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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. Methods We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations. Results We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08). Conclusions Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.

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Non-nutritive artificial sweeteners (NNSs) may have the ability to change the gut microbiota, which could potentially alter glucose metabolism. This study aimed to determine the effect of sucralose and aspartame consumption on gut microbiota composition using realistic doses of NNSs. Seventeen healthy participants between the ages of 18 and 45 years who had a body mass index (BMI) of 20–25 were selected. They undertook two 14-day treatment periods separated by a four-week washout period. The sweeteners consumed by each participant consisted of a standardized dose of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose. Faecal samples collected before and after treatments were analysed for microbiome and short-chain fatty acids (SCFAs). There were no differences in the median relative proportions of the most abundant bacterial taxa (family and genus) before and after treatments with both NNSs. The microbiota community structure also did not show any obvious differences. There were no differences in faecal SCFAs following the consumption of the NNSs. These findings suggest that daily repeated consumption of pure aspartame or sucralose in doses reflective of typical high consumption have minimal effect on gut microbiota composition or SCFA production.

CONTEXT: Nonnutritive sweetener (NNS) consumption is increasing among children, yet its long-term health impact is unclear, particularly when exposure occurs during early life.OBJECTIVE: To synthesize evidence from prospective studies evaluating the association of early-life NNS exposure and long-term metabolic health.DATA SOURCES: Medline, Embase, and Cochrane Library (inception to July 2015). STUDY SELECTION:We aimed to include randomized controlled trials (RCTs) evaluating NNSbased interventions and prospective cohort studies reporting NNS exposure among pregnant women, infants, or children (<12 years of age), with a minimum study duration of 6 months. DATA EXTRACTION:The primary outcome was BMI; secondary outcomes included growth velocity, overweight/obesity, adiposity, and adverse metabolic effects. Study quality and risk of bias were evaluated using validated assessment tools. RESULTS:We identified 6 eligible cohort studies and 2 RCTs (n = 15 641 children). Half of the cohorts reported increasing weight gain or fat mass accumulation with increasing NNS intake, and pooled data from 2 cohorts showed a significant correlation with BMI gain (weighted mean correlation 0.023, 95% confidence interval 0.006 to 0.041). RCTs reported contradictory effects on weight change in children receiving NNSs. No eligible studies evaluated prenatal or infant NNS exposure.LIMITATIONS: Meta-analysis was limited because of the small number of eligible studies and heterogeneity of populations and outcomes. CONCLUSIONS:There is limited and inconsistent evidence of the long-term metabolic effects of NNS exposure during gestation, infancy, and childhood. Further research is needed to inform recommendations for the use of NNSs in this sensitive population.

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The results suggest that subjects with high basal cholesterol synthesis are less responsive to PS treatment than are subjects with low basal cholesterol synthesis.

Phytosterols are a family of compounds similar to cholesterol which have been shown to lower cholesterol levels when supplemented in the diet. A daily dose of 2-3 g of phytosterols has been shown to reduce LDL-cholesterol levels by 5-15%. Phytosterol supplementation can be undertaken using phytosterol enriched functional foods or nutraceutical preparations. The type of phytosterol supplemented, such as plant sterol or saturated plant stanol appear to be equally effective in lowering cholesterol levels. Phytosterols, whether in esterified or free form have both been shown to lower cholesterol levels, with esterified phytosterol formulations having a greater number of clinical trials demonstrating efficacy. The functional food or nutraceutical matrix which is used to deliver supplemental phytosterols can significantly affect cholesterol lowering efficacy. Effective cholesterol lowering by phytosterols depends on delivery of phytosterols to the intestine in a form which can compete with cholesterol for absorption. New phytosterol functional food and nutraceuticals products should always be tested to demonstrate adequate delivery of phytosterol dose and effective total and LDL-cholesterol lowering. Phytosterol products which do not effectively lower cholesterol will negatively impact the perception and use of phytosterols, and must not be allowed on the marketplace.