physical therapy and exercise interventions in.5 · · 2018-01-23physical therapy and exercise...

Physical therapy and exercise interventions inHuntington’s disease: a mixed methods systematicreview protocol

Lori Quinn1 ! Monica Busse2 ! Judith Carrier3 ! Nora Fritz4 ! Jane Harden3 ! Lynda Hartel5 ! Deb Kegelmeyer1 !

Anne Kloos5 ! Ashwini Rao6

1Department of Biobehavioral Sciences, Teachers College, Columbia University, New York, USA, 2Centre for Trials Research, Cardiff University,Cardiff, UK, 3The Wales Centre for Evidence-Based Care, a Joanna Briggs Institute Centre of Excellence, School of Healthcare Sciences, College ofBiomedical and Life Sciences, Cardiff University, Cardiff, UK, 4Physical Therapy Program, Wayne State University, Detroit, USA, 5Physical TherapyDivision of Health and Rehabilitation Sciences, Ohio State University, Columbus, USA, and 6Program in Physical Therapy, Department ofRehabilitative and Regenerative Medicine, Columbia University, New York, USA

Review question/objective: The review seeks to evaluate the effectiveness of physical therapy and exerciseinterventions in Huntington’s disease (HD). The review question is: What is the effectiveness of physiotherapy andtherapeutic exercise interventions in people with HD, and what are patients’, families’ and caregivers’ perceptions ofthese interventions?The specific objectives are:! To determine the effectiveness of physiotherapy and therapeutic exercise interventions in people with HD

on physical and cognitive function.! To explore the perceptions of people with HD and their families and caregivers with regard to their experience

of physiotherapy and exercise interventions.This mixed methods review seeks to develop an aggregated synthesis of quantitative, qualitative and narrativesystematic reviews on physiotherapy and exercise interventions in HD, in an attempt to derive conclusions andrecommendations useful for clinical practice and policy decision-making.

Keywords Exercise; Huntington’s disease; physical activity; physical therapy; physiotherapy

JBI Database System Rev Implement Rep 2017; 15(7):1783–1799.

Background

H untington’s disease (HD) is a rare, predomi-nantly inherited, neurodegenerative condition

caused by a cytosine, adenine and guanine segmentrepeat expansion in the Huntingtin gene. Hunting-ton’s disease has a prevalence of six to 13 per100,000 in the general population1; a 2012 meta-analysis reported the worldwide prevalence of HDwas 2.71 per 100,000 (95% confidence interval:1.55–4.72).2 It predominantly affects the brain,causing dysfunction and death of medium spinystriatal projection neurons and thus disruption ofcorticostriatal pathways with resultant impairmentof cognition, motor function and behavior.1 These

impairments result in decreasing independence inactivities of daily living and quality of life3,4 evenfrom relatively early in the disease.

Therapeutic exercise interventions are a promisingarea of research in neurodegenerative diseases.5,6

Addressing motor and cognitive impairments in neu-rodegeneration may provide a long-term beneficialeffect to delay disease progression, maximize func-tional abilities and maintain independence over alonger period. Loss of independent mobility and caredependency have been shown to be important pre-dictors of nursing home admissions.7,8 Developinginterventions that facilitate independent living andstrategies to manage symptoms is urgently required.

Despite the potential for physiotherapy and exer-cise interventions, which may be provided by physio-therapists, exercise trainers or other healthcarepersonnel, to assist people with HD, there is littleevidence to suggest that people with HD are

Correspondence: Lori Quinn, [email protected]

Conflicts of interest: Authors of included papers who were also part ofthe review team were not included in the review or data extraction.

DOI: 10.11124/JBISRIR-2016-003274

JBI Database of Systematic Reviews and Implementation Reports ! 2017 THE JOANNA BRIGGS INSTITUTE 1783

SYSTEMATIC REVIEW PROTOCOL

©2017 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.

routinely referred for physical therapy.9 This may beattributable to the limited scientific support for theeffectiveness of physiotherapy and exercise interven-tions. The Physiotherapy Working Group of theEuropean Huntington Disease Network (EHDN)developed a Physiotherapy Guidance Document in2009.10 A systematic literature search was con-ducted to summarize the available evidence priorto this date, with the view to providing therapistswith information and recommendations for physi-otherapy standards of care for people with HD. ThisGuidance Document, however, was based largely onexpert opinion and the limited available literature atthe time, which involved a small number of mostlydescriptive studies. Subsequent to the publicationof the Guidance Document, the EHDN groupdeveloped treatment-based classifications to guideclinical decision-making over the life course of thedisease.11

In the past seven years, there has been a significantincrease in the number and quality of physiotherapyand exercise studies in HD.12-18 These studies haveranged from evaluation of short-term exercise pro-grams,13,14 video-game home interventions,15 as wellas inpatient multidisciplinary rehabilitation pro-grams.12,16,17 Studies have utilized both quantitativeand qualitative assessments, and in addition, there is agrowing body of textual references supporting exer-cise and physiotherapy in this population. While theEHDN Guidance Document19 and subsequent treat-ment-based classifications11,20 were an importantfirst step to provide information about patient man-agement in this relatively rare disease, we are now at apoint where more rigorous clinical guidelines can bedeveloped. Importantly, the treatment-based classifi-cations, and the evidence in support of associatedinterventions, require detailed validation.

We searched for previous or currently registeredsystematic reviews on the topic of physiotherapy andexercise in HD in the Cochrane and JBI Database ofSystematic Reviews and Implementation Reports(JBISRIR), PROSPERO, the World Health Organ-ization (WHO) International Clinical Trials Regis-try, Medline and CINAHL. In 2003, a systematicreview on the effectiveness of physiotherapy, occu-pational therapy and speech therapy in HD waspublished; however, at the time, there was minimalavailable literature to include.21 Studies examiningthe outcomes of physiotherapy, occupational therapy

and speech pathology interventions for people withHD up to May 2002 were included in this review, andit was concluded that there was a low level of evidenceto support the use of physiotherapy for addressingimpairments of balance, muscle strength and flexi-bility in HD. No other systematic reviews or protocolswere found following a search of the JBISRIR,Cochrane and PROSPERO databases.

In this proposed mixed methods review, the quan-titative component will seek to incorporate a widerrange of study designs, including, but not limited to,cohort studies (with control), case-controlled stud-ies, descriptive and case series designs. A qualitativeand textual component will also be incorporated tohelp understand why initiatives do or do not workfrom the perspective of people with HD, their familiesand caregivers. Combining quantitative, qualitativeand textual syntheses in the same review will makethis the first mixed methods systematic review thatconsiders the effectiveness of a range of physiotherapyand therapeutic exercise interventions in people withHD and the experiences and perceptions of patients,their families and caregivers with regard to theseinterventions. In addition, each study will be catego-rized according to the established treatment-basedclassifications,11,20 and the evidence for each classi-ficationwill be discussed in the narrative synthesis. If astudy cannot be adequately categorized, this will bediscussed separately and recommendations foradditional categories will be made as appropriate.

Inclusion criteriaTypes of participantsFor the first objective, the quantitative component ofthis review will include studies that include partici-pants of any age or gender who have been clinicallyor genetically diagnosed with HD, including thosewho have been tested positive for the HD gene inpremanifest, prodromal, early-, mid- or late-stage ofthe disease.

For the second objective, the qualitative and tex-tual component of this review will consider studiesthat include participants of any age or gender whohave been clinically or genetically diagnosed withHD, including those that have been tested positivefor the HD gene in premanifest, prodromal, early-,mid- or late-stage of the disease, in addition tostudies which include or focus on family membersand caregivers that relate to this patient group.

SYSTEMATIC REVIEW PROTOCOL L. Quinn et al.



Types of intervention(s)/phenomena of interestThe quantitative component of this review willconsider studies that evaluate physiotherapy andexercise interventions such as aerobic exercise,strengthening exercises, gait or walking training,treadmill training, balance training, yoga, Pilates,tai-chi (and variants), relaxation, technology-delivered exercise, dance, aquatics, daily livingstrategies, sensory stimulation, cueing (i.e. visual,verbal or physical prompts including attentionalstrategies with internal cues), chaining (i.e.breaking down the task), dual-task training (i.e.motor-cognitive training), task-specific training,education, flexibility range of motion exercises,breathing exercises, wheelchair evaluation, seating,wheelchair mobility training, positioning, splint-ing, posture (alignment and exercises), manuallyassisted cough and non-invasive ventilation. Otherphysiotherapy and exercise interventions as deter-mined by the literature in the area will also beincorporated, as necessary. The comparator ofinterest will be usual care, which currently involvesno specific intervention for individuals with HD.Studies whose primary aim is to evaluate a pharma-cological or psychological intervention will beexcluded.

The qualitative component of this review willconsider all studies that identify and explore theperceptions and experiences of people with HD,their families and caregivers with regard to physi-otherapy and exercise interventions.

The textual component of this review will con-sider all studies that describe the perceptions andexperiences of people with HD and their families andcaregivers with regard to physiotherapy and exerciseinterventions.

OutcomesThe quantitative component of this review will con-sider studies that include outcomes related tophysical and cognitive function regardless of howthey were measured. For example, outcomemeasures of physical function include: balance, fit-ness (cardiovascular function), goal attainment,motor function and performance, muscle strength,number of falls, physical activity, pulmonary func-tion, rate of chest infections, and ulcer staging,spatiotemporal and kinematic parameters of gaitand balance, walking ability and endurance.

For example, outcome measures of cognitivefunction include: cognition, psychological measures(depression, anxiety and apathy). Other physiother-apy outcomes as determined by the literature in thearea will also be incorporated, as necessary.

ContextThe qualitative component of this review will con-sider studies that investigate physiotherapy and exer-cise interventions that are carried out in thecommunity, hospital settings, clinics, rehabilitationcenters or patient’s homes.

Types of studiesThe quantitative component of the review will con-sider both experimental and epidemiological studydesigns, including randomized controlled trials, non-randomized controlled trials, quasi-experimentalstudies, before and after studies, prospective andretrospective cohort studies, case control studiesand analytical cross-sectional studies for inclusion.The quantitative component of the review will alsoconsider descriptive epidemiological study designs,including case series, individual case reports anddescriptive cross-sectional studies for inclusion.

The qualitative component of the review willconsider studies that focus on qualitative data,including, but not limited to, designs such as phe-nomenology, grounded theory, ethnography, actionresearch and feminist research.

The textual component of the review will considerdiscussion papers, position papers and other textbased on expert clinical opinion.

Search strategy

The search strategy aims to find both published andunpublished studies. A three-step search strategy willbe utilized for each component in this review. Aninitial limited search of PubMed and CINAHL willbe undertaken followed by an analysis of the textwords contained in the title and abstract, and of theindex terms used to describe the article. A secondsearch using all identified keywords and index termswill then be undertaken across all included data-bases. Third, the reference lists of all identifiedreports and articles will be searched for additionalstudies. Studies published in English only will beconsidered for inclusion in this review. Studies




published between May 2002 and the present will beconsidered for inclusion in this review. May 2002was the completion date for the previous systematicreview.21

The databases to be searched include: EBSCOCINAHL, PEDro, MEDLINE via PubMed,Cochrane Library, Scopus, SPORTDiscus andPsycINFO.

The search for unpublished studies will include:Google, Web of Science (Books, proceedings andother), ClinicalTrials.gov, WHO InternationalClinical Trials Registry Platform, ISRCTN Registry,Prospero, National Guideline Clearinghouse,Resources from professional organizations such as:Huntington Study Group, European Huntington’sDisease network (EHDN) and American PhysicalTherapy Association.

Initial keywords to be used will be: huntington"

disease, physical therap", physical activit", exercise,physiotherapy"

Assessment of methodological quality

Papers selected for retrieval will be assessed by twoindependent reviewers for methodological validityprior to inclusion in the review using standardizedcritical appraisal instruments from the Joanna BriggsInstitute Meta-Analysis of Statistics Assessment andReview Instrument (JBI-MAStARI) (Appendix I).Any disagreements that arise between the reviewerswill be resolved through discussion, or with a thirdreviewer.

Qualitative papers selected for retrieval will beassessed by two independent reviewers for methodo-logical validity prior to inclusion in the review usingstandardized critical appraisal instruments from theJoanna Briggs Institute Qualitative Assessment andReview Instrument (JBI-QARI) (Appendix I). Anydisagreements that arise between the reviewers willbe resolved through discussion, or with a thirdreviewer.

Textual papers selected for retrieval will beassessed by two independent reviewers for authen-ticity prior to inclusion in the review using stand-ardized critical appraisal instruments from theJoanna Briggs Institute Narrative, Opinion and TextAssessment and Review Instrument (JBI-NOTARI)(Appendix I). Any disagreements that arise betweenthe reviewers will be resolved through discussion, orwith a third reviewer.

Data extraction

Quantitative data will be extracted from papersincluded in the review using the standardized dataextraction tool from JBI-MAStARI (Appendix II).The data extracted will include specific details aboutthe interventions, populations, study methods andoutcomes of significance to the review question andspecific objectives.

Qualitative data will be extracted from papersincluded in the review using the standardized dataextraction tool from JBI-QARI (Appendix II). Thedata extracted will include specific details about thepopulations, phenomena of interest and context aswell as methodology, methods, settings and culturalinformation study methods related to the reviewquestion and specific objectives.

Textual data will be extracted from papersincluded in the review using the standardized dataextraction tool from JBI-NOTARI (Appendix II).The data extracted will include specific details aboutthe populations, study methods related to the reviewquestion and specific objectives.

All reviewers will have practiced using the extrac-tion tools in order to apply the tools consistently.Reviewers will extract data independently beforeconferring.

Authors of both quantitative and qualitativeprimary studies will be contacted for missing infor-mation or to clarify unclear data.

Following segregated synthesis of the includedquantitative and qualitative studies, the results ofeach single method synthesis included in the mixedmethod review will be extracted in numerical, tab-ular or narrative format. For example, for synthesisof quantitative data, this will consist of appropriateelements of the meta-analysis Forest plot or, whereapplicable, an evidence table; for qualitative data, itwill consist of appropriate elements of the QARI-view table; for textual opinion data, it will consist ofappropriate elements of the NOTARI-view table.

Data synthesis

Quantitative data will be, where possible, pooled instatistical meta-analysis using JBI-MAStARI. Allresults will be subject to double data entry. Effectsizes expressed as odds ratio (for categorical data)and weighted mean differences (for continuous data)and their 95% confidence intervals will be calculatedfor analysis. Heterogeneity will be assessed




statistically using the standard Chi-square. Wherestatistical pooling is not possible, the findings willbe presented in narrative form, including tables andfigures to aid in data presentation where appropriate.

Qualitative research findings will be pooled usingJBI-QARI. This involves the aggregation or synthesisof findings to generate a set of statements thatrepresent that aggregation, through assembling thefindings (Level 1 findings) rating according to theirquality, and categorizing these findings on the basisof similarity in meaning (Level 2 findings). Thesecategories will then be subjected to a meta-synthesisto produce a single comprehensive set of synthesizedfindings (Level 3 findings) that can be used as a basisfor evidence-based practice. Where textual pooling isnot possible, the findings will be presented in narra-tive form.

The findings of each single-method synthesisincluded in this review will be aggregated usingthe JBI method of meta-aggregation. This willinvolve the configuration of the findings to generatea set of statements that represent that aggregationthrough coding any quantitative to attribute a the-matic description to all quantitative data, assemblingall of the resulting themes from quantitative andqualitative syntheses, and the configuration of thesethemes to produce a set of synthesized findings in theform of a set of recommendations or conclusions.

The findings will be presented in narrative form,including tables and figures to aid in data presen-tation where appropriate.

AcknowledgementsFunding for this review is provided by the Hunting-ton Study Group, European Huntington DiseaseNetwork and Griffin Foundation.

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Appendix I: Appraisal instrumentsMAStARI appraisal instrument




QARI appraisal instrument




NOTARI appraisal instrument




Appendix II: Data extraction instrumentsMAStARI data extraction instrument




QARI data extraction instrument




NOTARI data extraction instrument




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