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Objective: We examined the sociodemographic, military, and health characteristics of current cigarette smokers, former smokers, and nonsmokers among Operation Enduring Freedom (OEF) / Operation Iraqi Freedom (OIF) veterans and estimated smoking prevalence to better understand cigarette use in this population. Methods: We analyzed data from the US Department of Veterans Affairs (VA) 2009-201 1 National Health Study for a New Generation of US Veterans. On the basis of a stratified random sample of 60 000 OEF/OIF veterans, we sought responses to a 72-item questionnaire via mail, telephone, or Internet. Cigarette smoking status was based on self-reported cigarette use in the past year. We used multinomial logistic regression to evaluate associations between smoking status and sociodemographic, military, and health characteristics. Results: Among 19 91 1 veterans who provided information on cigarette smoking, 5581 were current smokers (weighted percentage: 32.5%, 95% confidence interval [CI]: 31.7-33.2). Current smokers were more likely than nonsmokers or former smokers to be younger, to have less education or income, to be separated/divorced or never married/single, and to have served on active duty or in the army. Comparing current smokers and nonsmokers, some significant associations from adjusted analyses included the following: having a Mental Component Summary score (a measure of overall mental health) above the mean of the US population relative to below the mean (adjusted odds ratio [aOR] = 0.81, 95% CI: 0.73-0.90); having physician-diagnosed depression (aOR = 1.52, 95% CI: 1.33-1.74), respiratory conditions (aOR = 1.16, 95% CI: 1.04-1.30), or repeated seizures/blackouts/convulsions (aOR = 1.80, 95% CI: 1.22-2.67); heavy alcohol use vs never use (aOR = 5.49, 95% CI: 4.57-6.59); a poor vs excellent perception of overall health (aOR = 3.79, 95% CI: 2.60-5.52); and being deployed vs nondeployed (aOR = 0.87, 95% CI: 0.78-0.96). Using health care services from the VA protected against current smoking. Conclusion: Mental and physical health, substance use, and military service characteristics shape cigarette-smoking patterns in OEF/OIF veterans. [ABSTRACT FROM AUTHOR]

The United States Government (USG) public-private partnership "Accelerating COVID-19 Treatment Interventions and Vaccines" (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during "peacetime," as well., Competing Interests: None., (© The Author(s) 2024.)

In September 2020, the Department of Veterans Affairs (VA) launched a novel volunteer research registry to rapidly recruit eligible study participants for research on SARS-CoV-2 and COVID-19 vaccines and treatments at VA Medical Centers selected as study sites for COVID-19 clinical trials. Targeted multimedia outreach campaigns were used to recruit diverse populations, including those historically under-represented in medical research. By November 2022, 58,561 volunteers were enrolled in the registry, 19% of whom were women, 9% Hispanic/Latino, and 8% Black. The registry's strategic approach to outreach proved successful in recruiting diverse volunteers, with geotargeted e-mails recruiting the most diversity., Competing Interests: No competing financial interests exist., (© Mary M. Klote et al., 2023; Published by Mary Ann Liebert, Inc.)

Objectives: To examine differences in potentially traumatic events (PTEs), probable PTSD, and health-related quality of life (HRQoL) between lesbian, gay, and bisexual (LGB) and heterosexual Vietnam Era veterans. Method: Data are from the 2016-2017 Vietnam Era Health Retrospective Observational study survey ( n = 18,866; 45% response rate). PTEs were defined using the 10-item Brief Trauma Questionnaire and a dichotomous item about whether respondents witnessed sexual assault during military service. Current probable PTSD was measured with the Primary Care PTSD Screen, and mental and physical HRQoL was assessed with the SF-8™. Multivariable regression analyses were first adjusted for sociodemographic and military-related characteristics, and then with PTEs as a count variable ranging from 0-11. Survey weights accounted for the complex sampling design and nonresponse. Results: Approximately 1.5% of veterans were LGB. Compared to heterosexual veterans, LGB veterans were more likely to report exposure to natural disasters, childhood physical abuse, adulthood physical assault, and sexual assault, and they were less likely to report combat exposure, witnessing someone being seriously injured or killed, or witnessing sexual assault while in the military. Compared to heterosexual veterans, LGB veterans had greater odds of current probable PTSD (adjusted odds ratio [ aOR ] = 1.50, 95% CI [1.04, 2.16]) and poorer mental HRQoL ( B = -1.70, SE = .72, p = .018). PTEs attenuated sexual orientation differences in probable PTSD ( aOR = 1.27, 95% CI [.82, 1.97]) and poorer mental HRQoL ( B = -1.22, SE = .67, p = .067). Conclusions: Among Vietnam Era veterans, PTEs differ based on sexual orientation, and contribute to LGB veterans' greater prevalence of current probable PTSD and poorer mental HRQoL relative to heterosexual veterans. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment., Objective: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high., Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978)., Setting: Multicenter trial., Patients: Hospitalized patients with COVID-19 without end-organ failure., Intervention: Bamlanivimab (7000 mg) or placebo., Measurements: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections)., Results: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs., Limitation: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed., Conclusion: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting., Primary Funding Source: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Background: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19. Four agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed., Protocol Design and Implementation: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. TICO utilizes a MAMS design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo as well as the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and DSMB schedule was developed for the study of agents with limited in-human data., Challenges: Challenges included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff, and obtaining regulatory approvals across a global network of sites., Conclusion: Through a robust multi-network partnership, the TICO protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required.

Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19., Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5., Results: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47)., Conclusions: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.)., (Copyright © 2020 Massachusetts Medical Society.)