High-Intensity Versus Low-Intensity Physical Activity or Exercise in People With Hip or Knee Osteoarthritis (Review)
High-Intensity Versus Low-Intensity Physical Activity or Exercise in People With Hip or Knee Osteoarthritis (Review)
High-Intensity Versus Low-Intensity Physical Activity or Exercise in People With Hip or Knee Osteoarthritis (Review)
www.cochranelibrary.com
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review)
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . 4
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 21
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Analysis 1.1. Comparison 1 High versus low intensity exercise, Outcome 1 Pain (WOMAC). . . . . . . . . 47
Analysis 1.2. Comparison 1 High versus low intensity exercise, Outcome 2 Physical Function (WOMAC). . . . . 48
Analysis 1.3. Comparison 1 High versus low intensity exercise, Outcome 3 Adverse effects. . . . . . . . . . 49
Analysis 1.4. Comparison 1 High versus low intensity exercise, Outcome 4 Gait speed. . . . . . . . . . . . 50
Analysis 1.5. Comparison 1 High versus low intensity exercise, Outcome 5 Muscle strength. . . . . . . . . . 51
Analysis 1.6. Comparison 1 High versus low intensity exercise, Outcome 6 Aerobic capacity. . . . . . . . . . 52
Analysis 1.7. Comparison 1 High versus low intensity exercise, Outcome 7 Range of Motion. . . . . . . . . 52
Analysis 2.1. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 1 Pain. . . . . . . 53
Analysis 2.2. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 2 Function. . . . . 54
Analysis 2.3. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 3 Adverse effects. . . 55
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 62
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) i
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
Jean-Philippe Regnaux1 ,2,3 , Marie-Martine Lefevre-Colau3,4,5,6 , Ludovic Trinquart7 , Christelle Nguyen8 , Isabelle Boutron1,3,5,9 ,
Lucie Brosseau10 , Philippe Ravaud1 ,3,5,9
1 METHODS team, INSERM U1153, Paris, France. 2 EHESP Rennes, Sorbonne Paris Cit, Paris, France. 3 French Cochrane Center,
Paris, France. 4 ECaMO team, INSERM U1153, Paris, France. 5 Paris Descartes University, Sorbonne Paris Cit, Facult de Mdecine,
Paris, France. 6 Rheumatic and musculoskeletal disease Institute, Department of Physical Medicine and Rehabilitation AP-HP (Assis-
tance Publique des Hpitaux de Paris), Hpital Cochin, Paris, France. 7 French Cochrane Centre, Hpital Htel-Dieu, Paris, France.
8 Service de Mdecine Physique et de Radaptation, Hpital Cochin, Assistance publique-Hpitaux de Paris, Universit Paris-Descartes,
Paris, France. 9 Centre dpidmiologie Clinique, AP-HP (Assistance Publique des Hpitaux de Paris), Hpital Htel Dieu, Paris,
France. 10 School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
Contact address: Jean-Philippe Regnaux, METHODS team, INSERM U1153, Paris, France. jean-philippe.regnaux@ehesp.fr.
Citation: Regnaux JP, Lefevre-Colau MM, Trinquart L, Nguyen C, Boutron I, Brosseau L, Ravaud P. High-intensity versus low-
intensity physical activity or exercise in people with hip or knee osteoarthritis. Cochrane Database of Systematic Reviews 2015, Issue 10.
Art. No.: CD010203. DOI: 10.1002/14651858.CD010203.pub2.
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
Background
Exercise or physical activity is recommended for improving pain and functional status in people with knee or hip osteoarthritis. These are
complex interventions whose effectiveness depends on one or more components that are often poorly identified. It has been suggested
that health benefits may be greater with high-intensity rather than low-intensity exercise or physical activity.
Objectives
To determine the benefits and harms of high- versus low-intensity physical activity or exercise programs in people with hip or knee
osteoarthritis.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; issue 06, 2014), MEDLINE (194 8 to June 2014) ,
EMBASE (198 0 to June 2014), CINAHL (1982 to June 2014), PEDro (1929 to June 2014), SCOPUS (to June 2014) and the World
Health Organization (WHO) International Clinical Registry Platform (to June 2014) for articles, without a language restriction. We
also handsearched relevant conference proceedings, trials, and reference lists and contacted researchers and experts in the eld to identify
additional studies.
Selection criteria
We included randomized controlled trials of people with knee or hip osteoarthritis that compared high- versus low-intensity physical
activity or exercise programs between the experimental and control group.
High-intensity physical activity or exercise programs training had to refer to an increase in the overall amount of training time (frequency,
duration, number of sessions) or the amount of work (strength, number of repetitions) or effort/energy expenditure (exertion, heart
rate, effort).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 1
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Data collection and analysis
Two review authors independently assessed study eligibility and extracted data on trial details. We contacted authors for additional
information if necessary. We assessed the quality of the body of evidence for these outcomes using the GRADE approach.
Main results
We included reports for six studies of 656 participants that compared high- and low-intensity exercise programs; five studies exclusively
recruited people with symptomatic knee osteoarthritis (620 participants), and one study exclusively recruited people with hip or knee
osteoarthritis (36 participants). The majority of the participants were females (70%). No studies evaluated physical activity programs.
We found the overall quality of evidence to be low to very low due to concerns about study limitations and imprecision (small number
of studies, large confidence intervals) for the major outcomes using the GRADE approach. Most of the studies had an unclear or high
risk of bias for several domains, and we judged five of the six studies to be at high risk for performance, detection, and attrition bias.
Low-quality evidence indicated reduced pain on a 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC)
pain scale (mean difference (MD) -0.84, 95% confidence interval (CI) -1.63 to -0.04; 4% absolute reduction, 95% CI -8% to 0%;
number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 14 to 22) and improved physical function on
the 68-point WOMAC disability subscale (MD -2.65, 95% CI -5.29 to -0.01; 4% absolute reduction; NNTB 10, 95% CI 8 to 13)
immediately at the end of the exercise programs (from 8 to 24 weeks). However, these results are unlikely to be of clinical importance.
These small improvements did not continue at longer-term follow-up (up to 40 weeks after the end of the intervention). We are
uncertain of the effect on quality of life, as only one study reported this outcome (0 to 200 scale; MD 4.3, 95% CI -6.5 to 15.2; 2%
absolute reduction; very low level of evidence).
Our subgroup analyses provided uncertain evidence as to whether increased exercise time (duration, number of sessions) and level of
resistance (strength or effort) have an impact on the exercise program effects.
Three studies reported withdrawals due to adverse events. The number of dropouts was small. Only one study systematically monitored
adverse effects, but four studies reported some adverse effects related to knee pain associated with an exercise program. We are uncertain
as to whether high intensity increases the number of adverse effects (Peto odds ratio 1.72, 95% CI 0.51 to 5.81; - 2% absolute risk
reduction; very low level of evidence). None of the included studies reported serious adverse events.
Authors conclusions
We found very low-quality to low-quality evidence for no important clinical benefit of high-intensity compared to low-intensity exercise
programs in improving pain and physical function in the short term. There was insufficient evidence to determine the effect of different
types of intensity of exercise programs.
We are uncertain as to whether higher-intensity exercise programs may induce more harmful effects than those of lower intensity; this
must be evaluated by further studies. Withdrawals due to adverse events were poorly monitored and not reported systematically in each
group. We downgraded the evidence to low or very low because of the risk of bias, inconsistency, and imprecision.
The small number of studies comparing high- and low-intensity exercise programs in osteoarthritis underscores the need for more
studies investigating the dose-response relationship in exercise programs. In particular, further studies are needed to establish the
minimal intensity of exercise programs needed for clinical effect and the highest intensity patients can tolerate. Larger studies should
comply with the Consolidated Standards of Reporting Trials (CONSORT) checklist and systematically report harms data to evaluate
the potential impact of highest intensities of exercise programs in people with joint damage.
Benefits and harms of high- versus low-intensity exercise programs for hip or knee osteoarthritis
Review question
We searched the literature until June 2014 for studies on the benefits and harms of high- versus low-intensity exercise programs for
people with hip or knee osteoarthritis.
Background
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 2
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Osteoarthritis is a chronic condition that affects the joints (commonly hips, knees, spine, and hands). Over time, cartilage wears down
in joints. People with osteoarthritis generally feel pain and can have difficulties performing daily activities such as walking. Exercise or
physical activity programs are non-drug treatments usually recommended for people with hip or knee osteoarthritis. Many types of
exercises are prescribed, but it may be unclear whether or not they are effective. Several different components can play a role in the
effectiveness of an exercise regimen, such as exercise duration, frequency, or level of resistance. High intensity can be defined as an extra
amount of time (duration or frequency) or resistance (strength or effort) required in the exercise programs.
Study characteristics
We identified six randomized controlled trails with 656 participants. Five studies (620 participants) enrolled people with knee os-
teoarthritis, and one study (36 participants) enrolled people with knee or hip osteoarthritis. The studies included more women (70%)
than men.
Key results
On a scale of 0 to 20 points (lower scores mean reduced pain), people who completed a high-intensity exercise program rated their pain
0.84 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People who performed a
low-intensity exercise program rated their pain at 6.6 points.
On a scale of 0 to 68 points (lower scores mean better function), people who completed a high-intensity exercise program rated their
physical function 2.65 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People
who performed a low-intensity exercise program rated their pain at 20.4 points.
On a scale of 0 to 200 mm visual analog scale (higher score means better function), people who completed a high-intensity exercise
program rated their quality of life 4.3 mm higher (6.5 mm lower to 15.2 mm higher) (2% absolute improvement) than people who
performed a low-intensity exercise program. People who performed a low-intensity exercise program rated their quality of life at 66.7
mm.
Two per cent more people had adverse effects with high-intensity exercise, or 17 more people out of 1000.
39 out of 1000 people reported an adverse effect related to high-intensity exercise program
22 out of 1000 people reported an adverse effect related to low-intensity exercise program
Adverse events were not systematically monitored and and were incompletely reported by group. None of the included studies reported
serious adverse events.
Based on the evidence, people with knee osteoarthritis who perform high-intensity exercise may experience slight improvements in
knee pain and function at the end of the exercise program (8 to 24 weeks) when compared with a low-intensity exercise program. We
are uncertain as to whether high-intensity exercise improves quality of life or increases the number of people who experience adverse
events.
Quality of evidence
We graded the quality of evidence as low for pain and function and very low for quality of life. The small number of studies and
participants included in some analyses reduced the robustness and precision of these findings.
Adverse effects were poorly recorded. Very low quality evidence shows we are uncertain whether higher-intensity exercise programs
may result in more side effects than lower-intensity exercise programs. Further research may change the result.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 3
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of Participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Pain (at study comple- The m ean pain (at study The m ean pain (at study - 313
M D -0.84 (95% CI -
tion) com pletion) in the con- com pletion) in the inter- (4 studies) low1,2 1.63 to -0.04). Abso-
WOM AC (VAS or NRS) trol groups was vention groups was lute m ean reduction 4%
f rom 0 to 20; lower 6.6 points 0.84 lower with high intensity exer-
scores m ean reduced (1.63 to 0.04 lower) cise program s (95% CI
pain -8% m ore to 0% f ewer).
Follow-up: 8 to 24 Relative reduction -13%
weeks (95% CI -25% m ore to
0% f ewer)
NNTB = 11 (95% CI 14
to 22) 3,4
Physical function (at The m ean physical The m ean physical - 310
M D -2.65 (95% CI -5.
study completion) f unction (at study com - f unction (at study com - (4 studies) low1,2 29 to -0.01). Absolute
WOM AC (self adm in- pletion) in the control pletion) in the interven- m ean reduction 4% with
istered health status groups was tion groups was high intensity exercise
m easure) f rom 0 to 68; 20.4 points 2.65 lower program s (95% CI -8%
lower scores m ean bet- (5.29 to 0.01 lower) m ore to 0% f ewer). Rel-
ter f unction ative m ean reduction
Follow-up: 8 to 24 13% (95% CI -26% m ore
weeks to 0% f ewer)
4
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review)
NNTB = 10 (95% CI 8 to
13) 4,5
Quality of life (at study The m ean quality of lif e The m ean quality of lif e - 214
M D 4.3 (95% CI -6.
completion) (at study com pletion) in (at study com pletion) in (1 study) very low1,2,6 5 to 15.2). Absolute
EuroQol (VAS) f rom 0 the control groups was the intervention groups m ean im provem ent 2%
to 200 m m ; 66.7 mm was (95% CI -3% f ewer to
higher score m eans 4.3 higher 8% m ore). Relative im -
better f unction (6.5 to 15.2 higher) provem ent 6% (95% CI -
Follow-up: 8 weeks 10%f ewer to 23%m ore)
NNTB = NA 4,7
Adverse effects (re- 22 per 1000 39 per 1000 Peto OR 1.72 364
Absolute risk reduction
lated to the exercise (11 to 131 higher) (0.51 to 5.81) (4 studies) very low1,2,8,9 2% f ewer events with
programs) low intensity exercise
Follow-up: 8 to 24 program s (95% CI 11%
weeks f ewer to - 1% m ore)
. Relative risk reduc-
tion: 69% f ewer with
low intensity exercise
progam s (95% CI 425%
m ore to - 48% f ewer)
NNTH = 65 (95% CI
NNTB 92 to NNTH 11) 4
Severe adverse events See com m ent See com m ent Not estim able - See com m ent 3 studies reported drop-
or withdrawals (due to outs or withdrawals
adverse events) - not (due to adverse events)
reported . No severe adverse
events were observed 9
* The basis f or the assumed risk (e.g. the m edian control group risk across studies) is provided in f ootnotes. The corresponding risk (and its 95% conf idence interval) is
based on the assum ed risk in the com parison group and the relative effect of the intervention (and its 95% CI).
CI: conf idence interval; M D: m ean dif f erence; NA: not applicable; NNTB: num ber needed to treat f or an additional benef icial outcom e; NNTH: num ber needed to treat f or an
additional harm f ul outcom e; NRS: num eric rating scale; OR: odds ratio; SD: standard deviation; VAS: visual analog scale; WOM AC: Western Ontario and M cM aster Universities
Arthritis Index
5
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review)
m usculoskeletal.cochrane.org/ ), and f or dichotom ous outcom es using the Cates NNT calculator (www.nntonline.net/
visualrx/ ).
5
Calculations based on the control group baseline m ean (SD) WOM AC f unction: -4.5 (14.7) points on 0-68 scale (f rom
M cCarthy 2004) and an assum ed m inim al clinically im portant dif f erence of 14 points (Tubach 2012).
6 Only one study reported EuroQol data.
7 Calculations based on the control group baseline m ean (SD) EuroQol: 66.7 (18.2) points on 200 m m scale (f rom M cCarthy
2004) and an assum ed m inim al clinically im portant dif f erence of 15% of m ean baseline.
8 Downgraded because of inconsistency (only 1 of 6 studies system atically m onitored adverse ef f ects. Unbalanced withdrawals
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 7
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Types of participants Major outcomes
We included studies if they recruited at least 75% of participants The major outcomes were pain, function, and quality of life, as
with clinically or radiographically confirmed primary osteoarthri- currently recommended for osteoarthritis trials (Altman 1996;
tis of the knee or hip. We excluded studies of people with inflam- Pham 2004). For safety, the major outcomes were the number of
matory arthritis, such as rheumatoid arthritis. We did not consider participants who withdrew because of adverse events and number
studies of children. of participants experiencing any serious adverse events.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 8
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Minor outcomes (up to the two latest editions). We contacted authors and field
experts for any additional published or unpublished data.
To identify trials in progress, we used the WHO International
Physical global performance Clinical Trials Registry Platform (www.apps.who.int/trialsearch);
Walking ability, including gait speed and walking endurance ClinicalTrials.gov (www.clinicaltrials.gov); and the metaRegister
Muscle strength, using quantitative strength sensors of Controlled Trials (mRCT) (www.controlled-trials.com).
Aerobic capacity, including peak VO2 or peak work rate We contacted authors of active or completed trials for provisional
Range of motion results if they had not yet been published. We supplemented
Physical activity levels database searching and hand-searching and for the RCTs identi-
Number of steps fied by the rst step by tracking citations in SCOPUS (Appendix
6).
Joint imaging
Joint space narrowing measurement on radiography
Data collection and analysis
The Kellgren-Lawrence classification
Selection of studies
Search methods for identification of studies We removed duplicate records from retrieved references. Using the
inclusion and exclusion criteria, two review authors (JPR, CN)
independently screened the titles and abstracts identified by the
Electronic searches search strategy in order to identify potentially relevant studies.
We first searched the following databases the Cochrane Central These review authors obtained and screened the full-length articles
Register of Controlled Trials (CENTRAL,2012, Issue 10 ), MED- for selected titles and abstracts to check for eligibility and decide
LINE through OVID (1948 to October 2012), EMBASE through on their inclusion. Disagreements were resolved by discussion and
Elsevier (1980 to October 2012), CINAHL (1982 to October with the assistance of a third review author (MMLC) if needed.
2012) and PEDro (from 1929 to October 2012). The MEDLINE If results of eligible trials were available in an abstract only, we
search involved the Cochrane highly sensitive search strategy, sen- contacted the trial authors to ask for a report of the trial results.
sitivity-maximizing version (2008 revision). The EMBASE search We linked multiple reports relating to the same trial or trials with
involved the UK Cochrane Centre search filter to identify reports potentially overlapping populations. If we could not exclude the
of RCTs. We used the Google Scholar search engine to find addi- possibility of overlapping populations, we selected the more recent
tional references. trial.
We performed an updated search in all the databases on June 2014. To confirm the eligibility of studies, we assessed the intensity of
The Trials Search Co-ordinator for the Cochrane Musculoskele- exercise programs. Interventions in rehabilitation are in fact com-
tal Review Group helped develop search equations. The queries plex (Boutron 2008), involving several components that may in-
combined free text words and controlled vocabulary. The search teract separately or together, for difficulties in classification. For
strategy was based on synonyms of (physical activity OR ex- each included study, the two review authors (JPR, CN) used the
ercise) AND osteoarthritis. We used an adapted search strat- following steps:
egy to search MEDLINE (Appendix 1), EMBASE (Appendix 2), 1. identified the experimental and the control group; and
the Cochrane Central Register of Controlled Trials (CENTRAL; 2. rated the intensity of physical activity or exercise programs
Cochrane Library) (Appendix 3), CINAHL (Appendix 4), and in the experimental and control group as high or low on the basis
PEDro (Appendix 5). We did not restrict the search by language of their description.
of publication or publication status. We used a consensus method to resolve disagreements and con-
sulted a third review author (IB) if necessary. If the article did not
Searching other resources contain information on the exercise program intensity, we con-
tacted the trial authors for additional information. In the absence
we searched for aditional relevant systematic reviews in the
of sufficient information, we excluded the study. Review authors
Cochrane Database of Systematic Reviews and the Database of
were blinded to all characteristics of the trial except for the content
Abstracts of Reviews of Effects (DARE) (to J une 2014) .
of the interventions.
We handsearched the reference lists of selected trials and systematic
reviews identified from electronic searches.
We also searched conference proceedings available online for the Data extraction and management
American College of Rheumatology, European League Against Two review authors (JPR, MMLC) independently extracted re-
Rheumatism, and Osteoarthritis Research Society International sults of individual trials by using a standardized piloted extraction
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 9
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
form accompanied by a codebook. We resolved disagreements by risk of bias, or unclear risk of bias, depending on the informa-
consensus or by consulting a third review author (IB) if neces- tion supplied in the report.
sary. We based the extraction form on other forms used by the We classified studies as at low risk of bias if all key domains had
Cochrane Musculoskeletal Review Group and pilot-tested it with low risk of bias and no serious flaws; high risk of bias if one or
five reports of RCTs. more domains had high risk of bias; and unclear risk of bias if
Relevant information extracted were as follows: one or more domains had unclear risk of bias (Higgins 2011).
1. Trial characteristics: funding, settings and number of We resolved any disagreements by involving a third review author
centers, country, study design. (IB).
2. Participant characteristics: age, sex, measure of physical
function, level of pain, description of radiographic damage, non-
Measures of treatment effect
steroidal anti-inflammatory drugs or other drugs, coexisting
diseases, other. For dichotomous data, we expressed the results of each RCT as risk
3. Intervention characteristics: ratios (RRs) with corresponding 95% confidence intervals(CIs).
i) number of intervention groups; We used the Peto method to calculate a Peto Odds ratio from the
ii) content of each intervention (details); number of adverse effects reported by each study before combining
iii) qualitative data: a detailed description of the them (Deeks 2011).
interventions including the different components of the program For continuous outcomes, we summarized results as mean differ-
received by each group, mode of delivery (individual, in group, ence (MD) if the same tool was used to measure the same outcome
through Internet), with supervision or not (face-to-face or at across separate studies. Alternatively, we calculated the standard-
home), clinical expertise and background of the healthcare ized mean difference (SMD) when studies measured the same out-
professionals who provided the physical activity or exercise come but used different tools. The SMD expresses the size of the
programs (physiotherapist, fitness instructor, registered nurse, intervention effect in each study relative to the variability observed
other); and in that study. We calculated the SMD by dividing the MD by the
iv) quantitative data: number of sessions, timing and standard deviation (SD) for the outcome among participants. An
duration of each session, duration of each component, and SMD greater than 0 indicates a beneficial effect in favor of high-
overall duration. We hypothesized that more frequent intensity exercise or physical activity. We computed a 95% CI for
interventions conducted over a longer time may influence the SMD. We interpreted the SMD as described in Cohen 1988:
outcomes. We calculated the intensity of treatment and used this SMD = 0.2 is considered a small beneficial effect; 0.5 a medium
calculation to test whether greater intensity of exercise programs effect; and 0.8 a large effect.
had greater effects on outcomes. If the meta-analysis resulted in statistically significant overall esti-
4. Tolerance and adverse events: data on compliance of mates, we transformed the treatment effect measures (pooled es-
participants in each group and any adverse events or side effects timate of RR or SMD) into measures that are clinically useful in
related to the interventions as well as data on drop-out/ daily practice, such as the number needed to treat for an additional
adherence rates. beneficial outcome or harmful outcome and the absolute and/or
5. Outcome/data results: outcomes and time points used, relative improvement on the original units to express the final re-
results of each intervention group, number of participants sults of the review. We back-translated the results by multiplying
randomized, and number of participants used for the analysis in the SMD by the SD for a representative study (Akl 2011).
each group.
When necessary, we approximated the means and measures of
Unit of analysis issues
dispersion from data in the reports.
We entered data into Review Manager and checked it for accuracy For cross-over trials, we planned to extract data from the first pe-
(RevMan 2011). riod only, but we included none in this review. Whenever possible,
we used results from an intention-to-treat analysis.
For studies containing more than two intervention groups, allow-
Assessment of risk of bias in included studies ing for multiple pair-wise comparisons between all possible pairs
We evaluated the risk of bias in each included study according to of intervention groups, we included the same group of partici-
the Risk of bias tool recommended by The Cochrane Collabora- pants only once in the meta-analysis following the procedure rec-
tion. Two review authors (JPR, MMLC) independently examined ommended by The Cochrane Collaboration (Deeks 2011).
seven specific domains: sequence generation, allocation conceal-
ment, blinding of participants or personnel, blinding of outcome
assessors, incomplete outcome data, selective outcome reporting, Dealing with missing data
and other potential source of bias (that is design specific, baseline In case of missing outcome data, we contacted the original in-
imbalance). We scored each criterion as high risk of bias, low vestigators to request data. We performed sensitivity analyses to
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 10
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
assess how sensitive the results were to changes and addressed the Subgroup analysis and investigation of heterogeneity
potential impact of missing data on the review findings in the To explore heterogeneity in estimating the effect of intensity, we
Discussion section. performed subgroup analyses according to the type of exercise in-
tensity. We compared exercise program effect for pain and func-
tion whether the intensity varied in time (duration) and in resis-
Assessment of heterogeneity tance (strength or effort).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 11
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
musculoskeletal.cochrane.org). We determined the minimal clin- and 385 studies on abstract screening (see Figure 1). After selecting
ically important difference for the WOMAC score. We assumed 20 full-text reports, we excluded 11 reports because they did not
that for each subscale, a change of at least 4 points on the 15- meet the selection criteria: no randomization (one study) and no
point WOMAC pain scale (15% for absolute improvement) and comparison of high- versus low-intensity interventions (10 stud-
10 points on the 68-point WOMAC function scale (15% for abso- ies). The remaining nine eligible full-text reports corresponded to
lute improvement) was needed to be considered a clinically mean- six studies of interventions that were exclusively high-intensity ex-
ingful difference (Tubach 2012). ercise programs compared with low-intensity exercise programs.
McCarthy 2004 reported on additional variables in two different
reports, which were counted as one study for analysis. Likewise,
Foroughi 2011 reported on additional variables in two reports that
RESULTS were counted as one study. We found one report and a thesis of
one study that were counted as one study (Singh 2011). We had
insufficient information to determine inclusion eligibility for one
trial (Steinhilber 2012), and we could not contact the authors,
Description of studies
so we listed the study in the Characteristics of studies awaiting
classification section. In addition, we identified four ongoing trials
(see Characteristics of ongoing studies). We requested additional
Results of the search
information from eight authors and received responses from six
We included six studies (nine reports) (Mangione 1999; McCarthy (Ng 2010; Teixeira 2011; Foroughi 2011; Messier 2011; Pua 2012;
2004; Jan 2008; Ng 2010; Foroughi 2011; Singh 2011). The sters 2012) (see Appendix 7). The last searches were performed
search retrieved 6493 citations, and 3374 citations after duplicates in June 2014.
were removed. We excluded 2969 studies on citation screening
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 12
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 1. Study flow diagram.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 13
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
were partially or completely unsupervised, with an exercise pro-
Included studies
gram executed at home (McCarthy 2004; Ng 2010). The interven-
We have provided a full description of the six included studies in tion was delivered by an experienced or trained exercise therapist
Characteristics of included studies. in four studies and not clearly reported in two studies (Mangione
1999; Singh 2011).
Methods
Adherence to training interventions
All included studies were RCTs with a parallel-group design.
Adherence to the interventions was defined in terms of (1) atten-
dance at an appointment and (2) compliance with the training
advice or the content of the sessions provided by the healthcare
Sample size
professional (Brazzelli 2011).
The six studies included 656 participants. The median sample size We were not able to perform an analysis on attendance. In most
was 78 (lower quartile = 43; upper quartile = 176). of the studies, attendance or compliance was not clearly reported.
The included studies did not systematically report compliance.
Ng 2010 reported greater compliance with walking programs per-
Participants formed for three versus five days (100% versus 58% to 100%).
Two studies were conducted in Australia and one study each in
the United Kingdom, United States, Taiwan, and India. Most Outcomes
participants (70%) were female, and one study included females Only a limited number of studies reported the same outcomes
only (Foroughi 2011). The mean age of participants was 61 years prespecified in the protocols (see Additional tables). The six studies
(range 56 to 71 years). All studies recruited participants in a single considered the end of the intervention as the final data collection
center. point (range eight to 24 weeks).
The location of osteoarthritis was reported in all studies. The pre- Primary outcomes (Table 1): all six studies reported pain out-
dominant location was the knee. Only one study included par- comes. Four studies used the WOMAC pain scale (McCarthy
ticipants with hip or knee osteoarthritis (Ng 2010). Two stud- 2004; Jan 2008; Ng 2010; Foroughi 2011), one used a visual
ies reported the mean duration of osteoarthritis: 14 and 12 years analog scale (VAS) (Singh 2011), and one used the Arthritis Im-
(Mangione 1999; Foroughi 2011). pact Measurement Scale 2 (AIM2) subscale to assess pain intensity
(Mangione 1999). Five studies assessed physical function. All used
the WOMAC disability subscores (McCarthy 2004; Jan 2008;
Interventions Ng 2010; Foroughi 2011; Singh 2011). Only one study reported
All six included studies examined an exercise program and com- quality of life, by the Short Form 36 and the EuroQol consisting
pared outcomes of high and low intensity of exercise. No study of a 200 mm vertical VAS (McCarthy 2004).
examined a physical activity program with different intensity. Secondary outcomes (Table 2): included studies reported multi-
Three studies assessed the effect of exercise programs with the ple secondary outcomes but only few studies used the same out-
two levels of intensity by amount of time spent in the program come measures. Two studies reported gait speed, for a fast pace,
(McCarthy 2004; Ng 2010; Singh 2011), and two compared the in Mangione 1999 and Jan 2008, and normal pace, in Mangione
two levels by resistance (strength or effort) (Mangione 1999; Jan 1999 and Foroughi 2011. Three studies reported muscle strength
2008; Foroughi 2011). for knee extensor muscles (McCarthy 2004; Jan 2008; Foroughi
The duration of programs ranged from eight to 24 weeks. The 2011), two studies knee flexor muscles (Jan 2008; Foroughi 2011),
mean frequency was three sessions per week (range two to five per and two studies global strength (Foroughi 2011; Singh 2011). One
week). study examined aerobic capacity (Mangione 1999). Two studies
See Characteristics of included studies for a description of the examined range of motion (McCarthy 2004; Singh 2011). One
components of the exercise programs. study examined physical activity and number of steps (Ng 2010),
Three studies examined exercise programs with a single compo- and data could not be extracted.
nent: walking (Ng 2010), set of muscle repetitions (Foroughi Follow-up assessment : two studies provided follow-up assess-
2011), or cycling (Mangione 1999), and three studies examined an ments at mid-term (six to 16 weeks after the end of the interven-
exercise program with multiple components (Jan 2008; McCarthy tions) (McCarthy 2004; Ng 2010), and one study at long-term
2004; Singh 2011). Most exercise programs were supervised. Two (40 weeks after the end of the interventions) (McCarthy 2004).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 14
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Safety related to (1) no randomization assignment (1 study) and (2) no
Severe adverse events or withdrawal due to adverse events: clear difference in intensity in exercise programs between groups
three studies reported dropouts or adverse events. Foroughi 2011 (11 studies).
reported dropout events in the high- and low-intensity exercise
program groups. Mangione 1999 reported adverse events but did
Ongoing studies
not specify in which group they occurred. Ng 2010 reported
dropout events in both groups for health reasons. McCarthy See Characteristics of ongoing studies
2004, Jan 2008, and Singh 2011 did not report the presence or We identified four ongoing studies registered in WHO ICTRP
absence of adverse events. as potentially eligible for inclusion, but no findings were available
Adverse effects: only one study systematically reported yet. Three studies are comparing high versus low strength training
adverse effects related to the exercise programs (Foroughi 2011), on knee osteoarthritis: in the United States (Messier 2011), in
and three additional studies made specific reference to the Sweden (ng 2013) and in Singapore (Pua 2012). One study is
presence of adverse effects (McCarthy 2004; Jan 2008; Ng 2010) examining the effects of high versus low exercise program on hip
(see Characteristics of included studies). osteoarthritis in Norway (sters 2012).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 15
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 2. Risk of bias summary: review authors judgements about each risk of bias item for each included
study.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 16
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Allocation
Selective reporting
We considered allocation sequence generation adequate in five We found the research protocol for two studies (Ng 2010;
studies (Mangione 1999; McCarthy 2004; Jan 2008; Ng 2010; Foroughi 2011). We assessed four trials as at unclear risk of bias
Foroughi 2011), and unclear in one study (Singh 2011). Four of because they did not distinguish between primary and secondary
these studies used a computer-generated list for sequence genera- outcomes or outcomes data was not reported in a valid format, or
tion and one study a random table (Jan 2008). Although one study both (Mangione 1999; Jan 2008; Foroughi 2011; Singh 2011).
used a central allocation to conceal allocation from the investigator We assessed the remaining two studies as at high risk of bias be-
enrolling participants and was rated as low risk (McCarthy 2004), cause additional outcomes data were reported in separate reports
four studies were rated as at unclear risk of bias because they pro- or were not reported in the final publication, or both (McCarthy
vided insufficient information to determine allocation methods. 2004; Ng 2010). No studies were assessed as at low risk of bias.
We rated one study as at high risk of bias because the treatment
allocation was not concealed (Ng 2010).
Other potential sources of bias
The studies appeared to be free of other serious potential sources
Blinding of bias. Only one of the included studies reported differences in
compliance between the high- and low-intensity interventions (Ng
In exercise studies, participants and care providers are rarely 2010). The compliance was lower for high-intensity programs,
blinded from treatment allocation. In five studies, we rated per- which could have biased nal results. We noted no difference in
formance bias at high risk (Mangione 1999; McCarthy 2004; Jan baseline participant characteristics. Of the six included studies,
2008; Ng 2010; Singh 2011). We rated one study as at low risk three did not report a source of funding (Jan 2008; Foroughi 2011;
of bias because the participants were blinded to the investigators Singh 2011). Ng 2010 declared that Sanofi-Aventis Consumer
hypothesis (Foroughi 2011). For detection bias, we separated the Health Care, a pharmaceutical company, supplied the study glu-
assessment of blinded assessors for subjective and objective out- cosamine intakes but did not report if it has another role in the
comes. As five studies reported that participants were not blinded, trial. McCarthy 2004 and Mangione 1999reported that their tri-
we rated these as at high risk of bias; we rated one study as at low als were funded by the National Institute for Health Research and
risk of bias (Foroughi 2011). For the objective outcomes, we rated the Arthritis Foundation, respectively.
the studies as at low (McCarthy 2004; Jan 2008; Foroughi 2011),
high (Ng 2010; Singh 2011), and unclear risk of bias (Mangione
Effects of interventions
1999).
See: Summary of findings for the main comparison Summary
of findings table: Physical activity and exercise programs in
osteoarthritis; Summary of findings 2 Subgroup analysis: Exercise
Incomplete outcome data duration versus resistance in people with knee or hip osteoarthritis
We rated five studies as at high risk of bias. Five studies featured a All studies reported means and standard deviation data for the
median of 16% drop-out after inclusion (range 4% to 28%). Two outcomes at baseline and at the end of the intervention.
studies reported an intention-to-treat (ITT) analysis (McCarthy
2004; Jan 2008). Only one study mentioned a method of imputa-
Primary outcomes
tion (last observation carried forward) to replace the missing data
(McCarthy 2004). We considered this method inappropriate and
might introduce a bias in estimating the treatment effect. The three
other studies did not report an ITT analysis and showed a statis- Pain
tically significant rate (greater than 10%) of dropouts (Mangione Four studies assessed pain on the WOMAC pain subscale at the
1999; Ng 2010; Foroughi 2011). The last study reported no in- end of the exercise program (McCarthy 2004; Jan 2008; Ng 2010;
formation on dropouts (Singh 2011). Foroughi 2011). Pooled analysis (Figure 3; Analysis 1.1) revealed
The attrition rate at the end of exercise programs ranged from 0% a statistically significant reduction (mean difference (MD) (fixed-
to 32%. Overall, the proportion was larger with high- versus low- effect model): -0.84, 95% confidence interval (CI) -1.63 to -0.04, I
intensity programs, except in one trial in which the attrition was 2 = 0%, P = 0.04, low-quality evidence) on the 20-point WOMAC
larger in low- versus high-intensity programs (32% versus 12%) pain scale for the high- versus low-intensity exercise programs, an
(Ng 2010). absolute reduction in pain of 4% (8% better to 0% worse), and
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 17
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
relative reduction of 13% (25% better to 0% worse) (Summary of
findings for the main comparison). Between-study heterogeneity
was negligible (I2 = 0%). One study with 200 participants found
a statistically significant reduction (MD -1.7 cm, 95% CI -1.9
to -1.4) on a 10-cm VAS equivalent to a MD of -0.67 (95%
CI -0.8 to -0.6) on a Likert scale (Singh 2011). One study of
39 participants found no statistically significant difference on the
AIM2 pain subscale (MD -0.11, 95% CI -1.3 to 1.1) (Mangione
1999).
Figure 3. Forest plot of comparison: 1 High- versus low-intensity exercise, outcome: 1.1 Pain (WOMAC).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 18
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ercise), which is unlikely to be of clinical significance.
Figure 4. Forest plot of comparison: 1 High- versus low-intensity exercise, outcome: 1.2 Physical Function
(WOMAC).
Muscle strength
Range of motion
Many different muscle groups were tested, with heterogeneity in
number of methods used to evaluate muscle strength. We then cal- Two studies, of 190 and 200 participants, reported statistically
culated the effect size using standardized mean difference (SMD) significant effects of high- versus low-intensity exercise programs
to allow for pooling data resulting from different units of measure- on range of motion (McCarthy 2004; Singh 2011). As the data
ment. Three studies of 285 participants reported muscle strength showed signs of heterogeneity (I2 = 92%), we did not pool the
on the knee extensor (McCarthy 2004; Jan 2008; Foroughi 2011), data (Analysis 1.7).
and showed no statistically significant difference between high-
and low-intensity exercise programs immediately after treatment
(SMD (random-effects model): 0.38, 95% CI 0.04 to 0.72, I2 = Physical activity level and number of steps
42%, P = 0.03) (Analysis 1.5), although with substantial statis- Only one study reported the two outcomes (Ng 2010). Data were
tical heterogeneity (I2 = 42%). Two studies of 113 participants incomplete. We performed no analysis for these twp outcomes.
found no statistically significant difference (SMD (random-effects
model): 0.18, 95% CI -0.64 to 1.00) on strength of knee flexor
muscles immediately after treatment (Jan 2008; Foroughi 2011) Subgroup analysis
(Analysis 1.5), with large statistical heterogeneity (I2 = 78%). Two We conducted subgroup analyses (Figure 5, Figure 6) to explore
studies of 245 participants measured global strength (Foroughi possible differences in pooled MDs for immediate post-treatment
2011; Singh 2011), and showed an improvement with high- ver- on pain and physical function outcomes according to the type of
sus low-intensity exercise programs after treatment (SMD 1.01, intensity of exercise programs (time and level of resistance).
Figure 5. Forest plot of comparison: 2 Subgroup analysis: Exercise duration versus resistance, outcome: 2.1
WOMAC Pain.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 20
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Figure 6. Forest plot of comparison: 2 Subgroup analysis: Exercise duration versus resistance, outcome: 2.2
Physical Function.
Pain
Subgroup analysis (Analysis 2.1) showed a statistical significant This finding did not seem to be of clinical significance. High- and
difference (MD -1.37, 95% CI -2.47 to -0.28, I2 = 0%, P = 0.01, low-intensity exercise programs did not differ statistically in the
absolute mean reduction 7%, very low-quality evidence). With effect of resistance (MD -1.57, 95% CI -5.06 to 1.93, I2 = 33%, P
different amounts of time spent in exercise programs, pain on the = 0.38, absolute mean reduction 2%, very low-quality evidence).
20-point WOMAC pain scale was lower with higher than with Adverse events
lower intensity exercise.This finding did not seem to be of clinical No statistical difference was found between the subgroup exercise
significance. No statistical significant differences was found for programs (Analysis 2.3).
amount of resistance (MD -0.23, 95% CI -1.40 to 0.93, I2 = 0%, We did not conduct other subgroup analyses as described in the
P = 0.71, absolute mean reduction 1%, very low-quality evidence) protocol, as we found that data were insufficient.
(Summary of findings 2).
Physical Function Sensitivity analysis
Subgroup analysis (Analysis 2.2) showed a statistically significant
difference (MD -4.10, 95% CI -8.12 to -0.07, I2 = 0%, P = 0.05, The results were robust on excluding one trial, Ng 2010, that
absolute mean reduction 6%, very low-quality evidence) on the included participants with hip and knee osteoarthritis (results not
68-point WOMAC disability subscale. shown).
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 21
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) A D D I T I O N A L S U M M A R Y O F F I N D I N G S [Explanation]
Subgroup analysis: Exercise duration versus resistance in people with knee or hip osteoarthritis
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of Participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Pain - duration exer- The m ean pain - dura- The m ean pain - dura- - 200
M D -1.37 (95% CI-2.
cise tion exercise in the con- tion exercise in the in- (2 studies) very low1,2 47 to -0.28). Absolute
WOM AC (VAS or Likert) trol groups was tervention groups was m ean reduction 7% with
f rom 0 to 20 8.6 points 1.37 lower high intensity exercise
Follow-up: 8 to 12 (2.47 to 0.28 lower) program s (95% CI -12%
weeks m ore to 1% f ewer). Rel-
lower scores m ean re- ative m ean reduction
duced pain 16% (95% CI -29% m ore
to 3% f ewer). NNTB =
11 (95% CI 9 to 14) 3,4
Pain - resistance exer- The m ean pain - resis- The m ean pain - resis- - 113
M D -0.23 (-1.40 to 0.93)
cise tance exercise in the tance exercise in the in- (2 studies) very low1,2 . Absolute m ean reduc-
WOM AC (VAS or Likert) control groups was tervention groups was tion 1% with high inten-
f rom 0 to 20 4.6 points 0.23 lower sity exercise program s
Follow-up: 8 to 24 (1.4 lower to 0.93 (95% CI -7% m ore to 5%
weeks lower) f ewer). Relative m ean
lower scores m ean re- reduction 5% (95% CI -
duced pain 30%m ore to 20%f ewer)
. NNTB = 17 (95% CI 13
to 22) 4,5
22
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review)
Function - duration ex- The m ean f unction - du- The m ean f unction - du- - 200
M D -4.1 (-8.12 to -0.
ercise ration exercise in the ration exercise in the in- (2 studies) very low1,2 07). Absolute m ean re-
WOM AC f rom 0 to 68 control groups was tervention groups was duction 6% with high
Follow-up: 8 to 12 27 points 4.10 lower intensity exercise pro-
weeks (8.12 to 0.07 lower) gram s (95% CI -12%
lower scores m ean bet- m ore to 0% f ewer).
ter f unction Relative m ean reduc-
tion 15% (95% CI -
30% m oreto 0% f ewer ).
NNTB = 10 (95% CI 8 to
13) 4,6
Function - resistance The m ean f unction - re- The m ean f unction - - 113
M D -1.57 (-5.06 to 1.93)
exercise sistance exercise in the resistance exercise in (2 studies) low1,2 . Absolute m ean reduc-
WOM AC f rom 0 to 68 control groups was the intervention groups tion 2% with high inten-
Follow-up: 8 to 24 16.3 points was sity exercise program s
weeks 1.57 lower (95% CI -7% m ore to 3%
lower scores m ean bet- (5.06 to 1.93 lower) f ewer). Relative m ean
ter f unction reduction -10% (95% CI-
31%m ore to 12%f ewer)
. NNTB = 18 (95% CI 14
to 23) 4,7
* The basis f or the assumed risk (e.g. the m edian control group risk across studies) is provided in f ootnotes. The corresponding risk (and its 95% conf idence interval) is
based on the assum ed risk in the com parison group and the relative effect of the intervention (and its 95% CI).
CI: conf idence interval; M D: m ean dif f erence; NA: not applicable; NNTB: num ber needed to treat f or an additional benef icial outcom e; NNTH: num ber needed to treat f or an
additional harm f ul outcom e; NRS: num eric rating scale; SD: standard deviation; VAS: visual analog scale; WOM AC: Western Ontario and M cM aster Universities Arthritis Index
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24
DISCUSSION the potential impact of disease severity on the effects of exercise
programs.
Summary of main results All included studies assessed a variety of interventions, with dif-
ferent levels of intensity. The type of exercise programs differed
The main purpose of this review was to evaluate the effect of among the six studies. None of the studies compared the same
high- versus low-intensity physical activity or exercise programs exercise interventions. Programs included walking (Ng 2010), cy-
on reducing pain and improving physical function and quality of cling (Mangione 1999), global muscle strengthening (McCarthy
life for people with hip or knee osteoarthritis. We characterized 2004), dynamic resistance training (Jan 2008; Foroughi 2011),
the intensity of an activity or an exercise program either by the and isometric resistance training (Singh 2011). We could not de-
overall amount of training time (duration, number of sessions) termine the optimal type of exercise.
or the amount of resistance (strength or effort). We included six The studies assessed a variety of outcome measures relating to
studies involving 656 participants. pain, physical function, quality of life, and physical performance.
Based upon low-quality evidence, we found a small improvement The outcomes measured often differed between studies. For pain
in pain and function of high-intensity compared to low-inten- (4 studies) and physical function (5 studies), the WOMAC scales
sity exercise programs in people with knee osteoarthritis, but this were most commonly used (see Table 1). The same outcome (that
is unlikely to be of clinical importance. We are uncertain of the is WOMAC pain or disability subscore) was sometimes available
effect on quality of life.The pooled analysis showed small statis- in different units (Likert, visual analog scale, or numeric rating
tical effect sizes for pain (0.84 points) on a 20-point WOMAC scale) or different scales, and we had to rescale the data to pool the
scale and physical function (2.65 points) on a 68-point WOMAC measures in the analysis.
scale. The minimal clinically important difference values we used Apart from pain and physical function, quality of life and adverse
for the WOMAC measures were 15% for absolute improvement events were the main outcomes assessed in the studies. However,
and 20% for relative improvement (Tubach 2012). The statisti- only one study specified quality of life as an outcome, and few
cally significant differences we observed between high- and low- studies (n = 3) reported information on any adverse events. In ad-
intensity exercise were much smaller, and therefore unlikely to be dition, only one study reported the secondary outcomes we exam-
of clinical significance. In addition, the effects of high-intensity ined. Finally, the results were limited to short-term effects because
exercise were found only in the short-term after treatment. Based a limited number of studies reported follow-up assessments for
upon very low-quality evidence, we found a statistically significant longer times
difference in subgroup analyses depending on the type of intensity
of exercise programs (time and level of resistance). However, these
findings were unlikely to be of clinical importance. Quality of the evidence
In most of the included trials adverse events were poorly moni-
tored and poorly reported. We are uncertain as to whether higher- We found limitations in the included studies inherent to study
intensity exercise programs may induce more harmful effects than design (lack of blinding, incomplete data reporting, no intention-
lower-intensity programs. We downgraded the evidence from high to-treat (ITT) analysis) and imprecision (inadequate and small
to low or very low because of the risk of bias, imprecision (small sample sizes, and small number of studies).
number of studies or participants, large confidence interval, small We found the overall quality of evidence to be low for pain and
effects), and inconsistency in the reporting of adverse effects. physical function to very low for adverse effects for the primary
outcomes using the GRADE approach. Most of the studies had an
unclear or high risk of bias for several domains. We downgraded
most studies (n = 5) to high risk of bias for performance, detec-
Overall completeness and applicability of tion, and attrition bias because of lack of blinding and incomplete
evidence outcome data, which can affect the quality of the randomization.
Our evidence is limited to exercise programs for participants with Given that the primary outcomes of this review were participant
knee osteoarthritis. We did not perform a meta-analysis of phys- self reported pain and physical function, the treatment effect sizes
ical activity interventions or participants with hip osteoarthritis may be inflated. We assessed potential bias due to incomplete out-
because of the lack of data. Generalization of our findings to other come data as at high risk of bias because of the lack of ITT analysis
populations should be limited. Most participants in the included and high level of attrition (see Characteristics of included studies).
trials were women (greater than 70%), confirming the gender dif- Although sample size does not contribute to the assessment of
ferences noted in the prevalence of knee osteoarthritis (OConnor study risk of bias, most of the included six studies were under-
2007). However, the extracted data did not allow us to consider powered to provide clear answers, and we downgraded evidence
gender-related differences in the evaluation of the effectiveness of because of imprecision. Three studies had small sample sizes (less
exercise programs. We were also unable to determine whether knee than 100 participants), and two did not report a prospective sam-
osteoarthritis severity plays a role. More research is needed into ple size calculation. Due to the small sample sizes, we are unclear
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 25
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
whether the recruited participants represent all people with knee sion coefficients on meta-regression analysis of intensity resistance
osteoarthritis. The intervention may benet only a subset of people or effort, but equally by length of exercise program, number of
(that is selection bias) supervised sessions, duration of individual supervised sessions, or
Despite performing an extensive search, we included a limited number of sessions per week as covariates. This absence of the
number of studies (n = 6). We were unable to estimate the impact effect of high-intensity strength training of the lower limb was
of publication bias on our results. also reported in a study of older adults (Raymond 2013). In our
subgroup analysis, we also found no statistically significant differ-
ence between level of intensity with resistance exercises with the
Potential biases in the review process same length of program. Resistance exercises seem to have a pos-
itive impact on muscle strength improvements in healthy elderly,
The studies included in this review form the best available evi- in Fiatarone Singh 2004 and Porter 2006, or rheumatoid patient
dence for the review question. We conducted an extensive search population, in Baillet 2012. Furthermore, there is a large body of
of the literature in all relevant databases and included six studies evidence for many years showing changes in strength and mus-
of interventions for exercise programs in participants with knee cle composition in relation to different intensities (Beijersbergen
osteoarthritis. We also identified two ongoing trials for potential 2013).
additional data. We made all attempts to reduce the bias involved Strengthening may also be effective in people with knee os-
with the review process. For missing data, we made attempts to teoarthritis, but we lack data favoring a greater effect of exercise
extract data that were graphically displayed using software tools with high versus low resistance. The intensity of exercises for both
(that is http://arohatgi.info/WebPlotDigitizer/index.html) or to groups may not have been separated enough to differentiate be-
gather the information from authors of the included studies. tween the loadings achieved by the study groups. Future studies
should investigate a specific exercise program designed for a sham-
exercise group, whereby the joint receives low loading.
Agreements and disagreements with other Adverse events have been reported during exercising (Chilibeck
studies or reviews 2011). Recently, some data have suggested that physical exercise
may induce adverse effects in knee joints of animals (Siebelt 2014).
Systematic reviews, Wang 2012, Uthman 2013, and Juhl 2014,
High-resistance exercise should perhaps be used with caution, par-
and recommendations, Fernandes 2013, investigating the effects
ticularly for people with depleted cartilage or severity stage of os-
of exercise programs for knee osteoarthritis have been published,
teoarthritis. The lack of evidence of the beneficial effect of high re-
and have reported that exercise programs are effective for reduc-
sistance suggests a preference for moderate resistance in strength-
ing pain and improving functional outcome in people with knee
ening exercises for people with knee osteoarthritis, but with a long-
osteoarthritis. However, we lack information regarding the opti-
duration program.
mal intensity of exercise for people with knee or hip osteoarthritis.
Only a few studies have directly compared different intensities of
exercise programs, and the type of exercise varied widely, so speci-
fying the required dose for optimal benefit for symptoms of lower-
limb osteoarthritis is difficult. AUTHORS CONCLUSIONS
Previous systematic reviews of exercise suggested a relationship be-
tween the time spent in an exercise program and the size of out- Implications for practice
comes for various health conditions such as stroke, in Veerbeek We found very low- to low-quality evidence for no important clin-
2014, or back pain, in Ferreira 2010. A similar (positive dose- ical benefit of high-intensity compared to low-intensity exercise
response) relationship between the time spent in the exercise pro- programs in improving pain and physical function in the short
gram (number of supervised exercise sessions and session dura- term. We did not find important clinical difference in subgroup
tion) and the effect size for pain was reported by Juhl 2014 when analyses depending on the type of intensity of exercise programs
considering only aerobic exercise in the meta-regression analysis. (time and level of resistance).
However, this evidence was obtained from indirect comparisons,
We are unable to make a conclusion about the effects for qual-
with a global effect size computed by meta-regression (EUnetHTA
ity of life between high- and low-intensity exercise programs. Ad-
2013). All randomized controlled trials we included compared ex-
verse events related to exercise were minor, but they were poorly
ercise programs for which participants were randomized to a high-
recorded. It is uncertain if higher-intensity exercise programs may
or low-intensity group (direct comparisons) within each study.
induce more harmful effects than lower-intensity programs; this
This situation is reinforced by the results found by indirect com-
must be evaluated by further studies.
parisons and adds confidence to the findings.
In a meta-analysis considering only the exercise programs based Our review highlights the need for better reporting of exercise
on resistance, Juhl 2014 found no statistically significant regres- programs in clinical trials with explicit descriptions that enable
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 26
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
replication (Slade 2012). We could not investigate the effect of and the highest intensity that patients can tolerate. Dose selection
other exercise characteristics (for example delivery modalities such should be better justified, especially when the suboptimal dose is
as supervision or mono- or multi-modal exercise). Studies directly unknown.
comparing prescriptive elements (modality, intensity, duration of
Clinical studies in the field of rehabilitation should be carefully
exercise) are critically needed to advance this field.
designed and follow the most recent Consolidated Standards of
Reporting Trials (CONSORT) guidelines to report their data.
Implications for research Most studies included in this review did not use ITT analysis,
The small number of studies comparing high- and low-intensity concealed allocation, or blinding of assessors or did not report
exercise programs in osteoarthritis underscores the need for more data on common outcome measures. In addition, specific designs
studies to investigate the dose-response relationship. More research can also be considered to address some limitations that traditional
is required to further study the potential impact of clinical char- randomized controlled trials face, such as the small number of
acteristics of participants in terms of gender and disease severity participants in clinical trials of rehabilitation (Graham 2012).
on the effects of an exercise program.
The included studies did not provide any justification for the levels
of intensity of exercise programs. No authors reported evidence
ACKNOWLEDGEMENTS
for the minimal and maximal intensity that could be delivered. We
could not ensure that exercise of sufficient intensity was performed The review authors are grateful to Louise Falzon, the Trials Search
because exercises performed at high resistance failed to increase Co-ordinator for the Cochrane Musculoskeletal Group, for her as-
muscle strength of knee extensor or knee flexor, in Jan 2008 and sistance in designing the search strategy, and to Pr Serge Poiraudeau
Foroughi 2011, or aerobic capacity, in Mangione 1999. The dif- for his comments.
ference (small or large) between the high- and low-intensity pro-
We thank Dr Elizabeth Tanjong Ghogomu and Lara Maxwell,
grams varied across studies. The differences may be insufficient
Cochrane Musculoskeletal Review Group, for their valuable com-
to induce any effects, particularly for resistance exercise programs.
ments and expert advice.
In particular, further studies are needed to establish the minimal
effective intensity of programs required to produce a clinical effect We also thank Dr Ann Moseley for help searching studies.
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High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 31
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
CHARACTERISTICS OF STUDIES
Foroughi 2011
Outcomes At 24 weeks:
WOMAC (pain, physical function, global), adverse events, walking speed, muscle
strength (unilateral knee extension, bilateral knee flexion, leg press)
A Likert scale (range 0-20 or 0-68) in WOMAC
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 32
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Foroughi 2011 (Continued)
Risk of bias
Random sequence generation (selection Low risk Quote: participants were randomly allo-
bias) cated using a computer randomization pro-
gram.
Blinding of participants and personnel Unclear risk Quote: All participants were blinded to
(performance bias) the investigators hypothesis.
All outcomes Comment: Staff were not blinded. It un-
clear how this influenced the data
Blinding of outcome assessment (detection Low risk Comment: Performance was measured by
bias) a 3D motion acquisition system. It is
Subjective unlikely that this provided risk of bias,
even though the outcome assessor was not
blinded
Blinding of outcome assessment (detection Low risk Comment: Performance was measured
bias) through a 3D motion acquisition system.
Objective It is unlikely that this provided risk of bias,
even though the outcome assessor was not
blinded
Incomplete outcome data (attrition bias) High risk Comment: Unbalanced drop-out rate,
All outcomes >10%. No imputation method used. No
ITT analysis, which might introduce a bias
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 33
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jan 2008
Outcomes At 8 weeks: WOMAC (pain, physical function), walking time (level ground, stairs, figure-
eight pattern, spongy surface), muscle strength (flexion and extension of the knee; torque
tested at 60, 120, and 180/s). A Likert scale (range 0-20 or 0-68) for the WOMAC
Risk of bias
Random sequence generation (selection Low risk Quote: using a random numbers table from a ran-
bias) dom integer generator
Allocation concealment (selection bias) Unclear risk Comment: Unclear if the list of randomization is
concealed
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 34
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jan 2008 (Continued)
Blinding of participants and personnel High risk Comment: Participants and staff were not blinded
(performance bias)
All outcomes
Blinding of outcome assessment (detection High risk Comment: Participants not blinded
bias)
Subjective
Blinding of outcome assessment (detection Low risk Quote: All evaluations were performed by the same
bias) examiner, who was unaware of the participants
Objective group assignments.
Incomplete outcome data (attrition bias) High risk Quote: 3 participants in HR group discontinued
All outcomes the exercise intervention due to severe knee pain.
We speculate that the intensity and repetitions of the
resistance training might be 2 factors influencing the
training effect in patients with knee osteoarthritis
Comment: Despite an ITT analysis, the drop-out
rate was unbalanced between the 2 groups (3 vs 0)
and seems related to the intervention. No imputa-
tion technique was described
Selective reporting (reporting bias) Unclear risk Comment: Insufcient information. No protocol reg-
istration. Major and minor outcomes are not speci-
fied; unclear what they are
Other bias Low risk Comment: Power sample size calculation. No dif-
ference at baseline between groups. From the data
provided, no indication of other important risks of
bias
Mangione 1999
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 35
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mangione 1999 (Continued)
Outcomes At 10 weeks: subscale pain, Arthritis Impact Measurement Scale 2, walking speed, 6-
min walk test, peak oxygen consumption
Risk of bias
Random sequence generation (selection Low risk Comment: Computer generated random numbers used
bias)
Allocation concealment (selection bias) Unclear risk Comment: No procedure was described
Blinding of participants and personnel High risk Comment: Insufcient information, but it is unlikely that partic-
(performance bias) ipants and care providers were blinded
All outcomes
Blinding of outcome assessment (detection High risk Comment: Insufcient information, but it is unlikely that the
bias) participants were blinded
Subjective
Blinding of outcome assessment (detection Unclear risk Comment: No information on blinding of outcome assessors
bias) was provided. Unclear how this influenced the data
Objective
Incomplete outcome data (attrition bias) High risk Comment: No ITT analysis. High rate of drop-out (30%),
All outcomes which might introduce bias
Selective reporting (reporting bias) Unclear risk Comment: Insufficient information. No protocol registration.
Major and minor outcomes not declared; unclear what they are
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 36
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Mangione 1999 (Continued)
Other bias Unclear risk Comment: No sample size calculation provided. Baseline per-
formance seems similar between the 2 groups
McCarthy 2004
Participants Location: UK
Randomized: 225
Age: mean 64.7 years
Sample: 125 females and 89 males with knee osteoarthritis
Settings: academic, monocenter
Inclusion criteria: met the ACR clinical criteria (knee pain, knee radiograph, clinical
features) and radiological evidence of osteophytes
Exclusion criteria: symptomatic back or hip disease, knee osteoarthritis secondary to
inflammatory arthritis, symptoms affecting the ankles or feet, person unable or unwilling
to attend a physiotherapy treatment, psychiatric or medical morbidity that precludes
participation in exercise treatment, receiving an intra-articular steroid injection within
3 months
Interventions Intensity: Exercise program with different levels of time spent in exercise
High intensity (n = 111): frequency: 2 times/week * 8 weeks; session duration: 45 min;
intensity: home exercise + class exercise = circuit of exercise (5-min warm-up, 5-min
stretching, 5-min balance training, 10-min isotonic exercises, 5-min isometric quadriceps
exercises, 5-min cool-down). Progression: the class exercise program was increased and
decreased by the senior physiotherapist by clinical discretion and in discussion with the
participant
Low intensity (n = 103): frequency: no information; session duration: no information;
intensity: home exercise = muscle strengthening exercises, muscular endurance exercise,
range of motion, standing balance. The home exercise was progressed. The level of
intensity was fixed at 60% of the initial assessment, then reassessed and increased to 70%
after 4 weeks, then to 80%
All groups: Home and class exercises were progressed or reduced in case of an exacerbation
of symptoms
Supervision: senior therapist in the class exercise
Outcomes At 8 weeks: Pain VAS, WOMAC pain, WOMAC physical function, SF-36, EuroQol
(ED-5D), muscle strength, range of motion
3 months: EuroQol (ED-5D)
6 months: SF-36, EuroQol (ED-5D), muscle strength, pain VAS, WOMAC, range of
motion
9 months: EuroQol (ED-5D)
12 months: SF-36, EuroQol (ED-5D), muscle strength, pain VAS, WOMAC, range of
motion
Using a Likert scale (range 0-20 or 0-68) in WOMAC
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 37
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
McCarthy 2004 (Continued)
Risk of bias
Random sequence generation (selection Low risk Quote: Subject allocation was carried out using a computerised
bias) minimisation algorithm built into an access.
Comment: Adequate method was used
Allocation concealment (selection bias) Low risk Quote: The lead investigator provided participants details to
the trial data manager, who used a computerised, password-se-
cured randomisation system (Microsoft Access) to allocate pa-
tients, at a location separate from the trial investigators place of
work.
Comment: Allocation seemed to have remained concealed and
the risk of selection bias low
Blinding of participants and personnel High risk Quote: This design feature allowed the patients to know which
(performance bias) of the two treatment programs they were receiving.
All outcomes Comment: Participants and staff were not blinded
Blinding of outcome assessment (detection High risk Comment: Participants were not blinded, introducing a risk of
bias) bias for subjective outcomes
Subjective
Blinding of outcome assessment (detection Low risk Quote: To protect against bias, outcome assessments were made
bias) blind to allocation.
Objective
Incomplete outcome data (attrition bias) High risk Quote: An ITT analysis on the major outcomes 12-month
All outcomes data was conducted using last value carried forward (LVCF)
imputation to examine further the effect of missing data.
Comment: ITT conducted only on 12 months data. A drop-
out rate > 10% is noted and unbalanced among the 2 groups
immediately at the end of the intervention (83% and 94%)
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 38
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
McCarthy 2004 (Continued)
Selective reporting (reporting bias) High risk Comment: No protocol was found. Major and minor outcomes
were specified, but additional outcomes data was incompletely
reported in different reports (i.e. the SF-36 score is reported in
McCarthy a but not McCarthy b)
Other bias Low risk Comment: There is no indication of other important risks of
bias. Baseline performances seem similar between the 2 groups.
A sample size calculation was provided
Ng 2010
Interventions Intensity: Exercise program with different levels of time spent in exercise
High intensity (n = 17): frequency: 5 times/week * 12 weeks; duration: 30 to 60 minutes
Low intensity (n = 19): frequency: 3 times/week * 12 weeks; duration: 30 to 60 m inutes
Intensity and progression: all groups were asked to walk at least 3000 steps (30 min)
during 6 weeks and 6000 steps (60 min) during the 6 other weeks
Supervision: unsupervised
Outcomes At 12 weeks: WOMAC (pain, function, global) using a numerical rating scale (range 0-
10); Active Australia Physical Activity Questions, number of steps
Follow-up at 18 weeks: WOMAC (pain, function, global); Active Australia Physical
Activity Questions, number of steps
We converted the final scores expressed in a VAS to a Likert scale for the WOMAC pain
(range 0-20) and function (range 0-68) subscales
Risk of bias
Random sequence generation (selection Low risk Comment: A computer random-number generator was used
bias)
Allocation concealment (selection bias) High risk Quote: For practical reasons, allocation to group was not con-
cealed. The assessor and main analyst (NTMN) was not
blinded to group allocation and conducted the randomisation
process before baseline, which may have contributed to ascer-
tainment or performance biases.
Comment: Confirmed by the author that the allocation was not
concealed
Blinding of participants and personnel High risk Comment: Insufcient information, but it is unlikely that partic-
(performance bias) ipants and care providers were blinded
All outcomes
Blinding of outcome assessment (detection High risk Quote: assessor and main analyst (NTMN) were not blinded
bias) to group allocation
Subjective
Blinding of outcome assessment (detection High risk Quote: assessor and main analyst (NTMN) were not blinded
bias) to group allocation
Objective Comment: Participants were not likely blinded, introducing a
risk of bias
Incomplete outcome data (attrition bias) High risk Quote: data were analysed on a per protocol basis
All outcomes Comment: No ITT. Rate of drop-out is unbalanced between
the 2 groups (12% and 32%), and high in 1 group
Selective reporting (reporting bias) High risk Comment: Protocol registration. All the important outcomes
data were not reported in the final publication. The authors
kindly provided the data (WOMAC) on request
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 40
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Ng 2010 (Continued)
Other bias High risk Quote: Compliance was higher in the three-day walking group
than in the five-day walking group. Among participants in the
three-day walking group, there was 100% compliance with walk-
ing
three days per week during Weeks 8, 9, 12, 15, and 18. Among
participants in the five-day walking group, compliance ranged
from 93% (Week 7) to 58% (Week 16) during the 12-week
walking program.
Comment: Compliance in the 5-day group was lower and dif-
ferent than in the 3-day group, for a high risk of bias. No sample
size calculation
Singh 2011
Interventions Intensity: Exercise program with different levels of time spent in exercise
High intensity (n = 100): frequency: 5 times/week * 8 weeks; session duration: 40 min;
intensity: aerobic warm-up (5-10 min), walking (5-10 min), cycling at 60% of maximum
heart rate (15-20 min) in addition to the conventional exercise program
Low intensity (n = 100): frequency: 5 times/week * 8 weeks; duration: unknown min;
intensity: conventional exercise program = hot packs, isometric exercises to quadriceps
and hamstrings, range of motion, stretching and joint mobilization exercises, progressive
resisted exercises
All groups: participated in a conventional exercise program
The authors did not provide any information on the progression or the supervision of
the sessions
Outcomes At 8 weeks: pain (VAS), WOMAC (function), muscle strength (isometric and iso-
tonic strength measures), range of motion. Unclear whether VAS or Likert was used in
WOMAC
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 41
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Singh 2011 (Continued)
No information on funding
Risk of bias
Random sequence generation (selection Unclear risk Comment: No information on the process of randomization
bias)
Allocation concealment (selection bias) Unclear risk Comment: Insufcient information on allocation concealment
Blinding of participants and personnel High risk Comment: Insufficient information, but it is unlikely that par-
(performance bias) ticipants and care providers were blinded, for possible risk of
All outcomes bias
Blinding of outcome assessment (detection High risk Comment: Insufficient information, but it is unlikely that par-
bias) ticipants and care providers were blinded, for possible risk of
Subjective bias
Blinding of outcome assessment (detection High risk Comment: Insufficient information, but it is unlikely that par-
bias) ticipants and care providers were blinded
Objective
Incomplete outcome data (attrition bias) Unclear risk Comment: Insufcient information
All outcomes
Selective reporting (reporting bias) Unclear risk Comment: Insufficient information. WOMAC score could not
be extracted because of insufficient data presentation
Other bias Unclear risk Comment: Baseline performance seems similar between the 2
groups. No sample size calculation
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 42
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Characteristics of excluded studies [ordered by study ID]
Chang 2012 RCT but no variation of intensity between the 2 interventions. Compared exercise with elastic bands + conventional
modality treatments (shortwave diathermy, hot packs, transcutaneous electrical nerve stimulation, interferential
current versus conventional modality treatments
Diracoglu 2005 RCT but no variation of intensity between the 2 interventions. Compared strengthening exercise + balance versus
strengthening exercise alone
Eyigor 2004 Intervention not appropriate. Effect of intensity could not be evaluated between the 2 groups. Compared isokinetic
exercise program versus progressive resisted exercises program (isotonic regimen)
Fitzgerald 2011 RCT but no variation of intensity between the 2 interventions. Same amount of time in training between the 2
groups
Green 1993 RCT but no variation of intensity between the 2 interventions. Study compared home exercise versus hydrotherapy
Sevick 2000 RCT but no variation of intensity between the 2 interventions. Study compared an aerobic exercise program
consisting of walking on a treadmill at 50% to 70% of their heart reserve versus a resistance exercise program
consisting of strengthening major muscle groups of both the upper and lower extremities
Shakoor 2007 RCT but no variation in intensity between the 2 interventions. Compared exercise versus exercise + activity
modification advice
Teixeira 2011 This study appears to be the same trial as Fitzgerald 2011 and was excluded
Topp 2002 RCT but no variation in intensity between the 2 interventions. Compared dynamic resistance versus isometric
resistance versus no intervention
Veenhof 2006 RCT but no variation in intensity between the 2 interventions. Compared behavioral versus usual care
Steinhilber 2012
Methods RCT
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 43
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Steinhilber 2012 (Continued)
Messier 2011
Methods RCT
Interventions High-intensity strength training versus low-intensity strength training versus attention control
Outcomes Pain, knee joint compressive forces, function, mobility, inflammatory markers, thigh composition measured
at baseline, 6, 12, 18 months
Notes NCT01489462
Pua 2012
Trial name or title Eccentric resistance ergometry in knee osteoarthritis rehabilitation: a randomized clinical trial (EUREKA)
Methods RCT
Interventions Standard physiotherapy treatment and exercise on an eccentric ergometer versus standard physiotherapy
Outcomes Isometric knee extensor torque, gait speed, bridging, knee pain, knee passive range of motion, Short Form-
36, standing balance
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 44
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Pua 2012 (Continued)
Notes ACTRN12612000411842
ng 2013
Trial name or title Dose-response effects of medical exercise therapy in patients with osteoarthritis of the knee - a Nordic
multicenter clinical trial
Methods RCT
Outcomes Knee Injury and Osteoarthritis Outcome Score, VAS pain scale, self rated patient satisfaction scale, Hospital
Anxiety and Depression scale, Catastrophizing Scale, Tampa Scale of Kinesiophobia, 20-meter walk test, 30s
Maximal Repeated Unilateral Knee Bending test, Five Time Repeated Chair Stands
Notes NCT02024126
sters 2012
Trial name or title Dose-response: exercise therapy on hip osteoarthritis, a pilot study
Methods RCT
Outcomes Stairs, squats, WOMAC Index of Osteoarthritis (questionnaire) measured 8 weeks and 6 months
Notes NCT01700933
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 45
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DATA AND ANALYSES
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Pain (WOMAC) 4 Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.1 at study completion 4 313 Mean Difference (IV, Fixed, 95% CI) -0.84 [-1.63, -0.04]
1.2 at mid term 2 199 Mean Difference (IV, Fixed, 95% CI) -0.82 [-1.90, 0.26]
1.3 at long-term 1 138 Mean Difference (IV, Fixed, 95% CI) -1.33 [-2.56, -0.10]
2 Physical Function (WOMAC) 4 Mean Difference (IV, Fixed, 95% CI) Subtotals only
2.1 at study completion 4 313 Mean Difference (IV, Fixed, 95% CI) -2.65 [-5.29, -0.01]
2.2 at mid term 2 199 Mean Difference (IV, Fixed, 95% CI) -2.95 [-7.00, 1.10]
2.3 at long-term 1 138 Mean Difference (IV, Fixed, 95% CI) -4.20 [-9.32, 0.92]
3 Adverse effects 4 364 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.72 [0.51, 5.81]
4 Gait speed 3 Mean Difference (IV, Random, 95% CI) Subtotals only
4.1 Free walking speed 2 77 Mean Difference (IV, Random, 95% CI) 0.04 [-0.05, 0.13]
4.2 Fast walking speed 2 107 Mean Difference (IV, Random, 95% CI) 0.08 [-0.13, 0.29]
5 Muscle strength 4 Std. Mean Difference (IV, Random, 95% CI) Subtotals only
5.1 Knee extensor 3 285 Std. Mean Difference (IV, Random, 95% CI) 0.38 [0.04, 0.72]
5.2 Knee Flexor 2 113 Std. Mean Difference (IV, Random, 95% CI) 0.18 [-0.64, 1.00]
5.3 Global strength 2 245 Std. Mean Difference (IV, Random, 95% CI) 1.01 [0.74, 1.27]
6 Aerobic capacity 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
7 Range of Motion 2 Mean Difference (IV, Random, 95% CI) Totals not selected
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 46
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.1. Comparison 1 High versus low intensity exercise, Outcome 1 Pain (WOMAC).
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 at study completion
McCarthy 2004 93 7.5 (3.95) 79 9.04 (3.84) 46.9 % -1.54 [ -2.71, -0.37 ]
Foroughi 2011 20 3.8 (2.7) 25 4.4 (3.7) 18.2 % -0.60 [ -2.47, 1.27 ]
Jan 2008 34 4.8 (3.5) 34 4.8 (2.7) 28.9 % 0.0 [ -1.49, 1.49 ]
-10 -5 0 5 10
Favors High intensity Favors Low intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 47
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.2. Comparison 1 High versus low intensity exercise, Outcome 2 Physical Function (WOMAC).
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 at study completion
McCarthy 2004 93 23.6 (13.9) 79 28.1 (14.7) 37.6 % -4.50 [ -8.80, -0.20 ]
Jan 2008 34 14.7 (8.5) 34 14.8 (9.2) 39.3 % -0.10 [ -4.31, 4.11 ]
Foroughi 2011 20 13.3 (9.4) 25 18.1 (12) 17.8 % -4.80 [ -11.05, 1.45 ]
-20 -10 0 10 20
Favors High intensity Favors Low intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 48
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.3. Comparison 1 High versus low intensity exercise, Outcome 3 Adverse effects.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Peto Peto
Study or subgroup Experimental Control Odds Ratio Weight Odds Ratio
n/N n/N Peto,Fixed,95% CI Peto,Fixed,95% CI
Foroughi 2011 2/26 1/28 27.9 % 2.16 [ 0.21, 21.75 ]
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 49
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 High versus low intensity exercise, Outcome 4 Gait speed.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
Mangione 1999 19 1.1 (0.2) 20 1.01 (0.19) 44.6 % 0.09 [ -0.03, 0.21 ]
Mangione 1999 19 1.71 (0.3) 20 1.63 (0.36) 100.0 % 0.08 [ -0.13, 0.29 ]
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 50
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.5. Comparison 1 High versus low intensity exercise, Outcome 5 Muscle strength.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Std. Std.
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
1 Knee extensor
McCarthy 2004 93 71.1 (32.1) 79 59.9 (21.6) 47.6 % 0.40 [ 0.10, 0.70 ]
Jan 2008 34 88.1 (21.6) 34 86.7 (24.2) 30.5 % 0.06 [ -0.42, 0.54 ]
Foroughi 2011 20 57.4 (25.8) 25 40.3 (16.9) 21.8 % 0.79 [ 0.18, 1.40 ]
Foroughi 2011 20 110.6 (24.1) 25 93.5 (29.1) 47.5 % 0.62 [ 0.02, 1.23 ]
Foroughi 2011 20 1461.8 (504.1) 25 1092.1 (438.2) 19.0 % 0.78 [ 0.16, 1.39 ]
-2 -1 0 1 2
Favors Low intensity Favors High intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 51
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.6. Comparison 1 High versus low intensity exercise, Outcome 6 Aerobic capacity.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Mean Mean
Study or subgroup High intensity Low intensity Difference Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
-10 -5 0 5 10
Favors High intensity Favors Low intensity
Analysis 1.7. Comparison 1 High versus low intensity exercise, Outcome 7 Range of Motion.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Mean Mean
Study or subgroup High intensity Low intensity Difference Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
McCarthy 2004 104 124.9 (12.2) 86 119 (13.9) 5.90 [ 2.14, 9.66 ]
Singh 2011 100 121.3 (11.4) 100 107.3 (13.6) 14.00 [ 10.52, 17.48 ]
-20 -10 0 10 20
Favors Low intensity Favors High intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 52
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.1. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 1 Pain.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Outcome: 1 Pain
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 Duration exercise
McCarthy 2004 93 7.5 (3.95) 79 9.04 (3.84) 88.6 % -1.54 [ -2.71, -0.37 ]
Foroughi 2011 20 3.8 (2.7) 25 4.4 (3.7) 38.7 % -0.60 [ -2.47, 1.27 ]
-10 -5 0 5 10
Favors High intensity Favors Low intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 53
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.2. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 2 Function.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Outcome: 2 Function
Mean Mean
Study or subgroup High intensity Low intensity Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 Duration exercise
McCarthy 2004 93 23.6 (13.9) 79 28.1 (14.7) 87.6 % -4.50 [ -8.80, -0.20 ]
Foroughi 2011 20 13.3 (9.4) 25 18.1 (12) 31.2 % -4.80 [ -11.05, 1.45 ]
-20 -10 0 10 20
Favours High intensity Favours Low intensity
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 54
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 2.3. Comparison 2 Subgroup analysis: Exercise duration versus resistance, Outcome 3 Adverse
effects.
Review: High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis
Study or subgroup High intensity Low intensity Odds Ratio Weight Odds Ratio
n/N n/N IV,Fixed,95% CI IV,Fixed,95% CI
1 Duration exercise
McCarthy 2004 0/111 1/103 30.3 % 0.31 [ 0.01, 7.61 ]
ADDITIONAL TABLES
Table 1. Primary outcomes reported in included studies
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 55
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Table 1. Primary outcomes reported in included studies (Continued)
Gait speed Gait speed Muscle Muscle Muscle Aerobic Range of Physical Number
(fast) (normal) strength strength strength capacity motion activity of steps
(knee ex- (knee (global)
tensor) flexor)
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 56
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
APPENDICES
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 57
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Appendix 2. EMBASE search strategy
1. osteoarthritis/
2. (degenerative adj2 arthritis).tw.
3. (osteoarthr$ or arthrosis).tw.
4. or/1-3
5. knee/
6. knee$.tw.
7. hip/
8. (hip or hips).tw.
9. or/5-8
10. 4 and 9
11. knee osteoarthritis/
12. hip osteoarthritis/
13. or/10-12
14. exp exercise/
15. exp kinesiotherapy/
16. rehabilitation/
17. exp motor activity/
18. exercis$.tw.
19. physical activit$.tw.
20. strength$.tw.
21. ((isometric$ or isokinetic$ or aerobic$ or endurance or weigh$ or resistance) adj3 (train$ or therap$ or rehab$ or program$)).tw.
22. ((high or low) adj (intens$ or impact or dose$ or amount$)).tw.
23. exp physiotherapy/
24. (physical ther$ or physiother$).tw.
25. (run$ or jog$ or walk$ or treadmill$ or cycl$ or row$ or gait).tw.
26. or/14-25
27. 13 and 26
28. (random$ or placebo$).ti,ab.
29. ((single$ or double$ or triple$ or treble$) and (blind$ or mask$)).ti,ab.
30. controlled clinical trial$.ti,ab.
31. RETRACTED ARTICLE/
32. or/28-31
33. (animal$ not human$).sh,hw.
34. 32 not 33
35. 27 and 34
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Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Appendix 6. SCOPUS search strategy
1 TITLE-ABS-KEY(osteoarthr* OR degenerative arthritis OR arthrosis)
2 TITLE-ABS-KEY(hip OR hips OR knee*)
3 TITLE-ABS-KEY(exercis* OR physical activit* OR strength* OR isometric* train* OR isokinetic* train* OR aerobic* train* OR
endurance train* OR weigh* train* OR resistance train* OR isometric* therap* OR isokinetic* therap* OR aerobic* therap* OR
endurance therap* OR weigh* therap* OR resistance therap* OR isometric* rehab* OR isokinetic rehab* OR aerobic* rehab* OR
endurance rehab* OR weigh* rehab* OR resistance rehab* OR isometric program* OR isokinetic program* OR aerobic* program*
OR endurance program* OR weigh* program* OR resistance program*)
4 TITLE-ABS-KEY(high intens* OR low intens* OR high impact OR low impact OR high dose* OR low dose* OR high amount*
OR low amount*)
5 TITLE-ABS-KEY(physical ther* OR physiother* OR run* OR jog* OR walk* OR treadmill* OR cylc* OR row* OR gait)
6 3 OR 4 OR 5
7 1 AND 2 AND 6
8 Limit 7 to Conference Paper
[Study ID] [Study author contacted] [Study author replied] Current status
CONTRIBUTIONS OF AUTHORS
JPR and MMLC wrote the review.
LB wrote the previous systematic review that is the foundation of the current work.
JPR, MMLC, IB, LB, PR, and LT conceived of and designed the review and interpreted the data.
JPR and CN independently screened retrieved clinical studies for inclusion.
JPR and MMLC extracted data from included studies and performed the methodological quality assessment.
JPR, MMLC, and LT analyzed the data.
JPR, MMLC, IB, LT, LB, and PR reviewed the final manuscript prior to submission.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 61
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DECLARATIONS OF INTEREST
None of the researchers have a commercial for-prot interest in this review. There was no financial support from the pharmaceutical
industry for this review.
SOURCES OF SUPPORT
Internal sources
EHESP, French school of public health, France.
in-kind support
Centre de recherche Epidmiologies et Biostatistique, INSERM U1153, France.
in-kind support
Hpital Htel-Dieu, APHP, France.
in-kind support
External sources
No sources of support supplied
1. Measure of treatment effect in continuous outcomes: added mean difference calculation when the same tool was used to measure
the same outcome across separate studies.
2. Summary of findings tables: added minimum clinical important difference threshold and methods of calculation to express
absolute and relative changes for dichotomous or continuous outcome measures. We followed the recommendations provided by the
Cochrane Musculoskeletal Review Group.
3. We did not perform contour-enhanced funnel plots to assess the presence of small-study effects as the required statistical
conditions were not met.
4. We stated in the protocol that we would attempt to fit a bivariate random-effects meta-analysis to address the issue between
correlated outcomes and missing data. As no data were missing, we did not perform the analysis.
5. We did not perform subgroup analysis to explore whether a relationship exists between the type of treatments, type of
intervention, type of joint, indication of exercise, duration of treatment as insufficient data was available. Meta-regression was also not
possible due to the small number of included studies.
6. We stated in the protocol that would attempt to perform a sensitivity analysis to explore how the results of meta-analysis might
be affected by including only studies at low risk of bias. However, as all the identified studies were at high risk of bias, we did not
perform the analysis.
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 62
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
INDEX TERMS
High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis (Review) 63
Copyright 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.