bmj.h3728.full

7212019 Bmjh3728Full

httpslidepdfcomreaderfullbmjh3728full 114thebmj 983164 BMJ 2015351h3728 983164 doi 101136bmjh3728

RESEARCH

1

OPEN ACCESS

983089Mahidol-Oxord TropicalMedicine Research Unit Facultyo Tropical Medicine MahidolUniversity Bangkok Thailand983090School o Public HealthQueensland University oTechnology Brisbane Australia983091Department o TropicalHygiene Faculty o TropicalMedicine Mahidol UniversityBangkok Thailand983092Centre or Tropical Medicineand Global Health NuffieldDepartment o Clinical Medicine

University o Oxord Oxord UK983093Inection Control ProgramUniversity o Geneva Hospitalsand Faculty o MedicineGeneva 983089983090983089983089 Switzerland983094Departments o InectiousDiseases and MicrobiologyRoyal Prince Alred HospitalSydney 983090983088983093983088 Australia983095Institute o Health andBiomedical InnovationQueensland University oTechnology Brisbane Australia

Correspondence toN Luangasanatip Mahidol-OxordTropical Medicine Research Unit983092983090983088983094 983094983088th Anniversary

Chalermprakiat Building983091rd Floor Rajvithi Road BangkokThailand 983089983088983092983088983088nantasittropmedresac

Additional material is publishedonline only To view please visit

the journal online (ht tpdxdoiorg983089983088983089983089983091983094bmjh983091983095983090983096)

Cite this as BMJ 983090983088983089983093983091983093983089h983091983095983090983096doi 983089983088983089983089983091983094bmjh983091983095983090983096

Accepted 983090983090 June 983090983088983089983093

Comparative efficacy of interventions to promote hand hygiene

in hospital systematic review and network meta-analysis

Nantasit Luangasanatip983089 983090 Maliwan Hongsuwan983089 Direk Limmathurotsakul983089 983091 Yoel Lubell983089 983092 Andie S Lee983093 983094 Stephan Harbarth983093 Nicholas P J Day983089 983092 Nicholas Graves983090 983095 Ben S Cooper 983089 983092

ABSTRACT

OBJECTIVE

To evaluate the relative efficacy o the World Health

Organization 983090983088983088983093 campaign (WHO-983093) and other

interventions to promote hand hygiene among

healthcare workers in hospital settings and to

summarize associated inormation on use o

resources

DESIGN

Systematic review and network meta-analysis

DATA SOURCES

Medline Embase CINAHL NHS Economic EvaluationDatabase NHS Centre or Reviews and Dissemination

Cochrane Library and the EPOC register (December

983090983088983088983097 to February 983090983088983089983092) studies selected by the

same search terms in previous systematic reviews

(983089983097983096983088-983090983088983088983097)

REVIEW METHODS

Included studies were randomised controlled trials

non-randomised trials controlled beore-afer trials

and interrupted time series studies implementing

an intervention to improve compliance with hand

hygiene among healthcare workers in hospital

settings and measuring compliance or appropriate

proxies that met predefined quality inclusion criteria

When studies had not used appropriate analytical

methods primary data were re-analysed Random

effects and network meta-analyses were perormed

on studies reporting directly observed compliance

with hand hygiene when they were considered

sufficiently homogeneous with regard to

interventions and participants Inormation on

resources required or interventions was extracted

and graded into three levels

RESULTS

O 983091983094983091983097 studies retrieved 983092983089 met the inclusion criteria

(six randomised controlled trials 983091983090 interrupted time

series one non-randomised trial and two controlled

beore-afer studies) Meta-analysis o two randomised

controlled trials showed the addition o goal setting to

WHO-983093 was associated with improved compliance

(pooled odds ratio 983089983091983093 983097983093 confidence interval 983089983088983092

to 983089983095983094 I983090=983096983089) O 983090983090 pairwise comparisons rom

interrupted time series 983089983096 showed stepwise increases

in compliance with hand hygiene and all but our

showed a trend or increasing compliance afer the

intervention Network meta-analysis indicatedconsiderable uncertainty in the relative effectiveness

o interventions but nonetheless provided evidence

that WHO-983093 is effective and that compliance can be

urther improved by adding interventions including

goal setting reward incentives and accountability

Nineteen studies reported clinical outcomes data

rom these were consistent with clinically important

reductions in rates o inection resulting rom

improved hand hygiene or some but not all important

hospital pathogens Reported costs o interventions

ranged rom 983076983090983090983093 to 983076983092983094983094983097 (983203983089983092983094-983203983091983088983091983093 991404983090983088983092-

991404983092983090983090983097) per 983089983088983088983088 bed days

CONCLUSIONPromotion o hand hygiene with WHO-983093 is effective at

increasing compliance in healthcare workers Addition

o goal setting reward incentives and accountability

strategies can lead to urther improvements Reporting

o resources required or such interventions remains

inadequate

Introduction

At any point in time more than 983089983092 million patients

around the world experience healthcare associated

infections983089 983090 Such infections cause excess morbidity

and are associated with increased mortality983090 983091 Direct

contact between patients and healthcare workers whoare transiently contaminated with nosocomial patho-

gens is believed to be the primary route of transmission

for several organisms and can lead to patients becom-

ing colonised or infected Although hand hygiene is

widely thought to be the most important activity for the

prevention of nosocomial infections a review of hand

hygiene studies by the World Health Organization

(WHO) found that baseline compliance with hand

hygiene among healthcare workers was on average only

983091983096983095 (range 983093-983096983097)983092

In 983090983088983088983093 the WHO World Alliance for Patient Safety

launched a campaign the First Global Patient Safety

ChallengemdashldquoClean Care is Safer Carerdquomdashaiming toimprove hand hygiene in healthcare983092 This campaign

WHAT IS ALREADY KNOWN ON THIS TOPIC

Hand hygiene among healthcare workers is possibly one o the most effective

measures to reduce healthcare associated inections but compliance remains poor

in many hospital settings

In 983090983088983088983093 WHO launched a campaign to improve hand hygiene in healthcare settings

by promoting a multimodal strategy consisting o five components system change

training and education observation and eedback reminders in the hospital and a

hospital saety climate

WHAT THIS STUDY ADDS

These meta-analyses provide evidence that the WHO campaign is effective at

increasing compliance with hand hygiene in healthcare workers

There is evidence that additional interventions (used in conjunction with the WHO

campaign elements) including goal setting reward incentive and accountability

can lead to urther improvements

Reporting on resource implications o such interventions is limited


httpslidepdfcomreaderfullbmjh3728full 214doi 101136bmjh3728 983164 BMJ 2015351h3728 983164 thebmj

RESEARCH

2

(WHO-983093) promotes a multimodal strategy consisting of

five components system change training and educa-

tion observation and feedback reminders in the hospi-

tal and a hospital safety climate More recently

additional strategies for improving hand hygiene have

been evaluated including those based on behavioural

theory

We assessed the relative effectiveness of WHO-983093 and

other strategies for improving compliance with hand

hygiene in healthcare workers in hospital settings Eval-

uation of the evidence for the effectiveness of different

interventions is complicated by three factors firstly

most evaluations of interventions to promote hand

hygiene use non-randomised study designs and in

many cases the reported analysis is inappropriate or

methodological quality is too low to allow meaningful

conclusions to be drawn983093-983096 secondly there is wide vari-

ation between studies in the activities to promote hand

hygiene used in the comparison group thirdly direct

head-to-head comparisons of most interventions are

lacking983095

We aimed to overcome these problems by restricting

attention to randomised trials and high quality

non-randomised studies re-analysing data when nec-

essary explicitly accounting for activities to promote

hand hygiene in the comparison group in each study

and using network meta-analysis to allow indirect com-

parison between interventions

We also summarise information on changes in clini-

cal and microbiological outcomes associated with inter-

ventions when this was reported Information on

resources used in different interventions is essential for

those wanting to implement such interventions or eval-

uate their cost effectiveness983097 983089983088 An additional aim wastherefore to document information on resources used in

interventions to promote hand hygiene

Methods

We developed a protocol and used systematic methods

to identify relevant studies screen study eligibility and

assess study quality This protocol was not registered

This review is reported according to the Preferred

Reporting Items for Systematic Reviews and Meta-Anal-

yses (PRISMA) guidelines983089983089

Search strategy

We used a two stage search strategy Firstly we obtainedall studies considered in two previous reviews (covering

the period up to November 983090983088983088983097) including those that

had been reported as failing to meet inclusion criteria983093 983094

Secondly we extended the search from these studies

from December 983090983088983088983097 to February 983090983088983089983092 We searched

Medline Embase Cumulative Index to Nursing and

Allied Health (CINAHL) Database of Abstracts of

Reviews of Effects (DARE) National Health Service Eco-

nomic Evaluation Database (NHS-EED) National

Health Service Centre for Reviews and Dissemination

(NHS-CRD) and British Nursing Index (BNI) Cochrane

Library (Cochrane database of systematic reviews

Cochrane central register of controlled trials Cochranemethodology register Health Technology assessment

database) Clinical Trialgov Current Clinical Control

trial Cochrane Effective Practice and Organisation of

Care Group (EPOC) register American College of Physi-

cians journal and reviews of evidence based medicine

Results were limited to peer reviewed publications To

validate previous search results we also repeated the

electronic search for three earlier years (983089983097983096983088 983089983097983097983093 and

983090983088983088983097) The complete search strategy is provided in

appendix 983089

Inclusion and exclusion

Studies were included if they met all the following ini-

tial criteria they evaluated one or more interventions

intended to improve hand hygiene compliance among

healthcare workers in a hospital setting they measured

compliance with hand hygiene using opportunities

with prespecified indications or using proxies linked to

compliance (such as consumption of soap and alcohol

hand rub) they were either randomised controlled tri-

als non-randomised trials controlled before-after

studies or used an interrupted time series design

We placed no restrictions on promotion of hand

hygiene in the comparison group Studies were

excluded if they were not reported in peer reviewed

publications or not written in English

We applied a methodological filter by excluding stud-

ies that failed meet minimal quality criteria specified by

the Cochrane Effectiveness Practice and Organisation of

Care Group (EPOC) Acceptable study designs were ran-

domised controlled trials and non-randomised trials

(with at least two intervention and two control sites)

controlled before-after studies (with outcome measures

before and after the intervention from at least two inter-

vention and two comparable control sites) and inter-rupted time series (with a clearly defined point in time

for the intervention and outcome measures from at least

three time points in both baseline and intervention

periods)983089983090 983089983091

Patient involvement

No patients were involved in setting the research ques-

tion or the outcome measures nor were they involved in

the design and implementation of the study There are

no plans to involve patients in dissemination

Data extraction and assessment o quality

Two reviewers (NL and BSC) independently screenedthe titles and abstracts of the citations obtained from

the search to assess the eligibility Consensus was

reached by discussion if initial assessments differed NL

evaluated the full text and abstracted data which was

checked by BSC

The reviewers abstracted data including study design

and duration population activities to promote hand

hygiene in both intervention and comparison groups

hand hygiene outcomes clinical and microbiological

outcomes measurement methods and settings When

possible we classified hand hygiene promotion activi-

ties according to WHO guidelines on hand hygiene in

healthcare983092 We grouped activities into eight compo-nents system change education feedback reminders



RESEARCH

3

safety climate incentives goal setting and account-

ability (table 983089) Results and raw compliance data from

each study were extracted for further re-analyses In

addition we extracted the costs of hand hygiene inter-

ventions or data on use of resources (materials and time

spent on interventions) when appropriate Additional

information was obtained from the authors if it was not

clear from the manuscript For all included studies we

used prespecified definitions to record the level of infor-

mation (high moderate or low) about resources used

for promotion of hand hygiene (see appendix 983090)

Assessment o risk o bias in included studies

We used the Cochrane Collaborationrsquos tool to assess risk

of bias983089983092 Nine standard criteria for randomised con-

trolled trials non-randomised trials and controlled

before-after studies and seven standard criteria forinterrupted time series were applied and used to clas-

sify each studyrsquos risk of bias as low high or unclear

Data synthesis and statistical analysis

Data synthesis was performed separately for different

study designs The primary evidence synthesis was

based on studies that used direct observation to mea-

sure compliance with hand hygiene We restricted our

analysis to this outcome because it reflects the opportu-

nities for hand hygiene

For randomised controlled trials we used Cochrane

Review Manager (RevMan version 983093983089) to calculate the

natural logarithm of the odds ratio and associated vari-ance to estimate the pooled odds ratio with a random

effects model983089983093 The same method was applied to

non-randomised trials and controlled before-after

studies if applicable Heterogeneity between studies

was assessed with the I983090 statistic Risk of publication

bias was evaluated with an enhanced contour funnel

plot983089983094 983089983095

For interrupted time series if re-analysis was

required we used a generalised linear segmented

regression analysis to estimate the stepwise change in

level and change in trend associated with the interven-

tion983089983096 This approach is similar to that proposed by

Ramsey and colleagues983089983097 and Vidanapathirana and col-leagues983090983088 except that it accounts for the binomial

nature of the data appropriately weighting each data

point by the number of observations We accounted for

any evidence of autocorrelation by using Newey-West

standard errors983090983089 Analysis was performed with Stata 983089983091

(Statacorp LP College Station TX) We then estimated

two summary measures that combined both stepwise

and trend changes Firstly we calculated the mean nat-

ural logarithm of the odds ratio for hand hygiene asso-

ciated with the intervention a measure of relative

improvement Secondly we calculated the mean per-

centage change in compliance in the period after the

intervention (compared with that expected if there had

been no intervention) an absolute measure of improve-

ment in compliance Standard errors were derived with

the delta method by using the emdbook package in

R983090983090 983090983091 Appendix 983091 provides full details

Network meta-analysis

Network meta-analysis aims to combine all of the

evidence both direct and indirect to estimate the

comparative efficacy of all the interventions983090983092 Each

intervention strategy is represented by a node in the

network If a study directly compares two interventions

they are directly connected by a link on the network and

a direct comparison is possible If two interventions are

connected indirectly (for example if there are studies

comparing each with a third intervention) then indi-

rect comparison is possible

We used network meta-analysis to compare the rela-

tive effectiveness of four different strategies no promo-tion of hand hygiene single component interventions

WHO-983093 and WHO-983093 and others (table 983090 ) We included in

the network meta-analysis those studies that included

only these strategies and permitted a segmented regres-

sion analysis and directly observed compliance with

hand hygiene983090983093 983090983094

The effect sizes obtained from each comparison were

combined in a network meta-analysis with a random

effects model983090983093 Effect sizes were taken as the mean of

the natural logarithm of the odds ratio for the hand

hygiene intervention as estimated with the segmented

regression model Intervention rankings and associ-

ated credible intervals were obtained Model fitting forthe meta-analysis was carried out within a Bayesian

Table 983089 | Description o eight components o interventions to promote hand hygiene in healthcare workers

Component Description

System change Ensuring necessary inrastructure is available including access to water soap and towels and alcohol basedhandrub at point o care

Education and training Providing training or educational programme on importance o hand hygiene and correct procedures orhand hygiene or healthcare workers

Feedback Monitor ing hand hygiene pract ices among healthcare workers whi le providing compliance eedback to staff

Reminders at workplace Prompting healthcare workers either through printed material verbal reminders electronic communications orother methods to remind them about impor tance o hand hygiene and appropriate indications and procedures

Institutional saety climate Active participation at institutional level creating environment allowing prioritisation o hand hygiene

Goal setting Setting o specific goals aimed at improving compliance with hand hygiene which can both apply atindividual and group level and can include healthcare associated inection rates

Reward incentives Interventions providing any reward incentive or participants completing a particular task or reaching acertain level o compliance Both non-financial and financial rewards are included

Accountability Interventions involved with improving healthcare workersrsquo accountability both at individual and unit level

I the intervention period included changing the location or ormulation o alcohol based handrub or installing more handrub dispensers the baselineintervention was counted as no intervention or standard practice (no system change component) even i alcohol based handrub had been used duringthe baseline period



RESEARCH

4

framework using WinBUGS983090983094 Inconsistency checks

were performed for closed loops in the network983090983095 Full

model details are provided in appendix 983092

We performed a sensitivity analysis by excluding

studies that implemented multicomponent strategies in

a stepwise manner without sufficient data to evaluate

individual components This led to the exclusion of

three studies983090983096-983091983088

Results

Overall description

Figure 983089 shows a summary of the review process Of

983091983094983091983097 studies screened 983089983092983090 studies met initial inclusion

criteria and 983092983089 of these met EPOC criteria Among these

983092983089 studies six were randomised controlled trials

(including three cluster randomised controlled tri-

als)983091983089-983091983094 983091983090 were interrupted time series983090983096-983091983088 983091983095-983094983093 one

was a non-randomised trial983094983094 and two were controlled

before-after studies983094983095 983094983096 Appendix 983093 give details of the

reasons for exclusion Applying our search strategy to

three years covered by previous reviews did not yield

any studies meeting our inclusion criteria that had not

already been included

Seventeen studies applied interventions to the whole

hospital while 983090983089 studies enrolled hospital wards

Three studies allocated interventions to specific

healthcare workers983091983089 983091983091 983091983094 Twenty five studies were con-

ducted in either a hospital-wide setting or combined

intensive care units and general wards while 983089983089 were

conducted in intensive care units or general wards

alone Of 983089983088 studies conducted in more than one hospi-

tal three included two or more countries983092983090 983092983096 983093983088 Only

five of the 983092983089 studies were conducted in low or middle

income countries983091983091 983091983094 983092983094 983093983088 983093983089

Study periods ranged from two months to six years

In 983089983089 studies the period was up to one year in 983089983095 studies

it was more than a year and up to three years and in 983089983091

it was more than three years Among the 983091983090 interrupted

time series only 983089983089 were longer than 983089983090 months

In 983091983092 studies hand hygiene was observed in all types

of healthcare workers with patient contact while six

studies considered only nurses andor nursing assis-

tants983091983091 983091983092 983091983094 983094983088 983094983092 983094983096 One study recruited only nursing stu-

dents as participants983093983092 One study also included

patientsrsquo relatives983091983097

Six studies used a single faceted intervention four

implemented education alone983091983091 983092983094 983093983092 983094983096 and two applied

system change or reminders983091983097 983092983092 Seventeen studies

used interventions equivalent to WHO-983093 and six of

these added supplemental interventions including goal

setting incentives and accountability983090983096 983091983092 983092983088 983092983093 983093983094 983094983094 Nine-

teen studies implemented interventions with two tofour components four of these applied components not

in WHO-983093 including goal setting and incentives983091983095 983091983096 983092983089 983093983097

Thirty studies (four randomised controlled trials 983090983093

interrupted time series and one non-randomised trial)

used direct observation to measure compliance with

hand hygiene Two of these used a combination of video

recorders and external observers983091983095 983091983096 Proxy measures

were assessed in 983089983097 studies including the rate of hand

hygiene events consumption of hand hygiene products

(alcohol hand rub or soap) and a hand hygiene score

checklist (two randomised controlled trials 983089983093 inter-

rupted time series and two controlled before and after

studies) Clinical outcomes were reported in 983089983097 stud-ies983090983096-983091983088 983091983093 983092983090 983092983094-983093983090 983093983093-983093983095 983093983097 983094983090 983094983091 983094983094 983094983095 983094983097 Appendix 983094 provides full

study characteristics including study design setting

intervention and comparison groups

Examination of funnel plots (appendix 983095) did not pro-

vide any clear evidence of publication bias though evi-

dence for or against such bias was limited by the fact

that there were no more than four studies for any pair-

wise comparison of strategies

Quality assessment

Ten studies were considered to have a high risk of bias

Thirty one had either low or unclear risk High risk of

bias was present in all three non-randomised trials orcontrolled before-after studies but only in seven out of

Table 983090 | Mean odds ratios with 983097983093 credible intervals or interventions strategies topromote hand hygiene Results are rom random effects network meta-analysis model

Strategies Description Mean OR (983097983093 credible interval)

Nonecurrent pract ice No intervention or current pract ice Reerence

Single intervention Single intervention (system changeor education)

983092983091983088 (983088983092983091 to 983092983094983093983095)

WHO-983093dagger WHO-983093 components 983094983093983089 (983089983093983096 to 983091983089983097983089)

WHO-983093 + others WHO-983093 plus incentives goal settingor accountability

983089983089983096983091 (983090983094983095 to 983093983091983095983097)

Model fit statistic posterior mean residual deviance=983089983088983092983088 and deviance inormation criterion (DIC)=983090983091983096983094daggerContained five components system change education eedback reminders and institutional saety climate(see table 983089 or details)

Studies identified by Gould et al orHuis et al and meeting EPOC criteria

(1980 to Nov 2009) (n=10 studies)

Potentially relevant citations identifiedafter searching from electronic database(Dec 2009 to Feb 2014) (n= 7615 records)

Records screened after duplicates removed (n=3639)

Relevant studies included in systematic review (n=41) Randomised controlled trials (n=6) Interrupted time series (n=32)

Studies included in quantitative synthesis (n=10) Randomised controlled trials (n=2) Interrupted time series studies (n=8)

Non-randomised trials (n=1)Controlled before and after trials (n=2)

Full text articles assessed for eligibility (n=202)

Studies met initial inclusion criteria of these 41 studies met EPOC inclusion criteria (n=142)

Full text articles excluded (n=60) No hand hygiene outcome (n=21) No intervenion or not hand hygiene promotion (n=15) Not healthcare workers (n=1) Not hospital settings (n=5) Not intervention studies not peer reviewed (review protocol conference proceeding economic evaluation (n=12)

Non-English literature (n=6)

Records excluded by title and abstract screening (n=3437)

Records excluded by EPOC inclusion criteria (n=101) Controlled before and after with appropriate control (n=3) Uncontrolled before and after design (n=80) Interrupted time series trials with inadequate data collection points (n=18)

Fig 983089 | Flow chart o study identification in systematic review o interventions to promotehand hygiene in healthcare workers



RESEARCH

5

983091983090 interrupted time series No randomised controlled

trials or cluster randomised controlled trials were

thought to have a high risk of bias (fig 983090)

The two controlled before-after studies983094983095 983094983096 had high

risks for inadequate allocation sequence and conceal-

ment while one non-randomised trial983094983094 had high risk of

dissimilarity in baseline outcome between experimen-

tal and control groups

Fourteen studies (983091983092) had a low risk of bias due to

the knowledge of allocated intervention as these stud-

ies either measured objective outcomes (such as alco-

hol consumption or output from electronic counting

devices) or stated that the observers were blinded to

the intervention The rest of the studies had unclear

risk as they did not report whether the observers were

blinded

Risk of selective outcome reporting was unclear in 983091983091

studies as pre-specified protocols were reported only in

three randomised controlled trials983091983090 983091983092 983091983093 Two of the

interrupted time series had a high risk of selective out-

come reporting as they reported on a non-periodical

basis983090983096 983093983097 Among the interrupted time series six had a

high risk that outcomes were affected by other interven-

tions such as a universal chlorhexidine body washing

programme983092983090 983094983091 reinforcement of standard precau-

tions983092983090 screening and decolonisation for multidrug-re-

sistant micro-organisms983092983096 quality improvement

program983092983094 983093983097 and antibiotic use and healthcare associ-

ated infections control policy implemented at the same

time983093983094

Meta-analysisdata synthesis

Randomised controlled trials

Four of six randomised controlled trials measured com-

pliance with hand hygiene by direct observation with

indications similar to WHO-983093983091983090-983091983093 Two of these studies

compared WHO-983093 with WHO-983093 combined with goal set-

ting (WHO-983093+)983091983090 983091983092 Huis and colleagues performed a

cluster randomised trial in 983094983095 wards from three hospi-

tals in the Netherlands983091983092 Compliance immediately afterthe intervention increased from 983090983091 to 983092983090 in the

WHO-983093 arm and from 983090983088 to 983093983091 in the WHO-983093+ arm in

both arms improvements were sustained six months

later Fuller and colleagues used a three year stepped

wedge design in 983089983094 intensive care units and 983092983092 acute

care of the elderly wards and reported an absolute

increase in compliance of 983089983091-983089983096 and 983089983088-983089983091 respec-

tively in implementing wards983091983090 Only 983091983091 of 983094983088 enrolled

wards however implemented the intervention (983090983090 out

of 983092983092 elderly wards and 983089983089 out of 983089983094 intensive care units)

and the intention to treat analysis did not show

increased compliance in the elderly wards while com-

pliance in intensive care units increased by 983095-983097Meta-analysis (with intention to treat results) provided

evidence favouring the WHO-983093+ strategy The pooled

odds ratio was 983089983091983093 (983097983093 confidence interval 983089983088983092 to 983089983095983094

I983090=983096983089) (fig 983091 ) The large heterogeneity seemed to be

caused by the low fidelity to intervention in acute care

of the elderly wards Per protocol analyses gave similar

odds ratios for compliance to the study by Huis and col-

leagues (983089983094983095 (983097983093 confidence interval 983089983090983096 to 983090983090983090) for

elderly wards and 983090983088983097 (983089983093983093 to 983090983096983089) for intensive care

units) Two other randomised controlled trials directly

reported observed compliance with hand hygiene An

individually randomised trial of an education pro-

gramme versus no intervention for nurses in Chinareported an absolute improvement in compliance of

RCTs CCT CBA

Fuller 2012

Huis 2013

Mertz 2010

Huang 2002

Fisher 2013

Salamati 2013

Mayer 2011

Gould 2011

Benning 1997

W a s a l l o

c a t i o n s e q u e n c e a d e q u a t e l y g e n e r a t e d

W a s a l l o

c a t i o n a d e q u a t e l y c o n c e a l e d

W e r e b a s e l i n e o u t c o m e m e a s u r e m e n t s s i m i l a r

W e r e b a s e l i n e c h a r a t e r i s t i c s s i m i l a r

W e r e i n c

o m p l e t e o u t c o m e d a t a a d e q u a t e l y a d d r e s s e d

W a s s t u d y a d e q u a t e l y p r o t e c t e d a g a i n s t c o n t a m i n a t i o n

W a s s t u d y f r e e f r o m s e l e c t i v e o u t c o m e r e p o r t i n g

W a s s t u d y f r e e f r o m o t h e r r i s k s o f b i a s

W a s k n o

w l e d g e o f a l l o c a t e d i n t e r v e n t i o n s

a d e q u a t

e l y a d d r e s s e d

W a s k n o


a d e q u a t

e l y p r e v e n t e d d u r i n g s t u d y

Low risk of bias

Unclear risk of bias

High risk of bias

ITS

Derde 2014

Lee 2013

Marra 2013

Al-Tawfiq 2013

Armellino 2013

Armellino 2012

Chan 2013

Crews 2013

Salmon 2013

Talbot 2013Higgins 2013

Helder 2012

Kirkland 2012

Morgan 2012

Stone 2012

Jaggi 2012

Lee 2012

Mestre 2012

Koff 2011

Doron 2011

Marra 2011

Yngstrom 2001

Helms 2010

Chou 2010

Vernaz 2008

Whitby 2008

Grayson 2008

Eldrige 2006

Johnson 2005

Khatib 1999

Tibballs 1996

Dubbert 1990

W a s i n t e

r v e n t i o n i n d e p e n d e n t o f o t h e r c h a n g e s

W a s s h a p e o f i n t e r v e n t i o n e ff e c t p r e - s p e c i fi e d

W a s i n t e

r v e n t i o n u n l i k e l y t o a ff e c t d a t a c o l l e c t i o n

W e r e i n c




Fig 983090 | Assessment o risk o bias in included studies o interventions to promote handhygiene in healthcare workers



RESEARCH

6

983091983090983095 (983097983093 confidence interval 983089983093983094 to 983092983097983095) for

opportunities before contact with patients and 983090983088983092

(983093983094 to 983091983093983090) for opportunities after contact (baseline

compliance before and after contact was about 983090983093 and

983091983095 respectively in both arms)983091983091 In Canada a cluster

randomised trial of a bundle of education performance

feedback and visual reminders in 983091983088 hospital units

where alcohol hand rub was available at point of care in

both arms (but with no other interventions in the con-

trol arm) reported a higher adherence after the interven-

tion in the intervention arm (mean difference 983094983091

983097983093 confidence interval 983092983091 to 983096983092)983091983093 In both arms

baseline compliance was low (983089983094)

Fisher and colleagues randomised individuals to

either a control group where hand hygiene was not

actively promoted or an intervention arm that used

audio reminders and individual feedback983091983089 They

assessed compliance using an automated system at

entry to and exit from patientsrsquo rooms The interven-

tion was associated with a 983094983096 (983097983093 confidence

interval 983090983093 to 983089983089983089) improvement in complianceSalamati and colleagues randomised nursing person-

nel to either a motivational interviewing intervention

(a behaviour modification approach initially devel-

oped to treat patients with alcoholism) or a control

group983091983094 Both arms also received an educational inter-

vention The outcome measure was a composite hand

hygiene score which was found to increase in the

intervention arm The scoring details however were

unclear

Interrupted time series

Of 983091983090 interrupted time series 983090983093 measured hand

hygiene compliance Only 983089983096 studies with directobservation however reported the number of obser-

vations at each time point making them eligible for

re-analysis983090983096-983091983088 983091983095 983091983096 983092983088-983092983094 983092983096 983093983088 983093983092 983093983094 983094983088 983094983092 983094983093 As some of these

studies were conducted at multiple sites983092983096 or had multi-

ple intervention phases983093983094 983090983090 pairwise comparisons

from these 983089983096 studies were available for re-analysis (fig 983092 )

In four studies there was evidence of positive first order

autocorrelation983091983095 983091983096 983092983088 983093983094

The baseline compliance ranged from 983095983094 to 983097983089983091

Twelve of 983090983090 comparisons showed a declining trend in

compliance during the period before intervention

seven of these did not report any activities to promote

hand hygiene before intervention while another fourused only education or reminders Fifteen pairwise

contrasts showed a positive change in trend for com-

pliance with hand hygiene after the intervention

(table 983091 ) All but four contrasts showed both stepwise

increases in compliance with hand hygiene associated

with the intervention and increases in mean compli-

ance in the period after intervention compared with

that expected in the absence of the intervention The

range was wide the mean change in hand hygiene

attributed to the intervention varied between a

decrease of 983089983092983096 and an increase of 983096983091983091 (table 983091 )

Two studies had an intervention period lasting at least

two years neither showed evidence for any decline in

compliance over this period983092983088 983092983089 In only one study was

there a net trend for decreasing compliance after the

intervention (fig 983092)983092983093

Non-randomised trials and controlled beore-afer

studies

Mayer and colleagues compared WHO-983093 and reward

incentives (WHO-983093+) with a combination of system

change education and feedback using a staggeredintroduction of an intervention bundle across four out

of six patient units983094983094 The WHO-983093+ intervention was

associated with improved compliance which increased

from 983092983088 to 983094983092 in one two-unit cohort and from 983091983092

to 983092983097 in the other

Benning and colleagues reported a hospital-wide

trend of increased soap and alcohol consumption in

both intervention (package of system change remind-

ers and safety climate) and control (no intervention)

groups but found no evidence of an increased effect in

the intervention group983094983095 Gould and colleagues found

no evidence of improvement in frequency of hand

decontamination in surgical intensive care wardsresulting from a series of educational lectures com-

pared with no intervention (control)983094983096

Analysis o interrupted time series and network

meta-analysis

Among the 983090983090 pairwise comparisons from interrupted

time series 983089983096 had clear details about interventions and

similar indications for compliance with hand hygiene

among qualified healthcare workers In 983089983094 of these the

intervention period included additional intervention

components alongside measures to promote hand

hygiene used in the baseline period and all outcome

data favoured the intervention (fig 983093 ) In the two com-parisons where there was no improvement in hand

Fuller 2012 (acute care of elderly wards)

Fuller 2012 (intensive care units)

Huis

Total (95 CI)

Test for heterogeneityτ2=004

χ2=1063 df=2 P=0005 I2=81

Test for overall effect z=227 P=002

106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000

Author Mean odds ratio(95 CI)

Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental

Mean odds ratio(95 CI)

Fig 983091 | Forest plot o the associations between WHO-983093 and goal setting compared with WHO-983093 alone and compliance withhand hygiene rom randomised controlled trials using intention to treat results



RESEARCH

7

Time (months)

P r o b a b i l i t y o f h a n d

h y g i e n e c o m p l i a n c e

Lee et al 2013 hospital 4No intervention v WHO-5

0 5 10 15 20

Time (months)

Lee et al 2013 hospital 7WHO-5 v WHO-5

0 5 10 15 20

Time (months)

Lee et al 2013 hospital 8SYS v WHO-5

0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)



Higgins et alNo intervention v WHO-5+INC

0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al

No intervention v WHO-5+INC+GOAL

0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al

No intervention v WHO-5

0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)



Kirkland et alNo intervention v WHO-5

0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25

Al-Tawfiq et alNo intervention v WHO-5+GOAL

Time (months)

Talbot et al phase I-IIEDU v WHO-5+INC+GOAL

0 10 20 20 40

Talbot et al phase II-IIIWHO-5+INC+GOALv WHO-5+INC+GOAL+ACC

0

02

04

06

08

10



Derde et alREM v EDU+FED+REM

Time (months)

Doron et alSYS+EDU+FED+REMv WHO-5

0 5 10 15 20

Crews et alEDU v SYS+EDU+FED+REM+INC+GOAL

Dubbert et alNo intervention v EDU+FED

0

02

04

06

08

10



Tibballs et alSYS v SYS+EDU

Time (months)

Khatib et alEDU v EDU+FED

0 05 10 15 20

Time (months)

Jaggi et alUnclear interventions

0 10 20 30 40

Time (months)

Armellino et al 2012No intervention v FED+GOAL

0 2 4 6 80

02

04

06

08

10




Salmon et alNo intervention v EDU

0

02

04

06

08

10

Fig 983092 | Re-analysis o studies involving interrupted time series where the outcome was hand hygiene compliance Points represent observations solidlines show expected values rom fitted segmented regression models and broken lines represent extrapolated trends beore intervention SYS=system

change EDU=education FED=eedback REM=reminders SAF =institutional saety climate INC=incentives GOAL=goal setting ACC=accountabilityWHO-983093=combined intervention strategies including SYS EDU FED REM and SAF



RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013

Talbot phase I-II 2013

Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013

Talbot phase II-III 2013

026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)

No intervention v EDU+FED





No intervention v WHO-5+INC

No intervention v WHO-5+GOAL


SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED

EDU v SYS+EDU+FED+REM+INC+GOAL

EDU v WHO-5+INC+GOAL

REM v EDU+FED+REM

SYS v EDU+FED+REM v WHO-5

WHO-5 v WHO-5

WHO-5 v WHO-5

WHO-5+INC+GOALv WHO-5+INC+GOAL+ACC

-5 0 5 10

Author

Favours control Favours experimental

Mean log oddsratio (95 CI)


Fig 983093 | Forest plot showing effect size as mean log odds ratios or hand hygiene compliance or all direct pairwise comparisonsrom interrupted time series studies Lee and colleagues983092983096 was a multi-centre study In hospitals 983096 and 983097 baseline strategy wasalready equivalent to WHO-983093 SYS=system change EDU=education FED=eedback REM=reminders SAF =institutional saety

climate INC=incentives GOAL=goal setting ACC=accountability WHO-983093=combined intervention strategies including SYSEDU FED REM and SAF

Table 983091 | Results o re-analysis o studies using interrupted time series to assess compliance with hand hygiene

Study Comparison

Baseline (intercept)Coefficient (SE)or baseline trend

Coefficient (SE)or change intrend

Coefficient (SE)or change inlevel

Mean (983097983093 CI) change incompliance compliance Coefficient (SE)

Lee983092983096

Hospital 983092 No intervention v WHO-983093 983092983092983094 minus983088983090983089983093 (983088983091983088) minus983088983088983096983089 (983088983089983088) 983088983089983091983088 (983088983089983088) 983088983094983088983094 (983088983090983094) 983090983097983097 (983091983093 to 983093983094983092)

Hospital 983095 WHO-983093 v WHO-983093 983093983091983096 983088983089983093983092 (983088983090983097) 983088983090983096983089 (983088983088983095) minus983088983089983093983089 (983088983088983096) minus983089983088983092983090 (983088983090983093) minus983089983089983093 ( minus983089983091983093 to minus983097983093)

Hospital 983096 SYS v WHO-983093 983092983092983094 minus983088983090983089983093 (983088983090983094) 983088983088983093983097 (983088983088983094) 983088983088983089983092 (983088983088983094) 983088983093983094983091 (983088983089983097) 983089983091983091 ( minus983097983090 to 983091983093983096)

Hospital 983097 WHO-983093 v WHO-983093 983094983090983091 983088983093983088983091 (983088983091983091) 983088983088983096983096 (983088983089983091) minus983088983088983097983092 (983088983089983091) minus983088983088983088983095 (983088983093983089) minus983097983095 ( minus983094983091983094 to 983092983092983091)

Derde983092983090 REM v EDU+FED+REM 983093983090983096 983088983089983089983090 (983088983088983092) minus983088983088983089983093 (983088983088983089) 983088983089983091983091 (983088983088983090) 983088983091983092983094 (983088983088983093) 983089983094983091 (983089983091983094 to 983089983097983089)

Higgins983092983093 No intervention v WHO-983093+INC 983091983095983090 minus983088983092983090983096 (983088983089983095) minus983088983088983088983097 (983088983090983093) minus983088983088983091983088 (983088983088983091) 983090983092983092983096 (983088983090983093) 983092983096983096 (983092983093983092 to 983093983090983091)

Doron983092983091 SYS+EDU+FED+REM v WHO-983093 983095983088983095 983088983090983088983092 (983088983089983090) 983088983089983096983095 (983088983089983088) minus983088983088983092983088 (983088983088983091) 983088983093983096983094 (983088983088983089) 983092983095 (983090983091 to 983095983089)

Chou983092983088dagger No intervention v WHO-983093+INC+GOAL 983093983092983097 983088983089983097983096 (983088983088983091) minus983088983088983091983097 (983088983088983088) 983088983089983093983089 (983088983088983089) 983088983092983093983091 (983088983089983095) 983093983094983092 (983093983091983089 to 983093983097983096)

Marra983093983088 No intervention v WHO-983093 983092983093983095 minus983088983089983095983091 (983088983088983095) 983088983088983090983088 (983088983088983094) 983088983088983094983091 (983088983088983091) 983088983090983089983096 (983088983088983094) 983089983089983093 (983091983092 to 983089983097983094)

Helms983091983088 No intervention v WHO-983093 983097983089983091 983090983091983093983088 (983088983092983090) minus983088983090983097983095 (983088983089983096) 983088983091983093983092 (983088983089983097) 983088983095983088983094 (983088983091983091) 983091983093983097 ( minus983093983096 to 983095983095983095)

Kirkland983090983097 No intervention v WHO-983093 983093983089983091 983088983088983093983090 (983088983089983092) minus983088983088983097983095 (983088983088983092) 983088983089983089983089 (983088983088983092) 983092983092983092983091 (983089983088983091) 983096983091983091 (983095983095983088 to 983096983097983094)

Al-Tawfiq983090983096 No intervention v WHO-983093+GOAL 983092983089983091 minus983088983091983093983088 (983088983088983097) minus983088983088983089983092 (983088983088983090) 983088983088983096983089 (983088983088983095) 983090983091983090983096 (983088983090983089) 983092983097983097 (983092983090983096 to 983093983095983088)

Crews983092983089 EDU v SYS+EDU+FED+REM+INC+GOAL 983093983088983095 983088983088983090983096 (983088983089983090) minus983088983088983095983088 (983088983088983090) 983088983089983088983091 (983088983088983090) 983091983094983095983097 (983088983090983090) 983091983096983090 (983091983093983093 to 983092983088983097)

Talbot(phase I)983093983094dagger

EDU v WHO-983093+INC+GOAL 983093983094983095 983088983090983095983089 (983088983090983088) minus983088983088983088983094 (983088983088983090) 983088983089983088983097 (983088983088983090) 983088983091983094983091 (983088983092983089) 983089983096983093 ( minus983089983092 to 983091983096983092)

Talbot

(phase II)

983093983094

WHO-983093+INC+GOAL v

WHO-983093+INC+GOAL+ACC

983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)

Dubbert983094983088 No intervention v EDU+FED 983094983097983093 983088983096983090983090 (983088983091983092) 983088983094983091983094 (983088983091983097) 983090983097983088983096 (983089983093983095) minus983088983095983093983091 (983088983095983093) 983088983095 ( minus983089983088983088 to 983089983089983092)

Tibballs983094983093 SYS v SYS+EDU 983090983091983092 minus983089983089983096983094 (983088983093983091) 983088983089983096983095 (983088983089983088) minus983088983088983092983088 (983088983088983091) 983088983092983093983091 (983088983093983095) 983089983089983097 ( minus983089983096983092 to 983092983090983089)

Khatib983094983092 EDU v EDU+FED 983096983094983090 983089983096983091983094 (983088983089983095) minus983090983088983093983089 (983088983090983094) 983090983089983096983093 (983088983093983090) 983090983093983092983097 (983088983090983097) 983094983093983096 (983093983096983094 to 983095983091983088)

Jaggi983092983094 Unclear intervention details 983089983097983093 minus983089983092983090983088 (983088983090983094) 983088983088983096983088 (983088983088983090) minus983088983088983088983094 (983088983088983091) minus983088983093983096983094 (983088983091983092) minus983089983092983096 ( minus983091983091983089 to 983091983094)

Armellino983091983096dagger No intervention v FED+GOAL 983095983094 minus983090983092983097983091 (983088983089983093) minus983088983088983096 983096 (983088983089983091983091) 983088983096983092983097 (983088983090983091983093) 983091983088983092983094 (983088983094983096) 983092983093983092 (983091983096983093 to 983093983090983091)

Armellino983091983095dagger No intervention v FED+GOAL 983090983097983088 minus983088983096983097983093 (983088983088 983092) 983088983089983090983090 (983088983089983088) minus983088983089983088983097 (983088983088983096) 983090983090983094983095 (983088983089983092) 983095983092983097 (983094983093983093 to 983096983092983092)

Salmon983093983092Dagger No inter vention v EDU 983092983090983095 minus983088983090983097983093 (983088983089983095) 983088983088983088983091 (983088983088983090) 983088983088983090983089 (983088983088983090) 983088983092983096983093 (983088983090983090) 983089983095983097 ( minus983088983091 to 983091983094983090)

SYS=system change EDU=education FED=eedback REM=reminders SAF =institutional saety climate INC=incentives GOAL=goal setting ACC=accountability WHO -983093=combinedintervention strategies including SYS EDU FED REM and SAFMean change in hand hygiene compliance during period afer intervention period attributed to intervention accounting or baseline trends (see appendix 983091 or details)daggerEvidence o autocorrelation Newey-West standard errors reportedDaggerHand hygiene compliance measured in student nurses



RESEARCH

9

hygiene all components of the intervention were

already in place in the baseline period983092983096

Twelve pairwise comparisons met the criteria for net-

work meta-analysis and included direct comparisons

between all pairs of strategies except WHO-983093 versus

WHO-983093+ and no intervention versus single intervention

(fig 983094 ) The network meta-analysis showed that

although there was large uncertainty in effect sizes

among the pairwise comparisons point estimates for

all intervention strategies indicated an improvement in

compliance with hand hygiene compared with no inter-

vention (fig 983095 ) When two strategies WHO-983093 and WHO-

983093+ were compared with no intervention there was

strong evidence that they were effective (table 983090 ) The

WHO983093+ strategy also showed additional improvement

compared with single intervention strategies and

WHO-983093 alone For the latter comparison which

depended only on indirect comparisons the estimated

effect size was similar to that seen in the randomised

controlled trials though uncertainty was much larger

(odds ratio for WHO-983093 versus WHO-983093+ was 983089983096983090 983097983093

credible interval 983088983090 to 983089983090983090) WHO-983093+ had the highest

probability (983094983095) of being the best strategy in improv-

ing compliance (fig 983096)

After we excluded studies with multiple stepwise

interventions in the sensitivity analysis there was a

decrease in the effect size of all intervention strategies

(appendix 983092)

Clinical outcomes

Nineteen studies reported clinical or microbiological

outcomes alongside hand hygiene outcomes Six of

these were multicentre studies983091983093 983092983090 983092983096 983093983093 983094983090 983094983095 and 983089983091 were

based in a single hospital983090983096-983091983088 983092983094 983092983095 983092983097 983093983090 983093983094 983093983095 983093983097 983094983091 983094983094 983094983097 Allreported that improvements in hand hygiene were asso-

ciated with reductions in at least one measure of hospi-

tal acquired infection andor resistance rates In most

WHO-5

WHO-5+

None Single

Fig 983094 | Network structure or network meta-analysis o ourhand hygiene intervention strategies rom interrupted timeseries studies Intervention strategies were none (nointervention) single intervention WHO-983093 and WHO-983093+ (WHO-983093 with incentives goal-setting or accountability)

Intervention strategies

O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100

Fig 983095 | Box-and-whiskers plot showing relative efficacy odifferent hand hygiene intervention strategies comparedwith standard o care estimated by network meta-analysisrom interrupted time series studies Lower and upperedges represent 983090983093th and 983095983093th centiles rom posteriordistribution central line median Whiskers extend to 983093thand 983097983093th centiles Intervention strategies were single

intervention WHO-983093 and WHO-983093+ (WHO-983093 with incentivesgoal-setting or accountability) Appendix 983097 shows resultsrom sensitivity analysis that excluded studies whereinterventions were implemented as multiple time points

P r o b a b i l i t y

WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10

No interventioncurrent practice

Fig 983096 | Rankograms showing probabilities o possible rankings or each intervention strategy (rank 983089=best rank 983092=worst)



RESEARCH

10

case however either appropriate analysis was lacking

denominators were not reported time series data were

not shown (making interrupted time series designs vul-

nerable to pre-existing trends) or numbers were too

small to draw firm conclusions

There were however three single centre studies that

did not have these limitations983092983097 983093983095 983094983091 Two of these stud-

ies which lasted about seven years used time series

analysis to study associations between use of alcohol

hand rub and clinical outcomes with adjustment for

changing patterns of antibiotic use983092983097 983093983095 Lee and col-

leagues found strong evidence (Plt983088983088983088983089) that increased

use of alcohol hand rub was associated with reduced

incidence of healthcare associated infection and evi-

dence that it was associated with reduced healthcare

associated methicillin resistant Staphylococcus aureus

(MRSA) infection (P=983088983088983090)983092983097 Vernaz and colleagues

found strong evidence that increased use of alcohol

based hand rub was associated with reduced incidence

of MRSA clinical isolates per 983089983088983088 patient days

(Plt983088983088983088983089) reporting that 983089L of hand rub per 983089983088983088 patient

days was associated with a reduction in MRSA of 983088983088983091

isolates per 983089983088983088 patient days983093983095 No association was

found between increased use of alcohol based hand

rub and clinical isolates of Clostridium difficile John-

son and colleagues reported that an intervention in an

Australian teaching hospital associated with a mean

improvement of compliance with hand hygiene from

983090983089 to 983092983090 was also associated with declining trends

in clinical MRSA isolates (by 983091983094 months after the inter-

vention clinical isolates per discharge had fallen by

983092983088 compared with the baseline before the interven-

tion) declining trends in MRSA bacteraemias (983093983095

lower than baseline after 983091983094 months) and decliningtrends in clinical isolates of extended spectrum β lact-

amases (ESBL) producing E coli and Klebsiella (gt983097983088

below baseline 983091983094 months after intervention) though

there was no evidence of changes in patient MRSA col-

onisation at four or 983089983090 months after the intervention983094983091

In addition to hand hygiene however the intervention

included patient decolonisation and ward cleaning

and the relative importance of these measures cannot

be determined

Among the multicentre studies Grayson and col-

leagues described a similar hand hygiene intervention

(but without additional decolonisation or ward clean-

ing) initially introduced to six hospitals as a pilot studyand later to 983095983093 hospitals in Victoria Australia as part

of a state-wide roll out983094983090 Both the pilot and roll out

were associated with large improvements in compli-

ance (from about 983090983088 to 983093983088) and similar clinically

important trends after the intervention for reduced

MRSA bacteraemias and MRSA clinical isolates per

patient discharge (though in the state-wide roll out

hospitals there was also a decline in MRSA clinical iso-

lates before the intervention that continued after the

intervention)

Roll out of a similar hand hygiene intervention (the

Cleanyouhands campaign based on WHO-983093) in England

and Wales was reported to be associated with reducedrates of MRSA bacteraemia (from 983089983097 to 983088983097 cases per

983089983088 983088983088983088 bed days) and C difficile infection (from 983089983094983096 to

983097983093 cases per 983089983088 983088983088983088 bed days) but no association was

found with methicillin-sensitive S aureus (MSSA) bacte-

raemia983093983093 This study also reported independent associ-

ations between procurement of alcohol hand rub and

MRSA bacteraemias in the last 983089983090 months of the study

MRSA bacteraemias were estimated to have fallen by 983089

(983097983093 confidence interval 983093 to 983089983093) for each additional

mL of hand rub used per bed day (adjusted for other

interventions and hospital level mupirocin use a surro-

gate marker for MRSA screening and decolonisation)

Similarly each additional mL of soap used per bed day

was associated with a 983088983095 (983088983092 983089983088) reduction in

C difficile infection

Benning and colleagues described the evaluation of a

separate but contemporaneous patient safety interven-

tion that included a hand hygiene component in nine

English hospitals with nine matched controls983094983095 Both

intervention and control sites experienced large

increases in consumption of soap and alcohol hand rub

between 983090983088983088983092 and 983090983088983088983096 and substantial falls in rates of

MRSA and C difficile infection though in all cases (soap

hand rub and infections) there was no evidence that

differences between intervention and control sites

resulted from anything other than chance

In a two year study in 983091983091 surgical wards in 983089983088 Euro-

pean hospitals Lee and colleagues found that after

adjustment for clustering potential confounders and

temporal trends enhanced hand hygiene alone was not

associated with a reduction in MRSA clinical cultures

and MRSA surgical site infections and neither was a

strategy of screening and decolonisation but in wards

where both interventions were combined there was a

reduction in the rate of MRSA clinical cultures of 983089983090per month (adjusted incidence rate ratio 983088983096983096 983097983093 con-

fidence interval 983088983095983097 to 983088983097983096)983092983096

Among the randomised controlled trials Mertz and

colleagues found similar rates of hospital acquired

MRSA colonisation in intervention and control groups

(983088983095983091 v 983088983094983094 events per 983089983088983088983088 patient days respectively

P=983088983097983090) though adherence to hand hygiene was only

983094 higher in the intervention arm983091983093 Finally in a study

in 983089983091 European intensive care units Derde and col-

leagues reported a declining trend in acquisition of

antimicrobial resistant bacteria (weekly incidence rate

ratio 983088983097983095983094 983097983093 confidence interval 983088983097983093983092 to 983088983097983097983097)

associated with a hand hygiene intervention thatincreased compliance from about 983093983088 to over 983095983088983092983090

The decline was largely because of reduced MRSA

acquisition The intervention also included universal

chlorhexidine body washing and it is not possible to

establish the relative importance of hand hygiene

Level o inormation on resource use

Reporting of information on cost and resource use was

limited with 983091 983090983094 and 983089983090 studies classified as having

high moderate and low information respectively

(appendix 983096) Three studies reported costs associated

with both materials and person time983091983092 983093983090 983094983094 in two cases

these reports were in separate papers983095983088 983095983089 Table 983092 sum-marises the reported costs of interventions


httpslidepdfcomreaderfullbmjh3728full 1114



RESEARCH

12

data has also been proposed983095983094 Cost effectiveness anal-

ysis of promotion of hand hygiene is required to assess

under what circumstances these initiatives represent

good value for money and when resources might be bet-

ter directed at supplemental interventions including

care bundles983095983095 ward cleaning983095983096 and screening and

decolonisation983095983097 to complement well maintained com-

pliance with hand hygiene

Strengths and limitations o study

A particular strength of our study is that the network

meta-analysis allowed us to quantify the relative effi-

cacy among a series of different intervention strategies

with different baseline interventions even where the

direct head-to-head comparisons were absent

This study also has several limitations Firstly

details on implementation of components of the inter-

vention varied substantially For example personal

feedback and group feedback were classified together

but in practice the impacts of these strategies can

vary Moreover different studies might implement the

same programme with different quality of delivery and

level of adherence so called intervention fidelity or

type III error983096983088 Both issues are common to many inter-

ventions to improve the quality of care in hospital set-

tings and are likely to be responsible for much of the

unexplained heterogeneity between studies983096983089 983096983090 Sec-

ondly direct observation of compliance with hand

hygiene might induce an increase in compliance unre-

lated to the intervention (the Hawthorne effect)

Recent research suggests that such Hawthorne effects

can lead to substantial overestimation of compli-

ance983096983091 983096983092 Such effects however should not bias esti-

mates of the relative efficacy of different interventionsfrom randomised controlled trials and interrupted

time series unless the effects vary between study arms

intervention periods Thirdly it is possible that it is the

novelty of the intervention itself that leads to improve-

ments in compliance and that any sufficiently novel

intervention would do the same regardless of the com-

ponents used This clearly cannot be ruled out and is

not necessarily inconsistent with our findings that

interventions with more components tend to perform

better At present however there are too few high

quality studies to evaluate whether individual compo-

nents of interventions show consistent differences

that cannot be explained by novelty alone Fourthresults might be distorted by publication bias Fifth

there might also be a low level of language bias

because we excluded studies in languages other than

English The magnitude of such bias however is likely

to be small983096983093 983096983094

Finally linking improved compliance to clinical out-

comes such as number of infections prevented would

provide more direct evidence about the value of such

interventions983089983088 Such direct evidence is still limited in

hospital settings although the association is supported

by a growing body of indirect evidence as well as bio-

logical plausibility Moreover findings from studies

included in our review that reported clinical or microbi-ological outcomes are consistent with substantial

reductions in infections for some pathogens such as

MRSA resulting from large improvements in hand

hygiene983096983095 983096983096 The lack of a measureable effect of

improved hand hygiene on MSSA infections might seem

paradoxical but can be partly explained by the fact that

MSSA infections are much more likely to be of endoge-

nous origin whereas MRSA is more often linked to nos-

ocomial cross transmission Moreover predictions from

modelling studies that hand hygiene will have a dispro-

portionate effect on the prevalence of resistant bacteria

in hospitals (provided resistance is rare in the commu-

nity) seem to have been borne out in practice983096983097

Conclusions

While there is some evidence that single component

interventions lead to improvements in hand hygiene

there is strong evidence that the WHO-983093 intervention

can lead to substantial rapid and sustained improve-

ments in compliance with hand hygiene among health-

care workers in hospital settings There is also evidence

that goal setting reward incentives and accountability

provide additional improvements beyond those

achieved by WHO-983093 Important directions for future

work are to improve reporting on resource implications

for interventions increasingly focus on strong study

designs and evaluate the long term sustainability and

cost effectiveness of improvements in hand hygiene

We are grateul to all authors o the literature included in this reviewwho responded to requests or additional inormation We also thankthe inection control staff o Sappasithiprasong Hospital or technicalsupport and Cecelia Favede or help in editing

Contributors NL BSC YL DL NG and ND contributed to the studyconception and design NL and BSC extracted data and NL perormedthe data analysis NL wrote the first draf DL YL MH ASL SH NG ND

and BSC critically revised the manuscript or important intellectualcontent All authors read and approved the final manuscript NL andBSC are guarantors

Funding This research was part o the Wellcome Trust-MahidolUniversity-Oxord Tropical Medicine Research Programme supportedby the Wellcome Trust o Great Britain (983088983096983097983090983095983093Z983088983097Z) BSC wassupported by the Oak Foundation and the Medical Research Counciland Department or International Development (grant No MRK983088983088983094983097983090983092983089)

Competing interests All authors have completed the ICMJE uniormdisclosure orm at httpwwwicmjeorgcoi_disclosurepd anddeclare no financial relationships with any organisations that mighthave an interest in the submitted work in the previous three years noother relationships or activities that could appear to have inluencedthe submitted work

Ethical approval Not required

Data sharing The relevant data and code used in this study areavailable rom the authors

Transparency The lead author affirms that this manuscript is anhonest accurate and transparent account o the study being reportedthat no important aspects o the study have been omitted and thatany discrepancies rom the study as planned (and i relevantregistered) have been explained

This is an Open Access article distributed in accordance with the termso the Creative Commons Attribution (CC BY 983092983088) license whichpermits others to distribute remix adapt and build upon this work orcommercial use provided the original work is properly cited Seehttpcreativecommonsorglicensesby983092983088

983089 Weinstein RA Nosocomial inection update Emerg Infect Dis 983089983097983097983096983092983092983089983094-983090983088

983090 Jarvis WR Selected aspects o the socioeconomic impact onosocomial inections morbidity mortality cost and preventionInfect Control Hosp Epidemiol 983089983097983097983094983089983095983093983093983090-983095

983091 Rosenthal VD Maki DG Jamulitrat S et al International NosocomialInection Control Consortium (INICC) report data summary or983090983088983088983091-983090983088983088983096 issued June 983090983088983088983097 Am J Infect Control 983090983088983089983088983091983096983097983093-983089983088983092e983090



RESEARCH

13

983092 WHO guidelines on hand hygiene in health care (First global patientsaety challenge clean care is saer care) WHO 983090983088983088983097

983093 Gould DJ Moralejo D Drey N Chudleigh JH Interventions to improvehand hygiene compliance in patient care Cochrane Database SystRev 983090983088983089983089983097CD983088983088983093983089983096983094

983094 Huis A van Achterberg T de Bruin M et al A systematic review ohand hygiene improvement strategies a behavioural approachImplement Sci 983090983088983089983090983095983097983090

983095 Schweizer ML Reisinger HS Ohl M et al Searching or an optimal

hand hygiene bundle a meta-analysis Clin Infect Dis 983090983088983089983092983093983096983090983092983096-983093983097983096 Naikoba S Haryeard A The effectiveness o interventions aimed at

increasing handwashing in healthcare workersmdasha systematic review J Hosp Infect 983090983088983088983089983092983095983089983095983091-983096983088

983097 Drummond MF Sculpher MJ Torrance GW OrsquoBrien BJ Stoddart GLMethods or the economic evaluation o health care programmesOxord University Press 983090983088983088983093

983089983088 Graves N Halton K Page K Barnett A Linking scientific evidence anddecision making a case study o hand hygiene interventions InfectControl Hosp Epidemiol 983090983088983089983091983091983092983092983090983092-983097

983089983089 Moher D Liberati A Tetzlaff J Altman DG The PRISMA Group (983090983088983088983097)preerred reporting items or systematic reviews and meta-analysesthe PRISMA statement PLoS Med 983090983088983088983097983094e983089983088983088983088983088983097983095

983089983090 Effective Practice and Organisation o Care (EPOC) What study designsshould be included in an EPOC review EPOC Resources or reviewauthors Norwegian Knowledge Centre or the Health Services 983090983088983089983091httpepoccochraneorgepoc-specific-resources-review-authors

983089983091 Cochrane Effective Practice and Organisation o Care Review Group

Data Collection Checklist EPOC Resources or review author sNorwegian Knowledge Centre or the Health Services 983090983088983089983091 httpepoccochraneorgsitesepoccochraneorgfilesuploadsdatacollectionchecklistpd

983089983092 Higgins JPT Green S Cochrane handbook or systematic reviews ointerventions Version 983093983089983088 [updated March 983090983088983089983089] The CochraneCollaboration 983090983088983089983089 wwwcochrane-handbookorg

983089983093 DerSimonian R Laird N Meta-analysis in clinical trials Control ClinTrials 983089983097983096983094983095983089983095983095-983096983096

983089983094 Borenstein M Hedges LV Higgins JPT Rothstein HR Identiying andquantiying heterogeneity Part 983092 Heterogeneity In Introduction tometa-analysis John Wiley 983090983088983088983097983089983088983095-983090983093

983089983095 Peters JL Sutton AJ Jones DR Abrams KR Rushton L Contour-enhanced meta-analysis unnel plots help distinguish publicationbias rom other causes o asymmetry J Clin Epidemiol 983090983088983088983096983094983089983097983097983089-983094

983089983096 Taljaard M McKenzie JE Ramsay CR Grimshaw JM The use osegmented regression in analysing interrupted time seriesstudies an example in pre-hospital ambulance care Implement Sci

983090983088983089983092983097983095983095983089983097 Ramsay CR Matowe L Grilli R Grimshaw JM Thomas RE Interruptedtimeseries designs in health technology assessment lessons romtwo systematic reviews o behavior change strategies Int J Technol

Assess Health Care 983090983088983088983091983089983097983094983089983091-983090983091983090983088 Vidanapathirana J Abramson M Forbes A Fairley C Mass media

interventions or promoting HIV testing Cochrane Database Syst Rev 983090983088983088983093983091CD983088983088983092983095983095983093

983090983089 Newey WK West KD A simple positive semi-definiteheteroskedasticity and autocorrelation consistent covariance matrixEconometrica 983089983097983096983095983093983093983095983088983091-983096

983090983090 Bolker BM Ecological models and data in R Princeton UniversityPress 983090983088983088983096

983090983091 R Core Team R A language and environment or statisticalcomputing R Foundation or Statistical Computing 983090983088983089983092wwwR-projectorg

983090983092 Lu G Ades AE Combination o direct and indirect evidence in mixedtreatment comparisons Stat Med 983090983088983088983092983090983091983091983089983088983093-983090983092

983090983093 Sutton A Ades AE Cooper N Abrams K Use o indirect and mixed

treatment comparisons or technology assessmentPharmacoeconomics 983090983088983088983096983090983094983095983093983091-983094983095

983090983094 Spiegelhalter DJ Thomas A Best N Lunn D WinBUGS user manualVersion 983089983092 January 983090983088983088983091 wwwmrc-bsucamacukbugs

983090983095 Dias S Welton NJ Caldwell DM Ades AE Checking consistency inmixed treatment comparison meta-analysis Stat Med 983090983088983089983088983090983097983097983091983090-983092983092

983090983096 Al-Tawfiq JA Abed MS Al-Yami N Promoting and sustaining ahospital-wide multiaceted hand hygiene program resulted insignificant reduction in health care-associated inections

Am J Infect Control 983090983088983089983091983092983089983092983096983090-983094983090983097 Kirkland KB Homa KA Lasky RA et al Impact o a hospital-wide hand

hygiene initiative on healthcare-associated inections results o aninterrupted time series BMJ Qual Saf 983090983088983089983090983090983089983089983088983089983097-983090983094

983091983088 Helms B Dorval S Laurent P Winter M Improving hand hygienecompliance a multidisciplinary approach Am J Infect Control 983090983088983089983088983091983096983093983095983090-983092

983091983089 Fisher DA Seetoh T Oh May-Lin H et al Automated measures o handhygiene compliance among healthcare workers using ultrasoundvalidation and a randomized controlled trial Infect Control HospEpidemiol 983090983088983089983091983091983092983097983089983097-983090983096

983091983090 Fuller C Michie S Savage J et al The Feedback Intervention Trial(FIT)mdashimproving hand-hygiene compliance in UK healthcare workersa stepped wedge cluster randomised controlled trial PLoS ONE 983090983088983089983090983095e983092983089983094983089983095

983091983091 Huang J Jiang D Wang X et al Changing knowledge behavior andpractice related to universal precautions among hospital nurses inChina J Contin Educ Nurs 983090983088983088983090983091983091983090983089983095-983090983092

983091983092 Huis A Schoonhoven L Grol R et al Impact o a team andleaders-directed strategy to improve nursesrsquo adherence to hand

hygiene guidelines a cluster randomised trial Int J Nurs Stud 983090983088983089983091983093983088983092983094983092-983095983092983091983093 Mertz D Daoe N Walter SD Brazil K Loeb M Effect o a multiaceted

intervention on adherence to hand hygiene among healthcareworkers a cluster-randomized trial Infect Control Hosp Epidemiol 983090983088983089983088983091983089983089983089983095983088-983094

983091983094 Salamati P Poursharifi H Rahbarimanesh AA Koochak HE Najfi ZEffectiveness o motivational interviewing in promoting hand hygieneo nursing personnel Int J Prev Med 983090983088983089983091983092983092983092983089-983095

983091983095 Armellino D Trivedi M Law I et al Replicating changes in handhygiene in a surgical intensive care unit with remote video auditingand eedback Am J Infect Control 983090983088983089983091983092983089983097983090983093-983095

983091983096 Armellino D Hussian E Schilling ME et al Using high-technology toenorce low-technology saety measures the use o third-partyremote video auditing and real-time eedback in healthcare ClinInfect Dis 983090983088983089983090983093983092983089-983095

983091983097 Chan BP Homa K Kirkland KB Effect o varying the number andlocation o alcohol-based hand rub dispensers on usage in a generalinpatient medical unit Infect Control Hosp Epidemiol 983090983088983089983091983091983092983097983096983095-983097

983092983088 Chou T Kerridge J Kulkarni M Wickman K Malow J Changing theculture o hand hygiene compliance using a bundle that includes aviolation letter Am J Infect Control 983090983088983089983088983091983096983093983095983093-983096

983092983089 Crews JD Whaley E Syblik D Starke J Sustained improvement in handhygiene at a childrenrsquos hospital Infect Control Hosp Epidemiol 983090983088983089983091983091983092983095983093983089-983091

983092983090 Derde LPG Cooper BS Goossens H et al Interventions to reducecolonisation and transmission o antimicrobial-resistant bacteria inintensive care units an interrupted time series study and clusterrandomised trial Lancet Infect Dis 983090983088983089983092983089983092983091983089-983097

983092983091 Doron SI Kiuji K Hynes BT et al A multiaceted approach toeducation observation and eedback in a successul hand hygienecampaign Jt Comm J Qual Patient Saf 983090983088983089983089983091983095983091-983089983088

983092983092 Helder OK Weggelaar AM Waarsenburg DCJ et al Computer screensaver hand hygiene inormation curbs a negative trend in handhygiene behavior Am J Infect Control 983090983088983089983090983092983088983097983093983089-983092

983092983093 Higgins A Hannan M Improved hand hygiene technique andcompliance in healthcare workers using gaming technology

J Hosp Infect 983090983088983089983091983096983092983091983090-983095983092983094 Jaggi N Sissodia P Multimodal supervision programme to reducecatheter associated urinary tract inections and its analysis to enableocus on labour and cost effective inection control measures in atertiary care hospital in India J Clin Diagn Res 983090983088983089983090983094983089983091983095983090-983094

983092983095 Koff MD Corwin HL Beach ML Surgenor SD Lofus RW Reduction inventilator associated pneumonia in a mixed intensive care unit aferinitiation o a novel hand hygiene program J Crit Care 983090983088983089983089983090983094983092983096983097-983097983093

983092983096 Lee AS Cooper BS Malhotra-Kumar S et al Comparison o strategiesto reduce meticillin-resistant Staphylococcus aureus rates in surgicalpatients a controlled multicentre intervention trial BMJ Open 983090983088983089983091983091e983088983088983091983089983090983094

983092983097 Lee YT Chen SC Lee MC et al Time-series analysis o the relationshipo antimicrobial use and hand hygiene promotion with the incidenceo healthcare-associated inections J Antibiot (Tokyo) 983090983088983089983090983094983093983091983089983089-983094

983093983088 Marra AR Noritomi DT Westheimer Cavalcante AJ et al A multicenterstudy using positive deviance or improving hand hygienecompliance Am J Infect Control 983090983088983089983091983092983089983097983096983092-983096

983093983089 Marra AR Guastelli LR de Arauacutejo CM et al Positive deviancea program or sustained improvement in hand hygiene compliance

Am J Infect Control 983090983088983089983089983091983097983089-983093983093983090 Mestre G Berbel C Tortajada P et al ldquoThe 983091983091 strategyrdquo a successul

multiaceted hospital wide hand hygiene intervention based on WHOand continuous quality improvement methodology PLoS One 983090983088983089983090983095e983092983095983090983088983088

983093983091 Morgan DJ Pineles L Shardell M et al Automated hand hygienecount devices may better measure compliance than humanobservation Am J InfectControl 983090983088983089983090983092983088983097983093983093-983097

983093983092 Salmon S Wang XB Seetoh T Lee SY Fisher DA A novel approach toimprove hand hygiene compliance o student nurses AntimicrobResist Infect Control 983090983088983089983091983090983089983094

983093983093 Stone SP Fuller C Savage J et al Evaluation o the nationalCleanyourhands campaign to reduce Staphylococcus aureusbacteraemia and Clostridium difficile inection in hospitals in Englandand Wales by improved hand hygiene our year prospectiveecological interrupted time series study BMJ 983090983088983089983090983091983092983092e983091983088983088983093

983093983094 Talbot TR Johnson JG Fergus C et al Sustained improvement in handhygiene adherence utilizing shared accountability and financialincentives Infect Control Hosp Epidemiol 983090983088983089983091983091983092983089983089983090983097-983091983094



RESEARCH

983093983095 Vernaz N Sax H Pittet D et al Temporal effects o antibiotic use andhand rub consumption on the incidence o MRSA and Clostridiumdifficile J Antimicrob Chemother 983090983088983088983096983094983090983094983088983089-983095

983093983096 Whitby M McLaws ML Slater K Tong E Johnson B Three successulinterventions in health care workers that improve compliance withhand hygiene is sustained replication possible Am J Infect Control 983090983088983088983096983091983094983091983092983097-983093983093

983093983097 Yngstrom D Lindstrom K Nystrom K et al Healthcare-associatedinections must stop a breakthrough project aimed at reducing

healthcare-associated inections in an intensive-care unit BMJ QualSaf 983090983088983089983089983090983088983094983091983089-983094983094983088 Dubbert PM Dolce J Richter W Miller M Chapman SW Increasing ICU

staff handwashing effects o education and group eedback InfectControl Hosp Epidemiol 983089983097983097983088983089983089983089983097983089-983091

983094983089 Eldridge NE Wood SS Bonello RS et al Using the six sigma processto implement the Centers or Disease Control and Preventionguideline or hand hygiene in 983092 intensive care units J Gen Intern Med 983090983088983088983094983090983089(suppl 983090)S983091983093-983092983090

983094983090 Grayson ML Jarvie LJ Martin R et al Significant reductions inmethicillin-resistant Staphylococcus aureus bacteraemia and clinicalisolates associated with a multisite hand hygiene culture-changeprogram and subsequent successul statewide roll-out Med J Aust 983090983088983088983096983090983089983096983096983094983091983091-983092983088

983094983091 Johnson PD Martin R Burrell LJ et al Efficacy o an alcoholchlorhexidine hand hygiene program in a hospital with high rates onosocomial methicillin-resistant Staphylococcus aureus (MRSA)inection Med J Aust 983090983088983088983093983089983096983091983093983088983097-983089983092

983094983092 Khatib M Jamaleddine G Abdallah A Ibrahim Y Hand washing and

use o gloves while managing patients receiving mechanicalventilation in the ICU Chest 983089983097983097983097983089983089983094983089983095983090-983093

983094983093 Tibballs J Teaching hospital medical staff to handwash Med J Aust 983089983097983097983094983089983094983092983091983097983093-983096

983094983094 Mayer J Mooney B Gundlapalli A et al Dissemination andsustainability o a hospital-wide hand hygiene program emphasizingpositive reinorcement Infect Control Hosp Epidemiol 983090983088983089983089983091983090983093983097-983094983094

983094983095 Benning A Dixon-Woods M Nwulu U et al Multiple componentpatient saety intervention in English hospitals controlled evaluationo second phase BMJ 983090983088983089983089983091983092983090d983089983097983097

983094983096 Gould D Chamberlain A The use o a ward-based educationalteaching package to enhance nursesrsquo compliance with inectioncontrol procedures J Clin Nurs 983089983097983097983095983094983093983093-983094983095

983094983097 Marra AR Guastelli LR de Arauacutejo CM et al Positive deviance a newstrategy or improving hand hygiene compliance Infect Control HospEpidemiol 983090983088983089983088983091983089983089983090-983090983088

983095983088 Huis A Hulscher M Adang E et al Cost-effectiveness o a team andleaders-directed strategy to improve nursesrsquo adherence to hand

hygiene guidelines a cluster randomised trial Int J Nurs Stud 983090983088983089983091983093983088983093983089983096-983090983094983095983089 Mestre G Berbel G Tortajada P et al Monitoratge periogravedic retroaccioacute

immediata i treball en equip claus de lrsquoegravexit i sostenibilitat delrsquoestrategravegia 983091983091 drsquohigiene de mans Annals de Medicina 983090983088983089983091983097983094983089-983095

983095983090 Ansari F Grey K Nathwani D et al Outcomes o an intervention toimprove hospital antibiotic prescribing interrupted time series withsegmented regression analysis J Antimicrob Chemother 983090983088983088983091983093983090983096983092983090-983096

983095983091 Davey P Brown E Charani E et al Interventions to improve antibioticprescribing practices or hospital inpatients Cochrane Database SystRev 983090983088983089983091983091983088CD983088983088983091983093983092983091

983095983092 Marwick CA Guthrie B Pringle JEC et al A multiaceted interventionto improve sepsis management in general hospital wards withevaluation using segmented regression o interrupted time seriesBMJ Qual Saf 983090983088983089983092983090983091e983090

983095983093 Graves N Halton K Lairson D Economics and preventinghospital-acquired inection broadening the perspective InfectControl Hosp Epidemiol 983090983088983088983095983090983096983089983095983096-983096983092

983095983094 Page K Graves N Halton K Barnett AG Humans ldquothingsrdquo and spacecosting hospital inection control interventions J Hosp Infect 983090983088983089983091983096983092983090983088983088-983093

983095983095 Aboelela SW Stone PW Larson EL Effectiveness o bundledbehavioural interventions to control healthcare-associated inectionsa systematic review o the literature J Hosp Infect 983090983088983088983095983094983094983089983088983089-983096

983095983096 Dancer SJ Mopping up hospital inection J Hosp Infect 983089983097983097983097983092983091983096983093983089983088983088

983095983097 Harbarth S Fankhauser C Schrenzel J et al Universal screening or

methicillin-resistant Staphylococcus aureus at hospital admission andnosocomial inection in surgical patients JAMA 983090983088983088983096983090983097983097983089983089983092983097-983093983095983096983088 Carroll C Patterson M Wood S et al A conceptual ramework or

implementation fidelity Implement Sci 983090983088983088983095983091983088983092983088983096983089 Dijkstra R Wensing M Thomas R et al The relationship between

organisational characteristics and the effects o clinical guidelines onmedical perormance in hospitals a meta-analysis BMC Health ServRes 983090983088983088983094983090983096983093983091

983096983090 Turner RM Spiegelhalter DJ Smith GC Thompson SG Bias modellingin evidence synthesis J R Stat Soc Ser A Stat Soc 983090983088983088983097983089983095983090983090983089-983092983095

983096983091 Hagel S Reischke J Kesselmeier M et al Quantiying the HawthorneEffect in hand hygiene compliance through comparing directobservation with automated hand hygiene monitoring Infect ControlHosp Epidemiol 983090983088983089983093Apr 983090983091983089-983094

983096983092 Srigley JA Furness CD Baker GR Gardam M Quantification o theHawthorne effect in hand hygiene compliance monitoring using anelectronic monitoring system a retrospective cohort study BMJ QualSaf 983090983088983089983092983090983091983097983095983092-983096983088

983096983093 Juumlni P Holenstein F Sterne J Bartlett C Egger M Direction and impact

o language bias in meta-analyses o controlled trials empirical studyInt J Epidemiol 983090983088983088983090983091983089983089983089983093-983090983091

983096983094 Morrison A Polisena J Husereau D et al The effect o English-language restriction on systematic review-based meta-analysesa systematic review o empirical studies Int J Technol Assess HealthCare 983090983088983089983090983090983096983089983091983096-983092983092

983096983095 Bauer TM Oner E Just HM Just H Daschner F An epidemiologicalstudy assessing the relative importance o airborne and directcontact transmission o microorganisms in a medical intensive careunit J Hosp Infect 983089983097983097983088983089983093983091983088983089-983097

983096983096 Hugonnet S Pittet D Hand hygiene-belies or science Clin MicrobiolInfect 983090983088983088983088983094983091983093983088-983094

983096983097 Lipsitch M Bergstrom CT Levin BR The epidemiology o antibioticresistance in hospitals paradoxes and prescriptions Proc Natl AcadSci USA 983090983088983088983088983097983095983089983097983091983096-983092983091

copy BMJ Publishing Group Ltd 983090983088983089983093

Appendix 983089 Complete search strategy

Appendix 983090 Classification for level of information on

resources use

Appendix 983091 Analysis of interrupted time series data

Appendix 983092 WINBUGs code for network meta-analysis

Appendix 983093 Excluded studies with reason by EPOC

criteria

Appendix 983094 Details of included studies

Appendix 983095 Funnels plots figs A-D

Appendix 983096 Details of extracted intervention

components and level of information on resource use

Appendix 983097 Supplementary results from sensitivity

analysis



RESEARCH

2

(WHO-983093) promotes a multimodal strategy consisting of

five components system change training and educa-

tion observation and feedback reminders in the hospi-

tal and a hospital safety climate More recently

additional strategies for improving hand hygiene have

been evaluated including those based on behavioural

theory

We assessed the relative effectiveness of WHO-983093 and

other strategies for improving compliance with hand

hygiene in healthcare workers in hospital settings Eval-

uation of the evidence for the effectiveness of different

interventions is complicated by three factors firstly

most evaluations of interventions to promote hand

hygiene use non-randomised study designs and in

many cases the reported analysis is inappropriate or

methodological quality is too low to allow meaningful

conclusions to be drawn983093-983096 secondly there is wide vari-

ation between studies in the activities to promote hand

hygiene used in the comparison group thirdly direct

head-to-head comparisons of most interventions are

lacking983095

We aimed to overcome these problems by restricting

attention to randomised trials and high quality

non-randomised studies re-analysing data when nec-

essary explicitly accounting for activities to promote

hand hygiene in the comparison group in each study

and using network meta-analysis to allow indirect com-

parison between interventions

We also summarise information on changes in clini-

cal and microbiological outcomes associated with inter-

ventions when this was reported Information on

resources used in different interventions is essential for

those wanting to implement such interventions or eval-

uate their cost effectiveness983097 983089983088 An additional aim wastherefore to document information on resources used in

interventions to promote hand hygiene

Methods

We developed a protocol and used systematic methods

to identify relevant studies screen study eligibility and

assess study quality This protocol was not registered

This review is reported according to the Preferred

Reporting Items for Systematic Reviews and Meta-Anal-

yses (PRISMA) guidelines983089983089

Search strategy

We used a two stage search strategy Firstly we obtainedall studies considered in two previous reviews (covering

the period up to November 983090983088983088983097) including those that

had been reported as failing to meet inclusion criteria983093 983094

Secondly we extended the search from these studies

from December 983090983088983088983097 to February 983090983088983089983092 We searched

Medline Embase Cumulative Index to Nursing and

Allied Health (CINAHL) Database of Abstracts of

Reviews of Effects (DARE) National Health Service Eco-

nomic Evaluation Database (NHS-EED) National

Health Service Centre for Reviews and Dissemination

(NHS-CRD) and British Nursing Index (BNI) Cochrane

Library (Cochrane database of systematic reviews

Cochrane central register of controlled trials Cochranemethodology register Health Technology assessment

database) Clinical Trialgov Current Clinical Control

trial Cochrane Effective Practice and Organisation of

Care Group (EPOC) register American College of Physi-

cians journal and reviews of evidence based medicine

Results were limited to peer reviewed publications To

validate previous search results we also repeated the

electronic search for three earlier years (983089983097983096983088 983089983097983097983093 and

983090983088983088983097) The complete search strategy is provided in

appendix 983089

Inclusion and exclusion

Studies were included if they met all the following ini-

tial criteria they evaluated one or more interventions

intended to improve hand hygiene compliance among

healthcare workers in a hospital setting they measured

compliance with hand hygiene using opportunities

with prespecified indications or using proxies linked to

compliance (such as consumption of soap and alcohol

hand rub) they were either randomised controlled tri-

als non-randomised trials controlled before-after

studies or used an interrupted time series design

We placed no restrictions on promotion of hand

hygiene in the comparison group Studies were

excluded if they were not reported in peer reviewed

publications or not written in English

We applied a methodological filter by excluding stud-

ies that failed meet minimal quality criteria specified by

the Cochrane Effectiveness Practice and Organisation of

Care Group (EPOC) Acceptable study designs were ran-

domised controlled trials and non-randomised trials

(with at least two intervention and two control sites)

controlled before-after studies (with outcome measures

before and after the intervention from at least two inter-

vention and two comparable control sites) and inter-rupted time series (with a clearly defined point in time

for the intervention and outcome measures from at least

three time points in both baseline and intervention

periods)983089983090 983089983091

Patient involvement

No patients were involved in setting the research ques-

tion or the outcome measures nor were they involved in

the design and implementation of the study There are

no plans to involve patients in dissemination

Data extraction and assessment o quality

Two reviewers (NL and BSC) independently screenedthe titles and abstracts of the citations obtained from

the search to assess the eligibility Consensus was

reached by discussion if initial assessments differed NL

evaluated the full text and abstracted data which was

checked by BSC

The reviewers abstracted data including study design

and duration population activities to promote hand

hygiene in both intervention and comparison groups

hand hygiene outcomes clinical and microbiological

outcomes measurement methods and settings When

possible we classified hand hygiene promotion activi-

ties according to WHO guidelines on hand hygiene in

healthcare983092 We grouped activities into eight compo-nents system change education feedback reminders



RESEARCH

3

































plot983089983094 983089983095








































hand hygiene983090983093 983090983094





















RESEARCH

4








three studies983090983096-983091983088

Results

Overall description





























































Quality assessment








983092983091983088 (983088983092983091 to 983092983094983093983095)



983089983089983096983091 (983090983094983095 to 983093983091983095983097)



(1980 to Nov 2009) (n=10 studies)















RESEARCH

5
















blinded














time983093983094


































RCTs CCT CBA

Fuller 2012

Huis 2013

Mertz 2010

Huang 2002

Fisher 2013

Salamati 2013

Mayer 2011

Gould 2011

Benning 1997

W a s a l l o


W a s a l l o




W e r e i n c





W a s k n o


a d e q u a t


W a s k n o


a d e q u a t


Low risk of bias


High risk of bias

ITS

Derde 2014

Lee 2013

Marra 2013

Al-Tawfiq 2013

Armellino 2013

Armellino 2012

Chan 2013

Crews 2013

Salmon 2013


Helder 2012

Kirkland 2012

Morgan 2012

Stone 2012

Jaggi 2012

Lee 2012

Mestre 2012

Koff 2011

Doron 2011

Marra 2011

Yngstrom 2001

Helms 2010

Chou 2010

Vernaz 2008

Whitby 2008

Grayson 2008

Eldrige 2006

Johnson 2005

Khatib 1999

Tibballs 1996

Dubbert 1990

W a s i n t e



W a s i n t e


W e r e i n c







RESEARCH

6





























unclear
































studies


















meta-analysis











Huis

Total (95 CI)


χ2=1063 df=2 P=0005 I2=81


106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000


Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental





RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

3

































plot983089983094 983089983095








































hand hygiene983090983093 983090983094





















RESEARCH

4








three studies983090983096-983091983088

Results

Overall description





























































Quality assessment








983092983091983088 (983088983092983091 to 983092983094983093983095)



983089983089983096983091 (983090983094983095 to 983093983091983095983097)



(1980 to Nov 2009) (n=10 studies)















RESEARCH

5
















blinded














time983093983094


































RCTs CCT CBA

Fuller 2012

Huis 2013

Mertz 2010

Huang 2002

Fisher 2013

Salamati 2013

Mayer 2011

Gould 2011

Benning 1997

W a s a l l o


W a s a l l o




W e r e i n c





W a s k n o


a d e q u a t


W a s k n o


a d e q u a t


Low risk of bias


High risk of bias

ITS

Derde 2014

Lee 2013

Marra 2013

Al-Tawfiq 2013

Armellino 2013

Armellino 2012

Chan 2013

Crews 2013

Salmon 2013


Helder 2012

Kirkland 2012

Morgan 2012

Stone 2012

Jaggi 2012

Lee 2012

Mestre 2012

Koff 2011

Doron 2011

Marra 2011

Yngstrom 2001

Helms 2010

Chou 2010

Vernaz 2008

Whitby 2008

Grayson 2008

Eldrige 2006

Johnson 2005

Khatib 1999

Tibballs 1996

Dubbert 1990

W a s i n t e



W a s i n t e


W e r e i n c







RESEARCH

6





























unclear
































studies


















meta-analysis











Huis

Total (95 CI)


χ2=1063 df=2 P=0005 I2=81


106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000


Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental





RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

4








three studies983090983096-983091983088

Results

Overall description





























































Quality assessment








983092983091983088 (983088983092983091 to 983092983094983093983095)



983089983089983096983091 (983090983094983095 to 983093983091983095983097)



(1980 to Nov 2009) (n=10 studies)















RESEARCH

5
















blinded














time983093983094


































RCTs CCT CBA

Fuller 2012

Huis 2013

Mertz 2010

Huang 2002

Fisher 2013

Salamati 2013

Mayer 2011

Gould 2011

Benning 1997

W a s a l l o


W a s a l l o




W e r e i n c





W a s k n o


a d e q u a t


W a s k n o


a d e q u a t


Low risk of bias


High risk of bias

ITS

Derde 2014

Lee 2013

Marra 2013

Al-Tawfiq 2013

Armellino 2013

Armellino 2012

Chan 2013

Crews 2013

Salmon 2013


Helder 2012

Kirkland 2012

Morgan 2012

Stone 2012

Jaggi 2012

Lee 2012

Mestre 2012

Koff 2011

Doron 2011

Marra 2011

Yngstrom 2001

Helms 2010

Chou 2010

Vernaz 2008

Whitby 2008

Grayson 2008

Eldrige 2006

Johnson 2005

Khatib 1999

Tibballs 1996

Dubbert 1990

W a s i n t e



W a s i n t e


W e r e i n c







RESEARCH

6





























unclear
































studies


















meta-analysis











Huis

Total (95 CI)


χ2=1063 df=2 P=0005 I2=81


106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000


Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental





RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

5
















blinded














time983093983094


































RCTs CCT CBA

Fuller 2012

Huis 2013

Mertz 2010

Huang 2002

Fisher 2013

Salamati 2013

Mayer 2011

Gould 2011

Benning 1997

W a s a l l o


W a s a l l o




W e r e i n c





W a s k n o


a d e q u a t


W a s k n o


a d e q u a t


Low risk of bias


High risk of bias

ITS

Derde 2014

Lee 2013

Marra 2013

Al-Tawfiq 2013

Armellino 2013

Armellino 2012

Chan 2013

Crews 2013

Salmon 2013


Helder 2012

Kirkland 2012

Morgan 2012

Stone 2012

Jaggi 2012

Lee 2012

Mestre 2012

Koff 2011

Doron 2011

Marra 2011

Yngstrom 2001

Helms 2010

Chou 2010

Vernaz 2008

Whitby 2008

Grayson 2008

Eldrige 2006

Johnson 2005

Khatib 1999

Tibballs 1996

Dubbert 1990

W a s i n t e



W a s i n t e


W e r e i n c







RESEARCH

6





























unclear
































studies


















meta-analysis











Huis

Total (95 CI)


χ2=1063 df=2 P=0005 I2=81


106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000


Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental





RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

6





























unclear
































studies


















meta-analysis











Huis

Total (95 CI)


χ2=1063 df=2 P=0005 I2=81


106 (088 to 127)

144 (118 to 176)

164 (133 to 202)

135 (104 to 176)

343

331

326

1000


Weight()

0058

0365

0495

Log(odds ratio)

0092

0102

0106

Standarderror

02 05 1 2 5

Favourscontrol

Favoursexperimental





RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

7

Time (months)




0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 20

Time (months)


0 5 10 15 200

02

04

06

08

10

Time (months)




0 10 20 30

Time (months)

0 10 20 30

Time (months)

Chou et al


0 20 40 60

Time (months)

0 20 40 60

Time (months)

Marra et al


0 5 10 15

Time (months)

0 5 10 15

Time (months)

0 5 10 15

Time (months)

Helms et al


0 5 10 150

02

04

06

08

10

Time (months)




0 10 20 30 40 50

Time (months)

0 1 2 3 4 5

Time (months)

0 10 20 30 40 50

Time (months)

0 05 10 15 20 25

Time (months)

0 05 10 15 20 25


Time (months)


0 10 20 20 40


0

02

04

06

08

10




Time (months)


0 5 10 15 20



0

02

04

06

08

10




Time (months)


0 05 10 15 20

Time (months)


0 10 20 30 40

Time (months)


0 2 4 6 80

02

04

06

08

10





0

02

04

06

08

10





RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

8

Dubbert 1990

Marra 2011

Lee hospital 4 2013

Helms 2010

Kirkland 2012

Higgins 2013

Al-Tawfiq 2013

Chou 2010

Tibballs 1996

Lee hospital 8 2013

Khatib 1999

Crews 2013


Derde 2014

Doron 2011

Lee hospital 7 2013

Lee hospital 9 2013


026 (-078 to 131)

047 (015 to 079)

132 (-028 to 293)

194 (033 to 356)

550 (273 to 827)

227 (167 to 287)

245 (212 to 278)

287 (260 to 315)

049 (-072 to 170)

064 (-032 to 160)

331 (285 to 378)

585 (468 to 701)

080 (000 to 160)

068 (056 to 080)

038 (0080 to 069)

-187 (-309 to -066)

-052 (-293 to 188)

107 (084 to 129)









SYS v SYS+EDU

SYS v WHO-5

EDU v EDU+FED



REM v EDU+FED+REM


WHO-5 v WHO-5

WHO-5 v WHO-5


-5 0 5 10

Author







Study Comparison





Lee983092983096
















Talbot

(phase II)

983093983094



983096983089983089 983089983092983093983093 (983088983092983093) minus983088983088983090983088 (983088983088983089) 983088983088983094983088 (983088983088983089) 983088983092983094983092 (983088983088983093) 983089983093983088 (983089983088983094 to 983089983097983093)











RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

9




























(appendix 983092)

Clinical outcomes







WHO-5

WHO-5+

None Single



O

s r a t i o

Singleintervention

WHO-5 WHO-5+0

1

2

5

20

100




WHO-5+

1

0

02

04

06

08

10

2 3 4

WHO-5

1 2 3 4


Single intervention

0

02

04

06

08

10





RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

10










































be determined













intervention)

































































RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis





RESEARCH

12

















































to be small983096983093 983096983094





















Conclusions




























RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH

13































































RESEARCH










































resources use




criteria






analysis



RESEARCH










































resources use




criteria






analysis

bmj.h3728.full

Documents