Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis.

OBJECTIVE: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). METHODS: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. RESULTS: Twenty-two studies were included in the systematic review. A total of 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found. CONCLUSIONS: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.

A Descriptive Review and Meta-Regression Study of Demographic and Study Context Factors in US Clinical Trials of Cognitive Behavioral Interventions for Alcohol or Other Drug Use.

Objectives. Cognitive-Behaviorally Based Interventions (CBIs) are evidence-based treatments for alcohol and other drug (AOD) use with potential variable effectiveness by population sub-groups. This study used evidence synthesis to examine treatment effect by demographic and study context factors in clinical trials of CBI for AOD. Methods. Studies were systematically identified, and their characteristics and outcome data were extracted and summarized. Standardized mean differences were calculated for within- and between-condition effects on substance use outcomes. Demographic and study context moderators were identified during data acquisition and several sensitivity analyses were conducted. Results. The sample included K = 29 trials and a total of 15 study-level moderators were examined. Information on participants' age, biological sex, and race were reported in at least 26 trials, but information on gender identity, sexual orientation, and ethnicity were reported infrequently or in non-inclusive ways. The mean between-condition effect size was small and moderately heterogenous (d = 0.158, 95% CI = 0.079, 0.238, I2 = 46%) and the mean within-condition effect size was large and showed high heterogeneity (dz = 1.147, 95% CI = 0.811, 1.482, - I2 = 96%). The specific drug targeted in the study and whether biological assay-based outcomes were used moderated between-condition CBI efficacy and the inclusion of co-occurring mental health conditions and study publication date moderated within-condition CBI effects. Conclusions. Results provide preliminary data on study context factors associated with effect estimates in United States based clinical trials of CBI for AOD.

Long-term effects on clinical event, mental health, and related outcomes of CPAP for obstructive sleep apnea: a systematic review.

STUDY OBJECTIVES: We performed a systematic review of long-term health outcomes of continuous positive airway pressure (CPAP) use in adults with obstructive sleep apnea. METHODS: We updated prior systematic reviews with searches in multiple databases through January 3, 2023. We included randomized controlled trials (RCTs) and adjusted nonrandomized comparative studies that reported prespecified long-term (mostly > 1 year) health outcomes. We assessed risk of bias, conducted meta-analyses, and evaluated strength of evidence. RESULTS: We found 38 eligible studies (16 trials, 22 observational). All conclusions were of low strength of evidence given study and data limitations. RCTs found no evidence of effect of CPAP on mortality (summary effect size [ES] 0.89; 95% confidence interval [CI] 0.66, 1.21); inclusion of adjusted nonrandomized comparative studies yields an association with reduced risk of death (ES 0.57; 95% CI 0.44, 0.73). RCTs found no evidence of effects of CPAP for cardiovascular death (ES 0.99; 95% CI 0.64, 1.53), stroke (ES 0.99; 95% CI 0.73, 1.35), myocardial infarction (ES 1.05; 95% CI 0.78, 1.41), incident atrial fibrillation (ES 0.89; 95% CI 0.48, 1.63), or composite cardiovascular outcomes (all statistically nonsignificant). RCTs found no evidence of effects for incident diabetes (ES 1.02; 95% CI 0.69, 1.51) or accidents (all nonsignificant) and no clinically significant effects on depressive symptoms, anxiety symptoms, or cognitive function. CONCLUSIONS: Whether CPAP use for obstructive sleep apnea affects long-term health outcomes remains largely unanswered. RCTs and nonrandomized comparative studies are inconsistent regarding the effect of CPAP on mortality. Current studies are underpowered, with relatively short duration follow-up and methodological limitations. CITATION: Balk EM, Adam GP, Cao W, Bhuma MR, D'Ambrosio C, Trikalinos TA. Long-term effects on clinical event, mental health, and related outcomes of CPAP for obstructive sleep apnea: a systematic review. J Clin Sleep Med. 2024;20(6):895-909.

Scientific Inference Does Not Rest on Statistical Testing.

The Strategic Timing of AntiRetroviral Treatment (START) trial found that in patients with HIV and CD4+ cell counts above 500 cells/mm3 who had not previously received treatment, immediate initiation of antiretroviral therapy reduced the risk of serious adverse outcomes compared with delaying treatment initiation only when the CD4+ cell count fell below 350 cells/mm3.1 After the trial's completion, people with HIV not receiving therapy were offered the opportunity to start it without regard to their CD4+ cell count. In this issue of NEJM Evidence, the START group reports data from an additional 5 years of follow-up.2.

Assessing the Utility of Test-Based Prediction Models: Heart Failure as an Example.

Chirinos et al.1 demonstrated that endotrophin levels are strongly associated with all-cause mortality and a composite outcome in patients with heart failure with preserved ejection fraction (HFpEF). The authors established the association in a subset of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)2 and validated it in external data sets. At a minimum, their observation is new knowledge that may advance our understanding of the pathophysiology of HFpEF. It also indicates that endotrophin-based risk prediction has utility for patients, the health system, and designing future research.