Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.Peer reviewe

Dr. Jane Brunt: Her Diverse Formative Years

This story presents how Dr. Jane Brunt's diverse educational background prepared her for becoming a pioneering feline specialist, owning a successful feline-only practice, and serving as executive director of the grassroots initiative called CATalyst Council

Dr. Jane Brunt: The Making of a Feline Veterinarian

In addition to preparing for following her feline medicine interests, Dr. Jane Brunt’s career has included leadership in many aspects of organized veterinary medicine

Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

BACKGROUND: Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias. METHODS: This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8–17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient < 70; or treatment with CBT, PRT, antidepressant or antipsychotic medication within the last 6 months prior to trial entry. Participants are randomised 1:1 to the experimental intervention (FCBT) versus the control intervention (FPRT) each consisting of 14 75-min sessions. All therapists deliver both interventions. Follow-up assessments occur in week 4, 8 and 16 (end-of-treatment). The primary outcome is OCD symptom severity assessed with CY-BOCS at end-of-trial. Secondary outcomes are quality-of-life and adverse events. Based on sample size estimation, a minimum of 128 participants (64 in each intervention group) are included. DISCUSSION: In our trial design we aim to reduce risk-of-bias, enhance generalisability, and broaden the outcome measures by: 1) conducting an investigator-initiated, independently funded RCT; 2) blinding investigators; 3) investigating a representative sample of OCD patients; 3) using an active control intervention (FPRT) to tease apart general and specific therapy effects; 4) using equal dosing of interventions and therapist supervision in both intervention groups; 5) having therapists perform both interventions decided by randomisation; 6) rating fidelity of both interventions; 7) assessing a broad range of benefits and harms with repeated measures. The primary study limitations are the risk of missing data and the inability to blind participants and therapists to the intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03595098, registered July 23, 2018. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-021-03669-2