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Background Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members. Methods Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider’s diagnosis of PTSD or if they screened positive using the PTSD Checklist−Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition. Results Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma. Conclusions Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.

Celiac disease (CD) is an increasingly common disease that may affect as many as 1% of the North American population. Recent population-based data suggest a substantial increase in the prevalence of CD over the last several decades. Several factors are hypothesized as possible disease triggers including intercurrent illnesses, such as gastroenteritis, surgeries, and trauma. We used the active duty US military, a unique healthy worker population with essentially complete medical diagnostic coding, as an opportunity to describe trends in CD and deployment-related risk factors. Using electronic medical encounter data (1999-2008) on active duty US military (over 13.7 million person-years), a matched, nested case-control study describing the epidemiology and risk determinants of CD (based on ≥2 ICD-9 medical encounters) was conducted. Incidence and duration of CD-related medical care were estimated, and conditional logistic regression was utilized to evaluate CD risk following infectious gastroenteritis (IGE) occurring within 3 years before CD diagnosis while controlling for other risk factors. A total of 455 incident cases of CD were identified and age, gender, and time matched to 1,820 controls. The incidence of CD increased five-fold from 1.3 per 100,000 in 1999 to 6.5 per 100,000 in 2008, with the highest rates of increase among those over 34 years of age (average annual increase of 0.8 cases per 100,000). A total of 172 IGE episodes, predominately of \"viral etiology\" (60.5%), were documented. In multivariate models, a significant association between IGE and CD was found (Odds ratio (OR): 2.06, 95% confidence interval (CI) 1.43, 2.97). Risk generally increased with temporal proximity to, and non-viral etiology of, exposure. Other notable risk factors for CD in multivariate models were Caucasian race (OR: 3.1, P<0.001), non-Army service (OR: 1.5, P=0.001), and greater than a high-school education (OR: 1.3, P=0.05). Incidence of CD diagnosis in the US military is increasing, particularly among those in the fourth and fifth decades of life and appears higher than other population-based estimates. An association between antecedent IGE and risk of CD was noted, but the potential for exposure misclassification cannot be ruled out and further study is needed to link pathogen-specific exposure to incident CD anti-gluten antibody development or symptom onset.

In this study, we aimed to examine the association between gastrointestinal (GI) symptom presence during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevalence of GI symptoms and the development of post-infectious irritable bowel syndrome (PI-IBS). We used data from a prospective cohort and logistic regression to examine the association between GI symptom status during confirmed SARS-CoV-2 infection and prevalence of persistent GI symptoms at ≥45 days. We also report the incidence of PI-IBS following SARS-CoV-2 infection. Of the 1475 participants in this study, 33.8% (n = 499) had GI symptoms during acute infection. Cases with acute GI symptoms had an odds of persisting GI symptoms 4 times higher than cases without acute GI symptoms (odds ratio (OR) 4.29, 95% confidence interval (CI) 2.45–7.53); symptoms lasted on average 8 months following infection. Of those with persisting GI symptoms, 67% sought care for their symptoms and incident PI-IBS occurred in 3.0% (n = 15) of participants. Those with acute GI symptoms after SARS-CoV-2 infection are likely to have similar persistent symptoms 45 days and greater. These data indicate that attention to a potential increase in related healthcare needs is warranted.

Background Travelers’ diarrhea remains a prevalent illness impacting individuals visiting developing countries, however most studies have focused on this disease in the context of short term travel. This study aims to determine the regional estimates of travelers’ diarrhea incidence, pathogen-specific prevalence, and describe the morbidity associated with diarrheal disease among deployed military personnel and similar long term travelers. Methods We updated a prior systematic review to include publications between January 1990 and June 2015. Point estimates and confidence intervals of travelers’ diarrhea and pathogen prevalence were combined in a random effects model and assessed for heterogeneity. Eighty-two studies were included in the analysis, including 29 new studies since the prior systematic review. Results Military personnel were evaluated in 69% of studies and non-military long term travelers in 34%, with a median duration of travel of 4.9 months, and travel predominantly to the Middle East, Southeast Asia, and Latin America and the Caribbean. Sixty-two percent of tested cases were due to bacterial pathogens, with enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), and Campylobacter predominating, and significant regional variability. The incidence of TD from studies with longitudinal data was 36.3 cases per 100 person-months, with the highest rates in Southeast Asia, Latin America and the Caribbean, and the Middle East, with higher estimates from those studies using self-reporting of disease. Morbidity remained significant, with 21% being incapacitated or placed sick in quarters (SIQ) by their illness, 15% requiring intravenous fluids, and 3% requiring hospitalization. Conclusions In comparison to results from the prior systematic review, there were no significant differences in incidence, pathogen prevalence, or morbidity; however there was a trend toward improved care-seeking by sick individuals.

Travelers' diarrhea (TD) is the most prevalent illness encountered by deployed military personnel and has a major impact on military operations, from reduced job performance to lost duty days. Frequently, the etiology of TD is unknown and, with underreporting of cases, it is difficult to accurately assess its impact. An increasing number of ailments include an altered or aberrant gut microbiome. To better understand the relationships between long-term deployments and TD, we studied military personnel during two nine-month deployment cycles in 2015-2016 to Honduras. To collect data on the prevalence of diarrhea and impact on duty, a total of 1173 personnel completed questionnaires at the end of their deployment. 56.7% reported reduced performance and 21.1% reported lost duty days. We conducted a passive surveillance study of all cases of diarrhea reporting to the medical unit with 152 total cases and a similar pattern of etiology. Enteroaggregative E. coli (EAEC, 52/152), enterotoxigenic E. coli (ETEC, 50/152), and enteropathogenic E. coli (EPEC, 35/152) were the most prevalent pathogens detected. An active longitudinal surveillance of 67 subjects also identified diarrheagenic E. coli as the primary etiology (7/16 EPEC, 7/16 EAEC, and 6/16 ETEC). Eleven subjects were recruited into a nested longitudinal substudy to examine gut microbiome changes associated with deployment. A 16S rRNA amplicon survey of fecal samples showed differentially abundant baseline taxa for subjects who contracted TD versus those who did not, as well as detection of taxa positively associated with self-reported gastrointestinal distress. Disrupted microbiota was also qualitatively observable for weeks preceding and following the incidents of TD. These findings illustrate the complex etiology of diarrhea amongst military personnel in deployed settings and its impacts on job performance. Potential factors of resistance or susceptibility can provide a foundation for future clinical trials to evaluate prevention and treatment strategies.

Irritable bowel syndrome (IBS) is a heterogeneous disorder affecting 12% of the population worldwide. Several studies identify IBS as a sequela of infectious gastroenteritis (IGE) with reported prevalence ranging from 4% to 31% and relative risk from 2.5 to 11.9. This meta-analysis was conducted to explore the differences between reported rates and provide a pooled estimate of risk for postinfectious irritable bowel syndrome (PI-IBS). Electronic databases (MEDLINE, OLDMEDLINE, EMBASE, Cochrane database of clinical trials) and pertinent reference lists (including other review articles). Data were abstracted from included studies by two independent investigators; study quality, heterogeneity, and publication bias were assessed; sensitivity analysis was performed; and a summative effect estimate was calculated for risk of PI-IBS. Eight studies were included for analysis and all reported elevated risk of IBS following IGE. Median prevalence of IBS in the IGE groups was 9.8% (IQR 4.0-13.3) and 1.2% in control groups (IQR 0.4-1.8) (sign-rank test, p= 0.01). The pooled odds ratio was 7.3 (95% CI, 4.7-11.1) without significant heterogeneity (chi2 heterogeneity statistic, p= 0.41). Subgroup analysis revealed an association between PI-IBS risk and IGE definition used. This study provides supporting evidence for PI-IBS as a sequela of IGE and a pooled risk estimate revealing a sevenfold increase in the odds of developing IBS following IGE. The results suggest that the long-term benefit of reduced PI-IBS may be gained from primary prevention of IGE.

Antibodies reactive with the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein are associated with viral neutralization, however low antibody titers, specifically against SARS-CoV-2 variants, may result in reduced viral immunity post naturally acquired infection. A cohort study comprised of 121 convalescent individuals from northern Nevada was conducted looking at anti-RBD antibody levels by enzyme-linked immunosorbent assay. Serum was collected from volunteers by staff at the University of Nevada, Reno School of Medicine Clinical Research Center and assessed for antibodies reactive to various SARS-CoV-2 RBD domains relevant to the time of the study (2020–2021). A nonpaired group of vaccinated individuals were assessed in parallel. The goal of the study was to identify antibody levels against the RBD subunit in convalescent and vaccinated individuals from northern Nevada.

Background. Acinetobacter baumannii is usually associated with nosocomial pneumonia or bacteremia. Reports of A. baumannii skin and soft-tissue infection (SSTI) are uncommon. Methods. We performed a retrospective review of 57 inpatients admitted to a naval hospital ship and identified 8 patients with A. baumannii-associated SSTI. Demographic and clinical characteristics were compared between these patients and 49 patients with A. baumannii infections that were not SSTIs. We also reviewed 18 cases of A. baumannii-associated SSTI from the literature. Results. Our 8 cases of A. baumannii-associated SSTI were associated with combat trauma wounds. The median age of the patients was 26 years. Although not statistically significant, A. baumannii-associated SSTIs were more likely to be associated with gunshot wounds (75% vs. 55%) or external fixators (63% vs. 29%), compared with A. baumannii infections that were not SSTIs. Use of a central venous catheter and total parenteral nutrition was also more common for patients with SSTI. Our cases of A. baumannii-associated SSTI presented as cellulitis with a “peau d'orange” appearance with overlying vesicles and, when untreated, progressed to necrotizing infection with bullae (hemorrhagic and nonhemorrhagic). In our case series, all isolates were multidrug resistant, and clinical success was achieved for 7 of 8 patients with debridement and carbapenem therapy. Conclusions. A. baumannii-associated SSTI is an emerging infection in patients who experience trauma. Clinicians should be aware of the potential role of A. baumannii as a multidrug-resistant pathogen causing hospital-acquired SSTI, particularly when associated with previous trauma or use of invasive devices. It should be suspected in patients who experience trauma and have edematous cellulitis with overlying vesicles. Early empirical coverage for drug-resistant species (e.g., with carbapenem therapy), combined with debridement, is usually curative.

International travelers are frequently afflicted by acute infectious diarrhea, commonly referred to as travelers’ diarrhea (TD). Antibiotics are often prescribed as treatment or prophylaxis for TD; however, little is known about the impacts of these regimens on travelers’ gut microbiomes and carriage of antibiotic resistance genes (ARGs). Here, we analyzed two cohorts totaling 153 US and UK servicemembers deployed to Honduras or Kenya. These subjects either experienced TD during deployment and received a single dose of one of three antibiotics [Trial Evaluating Ambulatory Therapy of Travelers’ Diarrhea (TrEAT TD) cohort] or took once-daily rifaximin (RIF), twice-daily RIF, or placebo as prophylaxis to prevent TD [Trial Evaluating Chemoprophylaxis Against Travelers’ Diarrhea (PREVENT TD) cohort]. We applied metagenomic sequencing on 340 longitudinally collected stool samples and whole-genome sequencing on 54 Escherichia coli isolates. We found that gut microbiome taxonomic diversity remained stable across the length of study for most treatment groups, but twice-daily RIF prophylaxis significantly decreased microbiome richness post-travel. Similarly, ARG diversity and abundance were generally stable, with the exception of a significant increase for the twice-daily RIF prophylaxis group. We also did not identify significant differences between the ARG abundance of E. coli isolates from the TrEAT TD cohort collected from different treatment groups or timepoints. Overall, we found no significant worsening of gut microbiome diversity or an increase in ARG abundance following single-dose treatment for TD, underscoring that these can be effective with low risk of impact on the microbiome and resistome, and identified the relative microbiome risks and benefits associated with the three regimens for preventing TD. The travelers’ gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers’ diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers’ microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD—even in moderate to severe cases or in regions with high infectious disease burden—is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

Functional gastrointestinal disorders (FGDs) are recognized sequelae of infectious gastroenteritis (IGE). Within the active duty military population, a group with known high IGE rates, the population-based incidence, risk factors, and attributable burden of care referable to FGD after IGE are poorly defined. Using electronic medical encounter data (1999-2007) on active duty US military, a matched, case-control study describing the epidemiology and risk determinants of FGD (irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FD), dyspepsia (D)) was conducted. Incidence rates and duration of FGD-related medical care were estimated, and conditional logistic regression was utilized to evaluate FGD risk after IGE. A total of 31,866 cases of FGD identified were distributed as follows: FC 55% (n=17,538), D 21.2% (n=6,750), FD 2.1% (n=674), IBS 28.5% (n=9,091). Previous IGE episodes were distributed as follows: specific bacterial pathogen (n=65, 1.2%), bacterial, with no pathogen specified (n=2155, 38.9%), protozoal (n=38, 0.7%), viral (n=3431, 61.9%). A significant association between IGE and all FGD (odds ratio (OR) 2.64; P<0.001) was seen, with highest risk for FD (OR 6.28, P<0.001) and IBS (OR 3.72, P<0.001), and moderate risk for FC (2.15, P<0.001) and D (OR 2.39, P<0.001). Risk generally increased with temporal proximity to, and bacterial etiology of, exposure. Duration of FGD-related care was prolonged with 22.7% having FGD-associated medical encounters 5 years after diagnosis. FGD are common in this population at high risk for IGE. When considering effective countermeasures and mitigation strategies, attention directed toward prevention as well as the acute and chronic sequelae of these infections is needed.