Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses - the METSA systematic review.

BACKGROUND: Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis. METHODS: We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision. RESULTS: We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%). CONCLUSIONS: The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity. STUDY REGISTRATION: PROSPERO CRD42021273811.

Use of the EXOPULSE Mollii for severe ataxia in an adult male 4 months after cardiac arrest.

The EXOPULSE Mollii is designed to reduce spasticity through low-current electrical stimulation of major muscle groups. The effect on severe cerebellar ataxia has not been investigated. This case describes the use of the EXOPULSE Mollii in an adult male with severe cerebellar ataxia 4 months after cardiac arrest and ischaemic stroke. The patient used the suit in 15 of 19 possible sessions (78.9%). He improved in the sit-to-stand test, arm function test and 10 m walking test. He described improved visual focus, ability to speak and swallow. Improvements were maintained for 1 week after the last session. The EXOPULSE Mollii is relevant to consider in the early stages of inpatient rehabilitation for patients with severe ataxia, but further research is warranted.

Mapping physical activity patterns in hospitalised patients with moderate to severe acquired brain injury - MAP-ABI: Protocol for an observational study.

Introduction: The physical activity level in patients hospitalised for rehabilitation across multiple diagnoses is low. Moderate to severe acquired brain injury further reduces activity levels as impaired physical and cognitive functioning affect mobility independence. Therefore, supervised out-of-bed mobilisation and physical activity training are essential rehabilitation strategies. Few studies have measured the physical activity patterns in the early phases of rehabilitation after moderate to severe brain injury. Objectives: To map and quantify physical activity patterns in patients admitted to brain injury rehabilitation. Further, to investigate which factors are associated with activity and if the early physical activity level is associated with functional outcome at discharge. Methods: This observational study includes patients admitted to rehabilitation after moderate to severe acquired brain injury. Mobility and physical activity patterns are measured continuously during rehabilitation at two separate seven-day periods using a wearable activity tracker. Activity will be categorised into four levels and presented descriptively. Linear and logistic regression models will analyse associations between descriptive variables and activity levels. Discussion: This protocol describes an observational study investigating patients' mobility and physical activity patterns with moderate to severe acquired brain injury during in-hospital rehabilitation. The ability to increase the amount of mobilisation and physical activity in subgroups may have profound consequences on the rehabilitation outcome. Furthermore, data from this study may be used to inform a large variety of trials investigating physical rehabilitation interventions. (NCT05571462).

Effectiveness of physical activity monitors in adults: systematic review and meta-analysis.

OBJECTIVE: To estimate the effectiveness of physical activity monitor (PAM) based interventions among adults and explore reasons for the heterogeneity. DESIGN: Systematic review and meta-analysis. STUDY SELECTION: The electronic databases MEDLINE, Embase, SPORTDiscus, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on 4 June 2021. Eligible randomised controlled trials compared interventions in which adults received feedback from PAMs with control interventions in which no feedback was provided. No restrictions on type of outcome measurement, publication date, or language were applied. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were used to synthesise the results. The certainty of evidence was rated by the Grading of Recommendations Assessment and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: The three primary outcomes of interest were physical activity, moderate to vigorous physical activity, and sedentary time. RESULTS: 121 randomised controlled trials with 141 study comparisons, including 16 743 participants, were included. The PAM based interventions showed a moderate effect (standardised mean difference 0.42, 95% confidence interval 0.28 to 0.55) on physical activity, equivalent to 1235 daily steps; a small effect (0.23, 0.16 to 0.30) on moderate to vigorous physical activity, equivalent to 48.5 weekly minutes; and a small insignificant effect (-0.12, -0.25 to 0.01) on sedentary time, equal to 9.9 daily minutes. All outcomes favoured the PAM interventions. CONCLUSIONS: The certainty of evidence was low for the effect of PAM based interventions on physical activity and moderate for moderate to vigorous physical activity and sedentary time. PAM based interventions are safe and effectively increase physical activity and moderate to vigorous physical activity. The effect on physical activity and moderate to vigorous physical activity is well established but might be overestimated owing to publication bias. STUDY REGISTRATION: PROSPERO CRD42018102719.

Early head-up mobilisation versus standard care for patients with severe acquired brain injury: A systematic review with meta-analysis and Trial Sequential Analysis.

BACKGROUND: There is increasing focus on earlier rehabilitation in patients with traumatic or hypoxic brain injury or stroke. This systematic review evaluates the benefits and harms of early head-up mobilisation versus standard care in patients with severe acquired brain injury. METHODS: We searched Medline, CENTRAL, EMBASE, four other databases and 13 selected clinical trial registries until April 2020. Eligible randomised clinical trials compared early head-up mobilisation versus standard care in patients with severe acquired brain injury and were analysed conducting random- and fixed-effects meta-analyses and Trial Sequential Analysis (TSA). Certainty of evidence was assessed by GRADE. MAIN RESULTS: We identified four randomised clinical trials (total n = 385 patients) with severe acquired brain injury (stroke 86% and traumatic brain injury 13%). Two trials were at low risk and two at high risk of bias. We found no evidence of a difference between early mobilisation vs. standard care on mortality or poor functional outcome at end of the intervention (relative risk (RR) 1.19, 95% CI 0.93 to 1.53; I2 0%; very low certainty) or at maximal follow-up (RR 1.03, 95% CI 0.89 to 1.21; I2 0%; very low certainty). We found evidence against an effect on quality of life at maximal follow-up. The proportion of patients with at least one serious adverse event did not differ at end of intervention or at maximal follow-up. For most comparisons, TSA suggested that further trials are needed. CONCLUSIONS: We found no evidence of a difference between early mobilisation versus standard care for patients with severe acquired brain injury. Early mobilisation appeared not to exert a major impact on quality of life. This systematic review highlights the insufficient evidence in patients with severe brain injury, and no firm conclusions can be drawn from these data. TRIAL REGISTRATION: Protocol uploaded to PROSPERO: April 2018 (revised October 2018, CRD42018088790).

Feedback from physical activity monitors to enhance amount of physical activity in adults-a protocol for a systematic review and meta-analysis.

OBJECTIVE: The use of physical activity monitors (PAMs) in the adult population is increasing rapidly and previous systematic reviews are outdated. The objective of this systematic review and meta-analysis is to estimate the effect of PAM-based interventions on physical activity behavior in adults. Furthermore, the impact of intervention, study, and participants characteristics will be investigated. METHODS AND DESIGN: Randomized controlled trials and randomized cross-over trials including adult participants will be included if the study compares any PAM-based intervention where the participants receive feedback on their physical activity level measured by PAMs, to control interventions where participants do not receive feedback from PAMs. This protocol is detailed according to the recommendations of the Cochrane Handbook, and it is reported according to the preferred reporting items for systematic reviews and meta-analyses protocols statement. The results from the literature search will be presented in a PRISMA flow chart. The effects from individual studies will be summarized in a random effects meta-analysis and the impact of diagnosis of the participants, type of feedback, type of intervention, and control intervention will be investigated in stratified meta-analysis and meta-regressions analysis. The results on daily physical activity, moderate to vigorous physical activity, sedentary time, and adverse events will be presented in a summary of findings table. DISCUSSION: The results will be useful to researchers, policy makers, and health care professionals when the intention is to increase physical activity in the adult population. PROSPERO REGISTRATION: CRD42018102719.