Evidence on the effects of exercise therapy in the treatment of chronic disease

Transcription

1 Review Department of Health Sienes, University of Jyväskylä, Jyväskylä, Finland Correspondene to: U Kujala, Department of Health Sienes, University of Jyväskylä, PO Box 35 (LL), FIN , Finland; urho.kujala@ sport.jyu.fi Aepted 23 April 2009 Published Online First 29 April 2009 Evidene on the effets of exerise therapy in the treatment of hroni disease U M Kujala ABSTRACT Evidene on the effets of exerise in the treatment of patients with hroni diseases should be based on well designed randomised ontrolled trials. The most onsistent finding of the meta-analyses summarised in the present work is that aerobi/funtional apaity and musle strength an be improved by exerise training among patients with different diseases without having detrimental effets on disease progression. This is important, as with population aging exerise therapy may be an important means of reduing disability and inreasing the number of older people living independently. Additionally, there is aumulating evidene that in patients with hroni disease exerise therapy is effetive in improving the prognosti risk fator profile and, in ertain diseases, in delaying mortality. In some diseases, suh as osteoarthritis, pain symptoms may also be redued. Severe ompliations during the exerise therapy programs were rare. Conlusive evidene as to the benefits of exerise in the treatment of patients with hroni diseases within the limited resoures of the healthare system should be based on well designed randomised ontrolled trials (RCTs). These in turn should be based on a plausible aount of how (via what mehanisms) exerise benefits the patient. As patients with hroni diseases may be at risk for exerise-related ardiovasular or other ompliations, dotors often need to issue suh patients with guidelines for a safe training program. Exerise therapy for hroni diseases an be either generalised aerobi or strength training or ondition-speifi training. A typial example of generalised training is aerobi or strength training ausing systemi effets, suh as that on insulin sensitivity in the treatment of type 2 diabetes mellitus. Condition-speifi training may inlude, for example, a series of speifi movements with the aim of promoting good physial health, suh as strengthening the low bak musles in patients with low bak pain or pelvi floor musle training in patients with urinary inontinene. Reently, the number of RCTs evaluating the effets of physial exerise therapy in the treatment of speifi diseases and related funtional impairments has inreased substantially allowing systemati reviews inluding meta-analyses. This review summarises the evidene so far on the effets of exerise therapy in the treatment/ rehabilitation of different hroni diseases. METHODS Searh strategy and seletion riteria This paper is a summary of the evidene to date from systemati reviews of at least three randomised ontrolled trials investigating the effet of exerise therapy on the same outome among patients with the same hroni disease. For studies to be inluded in this summary review, the intervention and the ontrol groups had primarily to be ontrasted by exerise (most ommonly exerise training + usual are vs usual are). This review is based on previous repeated searhes of the literature 1 and ontats with the authors of different systemati reviews. For this update review, final literature searhes of omputer databases (PubMed, Cohrane Database of Systemati Reviews) were performed for the period from January 2001 up to and inluding Deember Reviews that were not updated after the year 2000, non-systemati reviews, reviews on nonrandomised trials and systemati reviews on exerise in the rehabilitation of aute injuries or musuloskeletal surgery were not inluded. Obesity was not onsidered as a disease in this review. Due to the large number of outome variables only the linially most important outomes are inluded; these were seleted on the basis of the author s linial experiene and ontats with different speialist dotors or sientists. Findings whih lak a plausible explanation of the possible mehanisms underlying the effetiveness of the exerise therapy or whih lak statistial power are not reported systematially in this review. In systemati reviews the results an be given using different qualitative or quantitative (metaanalyses) tehniques. For the most part, this summary review is based on the results of metaanalyses (table 1). Meta-analyses draw on a variety of tehniques. The hoie of tehnique depends on the nature of the data being analysed. For dihotomous (or binary) data the most ommonly used summary statistis in exerise therapy studies are pooled odds ratios (ORs) or relative risks (RRs). For ontinuous data, whenever outomes are measured in a standard way aross studies, the weighted mean differene (WMD) is preferable. Where ontinuous outomes are oneptually the same but measured in different ways, suh as different pain sores in osteoarthritis, the results an be summarised using standardised (for standard deviations in the outome measure) mean differenes (SMDs). In ases where the data available do not enable statistial pooling, qualitative analysis is performed. In this artile, ategories of levels of evidene are not systematially reported, but the effets of exerise therapy are quantified as reported by the authors of speifi meta-analyses. 550 Br J Sports Med 2009;43: doi: /bjsm

2 Before looking at the results of RCTs or the summary statistis of meta-analyses, ritial analysis of the methodologial quality of eah individual RCT is important. Biased results from poorly designed and reported trials an mislead poliy makers. 2 As the assessment of quality sores of different RCTs have not been performed in a standard way in all systemati reviews, study quality is not systematially reported in this paper. The most ommon quality problems are disussed below (see Disussion). SUMMARY OF FINDINGS Musuloskeletal diseases Based on a meta-analysis of 32 RCTs, land-based therapeuti exerise improved self-reported pain and self-reported physial funtion in patients with knee osteoarthritis (table 1). 3 The effets were stronger in interventions with more than 12 diretly supervised training sessions than in those with fewer suh sessions. Higher quality studies reported somewhat smaller effet sizes ompared to lower quality studies. Aerobi walking and lower limb strengthening exerises redued pain and disability. 3 5 The size of the effet of exerise in alleviating pain in hip osteoarthritis has been shown to be omparable to that in knee osteoarthritis. 6 The benefits of aquati exerise were rather similar to those of land-based exerise. 7 The effet of exerise on the progression of osteoarthritis is unlear. On the basis of more than 10 RCTs exerise therapy was effetive in inreasing aerobi apaity and musle strength in patients with rheumatoid arthritis, 8 9 although proper metaanalyses are laking. Additionally, on the basis of three RCTs in patients under 18 years of age with juvenile idiopathi arthritis funtional ability tended to be better after exerise therapy. 10 No detrimental effets on disease ativity and pain were observed. The effets of dynami exerise therapy on radiologial progression and ardiovasular disease need to be studied further. 8 9 Four RCTs ompared an exerise program with no intervention in patients with ankylosing spondylolitis and reported some inreases in spinal mobility and physial funtion. 11 Three RCTs found exerise therapy to be not more effetive than non-exerise for non-speifi aute (,6 weeks) low bak pain. 12 However, it should be noted that exerise therapy is not the same as advie to stay ative, whih is a reommended treatment strategy. In non-speifi hroni (.12 weeks) low bak pain, the evidene suggests that exerise therapy is effetive in improving pain outomes (table 1). 12 Additionally, a meta-analysis found that ondition-speifi funtional outomes improved, but that the effets were small (table 1). Individually designed strengthening or stabilising programs seem to be effetive in healthare settings. 12 On the basis of 43 trials of 72 exerise treatment and 31 omparison groups, and using Bayesian multivariable random-effets meta-regression, Hayden et al 13 found improved pain sores for individually designed programs, supervised home exerise and group and individually supervised programs ompared with home exerises only. In patients with fibromyalgia, aerobi exerise has been shown to inrease physial funtion and global well-being as well as improve pain and possibly tender point pressure threshold (table 1). 14 There is no onlusive evidene of the effets of strength training, although low quality evidene suggests that they are similar to those of aerobi training. Review Cardiovasular diseases Aording to the systemati review of Jolliffe et al 15 exerise therapy in ases of doumented oronary heart disease redued all-ause mortality by 27% and total ardia mortality by 31%, but not the ourrene of non-fatal myoardial infartion (table 1). The patients inluded in the trials were predominantly middle-aged men who had suffered myoardial infartion. In a later review by Taylor et al 16 in whih the effet of endurane training alone or in ombination with psyhologial or eduational interventions were studied, the results for exerise-based rehabilitation on all-ause and ardia mortality resembled those obtained earlier by Jolliffe et al 15 A review of 16 RCTs showed that exerise training inreased heart rate variability in patients with oronary artery disease. 17 A review of 14 RCTs found physiologial benefits of exerise therapy in heart failure patients. 18 A positive training effet was doumented in 12 out of 14 trials, with the results of 2 trials being inonlusive, and positive effets on some measures of quality of life were doumented in 7 out of 9 trials. 18 The patients inluded were predominantly men who were younger than most patients with heart failure and usually did not have other oexisting illnesses. In a later review by Rees et al 19 these findings were onfirmed with inreases in maximal oxygen uptake, exerise duration, maximum work apaity and distane walked in 6 min (table 1). In the meta-analysis of Smart and Marwik, 20 during the training and follow-up periods there was a statistially non-signifiant trend to redued mortality in the exerise ompared to ontrol groups (table 1). Physial training studies on intermittent laudiation onsistently reported that training inreases walking time and walking distane as well as pain-free walking time and walking distane (table 1), but not peak exerise alf blood flow. 21 Supervised training showed stronger improvement in maximal treadmill walking when ompared with the results of nonsupervised exerise therapy regimens. 22 Gait-oriented exerise training was effetive in improving walking speed and distane in patients with stroke (table 1). 23 RCTs on hypertensive subjets have shown a lear lowering effet on blood pressure of aerobi training (table 1). 24 In the exerise training groups vasular resistane, plasma norepinephrine and plasma renin ativity dereased. At the moment there is no onlusive evidene available on the effets of resistane training on blood pressure in hypertensive subjets. 25 In patients with ardiovasular disease a review of six studies onluded that aerobi exerise was effetive in inreasing HDL holesterol and a review of nine studies that aerobi exerise indued a redution in triglyerides (table 1). 26 Type 2 diabetes mellitus Postintervention glyated haemoglobin values were signifiantly lower in the exerise groups ompared with ontrol groups (table 1), while body mass was not. 27 The authors onluded that the group differene in glyated haemoglobin was large enough signifiantly to redue the risk of diabeti ompliations. Aording to another systemati review, based on nine RCTs, regular exerise has a statistially and linially signifiant effet on maximal oxygen uptake in type 2 diabeti individuals. 28 Interestingly, reently published randomised trials show that resistane training improves glyaemi ontrol in patients with type 2 diabetes. In a review of four studies aerobi exerise was effetive in reduing LDL holesterol in patients with type 2 diabetes (table 1). 31 Br J Sports Med 2009;43: doi: /bjsm

3 Review Table 1 Results of seleted meta-analyses of randomised ontrolled trials on the benefits of exerise therapy in the treatment of patients with speifi diseases Study, year Disease Outome measure No. studies (no. partiipants) Effet size of exerise ompared to ontrols, pooled statistis (95% CI)* Fransen et al, Osteoarthritis Self-reported pain 32 (3616) Standardised mean differene (20.50 to 20.30) Fransen et al, Osteoarthritis Self-reported physial funtion limitations 31 (3719) Standardised mean differene (20.49 to 20.25) Hernandez-Molina et al, Hip osteoarthritis Self-reported pain 8 (493) Standardised mean differene (20.64 to 20.28) Hayden et al, Non-speifi hroni (. 12 weeks) low bak pain Hayden et al, Non-speifi hroni (. 12 weeks) low bak pain Pain, visual analogue sale (saled to 0 to 100 points) Condition-speifi funtioning limitations (saled to 0 to 100 points) 8 (370) Weighted mean differene points ( to 21.31) 7 (337) Weighted mean differene points (26.48 to 0.53) Bush et al, Fibromyalgia Pain 4 (223) Standardised mean differene (21.47 to 20.15) Bush et al, Fibromyalgia Tender points 6 (349) Standardised mean differene (21.53 to 0.01) Bush et al, Fibromyalgia Global well-being 4 (269) Standardised mean differene 0.49 (0.23 to 0.75) Bush et al, Fibromyalgia Physial funtion 4 (253) Standardised mean differene 0.66 (0.41 to 0.92) Jolliffe et al, Coronary heart disease All ause mortality 12 (2582) Odds ratio 0.73 (0.54 to 0.98) Jolliffe et al, Coronary heart disease Cardia mortality 8 (2312) Odds ratio 0.69 (0.51 to 0.94) Jolliffe et al, Coronary heart disease Non-fatal myoardial infartion 9 (2104) Odds ratio 0.96 (0.69 to 1.35) Nolan et al, Coronary heart disease Heart rate variability 16 (631) Standardised mean differene 0.36 (0.18 to 0.55) Rees et al, Heart failure Maximal oxygen uptake 24 (848) Weighted mean differene 2.16 ml/kg/min (1.49 to 2.82) Rees et al, Heart failure Distane on 6-min walk 8 (282) Weighted mean differene 41 m (17 to 65) Smart and Marwik, Heart failure Mortality 30 (1197) Odds ratio 0.71 (0.37, 1.02) Watson et al, Intermittent laudiation Maximal walking time 7 (255) Weighted mean differene 5.12 min (4.51 to 7.52) van de Port et al, Stroke Maximum walking speed 12 (501) Standardised effet size 0.45 (0.27 to 0.63) van de Port et al, Stroke Walking distane 9 (451) Standardised effet size 0.62 (0.30 to 0.95) Cornelissen and Fagard, Hypertension Systoli blood pressure 30 (492) Mean net hange 26.9 mm Hg (29.1 to 24.6) Cornelissen and Fagard, Hypertension Diastoli blood pressure 30 (492) Mean net hange 24.9 mm Hg (26.5 to 23.3) Kelley et al, Cardiovasular disease HDL holesterol 6 (637) Weighted mean differene 3.7 mg/dl (1.2 to 6.1) Kelley et al, Cardiovasular disease Triglyerides 9 (1172) Weighted mean differene mg/dl (230.1 to 28.5) Thomas et al, Type 2 diabetes Glyated haemoglobin perentage (HbA 1 ) 13 (361) Weighted mean differene 20.62% (20.91% to 20.33%) Boyle et al, Type 2 diabetes Maximal oxygen uptake 9 (266) Standardised mean differene 0.53 (0.18 to 0.88) Kelley and Kelley, Type 2 diabetes LDL holesterol 4 (156) Weighted mean differene 26.4 mg/dl (211.8 to 21.1) Ram et al, Asthma Resting lung funtion (FEV1) 5 (129) Weighted mean differene 0.01 litres (20.14 to 0.16) Ram et al, Asthma Maximal ventilation (VE max ) 4 (111) Weighted mean differene 6.00 litres/min (1.57 to 10.43) Ram et al, Asthma Maximal oxygen uptake 7 (175) Weighted mean differene 5.4 ml/kg/min (4.2 to 6.6) Salman et al, COPD Walking distane 20 (979) Standardised effet size 0.71 (0.43 to 0.99) Salman et al, COPD Shortness of breath by Chroni 12 (723) Standardised effet size (20.91 to 20.26) Respiratory Disease Questionnaire Goodwin et al, Parkinson disease Physial funtioning limitations 7 (360) Standardised mean differene (20.82 to 20.12) Goodwin et al, Parkinson disease Health-related quality of life limitations 4 (292) Standardised mean differene (20.51 to 20.04) Heyn et al, Cognitive impairment Cardiovasular fitness 18 (1059) Standardised effet size 0.62 (0.45 to 0.78) Heyn et al Cognitive impairment Cognitive outomes 12 (820) Standardised effet size 0.57 (0.38 to 0.75) Mead et al, Depression Depression symptoms 23 (907) Standardised mean differene (21.12 to 20.51) Edmonds et al, Chroni fatigue syndrome Chalder fatigue sale 5 (286) Standardised mean differene (21.26 to 20.28) Edmonds et al, Chroni fatigue syndrome Quality of life limitations, SF-36 physial funtioning subsale 3 (162) Standardised mean differene (20.96 to 20.33) Shamliyan et al, Urinary inontinene Contingene rate 4 (647) Pooled risk differene 0.13 (0.07 to 0.20) Markes et al, Breast aner Cardiorespiratory fitness 5 (207) Standardised mean differene 0.66 (0.20 to 1.12) Cramp and Daniel, Caner Fatigue 30 (1662) Standardised mean differene (20.33 to 20.13) *All estimates reported in this table favour exerise groups; effet sizes as reported by the authors of original meta-analyses. COPD, hroni obstrutive pulmonary disease; HDL, high-density lipoprotein; FEV1, fored expiratory volume in 1 s; LDL, low-density lipoprotein, SF-36, Short Form 36 questionnaire. 552 Br J Sports Med 2009;43: doi: /bjsm

4 Pulmonary diseases Aording to the systemati review of Ram et al 32 ardiorespiratory fitness of patients with asthma an be inreased by physial training (table 1), although no evidene was found of an effet on measures of resting pulmonary funtion. Salman et al 33 found that rehabilitation groups (20 trials) of patients with hroni obstrutive pulmonary disease (COPD) did signifiantly better than ontrol groups in a walking test (table 1). In 12 trials where the Chroni Respiratory Disease Questionnaire had been administered the rehabilitation groups had less shortness of breath than the ontrols. In trials where only respiratory musle training was used no signifiant differene was observed between the rehabilitation and ontrol groups, whereas in trials inluding at least lower extremity training rehabilitation groups did signifiantly better than the ontrols in the walking test and had less shortness of breath. However, Geddes et al 34 reported in their systemati review that inspiratory musle training benefited patients with COPD, inluding improved 6-min walk test performane. The findings of the meta-analysis by Laasse et al 35 are in aordane with those of Salman et al, 33 showing that exerise-based rehabilitation dereases dyspnoea symptoms and inreases exerise apaity. Neurologial diseases Aording to a meta-analysis, exerise therapy/exerise-based physiotherapy improved physial funtioning (seven trials) and health-related quality of life (four trials) in patients with Parkinson disease. 36 In addition, the exerise groups had improved balane in four out of five trials and higher walking speed in three out of four trials. 36 A best evidene synthesis of six RCTs was strongly in favour of exerise therapy ompared to no exerise therapy of musle power funtion, exerise tolerane funtions and mobilityrelated ativities in patients with multiple slerosis. 37 Moderate evidene was found for improved mood. No effet was observed for exerise therapy on fatigue and pereption of handiap. There are too few studies on patients diagnosed as having dementia to allow onlusions to be drawn. However, physial exerise was benefiial for older persons (>65 years; 30 trials with a total of 2020 partiipants) with ognitive impairment or dementia as the interventions improved ardiovasular fitness, strength, flexibility, and funtional, ognitive and behavioural outomes (table 1). 38 Other diseases In a study of 23 RCTs, exerise intervention redued symptoms of depression (table 1), 39 although many of the RCTs were of low methodologial quality and the high quality studies showed results with lower effet sizes. Chroni fatigue syndrome is an illness haraterised by persistent, medially unexplained fatigue that has lasted for at least 6 months. A review of five RCTs found that subjets reeiving exerise therapy were less fatigued than ontrols. 40 Physial funtioning also signifiantly improved with exerise therapy. Shamliyan et al 41 found in their meta-analysis that pelvi floor musle training and bladder training onsistently inreased ontinene rates (table 1) in women with stress urinary inontinene. During adjuvant treatment for breast aner, RCTs have shown inreased ardiorespiratory fitness in the exerise groups Review ompared with ontrols. 42 Exerise was benefiial for anerrelated fatigue (table 1) during and after aner therapy. 43 DISCUSSION Clinially most important effets of exerise therapy and the size of effets Exerise therapy an have a positive effet on health via many disease-speifi mehanisms (fig 1). The most onsistent finding of the various studies onduted to date inluded in this summary review is that aerobi/funtional apaity and/or musle strength an be improved by exerise training among patients with different hroni diseases. This is important as the proportion of older people is inreasing and exerise therapy may be an important means to redue disability and inrease the numbers of those able to live independently in the ommunity. The finding that aerobi exerise training onsistently inreases physial performane apaity and maximal oxygen uptake in patients with hroni diseases is important as observational studies have shown that low aerobi fitness is an important risk fator for mortality in this population segment, 44 as it has been shown to be among apparently healthy people. 45 Higher intensity training is more effetive than lower-intensity training in inreasing maximal oxygen among healthy subjets 46 and among patients with ardia issues However, little researh evidene is available as yet on what training intensity would be most benefiial for the long-term prognosis of different diseases. Other ardiometaboli risk fators have also been found to benefit from exerise. Of partiular importane is the finding, on the basis of randomised trials, that exerise redues viseral fat among adults 50 and perentage body fat among hildren, 51 inluding in the absene of hanges in total body weight, as skeletal musle mass often inreases as a onsequene of exerise training. The effet sizes of exerise therapy on different outomes vary from no effet to strong effet (table 1). When ompared to pharmaologial therapy, exerise usually has positive effets via many different mehanisms (fig 1), although pharmaologial treatment targeted at a speifi parameter, suh as antihypertensive drugs, 52 may have an effet size as high, if not higher. The possible overall strong health benefit of exerise therapy in the prevention and treatment of a disease seems to be a sum effet mediated via different mehanisms. Methodologial onsiderations and main limitations Based on the most reent riteria for designing RCTs, the oldest RCTs in the literature are usually of low quality while reently published RCTs are generally of higher quality. Heterogeneity in the results often means that the studies are of low or varying quality, as is the ase, for example, in studies on depression. First, it should be borne in mind that linial trials using nonpharmaologial treatments, suh as exerise therapy, are less often rigorously blinded or plaebo-ontrolled than pharmaologial linial trials. 53 Some of the results of the trials may at least in part be explained by the plaebo effet. Another ommon problem in exerise therapy studies is the insuffiient doumentation and analysis of possible o-interventions, suh as hanges in mediation or diet. Compared with many pharmaologial trials the low number of partiipants and lak of doumentation of all the ompliations and side effets arising from many of the interventions is also a limitation. The fat that most trials are of short duration means that some benefits, suh as inreases in physial fitness, are attained Br J Sports Med 2009;43: doi: /bjsm

5 Review Figure 1 Main evidene-based pathways on how physial ativity or exerise therapy delays progression of diseases and ourrene of disability and deaths. within a few months. However, the duration of most RCTs usually is too short to provide onlusive evidene on the effets of exerise therapy on the true progression of disease. Generalisability may be a further problem as some RCTs inlude patients who are not representative of the general population of patients with respet to age, gender and oexisting diseases. This is typially seen in RCTs on oronary heart disease 15 and heart failure. 18 There is a need for high quality RCTs with long-term follow-ups inluding doumentation of suh outomes as survival rate, hospitalisation rate and healthare osts as well as side effets and ompliations. What is already known on this topi Published onsensus statements summarise that on the basis of observational follow-up studies it is known that baseline high physial ativity is assoiated with many health benefits later in life. Similar up-to-date summaries on the effets of exerise therapy in the treatment of hroni diseases are laking. What this study adds The findings of the meta-analyses of randomised ontrolled trials summarised in this paper inlude that aerobi/funtional apaity and musle strength as well as prognosti risk fator profile an be improved by exerise training among patients with different diseases. Exerise therapy an have positive effets on health via many disease-speifi mehanisms. Pratial hallenges Dotors play a entral role in the evaluation of risks and in patient motivation when presribing exerise to patients with hroni diseases. Sometimes ollaboration with an exerise physiologist, physiotherapist et. will be benefiial when determining orret exerise intensities and in tailoring and supervising training programs; however, dotors are still expeted to know what the guidelines 54 are when they presribe exerise therapy for their patients. In arefully designed RCTs, the sreening of the risks for patients and the exerise program take safety issues into aount on the individual level. To date only a few sattered studies have analysed the possible benefiial dose-response of speifi exerise therapies. Sine in exerise therapy long-term adherene is a general problem, supervised exerise programs usually give better results than non-supervised programs although the ost-effetiveness of non-supervised programs may be higher. Conlusions The most onsistent finding of the review studies summarised here is that aerobi/funtional apaity and musle strength an be improved by exerise training among patients with different diseases without having detrimental effets on disease progression. This is important, as with population aging exerise therapy may be an important means of reduing disability and inreasing the number of older people living independently. Severe ompliations during these arefully tailored programs were rare. In some diseases, suh as osteoarthritis, pain symptoms may also be redued. As this review shows, there is aumulating evidene that in patients with hroni disease exerise therapy is effetive in improving the prognosti risk fator profile. Competing interests: None. Provenane and peer review: Not ommissioned; externally peer reviewed. 554 Br J Sports Med 2009;43: doi: /bjsm

6 REFERENCES 1. Kujala UM. Evidene for exerise therapy in the treatment of hroni disease based on at least three randomized ontrolled trials summary of published systemati reviews. Sand J Med Si Sports 2004;14: Altman DG, Shulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 2001;134: Fransen M, MConnell S, Bell M. Exerise for osteoarthritis of the hip or knee. Cohrane Database Syst Rev 2008;4:CD Roddy E, Zhang W, Doherty M. Aerobi walking or strengthening exerise for osteoarthritis of the knee? A systemati review. Ann Rheum Dis 2005;64: Lange AK, VanWanseele B, Fiatore Singh MA. Strength training for treatment of osteoarthritis of the knee: a systemati review. Arthritis Rheum (Arthritis Care Res) 2008;59: Hernandez-Molina G, Reihenbah S, Zhang B, et al. Effet of therapeuti exerise for hip osteoarthritis pain: results of a meta-analysis. Arthritis Rheum (Arthritis Care Res) 2008;59: Bartels EM, Lund H, Hagen KB, et al. Aquati exerise for the treatment of knee and hip osteoarthritis. Cohrane Database Syst Rev 2007;4:CD Kettunen JA, Kujala UM. Exerise therapy for people with rheumatoid arthritis and osteoarthritis. Sand J Med Si Sports 2004;14: Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJCS, et al. Rheumatoid arthritis, ardiovasular disease and physial exerise: a systemati review. Rheumatology 2008;47: Takken T, Van Brussel M, Engelberg RH, et al. Exerise therapy in juvenile idiopathi arthritis. Cohrane Database Syst Rev 2008;4:CD Dagfinrud H, Kvien TK, Hagen KB. Physiotherapy interventions for ankylosing spondylolitis. Cohrane Database Syst Rev 2008;1:CD Hayden JA, van Tulder MW, Malmivaara AV, et al. Exerise therapy for non-speifi low bak pain. Cohrane Database Syst Rev 2005;3:CD Hayden JA, van Tulder MW, Tomlinson G. Systemati review: strategies for using exerise therapy to improve outomes in hroni low bak pain. Ann Intern Med 2005;142: Bush AJ, Barber KA, Overend TJ, et al. Exerise for treating fibromyalgia syndrome. Cohrane Database Syst Rev 2007;4:CD Jolliffe JA, Rees K, Taylor RS, et al. Exerise-based rehabilitation for oronary heart disease. Cohrane Database Syst Rev 2001;1:CD Taylor RS, Brown A, Ebrahim S, et al. Exerise-based rehabilitation for patients with oronary heart disease: systemati review and meta-analysis of randomized ontrolled trials. Am J Med 2004;116: Nolan RP, Jong P, Barry-Bianhi SM, et al. Effets of drug, biobehavioral and exerise therapies on heart rate variability in oronary artery disease: a systemati review. Eur J Cardiovas Prev Rehabil 2008;15: Lloyd-Williams F, Mair FS, Leitner M. Exerise training and heart failure: a systemati review of urrent evidene. Br J Gen Prat 2002;52: Rees K, Taylor RS, Singh S, et al. Exerise-based rehabilitation for heart failure. Cohrane Database Syst Rev 2004;3:CD Smart N, Marwik TH. Exerise training for patients with heart failure: a systemati review of fators that improve mortality and morbidity. Am J Med 2004;116: Watson L, Ellis B, Leng GC. Exerise for intermittent laudiation. Cohrane Database Syst Rev 2008;4:CD Bendermaher BLW, Willigendael EM, Teijink JAW, et al. Supervised exerise therapy versus non-supervised exerise therapy for intermittent laudiation. Cohrane Database Syst Rev 2006;2:CD Van de Port IGL, Wood-Dauphinee S, Lindeman E, et al. Effets of exerise training programs on walking ompeteny after stroke. A systemati review. Am J Phys Med Rehabil 2007;86: Cornelissen VA, Fagard RH. Effet of endurane training on blood pressure, blood pressure-regulating mehanisms, and ardiovasular risk fators. J Hypertens 2005;23: Cornelissen VA, Fagard RH. Effet of resistane training on resting blood pressure: a meta-analysis of randomized ontrolled trials. J Hypertens 2005;23: Kelley GA, Kelley KS, Franklin B. Aerobi exerise and lipids and lipoproteins in patients with ardiovasular disease: A meta-analysis of randomized ontrolled trials. J Cardiopulm Rehabil 2006;26: Thomas D, Elliot EJ, Naughton GA. Exerise for type 2 diabetes mellitus. Cohrane Database Syst Rev 2006;3:CD Boule NG, Kenny GP, Haddad E, et al. Meta-analysis of the effet of strutured exerise training on ardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia 2003;46: Review 29. Snowling NJ, Hopkins WG. Effet of different modes of exerise training on gluose ontrol and risk fators for ompliations in type 2 diabeti patients. A meta-analysis. Diabetes Care 2006;29: Sigal RJ, Kenny GP, Boule NG, et al. Effets of aerobi training, resistane training, or both on glyemi ontrol on type 2 diabetes: a randomized trial. Ann Intern Med 2007;147: Kelley GA, Kelley KS. Effets of aerobi exerise on lipids and lipoproteins in adults with type 2 diabetes: A meta-analysis of randomized-ontrolled trials. Publi Health 2007;121: Ram FSF, Robinson SM, Blak PN, et al. Physial training for asthma. Cohrane Database Syst Rev 2005;4:CD Salman GF, Mosier MC, Beasley BW, et al. Rehabilitation for patients with hroni obstrutive pulmonary disease: meta-analysis of randomized ontrolled trials. J Gen Intern Med 2003;18: Geddes EL, O Brien K, Reid WD, et al. Inspiratory musle training in adults with hroni obstrutive pulmonary disease: An update of a systemati review. Respirat Med 2008;102: Laasse Y, Goldstein R, Lasserson TJ, et al. Pulmonary rehabilitation for hroni obstrutive pulmonary disease. Cohrane Database Syst Rev 2006;4:CD Goodwin VA, Rihards SH, Taylor RS, et al. The effetiveness of exerise interventions for people with Parkinson s disease: a systemati review and metaanalysis. Mov Disord 2008;23: Rietberg MB, Brooks D, Uitdehaag BMJ, et al. Exerise therapy for multiple slerosis. Cohrane Database Syst Rev 2004;3:CD Heyn P, Abreu BC, Ottenbaher KJ. The effets of exerise training on elderly persons with ognitive impairment and dementia: a meta-analysis. Arh Phys Med Rehabil 2004;85: Mead GE, Morley W, Campbell P, et al. Exerise for depression. Cohrane Database Syst Rev 2008;4:CD Edmonds M, MGuire H, Prie J. Exerise therapy for hroni fatigue syndrome. Cohrane Database Syst Rev 2004;3:CD Shamliyan TA, Kane RL, Wyman J, et al. Systemati review: randomized, ontrolled trials of nonsurgial treatments for urinary inontinene in women. Ann Intern Med 2008;148: Markes M, Brokow T, Resh KL. Exerise for women reeiving adjuvant therapy for breast aner. Cohrane Database Syst Rev 2006;4:CD Cramp F, Daniel J. Exerise for the management of aner-related fatigue in adults. Cohrane Database Syst Rev 2008;2:CD Myers J, Prakash M, Froeliher V, et al. Exerise apaity and mortality among men referred for exerise testing. N Engl J Med 2002;346: Physial Ativity Guidelines Advisory Committee. Physial Ativity Guidelines Advisory Committee report, Washington, DC, USA: US Department of Health and Human Servies, Gormley SE, Swain DP, High R, et al. Effet of intensity of aerobi training on VO 2max. Med Si Sports Exer 2008;40: Rognmo O, Hetland E, Helgerud J, et al. High intensity aerobi interval exerise is superior to moderate intensity exerise for inreasing aerobi apaity in patients with oronary artery disease. Eur J Cardiovas Prev Rehabil 2004;11: Warburton DER, MKenzie DC, Haykowsky MJ, et al. Effetiveness of high-intensity interval training for the rehabilitation of patients with oronary artery disease. Am J Cardiol 2005;95: Wisloff U, Stoylen A, Loennehen JP, et al. Superior ardiovasular effet of aerobi interval training versus moderate ontinuous training in heart failure patients. Cirulation 2007;115: Ohkawara K, Tanaka S, Miyahi M, et al. A dose-response relation between aerobi exerise and viseral fat redution: systemati review of linial trials. Int J Obesity 2007;31: Atlantis E, Barnes EH, Fiatore Singh MA. Effiay of exerise for treating overweight in hildren and adolesents: a systemati review. Int J Obesity 2006;30: Law MR, Wald NJ, Morris JK, et al. Value of low dose ombination treatment with blood pressure lowering drugs: analysis of 354 randomized trials. BMJ 2003;326: Boutron I, Tubah F, Giraudeau B, et al. Methodologial differenes in linial trials evaluating nonpharmaologial and pharmaologial treatments of hip and knee osteoarthritis. JAMA 2003;290: Amerian College of Sports Mediine. ACSM s guidelines for exerise testing and presription, 7th edn. Philadelphia, Pennsylvania, USA: Lippinott Williams and Wilkins, 2005:366. Br J Sports Med 2009;43: doi: /bjsm