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disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).Background Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting. Methods This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2 × 2 factorial design, participants were randomly assigned (1111) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAn a motor vehicle accident). Interpretation We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. Funding Stanley Medical Research Institute.Background Cognitive bias modification (CBM) therapies, including attention bias modification, interpretation bias modification, or approach and avoidance training, are prototypical examples of mechanistically derived treatments, but their effectiveness is contentious. We aimed to assess the relative effectiveness of various CBM interventions for anxious and depressive symptomatology. Methods For this systematic review and network meta-analysis, we searched PubMed, PsycINFO, Embase, and Cochrane Central Register from database inception up until Feb 7, 2020. We included randomised controlled trials of CBM versus control conditions or other forms of CBM for adults aged 18 years and older with clinical or subclinical anxiety or depression measured with a diagnostic interview or a validated clinical scale. We excluded studies comparing CBM with a non-CBM active intervention. Two researchers independently selected studies and evaluated risk of bias with the Cochrane Collaboration tool. Primary outcomes encompassedrmine the reliability of these findings. Larger, definitive trials for interpretation bias modification for anxiety might be warranted, but insufficient evidence precludes conclusions for depression. Funding Romanian Ministry of Research and Innovation, The National Council for Scientific Research-The Executive Agency for Higher Education, Research, Development and Innovation Funding.Background Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (11) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chire had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding National Institute for Health Research, Health Technology Assessment programme.Background Patients ≥65 years old with hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency may have an altered response to treatment and be at higher risk for treatment-related adverse events (AEs) due to comorbidities and polypharmacy. Objective Investigate the safety and efficacy of subcutaneous (SC) C1-INH in patients ≥65 years old treated in an open-label extension of a phase 3 trial. Methods Eligible patients (≥4 attacks over 2 consecutive months) were randomized to receive twice-weekly C1-INH (SC) 40 IU/kg or 60 IU/kg for 52 to 140 weeks. Safety endpoints and efficacy outcomes were evaluated for patients aged ≥65 and 1 subject included injection-site bruising (n = 2, related), injection-site pain (n = 2, related), urinary tract infection (n = 2, unrelated), and diarrhea (n = 2, unrelated). ARV-825 concentration No thromboembolic events or cases of anaphylaxis were reported. Two subjects ≥65 years old experienced unrelated serious AEs (dehydration and hypokalemia in one and pneumonia and an HAE attack leading to hospitalization in another). Six of 9 evaluable subjects were responders, with ≥50% reduction in HAE attacks versus pre-study; 6/10 had less then 1 attack/4 weeks and 3 were attack-free (median 20-03-0141R1 attack rate, 0.52 attacks/month). Conclusion C1-INH (SC) was well tolerated and effective in the management of HAE in these subjects ≥65 years old with multiple comorbid conditions and polypharmacy.