Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19: A Randomized, Controlled Pilot Trial.

BACKGROUND: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. RESEARCH QUESTION: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? STUDY DESIGN AND METHODS: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. RESULTS: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. INTERPRETATION: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov.

An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data.

BACKGROUND: We have previously shown that an exclusively human milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was found. The current analysis re-evaluates these data from a different statistical perspective considering the probability or likelihood of needing TPN on any given day rather than the number of days on TPN. This study consisted of 207 premature infants randomized into three groups: one group receiving a control diet of human milk, formula and bovine-based fortifier ("control diet"), and the other two groups receiving only human milk and human milk-based fortifier starting at different times in the enteral feeding process (at feeding volumes of 40 or 100 mL/kg/day; "HM40" and "HM100", respectively). The counting process Cox proportional hazards survival model was used to determine the likelihood of needing TPN in each group. RESULTS: The two groups on the completely human-based diet had an 11-14 % reduction in the likelihood of needing nutrition via TPN when compared to infants on the control diet (p = 0.0001 and p = 0.001, respectively for the HM40 and HM100 groups, respectively). This was even more pronounced if the initial period of TPN was excluded (p < 0.0001 for both the HM40 and HM100 groups). CONCLUSIONS: A completely human milk-based diet significantly reduces the likelihood of TPN use for extremely premature infants when compared to a diet including cow-based products. This likelihood may be reduced even further when the human milk fortifier is initiated earlier in the feeding process. TRIAL REGISTRATION: This study was registered at http://www.clinicaltrials.gov reg. # NCT00506584.

Prevalence and extent of dyslipidemia and recommended lipid levels in US adults with and without cardiovascular comorbidities: the National Health and Nutrition Examination Survey 2003-2004.

BACKGROUND: Despite improvements in low-density lipoprotein cholesterol (LDL-C) levels, recent national data are limited regarding the proportion of adults at recommended lipid levels according to the presence of cardiovascular disease (CVD) and related comorbidities. We evaluated the proportion of US adults with and without these conditions at (and distance to) recommended levels of LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, and triglycerides. METHODS: We analyzed data from adults aged > or =20 who had fasted for 8 or more hours (n = 2,883, weighted to a US population of 128.5 million) in the National Health and Nutrition Examination Survey 2003-2004, a nationally representative cross-sectional survey. The number of adults at National Cholesterol Education Program recommended levels for LDL-C, non-HDL-C, HDL-C, triglycerides, and combined lipids, stratified by sex, age group, ethnicity, and the presence of CVD comorbidities was determined. RESULTS: Although 85% to 89% of persons without CVD or related comorbidities were at recommended levels for LDL-C, non-HDL-C, HDL-C, and triglycerides, only 36% to 37% of those with CVD or related comorbidities were at recommended levels for LDL-C and non-HDL-C, and only 17% were at recommended levels for all lipids. Treated persons compared with those untreated had significantly lower LDL-C (112.3 vs 156.7 mg/dL, P < .001) and non-HDL-C levels (145.9 vs 188.7 mg/dL, P < .001), but similar HDL-C (52.0 vs 50.1 mg/dL, P = .09) and triglyceride (160.1 vs 148.7 mg/dL, P = .20) levels. CONCLUSIONS: Despite improved LDL-C levels, many adults, especially with CVD or related comorbidities, are not at recommended levels for all lipids. Improved treatment efforts to target the spectrum of dyslipidemia are needed.

Global coronary heart disease risk assessment of individuals with the metabolic syndrome in the U.S.

OBJECTIVE: Although metabolic syndrome is related to an increased risk of coronary heart disease (CHD) events, individuals with metabolic syndrome encompass a wide range of CHD risk levels. This study describes the distribution of 10-year CHD risk among U.S. adults with metabolic syndrome. RESEARCH DESIGN AND METHODS: Metabolic syndrome was defined by the modified National Cholesterol Education Program (NCEP)/Third Adult Treatment Panel (ATP III) definition among 4,293 U.S. adults aged 20-79 years in the National Health and Nutrition Examination Survey 2003-2004. Low-, moderate-, moderately high-, and high-risk statuses were defined as <6, 6 to <10, 10-20, and >20% probability of CHD in 10 years (based on NCEP/ATP III Framingham risk score algorithms), respectively; those with diabetes or preexisting cardiovascular disease were assigned to high-risk status. RESULTS: The weighted prevalence of metabolic syndrome by NCEP criteria in our study was 29.0% overall (30.0% in men and 27.9% in women, P = 0.28): 38.5% (30.7% men and 46.9% women) were classified as low risk, 8.5% (7.9% men and 9.1% women) were classified as moderate risk, 15.8% (23.4% men and 7.6% women) were classified as moderately high risk, and 37.3% (38.0% men and 36.5% women) were classified as high risk. The proportion at high risk increased with age but was similar among Hispanics, non-Hispanic whites, and non-Hispanic blacks. CONCLUSIONS: Although many subjects with metabolic syndrome have a low calculated risk for CHD, about half have a moderately high or high risk, reinforcing the need for global risk assessment in individuals with metabolic syndrome to appropriately target intensity of treatment for underlying CHD risk factors.