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Countdown to London 2012: BMJ Group's Olympics portal highlights latest Olympics and sports medicine-themed research, comment and learning Research Physiotherapy intervention in Parkinson’s disease: systematic review and meta-analysis BMJ 2012; 345 doi: 10.1136/bmj.e5004 (Published 6 August 2012) Cite this as: BMJ 2012;345:e5004 Physiotherapy Sports and exercise medicine Clinical trials (epidemiology) Health economics Health policy More topics Health service research Sociology Fewer topics Article Related content Article metrics Claire L Tomlinson, systematic reviewer1, Smitaa Patel, statistician1, Charmaine Meek, research assistant1, Clare P Herd, research associate2, Carl E Clarke, professor23, Rebecca Stowe, senior systematic reviewer1, Laila Shah, research administrator1, Catherine Sackley, professor of physiotherapy research4, Katherine H O Deane, senior lecturer in research4, Keith Wheatley, professor5, Natalie Ives, senior statistician11Birmingham Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK2School of Clinical and Experimental Medicine, College of Medicine and Dental Sciences, University of Birmingham3Department of Neurology, Sandwell and West Birmingham Hospitals NHS Trust, City Hospital, Birmingham4University of East Anglia, Norwich, UK5Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of BirminghamCorrespondence to: C Tomlinson c.l.smith.1{at}bham.ac.ukAccepted 4 July 2012AbstractObjective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson’s disease.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012.Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson’s disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes.Results 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson’s disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson’s disease rating scale (in which one trial was found to be the cause of the heterogeneity).Conclusions Physiotherapy has short term benefits in Parkinson’s disease. A wide range of physiotherapy techniques are currently used to treat Parkinson’s disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson’s disease in the longer term.IntroductionParkinson’s disease is a complex neurodegenerative disorder1 with wide reaching implications for patients and their families. The management of Parkinson’s disease has traditionally centred on drug treatment,2 but even with optimal medical management, patients still experience a deterioration of body function, daily activities, participation,3 and decline in mobility.4 This can lead to increased dependence on others, inactivity,5 and social isolation,4 resulting in reduced quality of life.4 There has been increasing support for the inclusion of rehabilitation therapies as an adjuvant to pharmacological and neurosurgical treatment,6 3 and a call for the move towards multidisciplinary management.1 7 8 The physiotherapist is a member within this multidisciplinary team,1 9 with the purpose of maximising functional ability and minimising secondary complications through movement rehabilitation within a context of education and support for the whole person.10 11 Physiotherapy for Parkinson’s disease focuses on transfers, posture, upper limb function, balance (and falls), gait, and physical capacity and (in)activity. It also uses cueing strategies, cognitive movement strategies, and exercise to maintain or increase independence, safety, and quality of life.4 12Referral rates to physiotherapy for people with Parkinson’s disease have historically been low, owing to a weak evidence base and poor availability of physiotherapy services.13 14 In recent years, supportive evidence for the inclusion of physiotherapy in the management of Parkinson’s disease has grown, due to the increased number of trials particularly in the past five years.15 Recent management guidelines have supported physiotherapy, such as those from the United Kingdom National Institute for Health and Clinical Excellence (NICE)16 and the Royal Dutch Society of Physical Therapy.17 This has led to an increased number of referrals, with a survey by Parkinson’s UK in 2008 reporting that 54% of the 13?000 members surveyed had seen a physiotherapist.18To synthesise the latest trial reports with the older data, we have performed this systematic review and meta-analysis of all randomised controlled trials of physiotherapy in Parkinson’s disease. This review includes trials assessing a variety of different physiotherapy methods as used to treat people with Parkinson’s disease, to provide an overall assessment on the use of physiotherapy in this patient population. Previous reviews have focused on one type of physiotherapy (such as exercise or treadmill training).19 20 Detailed results have been published in the Cochrane Library21 updating the Cochrane review published in 2001.11MethodsSearch strategy and selection criteriaA systematic search of the literature to the end of January 2012 was undertaken using a highly sensitive search strategy as recommended by the Cochrane Collaboration.22 We combined text and, where appropriate, Medical Subject Heading terms for physiotherapy, physical therapy, exercise, or rehabilitation; and Parkinson, Parkinson’s disease, or parkinsonism. No language restrictions were applied. We identified relevant trials by electronic searches of general biomedical and science electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science), rehabilitation databases (Allied and Complimentary Medicine Database, REHABDATA, REHADAT, GEROLIT); English language databases of foreign language research and third world publications (Latin American and Caribbean Health Sciences Literature, MedCarib, Index medicus for the Eastern Mediterranean region); conference and grey literature databases (Conference Proceedings Citation Index, Dissertation Abstracts, Conference Papers Index, Index to Theses, Electronic Theses Online Service, ProQuest), and trial registries (Cochrane Central Register of Controlled Trials, CentreWatch Clinical Trials listing service, metaRegister of Controlled Trials, ClinicalTrials.gov, Research Portfolio Online Reporting Tools, Physiotherapy Evidence Database, National Institute of disability and rehabilitation register, National research register). We also hand searched relevant general (for example, Lancet, BMJ, JAMA) and specific journals (for example, Movement Disorders, Neurology, Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Physiotherapy, Physical Therapy), abstract books, and conference proceedings (International Congress of Parkinson’s Disease and Movement Disorders, World Congress on Parkinson’s Disease and Related Disorders), as well as examined the reference lists of identified papers and other reviews.Study selectionStudies eligible for this review were randomised controlled trials (including the first phase of crossover trials) of patients with Parkinson’s disease comparing a physiotherapy intervention with no intervention or placebo control. Physiotherapy encompasses a wide range of techniques, so we were inclusive in our definition of physiotherapy intervention, including trials of general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts versus no intervention. General physiotherapy was a broad category, including a variety of techniques traditionally used by physiotherapists to treat people with Parkinson’s disease. Trials in this category may include multifaceted interventions using both active participation in treatment by the patient (such as exercise and practising of functional activities) and hands-on techniques delivered by the therapist (for example, massage, passive stretching, the Bobath technique). Exercise interventions were those that included only active exercise participation techniques targeting a variety of symptoms, such as balance, falls prevention, and walking speed. An existing Cochrane review analysed trials of treadmill training for Parkinson’s disease, and thus these trials were considered separately to other exercise interventions. Martial arts and dance interventions included participation in universally recognised activities not specifically designed for treating disease, but which appeared in trials of Parkinson’s disease evaluating relevant physiotherapy outcome measures. We excluded trials of multidisciplinary team interventions because it was difficult to ascertain the amount of physiotherapy input. Ultimately, all trials were meta-analysed to give an overall picture of the effect of delivery of a physiotherapy intervention versus no physiotherapy intervention.Data extraction and quality assessmentAll articles were read by two independent review authors (CLT, SP, CM, or CPH) and data extracted according to predefined criteria, with any discrepancies resolved by discussion. Publications were assessed for methodological quality by recording specified eligibility criteria, method of randomisation and blinding, concealment of allocation, similarity of patients in treatment groups at baseline, variation in cointerventions received by patients throughout the trial period, whether an intention to treat analysis was performed, and the number of patients lost to follow-up.Quantitative data synthesisOutcome data included gait outcomes (such as the two or six min walk test, 10 or 20 m walk test, speed, cadence, stride and step length, freezing of gait questionnaire), functional mobility and balance outcomes (such as the timed up and go test, functional reach test, Berg balance scale, activities specific balance confidence scale), falls data (such as number of falls, falls efficacy scale), clinician rated disability scales (such as the unified Parkinson’s disease rating scale (UPDRS)), patient rated quality of life (such as Parkinson’s disease questionnaire 39), adverse events, compliance or withdrawals, and health economics where available.Results of each trial were combined using standard meta-analytic methods to estimate an overall effect for physiotherapy versus no intervention. Since all outcomes were continuous variables, weighted mean difference methods were used.23 Briefly, for each trial, this involved calculating the mean change (and standard deviation) from baseline to the time point after intervention, for both the intervention and no intervention groups. From these numbers, the mean difference and its variance between arms for each trial could be calculated and then combined using a fixed effects model.The primary analysis was a comparison of physiotherapy with no intervention (control) using change from baseline to the first assessment after treatment (which, in most cases, was immediately after intervention). This comparison was chosen as the primary analysis, because in most trials it was the main data analysis reported, and few trials reported data at assessment points in the longer term (that is, after six months). Some trials also allowed patients in the control group to receive physiotherapy intervention after this point, so this primary analysis allowed a clean comparison of physiotherapy intervention versus no intervention.Since the different trials implemented various types of physiotherapy, trials were divided according to the type of intervention (general physiotherapy, exercise, treadmill, cueing, dance, or martial arts). If any trials with three or more treatment arms were identified, we made two assumptions for the analysis. Firstly, if the trial was comparing two or more physiotherapy methods in the same category of intervention (as described above) versus control, then the data for those physiotherapy arms were combined to give one comparison of physiotherapy intervention versus control for that trial.Secondly, if the trial was comparing two or more physiotherapy methods that were in different categories (as described above) versus control, then the data for those physiotherapy arms were kept separate, and the data for that trial were included in the appropriate physiotherapy categories. Therefore, in some cases, the control arms for some trials were included twice in the analysis. However, this related to only a small number of trials and patients, and it was judged that this double inclusion would not overly influence the analysis. We used tests of heterogeneity to make indirect comparisons to investigate whether the treatment effect differed across the different intervention categories.24ResultsOf 76 potentially relevant studies identified, 31 were excluded (for example, studies were not properly randomised, or crossover trials did not report data for the first intervention period) and six were ongoing trials for which no data were available (fig 1?). Therefore, we included 39 randomised controlled trials of 1827 patients in the systematic review (fig 1, web table 1).25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 There were nine trials with multiple arms.27 31 37 38 40 45 52 55 60 In five trials, two intervention arms were in the same physiotherapy category; therefore, these arms were combined to give one physiotherapy comparison versus no intervention.37 40 52 55 60 In five trials, two intervention arms were in different physiotherapy categories, so the trial contributed data to two physiotherapy comparisons.27 31 38 45 60 This meant that these five trials were included multiple times in the analysis, and the control arms from these trials were counted more than once. Therefore, 39 trials contributed data for 44 comparisons within the six different physiotherapy interventions (physiotherapy n=7, exercise n=14, treadmill training n=8, cueing n=9, dance n=2, and martial arts n=4, table 1?).
View larger version:In a new windowDownload as PowerPoint SlideFig 1 Trial flow diagram to summarise the stages of systematic reviewView this table:View PopupView InlineTable 1 Physiotherapy intervention classifications and trial characteristicsMethodological qualityThe amount of methodological detail reported in the trials was variable, with several quality indicators not fully discussed in many publications (fig 2?, web table 2). Only six (15%) studies26 32 33 36 57 59 reported a sample size calculation in the trial report. Less than half of the trials described the randomisation method used, and information on concealment of treatment allocation was also poorly reported (14 (36%)). Blinded assessors were used in 24 (62%) studies (although in one study, the assessors correctly guessed the treatment allocation in nearly 30% of patients33). Finally, only nine trials stated intention to treat as the primary method of analysis,29 32 33 36 39 40 47 57 63 three trials stated per protocol as the primary method of analysis,34 52 55 and the remaining trials did not describe the method of analysis.
View larger version:In a new windowDownload as PowerPoint SlideFig 2 Review authors’ judgments about each risk of bias item, presented as percentage across all included studiesData available for analysisOf 13 trials reported in abstract form, five had data available for meta-analysis.34 37 39 51 55 From the studies with full publications, one trial had relevant data that could not be extracted because it was only available in graph form,56 and another trial published only median and interquartile range data, which could not be meta-analysed in this format.30 Therefore, data were not available from ten trials, and data available for meta-analysis was provided by 29 trials.Effects of intervention Gait outcomesSpeed was significantly increased with physiotherapy compared with no intervention (mean difference 0.04 m/s, 95% confidence interval 0.02 to 0.06; P<0.001, fig 3?). There were also benefits of borderline significance for the two or six minute walk test and the freezing of gait questionnaire. We saw a greater increase in the distance walked in two or six mins (13.37 m, 0.55 to 26.20; P=0.04, web figure 1) and an improvement in score for the freezing of gait questionnaire (-1.41, -2.63 to -0.19; P=0.02, web figure 2) after physiotherapy. By contrast, we saw borderline significance in favour of no intervention for the time taken to walk 10 or 20 m (0.40 s, 0.00 to 0.80; P=0.05, web figure 3). There was no significant difference between physiotherapy and no intervention for cadence (-1.57 steps/min, -3.81 to 0.67; P=0.17), stride length (0.03 m, -0.02 to 0.08; P=0.24), and step length (0.02 m, 0.00 to 0.04; P=0.06), (table 2?).
View larger version:In a new windowDownload as PowerPoint SlideFig 3 Comparison of physiotherapy interventions in relation to speed (m/s). Studies denoted as a or b distinguishes those published by the same first author and in the same yearView this table:View PopupView InlineTable 2 Summary of resultsFunctional mobility and balance outcomesWe found significant improvements with physiotherapy for the timed up and go test (-0.63 s, 95% confidence interval -1.05 to -0.21; P=0.003), functional reach test (2.16 cm, 0.89 to 3.43; P<0.001), and Berg balance scale (3.71 points, 2.30 to 5.11; P<0.001); (table 2, figs 4-6? ? ?). There was no difference with physiotherapy compared with no intervention for activity specific balance confidence scale (2.40 points, -2.78 to 7.57; P=0.36; table 2).
View larger version:In a new windowDownload as PowerPoint SlideFig 4 Comparison of physiotherapy interventions with controls in relation to the timed up and go test (s). Studies denoted as a or b distinguishes those published by the same first author and in the same year 
View larger version:In a new windowDownload as PowerPoint SlideFig 5 Comparison of physiotherapy interventions with controls in relation to the functional teach test (cm) 
View larger version:In a new windowDownload as PowerPoint SlideFig 6 Comparison of physiotherapy interventions with controls in relation to the Berg balance scale. Studies denoted as a or b distinguishes those published by the same first author and in the same year In the analysis for the timed up and go test, one trial was heavily weighted in the analysis owing to small standard deviations compared with other studies (fig 4).60 Furthermore, in the trial publication, a non-significant effect of martial arts intervention was reported (P=0.093), but when the data as reported in the paper were included in our analysis, a significant difference was found (P=0.003). We contacted the authors of this study to check whether the data reported in the paper were in fact standard errors, but they were confirmed as standard deviations. We therefore performed a sensitivity analysis, removing this study, and found that the overall result became not significant (-0.38 s, 95% confidence interval -0.96 to 0.21; P=0.21); thus, this result should be interpreted with caution.FallsSeven trials collected data for falls using a falls diary, reporting either the number of patients falling or the number of falls per patient.33 36 39 50 57 61 62 For both outcomes, there was a decrease in falls after physiotherapy. However, only three studies compared the two treatment groups, with two reporting no difference between the arms,50 57 and one reporting a significant difference favouring physiotherapy intervention.61 We saw no difference in the falls efficacy scale between the two treatment arms (-1.91 points, 95% confidence interval -4.76 to 0.94; P=0.19; table 2).Clinician rated disability on UPDRSThe UPDRS motor score improved with physiotherapy compared with no intervention (-5.01 points, 95% confidence interval -6.30 to -3.72; P<0.001, fig 7?). We also saw significant improvements in the UPDRS subscore for activities of daily living (-1.36 points, -2.41 to -0.30; P=0.01; web figure 4) and total scores with physiotherapy (-6.15, -8.57 to -3.73; P<0.001; web figure 5), but no difference in mental subscore (-0.44, -0.98 to 0.09; P=0.10; table 2).
View larger version:In a new windowDownload as PowerPoint SlideFig 7 Comparison of physiotherapy interventions with controls in relation to the UPDRS motor subscale. Studies denoted as a or b distinguishes those published by the same first author and in the same year Patient rated quality of life using Parkinson’s disease questionnaire 39Only data for the mobility domain and summary index of the Parkinson’s disease questionnaire 39 were available for meta-analysis. We saw no difference between treatment arms for either overall patient rated quality of life using the summary index (-0.38 points, 95% confidence interval -2.58 to 1.81; P=0.73) or the mobility domain (-1.43, -8.03 to 5.18; P=0.67).Treatment compliance, adverse events, and health economicsOnly 14 trials discussed patient compliance, with 1226 29 32 36 37 39 40 41 47 49 59 63 quantifying it in some form. No trials reported data for health economics, and only one commented on adverse events, stating that none had occurred during treatment sessions.36Subgroup analysisOnly one outcome, the UPDRS motor subscore, showed significant heterogeneity between the treatment effects of the different classes of intervention. In all other cases, there was no evidence of any differences (table 2). One outlying trial was the cause of this heterogeneity in the motor score;34 when this trial was excluded from the analysis, the result remained significant (-3.77 points, 95% confidence interval -5.15 to -2.39; P<0.001), but the test for between trial and between subgroup heterogeneity was no longer significant (P=0.44 and P=0.08, respectively).DiscussionA variety of physiotherapy methods are used to treat people with Parkinson’s disease. Previous reviews have focused on one type of physiotherapy (for example, exercise, treadmill training).19 20 This review brings together all the evidence from the numerous trials evaluating the various physiotherapy methods into one review to assess the overall effect of physiotherapy versus no physiotherapy, and it also allows an indirect comparison of the different physiotherapy methods used.This review provides evidence on the efficacy of physiotherapy in the short term (mean follow-up Open access PDFEasy ReadData supplementRespond to this article Tweet Services Email to friendDownload to citation managerAdd article to BMJ portfolioRequest permission Citations Articles by Claire L TomlinsonArticles by Smitaa PatelArticles by Charmaine MeekArticles by Clare P HerdArticles by Carl E ClarkeArticles by Rebecca StoweArticles by Laila ShahArticles by Catherine SackleyArticles by Katherine H O DeaneArticles by Keith WheatleyArticles by Natalie IvesCiting articles via Web of ScienceCiting articles via Scopus Social bookmarking 
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