http://orcid.org/0000-0002-2325-3380
Figures
Abstract
Globally, stroke remains a leading cause of death and disability, with older adults disproportionately affected. Numerous non-pharmacological stroke rehabilitation approaches are in use to address impairments, but their efficacy in older persons is largely unknown. This systematic review examined the evidence for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project conducted under an European Union funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [http://www.senator-project.eu]. A Delphi panel of European geriatric experts agreed activities of daily living and disability to be of critical importance as stroke rehabilitation outcomes. A comprehensive search strategy was developed and five databases (Pubmed, CINAHL, Embase, PsycInfo and Cochrane Database of Systematic Reviews) searched for eligible systematic reviews. Primary studies meeting our criteria (non-pharmacologic interventions, involving stroke survivors aged ≥65 years, assessing activities of daily living and/or disability as outcome) were then identified from these reviews. Eligible papers were double reviewed, and due to heterogeneity, narrative analysis performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence, allowing us to make recommendations regarding specific non-pharmacologic rehabilitation in older stroke survivors. In total, 72 primary articles were reviewed spanning 14 types of non-pharmacological intervention. Non-pharmacological interventions based on physiotherapy and occupational therapy techniques improved activities of daily living amongst older stroke survivors. However, no evidence was found to support use of any non-pharmacological approach to benefit older stroke survivors’ disability. Evidence was limited by poor study quality and the small number of studies targeting older stroke survivors. We recommend future studies explore such interventions exclusively in older adult populations and improve methodological and outcome reporting.
Citation: Stewart C, Subbarayan S, Paton P, Gemmell E, Abraha I, Myint PK, et al. (2018) Non-pharmacological interventions for the improvement of post-stroke activities of daily living and disability amongst older stroke survivors: A systematic review. PLoS ONE 13(10): e0204774. https://doi.org/10.1371/journal.pone.0204774
Editor: Antony Bayer, Cardiff University, UNITED KINGDOM
Received: June 26, 2018; Accepted: September 13, 2018; Published: October 4, 2018
Copyright: © 2018 Stewart et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This work was supported by the European Union Seventh Framework program (FP7/2007– 2013) under grant agreement no. 305930 (www.senator-project.eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: ADL, Activities of Daily Living; BI, Barthel Index; CIMT, Constraint Induced Movement Therapy; FAI, Frenchay Activities Index; FIM, Functional Independence Measure; GRADE, Grading of Recommendations, Development and Evaluation; IADL, Instrumental Activities of Daily Living; ONTOP, Optimal Evidence-Based Non-Drug Therapies in Older Persons; OT, Occupational Therapy; PT, Physiotherapy; SENATOR, Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons; TENS, Trans-electrical Nerve stimulation
Introduction
Globally, stroke remains a leading cause of death and disability, with older adults disproportionately affected[1–2]. While effective acute treatment has increased stroke survival within developed nations, increased survival increases the number of those affected by post-stroke impairments [2]. Therefore, effective rehabilitation which can reduce post-stroke impairment and restore a person’s functional abilities is imperative.
Stroke guidelines recommend utilising multi-disciplinary stroke rehabilitation teams [3–5]. This reflects the diverse physical, psychological and social rehabilitation needs of stroke survivors [3–5]. Rehabilitation is primarily non-pharmacologic in nature, and standard approaches include occupational therapy (OT), physiotherapy (PT), and speech therapy [3–5]. Several factors contribute towards the overall success of stroke rehabilitation and include stroke severity, the type and location of a stroke, and the patient’s general health and pre-stroke health [6]. The patient’s age is also generally accepted to be highly influential; older patients are at a higher risk of poorer outcomes following stroke rehabilitation [7].
The evidence base for many of non-pharmacologic stroke rehabilitation interventions is poor. For example, the National Clinical Guidelines for stroke [4], despite recommending that psychological care be offered to all stroke survivors, also describe the evidence behind many psychological therapies (e.g. Cognitive Behavioural Therapy, Counselling) as conflicting and inconclusive. Furthermore, the effectiveness of such interventions within the older stroke population is even less clear. Much of the literature reports upon trials involving participants below 65 years of age [8]. Older adults may differ from younger adults in terms of their rehabilitation needs and preferences [8]. Ageing brings more challenges; older stroke survivors often have higher pre- and post-stroke disability and impairments, some of which can be explained though the natural ageing process [9]. This may make rehabilitation more challenging, limiting benefits from rehabilitation attempts.
While non-pharmacological approaches to treat post-stroke impairments are predominant, they are also preferred for older patients. Older people have an increased risk of adverse drug reactions [10]. Additionally, many drugs commonly prescribed to older people have not been assessed in an older population [8]. Therefore, pharmacologic agents used to treat some post-stroke impairment, such as muscle spasticity and movement disorders, are unlikely to have been adequately tested in older patients and so their safety amongst this population group is unknown.
There are compelling reasons behind treating common conditions using non-drug therapies amongst older persons. The aim of this systematic review was to identify and review the evidence for such interventions as applied to older stroke survivors. This systematic review is part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project. The ONTOP project aims to systematically review 15 of the most prevalent and difficult to manage conditions in older people and produce a list of recommendations concerning the use of non-drug therapies for these conditions [11–12]. Many of these reviews have been completed, including for pressure ulcer risk reduction and treatment [13] reduction in incidence and treatment of delirium [12] and fall prevention [14]. ONTOP is in turn part of a larger, European Union (EU) funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [11]. Recommendations from ONTOP reviews are intended for use in the SENATOR project to produce a software programme that can advise clinicians on the use of pharmacological and non-pharmacological therapies in older persons, while limiting the risk of polypharmacy and adverse drug reactions [12].
Methods
The systematic review methodology was developed specifically for the ONTOP project. Fig 1 presents an outline of the stages this methodology involved. In summary, the methodology was devised to capture primary studies, RCTs or quasi-RCTs, from published systematic reviews. This process was followed in this review of non-pharmacological interventions for the treatment of older stroke survivors. Outcomes were determined by consensus opinion using the Delphi approach, as described below. Review protocol has not been registered but has been published [12].
Delphi process
Outcomes were selected by a panel of 13 European experts in geriatric medicine using a Delphi process, a structured, questionnaire-based method of reaching consensus [15]. A literature review generated a list of all outcome measures used in stroke research which was then given to panellists as a questionnaire. Panellists, anonymously, rated each outcome from 1–9 according to their perception of its clinical importance. The mean score for each outcome was then used to categorise outcomes by importance: not important (score of 1–3), important but not critical (score of 4–6), and critically importance (7–9). These boundaries were selected based on the Grading of Recommendations, Development and Evaluation (GRADE) method for evaluating the quality of evidence [16]. Panel members could suggest additional outcomes for consideration if they felt that an important outcome had been overlooked. Outcomes ranked as critical were used for this review. Activites of daily living (ADL), quality of life and disability were the only outcomes rated as being critically important. For brevity, in this paper we present the results for ADL and disability only. The results for quality of life will be reported in a separate publication.
Literature search strategy
A search strategy (Fig 1) was designed based on Montori’s highly specific search strategy for retrieving systematic reviews from PubMed [17]. This search strategy was then modified for use in other databases. In total, five databases were searched (Cinahl, Cochrane Database of systematic Reviews, Embase, PsycInfo, PubMed) without restrictions on publication status or date. The search strategy is presented as supplementary material (S1 Table).
Inclusion criteria
Systematic reviews.
- Full text was available in English, Spanish or Italian.
- Identified at least one primary study matching this review’s inclusion criteria.
- Specifically mentioned conducting a search of at least one medical literature database.
- Guidelines were also considered for inclusion provided that they used a transparent and systematic approach to retrieve the evidence.
Primary studies.
- All participants must be ≥65 years of age, or the mean age of participants must be ≥65 years of age
- All aetiologies, types and severity of stroke/ stroke symptoms included
- Involves any non-pharmacological intervention for stroke:
- a single or multi-component non-drug intervention used to improve symptoms post-stroke
- a non-drug intervention being a treatment or therapy that can be performed on or given to a patient, and/or taught to the patient for them to practice themselves.
- A non -drug intervention which is deliverable in clinical practice
- Treatment for any complications or specific disability of stroke (e.g. urinary incontinence, shoulder subluxation, neglect syndrome etc.) will be included if the study reports ≥1 relevant outcome
- Compares the non-pharmacologic treatment against no treatment, a sham intervention or a treatment considered standard practice at the time of the study.
- A study using Randomised Controlled Trial (RCT) or Quasi RCT methodology
- Paper must focus on at least one or more of three Delphi consensus derived outcome variables: ADL, quality of life or disability (global measures only).
- Papers published only in English, Italian and Spanish
Exclusion criteria
Primary studies.
- Any therapy for stroke prevention
- Any therapy using non-conventional products but administered in a conventional route (e.g. Chinese medicine, herbal supplements)
- Observational or before-after studies with historical controls
- The inclusion of participants with other neurological conditions
- Studies exploring the management of stroke in critical care/ Accident &Emergency
- Health services research evaluating the two different stroke units (hospital based, community or home-based), two or more different methods of delivering non-pharmacological therapy (e.g. face to face or telephone rehabilitation), or evaluating different methods of delivering/ co-ordinating discharge care (e.g. named person in charge of discharge/ post-discharge care versus usual care)
- Economic evaluations of non-pharmacological therapy
- Papers discussing the dose-response relationship (duration, intensity of therapy or time to commence treatment, including early discharge)
- Interventions which only involve the provision of education/ stroke information and general sign posting/ liaison with other services where the patient plays a passive role (NB: If these components are included in a broader structured multi-component intervention such as a self-management programme the intervention will be included).
Study selection
For this review, 18,932 potentially relevant articles were identified from database searches (Fig 2). After removing duplicates, 13,627 unique records were screened by title and abstract by two reviewers. Only 363 full texts of systematic reviews were deemed eligible based on their abstracts. Of these, 173 reviews matched the eligibility criteria and were read in full, and their references were hand searched to identify potentially relevant primary studies. The initial searches were conducted in December 2015, with no restrictions on publication date, and resulted in 83 primary articles for inclusion. The review was updated as above in April 2018 and a further six papers were added to the findings.
Data collection
The results of the database searches were amalgamated using Refworks 6.0 software (ProQuest LLC, USA). A list of the titles and abstracts of systematic reviews were screened by two independent assessors (EG, CS). Any disagreements over eligibility were resolved through discussion with other members of the research team (RS and PKM).
The full-text articles of potentially eligible reviews and meta-analyses were then retrieved and assessed for eligibility, again by two independent assessors (EG and CS). The references of the included studies in eligible systematic reviews were hand-searched to identify primary studies relevant to this review. A list of the titles and abstracts of potentially eligible primary studies was screened (EG, CS, SS, RS and PKM). Thereafter, the full-text articles of potentially relevant primary studies were retrieved and screened by EG and CS.
Data extraction
A data extraction form was designed by adapting the Cochrane Collaboration’s Data Extraction and Assessment Template. The information contained on the data extraction forms (study methodology, participant characteristics, and outcome data) was then transferred to an Excel spreadsheet for narrative analysis. Results were also transferred to RevMan 5.3 [Cochrane Collaboration, UK, http://community.cochrane.org/help/tools-and-software/revman-5] to facilitate risk of bias tables. Results were also transferred to the GRADE Pro online system [http://www.gradeworkinggroup.org] for the development of recommendations for each type of non-pharmacological intervention. Types, or categories, for non-pharmacological interventions were developed and applied to organise the included studies into meaningful categories of interventions for the analysis. Data extraction was performed by two independent assessors (CS & EG).
Risk of bias
Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool [18]. This tool assesses: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. A decision was made as to whether the risk of bias for each category should be described as low, unclear or high risk. The overall risk of bias for the study was then judged by taking account of the scores for each individual category. Results from the risk of bias assessment were entered into RevMan 5.3 software to enable the production of risk of bias graphs and summary tables.
Development of PICO questions
Clinical questions were formulated using the PICO (Population, Intervention, Comparator, and Outcome) framework for each intervention type and outcome assessed. Due to the small number of papers in each category of intervention, the PICO questions chosen were considered to be the most pertinent and inclusive questions. For most categories of intervention one question assessing the efficacy of intervention types upon each outcome was chosen. As physiotherapy and occupational therapy are often standard care in stroke rehabilitation, studies investigating these therapies did not have a no intervention control. Therefore, we split physiotherapy and occupational therapy studies depending upon whether they compared a more intensive (increased time and duration) of therapy against usual intensity, or if they compared two or more different forms of therapy.
Narrative analysis
All primary studies were included in a narrative assessment. The effects reported in each study were described as favouring the intervention, favouring the control, or as showing no significant difference. The overall findings of the studies were assessed qualitatively considering methodological quality and risk of bias. Patterns of effect across the studies were described and possible reasons for effect differences between studies explored, as per guidance offered by the ESRC [19]. Due to substantial clinical heterogeneity between studies and poor study reporting, meta-analysis of results was not considered appropriate. Clinical heterogeneity was assessed qualitatively by all authors and focused upon intervention content, target (e.g. upper or lower limb impairment), delivery, duration.
Assessing quality of evidence
After the completion of analysis, evidence for each non-pharmacological category was assessed using the GRADE method [16]. The GRADE approach assesses the evidence across all studies analysed for a given outcome, rather than assessing the evidence from each study individually. The GRADE framework allows the quality of the body of evidence, and consequentially any recommendations to be made from this evidence, to be judged across five criterions known to limit the quality of evidence. Further details regarding each of these criteria can be found on the GRADE website [http://www.gradeworkinggroup.org]. The quality of the evidence was assigned an overall rating of quality, as described below in Table 1.
Development of recommendations
After the quality of evidence had been determined, concise recommendations were designed regarding the use of non-pharmacological therapies after stroke in older persons. These recommendations were written taking account of the quantity, quality and GRADE score of the available evidence.
Results
Of 89 retrieved articles, 72 papers included ADL and/ or Disability as an outcome measure. Results are presented below, organised by type of non-pharmacological intervention; Acupuncture (n = 11), Caregiver Training (n = 1), Constraint Induced Movement Therapy (CIMT, n = 2), Device-assisted Physiotherapy (n = 8), Music Therapy (n = 1), Nerve Stimulation (n = 3), Occupational Therapy (OT, n = 12), Optical Interventions (n = 3), Physiotherapy (n = 17), Psychological Therapies (n = 6), Self-management Education (n = 6), Videogames (n = 1), and Wheelchair (n = 1).
Acupuncture
Studies.
Eleven randomised controlled trials (RCT) were included in this category. Five were conducted in China, two in Sweden, two in the UK and one each from Taiwan and Germany.
Participants.
In total, 1064 participants were involved. Mean ages ranged from 65.5 (SD 9.71) years [20] to 78.3 (SD 5.9) years [21]. Time between stroke onset and commencing intervention ranged from a mean of 14.2 (SD 19.2) hours [22] to 14.4 (SD 7.8) days [20]. Participant’s characteristics across the included studies are presented in Table 2.
Interventions.
Interventions varied in their design (for example number of points used or whether manual or electrical stimulation was applied) and in their duration. Intervention descriptions are summarised in Table 2.
Risk of Bias.
Eight (72.7%) studies were at risk of bias arising from unblinded or inadequately blinded participants. Many of the studies were unclear regarding their methods of randomisation and allocation concealment.
What is the effectiveness of acupuncture (traditional or electro) upon older stroke survivors ADL recovery in comparison to either usual rehabilitation care without acupuncture or sham treatment?
Of the 11 trials investigating the impact of acupuncture upon older stroke survivors ADL recovery (see Table 3), three studies demonstrated statistically significant benefit upon ADL scores favouring acupuncture [25–27]. Pei et.al. (2001) also found limited short term support for the use of acupuncture for ADL recovery, but any significant benefit had disappeared by week 2 post-intervention [29].
It should be noted that those reporting significant findings in relation to ADL recovery following acupuncture tended to be smaller trials. Quality assessment, using the GRADE approach identified the overall body of to be low (see Table 3) due to risks imposed by various biases and the heterogeneity between intervention content, delivery and duration. This means that further studies are very likely to have an important impact on the estimate of effect. Overall, the evidence does not support the use of acupuncture after stroke.
What is the effectiveness of acupuncture upon older stroke survivors’ disability recovery in comparison to usual rehabilitation care without acupuncture or sham treatment?
Liu et al (2016) was the only trial to assess the effect of acupuncture upon stroke survivors’ disability recovery [22]. In their small trial (n = 38) no significant differences (p = .15) in mean modified Rankin scale scores were identified between those receiving acupuncture (1.13, SD 1.25) and those receiving usual care only (1.27, SD 1.16) at 12 weeks post-intervention. A GRADE assessment found the evidence to be moderate but due to the limited number of studies, and the small sample size, further studies are likely to impact upon the expected effect identified in this review. We therefore cannot recommend acupuncture to improve older stroke survivors post-stroke disability.
Caregiver training
Studies.
Only one study investigated the effect of caregiver training upon older stroke survivors ADL recovery. The RCT [31] was conducted within an inpatient rehabilitation unit in one UK hospital.
Participants.
Of 300 participants, 53% (n = 160) were male. The intervention group had a median age of 76 years (IQR 70–80) versus the control group median of 76 years (IQR 70–82). Time between stroke onset and intervention was not reported.
Intervention.
Caregiver training consisted of three to five 30–45 minute sessions of instruction. Sessions covered common stroke related problems, their prevention and management, and included hands on training in moving and handling, mobility encouragement, transfers, and speech/ communication. Sessions were conducted in the hospital whilst the participant was an inpatient. One final session was delivered to the caregiver in the participant’s home environment following participants discharge. The control group participants received usual care only.
Can pre-discharge caregiver training influence post-discharge stroke survivor ADL recovery in comparison to those who receive no caregiver training?
One study, by Kalra et. al. (2004), investigated if caregiver training could influence ADL recovery [31]. Twelve months post intervention, the intervention group scored a median Frenchay Activities Index (FAI) score of 15 (IQR 9–23) versus the control participants median of 16 (IQR 8–22). The difference between groups on this measure was not significant. Using the Barthel Index (BI), presented as the number of persons considered 'improved', classified by BI score >18 at the measurement point, 51% (n = 77) of the intervention participants at three months were considered ‘improved’ versus 35% (n = 52) of the control participants. The difference in the number of persons ‘improved’ was found to be significant (p = .007). At 12 months, 62% (n = 93) of the intervention participants were considered improved, versus 50% (n = 75) of the control participants. However, the difference between groups at 12 months was not significant (p = .074); improvement in ADL recovery was not sustained over time. Pre-discharge caregiver training may offer some benefit to older stroke survivors ADL recovery in the short term. However, only one study investigated this type of intervention and actual BI scores were not presented. GRADE quality assessment was low. Insufficient evidence means we cannot make a recommendation for this type of intervention. There is, however, evidence warrants further investigation as to the potential benefits of such an intervention.
Can pre-discharge caregiver training effect post-discharge stroke survivor Disability scores in comparison to those who receive routine post-discharge advice with no caregiver training?
Only one study [31] investigated if caregiver training could influence participant disability scores. Disability was assessed with the modified Rankin score, presented as the number of persons considered 'improved' as classified by a Rankin score of 0–2. At three months, 53% (n = 80) of intervention participants, versus 42% (n = 63) of control participants, were considered improved. At 12 months, 66% (n = 100) of intervention participants, versus 58% (n = 87) of control participants, were considered improved. However, differences between groups were not significant at either time point (p = .054, p = .18). Very limited evidence from one RCT, with a GRADE assessment of low, suggests no benefit to older stroke survivors’ disability arising from caregiver training.
Constraint induced movement therapy
Studies.
Two RCTs exploring the benefits of Constraint induced movement therapy (CIMT) upon older stroke survivors were identified [32–33]. Both were conducted using rehabilitative outpatient departments, but one was conducted in Taiwan [33] and the other in China [32].
Participants.
The trials involved a total of 116 participants, 56% (n = 65) of whom were male. Mean age ranged from 65.07 (SD 6.7) years [32] to 71.94 (SD 6.79) years [33]. The mean time since stroke ranged from 8.44 (SD 0.62) days [32] to 7.5 months [33].
Interventions.
Wu et. al. (2007) employed a modified CIMT technique (n = 13) where subjects placed unaffected hands in self-adhesive strapping for six hours per day while at home [33]. In addition, participants received two-hour sessions of CIMT with a therapist for five days per week. Sessions, provided after participants’ regular OT appointments, focused on carrying out basic ADLs with the affected arm while the unaffected hand was constrained. This was compared against a traditional rehabilitation programme (n = 13) that focussed on practising ADLs but without constraining the affected limb.
Liu et. al. (2016) compared self-regulated modified CIMT (n = 30), modified CIMT (n = 30), and a control group (n = 30) employing conventional rehabilitation [32]. Self-regulated CIMT participants were encouraged to reflect on their abilities and come up with their own solutions to problems, rather than follow instructions. Modified CIMT participants received therapist feedback and improvement suggestions during arm restraint training sessions. Each group practised 10 tasks daily, through graded and progressive exercises, over two weeks, for one hour per day, five days per week.
Risk of bias.
Risk of bias from both studies is possible due to unblinded participants and lack of clarity surrounding allocation concealment.
What is the effectiveness of CIMT upon older stroke survivors ADL recovery in comparison to those receiving conventional rehabilitation only?
Wu et. al. (2007) reports there to have been no significant difference between the groups (p = .018) at 3 weeks follow-up [33]. Lui et. al. (2016) report that participants receiving self-regulated modified CIMT had significantly higher Instrumental Activities of Daily Living (IADL) scores at week 2 (p < .001) than those receiving modified CIMT alone or conventional therapy [32]. However, this difference had disappeared at 1 month follow up (p = .51). The limited number of studies, combined with a low GRADE quality assessment means that the evidence base is inadequate to conclude CIMT is effective for older stroke survivors ADL.
Device assisted physiotherapy
Studies.
Eight RCTs exploring device assisted physiotherapy were identified. Two each were conducted in France and Italy, and one each from the USA, China, Sweden and the UK.
Participants.
In total 422 participants were randomised, with mean ages ranging from 65 years [34] to 75 years [35]. Table 4 summarises participant characteristics.
Interventions.
Interventions varied in their content and duration and are described in Table 4. We subdivided trials into those using either robotic or non-robotic devices.
Risk of bias.
All studies were at risk of bias resulting from unblinded or inadequately blinded participants, although most had blinded assessors.
What is the effectiveness of a robotic physiotherapy device upon older stroke survivors ADL recovery in comparison to those receiving conventional physiotherapy?
Two studies [38,40] assessed effectiveness of robot-assisted therapy versus usual care (presented in Table 5). Maseiro et. al. (2007) compared a sensorimotor robotic training programme against usual care [38]. Although intervention participants had a significantly better Functional Independence Measure (FIM) score at 6 weeks than control participants, its benefit was not sustained at three or eight month follow-up. The findings of Rabadi et. al. (2008), in their comparison of arm ergometer training, the MIT-MANUS robotic trainer, and usual care, also suggest that additional physiotherapy devices offered no further benefit than usual rehabilitative care [40].
The substantial heterogeneity, combined with a serious risk of bias due to lack of methodological reporting, resulted in a downgrading of the quality of the evidence to very low (see Table 5).
What is the effectiveness of a non- robotic physiotherapy device upon older stroke survivors ADL recovery in comparison to those receiving conventional physiotherapy?
Six studies investigated the impact of non-robotic physiotherapy devices upon stroke survivors ADL recovery (presented in Table 6). Only one of the six studies, Wiart et. al. (1997), reported a moderate significant benefit favouring the non-robotic device at day 30, versus usual care control (p < .03) [41]. That said, there appears to be an imbalance between baseline scores of the two groups and there is no report if this was significant, nor any reporting of the difference between the change in means between groups. The quality of evidence of these studies was rated as very low (see Table 6), owing to a serious risk of bias and small sample size.
Music therapy
Studies.
One RCT, conducted in Italy, investigated the role of music therapy in the treatment of older stroke survivors ADL.
Participants.
The study [42] involved 38 participants, 42.1%(n = 16) of whom were male. The mean age of participants in the intervention arm was 70.4 (SD 8.9) years versus 75.4 (SD 7.6) of control participants. All participants commended intervention within six to eight weeks of stroke onset.
Intervention.
Intervention participants received Relational Active Music Therapy, conducted by trained musical therapists. Participants were encouraged to use rhythmical instruments during these sessions, which were provided three times per week and lasted for around 30 minutes per session. Participants received up to 20 sessions in total. Control participants received no additional intervention.
Risk of bias.
For most bias types, this study was rated as being unclear due to insufficient reporting
Can music therapy effect stroke survivors ADL recovery against usual care alone?
Both intervention and control participants in this small study improved over time (p < .001) but no significant difference between groups final scores or change in scores from baseline were identified [42]. Music therapy participants improved their mean FIM scores from 76.58 (20.35) at baseline, to 110.47 (9.9) at follow up. Similarly, control participants improved their FIM scores from 71.26 (19.33) to 106.89 (16.83). The inclusion of only one small study, with an unclear risk of bias, which demonstrated no improvement in ADL, means that we are not able to recommend the use of music therapy to improve ADL recovery amongst older stroke survivors. The evidence has been given a GRADE quality assessment of low, meaning that further studies are very likely to change the effect estimate.
Nerve stimulation
Studies.
Three RCTs presented findings in relation to nerve stimulation devices and ADL recovery amongst older stroke survivors. Two studies were undertaken in Sweden, and one study undertaken in the United States of America (USA).
Participants.
In total, 232 participants were randomised, of which 62.5% (n = 145) were male. Table 7 presents a summary of participant characteristics.
Interventions.
The three studies varied in their type of nerve stimulation, location of bodily impairment targeted and duration of treatment. Table 7 presents a summary of each intervention.
Risk of bias.
Of the three studies, two studies had a lack of or inadequate blinding procedures. Insufficient reporting to clarify risk of several other bias sources resulted in a number of bias assessments being unclear.
Can the use of nerve stimulation devices influence older stroke survivors ADL recovery in comparison to those who receive usual rehabilitation care or sham treatment only?
Three studies explored the efficacy of nerve stimulation device use upon older stroke survivors ADL recovery (see Table 8 for study results). Johansson et. al. (2001) and MacDonell et. al. (1994), who both studies participants in the acute phase of stroke recovery, found no significant difference in BI scores between those receiving nerve stimulation and those receiving usual care [43–44]. Conversely, Sonde et. al. (1998; 2000), in their 3-year follow up study involving chronic post-stroke survivors, suggests that Trans-electrical Nerve Stimulation (TENS) may not result in significant improvements in ADL immediately following intervention but may allow older stroke survivors to better maintain ADL scores in the 3 years following stroke [45–46]. While both the intervention and control groups ADL scores declined from 3 months to the 3 year follow up, the control groups reduction in ADL was significantly greater than those who received the TENS intervention [45–46].
The evidence for the use of nerve stimulation for ADL recovery in older stroke survivors is limited (see Table 8). Nerve stimulation does not appear to improve ADL in the immediate term, but may offer protective benefits over future decline in ADL in the years following stroke. Quality assessment suggests the evidence to be very low which means that further studies will likely have an impact on findings. At present, it is not possible to recommend the use of nerve stimulation in the treatment of older stroke survivors to enhance ADL recovery.
Occupational therapy
Studies.
Twelve RCTs were included. Eight were conducted in the UK, with one each from China, Holland, Canada and Italy.
Participants.
In total, 1632 participants were randomised, of which 49.6% (n = 810) were male. Mean ages ranged from 65.9 (SD 8.16) years [47] to 88.6 (SD 6.5) years [48]. Most studies did not report time between stroke onset and commencement of intervention. Those who did are presented in Table 9 alongside other participant characteristics.
Interventions.
Interventions varied widely in their content and duration and are summarised in Table 9.
Risk of bias.
Ten of the twelve studies involved unblinded or inadequately blinded participants, and two studies had inadequate assessor blinding.
Does increased occupational therapy intensity influence older stroke survivors ADL recovery against no occupational therapy or usual occupational therapy care?
As summarised (Table 10), only four of the ten RCTs reported any positive impact upon ADL scores from an occupational therapy (OT) intervention [49, 52, 54, 58]. In the study by Chiu et. al. (2004) both control and intervention participants mean FIM scores improved and the difference in mean change scores was significant (p = .001), favouring the additional occupational therapy [49]. However, no follow up beyond the end of intervention was conducted. Gilbertson et. al. (2000) found significant improvement in mean ADL scores between their control and intervention participants at eight weeks post-intervention, however these differences were not maintained at six months [52]. Conversely, Walker et. al. (1999) found significant improvement in ADL scores at six months post-intervention, favouring the home-based occupational therapy programme [58]. For the studies which were unable to demonstrate significant benefit, there was little, if any, change in ADL scores, regardless of outcome measure used.
In consideration of several risks of bias, heterogeneity between trials, and mixed findings, the quality of these findings is considered low using the GRADE rating system (see Table 10). This review proposes that increased OT may be beneficial regarding ADL and so should therefore be considered for older stroke survivors.
What is the effectiveness of alternative occupational therapy techniques upon older stroke survivors ADL recovery against traditional ADL based occupational therapy?
Regarding comparing alternative OT approaches, two studies presented relevant ADL data (Table 11). Jongbloed et. al. (1989) found no statistically significant differences between sensorimotor occupational therapy and ADL-based occupational therapy [53]. Donkervoort et. al. (2001) found a statistically significant difference between groups at eight-week follow-up (p<0.01) favouring strategy training over ADL training [51]. However, by five months the different no longer reached significance (p = .11). Very limited evidence and a low GRADE assessment score (see Table 11), means that we are unable to recommend one OT approach above another in relation to older stroke survivors ADL recovery.
What is the effectiveness of additional task-specific occupational therapy versus usual occupational therapy upon older stroke survivors disability scores?
Only one RCT, Parker et.al. (2001), explored the impact of additional OT upon disability scores [57]. They compared usual OT rehabilitation against participants receiving additional task specific training in either leisure activity engagement or self-care activities. Using the Oxford Handicap Scale, measured at six and twelve months post-intervention, the authors found no significant differences between the groups at any assessment (p-values not reported) [57]. Due to unblinded participants, the evidence was downgraded to moderate using the GRADE approach. At present, we are unable to recommend the use of additional OT to improve older stroke survivors post-stroke disability scores
Optical
Studies.
Three RCTs present findings in relation to the use of interventions designed to address visual neglect experienced by older stroke survivors. Studies were undertaken in the U.K. (n = 1), Japan (n = 1) and China (n = 1).
Participants.
In total, 123 participants were randomised, of which 55% (n = 68) were male. Participants mean age ranged from 66 (SD 11.5) [59] to 77.9 (SD 8.6) [60]. Time between stroke and intervention ranged from a median of six days (IQR 2-14days) [60] to 67.1 days (SD 18.4) [59]. Participant characteristics are summarised in Table 12.
Interventions.
Interventions ranged from spatio-motor cueing [60], the wearing of prism glasses [59] or eye patching [61]. Intervention descriptions are presented in Table 12.
Risk of bias.
Two of the three studies had no or inadequate participant blinding, although all three had adequate assessor blinding. Additionally, each of the three studies methods of allocation concealment were inadequately described.
Can optical interventions which target stroke related visual neglect influence stroke survivors ADL recovery in comparison to those receiving conventional rehabilitation only?
All three optical intervention studies measured ADL as an outcome (results presented in Table 13) [59–61]. However, not one of the studies reported significant benefit favouring the optical intervention. Overall, there is no evidence to support the use of interventions targeting visual neglect to improve ADL recovery amongst older stroke survivors. Concerns regarding bias, and the heterogeneity of the trials, results in the quality of evidence being considered very low (see Table 13). According to GRADE, this means that further studies are very likely to change the estimated effect. At present, the use of these approaches cannot be recommended.
Physiotherapy
Studies.
Seventeen RCTs presented findings in relation to physiotherapy (PT) interventions designed to improve ADL and/or disability recovery of older stroke survivors. Seven were conducted in the UK, three in the USA, two in Norway and one each from Finland, Holland, Ireland, Israel and Korea.
Participants.
In total, 1354 older stroke survivors participated in these trials, of which approximately 60.7% (n = 823) were male (N.B. Dickstein et. al., 1996 [62] and Duncan et. al., 1998 [63] did not present participants sex information). Participant characteristics are presented in Table 14 .
Interventions.
Intervention content, delivery and duration varied widely between studies and each intervention is summarised in Table 14 .
Risk of bias.
Almost all studies (n = 16) were at risk of bias from unblinded or inadequately blinded participants. This said, most studies (n = 15) had adequate outcome assessor blinding. Several studies were at potential risk from biases resulting from randomisation or allocation methods.
Does increased physiotherapy influence ADL recovery of older stroke survivors in comparison to those who receive usual rehabilitation care only?
As summarised in Table 15, of the 10 studies addressing this question, only three reported a significant benefit upon ADL favouring additional PT [65, 67, 77]. Each of these three studies identified this benefit only at an intermediate timepoint. Duncan et.al. (2003) found a significant difference in BI scores at three months favouring PT, but not at six months [65]. Similarly, Galvin et.al. (2011) and Sivenius et. al., (1985) also reported results favouring increased PT at in the intermediate term (8 weeks and 3 month respectively), but again differences were not maintained in the long term [67,77].
The degree of heterogeneity between interventions, combined with a number of sources of bias across included studies, resulted in the quality of evidence for this intervention being downgraded to low (see Table 15). According to GRADE further studies are very likely to change the effect estimate. In view of the limited evidence, this review proposes that increased PT may be beneficial regarding ADL recovery in the short term and so should be considered for older stroke survivors.
What is the effectiveness of specific physiotherapy approaches versus alternative physiotherapy approaches or usual care upon older stroke survivors ADL recovery?
Nine studies provided results to address this question, summarised in Table 16. Only one study [71] reported any benefit favouring an alternative PT approach, and the benefit was limited. In their three-arm trial, Kwakkel et. al. (1999) reported a statistically significant difference between additional arm training and leg training, favouring leg training, at the 20 week follow-up (p<0.05). However, no statistically significant differences between the three groups at 26-week or one-year follow-up were found [6].
There is little evidence to suggest that one PT technique benefits stroke survivors ADL recovery more than an alternative technique. GRADE assessment of quality suggests the overall evidence base as being low (see Table 16), largely as a result of substantial heterogeneity between intervention content. Therefore, it is not possible for this review to make any recommendations regarding specific PT approaches to enhance older stroke survivors ADL recovery.
Psychological therapies
Studies.
Six RCTs explored the use of psychological therapies amongst older stroke survivors, with three conducted in the UK, one in Holland, one in Australia and one in the USA.
Participants.
In total, 946 participants were randomised, of which 54.5% (n = 516) were male, with mean ages ranging from 65 (SD 15.1 SD) years [81] to 77.9 (SD 7.4) years [82]. Table 17 presents a summary of participant characteristics.
Interventions.
The six studies varied in their content and underlying theoretical basis, and included biofeedback [83], mental imagery [82], counselling [84], (cognitive behaviour therapy (CBT) [81, 85] and motivational interviewing [86]. A summary description of each intervention is presented in Table 17.
Risk of bias.
All studies had a risk of bias arising from either unblinded participants. However, all reported adequate assessor blinding, and all but one had a low risk of bias arising from randomisation or allocation methods.
Can psychological therapies influence older stroke survivors ADL recovery in comparison to those who receive usual rehabilitation care or sham treatment only?
Only one of the six studies addressing this question reported a significant improvement in ADL (see Table 18). In the study by Clark et. al. (2003), intervention participants who received counselling sessions from a trained social worker had a significantly greater improvement in ADL score than control participants at six month follow up [84]. It should, however, be noted that although statistical significance was reached, the difference between groups is arguably small and clinical significance questionable.
At present, the evidence was assessed by GRADE to be of low quality and does not support a recommendation for the use of psychological therapies to improve ADL recovery in older stroke survivors.
Can psychological therapies affect post-stroke disability in older stroke survivors in comparison to those who receive usual rehabilitation care or sham treatment only?
Only one study, Lincoln et. al. (2003), explored the use of CBT upon post stroke disability amongst older stroke survivors [81]. The three arm trial compared CBT, a sham talking treatment and usual care [81]. Using the London Handicap Scale (LHS), the study identified no significant difference in LHS scores between the groups at baseline, 3 or 6 months. The evidence was assessed by GRADE to be of low quality and therefore at this time, there is no evidence to recommend the use of CBT in older stroke survivor
Self-management education
Studies.
Six RCTs presented findings in relation to self-management education interventions targeting either older stroke survivors ADL recovery or disability. Four were conducted in the UK and one each from Sweden and Israel.
Participants.
In total, 1012 older stroke survivors participated in these trials, of which 531 (52.5%) were male. Participant characteristics are summarised in Table 19.
Interventions.
Each intervention focused upon providing education and developing self-management skills and plans, but their content and mode of delivery varied, as described in Table 19.
Risk of bias.
Each RCT had at least one significant risk of bias, most commonly from unblinded or inadequately blinded participants. Several studies also were at high risk of bias arising from their randomisation and allocation methods.
Do self-management education interventions influence ADL recovery of older stroke survivors in comparison to those who receive usual rehabilitation care only?
Six studies explored if a self-management education intervention could affect post stroke ADL recovery. Results are summarised in Table 20. Only one of the six studies, Nir et. al. 2004, identified a significant improvement in FIM scores following the intervention against a control group receiving usual care [92]. However, this study also measured ADL using the IADL questionnaire and found no significant difference between groups at any follow-up.
In summary, while several studies have explored the impact of self-management education interventions upon post-stroke ADL recovery, there is very little evidence to support their use. The evidence was considered to be of low quality and therefore we cannot recommend these interventions to benefit older stroke survivors.
Do self-management education interventions influence post-stroke disability scores of older stroke survivors in comparison to those who receive usual rehabilitation care?
Two studies explored the impact of self-management education interventions upon post-stroke disability score. One study, Rodgers et al 1999, did not report any original data but we are informed that there were no significant differences between the disability scores of the intervention and control participants [93]. In the study by Smith et al (2004), both intervention and control groups were found to improve their level of disability post-stroke, as measured by the London Handicap Score, but the difference between those who participated in the self-management education intervention, and those who did not, was not significant [94]. There is presently no evidence to support the use of self-management education programmes for older stroke survivors to improve post-stroke disability. An assessment of the quality of these studies, using the GRADE approach, rates the overall quality as very low. Principally, this is due to small sample size, heterogeneity between the RCTs and risk of bias.
Videogames
Studies.
One RCT investigating the role of videogames in the treatment of older stroke survivors was identified. This study, reported by Lee et. al. (2013) [95], was conducted in Korea, but is considered at high risk of bias due to a lack of reporting study methodological information.
Participants.
The trial randomised 14 participants, 9 (64%) of whom were male. The mean age of the intervention group was 71.71 (SD 9.14) years, and the control group 76.43 (SD 5.8) years. The intervention group had a mean time between stroke onset and commencement of intervention of 7.29 months (SD 1.38), in comparison to the control group mean of 8.29 months (SD 3.4).
Intervention.
The 6-week video gaming intervention involved participants being asked to choose two games on an Xbox Kinect games console to play while sitting or standing. The games were played in a separate room without distractions. The games were designed to complement conventional OT therapy and participants asked to participate in these 60-minute sessions three times per week. Control participants received usual rehabilitation care only.
Risk of bias.
For almost all bias types, this study was rated as being unclear due to insufficient reporting.
Can the use of video games in addition to conventional occupational therapy delivered within inpatient rehabilitation care influence stroke survivors ADL recovery against usual occupational therapy alone?
The small study (n = 14) by Lee et. al. (2013) found that both intervention and control groups significantly improved their FIM scores at the post-intervention assessment (Intervention group post-test: 71.42, SD 15 v control group post-test: 61.24, SD 11.9), but no significant difference between the groups in relation to their degree of improvement or final scores were identified (p values not given) [95]. Based upon one small study (n = 14), with a high risk of bias, which demonstrated no benefit, means that we are unable to recommend the use of videogames to improve ADL recovery amongst older stroke survivors. Using the GRADE system the results suggest the evidence is of low quality, meaning that further studies are very likely to change the effect estimate.
Wheelchair
Studies.
Only one RCT, conducted by Barrett et. al. 2001, was identified which investigated if self-propulsion of a wheelchair improved ADL recovery against non-self-propulsion [96]. It was conducted across two inpatient rehabilitation units within one UK hospital had a high risk of bias.
Participants.
This study involved forty participants, 24 (60%) of whom were male. The mean age of the intervention group was 67.5 years (SD 10.4) versus the control group of 66.7 years (SD 12.0). Intervention participants had a mean time between stroke and intervention of 16.1 days (SD 8.8) versus control participants 15.6 days (SD 8.1).
Intervention.
Intervention participants were encouraged to self-propel a wheelchair following instruction by a physiotherapist on how to self-propel. Intervention participants were encouraged by ward staff members to self-propel as much as they could, with weekly reminders from the study team. This encouragement continued until discharge or for a maximum of 8 weeks. Control participants were also provided a wheelchair but were actively discouraged from self-propulsion.
Risk of bias.
Lack of blinding and insufficient reporting resulted in this study being considered to be of unclear bias risk.
Can encouragement to self-propel a wheelchair influence ADL outcome amongst inpatient stroke survivors against discouragement to self-propel a wheelchair?
Only one paper, Barrett et. al. (2001), addresses this question [96]. Both groups improved their BI scores at 3 months (11.4 (4.0 SD) v 9.8 (5.0 SD)) and 12 months (11.9 (5.2 SD) v 11.9 (4.1 SD) but no significant difference between the groups was identified (no p value reported). Similarly, both groups improved their NeADL scores at 3 months (5.8 (5.2 SD) v 5.3 (4.0 SD)) and at 12 months (7.1 (4.7 SD) v 8.0 (5.3 SD) but again the difference between groups was not significant. Therefore, there is no evidence at present to recommend the encouragement of wheelchair propulsion as part of stroke rehabilitation care amongst older stroke survivors. With the bias risks imposed (no participant blinding, concerns about selection bias and small sample size) the evidence has been rated as low using the GRADE system meaning that further studies are very likely to have an important impact on the estimate of benefit.
Summary of recommendations
Table 21 presents a summary of the recommendations this study proposes based on the identified evidence.
Discussion
Acupuncture
Acupuncture is rarely mentioned as a therapy for stroke survivors within the guidelines. The Royal College of Physicians [4] refer to the limited evidence for acupuncture in the treatment of post-stroke dysphagia. The Scottish Intercollegiate Guidelines Network [5] state that they do not recommend acupuncture for the treatment of post-stroke pain syndromes due to insufficient evidence. Teasel et. al. (2003) report that the evidence linking acupuncture to post-stroke ADL recovery is conflicting [97]. Our current review corresponds with previous uncertainties. There was limited evidence to show that acupuncture can benefit older stroke survivors and further research is required.
Caregiver training
Stroke guidelines acknowledge the insufficient evidence behind the benefits of caregiver training as part of stroke rehabilitation, but do promote carer involvement in patient rehabilitation as good practice [4–5]. Our current review identified only one study exploring the impact of caregiver training upon older stroke survivors ADL. This study was sufficiently large, and demonstrated benefits in ADL recovery, but these were short term [31]. Therefore, caregiver training may be beneficial, but further research is required to examine this intervention further.
CIMT
Our current review found little evidence to support the use of CIMT with older stroke survivors, similar to the findings of Veerbeek et. al. (2014) [98]. Several stroke rehabilitation guidelines recommend CIMT to improve function of impaired upper limbs [3–5, 99]. In view of the evidence, SIGN (2010) specifically state that “Constraint induced movement therapy may be considered for carefully selected individuals with at least 10 degrees of finger extension, intact balance and cognition” (p20) [5]. RCP (2016) also explain that the benefits of CIMT often relate to arm function only and within the confines of the activities used within the intervention [4]. Similar to other stroke rehabilitation interventions, CIMT appears most effective when effectiveness is measured in terms of its immediate effect on physiological variables, such as muscle strength. But such benefits do not appear to be associated with improvements in more comprehensive or global outcomes of ADL or disability.
Device assisted physiotherapy
Our current review identified limited evidence to support the use of device assisted physiotherapy to enhance older stroke survivors stroke rehabilitation. Our findings are in line with other reviews and guidelines [4, 98]. The use of robotic devices has been recommended by Teasel et. al. (2003) as they considered this approach beneficial for those with impaired arm function [97], but this recommendation was based on achieving improved arm function, not improved ADL. Conversely, as a result of the overall low quality of evidence behind robot assisted movement therapies the RCP (2016) guidelines stipulate that this type of therapy should only be offered as an adjunct to conventional therapy and within the context of a clinical trial [4].
Music therapy
Only one study explored music therapy in relation to older stroke survivors ADL [42] and no evidence was found to support use of this intervention. Music therapy has been explored previously within neuro-rehabilitation and reviews have identified several benefits such as improved motor function, language and mood [100–102]. Nevertheless, their efficacy with older stroke survivors, and/or impact on global ADL or disability, remains unknown.
Nerve stimulation
Current stroke guidelines have all noted uncertainties surrounding the efficacy of nerve stimulation [4–5, 97, 99]. Evidence has shown that while nerve stimulation techniques can improve specific impairments, such as muscle strength or gait, these improvements do not lead to significant improvements in ADL or disability [4]. Within this review, limited evidence was identified supporting the efficacy of nerve stimulation upon older stroke survivors ADL. Therefore nerve stimulation may benefit older stroke survivors ADL, but the quality of evidence is weak. The number of included studies focusing exclusively upon older stroke survivors is small, making it difficult to sub-divide studies into those focusing on specific types of stimulation or use of stimulation in different locations (e.g. upper or lower body). Reviews which have included adult participants of all ages suggest the best evidence behind nerve stimulation may be found in its use for upper limb impairments [98, 103]. However, due to inconsistencies, current evidence remains insufficient to make any recommendations [5].
Occupational therapy
There was some evidence to show that additional OT can benefit older stroke survivors ADL. This is consistent with the reporting of uncertainties regarding the effects of increased intensity or frequency of OT [4–5]. This review found no evidence to suggest that one OT approach is more beneficial than anther, consistent with the review by Teasel et. al. (2003) [97]. All guidelines recommend ADL focused OT as an important feature of stroke rehabilitation, but acknowledge that optimal intensity and/or duration is yet to be determined [4–5].
Optical
Within the Royal College of Physicians (2016) stroke guidelines, optical interventions such as prism glasses are recommended for stroke survivors with visual neglect [4]. This said, it is noted that the evidence is very limited and that patient participation in such interventions would be most beneficial within the context of a clinical trial [4], a finding echoed by Langhorne, Bernhardt & Kwakkel (2011) [99]. A Cochrane review of interventions targeted at spatial neglect following stroke concluded that there was insufficient evidence to support the use of these interventions to improve disability and ADL [104]. However, the evidence was more promising for specific visual neglect measures [104]. This current review identified no evidence to support the use of these interventions. However, a combination of few studies and small sample sizes may obscure any potential positive impact from these interventions. As suggested by Bowen, Lincoln & Dewey (2007) [104], we also recommend further research involving larger high quality RCTs.
Physiotherapy
It has been reported that many PT interventions such as balance exercises, gait training, and fitness training do lead to benefits in their respective objectives i.e. improved balance, gait, cardiovascular fitness, but rarely lead to improvement in more global measures such as ADL and disability [97]. Veerbeek et. al. (2014) systematically reviewed 467 RCTS involving PT interventions to examine their efficacy in stroke rehabilitation [98]. The strongest evidence supported task specific functions and activities which are repeated at high intensity [98]. However, few global outcomes were reported; outcomes included muscle, joint, bone and sensory function, gait pattern, balance and walking [98]. Benefits in terms of basic ADL were reported to arise from interventions involving activity-based balance training, assisted gait training and VR training for paretic arm [98].
This current review identified limited evidence to demonstrate that additional PT can benefit older stroke survivors’ ADL in comparison to usual care. When restricted to older stroke survivors, and those reporting global measure of ADL or disability, the resulting number of included studies is considerably smaller than those cited in reviews such as that by Veerbeek et. al. (2014) [98]. Nevertheless, we found some evidence suggesting older stroke survivors may benefit from increased PT.
Psychological therapies
Within the guidelines for stroke rehabilitation it is recommended that all stroke survivors be considered and offered psychological care, and not just offer to those with an identified mental health disorder [4]. This recommendation is based upon good practice, possibly due to the frequent development of post-stroke depression [4–5]. In this review limited evidence was identified to show that psychological therapies benefit older stroke survivors. Therefore, psychological therapies may benefit older stroke survivors ADL but the evidence for this is weak and requires further investigation.
Self-management education
Self-management is reported to be capable of influencing function and social participation, and recommended for stroke survivors [4]. This review identified limited evidence to show that such interventions can benefit older stroke survivors. The quality of included studies varied from low to very low and therefore the evidence for this is weak. Further research focusing exclusively upon older stroke survivors and global outcomes is recommended.
Videogames
Current guidelines report that the evidence behind virtual reality as a stroke rehabilitation approach is weak to moderate [4–5]. A Cochrane review by Laver et. al. (2015) suggests that virtual reality can benefit upper limb impairments and ADL, but that evidence is limited to younger stroke survivors and those who are more than one-year post-stroke [105]. In addition to larger high quality RCTs, it has been recommended that research focus upon identifying what the important elements of virtual reality are, and if benefits can be sustained in the long term [105]. Another review suggests that the best evidence lies behind the efficacy of virtual reality upon gait improvement [97]. Based on the evidence generated in this current review it is not possible to recommend virtual reality for older stroke survivors’ rehabilitation. However, based on evidence identified by studies involving slightly younger stroke survivors, further research involving appropriately sized high quality RCTs is warranted.
Wheelchair use
Only one study was identified which investigated if self-propulsion of a wheelchair improved ADL recovery against non-self-propulsion, and there was no evidence of the efficacy of this approach. Current recommendations do not include such an intervention but do recommend the use of wheelchairs in those with impaired mobility to promote independence [4–5].
Limitations
This review has several limitations which must be considered alongside our findings. Firstly, we did not involve patients or carers in the Delphi process, and our identified critical outcomes may not reflect patient and carer preferences. Due to study heterogeneity and insufficient data this review has been limited to narrative analysis only. While describing comparisons between studies is important, it has potential for researcher bias through the imposition of the researchers own subjective ideas about the findings and lacks the rigour of qualitative and objective analysis. Although we used the GRADE criteria recommended by the Cochrane Collaboration this also introduced a degree of subjectivity. This means our results should be interpreted cautiously. We also cannot exclude the possibility that this review has omitted important studies.We have not searched the grey literature and our search strategy focused exclusively on identifying systematic reviews which may have resulted in omission of some trials, particularly those more recently published. However, our comprehensive strategy and the checking of reference lists and published clinical guidelines does go some way in reducing this risk. Categories of non-pharmacological interventions were developed in a somewhat arbitrary fashion. It could be argued that interventions exploring nerve stimulation devices, often delivered by trained physiotherapists, could be considered an alternative physiotherapy approach, as opposed to a category in its own right. Our decisions regarding categorising interventions were largely pragmatic and aimed to organise and present findings in a meaningful way. However, the findings should be interpreted with caution since the interventions lack specificity. We also do not consider the preferences of patients and their carers regarding intervention types. Little work has been done in this area and acceptability of these non-pharmacological approaches are unknown.
Finally, our review is restricted by the significant lack of published studies which met our age criteria (mean age≥ 65 years) and presented results using a global measure of ADL and/or disability. Age-based criteria allow us to examine the evidence as it specifically relates to older adults, but it risks excluding interventions which may be beneficial but have not been adequately tested in an older population. The impact of age as a modifier of treatment effect for many of the interventions examined is unknown. Similarly, the exclusion of so many studies due to lack of global outcome measures again risks excluding worthy interventions which may have demonstrated efficacy had a global outcome been assessed. Additionally, this review uncovered a number of methodological and reporting problems, making the ascertainment of the evidence challenging. Small sample sizes and failure to adequately report details regarding participant selection, randomisation, allocation concealment and data analysis, especially the management of missing data, led to many studies being deemed high risk of bias. One important challenge regarding RCTs involving non-pharmacological treatments is the lack of participant blinding. Although blinding of non-pharmacological treatments is challenging, reviews do highlight many creative approaches to doing so [106]. However, opinions regarding the importance of this are divided. Lack of patient blinding in RCTs presents opportunity for bias, particularly for subjective outcomes [106] such as those explored in the present manuscript. However, concerns have been raised about false negative results arising from RCTs involving non-pharmacological treatments as a result of blinded participants [107]. It is argued that what factors blinding controls for may be an integral component of non-pharmacological therapy [107]. For example, the additional care an intervention participant may receive as part of their acupuncture treatment may contribute towards overall benefit of the treatment [107]. In pharmacological RCTs this additional care would be considered incidental and would be controlled for through provision of similar care to control participants [106–107]. However, it has been argued that this takes away from some of the benefits non-pharmacological treatments bring, and therefore leads to findings of no-benefit [107]. It may be prudent for future work to explore the role of incidental and placebo effects in non-pharmacological treatments for stroke survivors to enhance our confidence in future results.
Conclusion
Due to the substantial heterogeneity, moderate to high risk of biases, and insufficient data provided, this review has had to make recommendations based on narrative analysis only.
Limited evidence suggests additional physiotherapy or occupational therapy may benefit older stroke survivors ADL. Very limited evidence also suggests acupuncture, self-management education, psychological therapies, nerve stimulation, CIMT, and caregiver training may benefit older stroke survivors ADL.
However, the current evidence base is limited by the low number and quality of studies. This review revealed a distinct lack of evidence behind the use of non-pharmacological interventions for stroke survivors aged 65 years and older. Of studies which did involve those aged 65 and older, evidence is limited by poor study designs and inadequate study reporting. Therefore, we also recommend that future studies explore these interventions exclusively in older adult populations, and ensure studies are adequately reported both in terms of methodological detail but also in terms of their outcomes.
Supporting information
S2 Table. References of studies included in the systematic review.
https://doi.org/10.1371/journal.pone.0204774.s003
(DOCX)
S3 Table. Description of all included interventions.
https://doi.org/10.1371/journal.pone.0204774.s004
(DOCX)
References
- 1. Owolabi M. O., Arulogun O., Melikam S., Adeoye A. M., Akarolo-Anthony S., Akinyemi R., et. al. (2015). The burden of stroke in africa: A glance at the present and a glimpse into the future. Cardiovascular Journal of Africa, 26(Supplement 1), 27–38.
- 2.
Stroke Association. (2017). State of the nation: Stroke statistics. Stroke Association. Available at: https://www.stroke.org.uk/sites/default/files/state_of_the_nation_2017_final_1.pdf [Accessed 19th September 2017]
- 3.
National Institute for Health and Care Excellence (NICE). (2013). Strok stroke rehabilitation in adults e rehabilitation in adults No. CG 162). Manchester: NICE.
- 4.
Royal College of Physicians Intercollegiate Stroke Working Party (RCP). (2016). National clinical guideline for stroke. 5th Ed. Royal College of Physicians. Published: 3rd October 2016. Available at: https://www.strokeaudit.org/SupportFiles/Documents/Guidelines/2016-National-Clinical-Guideline-for-Stroke-5t-(1).aspx [Accessed 19th September 2017]
- 5.
Scottish Intercollegiate Guidelines Network (SIGN). (2010). Management of patients with stroke: Rehabilitation, prevention and management of complications, and discharge planning A national clinical guideline. Guideline number 118. Edinburgh: Scottish Intercollegiate Guidelines Network. Published: June 2010. Available at: http://www.sign.ac.uk/sign-118-management-of-patients-with-stroke-rehabilitation,-prevention-and-management-of-complicati.html [Accessed 19th September 2017]
- 6. Kwakkel G., Kollen B. J., & Wagenaar R. C. (2002). Long term effects of intensity of upper and lower limb training after stroke: A randomised trial. Journal of Neurology, Neurosurgery, and Psychiatry, 72(4), 473–479. pmid:11909906
- 7. Lieberman D., & Lieberman D. (2005). Rehabilitation following stroke in patients aged 85 and above. Journal of Rehabilitation Research and Development, 42(1), 47. pmid:15742249
- 8. Watts G. (2012). Why the exclusion of older people from clinical research must stop. BMJ: British Medical Journal (Online), 344
- 9. Pohjasvaara T., Erkinjuntti T., Vataja R., & Kaste M. (1997). Comparison of stroke features and disability in daily life in patients with ischemic stroke aged 55 to 70 and 71 to 85 years. Stroke, 28(4), 729–735. pmid:9099187
- 10. Tangiisuran B., Wright J., Van der Cammen T., & Rajkumar C. (2009). Adverse Drug Reactions in Elderly: Challenges in Identification and Improving Preventative Strategies,
- 11. Soiza R.L., Subbarayan S., Cherubini A., Cruz-Jentoft A.J., Petrovic M., Gudmundsson A., et.al., The SENATOR project: developing and trialling a novel software engine to optimise medications and non-pharmacological therapy in older people with multimorbidity and polypharmacy. Ther Adv Drug Saf 2017;8:81–85. pmid:28382196
- 12. Abraha I., Cruz-Jentoft A., Soiza R. L., O'Mahony D., & Cherubini A. (2015). Evidence of and recommendations for non-pharmacological interventions for common geriatric conditions: The SENATOR-ONTOP systematic review protocol. BMJ Open, 5(1), e007488-2014-007488.
- 13. Lozano-Montoya I., Vélez-Díaz-Pallarés M., Abraha I., Cherubini A., Soiza R. L., O'Mahony D., et.al., (2016). Nonpharmacologic interventions to prevent pressure ulcers in older patients: an overview of systematic reviews (the software ENgine for the assessment and optimization of drug and non-drug therapy in older peRsons [SENATOR] definition of optimal evidence-based non-drug therapies in older people [ONTOP] series). Journal of the American Medical Directors Association, 17(4), 370–e1.
- 14. Rimland J. M., Abraha I., Dell’Aquila G., Cruz-Jentoft A., Soiza R., Gudmusson A., et.al, (2016). Effectiveness of non-pharmacological interventions to prevent falls in older people: a systematic overview. The SENATOR Project ONTOP Series. PloS one, 11(8), e0161579. pmid:27559744
- 15. Keeney S., Hasson F., & McKenna H. P. (2001). A critical review of the delphi technique as a research methodology for nursing. International Journal of Nursing Studies, 38(2), 195–200. pmid:11223060
- 16. Guyatt G. H., Oxman A. D., Vist G. E., Kunz R., Falck-Ytter Y., Alonso-Coello P., et. al. (2008). GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical Research Ed.), 336(7650), 924–926.
- 17. Montori V. M., Wilczynski N. L., Morgan D., Haynes R. B., & Hedges Team. (2005). Optimal search strategies for retrieving systematic reviews from medline: Analytical survey. BMJ (Clinical Research Ed.), 330(7482), 68.
- 18.
Higgins J. P., & Green S. (2011). Cochrane handbook for systematic reviews of interventions John Wiley & Sons.
- 19.
Popay, J., Roberts, H., Sowden, A., Petticrew, M., Arai, L., Rodgers, M., et.al., (2006). Guidance on the conduct of narrative synthesis in systematic reviews. A product from the ESRC methods programme Version, 1, b92. Available: http://www.lancaster.ac.uk/shm/research/nssr/research/dissemination/publications/NS_Synthesis_Guidance_v1.pdf [Accessed 6th August 2018].
- 20. Zhu Y., Zhang L., Ouyang G., Meng D., Qian K., Ma J., et.al., (2013). Acupuncture in subacute stroke: No benefits detected. Physical Therapy, 93(11), 1447–1455. pmid:23723385
- 21. Schuler M. S., Durdak C., Hösl N. M., Klink A., Hauer K. A., Oster P., et.al., (2005). Acupuncture treatment of geriatric patients with ischemic stroke: A randomized, double‐controlled, single‐blind study. Journal of the American Geriatrics Society, 53(3), 549–550. pmid:15743311
- 22. Liu C. H., Hsieh Y. T., Tseng H. P., Lin H. C., Lin C. L., Wu T. Y., et.al., (2016b). Acupuncture for a first episode of acute ischaemic stroke: an observer-blinded randomised controlled pilot study. Acupuncture in Medicine, 34(5), 349–355.
- 23. Gosman-Hedstrom G., Claesson L., Klingenstierna U., Carlsson J., Olausson B., Frizell , et.al., (1998). Effects of acupuncture treatment on daily life activities and quality of life: A controlled, prospective, and randomized study of acute stroke patients. Stroke, 29(10), 2100–2108. pmid:9756589
- 24. Hopwood V., Lewith G., Prescott P., & Campbell M. (2008). Evaluating the efficacy of acupuncture in defined aspects of stroke recovery. Journal of Neurology, 255(6), 858–866. pmid:18465110
- 25. Hsieh R., Wang L., & Lee W. (2007). Additional therapeutic effects of electroacupuncture in conjunction with conventional rehabilitation for patients with first-ever ischaemic stroke. Journal of Rehabilitation Medicine, 39(3), 205–211. pmid:17468788
- 26. Johansson K., Lindgren I., Widner H., Wiklund I., & Johansson B. B. (1993). Can sensory stimulation improve the functional outcome in stroke patients? Neurology, 43(11), 2189–2192. pmid:8232927
- 27. Min M., Xin C., Yuefeng C., Ping R., & Jian L. (2008). Stage-oriented comprehensive acupuncture treatment plus rehabilitation training for apoplectic hemiplegia. Journal of Traditional Chinese Medicine, 28(2), 90–93. pmid:18652112
- 28. Park J., White A. R., James M. A., Hemsley A. G., Johnson P., Chambers J., et.al., (2005). Acupuncture for subacute stroke rehabilitation: A sham-controlled, subject-and assessor-blind, randomized trial. Archives of Internal Medicine, 165(17), 2026–2031. pmid:16186474
- 29. Pei J., Sun L., Chen R., Zhu T., Qian Y., & Yuan D. (2001). The effect of electro-acupuncture on motor function recovery in patients with acute cerebral infarction: A randomly controlled trial. Journal of Traditional Chinese Medicine = Chung i Tsa Chih Ying Wen Pan, 21(4), 270–272. pmid:12014128
- 30. Sze F. K., Wong E., Yi X., & Woo J. (2002). Does acupuncture have additional value to standard poststroke motor rehabilitation? Stroke, 33(1), 186–194. pmid:11779909
- 31. Kalra L., Evans A., Perez I., Melbourn A., Patel A., Knapp M., et.al., (2004). Training carers of stroke patients: Randomised controlled trial. BMJ (Clinical Research Ed.), 328(7448), 1099. pmid:15130977
- 32. Liu K. P., Balderi K., Leung T. L. F., Yue A. S. Y., Lam N. C. W., Cheung J. T. Y., et.al., (2016a). A randomized controlled trial of self‐regulated modified constraint‐induced movement therapy in sub‐acute stroke patients. European journal of neurology, 23(8), 1351–1360.
- 33. Wu C., Chen C., Tsai W., Lin K., & Chou S. (2007). A randomized controlled trial of modified constraint-induced movement therapy for elderly stroke survivors: Changes in motor impairment, daily functioning, and quality of life. Archives of Physical Medicine and Rehabilitation, 88(3), 273–278. pmid:17321816
- 34. de Sèze M., Wiart L., Bon-Saint-Côme A., Debelleix X., de Sèze M., Joseph P., et.al., (2001). Rehabilitation of postural disturbances of hemiplegic patients by using trunk control retraining during exploratory exercises. Archives of Physical Medicine and Rehabilitation, 82(6), 793–800. pmid:11387585
- 35. Rydwik E., Eliasson S., & Akner G. (2006). The effect of exercise of the affected foot in stroke patients-a randomized controlled pilot trial. Clinical Rehabilitation, 20(8), 645–655. pmid:16944822
- 36. Bagley P., Hudson M., Forster A., Smith J., & Young J. (2005). A randomized trial evaluation of the oswestry standing frame for patients after stroke. Clinical Rehabilitation, 19(4), 354–364. pmid:15929503
- 37. Franceschini M., Carda S., Agosti M., Antenucci R., Malgrati D., Cisari C., et.al., (2009). Walking after stroke: What does treadmill training with body weight support add to overground gait training in patients early after stroke?: A single-blind, randomized, controlled trial. Stroke, 40(9), 3079–3085. pmid:19556526
- 38. Masiero S., Celia A., Rosati G., & Armani M. (2007). Robotic-assisted rehabilitation of the upper limb after acute stroke. Archives of Physical Medicine and Rehabilitation, 88(2), 142–149. pmid:17270510
- 39. Ng M. F., Tong R. K., & Li L. S. (2008). A pilot study of randomized clinical controlled trial of gait training in subacute stroke patients with partial body-weight support electromechanical gait trainer and functional electrical stimulation: Six-month follow-up. Stroke, 39(1), 154–160. doi:STROKEAHA.107.495705 [pii] pmid:18006861
- 40. Rabadi M., Galgano M., Lynch D., Akerman M., Lesser M., & Volpe B. (2008). A pilot study of activity-based therapy in the arm motor recovery post stroke: A randomized controlled trial. Clinical Rehabilitation, 22(12), 1071–1082. pmid:19052246
- 41. Wiart L., Saint Côme A. B., Debelleix X., Petit H., Joseph P. A., Mazaux J. M., et.al., (1997). Unilateral neglect syndrome rehabilitation by trunk rotation and scanning training. Archives of Physical Medicine and Rehabilitation, 78(4), 424–429. pmid:9111464
- 42. Raglio A., Zaliani A., Baiardi P., Bossi D., Sguazzin C., Capodaglio E., et.al., (2017). Active music therapy approach for stroke patients in the post-acute rehabilitation. Neurological Sciences, 38(5), 893–897. pmid:28138867
- 43. Johansson B. B., Haker E., von Arbin M., Britton M., Langstrom G., Terent A. Swedish Collaboration on Sensory Stimulation After Stroke. (2001). Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: A randomized, controlled trial. Stroke, 32(3), 707–713. pmid:11239191
- 44. Macdonell R. A., Triggs W., Leikauskas J., Bourque M., Robb K., Day B., et.al.,(1994). Functional electrical stimulation to the affected lower limb and recovery after cerebral infarction. Journal of Stroke and Cerebrovascular Diseases, 4(3), 155–160. pmid:26486052
- 45. Sonde L., Gip C., Ferneaus S., Nilsson C., & Viitanen M. (1998). Stimulation with low frequency (1.7 hz) transcutaneous electric nerve stimulation (low-tens) increases motor function of the post-stroke paretic arm. Scandinavian Journal of Rehabilitation Medicine, 30(2), 95–100. pmid:9606771
- 46. Sonde L., Kalimo H., Fernaeus S., & Viitanen M. (2000). Low TENS treatment on post-stroke paretic arm: A three-year follow-up. Clinical Rehabilitation, 14(1), 14–19. pmid:10688340
- 47. Walker M., Drummond A., & Lincoln N. (1996). Evaluation of dressing practice for stroke patients after discharge from hospital: A crossover design study. Clinical Rehabilitation, 10(1), 23–31.
- 48. Sackley C., Wade D. T., Mant D., Atkinson J. C., Yudkin P., Cardoso K., et.al., (2006). Cluster randomized pilot controlled trial of an occupational therapy intervention for residents with stroke in UK care homes. Stroke, 37(9), 2336–2341. doi:01.STR.0000237124.20596.92 [pii] pmid:16888263
- 49. Chiu C. W., & Man D. W. (2004). The effect of training older adults with stroke to use home-based assistive devices. OTJR: Occupation, Participation and Health, 24(3), 113–120.
- 50. Corr S., & Bayer A. (1995). Occupational therapy for stroke patients after hospital discharge—a randomized controlled trial. Clinical Rehabilitation, 9(4), 291–296.
- 51. Donkervoort M., Dekker J., Stehmann-Saris F. C., & Deelman B. G. (2001). Efficacy of strategy training in left hemisphere stroke patients with apraxia: A randomised clinical trial. Neuropsychological Rehabilitation, 11(5), 549–566.
- 52. Gilbertson L., Langhorne P., Walker A., Allen A., & Murray G. D. (2000). Domiciliary occupational therapy for patients with stroke discharged from hospital: Randomised controlled trial. BMJ (Clinical Research Ed.), 320(7235), 603–606.
- 53. Jongbloed L., Stacey S., & Brighton C. (1989). Stroke rehabilitation: Sensorimotor integrative treatment versus functional treatment. American Journal of Occupational Therapy, 43(6), 391–397. pmid:2741997
- 54. Landi F., Cesari M., Onder G., Tafani A., Zamboni V., & Cocchi A. (2006). Effects of an occupational therapy program on functional outcomes in older stroke patients. Gerontology, 52(2), 85–91. doi:90953 [pii] pmid:16508315
- 55. Logan P., Ahern J., Gladman J., & Lincoln N. (1997). A randomized controlled trial of enhanced social service occupational therapy for stroke patients. Clinical Rehabilitation, 11(2), 107–113. pmid:9199862
- 56. Logan P. A., Gladman J. R., Avery A., Walker M. F., Dyas J., & Groom L. (2004). Randomised controlled trial of an occupational therapy intervention to increase outdoor mobility after stroke. BMJ (Clinical Research Ed.), 329(7479), 1372–1375. doi:bmj.38264.679560.8F [pii]
- 57. Parker C., Gladman J. R., Drummond A. E., Dewey M., Lincoln N., Barer D., et.al., (2001). A multicentre randomized controlled trial of leisure therapy and conventional occupational therapy after stroke. Clinical Rehabilitation, 15(1), 42–52. pmid:11237160
- 58. Walker M., Gladman J., Lincoln N., Siemonsma P., & Whiteley T. (1999). Occupational therapy for stroke patients not admitted to hospital: A randomised controlled trial. The Lancet, 354(9175), 278–280.
- 59. Mizuno K., Tsuji T., Takebayashi T., Fujiwara T., Hase K., & Liu M. (2011). Prism adaptation therapy enhances rehabilitation of stroke patients with unilateral spatial neglect: A randomized, controlled trial. Neurorehabilitation and Neural Repair, 25(8), 711–720. pmid:21700922
- 60. Kalra L., Perez I., Gupta S., & Wittink M. (1997). The influence of visual neglect on stroke rehabilitation. Stroke, 28(7), 1386–1391. pmid:9227688
- 61. Tsang M., Sze K., & Fong K. (2009). Occupational therapy treatment with right half-field eye-patching for patients with subacute stroke and unilateral neglect: A randomised controlled trial. Disability and Rehabilitation, 31(8), 630–637. pmid:19360499
- 62. Dickstein R., Hocherman S., Pillar T., & Shaham R. (1986). Stroke rehabilitation: Three exercise therapy approaches. Physical Therapy, 66(8), 1233–1238. pmid:3737695
- 63. Duncan P., Richards L., Wallace D., Stoker-Yates J., Pohl P., Luchies C., et.al., (1998). A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke. Stroke, 29(10), 2055–2060. pmid:9756581
- 64. Askim T., Morkved S., Engen A., Roos K., Aas T., & Indredavik B. (2010). Effects of a community-based intensive motor training program combined with early supported discharge after treatment in a comprehensive stroke unit: A randomized, controlled trial. Stroke, 41(8), 1697–1703. pmid:20558830
- 65. Duncan P., Studenski S., Richards L., Gollub S., Lai S. M., Reker D., et.al., (2003). Randomized clinical trial of therapeutic exercise in subacute stroke. Stroke, 34(9), 2173–2180. pmid:12920254
- 66. Studenski S., Duncan P. W., Perera S., Reker D., Lai S. M., & Richards L. (2005). Daily functioning and quality of life in a randomized controlled trial of therapeutic exercise for subacute stroke survivors. Stroke, 36(8), 1764–1770. doi:01.STR.0000174192.87887.70 [pii] pmid:16040590
- 67. Galvin R., Cusack T., O'Grady E., Murphy T. B., & Stokes E. (2011). Family-mediated exercise intervention (FAME): Evaluation of a novel form of exercise delivery after stroke. Stroke, 42(3), 681–686. pmid:21233462
- 68. Gelber D. A., Josefczyk B., Herrman D., Good D. C., & Verhulst S. J. (1995). Comparison of two therapy approaches in the rehabilitation of the pure motor hemiparetic stroke patient. Journal of Neurologic Rehabilitation, 9(4), 191–196.
- 69. Glasgow Augmented Physiotherapy Study Group. (2004). Can augmented physiotherapy input enhance recovery of mobility after stroke? A randomized controlled trial. Clinical Rehabilitation, 18(5), 529. pmid:15293487
- 70. Green J., Forster A., Bogle S., & Young J. (2002). Physiotherapy for patients with mobility problems more than 1 year after stroke: A randomised controlled trial. The Lancet, 359(9302), 199–203.
- 71. Kwakkel G., Wagenaar R. C., Twisk J. W., Lankhorst G. J., & Koetsier J. C. (1999). Intensity of leg and arm training after primary middle-cerebral-artery stroke: A randomised trial. The Lancet, 354(9174), 191–196.
- 72. Kim S. M., Han E. Y., Kim B. R., & Hyun C. W. (2016). Clinical application of circuit training for subacute stroke patients: a preliminary study. Journal of physical therapy science, 28(1), 169 pmid:26957751
- 73. Langhammer B., & Stanghelle J. K. (2000). Bobath or motor relearning programme? A comparison of two different approaches of physiotherapy in stroke rehabilitation: A randomized controlled study. Clinical Rehabilitation, 14(4), 361–369. pmid:10945420
- 74. Langhammer B., & Stanghelle J. K. (2003). Bobath or motor relearning programme? A follow-up one and four years post stroke. Clinical Rehabilitation, 17(7), 731–734. pmid:14606738
- 75. Lincoln N. B., Parry R. H., & Vass C. D. (1999). Randomized, controlled trial to evaluate increased intensity of physiotherapy treatment of arm function after stroke. Stroke, 30(3), 573–579. pmid:10066854
- 76. Morris J. H., van Wijck F., Joice S., Ogston S. A., Cole I., & MacWalter R. S. (2008). A comparison of bilateral and unilateral upper-limb task training in early poststroke rehabilitation: A randomized controlled trial. Archives of Physical Medicine and Rehabilitation, 89(7), 1237–1245. pmid:18586126
- 77. Sivenius J., Pyorala K., Heinonen O. P., Salonen J. T., & Riekkinen P. (1985). The significance of intensity of rehabilitation of stroke—a controlled trial. Stroke, 16(6), 928–931. pmid:3911506
- 78. Sunderland A., Tinson D. J., Bradley E. L., Fletcher D., Langton Hewer R., & Wade D. T. (1992). Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial. Journal of Neurology, Neurosurgery, and Psychiatry, 55(7), 530–535. pmid:1640226
- 79. van Vliet P. M., Lincoln N. B., & Foxall A. (2005). Comparison of bobath based and movement science based treatment for stroke: A randomised controlled trial. Journal of Neurology, Neurosurgery, and Psychiatry, 76(4), 503–508. doi:76/4/503 [pii] pmid:15774435
- 80. Wade D. T., Collen F. M., Robb G. F., & Warlow C. P. (1992). Physiotherapy intervention late after stroke and mobility. BMJ (Clinical Research Ed.), 304(6827), 609–613.
- 81. Lincoln N. B., & Flannaghan T. (2003). Cognitive behavioral psychotherapy for depression following stroke: A randomized controlled trial. Stroke, 34(1), 111–115. pmid:12511760
- 82. Braun S. M., Beurskens A. J., Kleynen M., Oudelaar B., Schols J. M., & Wade D. T. (2012). A multicenter randomized controlled trial to compare subacute ‘treatment as usual’with and without mental practice among persons with stroke in dutch nursing homes. Journal of the American Medical Directors Association, 13(1), 85. e1–85. e7.
- 83. Bradley L., Hart B. B., Mandana S., Flowers K., Riches M., & Sanderson P. (1998). Electromyographic biofeedback for gait training after stroke. Clinical Rehabilitation, 12(1), 11–22. pmid:9549021
- 84. Clark M. S., Rubenach S., & Winsor A. (2003). A randomized controlled trial of an education and counselling intervention for families after stroke. Clinical Rehabilitation, 17(7), 703–712. pmid:14606735
- 85. Ertel K., Glymour M., Glass T., & Berkman L. (2007). Frailty modifies effectiveness of psychosocial intervention in recovery from stroke. Clinical Rehabilitation, 21(6), 511–522. pmid:17613582
- 86. Watkins C. L., Auton M. F., Deans C. F., Dickinson H. A., Jack C. I., Lightbody C. E., et.al., (2007). Motivational interviewing early after acute stroke: A randomized, controlled trial. Stroke, 38(3), 1004–1009. doi:01.STR.0000258114.28006.d7 [pii] pmid:17303766
- 87. Glass T. A., Berkman L. F., Hiltunen E. F., Furie K., Glymour M. M., Fay M. E., et.al., (2004). The families in recovery from stroke trial (FIRST): Primary study results. Psychosomatic Medicine, 66(6), 889–897. pmid:15564354
- 88. Forster A., & Young J. (1996). Specialist nurse support for patients with stroke in the community: A randomised controlled trial. BMJ (Clinical Research Ed.), 312(7047), 1642–1646.
- 89. Guidetti S., Andersson K., Andersson M., Tham K., & Koch L. V. (2010). Client-centred self-care intervention after stroke: A feasibility study. Scandinavian Journal of Occupational Therapy, 17(4), 276–285. pmid:20187757
- 90. Guidetti S., & Ytterberg C. (2011). A randomised controlled trial of a client-centred self-care intervention after stroke: A longitudinal pilot study. Disability and Rehabilitation, 33(6), 494–503. pmid:20597629
- 91. Johnston M., Bonetti D., Joice S., Pollard B., Morrison V., Francis J. J., et.al., (2007). Recovery from disability after stroke as a target for a behavioural intervention: Results of a randomized controlled trial. Disability and Rehabilitation, 29(14), 1117–1127. pmid:17612998
- 92. Nir Z., Zolotogorsky Z., & Sugarman H. (2004). Structured nursing intervention versus routine rehabilitation after stroke. American Journal of Physical Medicine & Rehabilitation, 83(7), 522–529. doi:00002060-200407000-00005 [pii]
- 93. Rodgers H., Atkinson C., Bond S., Suddes M., Dobson R., & Curless R. (1999). Randomized controlled trial of a comprehensive stroke education program for patients and caregivers. Stroke, 30(12), 2585–2591. pmid:10582982
- 94. Smith J., Forster A., & Young J. (2004). A randomized trial to evaluate an education programme for patients and carers after stroke. Clinical Rehabilitation, 18(7), 726–736. pmid:15573828
- 95. Lee G. (2013). Effects of training using video games on the muscle strength, muscle tone, and activities of daily living of chronic stroke patients. Journal of Physical Therapy Science, 25(5), 595–597. pmid:24259810
- 96. Barrett J., Watkins C., Plant R., Dickinson H., Clayton L., Sharma A., et.al.(2001). The COSTAR wheelchair study: A two-centre pilot study of self-propulsion in a wheelchair in early stroke rehabilitation. Clinical Rehabilitation, 15(1), 32–41. pmid:11237159
- 97. Teasell R. W., Foley N. C., Bhogal S. K., & Speechley M. R. (2003). An evidence-based review of stroke rehabilitation. Topics in Stroke Rehabilitation, 10(1), 29–58. pmid:12970830
- 98. Veerbeek J. M., van Wegen E., van Peppen R., van der Wees P.J., Hendriks E., Rietberg M., et. al. (2014). What is the evidence for physical therapy poststroke? A systematic review and meta-analysis. PloS One, 9(2), e87987. pmid:24505342
- 99. Langhorne P., Bernhardt J., & Kwakkel G. (2011). Stroke rehabilitation. The Lancet, 377(9778), 1693–1702.
- 100. Bradt J., Magee W.L., Dileo C., Wheeler B.L., McGilloway E. (2010) Music therapy for acquired brain injury. Cochrane Database Syst. Rev 7:CD006787
- 101. Särkämö T., Tervaniemi M., Laitinen S., Forsblom A., Soinila S., Mikkonen M., et.al., (2008). Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. Brain 131:866–876 pmid:18287122
- 102. Schneider S., Schonle P.W., Altenmuller E.& Munte T.F., (2007). Using musical instruments to improve motor skill recovery following a stroke. J Neurol 254(1339):46.
- 103. Vafadar A. K., Côté J. N., & Archambault P. S. (2015). Effectiveness of functional electrical stimulation in improving clinical outcomes in the upper arm following stroke: A systematic review and meta-analysis. BioMed Research International, 2015
- 104. Bowen A., Lincoln N., & Dewey M. (2007). Cognitive rehabilitation for spatial neglect following stroke. Cochrane Database Syst Rev, 2
- 105. Laver K. E., George S., Thomas S., Deutsch J. E., & Crotty M. (2015). Virtual reality for stroke rehabilitation. The Cochrane Library,
- 106. Boutron I., Guittet L., Estellat C., Moher D., Hróbjartsson A., & Ravaud P. (2007). Reporting methods of blinding in randomized trials assessing nonpharmacological treatments. PLoS medicine, 4(2), e61. pmid:17311468
- 107. Paterson C., & Dieppe P. (2005). Characteristic and incidental (placebo) effects in complex interventions such as acupuncture. BMJ: British Medical Journal, 330(7501), 1202. pmid:15905259