Exercise-based cardiac rehabilitation for adult patients with an implantable cardioverter defibrillator

Review question: We reviewed the benefits and harms of exercise-based cardiac rehabilitation programmes in adults who have been treated with an implantable cardioverter defibrillator from any cause. Background: An implantable cardioverter defibrillator is a very effective device that prevents sudden cardiac death. This is done by the use of either antitachycardia pacing, high-voltage shock therapy, or both. In spite of the potential mortality benefits, patients may also experience a negative impact on their health-related quality of life, increased readmission to hospital and healthcare facilities, loss of productivity and employment earnings, and increased morbidity and mortality. Exercise-based cardiac rehabilitation may benefit patients with an implantable cardioverter defibrillator. Study characteristics: We searched for randomised controlled trials (experiments in which participants are randomly allocated to an experimental intervention compared with a control intervention) that investigated exercise-based interventions compared with no exercise intervention control. We found eight trials published from 2004 to 2017 with a total of 1730 participants. Two trials did not report on funding and one trial reported funding from industry. The evidence is current to 30 August 2018. Key results: The review showed no evidence of an impact on the risk of death, harmful side effects or having antitachycardia pacing or shock therapy when comparing the exercise intervention to the control. There was also little or no evidence of a difference on health-related quality of life. However, there was an improvement in exercise capacity in favour of the exercise group. Quality of the evidence: The quality of the evidence ranged from moderate to very low for all outcomes. The number of events was low, it was possible for people in the trials to know to which intervention group they were randomised, the reporting of the results was not complete in some trials, and for some outcomes, the results varied across trials. These considerations limited our confidence in the overall results of the review. Conclusion: Further adequately powered and well-conducted randomised trials are needed to assess the impact of exercise-based cardiac rehabilitation in adults with an implantable cardioverter defibrillator

Exercise-based cardiac rehabilitation for adults with atrial fibrillation

BACKGROUND:Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria. OBJECTIVES:To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS:We searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and three clinical trial registers on 14 July 2016. We also checked the bibliographies of relevant systematic reviews identified by the searches. We imposed no language restrictions. SELECTION CRITERIA:We included randomised controlled trials (RCT) that investigated exercise-based interventions compared with any type of no-exercise control. We included trials that included adults aged 18 years or older with atrial fibrillation, or post-treatment for atrial fibrillation. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data. We assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. We performed meta-analyses using fixed-effect and random-effects models; we used standardised mean differences where different scales were used for the same outcome. We assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the 'Summary of findings' table. MAIN RESULTS:We included six RCTs with a total of 421 patients with various types of atrial fibrillation. All trials were conducted between 2006 and 2016, and had short follow-up (eight weeks to six months). Risks of bias ranged from high risk to low risk.The exercise-based programmes in four trials consisted of both aerobic exercise and resistance training, in one trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training.For mortality, very low-quality evidence from six trials suggested no clear difference in deaths between the exercise and no-exercise groups (relative risk (RR) 1.00, 95% confidence interval (CI) 0.06 to 15.78; participants = 421; I² = 0%; deaths = 2). Very low-quality evidence from five trials suggested no clear difference between groups for serious adverse events (RR 1.01, 95% CI 0.98 to 1.05; participants = 381; I² = 0%; events = 8). Low-quality evidence from two trials suggested no clear difference in health-related quality of life for the Short Form-36 (SF-36) physical component summary measure (mean difference (MD) 1.96, 95% CI -2.50 to 6.42; participants = 224; I² = 69%), or the SF-36 mental component summary measure (MD 1.99, 95% CI -0.48 to 4.46; participants = 224; I² = 0%). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by six minute walking test, or ergospirometry testing measuring VO2 peak. We found moderate-quality evidence from two studies that exercise-based rehabilitation increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95% CI 1.37 to 6.15; participants = 208; I² = 0%); and very low-quality evidence from four studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the six-minute walking test (MD 75.76, 95% CI 14.00 to 137.53; participants = 272; I² = 85%). When we combined the different assessment tools for exercise capacity, we found very low-quality evidence from six trials that exercise-based rehabilitation increased exercise capacity more than no exercise (standardised mean difference (SMD) 0.86, 95% CI 0.46 to 1.26; participants = 359; I² = 65%). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low. AUTHORS' CONCLUSIONS:Due to few randomised patients and outcomes, we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events. The evidence showed no clinically relevant effect on health-related quality of life. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, we could not be certain of the magnitude of the effect. Future high-quality randomised trials are needed to assess the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes

An Internet-based emotion regulation intervention versus no intervention for non-suicidal self-injury in adolescents:a statistical analysis plan for a feasibility randomised clinical trial

BACKGROUND: Non-suicidal self-injury (NSSI) has a lifetime prevalence of 17% in adolescents in the general population and up to 74% in adolescents with psychiatric disorders. NSSI is one of the most important predictors of later suicidal behaviour and death by suicide. The TEENS feasibility trial was initiated to assess the feasibility and safety of Internet-based Emotion Regulation Individual Therapy for Adolescents (ERITA) as an add-on to treatment as usual in 13–17-year-old patients with NSSI referred to the Child and Adolescent Mental Health Services. METHODS: The TEENS feasibility trial is a randomised clinical trial with a parallel-group design. The trial intervention is an 11-week online therapy which is tested as an add-on to treatment as usual versus treatment as usual. The primary feasibility outcomes are the fraction of participants who (1) completed 12 weeks of follow-up interview or assessment, (2) consented to inclusion and randomisation out of all eligible participants, and (3) were compliant with the experimental intervention, assessed as completion of at least six out of eleven modules in the programme. Since this is a feasibility trial, we did not predefine a required sample size. The exploratory clinical outcome, the frequency of NSSI episodes, assessed using Deliberate Self-Harm Inventory – Youth version (DSHI-Y), at the end of intervention, is planned to be the future primary outcome in a larger pragmatic definitive randomised clinical trial. After completion of the feasibility trial, blinded data will be analysed by two independent statisticians blinded to the intervention, where ‘A’ and ‘B’ refer to the two groups. A third party will compare these reports, and discrepancies will be discussed. The statistical report with the analyses chosen for the manuscript is being tracked using a version control system, and both statistical reports will be published as a supplementary material. Based on the final statistical report, two blinded conclusions will be drawn by the steering group. DISCUSSION: We present a pre-defined statistical analysis plan for the TEENS feasibility trial, which limits bias, p-hacking, data-driven interpretations. This statistical analysis plan is accompanied by a pre-programmed version-controlled statistical report with simulated data, which increases transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.govNCT04243603. Registered on 28 January 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05406-2

Exercise-based cardiac rehabilitation for adults after heart valve surgery:review

Exercise-based cardiac rehabilitation may benefit heart valve surgery patients. We conducted a systematic review to assess the evidence for the use of exercise-based intervention programmes following heart valve surgery.To assess the benefits and harms of exercise-based cardiac rehabilitation compared with no exercise training intervention, or treatment as usual, in adults following heart valve surgery. We considered programmes including exercise training with or without another intervention (such as a psycho-educational component).We searched: the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS (Bireme); and Conference Proceedings Citation Index-S (CPCI-S) on Web of Science (Thomson Reuters) on 23 March 2015. We handsearched Web of Science, bibliographies of systematic reviews and trial registers (ClinicalTrials.gov, Controlled-trials.com, and The World Health Organization International Clinical Trials Registry Platform).We included randomised clinical trials that investigated exercise-based interventions compared with no exercise intervention control. The trial participants comprised adults aged 18 years or older who had undergone heart valve surgery for heart valve disease (from any cause) and received either heart valve replacement, or heart valve repair.Two authors independently extracted data. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. We used the GRADE approach to assess the quality of evidence. We sought to assess the risk of random errors with trial sequential analysis.We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias.There was insufficient evidence at 3 to 6 months follow-up to judge the effect of exercise-based cardiac rehabilitation compared to no exercise on mortality (RR 4.46 (95% confidence interval (CI) 0.22 to 90.78); participants = 104; studies = 1; quality of evidence: very low) and on serious adverse events (RR 1.15 (95% CI 0.37 to 3.62); participants = 148; studies = 2; quality of evidence: very low). Included trials did not report on health-related quality of life (HRQoL), and the secondary outcomes of New York Heart Association class, left ventricular ejection fraction and cost. We did find that, compared with control (no exercise), exercise-based rehabilitation may increase exercise capacity (SMD -0.47, 95% CI -0.81 to -0.13; participants = 140; studies = 2, quality of evidence: moderate). There was insufficient evidence at 12 months follow-up for the return to work outcome (RR 0.55 (95% CI 0.19 to 1.56); participants = 44; studies = 1; quality of evidence: low). Due to limited information, trial sequential analysis could not be performed as planned.Our findings suggest that exercise-based rehabilitation for adults after heart valve surgery, compared with no exercise, may improve exercise capacity. Due to a lack of evidence, we cannot evaluate the impact on other outcomes. Further high-quality randomised clinical trials are needed in order to assess the impact of exercise-based rehabilitation on patient-relevant outcomes, including mortality and quality of life

SheppHeartCABG trial-comprehensive early rehabilitation after coronary artery bypass grafting:a protocol for a randomised clinical trial

INTRODUCTION: Patients undergoing coronary artery bypass graft surgery often experience a range of symptoms. Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation have a positive physiological and psychological effect in early outpatient rehabilitation. The SheppHeartCABG trial will investigate the effect of early comprehensive rehabilitation in early phase rehabilitation versus usual care. The aim of this paper is to present the protocol for the SheppHeartCABG trial. METHODS/ANALYSIS: SheppHeartCABG is an investigator-initiated randomised clinical superiority trial with blinded outcome assessment, employing 1:1 central randomisation to rehabilitation plus usual care versus usual care alone. On the basis of a sample size calculation, 326 patients undergoing coronary artery bypass grafting will be included from two clinical sites. All patients receive usual care and patients allocated to the experimental intervention follow 4 weeks rehabilitation consisting of an exercise programme, psycho-educative consultations and a compact mindfulness programme. The primary outcome is physical function measured by the 6-min walk test. The secondary outcomes are mental health and physical activity measured by the Medical Outcome Study Short Form (SF-12), anxiety and depression measured by the Hospital Anxiety and Depression Scale questionnaire, physical, emotional and global scores by the HeartQoL questionnaire, sleep measured by the Pittsburgh Sleep Quality Index, pain measured by the Örebro Musculoskeletal Screening Questionnaire and muscle endurance measured by the sit-to-stand test. A number of explorative analyses will also be conducted. ETHICS AND DISSEMINATION: SheppHeartCABG is approved by the regional ethics committee (no. H-4-2014-109) and the Danish Data Protection Agency (no. 30-1309) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form. Positive, neutral and negative results of the trial will be submitted to international peer-reviewed journals. Furthermore, results will be presented at national and international conferences relevant to the subject fields. TRIAL REGISTRATION NUMBER: NCT02290262; pre-results

Detailed statistical analysis plan for the Danish Palliative care trial (DanPaCT)

Acknowledgements We wish to thank the students who sent out the questionnaires, who entered and compared all data, help with data management, made material blind to the investigators, and were/will be outcome assessors of interventions given. They were: Nicla Rohde Christensen, Ellen Lundorff, Marc Klee Olsen, Charlotte Lund Rasmussen, and Nete Skjødt. This work was funded by the Tryg Foundation [journal number 7-10-0838A] and the Danish Cancer Society [journal number R16-A695]. Other than funding the trial, the funding body had no role in the design, conduct, analysis, or reporting of the present trial.Peer reviewedPublisher PD

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. Methods: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded

The effect of integrated cardiac rehabilitation versus treatment as usual for atrial fibrillation patients treated with ablation:the randomised CopenHeartRFA trial protocol

INTRODUCTION: Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components. AIM: To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation. METHODS AND ANALYSIS DESIGN: The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO(2) peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group. ETHICS AND DISSEMINATION: The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01523145

Selenium supplementation for patients with Graves' hyperthyroidism (the GRASS trial):Study protocol for a randomized controlled trial

BACKGROUND: Graves’ hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects on autoimmune hypothyroidism and on Graves' orbitopathy, but the effects of selenium on Graves' hyperthyroidism is unknown. We hypothesize that adjuvant selenium may be beneficial in the treatment of Graves' hyperthyroidism. The objective is to investigate if selenium supplementation plus standard treatment with anti-thyroid drugs versus standard treatment with anti-thyroid drugs will lead to a decrease in anti-thyroid drug treatment failure (that is, failure to remain euthyroid, without further treatment, one year after cessation of anti-thyroid drug treatment), faster and longer lasting remission (that is, anti-thyroid drug treatment success), and improved quality of life in patients with Graves’ hyperthyroidism. METHODS AND DESIGN: The trial is an investigator-initiated, randomised, blinded, multicentre clinical trial. Inclusion criteria are: age 18 years or older; diagnosis of active Graves' hyperthyroidism within the last two months; and informed consent. Exclusion criteria are major co-morbidity; previous radioactive iodine treatment; ongoing anti-thyroid drug treatment for more than two months; treatment with immunomodulatory drugs; known allergy towards the components in the selenium and placebo pills; pregnancy or breast-feeding; and intake of selenium supplementation above 70 μg per day. We plan to include 492 participants, randomised (1:1) to two tablets of 100 μg selenium once daily for the 24 to 30 months intervention period versus two identical placebo tablets once daily. The primary outcome is the proportion of participants with anti-thyroid drug treatment failure (see above) at the end of the intervention period (24 to 30 months). Secondary outcomes are: thyroid-specific quality of life during the first year after randomisation; level of thyroid stimulating hormone-receptor antibodies at 18 months after randomisation and at the end of the intervention period (24 to 30 months); hyperthyroid symptoms during the first year after randomisation; eye symptoms during the first year after randomisation, and at the end of the intervention period (24 to 30 months); adverse reactions during the intervention period; and serious adverse events during the intervention period. DISCUSSION: It was of great importance to the initiators of this trial, that the results would be directly applicable to daily clinical practice. Therefore, it was designed as a pragmatic trial: the patients follow their usual treatment at their usual hospitals. In order to still collect high quality data on the clinical course and quality of life, an elaborate trial management system was designed to keep track of patient input, need for trial personnel input and action, and to collect data from medical chart systems. Meticulous follow-up on missing responses to the QoL measurements has been incorporated into the system, to minimise missing quality of life data. Monitoring of adverse reactions and events is achieved by thorough instruction of the participants, surveillance of patient-reported outcomes, and integration with national databases regarding hospitalizations. A very long intervention period was necessary, since patients are not considered in remission until one year after stopping anti-thyroid drugs. Usually, patients are treated for 12 to 18 months with anti-thyroid drugs, yielding a total intervention period of 24 to 30 months. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01611896