Humans

This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary strategies for atherosclerosis prevention. A systematic search on PubMed was performed to identify meta-analyses of cohort studies and RCTs with CVD outcomes. The evidence is highly concordant in showing that, for the healthy adult population, low consumption of salt and foods of animal origin, and increased intake of plant-based foods—whole grains, fruits, vegetables, legumes, and nuts—are linked with reduced atherosclerosis risk. The same applies for the replacement of butter and other animal/tropical fats with olive oil and other unsaturated-fat-rich oil. Although the literature reviewed overall endorses scientific society dietary recommendations, some relevant novelties emerge. With regard to meat, new evidence differentiates processed and red meat—both associated with increased CVD risk—from poultry, showing a neutral relationship with CVD for moderate intakes. Moreover, the preferential use of low-fat dairies in the healthy population is not supported by recent data, since both full-fat and low-fat dairies, in moderate amounts and in the context of a balanced diet, are not associated with increased CVD risk; furthermore, small quantities of cheese and regular yogurt consumption are even linked with a protective effect. Among other animal protein sources, moderate fish consumption is also supported by the latest evidence, although there might be sustainability concerns. New data endorse the replacement of most high glycemic index (GI) foods with both whole grain and low GI cereal foods. As for beverages, low consumption not only of alcohol, but also of coffee and tea is associated with a reduced atherosclerosis risk while soft drinks show a direct relationship with CVD risk. This review provides evidence-based support for promoting appropriate food choices for atherosclerosis prevention in the general population.

IMPORTANCE Dental caries is the most common chronic disease in children in the US.
According to the 2011-2016 National Health and Nutrition Examination Survey, approximately
23% of children aged 2 to 5 years had dental caries in their primary teeth. Prevalence is higher
in Mexican American children (33%) and non-Hispanic Black children (28%) than in
non-Hispanic White children (18%). Dental caries in early childhood is associated with pain,
loss of teeth, impaired growth, decreased weight gain, negative effects on quality of life, poor
school performance, and future dental caries.
OBJECTIVE To update its 2014 recommendation, the US Preventive Services Task Force
(USPSTF) commissioned a systematic review on screening and interventions to prevent
dental caries in children younger than 5 years.
POPULATION Asymptomatic children younger than 5 years.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that there is a
moderate net benefit of preventing future dental caries with oral fluoride supplementation at
recommended doses in children 6 months or older whose water supply is deficient in
fluoride. The USPSTF concludes with moderate certainty that there is a moderate net benefit
of preventing future dental caries with fluoride varnish application in all children younger
than 5 years. The USPSTF concludes that the evidence is insufficient on performing routine
oral screening examinations for dental caries by primary care clinicians in children younger
than 5 years and that the balance of benefits and harms of screening cannot be determined.
RECOMMENDATION The USPSTF recommends that primary care clinicians prescribe oral fluoride
supplementation starting at age 6 months for children whose water supply is deficient in
fluoride. (B recommendation) The USPSTF recommends that primary care clinicians apply
fluoride varnish to the primary teeth of all infants and children starting at the age of primary
tooth eruption. (B recommendation) The USPSTF concludes that the current evidence is
insufficient to assess the balance of benefits and harms of routine screening examinations for
dental caries performed by primary care clinicians in children younger than 5 years. (I statement)

Objective: To examine the relationship between corticosteroid use and herpes zoster risk.

Methods: With data from a large cohort of adults (the 45 and Up Study) recruited between 2006 and 2009 and linked to health data sets, the effect of corticosteroid use on zoster risk was analyzed by Cox proportional hazards models, adjusting for age, sex, and other characteristics.

Results: During 602,152 person-years (median, 7.36 years) of follow-up, there were 20,048 new systemic corticosteroid users and 6294 incident herpes zoster events among 94,677 participants (zoster incidence, 11.0 per 1000 person-years). Compared with nonusers, the risk of zoster was 59% higher in those using systemic corticosteroids (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.48 to 1.71) and greater with higher cumulative doses: aHR of 1.32 (95% CI, 1.17 to 1.48), 1.74 (95% CI, 1.55 to 1.95), and 1.80 (95% CI, 1.61 to 2.02) for use of less than 500 mg, 500 mg to less than 1000 mg, and 1000 mg or more prednisolone equivalents, respectively (P value for trend, <.001). Compared with nonusers, zoster risk increased significantly (aHR, 6.00; 95% CI, 4.85 to 7.42) in the month after a single prescription of systemic corticosteroids and returned to levels similar to those in nonusers by the third month after dispensing (aHR, 0.91; 95% CI, 0.49 to 1.69).

Conclusion: Practitioners should be alert to the increased risk of zoster among patients taking systemic corticosteroids. Given the significant morbidity from zoster, particularly in older adults, these findings support judicious prescribing of corticosteroids, including using as low a dose and as short a course as possible.

Keywords: Cohort; Corticosteroids; Herpes zoster.

Abstract
Background: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29.

Results: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval, -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% confidence interval, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group.

Conclusions: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).