Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg depression rating scale, the gold standard clinician rating scale : a meta-analysis of randomised placebo-controlled trials

It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument's poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS)

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

Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD:a randomised clinical trial

INTRODUCTION: Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. METHODS: 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. RESULTS: 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. DISCUSSION: Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation. TRIAL REGISTRATION NUMBER: NCT01614951; Pre-results

Level of sedation in critically ill adult patients : a protocol for a systematic review with meta-analysis and trial sequential analysis

Publisher Copyright: © 2022 BMJ Publishing Group. All rights reserved.Introduction It is standard of care to provide sedation to critically ill patients to reduce anxiety, discomfort and promote tolerance of mechanical ventilation. Given that sedatives can have differing effects based on a variety of patient and pharmacological characteristics, treatment approaches are largely based on targeting the level of sedation. The benefits of differing levels of sedation must be balanced against potential adverse effects including haemodynamic instability, causing delirium, delaying awakening and prolonging the time of mechanical ventilation and intensive care stay. This systematic review with meta-analysis aims to investigate the current evidence and compare the effects of differing sedation levels in adult critically ill patients. Methods and analyses We will conduct a systematic review based on searches of preidentified major medical databases (eg, MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify trials meeting inclusion criteria. We will include randomised clinical trials comparing any degree of sedation with no sedation and lighter sedation with deeper sedation for critically ill patients admitted to the intensive care unit. We will include aggregate data meta-analyses and trial sequential analyses. Risk of bias will be assessed with domains based on the Cochrane risk of bias tool. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed using Grades of Recommendations, Assessment, Development and Evaluation. Ethics and dissemination No formal approval or review of ethics is required as individual patient data will not be included. This systematic review has the potential to highlight (1) whether one should believe sedation to be beneficial, harmful or neither in critically ill adults; (2) the existing knowledge gaps and (3) whether the recommendations from guidelines and daily clinical practice are supported by current evidence. These results will be disseminated through publication in a peer-reviewed journal.Peer reviewe

Drug-eluting stents versus bare-metal stents for stable ischaemic heart disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of drug‐eluting stents versus bare‐metal stents in participants with stable ischaemic heart disease

Dopamine in critically ill patients with cardiac dysfunction:A systematic review with meta-analysis and trial sequential analysis

Background Dopamine has been used in patients with cardiac dysfunction for more than five decades. Yet, no systematic review has assessed the effects of dopamine in critically ill patients with cardiac dysfunction. Methods This systematic review was conducted following The Cochrane Handbook for Systematic Reviews of Interventions. We searched for trials including patients with observed cardiac dysfunction published until 19 April 2018. Risk of bias was evaluated and Trial Sequential Analyses were conducted. The primary outcome was all-cause mortality at longest follow-up. Secondary outcomes were serious adverse events, myocardial infarction, arrhythmias, and renal replacement therapy. We used GRADE to assess the certainty of the evidence. Results We identified 17 trials randomising 1218 participants. All trials were at high risk of bias and only one trial used placebo. Dopamine compared with any control treatment was not significantly associated with relative risk of mortality (60/457 [13%] vs 90/581 [15%]; RR 0.91; 95% confidence interval 0.68-1.21) or any other patient-centred outcomes. Trial Sequential Analyses of all outcomes showed that there was insufficient information to confirm or reject our anticipated intervention effects. There were also no statistically significant associations for any of the outcomes in subgroup analyses by type of comparator (inactive compared to potentially active), dopamine dose (low compared to moderate dose), or setting (cardiac surgery compared to heart failure). Conclusion Evidence for dopamine in critically ill patients with cardiac dysfunction is sparse, of low quality, and inconclusive. The use of dopamine for cardiac dysfunction can neither be recommended nor refuted

Protocol for an individual patient data meta-analysis on blood pressure targets after cardiac arrest

Background Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. Methods This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65-70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. Conclusions This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences.Peer reviewe