Abstract: Eighteen studies (20 reports) involving a total of 933 participants with COPD, chronic respiratory disease, chronic heart failure, and/or thoracic cancer met the inclusion criteria for this update, an additional seven studies since the previous version of this review. All but one study that compared NMES to resistance training compared a programme of NMES to no treatment or placebo NMES. Most studies were conducted in a single centre and had a risk of bias arising from a lack of participant or assessor blinding and small study size. The quality of the evidence using GRADE comparing NMES to control was low for quadriceps muscle strength, moderate for occurrence of adverse events, and very low to low for all other secondary outcomes. We downgraded the quality of evidence ratings predominantly due to inconsistency among study findings and imprecision regarding estimates of effect. The included studies reported no serious adverse events and a low incidence of muscle soreness following NMES. NMES led to a statistically significant improvement in quadriceps muscle strength as compared to the control (12 studies; 781 participants; SMD 0.53, 95% confidence interval (CI) 0.19 to 0.87), equating to a difference of approximately 1.1 kg. An increase in muscle mass was also observed following NMES, though the observable effect appeared dependent on the assessment modality used (eight studies, 314 participants). Across tests of exercise performance, mean differences compared to control were statistically significant for the 6-minute walk test (seven studies; 317 participants; 35 m, 95% CI 14 to 56), but not for the incremental shuttle walk test (three studies; 434 participants; 9 m, 95% CI -35 to 52), endurance shuttle walk test (four studies; 452 participants; 64 m, 95% CI -18 to 146), or for cardiopulmonary exercise testing with cycle ergometry (six studies; 141 participants; 45 mL/minute, 95% CI -7 to 97). Limited data were available for other secondary outcomes, and we could not determine the most beneficial type of NMES programme. The overall conclusions have not changed from the last publication of this review, although we have included more data, new analyses, and an assessment of the quality of the evidence using the GRADE approach. NMES may be an effective treatment for muscle weakness in adults with advanced progressive disease, and could be considered as an exercise treatment for use within rehabilitation programmes. Further research is very likely to have an important impact on our confidence in the estimate of effect and may change the estimate. We recommend further research to understand the role of NMES as a component of, and in relation to, existing rehabilitation approaches. For example, studies may consider examining NMES as an adjuvant treatment to enhance the strengthening effect of programmes, or support patients with muscle weakness who have difficulty engaging with existing services.

Plain-language summary: We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. Overall, the quality of the evidence was low for the effect on thigh muscle strength and very low to moderate for the effects on other outcomes. There were problems with the design of some studies; often people taking part or assessors knew if they were receiving or testing NMES. In addition, the results for many outcomes were inconsistent or imprecise. This review suggests that NMES is a potentially effective treatment for muscle weakness in people with progressive diseases such as cancer, advanced chronic respiratory disease, and chronic heart failure, though the quality of the evidence is low. NMES might be considered for use within rehabilitation programmes. It was not possible to compare the effects of NMES to other forms of exercise, for example weight training, because the majority of studies compared NMES to a control group that received no treatment or a sham treatment. Further research is needed to understand the effect of NMES on the ability to exercise and quality of life.