Best Practices in Recruitment and Outreach to Women and Diverse Veterans for Coronavirus Research at the U.S. Department of Veterans Affairs.

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.

Ethical Applications of Artificial Intelligence: Evidence From Health Research on Veterans.

BACKGROUND: Despite widespread agreement that artificial intelligence (AI) offers significant benefits for individuals and society at large, there are also serious challenges to overcome with respect to its governance. Recent policymaking has focused on establishing principles for the trustworthy use of AI. Adhering to these principles is especially important for ensuring that the development and application of AI raises economic and social welfare, including among vulnerable groups and veterans. OBJECTIVE: We explore the newly developed principles around trustworthy AI and how they can be readily applied at scale to vulnerable groups that are potentially less likely to benefit from technological advances. METHODS: Using the US Department of Veterans Affairs as a case study, we explore the principles of trustworthy AI that are of particular interest for vulnerable groups and veterans. RESULTS: We focus on three principles: (1) designing, developing, acquiring, and using AI so that the benefits of its use significantly outweigh the risks and the risks are assessed and managed; (2) ensuring that the application of AI occurs in well-defined domains and is accurate, effective, and fit for the intended purposes; and (3) ensuring that the operations and outcomes of AI applications are sufficiently interpretable and understandable by all subject matter experts, users, and others. CONCLUSIONS: These principles and applications apply more generally to vulnerable groups, and adherence to them can allow the VA and other organizations to continue modernizing their technology governance, leveraging the gains of AI while simultaneously managing its risks.

Half- vs full-dose trivalent inactivated influenza vaccine (2004-2005): age, dose, and sex effects on immune responses.

BACKGROUND: Optimal public health strategies for managing influenza vaccine shortages are not yet defined. Our objective was to determine the effects of age, sex, and dose on the immunogenicity of intramuscular trivalent inactivated vaccine (TIV). METHODS: Healthy adults aged 18 to 64 years, stratified by age (18-49 and 50-64 years) and sex, were randomized to receive full- or half-dose TIV. Hemagglutination inhibition titers against vaccine antigens were measured before and 21 days after immunization. A primary outcome of noninferiority was defined as a difference of less than 20% in the upper 95% confidence interval (CI) of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Secondary outcomes included geometric mean titers, after vaccination side effects, and occurrences of influenza-like illnesses. RESULTS: Among previously immunized subjects (N = 1114) receiving half- vs full-dose TIV (age, 18-49 years, n = 284 [half] and n = 274 [full]; and age 50-64 years, n = 276 [half] and n = 280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18- to 49-year age group exceeded male responses for all strains: responses to half-dose TIV that were comparable with male full-dose responses for A/New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9-30.9) vs 25.6 (95% CI, 21.3-30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8-72.7) vs 44.1 (95% CI, 37.6-51.8); and B antigen, 64.4 (95% CI, 53.9-76.9) vs 60.7 (95% CI, 51.4-71.7) (findings were similar for the 50- to 64-year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P < .05], headache [P < .001], and impact of fatigue [P < .05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full-dose groups regardless of age. CONCLUSIONS: Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full-dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage.

Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis.

BACKGROUND: Patients who have angioedema after taking angiotensin-converting enzyme inhibitors (ACE-Is) have been reported to develop angioedema when taking an angiotensin receptor blocker (ARB), but few studies quantify the risk. OBJECTIVE: To perform a systematic review of the literature. METHODS: A literature search was performed in MEDLINE, EMBASE, BIOSIS, and Current Contents, with no limitations from January 1990 to May 2007. Any article that described a cohort of patients who had angioedema after taking an ACE-I, were subsequently exposed to an ARB, and were followed for a least 1 month were included. The percentage of patients who had angioedema was abstracted from each article, and confidence intervals were calculated using the exact binomial method. The pooled percentage was calculated with the inverse variance method. RESULTS: Two-hundred fifty-four unique articles were identified, and 3 articles met inclusion criteria, which described 71 patients with the outcome of interest. One was a randomized controlled trial and 2 were retrospective cohorts. These articles described both confirmed and possible cases of angioedema. The risk of angioedema was 9.4% (95% confidence interval, 1.6%-17%) for possible cases and 3.5% (95% confidence interval, 0.0%-9.2%) for confirmed cases. No fatal events were reported. No statistical heterogeneity was reported between trials (P > .3). CONCLUSIONS: Limited evidence suggests that for patients who develop angioedema when taking an ACE-I, the risk of development of any subsequent angioedema when taking an ARB is between 2% and 17%; for confirmed angioedema, the risk is 0% to 9.2%. This information will aid clinicians in counseling patients regarding therapy options after development of angioedema due to ACE-Is.

Persistence of vaccinia at the site of smallpox vaccination.

Persistence of vaccinia at vaccination sites may help determine the risk associated with secondary transmission. Culture, PCR, and antigen detection were performed on serial vaccination site swab specimens. On day 21 after vaccination, 37% of volunteers were culture positive, most of whom had received vaccine for the first time. Vaccinia is detectable at least through day 21 after vaccination.

Implications of venom hypersensitivity for a deploying soldier.

Venom immunotherapy (VIT) is a life-saving medical treatment for individuals allergic to Hymenoptera species. Delivery of VIT is a complex process that requires proper extract preparation, shipping, storage, refrigeration, and administration by qualified medical personnel in a facility that can manage a life-threatening allergic emergency (anaphylaxis). Successful VIT requires 3 to 5 years of uninterrupted maintenance injections, which may be difficult to maintain during deployments, particularly in combat operations. The complexity of VIT has resulted in service members being deemed nondeployable and has led to interruption or discontinuation of VIT for deployed service members in the past. We report the case of a 34-year-old Army National Guard soldier who successfully received maintenance VIT while deployed to Operation Iraqi Freedom. This case demonstrates that, with proper coordination and appropriate risk assessment, continuation of complex medical care, such as VIT, can be supported in a combat zone.

Risk factors for Mycobacterium tuberculosis in US chronic dialysis patients.

BACKGROUND: End-stage renal disease is known to disrupt the cell-mediated immune response that is responsible for the killing of intracellular organisms such as Mycobacterium tuberculosis. Risk factors that contribute to the development of tuberculosis (TB) disease in the US dialysis population have not been studied on a large scale. METHODS: A retrospective cohort study of TB disease in 272,024 patients in the US Renal Data System initiated on dialysis therapy between 1 April 1995 and 31 December 1999 with Medicare or Medicaid as primary payer were analysed. A total of 21 risk factors were analysed. RESULTS: Among the US population studied, there is a 1.2 and 1.6% cumulative incidence of TB in patients undergoing either peritoneal or haemodialysis, respectively. Ten risk factors for TB that proved to be statistically significant included advanced age (P<0.001), unemployment (P<0.001), Medicaid insurance (P<0.001), reduced body mass index (P<0.001), decreased serum albumin (P<0.001), haemodialysis (P=0.019), both Asian (P=0.010) and Native American (P=0.020) race, ischaemic heart disease (P=0.032), smoking (P=0.010), illicit drug use (P=0.018) and anaemia (P=0.028). TB was independently associated with increased mortality, adjusted hazard ratio (AHR) 1.42 (95% CI 1.18-1.70, P<0.001). CONCLUSIONS: The prevalence of TB disease in the US dialysis population is low compared with worldwide rates; however, the disease is associated with increased mortality. Of the 10 significant risk factors identified, five are potentially modifiable.

Absence of oropharyngeal vaccinia virus after vaccinia (smallpox) vaccination.

BACKGROUND: With the resumption of the vaccinia (smallpox) vaccination, questions regarding transmission risk prompted this study to determine whether vaccinia virus could be detected in the oropharynx of adults recently vaccinated with vaccinia (smallpox) vaccine. German, Russian, and American studies on the oropharyngeal presence of vaccinia virus revealed conflicting results in different age groups. OBJECTIVE: To measure vaccinia viral particle or antigen presence in the oropharynx of adult health care workers after vaccination with vaccinia (smallpox) vaccine using viral culture and high-sensitivity assays (polymerase chain reaction [PCR] and electrochemiluminescence) and to determine whether there is an association between the presence of vaccinia virus and adverse reactions. METHODS: A total of 155 adults (primary vaccinees and revaccinees) were enrolled for 1 baseline and 5 subsequent throat swabs. The swabs were evaluated using viral culture, PCR, and electrochemiluminescence. RESULTS: Of the 155 participants, 144 had more than 2 throat swabs in the 2 weeks after vaccination. Of the 801 specimens evaluated, there were no positive results by culture, PCR, or electrochemiluminescence except in the control samples (n = 6), which were positive by all 3 methods. CONCLUSIONS: Based on the absence of detectable vaccinia virus in this study population, one can be 95% certain that the true rate of vaccinia virus in the oropharynx of adults during the 2 weeks after vaccination with vaccinia (smallpox) vaccine is 0% to 3.3%. These data should be reassuring to the medical community and support the Advisory Committee on Immunization Practice guidelines that respiratory precautions are not necessary after vaccinia (smallpox) vaccination in healthy adults.

Hypersensitivity pneumonitis.

A case of hypersensitivity pneumonitis (HP) is presented and briefly discussed. The clinical characteristics, diagnosis, pathogenesis, and management of this syndrome are reviewed followed by clinical pearls and pitfalls for the practicing allergist. Most patients with acute HP recover completely with removal from the offending antigen. Treating symptoms only and not avoiding antigen triggers may lead to severe pulmonary fibrosis.

Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000.

The incidence, risk factors, and prognosis for Mycobacterium tuberculosis (MTB) infection have not been reported in a national population of renal transplant recipients. We performed a retrospective cohort study of 15,870 Medicare patients who received renal transplants from January 1, 1998 to July 31, 2000. Cox regression analysis derived adjusted hazard ratios (AHR) for factors associated with a diagnosis of MTB infection (by Medicare Institutional Claims) and the association of MTB infection with survival. There were 66 renal transplant recipients diagnosed with tuberculosis infection after transplant (2.5 cases per 1000 person years at risk, with some falling off of cases over time). The most common diagnosis was pulmonary TB (41 cases). In Cox regression analysis, only systemic lupus erythematosus (SLE) was independently associated with TB. Mortality after TB was diagnosed was 23% at 1 year, which was significantly higher than in renal transplant recipients without TB (AHR, 4.13, 95% CI, 2.21, 7.71, p < 0.001). Although uncommon, MTB infection is associated with a substantially increased risk of mortality after renal transplantation. High-risk groups, particularly those with SLE prior to transplant, might benefit from intensified screening.

Lack of vaccinia viremia after smallpox vaccination.

Although the transmission of certain viral infections (human immunodeficiency virus, hepatitis B and C viruses, and West Nile virus) through donated blood products is well described, the risk of transmitting vaccinia virus after smallpox vaccination is unknown. Blood samples from patients receiving the smallpox vaccine were obtained before vaccination; then from one-half of the study group on alternate days for each of the first 10 days after vaccination; then from all patients on days 14 and 21 after vaccination. Samples were analyzed by culture, polymerase chain reaction, and antigen detection (electrochemiluminescence) assay for the presence of vaccinia virus. Two hundred and twenty samples from 28 volunteers were processed by all 3 laboratory detection methods and all were negative for the presence of vaccinia virus (confidence interval, 0%-12.3%). Viremia with vaccinia virus after smallpox vaccination appears to be an uncommon occurrence.