Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial.

Importance: Sepsis 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 Measures: The 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.

Vermont's comprehensive public health framework for tobacco control and prevention.

When the Centers for Disease Control and Prevention published the Best Practices Guide for Comprehensive Tobacco Control - 2014 it provided an opportunity for Vermont's Tobacco Control Program to create a new state plan. Bringing together partner agencies, advocates and health organizations, the workgroup faced a challenge: there wasn't consensus around focusing on e-cigarettes. There was concern that if too much emphasis was placed on addressing this emerging product, it would be at the cost of reducing combustible use. Youth smoking rates were declining while adult smoking prevalence in Vermont remained stagnant and difficult to move downward. Through applying the lens of best practice and examining the data, the workgroup determined that an ambitious state plan was necessary. Adopting a set of principles grounded in public health and performance measurement, the plan's five goals are to reduce use of all tobacco products among youth and adults. The state plan established a vision of a Vermont free of tobacco use for the program and partners to use, emphasizing data-driven interventions and advancing policymaking, including addressing flavored tobacco products. The tobacco control and regulatory framework in Vermont has worked consistently at the state and local level on strategies involving youth engagement, coalition prevention activities, counter marketing and enforcement. Vermont's framework has evolved to recognize that no matter where a Vermonter is living or working, the protections and services provided by a tobacco program should be equitable. Future application of the public health framework includes exploring innovative policy approaches to curtail the vaping epidemic.

The National Epidemic of Gun Violence: The Vermont Department of Health Response.

This case study details a 2018 "near miss" school mass-shooting event in Vermont that involved a former student and occurred contemporaneously with the Parkland, Florida, tragedy. The situation "jolted" this rural state's governor, lending urgency to the need to enact sensible gun control laws. He comes to support a series of proactive bills already in the legislature and advocate for further preventive strategies. The state's commissioner of health plays public health's traditional role within state government as trusted health promotion and education resource to frame the issue in public health and public safety terms. He portrayed health data on firearm injuries and deaths and formed a public health strategy including surveillance, identification of risk factors, and resources for school- and community-based prevention. On April 11, 2018, Governor Phil Scott signed a package of gun-related legislation that included increasing the legal age for gun purchases, expanding background checks for private gun sales, banning high-capacity magazines and rapid-fire bump stocks, and extreme risk protection orders. The final results were examined from an evidence-based public health standpoint, acknowledging the lack of gun research by federal agencies since the 1996 enactment of the Dickey Amendment that prohibits the Centers for Disease Control and Prevention from conducting firearms-related research. The case study illustrates the paradox of moving forward on gun safety, where more research is needed, but research does not necessarily influence political leaders or policy. It also demonstrates how prevention of gun violence can be portrayed in a public health framework, drawing upon data and strategies used in upstream preventive efforts in areas such as early childhood development, mental health, and substance misuse.

Temporo-spacial microanatomical distribution of the murine sodium-dependent ascorbic acid transporters Slc23a1 and Slc23a2 in the kidney throughout development.

The two membrane transporters Slc23a1 and Slc23a2 mediate ascorbic acid uptake into cells. We recently determined the key role of Slc23a1 in renal re-absorption of ascorbic acid in a knockout mouse model. However, the renal spatial and temporal expression patterns of murine Slc23a1 and Slc23a2 are not defined. This study utilizes database evidence combined with experimental confirmation via in-situ hybridization to define the spatial and temporal expression of Slc23a1 in the murine kidney. Slc23a1 is expressed in the early proximal tubule, but not in its precursors during embryonic development, and exclusive proximal tubular expression persists throughout the animal's lifetime. In contrast, Slc23a2 is uniformly expressed in metabolic cell types such as stromal cells. The expression patterns appear to be conserved from rodent lineages to humans.

Teaching Health Professions Students About the Holocaust.

The legacy of health professionals' roles in the Holocaust is fundamental to understanding modern health care ethics, but teaching it is difficult. The University of Colorado Center for Bioethics and Humanities has developed a program that addresses 4 main pedagogical challenges of this content. This article identifies 3 core lessons and proposes 5 specific learning objectives related to health professionals' involvement in the Holocaust for any health professional training program.

Jobs, Housing, and Mask Wearing: Cross-Sectional Study of Risk Factors for COVID-19.

BACKGROUND: Many studies have focused on the characteristics of symptomatic patients with COVID-19 and clinical risk factors. This study reports the prevalence of COVID-19 in an asymptomatic population of a hospital service area (HSA) and identifies factors that affect exposure to the virus. OBJECTIVE: The aim of this study is to measure the prevalence of COVID-19 in an HSA, identify factors that may increase or decrease the risk of infection, and analyze factors that increase the number of daily contacts. METHODS: This study surveyed 1694 patients between April 30 and May 13, 2020, about their work and living situations, income, behavior, sociodemographic characteristics, and prepandemic health characteristics. This data was linked to testing data for 454 of these patients, including polymerase chain reaction test results and two different serologic assays. Positivity rate was used to calculate approximate prevalence, hospitalization rate, and infection fatality rate (IFR). Survey data was used to analyze risk factors, including the number of contacts reported by study participants. The data was also used to identify factors increasing the number of daily contacts, such as mask wearing and living environment. RESULTS: We found a positivity rate of 2.2%, a hospitalization rate of 1.2%, and an adjusted IFR of 0.55%. A higher number of daily contacts with adults and older adults increases the probability of becoming infected. Occupation, living in an apartment versus a house, and wearing a face mask outside work increased the number of daily contacts. CONCLUSIONS: Studying prevalence in an asymptomatic population revealed estimates of unreported COVID-19 cases. Occupational, living situation, and behavioral data about COVID-19-protective behaviors such as wearing a mask may aid in the identification of nonclinical factors affecting the number of daily contacts, which may increase SARS-CoV-2 exposure.

Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer.

AIM: The aim of this study was to test for the influence of ascorbic acid on tumorigenicity and metastases of implanted PAIII prostate cancer adenocarcinoma cells in syngeneic LW rats. MATERIALS AND METHODS: Hormone-refractory prostate cancer PAIII cells were implanted subcutaneously into immunologically intact, Lobund-Wistar (LW) rats. Intraperitoneal pharmacological doses of ascorbic acid were administered each day for the ensuing 30 days. On the 40th day, animals were sacrificed. Local tumor weights were measured, and metastases were counted. RESULTS: At the end of the 40 day experimental period, the primary tumors were found to be significantly reduced in weight (p=0.026). In addition, sub-pleural lung metastases were even more profoundly reduced in number and size (p=0.009). Grossly enlarged ipsilateral lymph node metastases declined from 7 of 15 rats to 1 of 15 rats. CONCLUSION: Pharmacological doses of ascorbic acid suppress tumor growth and metastases in hormone-refractory prostate cancer.

Ethical obligations of physicians participating in public health quarantine and isolation measures.

In dealing with outbreaks of communicable diseases, the medical profession should work with public health authorities to promote the use of interventions that achieve desired public health outcomes with minimal infringement upon individual liberties. This article endeavors to help physicians manage their dual responsibilities to their patients and to their communities when participating in appropriate quarantine and isolation measures. In implementing such measures, individual physicians should take necessary actions to promote patients' well-being. In addition, the medical profession and individual physicians share responsibility for taking appropriate precautionary measures to protect the health of individuals caring for patients with communicable diseases.

Teaching resident physicians to provide exercise counseling: a needs assessment.

PURPOSE: To determine the behaviors, knowledge, and attitudes of resident physicians regarding exercise counseling. METHOD: In 1997, a self-administered questionnaire was sent to 313 internal medicine resident physicians at six U.S. training programs. Pearson correlation coefficients examined associations between the resident physicians' practices, attitudes, and personal habits. Stepwise multiple linear regression identified predictors of exercise counseling by the resident physicians. RESULTS: A total of 251 resident physicians responded. Only 15.5% reported counseling more than 80% of the clinic patients about exercise. Over 93% understood the benefits of exercise, and almost all (96%) felt that it was a physician's responsibility to counsel patients about exercise. Only 29% felt successful at getting their patients to start exercising, and only 28% felt confident in their skills to prescribe exercise for patients. Ninety-one percent felt that training in exercise counseling would be worthwhile. The significant predictors of physician exercise counseling were perception of exercise counseling as a priority (p <.001), confidence in exercise-counseling skills (p <.001), and postgraduate year of training (p <.05) (R(2) =.18). The significant predictors of physicians' confidence in exercise-counseling skills included physician's gender (i.e., men) (p <.001), perception that exercise is important for a healthy 35-year-old (p <.01), feeling successful at exercise counseling (p <.001), perceiving less interference with counseling by barriers (p <.001), and prior training in exercise counseling (p <.05) (R(2) =.44). CONCLUSIONS: Resident physicians' perceptions of exercise counseling as a priority, confidence in counseling skills, and postgraduate year of training are important predictors of their providing exercise counseling. These factors should be addressed in future educational programs.