IMPORTANCESepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis.OBJECTIVE To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator-and vasopressor-free days compared with placebo in patients with sepsis.DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. INTERVENTIONS Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. MAIN OUTCOMES AND MEASURESThe primary outcome was the number of consecutive ventilator-and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. RESULTS Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator-and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of −1 day (95% CI, −4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group.CONCLUSIONS AND RELEVANCE Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator-and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference.

We evaluated a case management intervention to increase treatment entry among injecting drug users referred from a needle exchange program (NEP). A randomized trial of a strengths based case management (intervention) versus passive referral (control) was conducted among NEP attenders requesting and receiving referrals to subsidized, publicly funded opiate agonist treatment programs in Baltimore, MD. Logistic regression identified predictors of treatment entry within 7 days, confirmed through treatment program records. Of 247 potential subjects, 245 (99%) participated. HIV prevalence was 19%. Overall, 34% entered treatment within 7 days (intervention: 40% versus control: 26%, p = 0.03). In a multivariate "intention to treat' model (i.e., ignoring the amount of case management actually received), those randomized to case management were more likely to enter treatment within 7 days. Additional 'as treated' analyses revealed that participants who received 30 min or more of case management within 7 days were 33% more likely to enter treatment and the active ingredient of case management activities was provision of transportation. These findings demonstrate the combined value of offering dedicated treatment referrals from NEP, case management and transportation in facilitating entry into drug abuse treatment. Such initiatives could be implemented at more than 140 needle exchange programs currently operating in the United States. These data also support the need for more accessible programs such as mobile or office-based drug abuse treatment.

Introduction Few large studies describe quality control procedures and reproducibility findings in cardiovascular ultra-sound, particularly in novel techniques such as Speckle Tracking (STE). We evaluate the echocardiography assessment performance in the CARDIA study Y25 examination (2010-2011) and report findings from a quality control and reproducibility program conducted to assess Field Center image acquisition and Reading Center (RC) accuracy. Methods The CARDIA Y25 examination had 3,475 echocardiograms performed in 4 US Field Centers and analyzed in a Reading Center, assessing standard echocardiography (LA dimension, aortic root, LV mass, LV end-diastolic volume [LVEDV], ejection fraction [LVEF]), and STE (2- and 4-chamber longitudinal, circumferential, and radial strains). Reproducibility was assessed using intra-class correlation coefficients (ICC), coefficients of variation (CV), and Bland-Altman plots. Results For standard echocardiography reproducibility, LV mass and LVEDV consistently had CV above 10% and aortic root below 6%. Intra-sonographer aortic root and LV mass had the most robust values of ICC in standard echocardiography. For STE, the number of properly tracking segments was above 80% in short-axis and 4-chamber and 58% in 2-chamber. Longitudinal strain parameters were the most robust and radial strain showed the highest variation. Comparing Field Centers with Echo RC STE readings, mean differences ranged from 0.4% to 4.1% and ICC from 0.37 to 0.66, with robust results for longitudinal strains. Conclusion Echocardiography image acquisition and reading processes in the CARDIA study were highly reproducible, including robust results for STE analysis. Consistent quality control may increase the reliability of echocardiography measurements in large cohort studies.

Injection drug use is a growing but understudied problem in Tijuana, a city situated on the northwestern Mexico-U.S border. The authors studied factors associated with receptive needle sharing in an effort to inform prevention activities. In 2003, street-recruited injection drug users (IDUs) in Tijuana underwent interviews on injection risk behaviors and rapid HIV antibody tests. Logistic regression was used to identify correlates of receptive needle sharing at the last injection episode. Of 402 IDUs, 87.6% were male; the median age was 34. HIV prevalence was 4.01% (95% CI: 2.29-6.51). One third reported receptive needle sharing at last injection. Factors independently associated with receptive needle sharing were years living in Tijuana (Adjusted Odds Ratio [AdjOR]= 0.97 per year, 95% CI: 0.96-0.99), being bisexual/homosexual (AdjOR=2.12; 95% CI: 1.30 - 3.44), unemployed (AdjOR=2.5; 95% CI: 1.52-4.10), never having an HIV test (AOR: 4.02; 95% CI: 2.44-6.60), having friends who placed importance on avoiding HIV (AdjOR: 0.36; 95% CI: 0.19-0.68) and last injecting in a shooting gallery (AdjOR=1.98; 95% CI: 1.21-3.24). These results underscore the need to increase access to voluntary HIV testing and counseling to IDUs and migrants in Tijuana, as well as expand access to sterile syringes in an effort to avert widespread HIV transmission.