 was
arterial hypertension (23.9% of participants in intervention group
and 20.7% of participants in the control group). In this, more
people in the intervention group had type 2 diabetes mellitus and

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asthma than in the control group (diabetes mellitus: 11.2% in the
intervention group versus 3.9% in the control group; P = 0.007;
asthma: 9.1% in the intervention group versus 3.9% in the control
group; P = 0.042).

Participants were randomised in a median of six days in Yu 2021
and three days in Ramakrishnan 2021. In Clemency 2021, the
duration of symptoms prior to randomisation was not reported.
However, the participants had to have a positive SARS-CoV-2
PCR or antigen diagnostic sample obtained in the previous 72
hours prior to randomisation. The most common symptoms in the
SARS-CoV-2 concurrent randomisation population in Yu 2021 were
feeling unwell (96.6%), cough (84.2%), myalgia (75.6%), shortness
of breath (58.3%), and fever (51.9%). In Ramakrishnan 2021, it was
cough (79% in the intervention group versus 70% in the control
group), fever (70% in the intervention group versus 64% in the
control group), and headache (57% in the intervention group versus
55% in the control group). In contrast to Yu 2021, shortness of
breath had evolved only in 16% of the participants in each study
arm, myalgia in 9% (intervention group) and 16% (control group).
Clemency 2021 did not report the details of the symptoms at
baseline.

Interventions and comparators

Two studies compared budesonide plus standard care versus
standard care alone (Ramakrishnan 2021; Yu 2021). Budesonide
was administered as a dry powder inhaler (Pulmicort Turbuhaler,
AstraZeneca, Gothenburg, Sweden) at a dose of 400 μg per
actuation (two puGs to be taken twice per day; total dose
1600 μg). In Yu 2021, the participants administered budesonide
for 14 days, while in Ramakrishnan 2021, they were asked to
stop taking the inhaler when they felt they had recovered (self-
reported symptom recovery) or if they achieved the primary
outcome (COVID-19-related urgent care visits, including emergency
department assessment or hospitalisation). As result, 79.9% of
participants randomised to budesonide in this study reported
taking budesonide for at least seven days.

Clemency 2021 compared ciclesonide metered-dose inhaler (MDI)
in addition to standard care to placebo plus standard care.
Ciclesonide was administered in a dose of 160 μg per actuation, two
actuations twice a day (total daily dose 640 μg). The duration of the
therapy was 30 days. Placebo was not further specified in this study.

Standard care in Ramakrishnan 2021 included antipyretics for
symptoms of fever (products containing paracetamol, or non-
steroidal anti-inflammatory drugs such as aspirin and ibuprofen)
and honey for symptoms of cough. In Yu 2021, standard care was
specified as antipyretics and antibiotics if bacterial pneumonia was
suspected. The concomitant therapy in Clemency 2021 included
mostly antipyretics and only in a few cases antibiotics (5%
of participants) and antivirals (1% of participants). Neutralising
monoclonal antibodies were given only in one participant in the
intervention group.

Outcomes

The primary outcome in Ramakrishnan 2021 was defined
as COVID-19-related urgent care visits, including emergency
department assessment or hospitalisation. Yu 2021 had two co-
primary endpoints measured within 28 days of randomisation:
time to first reported recovery, defined as the first instance that
a participant reported feeling recovered; and hospitalisation or

death related to COVID-19. In Ramakrishnan 2021, secondary
outcomes included clinical recovery, defined by self-reported
time to symptom resolution; viral symptoms measured by the
Common Cold Questionnaire (CCQ) 12 and the InFLUenza Patient-
Reported Outcome (FLUPro)13 questionnaire; blood oxygen
saturations and body temperature; and SARS-CoV-2 viral load.
In Yu 2021, secondary outcomes included the rating of how
well participants felt (scale 1 to 10), time to sustained recovery,
early sustained recovery, time to initial alleviation of symptoms,
time to sustained alleviation of symptoms, time to initial
reduction of severity of symptoms, contacts with health services,
hospital assessment without admission, oxygen administration,
ICU admission, mechanical ventilation, and WHO-5 Well-Being
Index.

In Clemency 2021, the primary endpoint was time to alleviation
of all COVID-19-related symptoms (cough, dyspnoea, chills, feeling
feverish, repeated shaking with chills, muscle pain, headache,
sore throat, and new loss of taste or smell) by day 30 as
self-reported in the participant’s eDiary. Secondary endpoints
included subsequent emergency department visits or hospital
admissions for reasons attributable to COVID-19, incidence of
hospital admissions or death, all-cause mortality, COVID-19-related
mortality, impact on the time to hospital admission or death
compared with placebo plus standard supportive care, alleviation
of all COVID-19-related symptoms by days seven, 14, and 30 as well
as additional secondary outcomes such as oxygen saturation levels,
COVID-19 viral load, and safety assessments.

Studies awaiting classification

We found five study registries with inhaled corticosteroids: two
studies “completed” (Alsultan 2021; EUCTR2020-001616-18-ES/
NCT04355637), two studies terminated for insuGicient recruitment
(NCT04331054; NCT04435795), and one study with a preprint
including results (Song 2021). See Table 2.

EUCTR2020-001616-18-ES/NCT04355637 had planned to include
300 participants with moderate COVID-19. Participants were
treated with budesonide plus standard care and compared to
participants treated with standard care (with/without placebo –
unclear registry entry classifying the study as “open-label” but
with the use of a placebo). Song 2021 compared ciclesonide
plus hydroxychloroquine to standard care and ciclesonide versus
standard care in 61 participants with unclear indication for
hospitalisation. For the comparison ciclesonide versus standard
care, the study did not provide any data. The publication only
provided data for participants in the intervention arm partly
receiving a combination of ciclesonide and hydroxychloroquine, so
that the observed eGect cannot be attributed to the corticosteroids
with certainty.

We contacted the authors of EUCTR2020-001616-18-ES/
NCT04355637, JRCTS031190269, and Song 2021 via email to obtain
data from participants of interest but have not yet received a reply.

Ongoing studies

We identified 10 ongoing RCTs that compared inhaled
corticosteroids versus standard care or placebo; see Table 3.
Five studies were classified as “recruiting” or “ongoing” and the
remaining five as “not yet recruiting”, according to the study
registration data. These 10 trials intend to recruit 4114 participants:

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1426 participants with mild COVID-19 and 2688 participants with
moderate COVID-19.

Five RCTs are designed to study the eGect of ciclesonide, two of
which will compare ciclesonide plus standard care versus standard
care alone, one versus vitamin D, one versus placebo (both in
addition to standard care), and one study does not define a
comparator.

Three studies are designed to study budesonide: one RCT will
compare budesonide plus formoterol plus standard care versus
placebo plus standard care, one budesonide plus standard care
versus standard care alone, and one budesonide plus arformoterol
plus standard care versus placebo plus standard care.

The only study that investigates inhaled fluticasone in addition
to standard care compares it against the standard care alone
(NCT05054322).

One study compares beclomethasone or beclomethasone-
formoterol-glycopyrronium plus standard care with standard care
alone (NCT04937543).

Excluded studies

We excluded one study that did not meet our inclusion criteria as
it designated the route of application as inhaled, but it was topical
(IRCT20200522047542N1).

Risk of bias in included studies

We assessed the risk of bias for three RCTs that contributed 13 study
results to nine outcomes for outpatient participants (Clemency
2021; Ramakrishnan 2021; Yu 2021).

The completed RoB 2 tool with responses to all assessed
signalling questions is available online at: https://zenodo.org/
record/6334453#.YiX55nrMJPZ.

Overall judgements for studies that included people with a
confirmed diagnosis of moderate-to-severe COVID-19

We found no studies with people with a confirmed diagnosis of
moderate-to-severe COVID-19.

Overall judgements for studies that included people with a
confirmed diagnosis of asymptomatic SARS-CoV-2 infection or
mild COVID-19

Overall risk of bias by study

From 13 study results, we rated six (46%) at low risk of bias, six (46%)
at high risk of bias, and we had concerns for one study. Regarding
the respective studies, from Clemency 2021 four low and two high
risk results were included, from Ramakrishnan 2021 one high risk
and one of some concerns and from Yu 2021 two low risk and three
high risk.

Overall risk of bias by outcome

Inhaled corticosteroids (plus standard care) versus standard care (with
or without placebo)

We judged admission to hospital or death, adverse events and
infections at low risk across studies. For the outcome all-cause
mortality, two of three studies were at low risk of bias and one study
with some concerns due to missing prespecification of the outcome

(Ramakrishnan 2021). The following outcomes received high risk
of bias judgements: symptom resolution: all initial symptoms
resolved at day 14 (Clemency 2021; Yu 2021), symptom resolution:
all initial symptoms resolved at day 30 (Clemency 2021), symptom
resolution: mean time to recovery (Ramakrishnan 2021), quality
of life (Yu 2021) and serious adverse events (Yu 2021) due to
measurement of the outcome and selection of the reported result.
In case of unblinded study design and subjective outcomes, risk of
bias was high (Ramakrishnan 2021; Yu 2021). Also, the withdrawal
of consent aUer randomisation in an open-label study is likely to be
due to the experimental context. Two outcomes in one study were
added only aUer the conduction of the study and not part of the
initial outcome set in the study registration (Clemency 2021).

E8ects of interventions

See: Summary of findings 1 Inhaled corticosteroids plus standard
care compared to standard care (with or without placebo) for adults
with a confirmed diagnosis of mild COVID-19

People with confirmed diagnosis of moderate-to-severe
COVID-19

We found no RCTs reporting outcomes for people with moderate-
to-severe disease treated with inhaled corticosteroids.

People with a confirmed diagnosis of asymptomatic SARS-
CoV-2 infection or mild COVID-19

We found no RCTs reporting outcomes for people with
asymptomatic SARS-CoV-2 infection.

All included participants had a confirmed diagnosis of COVID-19
and mild symptoms according to  Marshall 2020’s WHO clinical
progression scale.

Inhaled corticosteroids (plus standard care) versus standard
care (with or without placebo)

The evidence profile is presented in  Summary of findings 1.
Regarding missing participant data, we judged all study results
presented below at low risk of bias in domain 3 and assumed
missingness at random in line with our methods without further
investigation. Missing outcome data aGected quality of the
evidence for serious adverse events and adverse events.

All-cause mortality at up to day 30

Three studies with 2132 participants reported data on all-cause
mortality (Clemency 2021; Ramakrishnan 2021; Yu 2021). For two
studies, the observation period was 28 days (Ramakrishnan 2021;
Yu 2021), and for one study, it was 30 days (Clemency 2021). Overall,
6/1057 participants in the intervention group died compared to
10/1075 participants in the control group. Inhaled corticosteroids
may result in little to no diGerence in all-cause mortality up to
day 30 (RR 0.61, 95% CI 0.22 to 1.67; 9 deaths per 1000 in the
control group versus 6 deaths per 1000 (95% CI 2 to 16 deaths

per 1000) in the intervention group; random-eGects model; I2 not
applicable;low-certainty evidence; Analysis 1.1). We downgraded
the certainty of evidence from high to low due to very serious
imprecision (very low number of events, wide CI).

Subgroup analyses

There were insuGicient data to conduct subgroup analyses taking
into account sociodemographic characteristics (e.g. sex, age,

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ethnicity), comorbidities, diGerent dosages, diGerent timings, and
vaccination status. The setting of all three studies was primary care
in high-income countries, therefore, no subgroup analysis related
to these factors was possible.

Sensitivity analyses

We summarised the eGects of sensitivity analyses in Table 4. As
in  Clemency 2021  and  Ramakrishnan 2021, no participant had
died, there was no diGerence in the overall eGect estimate when
we compared the fixed-eGect versus random-eGects model or
excluded the preprint Clemency 2021. As we found only a low risk
of bias or some concerns in our included RCTs for this outcome,
there was no opportunity to exclude studies at high risk of bias for
sensitivity analysis (see Table 4). Across all studies, approximately
5% of data were missing, but this was balanced between study
arms. Due to the low number of missing data, we did not perform
a sensitivity analysis.

Admission to hospital or death within 30 days

Two studies with 2025 participants reported data on admission to
hospital or death (Clemency 2021; Yu 2021). Inhaled corticosteroids
probably reduce the admission to hospital or occurrence of death
up to day 30 (RR 0.72, 95% CI 0.51 to 0.99; 79 events per 1000 in
the control group versus 57 events per 1000 (95% CI 40 to 78 events

per 1000) in the intervention group; random-eGects model; I2 =
0%; moderate-certainty evidence;  Analysis 1.2). We downgraded
the certainty of evidence from high to moderate due to serious
imprecision (calculation of the optimal information size for an 80%
power: 3764 participants would have been needed).

Symptom resolution: all initial symptoms resolved (asymptomatic) at
day 14

Two studies with 1986 participants reported data on all initial
symptoms resolved at day 14 (Clemency 2021; Yu 2021). Inhaled
corticosteroids probably increase symptom resolution at day 14 (RR
1.19, 95% CI 1.09 to 1.30; 465 events per 1000 in the control group
versus 553 events per 1000 (95% CI 507 to 605 events per 1000) in

the intervention group; random-eGects model; I2 = 0%; moderate-
certainty evidence; Analysis 1.3). We downgraded the certainty of
evidence from high to moderate for serious risk of bias.

Symptom resolution: mean time to recovery (days)

Ramakrishnan 2021  reported a mean time to recovery for 129
participants. While the mean time in the budesonide group was 8
(SD 5) days, the standard care group needed 12 (SD 8) days. Inhaled
corticosteroids may decrease the duration of symptom resolution
(MD −4 days, 95% CI −6.22 to −1.78 days; 139 participants; random-

eGects model; I2 not applicable; low-certainty evidence; Analysis
1.4). Our main reasons for downgrading were serious risk of bias
(one level) due to the very subjective outcome measured in an
open-label study, and serious imprecision (one level) given the low
number of participants.

Clemency 2021 reported the median time to recovery of 19 days
(interquartile range (IQR) 14 to 21) for the ciclesonide group and
19 days (IQR 16 to 23) for the placebo group. As this study did not
report the mean data, we did not include the results in the meta-
analyses.

Symptom resolution: all initial symptoms resolved (asymptomatic) at
day 30

One study with 400 participants reported data on all initial
symptoms resolved at day 30 (Clemency 2021). Overall, 139/197
participants in the intervention group felt recovered of all initial
symptoms compared to 129/203 participants in the control group

(RR 1.11, 95% CI 0.97 to 1.27; random-eGects model; I2 not
applicable; Analysis 1.5).

Quality of life, including fatigue and neurological status, assessed
with standardised scales (e.g. WHOQOL-100) up to 28 days

Yu 2021 with 1434 participants reported quality of life at 28 days
on the WHO-5 Well-Being Questionnaire with scores ranging from 0

to 100 (MD 2.60, 95% CI 0.02 to 5.18; random-eGects model; I2 not
applicable; Analysis 1.6).

Serious adverse events during the study period

One study with 1586 participants reported data on serious adverse
events (Yu 2021). Overall, 2/787 participants in the intervention
group had a serious adverse event compared to 4/799 participants
in the control group. The evidence is very uncertain about the eGect
of inhaled corticosteroids on serious adverse events (RR 0.51, 95%
CI 0.09 to 2.76; 5 events per 1000 in the control group versus 3
events per 1000 (95% CI 0 to 14 events per 1000) in the intervention

group; I2 not applicable; random-eGects model; very low-certainty
evidence; Analysis 1.7). We downgraded the certainty of evidence
from high to very low for very serious imprecision due to a very low
number of events and a wide CI and for serious risk of bias as the
other two studies did not report serious adverse events (Clemency
2021; Ramakrishnan 2021).

Adverse events (any grade) up to day 30

One study with 400 participants reported data on adverse events
(any grade) (Clemency 2021). Overall, 22/197 participants in the
intervention group had an adverse event compared to 29/203
participants in the control group. Inhaled corticosteroids may
result in little to no diGerence in adverse events (RR 0.78, 95%
CI 0.47 to 1.31; 143 events per 1000 in the control group versus
111 events per 1000 (95% CI 67 to 187 events per 1000) in the

intervention group; I2 not applicable; random-eGects model; low-
certainty evidence; Analysis 1.8). We downgraded the certainty of
evidence from high to low due to serious imprecision with a low
number of events/participants and wide CI and for serious risk of
bias as the other two studies did not report adverse events or did
not report them in an adequate manner (Ramakrishnan 2021; Yu
2021).

Ramakrishnan 2021  reported five adverse events for 146
participants; all in the intervention arm. The manner of reporting
suggests that only treatment-related adverse events or side eGects
were reported. Therefore, we did not include the results in a meta-
analysis.

Infections during the study period

One study with 400 participants reported data on infections
(Clemency 2021). Overall, 6/197 participants in the intervention
group had an infection compared to 7/203 participants in the
control group. Inhaled corticosteroids may result in little to no
diGerence in infections (RR 0.88, 95% CI 0.30 to 2.58; 34 events per
1000 in the control group versus 30 events per 1000 (95% CI 10 to

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89 events per 1000) in the intervention group; I2 not applicable;
random-eGects model; low-certainty evidence;  Analysis 1.9). We
downgraded the certainty of evidence from high to low for very
serious imprecision due to very low number of events and wide CI.

D I S C U S S I O N

Summary of main results

We aimed to assess the eGicacy and safety of inhaled
corticosteroids for the treatment of COVID-19. We found no studies
for people with asymptomatic infection or confirmed diagnosis of
COVID-19 and moderate-to-severe disease.

For people with a confirmed diagnosis of COVID-19 and mild
disease, we identified three RCTs (3607 participants) evaluating
inhaled corticosteroids compared to standard care (with or without
placebo). Two RCTs (3207 participants) compared budesonide plus
standard care to standard care alone, of which we analysed all cases
with PCR-confirmed diagnosis and being concurrently randomised
(1625 participants), and one RCT (400 participants) compared
ciclesonide plus standard care to standard care plus placebo.

• Inhaled corticosteroids may result in little to no diGerence in all-
cause mortality in outpatients with mild COVID-19 (low-certainty
evidence). We could not explore diGerences in the eGect of
inhaled corticosteroids based on sex, comorbidities, diGerent
timing, and diGerent dosage due to insuGicient data.

• Inhaled corticosteroids probably reduce the risk of admission to
hospital or death at up to day 30 (moderate-certainty evidence).
Further, the intervention probably increases the resolution of all
initial symptoms at day 14 and may decrease the duration to
symptoms resolved (low-certainty evidence).

• Regarding adverse events and infections, inhaled
corticosteroids may result in little to no diGerence, and the
certainty of evidence was low for both outcomes. In terms of
serious adverse events, the evidence is very uncertain about the
eGect of inhaled corticosteroids (very-low certainty evidence).

Overall completeness and applicability of evidence

The included studies were conducted in high-income countries
with 2171 participants in our analyses. The numbers available
for analysis ranged between 139 and 2132 owing to availability
of data. All studies investigated participants with mild disease in
outpatient settings. Currently, there is no evidence for people with
asymptomatic SARS-CoV-2 infection or inpatients with moderate-
to-severe disease.

For our main eGicacy outcomes, mortality and admission to
hospital or death, the overall event rate was very low (less than
1% for mortality, less than 10% for admission to hospital or death),
resulting in low- to moderate-certainty evidence and very small
diGerences in eGects between the intervention and control group.
In two of three RCTs, there were no deaths. We do not expect
the evidence to change in the near future because completed but
unpublished studies awaiting classification would only yield data
on about 700 participants while our review is already comprising
more than 2000 participants. Furthermore, the applicability of
the evidence is unlikely to be enhanced by the ongoing studies
that address similar populations and medicines to the studies we
already have. Due to the living character of this review, it will be
updated as soon as new relevant evidence arises.

With regard to diagnostic workup and timing of the intervention,
we chose to analyse only those participants who had laboratory-
confirmed SARS-CoV-2 infection, and who had been allocated to
intervention and control arms at the same time. This meant that
we excluded a large amount of data from Yu 2021. We assumed that
testing is feasible in almost every setting where the intervention
would be available. It is likely that changes in epidemiology,
legislation, standard care, and respective media coverage have
occurred over time. This could aGect the outcomes of interest in this
review.

The weight of Yu 2021 in the meta-analyses of mortality, hospital
admission or death, and symptom resolution ranged from 88% to
100%. Given the large weight of this study, the generalisability of
the review is influenced by the characteristics of the participants:
aged 50 to 64 years with comorbidities or aged 65 years and
older irrespective of comorbidities. However, participants who
were unable to use the inhaler appropriately were excluded. This
means that direct evidence can only be derived for people within
this certain age group excluding the younger people (aged less than
50 years) and any people unable to use an inhaler. No prior use
of inhaled corticosteroids was allowed, meaning that participants
had no long-term experience with how to use an inhaler correctly.
This might have consequences on potential benefits and harms
of the inhaler and the medicine it delivers, although it should
be noted that the risk of systemic adverse eGects is likely to be
negligible even with poor inhaler technique (swallowing) because
of the favourable pharmacokinetics of budesonide with low oral
bioavailability and especially ciclesonide owing to its on-site
activation (Derendorf 2006).

Ramakrishnan 2021 and Yu 2021 administered budesonide using
the Pulmicort Turbuhaler device, which might not be readily
available worldwide. Moreover, ciclesonide, the corticosteroid
intervention in Clemency 2021, is still protected by a patent and
not available as a generic drug. Hence, both availability and pricing
might be a barrier to its use on a global scale (Google Patent
Overview Ciclesonide).

Moreover, the timing of the recruitment periods of the included
studies may be aGected by rapidly emerging knowledge in
epidemiology and therapeutic interventions. Most data in this
review has been collected before spring 2021 (Yu 2021: 27
November 2020 to 31 March 2021; Clemency 2021: 11 June 2020
to 3 November 2020; Ramakrishnan 2021: 16 July 2020 to 9
December 2020). Consequently, most participants were not fully
vaccinated (13% received one dose and 1% received the second
dose in Yu 2021, and no vaccinations in Clemency 2021 and
Ramakrishnan 2021). Even if the absolute number of patients with
mild disease and a severe course of COVID-19 can be reduced
through vaccination, we currently assume that the eGects shown
in the investigated population are also valid for fully vaccinated
patients showing symptoms (i.e. WHO grade 3 or 4).

In contrast to SARS-CoV-2-specific monoclonal antibodies, inhaled
corticosteroids do not directly interact with the spike protein
of the virus, and so diGerent variants of the virus are unlikely
to influence the potential benefits and harms of the inhaled
corticosteroids. The delta variant of SARS-CoV-2 is more virulent
than its predecessors, but pathogenicity appears to be similar
or even favourable to the evaluated intervention. Together with
the pleiotropic immunomodulatory eGect of corticosteroids, we
assume that in contrast to more targeted therapies also in future

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variants, evidence can be seen as direct. Delta variant virus
particles have been shown in vitro to have a higher ACE2 receptor
aGinity and increased infectivity caused by a change in antigenic
properties (Motozono 2021). The variant evades cellular immunity
and increases infectivity. From this perspective, a reduction of the
expression of the ACE2 receptor, which is postulated for inhaled
corticosteroids (Finney 2021; Peters 2020), could be a promising
mechanism of action against the delta variant of SARS-CoV-2.
However, the potential enhanced eGect needs to be verified in
future RCTs.

Quality of the evidence

Inhaled corticosteroids (plus standard care) versus standard
care (with or without placebo)

We included data from three RCTs in the analysis of eGicacy and
safety of inhaled corticosteroids. The population of interest was
people with a confirmed diagnosis of mild COVID-19.

We rated the certainty of the evidence as moderate to very low
(see Summary of findings 1). We downgraded the certainty of
evidence due to risk of bias arising from the unblinded study design
for all patient-reported outcomes. However, we acknowledge
that within trial platforms such as PRINCIPLE (Yu 2021), blinding
is diGicult to implement. Low number of events/imprecision
aGected all endpoints except symptom resolution at day 14 and
led to downgrading by one point. In addition, missing safety
outcome data (adverse events and serious adverse events) led to
downgrading for reporting bias. At least the latter issue could easily
be improved in future publications.

Potential biases in the review process

To avoid potential biases in the review process we did all
steps in duplicate (e.g. screening search results, data extraction,
bias assessment, assessing certainty using the GRADE approach)
and had intense discussions involving both clinicians and
methodologists to agree on data analyses and interpretation. As
the definition of clinical outcomes such as symptom resolution
varied across included studies it is highly relevant to involve clinical
experts, not to misinterpret data.

In addition to peer-reviewed, full-text articles, we also included
one preprint. The results of the sensitivity analyses did not diGer
between with or without preprint. We are aware of the potentially
lower quality of preprint publications, and that results could
change once the peer-reviewed journal publications are available.
In cases of missing data, we contacted study authors for additional
data or relevant details if we needed more information. However,
we have not yet received an answer. We are confident that we
identified all relevant studies and will monitor ongoing studies as
well as full publications of preprints closely aUer the publication of
this review.

Since only a few data (about 5%) were missing across all studies,
we do not expect this to result in a risk of bias.

Agreements and disagreements with other studies or
reviews

We could not find current published RCT-based peer-reviewed
systematic reviews focussing on inhaled corticosteroids in people
without prior use. Apart from that, one the regularly updated living

guideline for people with confirmed COVID-19 of 24 September
2021 did not include the intervention (WHO 2021d). One living
systematic review published in March 2021 only included the
preprint of Ramakrishnan 2021 without further mention of inhaled
corticosteroids (Siemieniuk 2020).

One living network meta-analysis includes budesonide as an
intervention, using data from Ramakrishnan 2021 and Yu 2021
in the analysis of mortality and clinical progression (COVID-NMA
2021). Notably, they seemed to have included participants without
laboratory-confirmed testing or from asynchronous allocation
from Yu 2021. The diGerent choice of the cohort for analysis comes
with implications for directness and applicability of the evidence.
Irrespective of this diGerent approach, COVID-NMA 2021 assessed
the certainty of the evidence similarly to our review. The main
diGerences were to outcomes related to the diGerent populations
from the same included studies and the exclusion of the Clemency
2021 preprint.

A U T H O R S ‘   C O N C L U S I O N S

Implications for practice

In people with confirmed COVID-19 and mild symptoms who are
able to use inhaler devices, we found moderate-certainty evidence
that inhaled corticosteroids probably reduce the combined
endpoint of mortality or hospitalisation and increases symptom
resolution at day 14. Low-certainty evidence suggests that inhaled
corticosteroids make little to no diGerence in all-cause mortality at
up to day 30 and decrease the duration to symptom resolution.

Due to heterogeneity in the reporting of serious adverse events
across the studies, we do not know whether inhaled corticosteroids
increase or decrease the risk of this outcome. There is low-certainty
evidence that inhaled corticosteroids may decrease infections.

Most practitioners in family and internal medicine are familiar with
prescription, eGicacy, adherence, and favourable safety profiles of
inhaled corticosteroids in hyperinflammatory pulmonary disease.
However, data for use in COVID-19 are not as clear. Moreover, the
data presented in our review only apply directly to a subpopulation
of people with COVID-19 with mild disease and within a group of
adults aged 50 years and above who have not been using inhaled
corticosteroids. The evidence we identified came from studies
in high-income settings prior to vaccination roll-out and current
variants (delta, omicron) of SARS-CoV-2, yet we assume that neither
has a relevant eGect on the expected benefits and harms.

Implications for research

We noted the lack of safety data for serious adverse events, adverse
events, and infections reported by included studies: only one
evaluated serious adverse events for 1586 participants, only one
randomised controlled trial (RCT) provided adequate information
on adverse events and infections for 400 participants.

As studies reported a lack of compliance with the treatment, future
assessment of patient-reported experience measures (PREMs)
could help to identify further unwanted eGects or targets to improve
compliance.

There was no information related to treatment of participants
with asymptomatic SARS-CoV-2 infection that could be of special
interest in countries with (temporally) reduced medical resources.

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Also, the use of inhaled corticosteroids for people with moderate-
to-severe disease has not yet been examined. Studies in more
severely ill populations should measure ventilator-free days, or the
occurrence of new invasive mechanical ventilation or death.

We suggest there is a need for further research into the impact of
inhaled corticosteroids on quality of life in people with COVID-19
and diGerent dosages or diGerent inhaled corticosteroids. We deem
it crucial to use blinding through placebo-control to reduce the risk
of bias.

The 10 ongoing and five completed, unpublished RCTs we identified
in trial registries address broadly similar questions to those in the
published evidence to date. We expect to incorporate the findings
of these studies in future versions of this review.

In line with our living approach to this work, we will monitor
newly published results of RCTs on inhaled corticosteroids on a
monthly basis and will update the review when the evidence or our
confidence in the evidence changes.

A C K N O W L E D G E M E N T S

ALF, FF, and MG are thankful for the support of their colleagues with
the Department of Anesthesia and Intensive Care at the University
of Leipzig Medical Center (Leipzig, Germany) while working on the
manuscript of this review during the COVID-19 pandemic.

The research was part of a project supported by the German Federal
Ministry of Education and Research (NaFoUniMedCovid19, funding

number: 01KX2021; part of the ‘CEOSys’ project). The contents
of this document reflect only the review authors’ views and the
German Ministry is not responsible for any use that may be made
of the information it contains.

Cochrane Airways group supported us in the development of this
review. The following people conducted the editorial process for
this article.

• Sign-oG Editor (final editorial decision): Toby Lasserson,
Cochrane Evidence Production & Methods Directorate.

• Managing Editor (selected peer reviewers, provided comments,
collated peer-reviewer comments, provided editorial guidance
to authors, edited the article): Lara Kahale, Cochrane Central
Editorial Service.

• Editorial Assistant (conducted editorial policy checks and
supported editorial team): Leticia Rodrigues, Cochrane Central
Editorial Service.

• Copy Editor (copy-editing and production): Anne Lawson,
Cochrane Copy Edit Support.

• Peer-reviewers (provided comments and recommended an
editorial decision): Syed Shahzad Hasan, University of
Huddersfield, UK and Iain Crossingham, East Lancashire
Hospitals NHS Trust, UK (clinical/content review); Stella
Maria O’Brien (consumer review); Nuala Livingstone, Cochrane
Evidence Production & Methods Directorate (methods review);
and Elizabeth Stovold (search review).

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R E F E R E N C E S
 

References to studies included in this review

Clemency 2021 {published data only}

Clemency BM, Varughese R, Gonzalez-Rojas Y, Morse CG,
Phipatanakul W, Koster DJ, et al.A randomised controlled
trial of inhaled ciclesonide for outpatient treatment of
symptomatic COVID-19 infections. medRxiv 2021:1-24. [DOI:
doi.org/10.1101/2021.09.07.21261811]

Ramakrishnan 2021 {published data only}

*  Ramakrishnan S, Nicolau DV Jr, Langford B, Mahdi M,
JeGers H, Mwasuku C, et al.Inhaled budesonide in the treatment
of early COVID-19(STOIC): a phase 2, open-label, randomised
controlled trial. Lancet Respiratory Medicine 2021;9(7):763-72.
[DOI: doi.org/10.1016/S2213-2600(21)00160-0]

Ramakrishnan S, Nicolau DV Jr, Langford B, Mahdi M, JeGers H,
Mwasuku C, et al.Inhaled budesonide in the treatment of
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Inhaled corticosteroids for the treatment of COVID-19 (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Better health.

 
 

Cochrane Database of Systematic Reviews

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* Indicates the major publication for the study

 

C H A R A C T E R I S T I C S   O F   S T U D I E S

Characteristics of included studies [ordered by study ID]

 

Study characteristics

Methods Trial design: multicentre, double-blind, RCT

Type of publication: preprint

Setting: outpatient

Recruitment dates: 11 June 2020 to 3 November 2020

Country: US

Language: English

Number of centres: 10

Trial registration number: NCT04377711

Date of trial registration: 5 May 2020

Participants Age: mean:

Clemency 2021 

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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• 43.7 (SD 17.53) years in the intervention group

• 42.9 (SD 16.28) years in the control group

Sex:

• 85 (43%) male and 112 (57%) female in the intervention group

• 94 (46%) male and 109 (54%) female in the control group

Proportion of confirmed infections: positive SARS-CoV-2 molecular or antigen diagnostic sample was
inclusion criteria

Ethnicity: Asian, black or African American, Native Hawaiian or other Pacific Islander, white

Number of participants:

• recruited: 400

• allocated: 197 in the intervention group and 203 in the control group

• evaluated: 197 in the intervention group and 203 in the control group

Severity of condition according to study definition: participants had an oxygen saturation of ≥ 93% on
room air

Comorbidities: hypertension, drug hypersensitivity, hyperlipidaemia, type 2 diabetes mellitus, asthma

Inclusion criteria:

• aged ≥ 12 years

• positive SARS-CoV-2 molecular or antigen diagnostic sample obtained in the previous 72 hours

• not hospitalised or under consideration for hospitalisation

• oxygen saturation ≥ 93% on room air

• able to demonstrate successful use of an MDI

• ≥ 1 of the following symptoms of COVID: fever, cough, or dyspnoea

Exclusion criteria:

• history of hypersensitivity to ciclesonide

• taken an inhaled or intranasal corticosteroid within 14 days

• taken oral corticosteroids within 90 days

• participated in any other clinical trial or use of any investigational agent within 30 days

• history of cystic fibrosis

• history of idiopathic pulmonary fibrosis

• receiving treatment with hydroxychloroquine/chloroquine

• pregnant

Previous treatments: not reported

Interventions Intervention group: ciclesonide 160 μg per actuation, 2 actuations twice a day (total daily dose 640 μg)
+ standard care

Control group: placebo + standard care

Concomitant therapy: paracetamol, NSAIDS, antibiotics, antivirals, monoclonal antibodies

Duration of follow-up: 30 days

Treatment cross-overs: no

Compliance with assigned treatment: yes

Clemency 2021  (Continued)

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Outcomes Primary study outcome: time to alleviation of all COVID-19-related symptoms (cough, dyspnoea, chills,
feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste
or smell) by day 30

Secondary outcomes: incidence of subsequent emergency department visits or hospital admissions
for reasons attributable to COVID-19, incidence of hospital admissions or death, all-cause mortality,
COVID-19-related mortality, percentage of participants with alleviation of COVID-19-related symptoms,
time to hospital admission or death, alleviation of all COVID-19-related symptoms by days 7, 14, and 30,
oxygen saturation levels, COVID-19 viral load, and safety assessments

Notes Date of publication: 12 September 2021

Sponsor/funding: Covis Pharma GmbH

Clemency 2021  (Continued)

 
 

Study characteristics

Methods Trial design: randomised, open-label

Type of publication: journal publication

Setting: outpatient

Recruitment dates: 16 July 2020 to 9 December 2020

Country: UK

Language: English

Number of centres: not reported

Trial registration number: NCT04416399

Date of trial registration: 4 June 2020

Participants Age: mean:

• 44 (range 19–71) years in the intervention group

• 46 (range 19–79) years in the control group

Sex:

• 31 (44%) male and 39 (56%) female in the intervention group

• 28 (41%) male and 41 (59%) female in the control group

Proportion of confirmed infections: positive: 94% in the intervention group and 94% in the control
group

Ethnicity: white: 65 (93%) in the intervention group and 64 (93%) in the control group; non-white: 5
(7%) in the intervention group and 5 (7%) in the control group

Number of participants (recruited/allocated/evaluated): 146 recruited, of them 73 in the interven-
tion group and 73 in the control group allocated and 70 in the intervention group and 69 in the control
group evaluated

Severity of condition according to study definition: with symptoms of COVID-19 (new-onset cough and
fever or anosmia or both) within 7 days

Comorbidities: cardiovascular disease, diabetes, past or current asthma

Ramakrishnan 2021 

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Inclusion criteria:

• willing and able to give informed consent for participation in the trial

• male or female

• aged ≥ 18 years

• new onset of symptoms suggestive of COVID-19, e.g. new-onset cough, fever, loss of smell or taste
within 7 or fewer days of participant being seen at visit 1

Exclusion criteria:

• known allergy to investigational medicine product (budesonide)

• any known contraindication to any of the investigational medicine products (budesonide)

• currently prescribed inhaled or systemic corticosteroids

• recent use, within the previous 7 days of inhaled or systemic corticosteroids

• needs hospitalisation at time of study consent

• any other significant disease or disorder which, in the opinion of the investigator, may either have put
the participants at risk because of participation in the trial, or may have influenced the result of the
trial, or the participant’s ability to participate in the trial

• participants who had participated in another research trial involving an investigational product in the
past 12 weeks

Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): no

Interventions Intervention group: inhaled budesonide 400 µg per actuation (2 puGs twice per day; total dose 1600 µg)
+ standard care

Control group: standard care

Concomitant therapy: antipyretics for symptoms of fever (products containing paracetamol, or NSAIDs
such as aspirin and ibuprofen) and honey for symptoms of cough

Duration of follow-up: 14 days

Treatment cross-overs: no

Compliance with assigned treatment: yes

Outcomes Primary outcome: COVID-19-related urgent care visits, including emergency department assessment or
hospitalisation

Secondary outcome: clinical recovery, as defined by self-reported time to symptom resolution; viral
symptoms measured by the Common Cold Questionnaire (CCQ) 12 and the InFLUenza Patient-Report-
ed Outcome (FLUPro)13 questionnaire; blood oxygen saturations and body temperature; and SARS-
CoV-2 viral load

Notes Date of publication: 9 April 2021

Sponsor/funding: National Institute for Health Research Biomedical Research Centre and AstraZeneca

Ramakrishnan 2021  (Continued)

 
 

Study characteristics

Methods Trial design: randomised platform trial

Type of publication: journal publication

Setting: outpatient

Yu 2021 

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Recruitment dates: 27 November 2020 to 31 March 2021

Country: UK

Language: English

Number of centres: not reported

Trial registration number: ISRCTN86534580

Date of trial registration: 25 March 2021

Participants Age: mean

• primary analysis population:
◦ 64.7 (SD 7.3) years in the intervention group

◦ 63.8 (SD 7.8) years in the control group

• concurrent randomisation population:
◦ 64.7 (SD 7.3) years in the intervention group

◦ 64.5 (SD 7.7) years in the control group

Sex:

• primary analysis population:
◦ 404 (48%) male and 429 (52%) female in the intervention group

◦ 540 (48%) male and 586 (52%) female in the control group

• concurrent randomisation population:
◦ 404 (48%) male and 429 (51%) female in the intervention group

◦ 431 (49%) male and 455 (51%) female in the control group

Proportion of confirmed infections:

• positive: 80% in the intervention group and 57.5% in the control group

• negative: 13% in the intervention group and 28.4% in the control group

• no result: 1% in the intervention group and 0.5% in the control group

Missing: 7% in the intervention group and 13.6% in the control group

Ethnicity:

• primary analysis population:
◦ white: 767 (92%) in the intervention group and 1038 (92%) in the control group

◦ mixed: 9 (1%) in the intervention group and 5 (< 1%) in the control group

◦ South Asian: 43 (5%) in the intervention group and 64 (6%) in the control group

◦ black: 6 (1%) in the intervention group and 4 (< 1%) in the control group

◦ other: 8 (1%) in the intervention group and 14 (1%) in the control group

◦ missing: 0 in the intervention group and 1 (< 1%) in the control group

• concurrent randomisation population:
◦ white: 767 (92%) in the intervention group and 820 (93%) in the control group

◦ mixed: 9 (1%) in the intervention group and 4 (< 1%) in the control group

◦ South Asian: 43 (5%) in the intervention group and 48 (5%) in the control group

◦ black: 6 (1%) in the intervention group and 3 (< 1%) in the control group

◦ other: 8 (1%) in the intervention group and 11 (1%) in the control group

◦ missing: 0 in the intervention group and 0 in the control group

Number of participants:

• recruited: 4720

• allocated: 1073 in the intervention group and 1988 in the control group

Yu 2021  (Continued)

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• evaluated: 787 in the intervention group and 838 in the control group (concurrent randomisation
SARS-CoV-2-positive population)

Severity of condition according to study definition: ongoing symptoms of confirmed or suspected COV-
ID-19 (high temperature or new, continuous cough or change in sense of smell/taste, or a combination
of these) within 14 days

Comorbidities: asthma, chronic obstructive pulmonary disease, lung disease, diabetes mellitus, heart
problems, liver disease, stroke or neurological problem, hypertension requiring medication

Inclusion criteria:

• aged ≥ 65 years, or ≥ 50 years with comorbidities (heart disease, hypertension, asthma or lung disease,
diabetes, hepatic impairment, stroke or neurological problems, weakened immune system, self-re-
ported obesity)

• had ongoing symptoms from polymerase chain reaction (PCR) confirmed or suspected COVID-19
which started within the past 14 days

Exclusion criteria:

• already taking inhaled or systemic corticosteroids

• unable to use an inhaler

• contraindication to inhaled budesonide

Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): no

Interventions Intervention group: inhaled budesonide 800 µg twice daily for 14 days + standard care

Control group: standard care (antipyretics, antibiotics)

Concomitant therapy: no

Outcomes Primary outcomes: time to self-reported recovery, defined as the first instance that a participant re-
ported feeling recovered from possible COVID-19; hospitalisation or death or both (both within 28 days)

Secondary outcomes: rating of how well participants felt (scale 1–10); time to sustained recovery (date
participant first reported feeling recovered and subsequently remained well until 28 days); early sus-
tained recovery (reported feeling recovered within the first 14 days from randomisation and remained
recovered until day 28); time to initial alleviation of symptoms (date participant first reported all symp-
toms as minor or none); time to sustained alleviation of symptoms; time to initial reduction of severity
of symptoms; contacts with health services; hospital assessment without admission; oxygen adminis-
tration; intensive care unit admission; mechanical ventilation; WHO-5 Well-Being Index

Notes Date of publication: 10 August 2021

Sponsor/funding: National Institute of Health Research and United Kingdom Research Innovation

Yu 2021  (Continued)

COVID-19: coronavirus disease 2019; MDI: metered-dose inhaler; NSAID: non-steroidal anti-inflammatory drug; RCT: randomised controlled
trial; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SD: standard deviation; WHO: World Health Organization.
 

Characteristics of excluded studies [ordered by study ID]

 

Study Reason for exclusion

IRCT20200522047542N1 Designated route of application was inhaled but was topical.

 

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Characteristics of studies awaiting classification [ordered by study ID]

 

Methods Trial design: randomised trial

Sample size: 49

Setting: inpatient

Language: English

Number of centres: 1

Type of intervention: treatment

Participants Inclusion criteria:

• adult (aged ≥ 18 years)

• positive PCR test of COVID-19 virus in specimens taken from the respiratory tracts, and people with
negative PCR test but had clinical signs and symptoms of viral illness with chest CT scan showing
the radiological findings of viral pneumonia, which was defined as new, unexplained, and bilateral
infiltrates on the lungs

Exclusion criteria:

• people admitted to hospital for other conditions with oxygen saturation ≥ 94% without viral symp-
toms but had infiltrations on chest CT scan (mild form of COVID-19)

• received other antiviral or investigational therapies for COVID-19

• died or transmitted to ICU during the first 24 hours

• people who presented with persistent treatment of corticosteroid inhalers

Interventions Intervention group: inhaled budesonide 200 µg, twice daily for 5 days + supportive care

Control group: supportive care (oxygen supplementation, vitamins, anticoagulants, dexametha-
sone, prone position, non-invasive ventilation (CPAP or BIPAP), antibiotics, and fluids)

Concomitant therapy: no

Outcomes No distinction between primary and secondary outcomes: time of hospitalisation (mean), time on
oxygen supplementation from admission to cure (mean), admission PiO2/FiO2 ratio vs discharge

PiO2/FiO2 ratio (mean), admission oxygen saturation + oxygen supplementation vs discharge oxy-

gen saturation (mean)

Notes Recruitment status: completed

Prospective completion date: not stated

Date last update was posted: not stated

Sponsor/funding: not stated

Alsultan 2021 

 
 

Methods Trial design: randomised, open-label

Sample size: 300

Setting: inpatient

Language: English

EUCTR2020-001616-18-ES/NCT04355637 

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Number of centres: 10 centres listed “recruiting”, another 4 centres listed “not recruiting”

Type of intervention: treatment

Participants Inclusion criteria:

• COVID-19

• age ≥ 18 years and < 80 years

• admitted for pneumonia (status #3 and #4 OMS scale)

• informed consent

Exclusion criteria

• pregnancy

• contraindications for inhaled corticosteroid therapy

• participation in another intervention trial on COVID-19

• current treatment with inhaled or systemic corticosteroids

• current treatment with anti-IL-1 or anti-IL-6 drugs

• receiving high flow oxygen therapy

• receiving mechanical ventilation

Interventions Intervention group: inhaled budesonide 800 µg

Control group: placebo

Concomitant therapy: no

Outcomes Primary outcomes: proportion of participants with therapeutic failure (as a composite outcome:
people requiring non-invasive or invasive mechanical ventilation, high flow oxygen therapy, all-
cause mortality, or a combination)

Secondary outcome: clinical evolution (discharge, ARDS, death, ICU refusal), temperature, heart
rate, blood pressure, PaO2/FiO2, systemic biomarkers, duration of hospital stay, complications dur-

ing admittance (infectious, cardiovascular, metabolic, others), all-cause mortality, vital status,
changes in clinical status (OMS 7-point scale)

Notes Recruitment status: completed

Prospective completion date: not reported

Date last update was posted: 22 September 2021

Sponsor/funding: Fundacion Clinic per a la Recerca Biomédica

EUCTR2020-001616-18-ES/NCT04355637  (Continued)

 
 

Methods Trial design: open-label, RCT

Sample size: 146

Setting: inpatient

Language: English

Number of centres: not reported

Type of intervention: treatment

Participants Inclusion criteria:

NCT04331054 

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• aged ≥ 18 years and ≤ 75 years

• laboratory-confirmed infection by COVID-19 by RT-PCR on a respiratory biological sample within
2 days

• hospitalisation required according to current local recommendations

• patient affiliated to a social security regimen

• able to give free, informed, and written consent

Exclusion criteria:

• oxygen flow rate > 8 L/minute at inclusion

• current treatment with any inhaled steroid (any other form of steroid administration does not
exclude the patient)

• ICU required (based on investigator judgement)

• with cognitive impairment that does not guarantee proper use of the treatment by the patients
themselves

• pregnant (positive β-human chorionic gonadotropin at inclusion) or breastfeeding women

• participation in another interventional drug study involving humans and concerning COVID-19
infection or being in the exclusion period of a previous study involving humans

• contraindications to treatments (history of hypersensitivity)

• admitted for isolation, for social reason or due to comorbidities without gravity sign

• long-term patient treated with digitalis, disopyramide, procainamide, or phenothiazine that
could lengthen the QT space

Interventions Intervention group: inhaled SYMBICORT RAPIHALER 2 puGs twice daily for 30 days + standard care

Control group: standard care

Concomitant therapy: no

Outcomes Primary outcomes: time (in days) to clinical improvement within 30 days after randomisation, de-
fined as the time from randomisation to an improvement of 2 points (from the status at randomisa-
tion) on a 7-category ordinal scale or live discharge from the hospital, whichever came first within
30 days. The 7-category ordinal scale consisted of the following categories:

1. Not hospitalised with resumption of normal activities

2. Not hospitalised, but unable to resume normal activities

3. Hospitalised, not requiring supplemental oxygen

4. Hospitalised, requiring supplemental oxygen

5. Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or
both;

6. Hospitalised, requiring extracorporeal membrane oxygenation, invasive mechanical ventilation,
or both

7. Death

These parameters will be evaluated daily during hospitalisations.

Secondary outcomes: mortality rate at day 30; time (in days) from randomisation to death up to 30
days; number of days alive outside ICU within 30 days; number of days alive free of invasive or non-
invasive ventilation within 30 days; number of days alive with oxygen therapy within 30 days; maxi-
mal oxygen rate within 30 days; difference between PaO2/FiO2 ratio at randomisation and day 7 (or

at the time of stopping oxygen therapy or discharge if occurs before day 7); number of days alive
outside hospital within 30 days; use of antibiotics for respiratory (confirmed or suspected) infec-
tion within 30 days; difference between C-reactive protein levels at randomisation and day 7 (or at
the time of discharge if occurs before day 7)

Safety outcomes included events that occurred during treatment, serious adverse events, and pre-
mature discontinuation of treatment up to 30 days after randomisation

Notes Recruitment status: terminated (insufficient recruitment)

NCT04331054  (Continued)

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Prospective completion date: 28 May 2021

Date last update was posted: 3 August 2021

Sponsor/funding: Assistance Publique – Hôpitaux de Paris

NCT04331054  (Continued)

 
 

Methods Trial design: randomised controlled, triple-blind trial

Sample size: 215

Setting: outpatient

Language: English

Number of centres: 1

Type of intervention: treatment

Participants Inclusion criteria:

• symptomatic adults positive by PCR for COVID-19 within 5 days of enrolment with fever, cough,
or shortness of breath

• provision of informed consent

• at day 0, patients should be at home

Exclusion criteria:

• already receiving inhaled corticosteroid medication

• currently using systemic corticosteroids (oral or intravenous or intramuscular such as pred-
nisone) or use of steroids 7 days prior to enrolment

• severely ill at enrolment (i.e. admitted to ICU at admission)

• unable to self-administer the inhaler

• known or suspected pregnancy and breastfeeding

• known allergy to study medication or its components (non-medicinal ingredients; including lac-
tose allergy (type I))

• with untreated fungal, bacterial, or tubercular infections of the respiratory tract

• current hospitalisation

• current use of oxygen at home or in the hospital

Interventions Intervention group: intranasal ciclesonide 50 μg twice daily to each nostril and inhaled ciclesonide
600 μg twice daily for 14 days

Control group: intranasal normal saline twice daily and inhaled placebo 3 puGs by MDI twice daily

Concomitant therapy: no

Outcomes Primary outcome: proportion of participants with no symptoms of cough, fever, or dyspnoea at day
7

Secondary outcomes: proportion of participants with no symptoms of cough, fever, or dyspnoea
at day 14; overall feeling – proportion who reporting they are “very much improved” or “much im-
proved” at day 7; overall feeling – proportion who reporting they are “very much improved” or
“much improved” at day 14; improvement in dyspnoea at days 7 and 14 (dyspnoea defined as re-
porting “shortness of breath” or “chest congestion” or “chest tightness”. In those who reported
dyspnoea at baseline, resolution will be defined as having no symptoms in these 3 areas); Visual
Analog scale for Cough – wet or dry cough at days 7 and 14; hospitalisation for SARS-CoV-2 and hos-
pitalisation for SARS-CoV-2-related illness at day 14; 2-point change in PROMIS Dyspnoea Severity

NCT04435795 

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Scale at days 7 and 14; 2-point changes in PROMIS Dyspnoea Severity Scale at days 7 and 14; inci-
dence of new oxygen use during the trial (defined as oxygen use not present at randomisation) at
day 14; all-cause mortality at days 14 and 29; PROMIS Anxiety 7a scale 1–5 (1 = never had symptoms
and 5 = always had symptoms) at days 7 and 14; PROMIS Sleep Disturbance 4a scale from 1 to 5 (1 =
very good and 5 = very poor) at days 7 and 14

Notes Recruitment status: terminated (could not meet target enrolment)

Prospective completion date: 8 June 2021

Date last update was posted: 30 July 2021

Sponsor/funding: McGill University Health Centre/Research Institute of the McGill University Health
Centre

NCT04435795  (Continued)

 
 

Methods Trial design: open-label, randomised

Type of publication: journal publication

Setting: inpatient

Recruitment dates: 8 May 2020 to 31 March 2021

Country: South Korea

Language: English

Number of centres: 6

Trial registration number: NCT04330586

Date of trial registration: 31 March 2020

Participants Age: mean:

• 44.9 (SD 17.9) years in the intervention group

• 49.0 (SD 16.8) years in the control group

Sex:

• 11 (31.4%) male in the intervention group

• 9 (34.6%) male in the control group

Proportion of confirmed infections: 100% (confirmed by qRT-PCR)

Ethnicity: not stated

Number of participants:

• recruited: 61

• allocated: 35 the intervention group and 26 in the control group

• evaluated: 35 in intervention group and 26 in the control group

Severity of condition according to study definition: low NEWS

Comorbidities: diabetes, hypertension, cerebrovascular diseases

Inclusion criteria:

Song 2021 

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• low NEWS ranging from 0 to 4 (NEWS is a scoring system based on routine physiological parame-
ters (respiratory rate, oxygen saturation, supplemental oxygen, body temperature, systolic blood
pressure, heart rate, and level of consciousness))

Exclusion criteria:

• oxygen saturation < 95% breathing room air

• pregnancy or breastfeeding

• renal impairment (estimated creatinine clearance < 30 mL/minute)

• hepatic dysfunction (alanine aminotransferase or aspartate aminotransferase levels > 5 times the
upper limit of normal)

• immunocompromising conditions

• severe uncontrolled comorbidities

• chronic airway diseases (asthma and chronic obstructive lung disease)

• contraindications for use of ciclesonide inhaler

Previous treatments (e.g. experimental drug therapies, oxygen therapy, ventilation): no

Interventions Intervention group: inhaled ciclesonide 320 µg twice daily for 14 days

Control group: standard care

Concomitant therapy: standard care (intravenous fluid, supplementary oxygen, antibiotics)

Duration of follow-up: 14 days

Treatment cross-overs: no

Compliance with assigned treatment: yes

Outcomes Primary outcome: SARS-CoV-2 eradication rate based on qRT-PCR on day 14

Secondary outcomes: SARS-CoV-2 eradication rate based on at days 7 and 10 from study enrol-
ment; rate of clinical improvement (resolution of all systemic and respiratory symptoms) at days
7, 10, and 14 from study enrolment; rate of clinical failure within 28 days; safety/tolerability of ci-
clesonide

Notes Date of publication: 12 August 2021

Sponsor/funding: National Research Foundation of Korea (NRF) grant [2020M3A9I2081699] and Ko-
rea University Guro Hospital grant (I2000171)

Song 2021  (Continued)

ARDS: acute respiratory distress syndrome; BIPAP: bilevel positive airway pressure; COVID-19: coronavirus disease 2019; CPAP: continuous
positive airway pressure; CT: computer tomography; ICU: intensive care unit; IL: interleukin; NEWS: National Early Warning Score; OMS:
ordinal measurement scale; PCR: polymerase chain reaction; PiO2/FiO2: inspired oxygen tension/fraction of inspired oxygen; PaO2/FiO2:

arterial oxygen partial pressure/fraction of inspired oxygen; PROMIS: Patient-Reported Outcomes Measurement Information System; qRT-
PCR: quantitative reverse transcription polymerase chain reaction; RCT: randomised controlled trial; RT-PCR: real-time polymerase chain
reaction.
 

Characteristics of ongoing studies [ordered by study ID]

 

Study name Efficacy of hydroxychloroquine, ciclesonide and ivermectin in treatment of moderate COVID-19 ill-
ness: an open-label randomised controlled study

Methods Trial design: randomised, parallel-group trial

Sample size: 120

CTRI/2020/04/024948 

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Setting: inpatient

Language: English

Number of centres: 1

Type of intervention: treatment

Participants Inclusion criteria:

• adults (aged > 18 years) with COVID-19

• positive throat swab (by real-time PCR) obtained from a patient suspected to be COVID-19 or from
a contact (or healthcare worker) of person with COVID-19 will be considered to be a COVID-19 case

• presence of moderate COVID-19 as defined by the presence of pneumonia (clinical and radiolog-
ical signs) with a respiratory rate 15–30/minute or oxygen saturation 90–94% on room air, or both

Exclusion criteria:

• people with renal or hepatic dysfunction (serum creatinine > 1.5 mg/dL and serum transaminase
levels > 120 U/L)

• people with clinical heart failure/known coronary artery disease

• known cases of neoplasms or immunodeficiency syndromes

• people receiving chemotherapy, immunosuppressive agents, steroids or antiviral agents, or have
received in the preceding 4 weeks

• pregnant and lactating women

• unco-operative people (in the opinion of the investigator)

Interventions Intervention group: inhaled ciclesonide 200 μg twice daily for 7 days

Control group: supportive management as per national guidelines

Concomitant therapy: no

Outcomes Primary outcome: proportion of people having virological cure on day 6 of treatment initiation

Secondary outcomes: proportion of people with resolution of symptoms/signs on days 7 and 14;
proportion of rescue criteria on days 7 and 14; adverse effects on days 7 and 14

Starting date 15 May 2020

Contact information Anupam Prakash

Department of Medicine Lady Hardinge Medical College Shahid Bhagat Singh Marg New Delhi
110001 India

[email protected]

Notes Recruitment status: not yet recruiting

Prospective completion date: not reported

Date last update was posted: 30 April 2020

Sponsor/funding: Lady Hardinge Medical College

CTRI/2020/04/024948  (Continued)

 
 

Study name Clinical trial to study the effect of budesonide taken through inhalation in mild COVID cases

CTRI/2020/10/028581 

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Methods Trial design: randomised, parallel-group, controlled trial

Sample size: 1000

Setting: outpatient

Language: English

Number of centres: 4

Type of intervention: treatment

Participants Inclusion criteria:

• people with RT-PCR or rapid antigen confirmed diagnosis of COVID-19

• asymptomatic person with mild symptoms of < 5 days of duration

• oxygen saturation > 94% on room air

• no radiological evidence of pneumonia

• aged > 18 years to 99 years

Exclusion criteria:

• requiring hospitalisation

• unable to take the drug as directed and comply with study procedure

• vulnerable population (pregnant women, lactating women, Prisoners, unable to consent)

• receiving systemic/inhalational steroids

Interventions Intervention group: inhaled Rotacaps or Dry powder inhalation of budesonide 200 μg twice daily +
standard care for 10–14 days depending on onset of symptoms

Control group: standard care for mild COVID-19 cases as provided by the centre

Concomitant therapy: no

Outcomes Primary outcome: hospitalisation with time points of 10–14 days depending on the onset of symp-
toms

Secondary outcomes: none

Starting date 23 October 2020

Contact information Dr Tushar Patel

SPARSH Chest Disease Centre, 100B Swastik Society, Opposite Samved Hospital, Navrangpura,
Ahmedabad Respiratory Medicine Department, GCS Hospital, Near Chamunda Bridge, Naroda
road, Ahmedabad 380025 Ahmadabad GUJARAT 380009 India

[email protected]

Notes Recruitment status: not yet recruiting

Prospective completion date: not reported

Date last update was posted: 23 October 2020

Sponsor/funding: Dr Tushar Patel, SPARSH Chest Disease Centre, 100B Swastik Society, Opposite
Samved Hospital, Navrangpura, Ahmedabad

CTRI/2020/10/028581  (Continued)

 
 

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Study name CIMMCov: a randomised clinical study for prevention of severe disease in mild-to-moderate COV-
ID-19 patients, using the inhaled medication ciclesonide

Methods Trial design: randomised, controlled, double-blind trial

Sample size: 138

Setting: outpatient

Language: English

Number of centres: not reported

Type of intervention: treatment

Participants Inclusion criteria:

• people admitted to a COVID-19 emergency department < 24 hours due to COVID-19-like symptoms

• people previously tested positive for COVID-19 at out-of-hospital test sites, hospital-driven dri-
ve-in testing sites, via a general practitioner etc., but with no previous hospital contact or admis-
sion due to COVID-19

• age ≥ 18 years

• positive COVID-19 PCR from oropharyngeal or nasopharyngeal swab or a tracheal suction fluid
sample

Exclusion criteria:

• treatment with ciclesonide within the last 3 months

• allergy to ciclesonide or other compounds in the inhalation formulation

• treatment with a potent CYP3A4 inhibitor (oral azoles, ritonavir)

• pregnancy

• negative urine β-human chorionic gonadotropin test required in fertile women

• breastfeeding

• insufficient inhaler or spacer technique (or both), including failure to use the supplied spacer de-
vice – investigator judged

Interventions Intervention group: inhaled ciclesonide 320 μg, twice daily

Control group: placebo: inhalation vapour, liquid

Concomitant therapy: no

Outcomes Primary outcome: reduction in healthcare resource utilisation (defined as renewed contact to gen-
eral practitioner, emergency department, admission to hospital, or a combination) due to COV-
ID-19-related symptoms at 28 days

Secondary outcomes: time to clinical recovery; intensive care unit admission rate; all-cause hos-
pitalisation at days 14 and 28; COVID-specific hospitalisation at days 14 and 28; symptom burden,
measured as change in Asthma Control Questionnaire, the COPD Assessment Test, and St George
Respiratory Questionnaire score at days 1, 14, 28 days; proportion of participants receiving me-
chanical ventilation during hospitalisations; mortality at days 14, 28, and 90; safety and tolerability
of the study drug (number of adverse effects, proportion of early discontinuation)

Starting date 29 April 2021

Contact information  

Notes Recruitment status: ongoing

Prospective completion date: not reported

EUCTR2020-002208-37-DK 

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Date last update was posted: not reported

Sponsor/funding: Respiratory Research Unit 237, Hvidovre Hospital, Denmark

EUCTR2020-002208-37-DK  (Continued)

 
 

Study name A multicenter, open-label, randomised controlled phase II study to evaluate the efficacy and safety
of inhaled ciclesonide for asymptomatic and mild patients with COVID-19 (RACCO trial)

Methods Trial design: randomised, open-label

Sample size: 90

Setting: outpatient

Language: English/Japanese

Number of centres: “multicentre”

Type of intervention: treatment

Participants Inclusion criteria:

• given written consent to participate in the study

• age > 20 years, regardless of sex

• SARS-CoV-2 PCR positive

• no apparent pneumonia due to COVID-19 on plain chest radiographs

• who can be hospitalised during study drug administration (including accommodation and med-
ical treatment)

• can inhale ciclesonide using inhalation assist device

Exclusion criteria:

• history of hypersensitivity to ciclesonide

• except for COVID-19, who have infectious disease or deep mycosis without an effective antibac-
terial agent

• using inhaled or oral steroids

• with fever of 37.5 °C for 7 days

• co-administering treatments that may have therapeutic effects on COVID-19

• considered inappropriate for inclusion in the study by the investigator

Interventions Intervention group: inhaled ciclesonide 400 µg 3 times per day

Control group: not reported

Concomitant therapy: not reported

Outcomes Primary outcome: pneumonia incidence on day 8 of ciclesonide inhalation

Secondary outcomes: changes in clinical findings; changes in laboratory findings; SARS-CoV-2 virus
genome amount; incidence rates of adverse events

Starting date 3 April 2020

Contact information Sugiyama Haruhito: [email protected]

Notes Recruitment status: “not recruiting”

JRCTS031190269 

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Prospective completion date: not reported

Date last update was posted: 24 September 2020

Sponsor/funding: not reported

JRCTS031190269  (Continued)

 
 

Study name Arrest respiratory failure from pneumonia (ARREST PNEUMONIA)

Methods Trial design: randomised, controlled, triple-blind trial

Sample size: 600

Setting: inpatient

Language: English

Number of centres: 10 academic medical centres

Type of intervention: treatment

Participants Inclusion criteria:

• severe pneumonia defined as hospitalisation for acute (< 7 days) onset of symptoms (cough, spu-
tum production, or dyspnoea) and radiographic evidence of pneumonia by chest radiograph or
CT scan and evidence of systemic inflammation (temperature < 35 °C or > 38 °C or white blood cell
count > or < upper or lower limits for site or PCT > 0.5 μg/L), or known current immunosuppression
preventing inflammatory response

• AND hypoxaemia defined as new requirement for supplemental oxygen with oxygen saturation
< 90% on room air, ≤ 96% on ≥ 2 L/minute oxygen, or > 6 L/minute or non-invasive ventilation
(regardless of oxygen saturation) at enrolment

• AND no clinical suspicion for COVID-19 pneumonia or confirmed negative test for SARS-CoV-2 in-
fection

Exclusion criteria:

• inability to obtain consent within 24 hours of presentation to emergency department

• intubation (or impending intubation) prior to enrolment (this does not include those patients re-
ceiving HFNC oxygen or non-invasive ventilation prior to enrolment)

• a condition requiring inhaled corticosteroids or beta-agonists, or chronic systemic steroid thera-
py equivalent to a dose >10 mg prednisone (this does not include patients receiving inhaled be-
ta-agonists in the emergency department without an established indication if treating clinician is
willing to discontinue subsequent treatments)

• chronic lung or neuromuscular disease requiring daytime oxygen or mechanical ventilation other
than for obstructive sleep apnoea or obesity hypoventilation syndrome

• not anticipated to survive > 48 hours or not expected to require > 48 hours of hospitalisation

• contraindication or known allergy to inhaled corticosteroids or beta-agonists

• patients with heart rate > 130 beats/minute, ventricular tachycardia, or new supraventricular
tachycardia within last 4 hours will be potentially eligible for enrolment after the condition has
resolved

• patients with potassium < 3.0 will be potentially eligible for enrolment after the condition has
resolved

• patient not committed to full support other than intubation or resuscitation (i.e. do not resusci-
tate/do not intubate status allowed)

• pregnancy

• incarcerated person

• physician refusal of consent to protocol

NCT04193878 

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• patient/surrogate refusal of consent to protocol

Interventions Intervention group: inhaled aerosolised formoterol 20 μg/2 mL and budesonide 1.0 mg/2 mL every
12 hours for 10 doses. Pulmicort Respules (budesonide) and Perforomist (formoterol)

Control group: placebo. aerosolised saline 4 mL of 0.9% saline twice daily for up to 5 days

Concomitant therapy: no

Outcomes Primary outcome: acute respiratory failure within 7 days of randomisation; HFNC or NIV (or both)
use for > 36 hours OR invasive mechanical ventilation for > 36 hours OR death in a patient placed on
respiratory support (HFNC, NIV, ventilator) who dies before 36 hours

Secondary outcome: hospital length of stay within 60 days of randomisation; duration of need for
supplemental oxygen within 60 days of randomisation; proportion of patients intubated for respi-
ratory failure within 7 days of randomisation

Starting date 1 June 2020

Contact information Principal Investigator: Joe Levitt, MD Stanford University

Principal Investigator: Emir Festic, MD Mayo Clinic

Notes Recruitment status: enrolling by invitation

Prospective completion date: 1 April 2024

Date last update was posted: 19 March 2021

Sponsor/funding: Stanford University

NCT04193878  (Continued)

 
 

Study name Trial of COVID-19 outpatient treatment in individuals with risk factors for aggravation (COVERAGE-
France)

Methods Trial design: multicentre, open-label, RCT

Sample size: 820

Setting: outpatient

Language: English

Number of centres: 11 centres

Type of intervention: treatment

Participants Inclusion criteria:

• clinical picture suggestive of COVID-19 dated ≤ 7 days

• positivity test proving an acute SARS-CoV-2 infection, according to current recommendations

• absence of criteria for hospitalisation or oxygen therapy according to current recommendations

NCT04356495 

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• age:
◦ ≥ 60 years with no risk factors

◦ 50–59 years and the presence of ≥ 1 of following risk factors:
▪ arterial hypertension under treatment (all stages)

▪ obesity (BMI ≥ 30 kg/m2)

▪ diabetes under treatment (all types)

▪ ischaemic heart disease (all stages)

▪ heart failure (all stages)

▪ stroke history

▪ chronic obstructive pulmonary disease (all stages)

▪ stage 3 chronic renal failure (30 ≤ estimated GFR < 60 mL/minute/1.73 m2)

▪ malignancies (solid tumours or blood malignancies) that are progressive or were diagnosed
< 5 years ago

▪ immunodeficiency

• of therapeutic origin (solid organ transplant or haematopoietic stem cell transplant, cancer
chemotherapy, immunosuppressive therapy, corticosteroids > 15 mg/day of prednisone equiva-
lent taken for ≥ 2 months)

• HIV infection with CD4 < 200/mm3

• valid, ambulatory person, fully able to understand the issues of the trial

• beneficiary of a social security scheme

• signed informed consent

Exclusion criteria:

• asymptomatic person

• inability to make a decision to participate (dementia, person under legal protection, curatorship,
or guardianship)

• ongoing illness or chronic treatment contraindicated by taking 1 of the trial drugs

Interventions Intervention group: inhaled ciclesonide 160 µg (2 puGs twice a day) for 10 days

Control group: vitamin supplement (“AZINC forme et vitalité”), 2 tablets daily for 10 days

Concomitant therapy: no

Outcomes Primary outcomes:

Pilot phase: proportion of participants who had a grade 3 or 4 adverse event from inclusion (day 0)
to day 14

Efficacy phase: death from inclusion (day 0) to day 14; proportion of participants with an occur-
rence of death

Efficacy phase: oxygen therapy from inclusion (day 0) to day 14; proportion of participants who had
an indication for oxygen therapy

Efficacy phase: hospitalisation from inclusion (day 0) to day 14; proportion of participants who had
an indication for hospitalisation

Secondary outcomes: proportion of hospitalisations, overall and by cause from inclusion (day 0)
to day 28; death and causes of death from inclusion (day 0) to day 28; proportion of intensive care
hospitalisations, overall and by cause from inclusion (day 0) to day 28; proportion of participants
with negative SARS-CoV-2 RT-PCR at day 7; haematological markers (white blood count, prothrom-
bin level, INR) evolution from inclusion (day 0) to day 7; inflammatory markers evolution (PCT, CRP)
from inclusion (day 0) to day 7; number and proportion of grade 1, 2, 3, 4 adverse events from in-
clusion (day 0) to day 28; number and proportion of grade 1, 2, 3, 4 adverse reactions from inclu-
sion (day 0) to day 28; acceptability of treatment assessed by interview from inclusion (day 0) to
day 10; proportion of participants who received ≥ 1 day of antibiotic therapy from inclusion (day 0)
to day 28; proportion of participants who experienced a worsening of oxygen saturation from inclu-

NCT04356495  (Continued)

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sion (day 0) to day 28; proportion of participants who completed the prescribed protocol treatment
from inclusion (day 0) to day 10

Starting date 29 July 2020

Contact information Denis MALVY, [email protected]

Xavier ANGLARET, [email protected]

Notes Recruitment status: recruiting

Prospective completion date: 29 January 2022

Date last update was posted: 3 August 2021

Sponsor/funding: University Hospital, Bordeaux, France

NCT04356495  (Continued)

 
 

Study name Inhalation of ciclesonide for patients with COVID-19: a randomised open treatment study (HALT
COVID-19)

Methods Trial design: randomised, multicentre, open-label

Sample size: 446

Setting: inpatient

Language: English

Number of centres: 6 centres recruiting

Type of intervention: treatment

Participants Inclusion criteria:

• aged ≥ 18 year who are willing and able to provide written informed consent

• laboratory-confirmed (PCR-positive) SARS-CoV-2 infection

• receiving supplemental oxygen therapy with start < 48 hours before inclusion

• negative pregnancy test (women of fertile age)

• agreeing to take highly effective contraceptive measures according to Clinical Trial Facilitation
Group criteria during the duration of treatment plus 7 days (women of fertile age)

Exclusion criteria:

• pregnant or breastfeeding women

• history of hypersensitivity to ciclesonide or other substances included in the treatment

• ongoing use of corticosteroids, ketoconazole, itraconazole, ritonavir, or nelfinavir

• receiving oxygen > 8 L/minute or > 50% oxygen with nasal high flow therapy

• ongoing or planned palliative care or an expected survival of < 72 hours

• expected admission to intensive care unit within 48 hours

• active or inactive pulmonary tuberculosis

• severe liver failure (Child-Pugh C)

• pulmonary arterial hypertension or fibrosis

• cognitive or physical impairment or insufficient language skills which precludes understanding
of information given about the study

• participation in a clinical trial within past 30 days

NCT04381364 

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Interventions Intervention group: inhaled ciclesonide 320 µg twice daily for 14 days

Control group: standard care

Concomitant therapy: no

Outcomes Primary outcome: duration of received supplemental oxygen therapy 30 days after study inclusion

Secondary outcome: invasive mechanical ventilation or all-cause death (key secondary outcome)
30 days after study inclusion; all-cause mortality 30 days after study inclusion; invasive mechani-
cal ventilation 30 days after study inclusion; remaining dyspnoea symptoms at 30–35 days and 5–7
months after inclusion

Starting date 29 May 2020

Contact information Daniel Brodin, MD; +46736313527; [email protected]

Daniel P Andersson, MD, PhD; +46704490004; [email protected]

Notes Recruitment status: recruiting

Prospective completion date: 1 December 2021

Date last update was posted: 10 May 2021

Sponsor/funding: Ola Blennow, St Goran’s Hospital, Stockholm, Sweden

NCT04381364  (Continued)

 
 

Study name Efficacy of inhaled therapies in the treatment of acute symptoms associated with COVID-19
(TRIVID)

Methods Trial design: open-label, RCT

Sample size: 260

Setting: probably inpatient

Language: English

Number of centres: not reported

Type of intervention: treatment

Participants Inclusion criteria:

• men or women aged ≥ 18 years

• PCR-positive SARS-CoV-2

• symptomatic participants must have ≥ 1 of the following symptoms: fever or self-reported fever
perception in the last 24 hours, headache, sore throat, dry cough, fatigue, chest pain or choking
sensation (without associating to respiratory distress), myalgia, anosmia, ageusia, or gastroin-
testinal symptoms with up to 10 days onset

• with oxygen saturation ≥ 92% in room air at inclusion

NCT04937543 

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• with the following haematological and biochemical laboratory parameters obtained in the period
of 7 days before day 0:
◦ haemoglobin > 9.0 g/dL

◦ absolute neutrophil count ≥ 1000 mm3

◦ platelets ≥ 100,000 mm3

◦ creatinine clearance ≥ 30 mL/minute using the Cockcroft-Gault formula

◦ alkaline phosphatase < 10 × upper limit of normal, AST and ALT < 10 × upper limit of normal

◦ negative pregnancy test

• Exclusion criteria:
◦ with moderate or severe acute respiratory failure or needing non-invasive ventilation or oxy-

gen, or with oxygen saturation < 92% or tachypnoea (respiratory rate ≥ 30 breaths/minute)

◦ with pre-existing, severe, and uncontrolled organ failure, which prevents participation in the
study by the investigator’s judgement (non-relevant cardiac disease)

◦ diagnosed with previous asthma using inhaled or oral corticosteroids in the last 4 weeks

◦ with previous use, in the last 10 days of randomisation, of inhaled, oral, or injectable corticos-
teroids

◦ with previous diagnosis of chronic obstructive pulmonary disease, even if they are not using
any inhaled medication

◦ pregnant or lactating women

◦ use of any product under investigation or unregistered within 3 months or within 5 half-lives
before baseline, whichever is longer

◦ hypersensitivity to the drug or its excipients

◦ any condition that, in the investigator’s opinion, could compromise the participant’s safety or
their adherence to the study protocol

Interventions Intervention group: inhaled beclomethasone (dose not stated) + standard care; beclometha-
sone/formoterol/glycopyrronium (dose not stated) + standard care

Control group: standard care

Concomitant therapy: no

Outcomes Primary outcome: proportion of participants using health resources 28 days after treatment

Secondary outcome: airway obstruction using spirometry 28 days after treatment; small airway ob-
struction using CT 28 days after treatment

Starting date 28 June 2021

Contact information Suzana Minamoto: [email protected]

Luana Pagan: [email protected]lunos.fmb.unesp.br

Notes Recruitment status: not yet recruiting

Prospective completion date: 30 October 2021

Date last update was posted: 30 June 2021

Sponsor/funding: UPECLIN HC FM Botucatu Unesp

NCT04937543  (Continued)

 
 

Study name FLuticasone in cOvid Treatment (FLOT)

Methods Trial design: open-label, RCT

NCT05054322 

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Sample size: 500

Setting: outpatient

Language: English

Number of centres: not reported

Type of intervention: treatment

Participants Inclusion criteria:

• signing consent to participate in the study

• having COVID-19-related symptoms within 5 days prior to randomisation

• confirmed diagnosis of COVID-19 by rapid antigen test or PCR test within 5 days prior to randomi-
sation

• aged > 50 years old or 18–49 years and have ≥ 1 risk factors for severe COVID-19

Exclusion criteria:

• pregnant or breastfeeding women

• allergy or contraindications (or both) to inhaled fluticasone

• current or previous administration of inhaled corticosteroids within the 15 days prior to randomi-
sation

• current or previous administration of high-dose systemic corticosteroids (> 3.75 mg dexametha-
sone/day or equivalent doses of other corticosteroids) or anticoagulants etc. ≥ 2 days within 15
days prior randomisation, or taking any other antiviral drugs (such as remdesivir, favipiravir, etc.)

• indication for start of systemic corticosteroids or oxygen therapy or hospitalisation due to COV-
ID-19 within next 24 hours

• already participated in other interventional COVID-19 studies

• any conditions for which the investigator believes that the patient should not participate for the
benefit of the patient or that would prevent, limit, or distort the evaluation of the study procedure

Interventions Intervention group: inhaled fluticasone 125 μg with spacer, 4 puGs, twice a day + standard care

Control group: standard care

Concomitant therapy: no

Outcomes Primary outcome: incidence of adverse outcomes day 28 after randomisation

Secondary outcomes: duration of isolation based on WHO’s criteria day 28 after randomisation; in-
cidence of patients with oxygen saturation by pulse oximetry (oxygen saturation) < 94% day 28 af-
ter randomisation; self-reported recovery rate day 28 after randomisation

Starting date 22 September 2021

Contact information Thi Tuyet Lan Le, PhD, MD; [email protected]

Notes Recruitment status: recruiting

Prospective completion date: 31 January 2022

Date last update was posted: 23 September 2021

Sponsor/funding: University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam

NCT05054322  (Continued)

 
 

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Study name Arformoterol/budesonide for COVID-19 (ABC)

Methods Trial design: randomised, controlled, triple-blind trial

Sample size: 140

Setting: unclear, probably outpatient

Language: English

Number of centres: not reported

Type of intervention (treatment/prevention): treatment

Participants Inclusion criteria:

• adults aged ≥ 19 years

• new onset of symptoms suggestive of COVID-19 (fever, cough, sore throat, etc.) or diagnosed with
COVID-19 within 7 days of participant being seen at visit 1

• in the Investigator’s opinion, is able and willing to comply with all trial requirements

Exclusion criteria:

• a condition requiring invasive oxygen support

• history of hypersensitivity to budesonide and arformoterol

• pregnancy, breastfeeding

• participation in other clinical studies within 4 weeks prior to enrolment in this study

• refusal of the patient to continue participating in the study/withdrawal of informed consent by
the patient

Interventions Intervention group: inhaled budesonide/arformoterol dry powder inhaler 3 inhalations twice daily
at 3 days and 2 inhalations twice daily at 11 days

Control group: placebo for 2 weeks

Concomitant therapy: no

Outcomes Primary outcome: time to clinical improvement on WHO Ordinal Scale at 28 days

Secondary outcomes: WHO Ordinal Scale for Clinical Improvement at 28 days; WHO Ordinal Scale
change at 28 days; clinical cure rate at 28 days

Starting date 1 November 2021

Contact information Korea United Pharm Inc.

Notes Recruitment status: not yet recruiting

Prospective completion date: 1 October 2022

Date last update was posted: 24 September 2021

Sponsor/funding: Korea United Pharm. Inc.

NCT05055414 

ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; COPD: chronic obstructive pulmonary disease;
COVID-19: coronavirus disease 2019; CRP: C-reactive protein; CT: computer tomography; GFR: glomerular filtration rate; HFNC: high flow
nasal cannula; INR: international normalised ratio; NIV: non-invasive ventilation; PCR: polymerase chain reaction; PCT: procalcitonin; RCT:
randomised controlled trial; RT-PCR: real-time polymerase chain reaction; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2;
WHO: World Health Organization.
 

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R I S K   O F   B I A S

Legend:     Low risk of bias      High risk of bias      Some concerns     

 
Risk of bias for analysis 1.1 All-cause mortality at up to day 30

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

Ramakrishnan
2021

Yu 2021

 
 
Risk of bias for analysis 1.2 Admission to hospital or death at up to 30 days

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

Yu 2021

 
 
Risk of bias for analysis 1.3 Symptom resolution: all initial symptoms resolved (asymptomatic) at day 14

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

Yu 2021

 
 

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Risk of bias for analysis 1.4 Symptom resolution: mean time to recovery (days)

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Ramakrishnan
2021

 
 
Risk of bias for analysis 1.5 Symptom resolution: all initial symptoms resolved at up to day 30

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

 
 
Risk of bias for analysis 1.6 Quality of life at day 28: mean in well-being (WHO-5 Well-Being Questionnaire)

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Yu 2021

 
 
Risk of bias for analysis 1.7 Serious adverse events

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Yu 2021

 
 

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Risk of bias for analysis 1.8 Adverse events

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

 
 
Risk of bias for analysis 1.9 Infections

Bias

Study Randomisation
process

Deviations
from intended
interventions

Missing
outcome data

Measurement
of the outcome

Selection of
the reported

results

Overall

Clemency 2021

 

 

D A T A   A N D   A N A L Y S E S

 

Comparison 1.   Inhaled corticosteroids (plus standard care) versus standard care (with or without placebo)

Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

1.1 All-cause mortality at up to day 30 3 2132 Risk Ratio (M-H, Random,
95% CI)

0.61 [0.22, 1.67]

1.2 Admission to hospital or death at
up to 30 days

2 2025 Risk Ratio (M-H, Random,
95% CI)

0.72 [0.51, 0.99]

1.3 Symptom resolution: all initial
symptoms resolved (asymptomatic) at
day 14

2 1986 Risk Ratio (M-H, Random,
95% CI)

1.19 [1.09, 1.30]

1.4 Symptom resolution: mean time to
recovery (days)

1   Mean Difference (IV, Ran-
dom, 95% CI)

Totals not select-
ed

1.5 Symptom resolution: all initial
symptoms resolved at up to day 30

1   Risk Ratio (M-H, Random,
95% CI)

Totals not select-
ed

1.6 Quality of life at day 28: mean in
well-being (WHO-5 Well-Being Ques-
tionnaire)

1   Mean Difference (IV, Ran-
dom, 95% CI)

Totals not select-
ed

1.7 Serious adverse events 1   Risk Ratio (M-H, Random,
95% CI)

Totals not select-
ed

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Outcome or subgroup title No. of studies No. of partici-
pants

Statistical method Effect size

1.8 Adverse events 1   Risk Ratio (M-H, Random,
95% CI)

Totals not select-
ed

1.9 Infections 1   Risk Ratio (M-H, Random,
95% CI)

Totals not select-
ed

 
 

Analysis 1.1.   Comparison 1: Inhaled corticosteroids (plus standard care) versus
standard care (with or without placebo), Outcome 1: All-cause mortality at up to day 30

Study or Subgroup

Clemency 2021
Ramakrishnan 2021
Yu 2021

Total (95% CI)
Total events:
Heterogeneity: Not applicable
Test for overall effect: Z = 0.96 (P = 0.33)
Test for subgroup differences: Not applicable

Inhaled corticosteroid (plus standard care)
Events

0
0
6

6

Total

197
73

787

1057

Standard care (with/without placebo)
Events

0
0

10

10

Total

203
73

799

1075

Weight

100.0%

100.0%

Risk Ratio
M-H, Random, 95% CI

Not estimable
Not estimable

0.61 [0.22 , 1.67]

0.61 [0.22 , 1.67]

Risk Ratio
M-H, Random, 95% CI

0.1 0.2 0.5 1 2 5 10
Favours inhaled corticosteroid (plus standard care) Favours standard care (with/without placebo)

Risk of Bias
A

+
+
+

B

+
+
+

C

+
+
+

D

+
+
+

E

+
?
+

F

+
?
+

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.2.   Comparison 1: Inhaled corticosteroids (plus standard care) versus standard
care (with or without placebo), Outcome 2: Admission to hospital or death at up to 30 days

Study or Subgroup

Clemency 2021
Yu 2021

Total (95% CI)
Total events:
Heterogeneity: Tau² = 0.00; Chi² = 0.53, df = 1 (P = 0.47); I² = 0%
Test for overall effect: Z = 1.99 (P = 0.05)
Test for subgroup differences: Not applicable

Inhaled corticosteroid (plus standard care)
Events

3
52

55

Total

197
787

984

Standard care (with/without placebo)
Events

7
75

82

Total

203
838

1041

Weight

6.1%
93.9%

100.0%

Risk Ratio
M-H, Random, 95% CI

0.44 [0.12 , 1.68]
0.74 [0.53 , 1.04]

0.72 [0.51 , 0.99]

Risk Ratio
M-H, Random, 95% CI

0.1 0.2 0.5 1 2 5 10
Favours inhaled corticosteroid (plus standard care) Favours standard care (with/without placebo)

Risk of Bias
A

+
+

B

+
+

C

+
+

D

+
+

E

+
+

F

+
+

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Inhaled corticosteroids for the treatment of COVID-19 (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

53

Cochrane
Library

Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

Analysis 1.3.   Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or
without placebo), Outcome 3: Symptom resolution: all initial symptoms resolved (asymptomatic) at day 14

Study or Subgroup

Clemency 2021
Yu 2021

Total (95% CI)
Total events:
Heterogeneity: Tau² = 0.00; Chi² = 0.47, df = 1 (P = 0.49); I² = 0%
Test for overall effect: Z = 3.94 (P < 0.0001)
Test for subgroup differences: Not applicable

Inhaled corticosteroid (plus standard care)
Events

81
462

543

Total

197
787

984

Standard care (with/without placebo)
Events

76
390

466

Total

203
799

1002

Weight

12.5%
87.5%

100.0%

Risk Ratio
M-H, Random, 95% CI

1.10 [0.86 , 1.40]
1.20 [1.10 , 1.32]

1.19 [1.09 , 1.30]

Risk Ratio
M-H, Random, 95% CI

0.5 0.7 1 1.5 2
Favours standard care (with/without placebo) Favours inhaled corticosteroid (plus standard care)

Risk of Bias
A

+
+

B

+
+

C

+
+

D

+

E


+

F


Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.4.   Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care
(with or without placebo), Outcome 4: Symptom resolution: mean time to recovery (days)

Study or Subgroup

Ramakrishnan 2021

Inhaled corticosteroids (plus standard care)
Mean

8

SD

5

Total

70

Standard care (with/without placebo)
Mean

12

SD

8

Total

69

Mean Difference
IV, Random, 95% CI

-4.00 [-6.22 , -1.78]

Mean Difference
IV, Random, 95% CI

-10 -5 0 5 10
Favours inhaled corticosteroids (plus standard care) Favours standard care (with/without placebo)

Risk of Bias
A

+

B

+

C

+

D

E

?

F

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.5.   Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with
or without placebo), Outcome 5: Symptom resolution: all initial symptoms resolved at up to day 30

Study or Subgroup

Clemency 2021

Inhaled corticosteroids (plus standard care)
Events

139

Total

197

Placebo (plus standard care)
Events

129

Total

203

Risk Ratio
M-H, Random, 95% CI

1.11 [0.97 , 1.27]

Risk Ratio
M-H, Random, 95% CI

0.5 0.7 1 1.5 2
Favours placebo (plus standard care) Favours inhaled corticosteroids (plus standard care)

Risk of Bias
A

+

B

+

C

+

D

+

E

F

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.6.   Comparison 1: Inhaled corticosteroids (plus standard care) versus standard care (with or
without placebo), Outcome 6: Quality of life at day 28: mean in well-being (WHO-5 Well-Being Questionnaire)

Study or Subgroup

Yu 2021

Inhaled corticosteroids (plus standard care)
Mean

54.6

SD

25.1

Total

713

Standard care (with/without placebo)
Mean

52

SD

24.8

Total

721

Mean Difference
IV, Random, 95% CI

2.60 [0.02 , 5.18]

Mean Difference
IV, Random, 95% CI

-10 -5 0 5 10
Favours standard care (with/without placebo) Favours inhaled corticosteroids (plus standard care)

Risk of Bias
A

+

B

+

C

+

D

E

+

F

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Inhaled corticosteroids for the treatment of COVID-19 (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

54

Cochrane
Library

Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

Analysis 1.7.   Comparison 1: Inhaled corticosteroids (plus standard care) versus
standard care (with or without placebo), Outcome 7: Serious adverse events

Study or Subgroup

Yu 2021

Inhaled corticosteroids (plus standard care)
Events

2

Total

787

Standard care (with/without placebo)
Events

4

Total

799

Risk Ratio
M-H, Random, 95% CI

0.51 [0.09 , 2.76]

Risk Ratio
M-H, Random, 95% CI

0.05 0.2 1 5 20
Favours inhaled corticosteroids (plus standard care) Favours standard care (with/without placebo)

Risk of Bias
A

+

B

+

C

+

D

E

+

F

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.8.   Comparison 1: Inhaled corticosteroids (plus standard care)
versus standard care (with or without placebo), Outcome 8: Adverse events

Study or Subgroup

Clemency 2021

Inhaled corticosteroid (plus standard care)
Events

22

Total

197

Standard care (with/without placebo)
Events

29

Total

203

Risk Ratio
M-H, Random, 95% CI

0.78 [0.47 , 1.31]

Risk Ratio
M-H, Random, 95% CI

0.005 0.1 1 10 200
Favours inhaled corticosteroid (plus standard care) Favours standard care (with/without placebo)

Risk of Bias
A

+

B

+

C

+

D

+

E

+

F

+

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 
 

Analysis 1.9.   Comparison 1: Inhaled corticosteroids (plus standard care)
versus standard care (with or without placebo), Outcome 9: Infections

Study or Subgroup

Clemency 2021

Inhaled corticosteroids(plus standard care)
Events

6

Total

197

Placebo (plus standard care)
Events

7

Total

203

Risk Ratio
M-H, Random, 95% CI

0.88 [0.30 , 2.58]

Risk Ratio
M-H, Random, 95% CI

0.02 0.1 1 10 50
Favours inhaled corticosteroids (plus standard care) Favours placebo (plus standard care)

Risk of Bias
A

+

B

+

C

+

D

+

E

+

F

+

Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias

 

 

Inhaled corticosteroids for the treatment of COVID-19 (Review)

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

55

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6

A D D I T I O N A L   T A B L E S

Study ID Intervention and regi-
men

Control Randomised
to steroids
and analysed
in this review

Randomised
to control
and analysed
in this review

Design Setting Population/disease severity at ran-
domisation

Clemency
2021

Ciclesonide 160 μg per ac-
tuation, 2 actuations twice
daily (total daily dose 640
μg) + standard care

Placebo +
standard care

197 203 Double-blind
RCT

Outpatient Participants had an oxygen satura-
tion of ≥ 93% on room air; had ≥ 1
of the following symptoms of COV-
ID-19: fever, cough, or dyspnoea

Ramakrish-
nan 2021

Budesonide, 400 µg per
actuation (2 puGs twice
daily; total dose 1600 µg)
+ standard care (antipyret-
ics and honey)

Standard care 73 73 Open-label,
RCT

Outpatient With symptoms of COVID-19 (new-
onset cough and fever or anosmia, or
both) within 7 days

Yu 2021 Budesonide 800 µg twice
daily + standard care for
14 days

Standard care 787 (analysed
concurrent
and SARS-
CoV-2-posi-
tive popula-
tion)

838 (analysed
concurrent
andSARS-
CoV-2-posi-
tive popula-
tion)

Open-label,
platform trial

Outpatient Ongoing symptoms of confirmed or
suspected COVID-19 (high temper-
ature or new, continuous cough or
change in sense of smell/taste, or a
combination of these) within 14 days

Table 1.   Characteristics of included studies for the comparison: inhaled corticosteroid plus standard care versus standard care (with or without
placebo) 

RCT: randomised controlled trial; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.
 
 

Study ID Sponsor/developer Design Population/disease severity Setting Intervention Control Number
of partici-
pants

Status

Alsultan
2021

Not stated RCT Excluded: expired or trans-
mitted to ICU during the first
24 hours

Included: oxygen saturation ≤
93%

Inpatient Budesonide
+ supportive
care

Supportive
care

49 Completed

Table 2.   Characteristics of studies awaiting classification 

C
o
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ra

n
e

L
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T
ru

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lth

.

  

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tic

R
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7

EUC-
TR2020-001616-18-ES/
NCT04355637

Fundacion Clinic per a la
Recerca Biomédica

RCT Admitted for pneumonia (sta-
tus #3 and #4 OMS scale)

Inpatient Budesonide Placebo 300 Completed

NCT04331054 Assistance Publique –
Hôpitaux de Paris

RCT Hospitalised, but not admit-
ted to ICU

Inpatient SYMBICORT
RAPIHALER +
standard care

Standard
care

146 Terminated
(insufficient
recruitment)

NCT04435795 McGill University Health
Centre/Research Insti-
tute of the McGill Univer-
sity Health Centre

RCT Symptomatic adults positive
by PCR for COVID-19 within 5
days of enrolment with fever,
cough, or shortness of breath

Outpatient Ciclesonide
intranasal
and inhaled

Placebo 215 Terminated
(could not
meet target
enrolment)

Song 2021 National Research
Foundation of Ko-
rea (NRF) grant
[2020M3A9I2081699]
and Korea Universi-
ty Guro Hospital grant
(I2000171)

RCT Low National Early Warning
Score

Probably in-
patient

Ciclesonide
+ hydroxy-
chloroquine

Standard
care

61 Setting un-
clear; no
data for ci-
clesonide
alone vs stan-
dard care

Table 2.   Characteristics of studies awaiting classification  (Continued)

COVID-19: coronavirus disease 2019; ICU: intensive care unit; PCR: polymerase chain reaction; RCT: randomised controlled trial.
 
 

Study ID Sponsor/de-
veloper

Design Population/disease severity Setting Interven-
tion

Control Number
of partici-
pants

Status

NCT04193878 Stanford Uni-
versity

Triple-blind,
RCT

Severe pneumonia defined as hospitalisa-
tion for acute (< 7 days) onset of symptoms
(cough, sputum production, or dyspnoea)
and radiographic evidence of pneumonia by
chest radiograph or CT scan and evidence of
systemic inflammation (temperature < 35 °C
or > 38 °C or WBC count > or < upper or low-
er limits for site or procalcitonin > 0.5 μg/L),
or known current immunosuppression pre-
venting inflammatory response AND hypox-
aemia defined as new requirement for sup-
plemental oxygen with oxygen saturation
< 90% on room air, ≤ 96% on ≥ 2 L/minute

Inpatient Formoterol
+ budes-
onide

Placebo 600 Enrolling by
invitation

Table 3.   Characteristics of ongoing studies 

C
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ra
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In

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s.

B
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.

  

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R
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5
8

oxygen, or > 6 L/minute or NIV (regardless of
oxygen saturation) at enrolment

NCT04381364 Ola Blennow,
St Goran’s
Hospital

Open-label,
RCT

People with PCR-positive SARS-CoV-2 re-
ceiving supplemental oxygen therapy with
start < 48 hours

Inpatient Ciclesonide Standard
care

446 Recruiting

NCT04937543 UPECLIN HC
FM Botucatu
Unesp

Open-label,
RCT

People with PCR-positive SARS-CoV-2 with
arterial pulse oximetry (oxygen saturation)
saturation ≥ 92% in room air

Probably in-
patient

Be-
clometha-
sone +
standard
care; be-
clometha-
sone/for-
moterol/gly-
copyrroni-
um + stan-
dard care

Standard
care

260 Not yet re-
cruiting

NCT04356495 University
Hospital, Bor-
deaux

Open-label,
RCT

SARS-CoV-2-confirmed cases with absence
of criteria for hospitalisation or oxygen ther-
apy

Outpatient Ciclesonide Vitamin D 820 Recruiting

JRC-
TS031190269

Not reported Open-label,
RCT

SARS-CoV-2-positive cases with no appar-
ent pneumonia due to COVID-19

Outpatient Ciclesonide Not report-
ed

90 Not recruit-
ing

CTRI/2020/04/024948Lady
Hardinge
Medical Col-
lege

RCT Presence of moderate COVID-19 disease as
defined by presence of pneumonia (clini-
cal and radiological signs) with respiratory
rate 15–30/minute or oxygen saturation 90–
94% on room air (or both). PCR throat swab-
positive patients and contacts of confirmed
COVID-19 cases will be considered as a COV-
ID-19 case

Inpatient Ciclesonide Standard
care

120 Not yet re-
cruiting

CTRI/2020/10/028581Dr Tushar Pa-
tel, SPARSH
Chest Disease
Centre, 100B
Swastik So-
ciety, Oppo-
site Samved
Hospital,

RCT Asymptomatic people with mild symptoms
of < 5 days of duration;

oxygen saturation > 94% at room air

Outpatient Budesonide
+ standard
care

Standard
care

1000 Not yet re-
cruiting

Table 3.   Characteristics of ongoing studies  (Continued)
C
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R
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In
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rtico
ste

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Navrangpura,
Ahmedabad

EUC-
TR2020-002208-37-DK

Respiratory
Research Unit
237, Hvidovre
Hospital, Den-
mark

Dou-
ble-blind,
RCT

People admitted to a COVID-19 emergency
department < 24 hours due to COVID-19-like
symptoms

Outpatient Ciclesonide Placebo 138 Ongoing

NCT05054322 University of
Medicine and
Pharmacy at
Ho Chi Minh
City

Open-label,
RCT

Having COVID-related symptoms within 5
days prior to randomisation

Outpatient Fluticasone
+ standard
care

Standard
care

500 Recruiting

NCT05055414 Korea United
Pharm. Inc.

Triple-blind,
RCT

New onset of symptoms suggestive of COV-
ID-19 (fever, cough, sore throat, etc.) or di-
agnosed with COVID-19 within 7 days of par-
ticipant being seen at visit 1

Unclear,
probably
outpatient

Budes-
onide/arfor-
moterol

Placebo 140 Not yet re-
cruiting

Table 3.   Characteristics of ongoing studies  (Continued)

COVID-19: coronavirus disease 2019; CT: computer tomography; NIV: non-invasive ventilation; PCR: polymerase chain reaction; RCT: randomised controlled trial; SARS-CoV-2:
severe acute respiratory syndrome coronavirus 2; WBC: white blood cell.
 

C
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In

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isio

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s.

B
e
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Cochrane
Library

Trusted evidence.
Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

 

Outcome Main analyses Risk of bias (excluding studies at
high risk of bias)

Fixed-effect vs ran-
dom-effects model

Preprint vs journal
publication

All-cause mortal-
ity at up to day
30

RR 0.61, 95% CI
0.22 to 1.67; 3
studies, 2132 par-
ticipants

There were no RCTs with high risk
of bias concerning this outcome.

RR 0.61, 95% CI 0.22 to
1.67; 3 studies, 2132 par-
ticipants

RR 0.61, 95% CI 0.22 to
1.67; 3 studies, 2132
participants

Table 4.   Sensitivity analyses for the comparison: inhaled corticosteroids plus standard care versus standard care
with or without placebo 

CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
 

 

A P P E N D I C E S

Appendix 1. Search strategies

The search strategy was used to inform two Cochrane Reviews (inhaled and systemic corticosteroids, therefore also including search terms
related to systemic corticosteroids).

Cochrane COVID-19 Study Register

Search string:

corticosteroid* OR corticoid* OR prednison* OR dehydrocortison* OR deltason* OR decortin* OR orasone* OR deltra* OR meticorten* OR
cortancyl* OR deltacorten* OR dacortin* OR adasone* OR “delta-cortison” OR panasol* OR decorton* OR metacortandracin* OR paracort*
OR predicor* OR decortisyl* OR delta-1-cortison* OR “delta-dome” OR deltadehydrocortison* OR ofisolon* OR panafcort* OR predicorten*
OR predni* OR econonson* OR promifen* OR servison* OR deltison* OR lisacort* OR meproson* OR rayos OR sterapred* OR “liquid pred”
OR cortan* OR rectodelt* OR predeltin* OR prednisolon* OR methylprednisolon* OR medrol OR “pred forte” OR medrone OR urbason
OR wyacort OR “Delta-F” OR duralon* OR medrate OR omnipred OR adlone OR caberdelta OR depmedalon* OR “Depo Moderin” OR
“Depo-Nisolone” OR Emmetipi OR esameton* OR firmacort OR medlon* OR “Mega-Star” OR meprolon* OR metilbetason* OR metrocort OR
metypresol OR metysolon* OR orapred OR “Predni-M-Tablinen” OR radilem OR sieropresol OR solpredon* OR “A-MethaPred” OR prelone
OR medrone OR aprednislon OR pediapred OR hostacortin OR “Di-Adreson-F” OR adnisolon* OR capsoid OR cortalon* OR cortisolon* OR
deltacortril OR estilsona OR panafcortelone OR sterane OR “Delta-Cortef” OR econopred OR dacortin OR decaprednil OR “Delta-Diona” OR
“Delta-Phoricol” OR deltahydrocortison* OR deltasolon* OR deltidrosol OR dhasolone OR fisopred OR frisolona OR gupison* OR hydeltra
OR hydeltrasol OR klismacort OR kuhlprednon OR lenisolon* OR “Lepi-Cortinolo” OR “Linola-H” OR longiprednil OR metacortandralon*
OR “Meti Derm” OR meticortelon* OR opredsone Or precortisyl OR “Pred-Clysma” OR predeltilon* OR prenilone OR hydrocortancyl OR
“Solu Moderin” OR predonin* OR metypred OR prednisol OR dexamethason* OR “BB 1101” OR decadron OR hexadrol OR fortecortin
OR dexameth OR dexone OR hexadecadrol OR desamethason* OR ozurdex OR deronil OR baycuten OR aacidexam OR spersadex OR
dexacortal OR gammacorten OR visumetazon* OR adexone OR “Alba-Dex” OR cortidexason OR decacort OR decadrol OR dectancyl OR
desameton OR loverine OR millicorten OR orgadrone OR alin OR auxiloson OR cortisumman OR decalix OR decameth OR decasone
OR dekacort OR deltafluorene OR “Dexa-Mamallet” OR dexafluorene OR dexalocal OR dexamecortin OR dexamonozon OR dexapos OR
dexinoral OR fluorodelta OR lokalison OR methylfluorprednisolon* OR mymethason* OR “Dexa-Rhinosan” OR “Dexa-Scheroson” OR “Dexa-
sine” OR dexacortin OR dexafarma OR dinormon OR baycadron OR “Aeroseb-Dex” OR Maxidex OR Dextenza OR dexasone OR dexpak OR
hydrocortison* OR cortisol OR cortef OR hydrocorton* OR cetacort OR barseb OR aeroseb OR “Cort-Dome” OR cortenema OR cortril OR
cortifan OR cortispray OR dermacort OR domolene OR eldecort OR hautosone OR “Heb-Cort” OR hytone OR Komed OR Nutracort OR
Proctocort OR Rectoid OR Hydrocort OR locoid OR Solu-Glyc OR glucocorticoid* OR alclometason* OR amcinonid* OR beclomethason*
OR betamethason* OR budesonid* OR ciclesonid* OR clobetas* OR clocortolon* OR desoximetason* OR dichlorison* OR diflorason*
OR diflucortolon* OR difluprednate OR drocinonid* OR flumethason* OR fluocinolon* OR fluocinonid* OR fluocortin OR fluocortolon*
OR fluorometholon* OR fluperolon* OR flupredni* OR flurandrenolone* OR fluticason* OR FX006 OR halometason* OR medryson* OR
melengestrol OR paramethason* OR rimexolon* OR terofenamat* OR triamcinolon* OR mometason*

Study characteristics:
1) “Intervention assignment”: “Randomised” OR
2) “Study design”: “Parallel/Crossover” AND “Unclear” OR
3) “Study type”: “Adaptive/Platform”
= 324 studies (552 references)

Selections on the CCSR used to monitor RCTs and quasi RCTs on a weekly basis:

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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Cochrane Database of Systematic Reviews

Results available: “Report Results”
Study type: “Interventional”
Intervention assignment: “Randomised” or “Quasi Randomised”

Web of Science Core Collection (Advanced search)

#1 TI=( corticosteroid* OR corticoid* OR prednison* OR dehydrocortison* OR deltason* OR decortin* OR orasone* OR deltra* OR meticorten*
OR cortancyl* OR deltacorten* OR dacortin* OR adasone* OR “delta-cortison” OR panasol* OR decorton* OR metacortandracin* OR
paracort* OR predicor* OR decortisyl* OR delta-1-cortison* OR “delta-dome” OR deltadehydrocortison* OR ofisolon* OR panafcort* OR
predicorten* OR predni* OR econonson* OR promifen* OR servison* OR deltison* OR lisacort* OR meproson* OR rayos OR sterapred* OR
“liquid pred” OR cortan* OR rectodelt* OR predeltin* OR prednisolon* OR methylprednisolon* OR medrol OR “pred forte” OR medrone
OR urbason OR wyacort OR “Delta-F” OR duralon* OR medrate OR omnipred OR adlone OR caberdelta OR depmedalon* OR “Depo
Moderin” OR “Depo-Nisolone” OR Emmetipi OR esameton* OR firmacort OR medlon* OR “Mega-Star” OR meprolon* OR metilbetason* OR
metrocort OR metypresol OR metysolon* OR orapred OR “Predni-M-Tablinen” OR radilem OR sieropresol OR solpredon* OR “A-MethaPred”
OR prelone OR medrone OR aprednislon OR pediapred OR hostacortin OR “Di-Adreson-F” OR adnisolon* OR capsoid OR cortalon* OR
cortisolon* OR deltacortril OR estilsona OR panafcortelone OR sterane OR “Delta-Cortef” OR econopred OR dacortin OR decaprednil OR
“Delta-Diona” OR “Delta-Phoricol” OR deltahydrocortison* OR deltasolon* OR deltidrosol OR dhasolone OR fisopred OR frisolona OR
gupison* OR hydeltra OR hydeltrasol OR klismacort OR kuhlprednon OR lenisolon* OR “Lepi-Cortinolo” OR “Linola-H” OR longiprednil OR
metacortandralon* OR “Meti Derm” OR meticortelon* OR opredsone Or precortisyl OR “Pred-Clysma” OR predeltilon* OR prenilone OR
hydrocortancyl OR “Solu Moderin” OR predonin* OR metypred OR prednisol OR dexamethason* OR “BB 1101” OR decadron OR hexadrol OR
fortecortin OR dexameth OR dexone OR hexadecadrol OR desamethason* OR ozurdex OR deronil OR baycuten OR aacidexam OR spersadex
OR dexacortal OR gammacorten OR visumetazon* OR adexone OR “Alba-Dex” OR cortidexason OR decacort OR decadrol OR dectancyl
OR desameton OR loverine OR millicorten OR orgadrone OR alin OR auxiloson OR cortisumman OR decalix OR decameth OR decasone
OR dekacort OR deltafluorene OR “Dexa-Mamallet” OR dexafluorene OR dexalocal OR dexamecortin OR dexamonozon OR dexapos OR
dexinoral OR fluorodelta OR lokalison OR methylfluorprednisolon* OR mymethason* OR “Dexa-Rhinosan” OR “Dexa-Scheroson” OR “Dexa-
sine” OR dexacortin OR dexafarma OR dinormon OR baycadron OR “Aeroseb-Dex” OR Maxidex OR Dextenza OR dexasone OR dexpak OR
hydrocortison* OR cortisol OR cortef OR hydrocorton* OR cetacort OR barseb OR aeroseb OR “Cort-Dome” OR cortenema OR cortril OR
cortifan OR cortispray OR dermacort OR domolene OR eldecort OR hautosone OR “Heb-Cort” OR hytone OR Komed OR Nutracort OR
Proctocort OR Rectoid OR Hydrocort OR locoid OR Solu-Glyc OR glucocorticoid* OR alclometason* OR amcinonid* OR beclomethason*
OR betamethason* OR budesonid* OR ciclesonid* OR clobetas* OR clocortolon* OR desoximetason* OR dichlorison* OR diflorason*
OR diflucortolon* OR difluprednate OR drocinonid* OR flumethason* OR fluocinolon* OR fluocinonid* OR fluocortin OR fluocortolon*
OR fluorometholon* OR fluperolon* OR flupredni* OR flurandrenolone* OR fluticason* OR FX006 OR halometason* OR medryson* OR
melengestrol OR paramethason* OR rimexolon* OR terofenamat* OR triamcinolon* OR mometason*) OR AB=( corticosteroid* OR corticoid*
OR prednison* OR dehydrocortison* OR deltason* OR decortin* OR orasone* OR deltra* OR meticorten* OR cortancyl* OR deltacorten* OR
dacortin* OR adasone* OR “delta-cortison” OR panasol* OR decorton* OR metacortandracin* OR paracort* OR predicor* OR decortisyl*
OR delta-1-cortison* OR “delta-dome” OR deltadehydrocortison* OR ofisolon* OR panafcort* OR predicorten* OR predni* OR econonson*
OR promifen* OR servison* OR deltison* OR lisacort* OR meproson* OR rayos OR sterapred* OR “liquid pred” OR cortan* OR rectodelt*
OR predeltin* OR prednisolon* OR methylprednisolon* OR medrol OR “pred forte” OR medrone OR urbason OR wyacort OR “Delta-F” OR
duralon* OR medrate OR omnipred OR adlone OR caberdelta OR depmedalon* OR “Depo Moderin” OR “Depo-Nisolone” OR Emmetipi OR
esameton* OR firmacort OR medlon* OR “Mega-Star” OR meprolon* OR metilbetason* OR metrocort OR metypresol OR metysolon* OR
orapred OR “Predni-M-Tablinen” OR radilem OR sieropresol OR solpredon* OR “A-MethaPred” OR prelone OR medrone OR aprednislon
OR pediapred OR hostacortin OR “Di-Adreson-F” OR adnisolon* OR capsoid OR cortalon* OR cortisolon* OR deltacortril OR estilsona
OR panafcortelone OR sterane OR “Delta-Cortef” OR econopred OR dacortin OR decaprednil OR “Delta-Diona” OR “Delta-Phoricol” OR
deltahydrocortison* OR deltasolon* OR deltidrosol OR dhasolone OR fisopred OR frisolona OR gupison* OR hydeltra OR hydeltrasol OR
klismacort OR kuhlprednon OR lenisolon* OR “Lepi-Cortinolo” OR “Linola-H” OR longiprednil OR metacortandralon* OR “Meti Derm” OR
meticortelon* OR opredsone Or precortisyl OR “Pred-Clysma” OR predeltilon* OR prenilone OR hydrocortancyl OR “Solu Moderin” OR
predonin* OR metypred OR prednisol OR dexamethason* OR “BB 1101” OR decadron OR hexadrol OR fortecortin OR dexameth OR dexone
OR hexadecadrol OR desamethason* OR ozurdex OR deronil OR baycuten OR aacidexam OR spersadex OR dexacortal OR gammacorten OR
visumetazon* OR adexone OR “Alba-Dex” OR cortidexason OR decacort OR decadrol OR dectancyl OR desameton OR loverine OR millicorten
OR orgadrone OR alin OR auxiloson OR cortisumman OR decalix OR decameth OR decasone OR dekacort OR deltafluorene OR “Dexa-
Mamallet” OR dexafluorene OR dexalocal OR dexamecortin OR dexamonozon OR dexapos OR dexinoral OR fluorodelta OR lokalison OR
methylfluorprednisolon* OR mymethason* OR “Dexa-Rhinosan” OR “Dexa-Scheroson” OR “Dexa-sine” OR dexacortin OR dexafarma OR
dinormon OR baycadron OR “Aeroseb-Dex” OR Maxidex OR Dextenza OR dexasone OR dexpak OR hydrocortison* OR cortisol OR cortef OR
hydrocorton* OR cetacort OR barseb OR aeroseb OR “Cort-Dome” OR cortenema OR cortril OR cortifan OR cortispray OR dermacort OR
domolene OR eldecort OR hautosone OR “Heb-Cort” OR hytone OR Komed OR Nutracort OR Proctocort OR Rectoid OR Hydrocort OR locoid
OR Solu-Glyc OR glucocorticoid* OR alclometason* OR amcinonid* OR beclomethason* OR betamethason* OR budesonid* OR ciclesonid*
OR clobetas* OR clocortolon* OR desoximetason* OR dichlorison* OR diflorason* OR diflucortolon* OR difluprednate OR drocinonid*
OR flumethason* OR fluocinolon* OR fluocinonid* OR fluocortin OR fluocortolon* OR fluorometholon* OR fluperolon* OR flupredni*
OR flurandrenolone* OR fluticason* OR FX006 OR halometason* OR medryson* OR melengestrol OR paramethason* OR rimexolon* OR
terofenamat* OR triamcinolon* OR mometason*)

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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Informed decisions.
Better health.

 
 

Cochrane Database of Systematic Reviews

#2 TI=(COVID OR COVID19 OR “SARS-CoV-2” OR “SARS-CoV2” OR SARSCoV2 OR “SARSCoV-2” OR “SARS coronavirus 2” OR “2019 nCoV”
OR “2019nCoV” OR “2019-novel CoV” OR “nCov 2019” OR “nCov 19” OR “severe acute respiratory syndrome coronavirus 2” OR “novel
coronavirus disease” OR “novel corona virus disease” OR “corona virus disease 2019” OR “coronavirus disease 2019” OR “novel coronavirus
pneumonia” OR “novel corona virus pneumonia” OR “severe acute respiratory syndrome coronavirus 2”) OR AB=(COVID OR COVID19 OR
“SARS-CoV-2” OR “SARS-CoV2” OR SARSCoV2 OR “SARSCoV-2” OR “SARS coronavirus 2” OR “2019 nCoV” OR “2019nCoV” OR “2019-novel
CoV” OR “nCov 2019” OR “nCov 19” OR “severe acute respiratory syndrome coronavirus 2” OR “novel coronavirus disease” OR “novel
corona virus disease” OR “corona virus disease 2019” OR “coronavirus disease 2019” OR “novel coronavirus pneumonia” OR “novel corona
virus pneumonia” OR “severe acute respiratory syndrome coronavirus 2”)

#3 #1 AND #2

#4 TI=(random* OR placebo OR trial OR groups OR “phase 3” or “phase3” or p3 or “pIII”) OR AB=(random* OR placebo OR trial OR groups
OR “phase 3” or “phase3” or p3 or “pIII”)

#5 #3 AND #4

Indexes=SCI-EXPANDED, ESCI Timespan=2020-2021
= 809 references

WHO COVID-19 Global literature on coronavirus disease

Title, abstract, subject: (corticosteroid* OR corticoid* OR prednis* OR hydrocorti* OR methylpredni* OR deltahydrocorti* OR dehydrocorti*
OR dexameth* OR desameth* OR glucocorticoid* OR beclomethason* OR budesonid* OR ciclesonid* OR fluticason* OR mometason*) AND
(random* OR placebo OR trial OR groups OR “phase 3” or “phase3” or p3 or “pIII”)
– without databases: ICTRP, MEDLINE, EMBASE, Web of Science, PMC, PubMed = 199 references

W H A T ‘ S   N E W

 

Date Event Description

15 March 2022 Amended Affiliation of information specialist corrected under Meth-
ods-Search methods for identification of studies

 

H I S T O R Y

Review first published: Issue 3, 2022

 

Date Event Description

11 March 2022 Amended Correction of typographical error in Background section

 

C O N T R I B U T I O N S   O F   A U T H O R S

MG: data extraction, risk of bias assessment, characteristics of included studies, meta-analysis, writing of the review, clinical expertise,
taking responsibility for reading and checking the review before submission.

CW: screening, data extraction, risk of bias assessment, characteristics of included studies, characteristics of ongoing studies,
characteristics of studies awaiting classification, meta-analysis, writing of the review, taking responsibility for reading and checking the
review before submission.

AM: clinical expertise, writing of the review, extraction, taking responsibility for reading and checking the review before submission.

MS: clinical expertise, checking characteristics of ongoing studies, taking responsibility for reading and checking the review before
submission.

FF: clinical expertise, securing the funding, taking responsibility for reading and checking the review before submission.

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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Informed decisions.
Better health.

 
 

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MM: design and conduct of searches, draUing of search methods section, taking responsibility for reading and checking the review before
submission.

AN: clinical expertise, risk of bias assessment, checking characteristics of ongoing studies, writing of the review, taking responsibility for
reading and checking the review before submission.

JD: clinical expertise, risk of bias assessment, checking characteristics of ongoing studies, writing of the review, taking responsibility for
reading and checking the review before submission.

AF: clinical expertise, data extraction, risk of bias assessment, writing of the review, taking responsibility for reading and checking the
review before submission.

NS: methodological expertise and advice, conception and writing of the review, securing the funding, taking responsibility for reading and
checking the review before submission.

D E C L A R A T I O N S   O F   I N T E R E S T

MG: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the
‘CEOSys’ project, which was paid to the institution); works as a resident with the Department of Anesthesiology and Intensive Care at the
University of Leipzig Medical Center; is a member of the German Society for Anaesthesia and Intensive Care.

CW: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the
‘CEOSys’ project, which was paid to the institution); is a part of Cochrane Haematology editorial team, and was not involved in the editorial
process.

AM: is a member of the ‘CEOSys’ project (no direct funding) and co-ordinator of COVRIIN section and works in oGice of STAKOB (Competence
and Treatment Centres for high consequence infectious diseases) at Robert Koch Institute Centre for Biological Threats and Special
Pathogens (ZBS), Section Clinical Management and Infection Control.

MS: none.

FF: is a member of the ‘CEOSys’ project (no direct funding); works as an Intensive Care Medicine Consultant with the Department of
Anesthesiology and Intensive Care at the University of Leipzig Medical Center; is a member of the German Society for Anaesthesia and
Intensive Care and the German Interdisciplinary Association for Intensive Care and Emergency Medicine, and leading role in German
guideline on respiratory failure and invasive mechanical ventilation.

MM: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the
‘CEOSys’ project, which was paid to the institution).

AN: none.

JD: none.

AF: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the
‘CEOSys’ project, which was paid to the institution), and works as a fellow with the Department of Anesthesiology and Intensive Care at
the University of Leipzig Medical Center.

NS: none. Part of Cochrane Haematology editorial team, and was not involved in the editorial process.

S O U R C E S   O F   S U P P O R T

Internal sources

• University Hospital of Cologne, Germany

Cochrane Cancer, Department I of Internal Medicine

• Leipzig University Hospital, Germany

Department of Anaesthesiology and Intensive Care

• Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany,
Germany

Department of Infectious Diseases and Respiratory Medicine

• Christian Medical College, Vellore, Tamil Nadu, India

Department of Respiratory Medicine and Department of Pulmonary Medicine

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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63

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Trusted evidence.
Informed decisions.
Better health.

 
 

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External sources

• Federal Ministry of Education and Research, Germany

NaFoUniMedCovid19 (funding number: 01KX2021) part of the ‘CEO-Sys’ project

D I F F E R E N C E S   B E T W E E N   P R O T O C O L   A N D   R E V I E W

Title

• For simplification and clarification we deleted “prevention” from the registered title because we did not intend to investigate inhaled
corticosteroids as primary prevention in uninfected people. In line with other COVID-19 reviews of this series, we refer to treatment of
COVID-19 at any stage of the disease including the asymptomatic infection.

Types of studies

• We added that cross-over trials in acute COVID-19 would have been excluded because of the short duration of the disease and potential
carry-over eGect; however, we did not identify any.

Types of outcomes

• In review updates, we will add patient-reported experience measures (PREMS) as an outcome, as suggested by the consumer editor
during the review process.

Summary of findings table

• We omitted symptom resolution: all initial symptoms resolved at day 30 from the summary of findings table and abstract. To further
reduce the number of outcomes in the table to seven, we also omitted quality of life.

N O T E S

Parts of the review’s methods section and of the background were adopted from Cochrane Reviews published in the COVID-19 series
(Kreuzberger 2021; Piechotta 2021).

Inhaled corticosteroids for the treatment of COVID-19 (Review)

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64

64 Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019

Investigating the role of practice nurses in
the early identification and management of

chronic kidney disease in the general practice
setting: An integrative review
Graeme L Turner, Sandra Grace, Christina Aggar and Rae Rafferty

Submitted 1 April 2019, Accepted 27 May 2019

Abstract
Aim The aim of this study was to critically review research literature investigating the role of practice nurses in the early
identification and management of chronic kidney disease (CKD) in the general practice setting.

Method An integrative review was performed to determine the extent to which the topic has been investigated.
Quantitative and qualitative research papers were systematically located in peer-reviewed journals in electronic
databases. Included papers were critically appraised using the relevant CASP appraisal tools.

Findings There is a paucity of research investigating the role of practice nurses in the early identification and
management of CKD in primary health care. Three articles published between 2013 and 2017 were identified: two
quantitative studies and one qualitative study. One study from The Netherlands quantified positive outcomes of practice
nurse-centred management of CKD in general practice.

Conclusion Practice nurses may be effective in the early identification and management of CKD, including improving
blood pressure control. Providing education to practice nurses appears to be a key factor in increasing practice
nurses’ involvement in identification and management of CKD. Further research is warranted to see if the results are
transferable to other jurisdictions.

Keywords Chronic kidney disease, practice nurse, general practice, primary health care.

For referencing Turner, G. L. et al. (2019). Investigating the role of practice nurses in the early identification and management of

chronic kidney disease in the general practice setting: An integrative review. RSAJ Journal, 15(2):64-70.

DOI https://doi.org/10.33235/rsaj.15.2.64-70

Graeme L Turner RN, GradCert (Clinical Nursing)(Edith Cowan), MNursing (Nurse Practitioner)(Newcastle)
Northern NSW Local Health District, PO Box 419, Lismore, NSW 2480, Australia
Southern Cross University School of Health and Human Sciences, Lismore, NSW 2480, Australia
Email [email protected]

Sandra Grace DipEd(US), BA(US), GradCert(SportsChiro)(Melb), MSc(Macquarie), PhD(US), DC(SydCollege),
DO(SydCollege)
Southern Cross University School of Health and Human Sciences, Lismore, NSW 2480, Australia
Email [email protected]

Christina Aggar BNurs(Hons)(Sydney), GradCertEdStud(HigherEd)(Sydney), PhD(Sydney)
Southern Cross University School of Health and Human Sciences, Gold Coast, Qld, Australia
Email [email protected]

Rae Rafferty MSc (SCU), MBA (CSU), BHSc (CSU), RN
Northern NSW Local Health District, PO Box 419, Lismore, NSW 2480, Australia
Email [email protected]

Correspondence to: Graeme Turner, PO Box 419, Lismore, NSW 2480, Australia
Email [email protected]

Literature review

Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019 65

Summary statement
What is known about this topic?

• There is a paucity of research investigating the role of

practice nurses in the early identification and management

of chronic kidney disease in the general practice setting.

What does this paper add?

• Literature suggests that practice nurses can play an

important role in the early identification and management

of chronic kidney disease when provided with appropriate

education and resources.

Introduction
Diseases of the kidney and urinary tract are the ninth

leading cause of death in Australia (Australian Bureau of

Statistics, 2014). Dialysis treatment is the number one cause

of hospitalisation in NSW (NSW Dialysis Costing Studies,

2009). The early stages of chronic kidney disease (CKD)

are asymptomatic and if detected early and managed

appropriately, the otherwise inevitable progression of kidney

disease can be reduced and may even be reversible (Kidney

Disease: Improving Global Outcomes, 2013). Early detection

and appropriate management can slow or halt the progression

of the disease to the restrictive regime of dialysis and decrease

mortality. In Australia, one in 10 adults have indicators of

CKD such as reduced kidney function and/or albumin in

urine (Australian Bureau of Statistics, 2013). However, fewer

than 10% of people with CKD are aware that they have this

condition (Australian Bureau of Statistics, 2012).

General population-based screening for CKD is not cost-

effective (Komenda et al., 2014). Mathew et al. (2010)

conducted a pilot study in Australia screening for CKD in

the community and workplace. While this pilot was effective

in identifying early CKD, it was an expensive procedure. In

another Australian study, Howard et al. (2006) looked at the

cost-effectiveness of early detection and intervention to prevent

the progression of CKD. They found that general practice-

based opportunistic screening of patients with risk factors for

CKD to be a likely cost-effective strategy for early detection

and management of CKD. This approach of screening high-

risk individuals was also supported in the systematic review

conducted by Komenda et al. (2014). General practice is

the logical setting for early detection of CKD. Eighty-five per

cent of Australians visit a general practitioner (GP) each year

(Razavian et al., 2011); 35% of consultations are associated

with chronic disease management (Australian Institute of

Health and Welfare, 2018). However, CKD remains significantly

under-diagnosed and under-treated in general practice. In the

AusHEART study, Razavian et al. (2011) found that only 18% of

patients with indicators for CKD had a CKD diagnosis recorded

in their medical record. Increased levels of protein in the urine

correlates directly with increased risk of progression of kidney

disease to kidney failure and increased cardiovascular risk

(Levey et al., 2011). Proteinuria screening was performed in

less than 60% of people with decreased estimated glomerular

filtration rate (eGFR) (Razavian et al., 2011). In Australia, one in

five patients commencing renal replacement therapy were late

referrals to nephrology services (Foote et al., 2014).

Peak national nephrology organisations such as Kidney Health

Australia (KHA) and the National Kidney Foundation in the

United States provide CKD education for health professionals,

including practice nurses (Kidney Health Australia, 2019;

National Kidney Foundation, 2019). KHA’s primary care

education program provides a variety of two-hour CKD

education modules, each presented by an expert speaker.

The program, which is accredited for continuing professional

development, reaches around 43,000 primary health care

professionals, including practice nurses each year (Kidney

Health Australia, 2019). However, it appears that evaluations

of KHA’s primary care education program have not been

published.

In Australia, the term ‘practice nurse’ is generally applied to

qualified nurses employed in the general practice setting (Jolly,

2007). This definition is used in this review. Practice nursing

is a growth area in the Australian general practice workforce.

Approximately 63% of general practices in Australia employ

at least one practice nurse (Agency for Clinical Innovation,

2015) and they have become an integral part of the general

practice team. Adult health checks, preparing chronic disease

management plans and chronic disease education and

management are all within the scope of practice nurses in

Australia (Australian Medicare Local Alliance, 2012). GPs report

increasing workloads that impact negatively on consultation

times and their capacity to deliver adequate care to complex

patients with chronic conditions (Agency for Clinical Innovation,

2015). They are often caught up in the business of diagnosis

and management of clients with acute symptoms, leaving

chronic disease management and follow-up to be managed by

practice nurses employed within the practice. Consequently,

practice nurses are ideally placed at the coal face in general

practice to assist GPs in the identification and management of

chronic conditions.

In order to determine the extent of the role of practice nurses,

specifically in the early identification and management of

CKD in the primary health setting, an integrative review of the

literature was conducted.

Method
Design
An integrative review is a comprehensive literature review

that includes both qualitative and quantitative methodologies

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

66 Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019

(Whittemore & Knafl, 2005). The integrative review method

involves identifying, selecting, appraising and synthesising

research in a structured and replicable format (Souza, Silva &

Carvalho, 2010).

Search strategy
In March 2018, a systematic search was undertaken using five

electronic databases: Medline, Embase, CINAHL, Aushealth,

Nursing @ Ovid. The search consisted of seven steps using

MESH headings, relevant terms and abbreviations (Table 1).

At each step, articles were limited to English language and

to publication between 2007 and 2017. CINAHL search was

limited to “original research” as this filter was available in

CINAHL database search. Duplicates were removed. Citation

tracking and reference list inspections were undertaken to

search for further relevant papers. Quantitative and qualitative

research papers were systematically identified in peer-reviewed

journals. Two independent reviewers reviewed 38 abstracts

and 21 full text papers to identify suitable articles for inclusion

in the review.

also excluded. During the process of reviewing studies for

inclusion in the review, a number of studies involving short-term

interventions by specialist nephrology nurses visiting general

practices to assist with identification and management of

kidney disease were identified. These studies did not include

long-term follow-up, and sustainability of these interventions

may prove challenging. These studies did not meet review

criteria so were not included in this review.

Search outcome
The systematic search strategy produced 38 citations; 5

were duplicates; 33 titles and abstracts were reviewed and

17 papers were excluded with reason. Five additional primary

research articles were identified from references in systematic

reviews, 3 were excluded with reason. The remaining 21 full

text papers were reviewed (Figure 1). Three studies were finally

included in the review.

Quality appraisal, abstraction and
synthesis
The Critical Appraisal Skills Programme (CASP) system of

appraisal was adopted to appraise the final three studies for

rigour, method, credibility and relevance (Critical Appraisal

Skills Programme, 2016). The CASP system of appraisal is a

well-utilised tool that can enhance the utility of evidence-based

research by health professionals through the identification of

quality research. The studies were critiqued for design, method,

aims, ethical considerations, sample population and size,

interventions and outcome measures (Table 2).

Results
The three studies included in the review were published

between 2013 and 2018. One study was from The Netherlands

(Scherpbier-de Haan et al., 2013), one from Australia (Sinclair,

Day, Levett-Jones & Kable, 2017) and one from the United

States (Thompson-Martin, McCullough & Agawal, 2015).

Study design
Methodological design varied between the three studies. The

study by Scherpbier-de Haan et al. (2013) was a quantitative,

cluster, randomised control trial comparing shared care

management between practice nurses and GPs with standard

care provided by a GP alone. The primary outcome measure

was a decrease in blood pressure (BP) in hypertensive patients

with CKD. Blood pressures were compared prior to the study

and at 12 months. Thompson-Martin et al. (2015) also used

quantitative methodology. Their study was quasi-experimental

using longitudinal knowledge surveys completed by practice

nurses. A pre-knowledge survey testing knowledge of Kidney

Disease Outcomes Quality Initiative (KDOQI) guidelines was

completed by participants before attending an educational

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

Table 1: Search strategy to identify papers for review

Step Search term
1. Keyword OR subject Heading ‘chronic kidney disease’

‘renal insufficiency, chronic’ (15920)

2. Keyword OR subject heading ‘nurse’ nurses, nurse prac-
titioners, family nurse practitioners, nurse specialist, nurse
clinicians, nurses, community health, nurses, public health
(33848)

3. Keyword OR subject heading ‘General practice’ general
practice, family practice (45088)

4. Keyword OR subject heading ‘primary care’ primary health
care

5. Keyword OR subject heading ‘Community health services’

6. 3 or 4 or 5

7. 1 and 2 and 6 (38)

Inclusion and exclusion criteria
Articles were included if they reported primary research

articles that focused on the role of practice nurses employed

in the general practice setting in the early identification and

management of CKD. Articles were excluded if they were not

published in the English language, were not primary research, if

the disease was not CKD, if the research was not in the general

practice setting and if the research did not report specifically

on the role of the nurse who was employed in the general

practice. Research where the patients had end-stage kidney

disease and were undertaking renal replacement therapy, or

had a renal transplant were also excluded. As the focus of

the review was to investigate the role of practice nurses in the

early identification and management of CKD in the general

practice setting, papers not differentiating practice nurses’ role

from that of the GP or other allied health professionals were

Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019 67

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

Table 2: Quality appraisal

Authors, date
and location

Study design Primary aims/s
Ethical

considerations

Sample
population

and size

Comparative
interventions

Outcome measures/
instruments

Main findings

Scherpbier-
de Haan,
Vervoot et
al. ,
Netherlands,
2013

Cluster
randomised
control trial

Assess effect
of a shared
care model
in managing
patients with
CKD who
also have
diabetes and
hypertension

Not required
as covered
under
data-sharing
agreement
from larger
trial

Patients from
9 general
practices in
Netherlands.
90
intervention
and 74
control
patients

Structured
care involving
NP in general
practice setting
vs standard GP
managed care

Achievement of
BP targets 130/80
and lowering of
BP in patients with
diabetes mellitus or
hypertension and
an eGFR less than
70ml/min/1.73m2

Intervention group
BP decreased by
8.1 (95% CI =4.8 to
11.3)/1.1 (95% CI
=–1–3.2) compared
to –0.2 (95% CI=-
3.8-3.3) / –0.5 (95%
CI=–2.9–1.8) in
control group. Use of
lipid-lowering drugs,
angiotensin system-
inhibiting drugs and
Vitamin D higher in
intervention group

Sinclair,
Day et al.,
Newcastle,
Australia,
2017

Elicitation
questionnaire
to inform
Theory of
Planned
Behaviour

To identify
barriers and
facilitators to
CKD screening
by practice
nurses working
in general
practice in
regional NSW,
Australia

Yes 26 practice
nurses
working
in general
practice in
regional NSW

N/A Elicitation
questionnaire to
inform Theory of
Planned Behaviour.
Two researchers
independently
conducted a
direct content and
frequency analysis
of participant
responses to
questionnaire

Participants
acknowledged that
PNs were ideally
placed to undertake
CKD screening.
Some participants
recognised they had
a knowledge deficit of
best practice for CKD
screening.
No financial incentive
for practice to
perform CKD
screening.
Concern of harm to
patient by causing
stress due to
additional health
problem.
Lack of knowledge
to answer patient
questions about CKD

Thompson-
Martin,
McCullough
et al.,
Kansas,
USA,
2015

Quasi-
experimental,
pre, post
and 1 month
follow-up

Change in
knowledge of
the National
Kidney
Foundation
Kidney Disease
Outcomes
Quality Initiative
Guidelines
(NKF KDOQI
guidelines) and
knowledge
retention of
NKF KDOQI
guidelines at 1
month

Yes 14 advanced
practice
nurses
working in
primary health
care in urban
mid-western
USA

Pre and post
education event
surveys

Questionnaire to
measure knowledge
of NKF KDOQI
guidelines pre,
post and 1 month
following APN
educational meeting
on NKF KDOQI
guidelines

Increase of
knowledge of CKD
KDOQI guidelines
following educational
meeting; knowledge
was retained 1 month
later

meeting. One month after the meeting, they completed an

identical survey to test if the educational meeting had increased

practice nurses’ knowledge of KDOQI guidelines. Sinclair et

al. (2017) conducted a qualitative study, utilising an eight-item

elicitation questionnaire to investigate behavioural, normative

and control beliefs of practice nurses regarding screening for

CKD, informed by the Theory of Planned Behaviour.

Quality appraisal
The study by Scherpbier-de Haan et al. (2013) was a high-

quality study. It was a well-powered, cluster, randomised

control trial and was able to provide statistical significance in its

primary endpoint, namely a decrease in BP.

The study by Thompson-Martin et al. (2015) used a quasi-

experimental design. While this was also a quantitative study,

it was of lower quality as randomisation was not used and

measurement was longitudinal. These factors make it difficult

to eliminate confounding factors that may influence results.

The authors used a small sample size, with 14 practice nurses

completing the study and convenience sampling, which further

68 Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

limited generalisability of the results. A strength of the study

was that the authors utilised a validated assessment tool to

test the practice nurses’ knowledge and found an improvement

in the primary endpoint, that is an increase in practice nurses’

knowledge of KDOQI guidelines.

In contrast to the two quantitative studies described above,

Sinclair et al. (2017) used a qualitative study design to elicit

practice nurses’ beliefs about barriers and facilitators to

opportunistic screening for CKD in general practice. Twenty-

one practice nurses were recruited via convenience sampling.

The CASP qualitative checklist was used to assess the study

and it was deemed to be of rigorous design with credible

results. Qualitative results are context-dependent and generally

not intended to be generalised, although the findings may be of

use in other similar contexts.

The extent and effectiveness of practice nurses’ role in

the early identification and management of CKD in the

primary health care setting

This integrative review identified that there is a paucity of

literature regarding the role of practice nurses in the early

identification and management of CKD. Scherpbier-de Haan

et al. (2013) found that shared care between practice nurses

and GPs led to improvement in BP control in people with CKD

compared to management by GPs alone. Thompson-Martin

et al. (2015) were successful in improving practice nurses’

knowledge of the KDOQI guidelines using an education

session. Sinclair et al. (2017) found that practice nurses

believed they had a role to play in the early identification of

CKD, but were challenged by knowledge, time and financial

barriers. The three studies reviewed, although undertaken in

different health jurisdictions, all support the notion that practice

38 citations identified through Boolean
database searches

38 citation titles and abstracts reviewed
22 Papers excluded with reason:

• Duplicate (n=5)
• Not chronic kidney disease (n=5)
• Research protocol (n=4)
• Not general practice setting (n=4)
• Not practice nurse specific (n=4)

16 full text papers reviewed

Additional 5 full text papers identified in
systematic reviews appraised.

Total 21 full text papers reviewed.

2 Systematic Reviews
• Primary articles from systematic reviews

obtained(n=8)
• Duplicates excluded (n=3)
• Full text papers reviewed (n=5)

3 full text papers included in integrative
review

18 Papers excluded with reason:
• Not general practice setting (n=7)
• Multidisciplanary care, not nursing

specific (n=5)
• Advanced practice nurse external from

general practice team, not practice nurse
(n=4)

• Not chronic kidney disease (2)

Figure 1: Search flow chart

Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019 69

nurses can play a role in the early detection and management

of CKD.

Discussion
The aim of this study was to critically appraise the research

literature to determine the extent to which the practice nurses’

role in the early identification and management of CKD in the

primary health care setting has been investigated. The review

highlighted that there has been little work completed in this
area and only three studies were identified for inclusion in the
integrative review.

All three studies included in the review discussed shortcomings
in the early identification and management of CKD in the GP
setting and suggested that practice nurses could play a role
in improving early identification and management of CKD in
the general practice setting. The Scherpbier-de Haan et al.
(2013) study was the only study that attempted to measure
effectiveness of a shared care model with the practice nurse
(nurse practitioner) playing a central role in management of
CKD compared to standard GP care of CKD. The remaining
two studies focused on facilitators and barriers to practice
nurses’ involvement in identification and management of CKD.
Thompson-Martin et al. (2015) suggested practice nurses’
CKD knowledge deficit was a barrier that could be addressed
through education. Sinclair et al. (2017) took a qualitative
look at barriers and facilitators to practice nurses providing
opportunistic screening for CKD. Facilitators identified included
beliefs that practice nurses were ideally positioned to identify
CKD and that early identification of CKD benefits patients.
Barriers included practice nurse knowledge deficit, nursing time
constraints and lack of financial reimbursement to practices for
CKD screening activities.

Two themes emerged that were common to all three papers
reviewed. The first theme to emerge from the studies was that
it is perceived that practice nurses can indeed play a role in
early identification and management of CKD. Results from the
Scherpbier-de Haan et al. (2013) study support this hypothesis.
They achieved their primary endpoint of improvement in
BP control in people with CKD, with statistical significance
using a shared care model, with the practice nurse playing
a central role in management of CKD. In the Dutch general
practice setting, nurse practitioners (referred to as advanced
practice nurses in the paper) were employed in the general
practice setting. These nurse practitioners were masters-
prepared advanced practice nurses (Dutch Professional Nurse
Practitioner Organisation V&VN VS, 2015). In Australia, the
vast majority of practice nurses are baccalaureate-prepared
registered nurses or diploma-trained enrolled nurses.
Practice nursing is not as well recognised in Australia, as an
independent nursing specialty, as it is in some other countries
(Halcomb, Salamonson, Davidson, Kaur & Young, 2014).
Further research is required to determine if the Dutch results
are transferable to the Australian general practice setting with

its bachelor- and diploma-qualified practice nurses. The fact
that Sinclair et al. (2017) found that practice nurses themselves
believe that they are ideally placed to play a role in the early
detection of CKD in the Australian setting, suggests that the
findings from the Scherpbier-de Haan et al. (2013) study may
be transferable to the Australian setting. Thompson-Martin
et al. (2015) hypothesised that increasing practice nurse
knowledge of KDOQI guidelines would increase appropriate
referral of people with CKD to specialist nephrologists — a
clear indicator of the role that practice nurses can play in the
early detection and management of CKD.

The second theme was practice nurses’ knowledge about
CKD. Both the Scherpbier-de Haan et al. (2013) and
Thompson-Martin et al. (2015) studies involved increasing
practice nurses’ CKD knowledge to facilitate their involvement
in management of CKD. In the Scherpbier-de Haan et al.
(2013) study, specialist nephrology staff provided education
sessions to practice nurses at the start of the study, thereby
attempting to increase practice nurses’ CKD knowledge. The
study established a connection between the practice nurses
and a specialist nephrology nurse, allowing the practice nurse
to consult with the nephrology nurse, as required. Thompson-
Martin et al. (2015) increased practice nurses’ knowledge of
KDOQI guidelines through successful provision of an education
session to practice nurses. Practice nurses surveyed by
Sinclair et al. (2017) perceived a lack of CKD knowledge as a
barrier to their role in the early identification of CKD. Education
opportunities similar to those described by Scherpbier-de
Haan et al. (2013) and Thompson-Martin et al. (2015) could go
some way to addressing Sinclair et al. (2017) practice nurses’
knowledge deficit barrier.

Other barriers to practice nurses’ involvement in the early
identification of CKD highlighted by Sinclair et al. (2017)
included nursing time constraints and lack of financial
reimbursement to practices for CKD screening activities. The
Australian Primary Health Care Nurses Association (2017)
states that health promotion, illness prevention and chronic
disease management are skills that can be undertaken by
practice nurses. They go on to state that primary health
care nurses can facilitate increased access to health care.
The practice nurse workforce in Australia is increasing
(Australian Medicare Local Alliance, 2012). In fact, in general
practices employing nurses, practice nurse to GP ratio
increased from 0.49PN/1.0GP in 2007 to 0.56PN/1.0GP in
2012. Consequently, the available practice nurse resource
is increasing in general practice in Australia. This should go
some way to addressing time constraint issues. In Australia,
the Practice Nurse Incentive Program (PNIP) has been

introduced to assist general practices to fund practice nurse

positions. There are also a number of Medicare items that

apply to particular skill sets or services undertaken by practice

nurses (Agency for Clinical Innovation, 2015). This means that

government subsidies apply to those items. Iles et al. (2014)

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

70 Renal Society of Australasia Journal I Vol 15 I No. 2 I July 2019

found that practice nurse-led care for chronic diseases was

economically viable for general practices in Australia. The

financial barrier to practice nurse involvement in identification of

CKD recognised by Sinclair et al. (2017) may be addressed by

providing education to general practice managerial and clinical

staff on financial reimbursement available through PNIP and

Medicare item numbers in Australia.

Conclusion
Research investigating the role of practice nurses in the early

identification and management of CKD in the general practice

setting is scant. The three studies included in the review all

suggest that there is a role for practice nurses in the early

identification and management of CKD, including effectiveness

of the role in improving BP control. Providing education

to practice nurses in early identification and management

of CKD appears to be a key factor in increasing practice

nurses’ involvement in the identification and management

of CKD. These education programs could include clinical

education for practice nurses as well as education regarding

financial reimbursement for chronic disease identification and

management for their general practices. Further research

is warranted to evaluate the role that practice nurses could

have in the early identification of CKD in the Australian general

practice setting, subsequently reducing the burden of disease

to both patients and their communities.

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Conflicts of interest
The authors declare no conflicts of interest.

Acknowledgements
This work is supported by a research grant from NSW Agency

for Clinical Innovation.

Investigating the role of practice nurses in the early identification and management of chronic kidney disease in the general practice
setting: An integrative review

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