Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.

Mavacamten: a novel small molecule modulator of ß-cardiac myosin for treatment of hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a common known monogenetic cardiovascular disorder which frequently leads to symptoms such as dyspnea and exercise intolerance. Current guideline-recommended pharmacotherapies have variable therapeutic responses. Mavacamten, a small molecule modulator of ß-cardiac myosin, reduces hypercontractility, a central mechanism in the pathogenesis of HCM. Mavacamten has recently been evaluated in Phase 2 and 3 clinic trials for obstructive and nonobstructive symptomatic HCM. AREAS COVERED: This article reviews available preclinical and clinical trials assessing the efficacy and safety of Mavacamten for the treatment of symptomatic obstructive and nonobstructive HCM. EXPERT OPINION: Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), Overall Summary Score (OSS), and numerical rating scale (NRS) dyspnea scores; and patients with both obstructive and nonobstructive HCM had significant improvement in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.

IL6 plasma concentrations in patients with sepsis receiving SLED and antibiotics: a predictor for survival.

BACKGROUND: The present study evaluated interleukin-6 (IL6) as a predictor of mortality in patients and sepsis with acute kidney injury (AKI) receiving sustained low-efficiency dialysis (SLED) and antibiotic therapy. PATIENTS AND METHODS: Seven patients with sepsis receiving antibiotics and SLED for AKI were studied. Blood was obtained at baseline prior to SLED and antibiotics, during SLED, and then after stopping SLED. IL6 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean plasma IL6 concentrations ranged between 700 and 900 pg/ml for the first 8 h after starting SLED but was significantly lower after discontinuation of SLED (200-250 pg/ml) (p=0.0044). Three out of seven patients survived to be discharged from the hospital and all three had significantly lower concentrations of IL6 during the first 8 h compared to those who died in the hospital (p<0.0001). CONCLUSION: The combination of SLED and antibiotic therapy was unable to lower the initial high plasma IL6 concentrations, and high initial IL6 concentrations predicted in-hospital mortality.

Socioeconomic status and comorbidity as predictors of preoperative quality of life in cardiac surgery.

OBJECTIVE: Preoperative quality of life of patients undergoing cardiac surgical procedures has been associated with postoperative morbidity, survival, and quality of life. Patients of lower socioeconomic status have disproportionately greater cardiovascular disease burden and more complications of cardiovascular disease. We examined the interactive effects of demographic characteristics, socioeconomic status, and comorbidity on preoperative functional quality of life measured by the well-validated cardiovascular disease-specific Duke Activity Status Index. METHODS: The patient population consisted of 5581 patients between May 1995 and January 1999 who underwent operations on cardiopulmonary bypass: isolated coronary artery bypass grafting, isolated valve procedures, or combined coronary artery bypass grafting and valve procedures and had a preoperative Duke Activity Status Index, along with socioeconomic status information from United States 2000 census data. Predictors were identified by logistic regression for maximum value of baseline DASI and linear regression for DASI scores less than maximum by means of bagging variable selection. RESULTS: Lower socioeconomic status was associated of lower risk-adjusted quality of life (maximum Duke Activity Status Index P = .0002, less than maximum Duke Activity Status Index P = .0007). Older age, female sex, certain comorbidities, higher New York Heart Association class, lower left ventricular function, and reoperation were also statistically significantly associated with lower preoperative Duke Activity Status Index. CONCLUSION: Lower socioeconomic status is associated with lower risk-adjusted quality of life for patients undergoing cardiac surgery. Quality of life affects morbid outcomes, so further characterization of risk factors for poor quality of life offers an opportunity for intervention.