Chlamydial and Gonococcal Infections and Adverse Reproductive Health Conditions Among Patients Assigned Female at Birth in the Veterans Health Administration.

BACKGROUND: Reproductive age female individuals comprise the fastest-growing segment of Veterans Health Administration patients, but little is known about rates of reproductive health outcomes among those with chlamydia or gonorrhea infections. Our aim was to estimate the risk of pelvic inflammatory disease, ectopic pregnancy, infertility, and pelvic pain in female veterans tested for chlamydia or gonorrhea. METHODS: We performed a retrospective cohort analysis of female veterans tested for chlamydia or gonorrhea between January 1, 2010, and December 31, 2020. We calculated rates of pelvic inflammatory disease, ectopic pregnancy, infertility, and pelvic pain per 100,000 person-years and used Cox proportional hazards regression models to estimate the risk of these reproductive health conditions according to infection status after adjustment for age, race, ethnicity, military sexual trauma, mental health diagnoses, and substance use disorder. RESULTS: Of female veterans, 232,614 were tested at least once for chlamydia or gonorrhea, with a total of 1,665,786 person-years of follow-up. Of these, 12,971 had positive chlamydia or gonorrhea results (5.8%, 796 cases per 100,000 person-years). Compared with people who tested negative, those testing positive had double the risk of pelvic inflammatory disease (adjusted hazard ratio [aHR], 1.94; 95% confidence interval [CI], 1.81-2.07), 11% increased risk of infertility (aHR, 1.11; 95% CI, 1.04-1.18), 12% increased risk of pelvic pain (aHR, 1.12; 95% CI, 1.08-1.17), and 21% increased risk of any of these conditions (aHR, 1.21; 95% CI, 1.17-1.25). People with positive chlamydia or gonorrhea testing tended to have an increased risk of ectopic pregnancy (aHR, 1.14; 95% CI, 1.0-1.30). Among those with a positive test result, 2218 people (17.1%) had 1 or more additional positive test results. Compared with those with 1 positive test result, people with more than 1 positive test result had a significantly increased risk of pelvic inflammatory disease (aHR, 1.37; 95% CI, 1.18-1.58), infertility (aHR, 1.20; 95% CI, 1.04-1.39), and pelvic pain (aHR1.16; 95% CI, 1.05-1.28), but not ectopic pregnancy (aHR, 1.09; 95% CI, 0.80-1.47). CONCLUSIONS: Female veterans with positive chlamydia or gonorrhea results experience a significantly higher risk of pelvic inflammatory disease, infertility, and pelvic pain, especially among those with repeat infection.

Gonorrhea and Chlamydia Testing and Case Rates Among Women Veterans in the Veterans Health Administration.

BACKGROUND: United States (US) rates of sexually transmitted infection (STI) in women, especially gonorrhea and chlamydia, have increased over the past decade. Women Veterans may be at increased risk for STIs due to high rates of sexual trauma. Despite the availability of effective diagnostic tests and evidence-based guidelines for annual screening among sexually active women under age 25, screening rates for gonorrhea and chlamydia remain low in the US and among Veterans. OBJECTIVE: To examine patient characteristics and health system factors associated with gonorrhea and chlamydia testing and case rates among women Veterans in the Veterans Health Administration (VHA) in 2019. DESIGN: We performed a retrospective cohort study of all women Veterans in VHA care between January 1, 2018, and December 31, 2019. PARTICIPANTS: Women Veteran patients were identified as receiving VHA care if they had at least one inpatient admission or outpatient visit in 2019 or the preceding calendar year. KEY RESULTS: Among women under age 25, 21.3% were tested for gonorrhea or chlamydia in 2019. After adjusting for demographic and other health factors, correlates of testing in women under age 25 included Black race (aOR: 2.11, CI: 1.89, 2.36), rural residence (aOR: 0.84, CI: 0.74, 0.95), and cervical cancer screening (aOR: 5.05, CI: 4.59, 5.56). Women under age 25 had the highest infection rates, with an incidence of chlamydia and gonorrhea of 1,950 and 267 cases/100,000, respectively. Incidence of gonorrhea and chlamydia was higher for women with a history of military sexual trauma (MST) (chlamydia case rate: 265, gonorrhea case rate: 97/100,000) and those with mental health diagnoses (chlamydia case rate: 263, gonorrhea case rate: 72/100,000.) CONCLUSIONS: Gonorrhea and chlamydia testing remains underutilized among women in VHA care, and infection rates are high among younger women. Patient-centered, system-level interventions are urgently needed to address low testing rates.

Robust Hepatitis A Vaccination Response Within the United States Veterans Health Administration in the Wake of State Outbreaks.

We assessed hepatitis A (HepA) vaccine receipt among susceptible individuals in outbreak and matched nonoutbreak states. Difference-in-differences models and multivariable logistic regression were used to compare HepA vaccination rates in these states. In the postoutbreak year, there was a 112% increase in HepA vaccinations in outbreak states versus a 6% decrease in nonoutbreak states. Differences persisted in our multivariable model (adjusted odds ratio = 2.53; 95% confidence interval = 2.45, 2.61). HepA vaccination rates increased dramatically in outbreak states, but many individuals susceptible to hepatitis A virus remain unvaccinated. (Am J Public Health. 2022;112(7):990-994. https://doi.org/10.2105/AJPH.2022.306845).

Participant Characteristics and Attendance Patterns for a Multispecialty Veterans Affairs ECHO Program 2012-2018.

Introduction: The Veteran Integrated Service Network (VISN) 20 Veterans Affairs-Extension for Community Healthcare Outcomes (VA-ECHO) program connects specialty and primary care providers (PCPs) across large geographic areas, utilizing video-teleconferencing with the intention of increasing access to care among underserved and isolated populations. No previously published work describes participation patterns of a multispecialty ECHO program. We describe the development of VISN 20 VA-ECHO program to inform the design and evaluation of ECHO programs. Methods: The participant cohort included VA-affiliated licensed health care professionals, including trainees, who attended at least one VISN 20 VA-ECHO session between April 2012 and December 2018. Participant characteristics reported include gender, clinical location, clinical specialty, discipline, and rurality. Results: Over the 6-year time frame, VISN 20 VA-ECHO offered 945 sessions in 14 clinical specialties and recorded 17,893 hours of attendance. The cohort included 1,346 participants, 74.3% of whom were female, 85.2% employed in medical centers, and 40.7% affiliated with primary care. Most participants (62.3%) attended one specialty exclusively; among all participants, 40% attended five or more sessions. Discussion: Although VA-ECHO was implemented to develop single specialty expertise among PCPs, our participant cohort represented a more diverse audience from a range of disciplines and specialties. Our experience may be valuable to other teams implementing ECHO programs. Conclusions: Through adaptability and strategies that actively promoted inclusion of a diverse audience, VISN 20 VA-ECHO expanded to include multiple clinical specialties and successfully engaged an audience across a large geographic area and beyond PCPs.

Testing Practices and Incidence of Chlamydial and Gonococcal Infection in the Veterans Health Administration, 2009-2019.

BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae cases reached a record high in the United States in 2018. Although active-duty military service members have high rates of chlamydia and gonorrhea infection, trends in chlamydia and gonorrhea in the Veterans Health Administration (VHA) system have not been previously described, including among patients living with human immunodeficiency virus (HIV) and young women. METHODS: We identified all veterans in VHA care from 2009 through 2019. Tests and cases of chlamydia and gonorrhea were defined based on laboratory results in the electronic health record. Chlamydia and gonorrhea incidence rates were calculated each year by demographic group and HIV status. RESULTS: In 2019, testing for chlamydia and gonorrhea occurred in 2.3% of patients, 22.6% of women aged 18-24 years, and 34.1% of persons living with HIV. The 2019 incidence of chlamydia and gonorrhea was 100.8 and 56.3 cases per 100 000 VHA users, an increase of 267% and 294%, respectively, since 2009. Veterans aged ≤34 years accounted for 9.5% of the VHA population but 66.9% of chlamydia and 42.9% of gonorrhea cases. Chlamydia and gonorrhea incidence rates in persons living with HIV were 1432 and 1687 per 100 000, respectively. CONCLUSIONS: The incidence of chlamydia and gonorrhea rose dramatically from 2009 to 2019. Among tested persons, those living with HIV had a 15.2-fold higher unadjusted incidence of chlamydia and 34.9-fold higher unadjusted incidence of gonorrhea compared with those not living with HIV. VHA-wide adherence to chlamydia and gonorrhea testing in high-risk groups merits improvement.

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

Effects of partnership change on microbicide gel adherence in a clinical trial (HPTN 035).

Use of HIV prevention methods may vary for women by types of sexual partners. In a microbicide safety and effectiveness trial (HPTN 035) differences in adherence to a microbicide study gel were compared between women with new versus ongoing partnerships over time. 1,757 women in the three HPTN 035 trial's arms completed the Follow-up Partner Status (FPS) questionnaire at their last study visit. Women married at baseline were asked if they had the same husband, new husband or new partner. Unmarried women were asked if they had changed partners or married. Self-reported gel adherence during the last sex act was compared at each quarterly visit between women with ongoing versus new partners. High gel adherence was compared with low gel adherence (85-100 vs. <85 % of last vaginal sex acts reported with gel use, respectively) in multivariable models to assess associations with partner change. Overall 7 % of women (n = 123) reported a new partner and 41 % (51) of those reported a new husband. Median gel adherence was reported to be 100 % in women with ongoing partners and 75 % for women with new partners (p < 0.001). In women reporting no gel use in their last sex act, only 12.5 % of the women with a new partner and none of those with an ongoing partner reported using condoms (p < 0.001). Fewer women with new partners reported using both the gel and condom during the last sex act as compared to women with ongoing partners (median 50 vs. 71.4 %, p < 0.001). After adjusting for age, site, education level, and sexual frequency, women with ongoing partners were more likely to report high gel adherence than those with new partners (AOR 2.5, 95 % CI 1.6, 3.9). This pattern persisted when gel use over time was compared between women with new versus ongoing partners. In the HPTN 035 trial, women with new partners had higher HIV incidence and reported less gel use and higher condom use. Specific counseling and support are needed to help women use potential HIV prevention methods, including microbicides, when they are changing partners.

Testing and Case Rates of Gonorrhea, Chlamydia, Syphilis, and HIV among People with Substance Use Disorders in the Veterans Health Administration.

BACKGROUND: Little is known about national patterns of sexually transmitted infection (STI) testing and infections among people with substance use disorders (SUDs). METHODS: This study used a national retrospective analysis of people with SUDs receiving healthcare in the Veterans Health Administration in 2019 (N = 485,869). We describe testing rates, test positivity, and case rates for gonorrhea, chlamydia, syphilis, and HIV among individuals with alcohol, opioid, cocaine, and noncocaine stimulant use disorders in a national cohort of Veterans Health Administration patients. RESULTS: Test and case rates for all STIs were highest among people with noncocaine stimulant use. People with alcohol use disorder had the lowest testing rates but intermediate incidence for all STIs. People with multiple SUDs had higher incidence of all STIs than those with single SUDs. Mental health diagnoses and houselessness were common. The HIV test positivity was 0.14% to 0.36% across SUD groups. CONCLUSIONS: Sexually transmitted infection testing rates between SUD groups were discordant with their respective case rates. High STI rates in people with SUDs suggest a need for more comprehensive testing, particularly for those with noncocaine stimulant use and those with comorbid houselessness or mental health diagnoses.

Sexually Transmitted Infection Testing in the National Veterans Health Administration Patient Cohort During the Coronavirus Disease 2019 Pandemic.

Background: We performed a retrospective study of chlamydia, gonorrhea, syphilis, and human immunodeficiency virus (HIV) testing in the Veterans Health Administration (VHA) during 2019-2021. Methods: We determined the annual number of chlamydia, gonorrhea, syphilis, and HIV tests from 2019 through 2021 using electronic health record data. We calculated rates by age, birth sex, race, census region, rurality, HIV status, and use of preexposure prophylaxis. Results: The VHA system experienced a 24% drop in chlamydia/gonorrhea testing, a 25% drop in syphilis testing, and a 29% drop in HIV testing in 2020 versus 2019. By the conclusion of 2021, testing rates had recovered to 90% of baseline for chlamydia/gonorrhea, 91% for syphilis, and 88% for HIV. Declines and subsequent improvements in sexually transmitted infection (STI) testing occurred unequally across age, sex, race, and geographic groups. Testing for all 4 STIs in 2021 remained below baseline in rural Veterans. Excluding those aged <25 years, women experienced a steeper decline and slower recovery in chlamydia/gonorrhea testing relative to men, but quicker recovery in HIV testing. Asian Americans and Hawaiian/Pacific Islanders had a steeper decline and a slower recovery in testing for chlamydia/gonorrhea. Black and White Veterans had slower recovery in HIV testing compared with other race groups. People living with HIV experienced a smaller drop in testing for syphilis compared with people without HIV, followed by a near-total recovery of testing by 2021. Conclusions: After dramatic reductions from 2019 to 2020, STI testing rates returned to near-baseline in 2021. Testing recovery lagged in rural, female, Asian American, Hawaiian/Pacific Islander, and Black Veterans.

Differences in Syphilis Incidence Using a Laboratory Algorithm in People With and Without HIV in an 11-Year Nationwide Cohort Study.

BACKGROUND: To measure the incidence of syphilis diagnoses among people with HIV vs those without HIV in a national multiyear retrospective cohort. METHODS: Treponemal and nontreponemal tests, HIV status, and demographic data were identified among all individuals receiving Veterans Health Administration (VHA) care between January 1, 2009, and December 31, 2019. Syphilis testing rates and incident syphilis diagnoses as defined by a laboratory algorithm were stratified by HIV status. RESULTS: Syphilis was diagnosed in 1.2% (n = 2283) of 194 322 tested individuals in VHA care in 2019. Among individuals with HIV tested for syphilis, 6.1% met criteria for syphilis compared with 0.7% without HIV. Syphilis incidence in 2019 was 35/100 000, a 17% increase from 2009 (30/100 000). In 2019, syphilis incidence was 3381 per 100 000 persons among individuals with HIV and 19 per 100 000 in those without HIV. CONCLUSIONS: Using a laboratory-based diagnostic algorithm, a 178-fold difference in syphilis incidence was observed between individuals with and without HIV in 2019. US syphilis incidence data that incorporate HIV status are needed. Interventions to monitor and prevent sexually transmitted infections should address the role of HIV status.

Impact of Sleep Telementorship in Primary Care: Sleep VA-ECHO (Veterans Affairs-Extension for Community Healthcare Outcomes).

Sleep VA-ECHO (Veterans Affairs-Extension for Community Healthcare Outcomes) is a national telementorship program intended to improve knowledge about sleep disorders among non-specialty providers. The project goal was to describe the characteristics of Sleep VA-ECHO participants from primary care and their use of program-obtained knowledge in practice. Sleep VA-ECHO consisted of 10 voluntary, 75-min teleconference sessions combining didactics and case discussion. Out of 86 participants, 21 self-identified as primary care team members and completed a program evaluation. Participants self-reported their application of knowledge gained, including changes to practice as a result of program participation. These 21 participants represented 18 sites in 11 states and attended a median of 5.0 sessions. They included physicians (29%), nurse practitioners (24%), and registered nurses (24%). Nearly all participants (95%) reported using acquired knowledge to care for their own patients at least once a month; 67% shared knowledge with colleagues at least once a month. Eighty-five percent reported improved quality of sleep care for their patients, and 76% reported an expanded clinical skillset. The greatest self-reported change in practice occurred in patient education about sleep disorders (95%) and non-pharmacologic management of insomnia (81%).

Incidence, Risk Factors, and Outcomes Associated With In-Hospital Acute Myocardial Infarction.

Importance: Studies of acute myocardial infarction (AMI) occurring outside the hospital have informed approaches to addressing risk, treatment, and patient outcomes. Similar insights for in-hospital AMI are lacking. Objective: To determine the incidence, risk factors, and outcomes associated with in-hospital AMI. Design, Setting, and Participants: Cohort, nested case-control, and matched cohort study of patients hospitalized in US Veterans Health Administration facilities between July 2007 and September 2009. The incidence of in-hospital AMI was determined from a complete cohort of in-hospital AMI relative to the total number of inpatient admissions. From the in-hospital AMI cohort, detailed medical record review was performed on 687 cases and 687 individually matched controls. Risk factors and outcomes associated with in-hospital AMI were determined from matched comparison of in-hospital AMI cases to hospitalized controls. Exposures: Candidate risk factors for in-hospital AMI included characteristics at the time of admission and in-hospital variables prior to the index date. Main Outcomes and Measures: In the determination of the incidence and risk factors associated with in-hospital AMI, the outcome of interest was in-hospital AMI. All-cause mortality was the main outcome of interest following in-hospital AMI. Results: A total of 5556 patients with in-hospital AMI (mean [SD] age, 73 [10] years; 5456 [98.2%] male) were identified among 1.3 million admissions, with an incidence of 4.27 in-hospital AMI events per 1000 admissions. Independent risk factors associated with in-hospital AMI included intensive care unit setting, history of coronary artery disease, heart rate greater than 100 beats/min, hemoglobin level less than 8 g/dL, and white blood cell count 14 000/µL or greater. Compared with the matched control group, mortality was significantly higher for patients with in-hospital AMI (in-hospital mortality, 26.4% vs 4.2%; 30-day mortality, 33.0% vs 10.0%; 1-year mortality, 59.2% vs 34.4%). Conclusions and Relevance: In-hospital AMI was common and associated with common cardiovascular risk factors and markers of acute illness. Patient outcomes following in-hospital AMI were poor, with 1-year mortality approaching 60%. Further study of in-hospital AMI may yield opportunities to reduce in-hospital AMI risk and improve patient outcomes.

Association between hyperglycemia at admission during hospitalization for acute myocardial infarction and subsequent diabetes: insights from the veterans administration cardiac care follow-up clinical study.

OBJECTIVE: Among patients with acute myocardial infarction (AMI) without known diabetes, hyperglycemia at admission is common and associated with worse outcomes. It may represent developing diabetes, but this association is unclear. Therefore, we examined the association between hyperglycemia (≥140 mg/dL) at admission and evidence of diabetes among patients with AMI without known diabetes within 6 months of their hospitalization. RESEARCH DESIGN AND METHODS: We studied a national cohort of consecutive patients with AMI without known diabetes presenting at 127 Veterans Affairs hospitals between October 2005 and March 2011. Evidence of diabetes either at discharge or in the following 6 months was ascertained using diagnostic codes, medication prescriptions, and/or elevated hemoglobin A1c. Association between hyperglycemia at admission and evidence of diabetes was evaluated using regression modeling. RESULTS: Among 10,499 patients with AMI without known diabetes, 98% were men and 1,761 (16.8%) had hyperglycemia at admission. Within 6 months following their index hospitalization, 208 patients (11.8%) with hyperglycemia at admission had evidence of diabetes compared with 443 patients (5.1%) without hyperglycemia at admission (P < 0.001). After multivariable adjustment, hyperglycemia at admission was significantly associated with subsequent diabetes odds ratio 2.56 (95% CI 2.15-3.06). Among those with new evidence of diabetes, 41% patients (267 of 651) had a hemoglobin A1c ≥6.5% without accompanying diagnostic codes or medication prescriptions, suggesting they had unrecognized diabetes. CONCLUSIONS: Hyperglycemia at admission occurred in one of six patients with AMI without known diabetes and was significantly associated with new evidence of diabetes in the 6 months following hospitalization. In addition, two of five patients with evidence of diabetes were potentially unrecognized. Accordingly, diabetes-screening programs for hyperglycemic patients with AMI may be an important component of optimal care.

Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732). Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36) or Ad5-seropositive (titer >200; n = 34). Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes). At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008), and significantly more IP-10 (p = 0.0009), IL-2 (p = 0.006) and IL-10 (p = 0.05) in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these results suggest that vector-specific humoral responses may reduce vaccine-induced T-cell responses by previously undetected mechanisms.