Abstract: We included nine trials about CME, of which six trials with 333 patient-caregiver couples were included in the meta-analysis. The small number of studies, participants, and a variety of outcome measures rendered summarising and combining of data in meta-analysis difficult. In addition, in some studies, CME was the only intervention (CME-core), whereas in other studies, caregivers provided another, existing intervention, such as constraint-induced movement therapy. For trials in the latter category, it was difficult to separate the effects of CME from the effects of the other intervention. We found no significant effect of CME on basic ADL when pooling all trial data post intervention (4 studies; standardised mean difference (SMD) 0.21, 95% confidence interval (CI) -0.02 to 0.44; P = 0.07; moderate-quality evidence) or at follow-up (2 studies; mean difference (MD) 2.69, 95% CI -8.18 to 13.55; P = 0.63; low-quality evidence). In addition, we found no significant effects of CME on extended ADL at post intervention (two studies; SMD 0.07, 95% CI -0.21 to 0.35; P = 0.64; low-quality evidence) or at follow-up (2 studies; SMD 0.11, 95% CI -0.17 to 0.39; P = 0.45; low-quality evidence). Caregiver burden did not increase at the end of the intervention (2 studies; SMD -0.04, 95% CI -0.45 to 0.37; P = 0.86; moderate-quality evidence) or at follow-up (1 study; MD 0.60, 95% CI -0.71 to 1.91; P = 0.37; very low-quality evidence). At the end of intervention, CME significantly improved the secondary outcomes of standing balance (3 studies; SMD 0.53, 95% CI 0.19 to 0.87; P = 0.002; low-quality evidence) and quality of life (1 study; physical functioning: MD 12.40, 95% CI 1.67 to 23.13; P = 0.02; mobility: MD 18.20, 95% CI 7.54 to 28.86; P = 0.0008; general recovery: MD 15.10, 95% CI 8.44 to 21.76; P < 0.00001; very low-quality evidence). At follow-up, we found a significant effect in favour of CME for Six-Minute Walking Test distance (1 study; MD 109.50 m, 95% CI 17.12 to 201.88; P = 0.02; very low-quality evidence). We also found a significant effect in favour of the control group at the end of intervention, regarding performance time on the Wolf Motor Function test (2 studies; MD -1.72, 95% CI -2.23 to -1.21; P < 0.00001; low-quality evidence). We found no significant effects for the other secondary outcomes (i.e. patient: motor impairment, upper limb function, mood, fatigue, length of stay and adverse events; caregiver: mood and quality of life). In contrast to the primary analysis, sensitivity analysis of CME-core showed a significant effect of CME on basic ADL post intervention (2 studies; MD 9.45, 95% CI 2.11 to 16.78; P = 0.01; moderate-quality evidence). The methodological quality of the included trials and variability in interventions (e.g. content, timing, and duration), affected the validity and generalisability of these observed results. There is very low- to moderate-quality evidence that CME may be a valuable intervention to augment the pallet of therapeutic options for stroke rehabilitation. Included studies were small, heterogeneous, and some trials had an unclear or high risk of bias. Future high-quality research should determine whether CME interventions are (cost-)effective.

Plain-language summary: We identified nine clinical trials to October 2015, which all investigated some form of caregiver-mediated exercises compared with usual care, no treatment (intervention), or another intervention that was not caregiver-mediated. We included 333 patient-caregiver couples in the review. We found trials in which caregiver-mediated exercises themselves were the studied subject (called CME-core). In addition, we found trials in which the caregiver was the provider of another, already existing intervention. In the latter category, it was difficult to separate the effect of caregiver-mediated exercises from the effect of the other intervention. We found evidence that caregiver-mediated exercises could have a positive effect on patients' standing balance (low-quality evidence) and quality of life (very low-quality evidence) directly after the intervention. In the long term, we found very low-quality evidence for a positive effect on walking distance. For speed of use of the arm and hand, we found low-quality evidence in favour of the control group. We found no significant side effects or beneficial effects on caregiver strain; we judged the quality of this evidence as moderate (after intervention) to very low (long term). Furthermore, we found no significant effects for basic activities of daily living, such as dressing and bathing, after intervention (moderate-quality evidence) or follow-up (low-quality evidence). In addition, we found no significant effects for extended activities of daily living, such as cooking and gardening, after intervention or at follow-up (both low-quality evidence). In the CME-core analysis, we found moderate-quality evidence for a positive effect of caregiver-mediated exercises for basic activities of daily living. It can be concluded that caregiver-mediated exercises may be a promising form of therapy to add to usual care. The number of included trials was small and the level of evidence was of very low to moderate quality. Therefore, results should be interpreted with caution.