Caregiver-mediated exercises for improving outcomes after stroke

  • Protocol
  • Intervention

Authors

  • Judith DM Vloothuis,

    Corresponding author
    1. Amsterdam Rehabilitation Research Centre, Reade, Department of Neurorehabilitation, Amsterdam, Netherlands
    • Judith DM Vloothuis, Department of Neurorehabilitation, Amsterdam Rehabilitation Research Centre, Reade, Overtoom 283, PO Box 58271, Amsterdam, 1054 HW, Netherlands. j.vloothuis@reade.nl.

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  • Erwin EH van Wegen,

    1. VU University Medical Center, Department of Rehabilitation Medicine, MOVE Research Institute Amsterdam, Amsterdam, Netherlands
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  • Janne M Veerbeek,

    1. VU University Medical Center, Department of Rehabilitation Medicine, MOVE Research Institute Amsterdam, Amsterdam, Netherlands
    2. VU University Medical Center, Department of Rehabilitation Medicine, Physical Therapy, Amsterdam, Noor-Holland, Netherlands
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  • Manin Konijnenbelt,

    1. Amsterdam Rehabilitation Research Centre, Reade, Department of Neurorehabilitation, Amsterdam, Netherlands
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  • Johanna MA Visser-Meily,

    1. University Medical Center Utrecht and De Hoogstraat, Brain Center Rudolf Magnus, Utrecht, Netherlands
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  • Gert Kwakkel

    1. VU University Medical Center, Department of Rehabilitation Medicine, MOVE Research Institute Amsterdam, Amsterdam, Netherlands
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Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To investigate the effects of caregiver-mediated exercises on outcome in terms of body function, activities and participation of the person with stroke, as well as its impact on mood and burden of their caregiver.

The primary objective is to determine if caregiver-mediated exercises improve functional ability in adults after stroke in basic and extended activities of daily living (ADL), and to determine the effect on mood, burden and QoL of the caregiver.

The secondary objective is to determine the effect of caregiver-mediated exercises on outcome measures of gait, motor impairment, QoL, mood, fatigue, adverse outcomes, upper limb function and length of stay or treatment period.

Background

Description of the condition

Stroke is a major cause of long-term disability in adults in developed countries. The percentage of people unable to walk independently indoors, three weeks after stroke is 40%, and six months after stroke is 15% (Wade 1987). Any treatment that improves functional outcome can potentially reduce the burden of this illness on the individual, their family and caregivers, and society. Rehabilitation is the cornerstone of interdisciplinary stroke care (Langhorne 2001).

Description of the intervention

Several systematic reviews have shown that a higher intensity of training in terms of time spent on exercise therapy can lead to better functional outcome in people with stroke (Kwakkel 2004; Kwakkel 2006; French 2007; Galvin 2008; Langhorne 2011; Veerbeek 2011). A (novel) method to increase intensity of training could be to involve caregivers in exercise training (De Weerdt 2002). We have defined caregiver-mediated exercises as the person with stroke performing exercises together with a caregiver under the auspices of a physical or occupational therapist. "Under the auspices" means that the therapist is involved as a coach by (1) instructing both patient and caregiver on how to perform the exercises, and (2) evaluating them on a regular basis. Hereby, the exercises are repetitive, with the main aim being to improve motor function. Exercises can be delivered at home, or in outpatient or inpatient settings.

How the intervention might work

Performing exercises together with a caregiver has the potential to augment the intensity of practice without increasing healthcare costs. This could improve outcomes in terms of body functions, activities and participation in people with stroke.

In addition, caregivers are more actively involved in caregiver-mediated exercises than in the usually applied services, which may increase feelings of empowerment with reduced levels of caregiver burden (Brereton 2002; Smith 2004). This could lead to a reduced length of inpatient stay or outpatient treatment in hospitals, rehabilitation and nursing settings, and may improve outcomes in self-management, empowerment and quality of life of patients and caregivers.

Why it is important to do this review

Several systematic reviews have indicated that additional exercise therapy and repetitive task training have a significant, favourable effect on functional outcome after stroke, and they have concluded that the more time spent on exercise therapy (Kwakkel 2004; Kwakkel 2006; Galvin 2008; Veerbeek 2011) and the higher the number of repetitions, the better (French 2007; Langhorne 2011). Clinical guidelines conclude therefore, that people who are in a rehabilitation setting should have the opportunity to train intensively (ESO 2008; SIGN 2010; NICE 2013). The guideline in the UK, for example, recommends a daily dose of 45 minutes of therapy.

Currently, the resources in inpatient settings are not sufficient to meet these recommendations. Most people admitted to stroke units (Bernhardt 2004), rehabilitation wards and nursing homes (Smith 2008; West 2012) spend most of their waking time during the working week inactive, and on weekends, rehabilitation services (including exercise therapy) in most hospital and rehabilitation settings are not available (Otterman 2012). Therefore, it is important to find innovative methods such as caregiver-mediated exercises to improve intensity of training after stroke, without increasing costs.

However, the caregiver taking the role of a therapist (instead of a family role) may lead to conflicts between patient and caregiver (Gordon 2004). Therefore, it is important to systematically study the mood, burden and quality of life (QoL) of the caregiver when involved in caregiver-mediated exercises. No systematic review has been done to date to evaluate the effect of caregiver participation in exercise training on functional outcome after stroke, nor to evaluate the effect on mood and burden of the caregiver when involved in caregiver-mediated exercises.

Objectives

To investigate the effects of caregiver-mediated exercises on outcome in terms of body function, activities and participation of the person with stroke, as well as its impact on mood and burden of their caregiver.

The primary objective is to determine if caregiver-mediated exercises improve functional ability in adults after stroke in basic and extended activities of daily living (ADL), and to determine the effect on mood, burden and QoL of the caregiver.

The secondary objective is to determine the effect of caregiver-mediated exercises on outcome measures of gait, motor impairment, QoL, mood, fatigue, adverse outcomes, upper limb function and length of stay or treatment period.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs), including cluster-RCTs. We will also include RCTs with a cross-over design. However, we will interpret these RCTs as having a parallel group design up to the point of cross-over.

One arm of the trial must include caregiver-mediated exercises and we will consider this arm as the experimental group for the purpose of this review.

The other (control) arm can receive usual treatment, no treatment or any other type of rehabilitation intervention or attention-control group as long as it is not caregiver-mediated. We will accept usual treatment when it is described as usual care in the setting of the patient. Therefore, it is important that caregiver-mediated exercises are not explicitly asked for in the control group.

Types of participants

People, at least 18 years old, who have suffered a stroke. Stroke is defined by the World Health Organization as "a clinical syndrome typified by rapidly developing signs of focal or global disturbance of cerebral functions, lasting more than 24 hours or leading to death, with no apparent causes other than of vascular origin" (WHO 1989). We will include RCTs regardless of timing after stroke and setting.

Types of interventions

One arm of the RCT must include exercises done together with a caregiver, whereas the caregiver involvement is not explicitly asked for in the other arm of the RCT. 

We will include trials in which the patient and their caregiver are trained or instructed together, as well as trials in which the caregiver alone is trained or instructed.

There will be no limit to the number of sessions or to the frequency of delivery. We will include all types of exercises as long as they are aimed at improving motor function. Therefore, we will exclude RCTs of speech, swallowing or cognitive interventions done together with a caregiver.

A caregiver will be defined as someone who is willing and able to do exercises together with the patient. This can be someone close to the patient, for example a partner, family member or friend. This can also be a volunteer. A caregiver is not a professional and is not paid for their efforts.

We will include interventions delivered at any location, for example at home, in hospital or in a rehabilitation setting.

We will carefully judge trials that combine caregiver-mediated exercises with other interventions. If the interventions and outcomes can be separated, we will include them. We will exclude trials where the influence of the caregiver-mediated exercises cannot be isolated.

We will contact trial authors if it is unclear whether a trial meets our definition.

Types of outcome measures

Primary outcomes
  1. Patient: ADL measures, such as the Barthel index (BI) (Mahoney 1965; Collin 1988), Functional Independence Measure (FIM) (Dodds 1993), modified Rankin Scale (mRS) (De Haan 1995; Dromerick 2003), Nottingham Extended ADL index (NEADL) (Nouri 1987), or Frenchay Activities Index (FAI) (Wade 1985). We will combine the BI and FIM in our analyses as they are both measurements of basic ADL. The mRS is often dichotomised into good or poor outcomes. When this is done we will analyse the scale separately. When the mRS is not dichotomised we will combine it with the BI and FIM. We will combine the NEADL and FAI because they are both measurements of extended ADL.

  2. Caregiver: measures of mood, burden and QoL, for example Caregiver Strain Index (CSI) (Robinson 1983), Hospital Anxiety and Depression Scale (HADS) (Zigmond 1983; Herrmann 1997; Aben 2002; Bjelland 2002), or CarerQoL (Brouwer 2006; Hoefman 2011). These scales measure different constructs and we will not combine them.

We will distinguish between caregivers who are family or friends and other volunteer caregivers for the above-mentioned measures of outcome.

Secondary outcomes
  1. Gait and gait related measures: walking speed, walking distance, Timed-Up-and-Go test (TUG) (Collen 1990; Flansbjer 2005), Rivermead Mobility Index (RMI) (Collen 1991; Hsieh 2000; Hsueh 2003), Berg Balance Scale (BBS) (Berg 1992; Berg 1995; Stevenson 2001; Mao 2002). These scales measure different constructs and we will not combine them.

  2. Measures of motor impairment: Motricity Index (MI) (Collin 1990), Fugl-Meyer Assesment (FMA) (Duncan 1983; Sanford 1993; Shelton 2001). We will combine the MI and FMA in our analyses.

  3. Measures of mood and QoL of the patient, for example, measured by the Stroke Impact Scale (SIS) (Duncan 1999; Duncan 2002; Duncan 2003) and HADS (Zigmond 1983; Herrmann 1997; Aben 2002; Bjelland 2002). We will only combine measurement scales if they measure the same construct, e.g. mood or QOL.

  4. Measures of fatigue of the patient, for example, measured by the Fatigue Severity Scale (FSS) (Valko 2008).

  5. Adverse outcomes, for example, pain, injury, or falls. If possible, we want to compare the total number of falls between groups, and the number of patients experiencing at least one fall between groups.

  6. Measures of upper limb activities of function, for example, Action Research Arm Test (ARAT) (Hsieh 1998; Platz 2005; Chen 2012).

  7. Length of stay in hospital, rehabilitation centre or nursing home, or treatment in an outpatient clinic. 

We will not exclude trials with outcome measures that differ from the ones mentioned above. We will verify if they measure the same construct. If this is the case, we will pool them, if they do not measure the same construct, we will systematically report these outcomes. 

Search methods for identification of studies

See the 'Specialized register' section in the Cochrane Stroke Group module. We will search for trials in all languages and arrange translation of papers published in languages other than English.

Electronic searches

We will search the Cochrane Stroke Group Trials Register and the following electronic databases and trials registers:

  • Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue);

  • Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library, latest issue);

  • Cochrane Methodology Register (CMR) (The Cochrane Library, latest issue);

  • Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library, latest issue);

  • Health Technology Assessment Database (HTA) (The Cochrane Library, latest issue);

  • NHS Economic Evaluation Database (NHS EED)  (The Cochrane Library, latest issue);

  • MEDLINE (Ovid) (from 1946) (Appendix 1);

  • EMBASE (Ovid) (from 1980);

  • CINAHL (Cumulative Index of Nursing and Allied Health Literature) (EBSCO) (from 1982);

  • SPORTDiscus (EBSCO) (from 1985);

  • AMED (Alternative and Complementary Medicine) (Ovid) (from 1985);

  • Physiotherapy Evidence Database (PEDro) (http://www.pedro.org.au/);

  • REHABDATA (http://www.naric.com/?q=en/REHABDATA);

  • ClinicalTrials.gov (http://www.clinicaltrials.gov/);

  • EU Clinical Trials Register (https://www.clinicaltrialsregister.eu);

  • Stroke Trials Registry (www.strokecenter.org/trials/);

  • Current Controlled Trials (www.controlled-trials.com);

  • WHO International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/);

  • Australian New Zealand Clinical Trials Registry (www.anzctr.org.au/).

We developed the MEDLINE search strategy with the help of the Cochrane Stroke Group Trials Search Co-ordinator (Brenda Thomas) and we will adapt this for the other databases (Appendix 1). 

Searching other resources

We will carry out the following additional searches to identify further published, unpublished and ongoing studies:

  • search the reference lists of all included articles;

  • contact experts in the field;

  • contact authors of conference abstracts for full-text publications, if available; and

  • use Science Citation Index Cited Reference Search for forward tracking of important articles.

Data collection and analysis

Selection of studies

Two review authors (JV, JMV) will independently screen the titles and abstracts of the records obtained from the electronic searches and exclude obviously irrelevant studies. We will obtain the full text of the remaining studies and the same two authors will select studies for inclusion in the review based on the inclusion criteria described previously. We will resolve any disagreements by discussion and, where necessary, in consultation with a third review author (EvW).

Data extraction and management

Two review authors (JV, JMV) will conduct data extraction and will review the risk of bias of the eligible trials. The review authors will not be blinded to study authors, journals or outcomes. We will resolve any disagreements by discussion. If no consensus is reached, a third author (EvW) will make the final decision. One review author (JV) will extract the data and a second review author (JMV) will cross check the extracted data using a standard checklist, including randomisation method, study population, intervention methods and delivery, outcome measures, and follow-up.

Assessment of risk of bias in included studies

We will use the tool for assessing risk of bias in included RCTs as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will assess all forms of bias (selection bias, performance bias, attrition bias, detection bias, reporting bias and other bias) with their domains (random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias). We will present the results in 'Risk of bias' tables. For each entry our judgement ('low risk', 'high risk' or 'unclear risk') will be given, followed by a description of the judgement. We will make our judgements transparent, and will use comments or quotes when necessary.

Measures of treatment effect

For continuous outcomes using similar measurement scales, we will use the mean difference (MD) with 95% confidence intervals (CIs). If similar outcomes are measured on different scales we will use Hedges’ g and calculate the 95% CI.

We will report the direction of the effect for every scale in order to align the treatment effects between outcomes scales. Scales in which a low score reflects a favourable outcome and a high score an unfavourable outcome, will be multiplied by -1.

We will extract means and standard deviations (SDs) of post-intervention scores and follow-up scores. Where available, we will also extract means and SDs of change from baseline.

For dichotomous outcomes (e.g. falls: yes/no) we will calculate summarised odds ratios (ORs) with 95% CIs.

We will use Review Manager 5.2 for all quantitative analyses (RevMan 2012).

Unit of analysis issues

We will take into account that studies can have different levels of randomisation, e.g. at the level of a participating person, or at the level of a group of participating people (cluster randomisation).

When there are multiple observations because of follow-up measurements, we will analyse outcomes for the different follow-up categories (short-term: zero to three months, medium-term:four to six months, and long-term: six months and more).

If we identify studies with multiple intervention groups, we will make multiple pair-wise comparisons between all possible pairs of intervention groups. We will make sure that participants are not double-counted in the analysis.

Dealing with missing data

If data are missing or not in a form suitable for quantitative pooling, we will contact the trial authors for additional information.

Assessment of heterogeneity

Heterogeneity between the included RCTs will be inevitable (Higgins 2011). Therefore, we will assess the impact of heterogeneity in the meta-analysis for each outcome with the I² statistic. When there is substantial statistical heterogeneity (I² > 50%) we will use a random-effects model, otherwise we will use a fixed-effect model for meta-analysis.

Assessment of reporting biases

We will assess reporting bias by a funnel plot in which the effect estimates and precision (standard error) of each individual RCT will be plotted.

Data synthesis

When we find two or more RCTs with a low risk of bias in which study population, intervention and outcome measures are the same, we will perform a meta-analysis of the comparison caregiver-mediated exercises versus the control group (usual care, no intervention, or any other intervention).

We will include a 'Summary of findings' table using the Cochrane template. The following seven outcomes will be included: ADL measures, burden of the caregiver, walking speed, walking distance, mood of the patient, length of stay, and adverse events.

For each outcome we will include, the number of participants, the overall quality of the evidence using GRADE levels of evidence, the magnitude of the effect, a measure of burden of the outcome and comments.

If there are not enough studies for a meta-analysis we will synthesise the findings of the included studies systematically in a table. Hereby, we will use the GRADE levels of evidence to define the quality of the studies (Higgins 2011).

In the same way we will systematically report other outcome measures that we cannot include in a meta-analysis because they do not measure the same construct as our predefined outcome measures.

We will use Review Manager 5.2 for the analyses (RevMan 2012).

Subgroup analysis and investigation of heterogeneity

If we find sufficient studies (e.g. two or more for a subgroup) we will perform subgroup analyses for type of experimental intervention (caregiver-mediated exercises in addition to regular therapy versus caregiver-mediated exercises done alone), type of control group (control intervention or no intervention) and timing post-stroke ((sub)acute stage: less than six months versus chronic stage: more than six months).

Sensitivity analysis

Where we use a fixed-effect model, we will apply a random-effects model to assess the robustness of the results to the method used.

Acknowledgements

We wish to acknowledge the support of Brenda Thomas and Hazel Fraser from the Cochrane Stroke Group for their help with this protocol.

Appendices

Appendix 1. MEDLINE search strategy (Ovid)

1. cerebrovascular disorders/ or exp basal ganglia cerebrovascular disease/ or exp brain ischemia/ or exp carotid artery diseases/ or exp intracranial arterial diseases/ or exp intracranial arteriovenous malformations/ or exp "intracranial embolism and thrombosis"/ or exp intracranial hemorrhages/ or stroke/ or exp brain infarction/ or vasospasm, intracranial/ or vertebral artery dissection/ or brain injuries/ or brain injury, chronic/
2. (stroke or poststroke or post-stroke or cerebrovasc$ or brain vasc$ or cerebral vasc$ or cva$ or apoplex$ or SAH).tw.
3. ((brain$ or cerebr$ or cerebell$ or intracran$ or intracerebral) adj5 (isch?emi$ or infarct$ or thrombo$ or emboli$ or occlus$)).tw.
4. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracranial or subarachnoid) adj5 (haemorrhage$ or hemorrhage$ or haematoma$ or hematoma$ or bleed$)).tw.
5. hemiplegia/ or exp paresis/
6. (hempar$ or hemipleg$ or brain injur$).tw.
7. Gait Disorders, Neurologic/
8. or/1-7
9. caregivers/ or friends/ or exp parents/ or spouses/ or visitors to patients/
10. voluntary workers/ or hospital volunteers/ or home health aides/ or exp parent-child relations/ or exp interpersonal relations/
11. family/ or exp family characteristics/ or family relations/ or intergenerational relations/
12. family therapy/ or family health/
13. (carer$ or caregiver$ or care giver$ or care-giver$).tw.
14. (family$ or families or spous$ or parent or parents or father$ or mother$ or friend or friends or husband$ or wife or wives or partner or partners or neighbour or neighbours).tw.
15. next of kin.tw.
16. ((non-professional or non professional or informal or volunteer$ or relative or relatives) adj5 (exercise$ or rehabilitat$ or therap$ or train$)).tw.
17. or/9-16
18. rehabilitation/ or "activities of daily living"/ or exp exercise therapy/ or occupational therapy/ or physical therapy modalities/ or exp exercise movement techniques/ or exp Exercise/ or Physical Fitness/ or physical endurance/ or early ambulation/ or walking/ or exp "Physical and Rehabilitation Medicine"/
19. (rehabilitat$ or activities of daily living or ADL or exercis$ or physiotherap$ or occupational therap$ or physical therap$ or physical fitness or physical endurance or ambulat$ or walk$ or progressive resist$).tw.
20. (muscle adj5 strengthen$).tw.
21. 18 or 19 or 20
22. 8 and 17 and 21
23. cerebrovascular disorders/rh or exp basal ganglia cerebrovascular disease/rh or exp brain ischemia/rh or exp carotid artery diseases/rh or exp intracranial arterial diseases/rh or exp intracranial arteriovenous malformations/rh or exp "intracranial embolism and thrombosis"/rh or exp intracranial hemorrhages/rh or stroke/rh or exp brain infarction/rh or vasospasm, intracranial/rh or vertebral artery dissection/rh or brain injuries/rh or brain injury, chronic/rh or hemiplegia/rh or exp paresis/rh or Gait Disorders, Neurologic/rh
24. 17 and 23
25. 22 or 24
26. Randomized Controlled Trials as Topic/
27. random allocation/
28. Controlled Clinical Trials as Topic/
29. control groups/
30. clinical trials as topic/
31. double-blind method/
32. single-blind method/
33. cross-over studies/
34. Therapies, Investigational/
35. Research Design/
36. randomized controlled trial.pt.
37. controlled clinical trial.pt.
38. clinical trial.pt.
39. (random$ or RCT or RCTs).tw.
40. (controlled adj5 (trial$ or stud$)).tw.
41. (clinical$ adj5 trial$).tw.
42. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
43. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
44. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
45. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
46. (cross-over or cross over or crossover).tw.
47. trial.ti.
48. (assign$ or allocate$).tw.
49. or/26-48
50. 25 and 49

Contributions of authors

Judith Vloothuis wrote this protocol. The other authors directed protocol focus and quality, and commented on the protocol.

Declarations of interest

None known.

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