A cluster-randomized, placebo-controlled trial to evaluate the efficacy of a spatial repellent (Mosquito Shield™) against Aedes-borne virus infection among children ≥ 4-16 years of age in the Gampaha District, Sri Lanka: study protocol (the AEGIS program).

BACKGROUND: Spatial repellents (SRs) have been widely used for prevention of mosquito bites, but their efficacy in reducing Aedes-borne viruses (ABV) has not been tested rigorously at large scale in Asia. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a transfluthrin SR, was developed in Gampaha District of Sri Lanka across three Medical Officer of Health areas; i.e., Negombo, Wattala, and Kelaniya. METHODS: This trial is a cluster-randomized, placebo-controlled, double-blinded clinical trial. A total of ~14,430 subjects aged ≥ 6 months in 30 clusters (15 intervention, 15 placebo) from ~3900 households (HH) will be randomly selected for enrolment into a "febrile surveillance cohort." A subset of the surveillance cohort, ~3570 subjects aged ≥4-16 years that test seronegative (naïve) or are serologically positive for a previous single dengue virus (DENV) infection (monotypic) at baseline sampling, will be enrolled into a "longitudinal cohort" for measuring DENV infection based on laboratory-confirmed seroconversion during the trial. Persons identified positive for antibodies against multiple DENV serotypes (multitypic) at baseline will be monitored for secondary analyses. Active ABV disease will be assessed using an enhanced passive surveillance system with case ascertainment performed in designated healthcare facilities. Serum samples will be taken from longitudinal cohort subjects within 1-2 weeks of when intervention is first deployed (T0) with additional samples taken ~12 (T1) and ~24 months (T2) from baseline sampling. DENV seroconversion and ABV active disease rates from baseline (pre-intervention) and follow-up (post-intervention) samples will be compared between intervention and placebo clusters. Participating houses will be monitored entomologically (indoor adult Aedes aegypti population densities and adult female blood fed status) within 3 months before intervention deployment and monthly during the intervention phase. Entomological surveys will monitor indoor adult Ae. aegypti population densities and blood fed status. Dengue incidence in each cohort will be estimated and compared to determine the public health benefit of using an SR. Entomological parameters will be measured to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. DISCUSSION: The trial will serve as an efficacy assessment of SR products in South Asia. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of SRs in ABV control programs. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry SLCTR /2022/018. Registered on July 1, 2022. CLINICALTRIALS: gov NCT05452447 . Registered on July 11, 2022. The Universal Trial Number is U1111-1275-3055.

Sex-Specific Differences in Percutaneous Coronary Intervention Outcomes After a Cardiac Event: A Cohort Study Examining the Role of Depression, Worry and Autonomic Function.

BACKGROUND: To determine whether differential all-cause hospital readmission exists for men and women 2 years after percutaneous coronary intervention (PCI) treatment for acute coronary syndrome (ACS), and to identify potential autonomic and psychological pathways contributing to this association. METHODS: Four hundred and sixteen (416) patients admitted with ACS were recruited from coronary care wards. Participants attended the study centre at one (T0) and 12 (T1) months following discharge. Heart rate variability (HRV) was used to assess autonomic functioning measured via a three-lead electrocardiogram. Psychological variables of interest (pathological worry, depression and phobic anxiety) were measured using validated self-report questionnaires. Percutaneous coronary intervention treatment data were collected from hospital records. The primary outcome was 2-year all-cause hospital readmission (yes/no). Logistic regression modelling using both complete case analysis and multiple imputation analysis was applied. RESULTS: Men who received PCI had a significant reduction in the odds of being rehospitalised over the following 2 years, relative to women who did not (OR=0.45, 95% CI=0.20, 0.98). No other group benefited to this extent. Adjustment for age, ACS severity and Very Low Frequency (VLF) Power appeared to strengthen the association in both the complete case analysis and multiple imputation analysis models. The inclusion of depression and worry also marginally explained these associations in the multiple imputation analysis model. CONCLUSIONS: Men who receive PCI after ACS were less likely to be readmitted to hospital over the following 2 years than their female counterparts. The small sample size of women and observational study design limit interpretation of the findings. However, heart rate variability, specifically VLF power, requires further investigation as a driver of such sex-specific outcomes.