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Importance: Suicidal ideation and suicide attempts are debilitating mental health problems that are often treated with indirect psychotherapy (ie, psychotherapy that focuses on other mental health problems, such as depression or personality disorders). The effects of direct and indirect psychotherapy on suicidal ideation have not yet been examined in a meta-analysis, and several trials have been published since a previous meta-analysis examined the effect size of direct and indirect psychotherapy on suicide attempts., Objective: To investigate the effect sizes of direct and indirect psychotherapy on suicidal ideation and the incidence of suicide attempts., Data Sources: PubMed, Embase, PsycInfo, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up until April 1, 2023., Study Selection: Randomized clinical trials of psychotherapy for any mental health problem, delivered in any setting, compared with any control group, and reporting suicidal ideation or suicide attempts were included. Studies measuring suicidal ideation with 1 item were excluded., Data Extraction and Synthesis: PRISMA guidelines were followed. Summary data were extracted by 2 independent researchers and pooled using 3-level meta-analyses., Main Outcomes and Measures: Hedges g was pooled for suicidal ideation and relative risk (RR) was pooled for suicide attempts., Results: Of 15 006 studies identified, 147 comprising 193 comparisons and 11 001 participants were included. Direct and indirect psychotherapy conditions were associated with reduced suicidal ideation (direct: g, -0.39; 95% CI, -0.53 to -0.24; I2, 83.2; indirect: g, -0.30; 95% CI, -0.42 to -0.18; I2, 52.2). Direct and indirect psychotherapy conditions were also associated with reduced suicide attempts (direct: RR, 0.72; 95% CI, 0.62 to 0.84; I2, 40.5; indirect: RR, 0.68; 95% CI, 0.48 to 0.95; I2, 0). Sensitivity analyses largely confirmed these results., Conclusions and Relevance: Direct and indirect interventions had similar effect sizes for reducing suicidal ideation and suicide attempts. Suicide prevention strategies could make greater use of indirect treatments to provide effective interventions for people who would not likely seek treatment for suicidal ideation or self-harm.

AimHigh-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo.ObjectiveTo investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA).Design and settingA prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion.PatientsFive hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively.InterventionPatients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001.Main outcome measuresThe primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints.ResultsThe nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups.ConclusionCER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;Trial registration numberNCT01201837.

Background: The Amplatzer™ Trevisio™ Intravascular Delivery System (Trevisio DS; Abbott Laboratories, Chicago, IL, USA) facilitates the delivery of Amplatzer™ Occluders and features an ultraflexible tip, which improves assessment of occluder position before release., Aims: To assess the safety and efficacy of the Trevisio DS for transcatheter closure of patent foramen ovale and atrial septal defect., Methods: The Amplatzer™ Trevisio™ Intravascular Delivery System Post-Approval Study was a prospective, postmarket, single-arm, multicentre, observational study of the Trevisio DS. Enrolled patients were indicated for transcatheter closure of patent foramen ovale or atrial septal defect. In all procedures, the Trevisio DS was used to deliver Amplatzer™ Occluders. Technical success was defined as successful deployment and release of at least one occluder. Device- or procedure-related serious adverse events were tracked until discharge or day 7, whichever occurred earlier., Results: The study enrolled 144 patients with patent foramen ovale and 107 patients with atrial septal defect at 22 European sites; 53 patients with atrial septal defect (49.6%) were aged<18years. The rate of technical success was 98.4% (97.2% for atrial septal defect, 99.3% for patent foramen ovale). There was one serious adverse event (0.4%), an acute periprocedural device embolization that occurred after occluder release in a patient with atrial septal defect; the device was retrieved percutaneously. This was determined by the implanter to be unrelated to the performance of the Trevisio DS., Conclusions: The Trevisio DS exhibited a high rate of technical success and an excellent safety profile during transcatheter closure of patent foramen ovale and atrial septal defect., (Copyright © 2023 Abbott Laboratories. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Patients with excess epicardial adipose tissue (EAT) are at increased risk of developing cardiac arrhythmias. EAT promotes arrhythmias by depolarizing the resting membrane of cardiomyocytes, which slows down conduction and facilitates re-entrant arrhythmias. We hypothesized that EAT slows conduction by secreting extracellular vesicles (EVs) and their microRNA (miRNA) cargo., Objective: We aimed to determine the role of EAT-derived EVs and their miRNA cargo in conduction slowing., Methods: EAT and subcutaneous adipose tissue (SAT) were collected from patients with atrial fibrillation. Adipose tissue explants were incubated in culture medium and secretome was collected. The numbers of EVs in the EAT and SAT secretome were measured by calibrated flow cytometry. EVs in the EAT secretome were isolated by size exclusion chromatography and miRNAs were sequenced. Pathway analysis was performed to predict candidates involved in cardiac electrophysiology. The candidates were validated in the EAT and SAT by quantitative real-time polymerase chain reaction. Finally, miRNA candidates were overexpressed in neonatal rat ventricular myocytes., Results: The EV concentration was higher in the EAT secretome than in the SAT and control secretomes. miRNA sequencing of EAT-derived EVs detected a total of 824 miRNAs. Pathway analysis led to the identification of 7 miRNAs potentially involved in regulation of cardiac resting membrane potential. Validation of those miRNA candidates showed that they were all expressed in EAT, and that miR-1-3p and miR-133a-3p were upregulated in EAT in comparison with SAT. Overexpression of miR-1-3p and miR-133a-3p in neonatal rat ventricular myocytes led to conduction slowing and reduced Kcnj2 and Kcnj12 expression., Conclusion: miR-1-3p and miR-133a-3p are potential mediators of EAT arrhythmogenicity., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Thirty years, 1993-2023, is a huge time frame in science. We address some major developments in the field of evolutionary algorithms, with applications in parameter optimization, over these 30 years. These include the covariance matrix adaptation evolution strategy and some fast-growing fields such as multimodal optimization, surrogate-assisted optimization, multiobjective optimization, and automated algorithm design. Moreover, we also discuss particle swarm optimization and differential evolution, which did not exist 30 years ago, either. One of the key arguments made in the paper is that we need fewer algorithms, not more, which, however, is the current trend through continuously claiming paradigms from nature that are suggested to be useful as new optimization algorithms. Moreover, we argue that we need proper benchmarking procedures to sort out whether a newly proposed algorithm is useful or not. We also briefly discuss automated algorithm design approaches, including configurable algorithm design frameworks, as the proposed next step toward designing optimization algorithms automatically, rather than by hand., (© 2023 Massachusetts Institute of Technology.)