Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Special Report: Entrustable Professional Activities in Sex- and Gender-Based Women's Health.

BACKGROUND: A set of core competencies in sex- and gender-based women's health (SGWH) has been endorsed by the Society of General Internal Medicine (SGIM), but many residencies lack the resources to implement curricula and clinical assessments that would support achievement of these competencies. AIM: Develop entrustable professional activities (EPA) to support implementation and assessment of clinical care for SGIM's SGWH Core Competencies. PROGRAM DESCRIPTION: Members of SGIM's SGWH Education Interest Group developed 18 SGWH EPAs for internal medicine residents. A team of clinician educators coordinated the preparation, drafting, quality control, and curriculum alignment of the SGWH EPAs through a rigorous process aligned with best practices for EPAs. All EPAs are mapped to the larger competency domains from the Accreditation Council for Graduate Medical Education (ACGME), for use with ACGME Milestones. The authors provide suggestions for the implementation of the EPAs into residency training. CONCLUSION: As residency education moves towards a competency-based structure, EPAs are needed to translate broad competencies into observable clinical skills. The SGWH EPAs provide a rigorously developed and ready-made tool for programs to link the SGWH core competencies to residency curriculum development, clinical assessment, and program evaluation.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Understanding "Hybrid Immunity": Comparison and Predictors of Humoral Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) Vaccines.

BACKGROUND: Comparison of humoral responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/ infection ("hybrid immunity") may clarify predictors of vaccine immunogenicity. METHODS: We studied 2660 US Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-immunoglobulin G (IgG) responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or subclinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated that vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (P < .01), regardless of prior infection severity. An increased time between infection and vaccination was associated with greater post-vaccination IgG response (P < .01). Vaccination-alone elicited a greater IgG response but more rapid waning of IgG (P < .01) compared with infection-alone (P < .01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared with JNJ-78436735 vaccine-receipt (P < .01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (P < .01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared with vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

Position Paper: SGIM Sex- and Gender-Based Women's Health Core Competencies.

Women's health care has evolved significantly since it was first acknowledged as an integral part of internal medicine training more than two decades ago. To update and clarify core competencies in sex- and gender-based women's health for general internists, the Society of General Internal Medicine (SGIM) Women and Medicine Commission prepared the following Position Paper, approved by the SGIM council in 2023. Competencies were developed using several sources, including the 2021 Accreditation Council for Graduate Medical Education Program Requirements for Internal Medicine and the 2023 American Board of Internal Medicine Certification Examination Blueprint. These competencies are relevant to the care of patients who identify as women, as well as gender-diverse individuals to whom these principles apply. They align with pivotal advances in women's health and acknowledge the changing context of patients' lives, reaffirming the role of general internal medicine physicians in providing comprehensive care to women.

Military occupation and testicular germ cell tumour risk among US Air Force servicemen.

OBJECTIVES: Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy among active duty US military servicemen. Occupational risk factors may play a role in TGCT aetiology, although the evidence is inconclusive. The objective of our study was to investigate associations between military occupations and TGCT risk among US Air Force (USAF) servicemen. METHODS: This nested case-control study among active duty USAF servicemen obtained information on military occupations for 530 histologically confirmed TGCT cases diagnosed during 1990-2018 and 530 individually matched controls. We determined military occupations using Air Force Specialty Codes ascertained at two time points: at case diagnosis and at a time point on average 6 years earlier. We computed adjusted ORs and 95% CIs from conditional logistic regression models to evaluate associations between occupations and TGCT risk. RESULTS: The mean age at TGCT diagnosis was 30 years. Increased TGCT risk was observed for pilots (OR=2.84, 95% CI: 1.20-6.74) and servicemen with aircraft maintenance jobs (OR=1.85, 95% CI: 1.03-3.31) who held those jobs at both time points. Fighter pilots (n=18) and servicemen with firefighting jobs (n=18) at the time of case diagnosis had suggestively elevated TGCT odds (OR=2.73, 95% CI: 0.96-7.72 and OR=1.94, 95% CI: 0.72-5.20, respectively). CONCLUSIONS: In this matched, nested case-control study of young active duty USAF servicemen, we found that pilots and men with aircraft maintenance jobs had elevated TGCT risk. Further research is needed to elucidate specific occupational exposures underlying these associations.

Health outcomes among offspring of US Coast Guard responders to the Deepwater Horizon oil spill, 2010-2011.

OBJECTIVE: To evaluate the potential for adverse health outcomes among infants born to US Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill disaster. METHODS: Department of Defense Birth and Infant Health Research programme data identified a cohort of singleton infants born 2010-2011 to USCG personnel in the DWH Oil Spill Coast Guard Cohort study. Infants were included if their military parent ('sponsor') responded to the oil spill during a selected reproductive exposure window (ie, 3 months preconception for male sponsors and periconception through pregnancy for female sponsors), or if their sponsor was a non-responder. χ2 tests and multivariable log-binomial regression were used to compare the demographic and health characteristics of infants born to spill responders and non-responders. RESULTS: Overall, 1974 infants with a male sponsor (n=182 responder, n=1792 non-responder) and 628 infants with a female sponsor (n=35 responder, n=593 non-responder) in the DWH Oil Spill Coast Guard Cohort were identified. Health outcomes were similar among the offspring of male responders and non-responders. The frequency of any poor live birth outcome (ie, low birth weight, preterm birth or birth defect) was higher among infants born to female responders (17.1%, n=6) than non-responders (8.9%, n=53); the maternal age-adjusted association was suggestively elevated (risk ratio 1.93, 95% CI 0.89 to 4.16). CONCLUSION: Infant health outcomes were comparable between the offspring of male USCG oil spill responders and non-responders. Findings were limited by the small number of infants identified, particularly among female responders, and should be interpreted with caution.

Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study - Five years of follow-up.

BACKGROUND: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. METHODS: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. RESULTS: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. CONCLUSION: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

An Expanded Primary Care-Based Women's Health Clinic to Improve Resident Education and Patient Care in Resident Continuity Clinic.

BACKGROUND: Internal medicine (IM) residents are underprepared in women's health. Lack of properly trained faculty and clinic culture limits the ability to provide bedside teaching. AIM: Assess the impact of a primary care-based, women's clinic on residents' quality of care for females. SETTING: Large academic, urban primary care clinic with resident and faculty practices PARTICIPANTS: PGY-2 IM and Med-Peds (MP) residents PROGRAM DESCRIPTION: A weekly half-day, women's clinic to provide expanded women's healthcare to primary care group patients. Residents rotate through the clinic to receive bedside teaching. PROGRAM EVALUATION: Chart review was performed for a representative sample of reproductive-aged women seen in primary care before and after the establishment of the women's clinic. A total of 666 charts were reviewed (314 pre, 352 post). Improvement was seen in residents' rate of sexual histories (54% vs 75%, p< 0.01) with a significant decrease in women not asked about contraception (15% vs 3%, p<0.01). Overall there was a decrease in gynecology referrals (18 to 11%, p=0.02). DISCUSSION: After implementing the women's health clinic, more women were asked about sexual health needs, and fewer were referred to gynecology, suggesting increased women's healthcare provided by residents.

Incidence of chronic respiratory conditions among oil spill responders: Five years of follow-up in the Deepwater Horizon Oil Spill Coast Guard Cohort study.

BACKGROUND: Over ten years after the Deepwater Horizon (DWH) oil spill, our understanding of long term respiratory health risks associated with oil spill response exposures is limited. We conducted a prospective analysis in a cohort of U.S. Coast Guard personnel with universal military healthcare. METHODS: For all active duty cohort members (N = 45,193) in the DWH Oil Spill Coast Guard Cohort Study we obtained medical encounter data from October 01, 2007 to September 30, 2015 (i.e., ~2.5 years pre-spill; ~5.5 years post-spill). We used Cox Proportional Hazards regressions to calculate adjusted hazard ratios (aHR), comparing risks for incident respiratory conditions/symptoms (2010-2015) for: responders vs. non-responders; responders reporting crude oil exposure, any inhalation of crude oil vapors, and being in the vicinity of burning crude oil versus responders without those exposures. We also evaluated self-reported crude oil and oil dispersant exposures, combined. Within-responder comparisons were adjusted for age, sex, and smoking. RESULTS: While elevated aHRs for responder/non-responder comparisons were generally weak, within-responder comparisons showed stronger risks with exposure to crude oil. Notably, for responders reporting exposure to crude oil via inhalation, there were elevated risks for allsinusitis (aHR = 1.48; 95%CI, 1.06-2.06), unspecified chronic sinusitis (aHR = 1.55; 95%CI, 1.08-2.22), chronic obstructive pulmonary disease (COPD) and other allied conditions (aHR = 1.43; 95%CI, 1.00-2.06), and dyspnea and respiratory abnormalities (aHR = 1.29; 95%CI, 1.00-1.67); there was a suggestion of elevated risk for diseases classified as asthma and reactive airway diseases (aHR = 1.18; 95%CI, 0.98-1.41), including the specific condition, asthma (aHR = 1.35; 95%CI, 0.80-2.27), the symptom, shortness of breath (aHR = 1.50; 95%CI, 0.89-2.54), and the overall classification of chronic respiratory conditions (aHR = 1.18; 95%CI, 0.98-1.43). Exposure to both crude oil and dispersant was positively associated with elevated risk for shortness of breath (HR = 2.24; 95%CI, 1.09-4.64). CONCLUSIONS: Among active duty Coast Guard personnel, oil spill clean-up exposures were associated with moderately increased risk for longer term respiratory conditions.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Risk factors for acute mental health symptoms and tobacco initiation in Coast Guard Responders to the Deepwater Horizon oil spill.

Acute mental health symptoms experienced during oil spill response work are understudied, especially among nonlocal responders. We assessed potential risk factors for acute mental health symptoms and tobacco initiation among U.S. Coast Guard responders to the 2010 Deepwater Horizon (DWH) oil spill who completed a deployment exit survey. Cross-sectional associations among responder characteristics, deployment-related stressors (deployment duration, timing, crude oil exposure, physical symptoms, injuries), and professional help-seeking for stressors experienced with concurrent depression/anxiety and tobacco initiation were examined. Log-binomial regression was used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals. Sensitivity analyses excluded responders with a history of mental health conditions using health encounter data from the Military Health System Data Repository. Of the 4,855 responders, 75.5% were deployed from nonlocal/non-Gulf home stations, 5.8% reported concurrent depression and anxiety, and 2.8% reported the initiation of any tobacco product during oil spill response. Self-report of concurrent depression and anxiety was more prevalent among female responders and positively associated with longer deployments, crude oil exposure via inhalation, physical symptoms and injuries, and professional help-seeking during deployment, aPRs = 1.54-6.55. Tobacco initiation was inversely associated with older age and officer rank and positively associated with deployment-related stressors and depression/anxiety during deployment, aPRs = 1.58-4.44. Associations remained robust after excluding responders with a history of mental health- and tobacco-related health encounters up to 3 years before deployment. Depression, anxiety, and tobacco initiation were cross-sectionally associated with oil spill response work experiences among DWH responders, who largely originated outside of the affected community.

A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill.

In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.

Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

BACKGROUND: There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury. METHODS: We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models. RESULTS: The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (µ = - 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (µ = - 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (µ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (µ = - 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (µ = 1859.60 pg/ml; s.e. = 1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases. CONCLUSION: The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.

Race and overall survival in men diagnosed with prostate cancer in the Department of Defense Military Health System, 1990-2010.

BACKGROUND: In the U.S. general population, black men experience poorer survival after prostate cancer (CaP) diagnosis compared to white men, and findings may be impacted by unequal access to healthcare. The objective of the study is to investigate racial differences in overall survival (OS) among Department of Defense beneficiaries diagnosed with CaP. METHODS: A retrospective cohort study was conducted utilizing the Automated Central Tumor Registry within the Military Healthcare System, a system designed to provide equal access. Men diagnosed with primary prostate adenocarcinomas between 1990 and 2010 [n = 18,484; 24% Non-Hispanic black (NHB), 76% Non-Hispanic white (NHW)] were followed through 2013 for vital status. Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards (PH) regression models were used to examine racial differences in OS. RESULTS: Age-specific Kaplan-Meier analyses showed equivalent OS for NHW and NHB men in all age groups, except for 75+, where NHB had poorer OS (p = 0.0048). Multivariable Cox PH models revealed no significant differences in OS for race (HR 1.02; 95% CI 0.95-1.08), except in men aged ≥ 75 years, where NHB men had poorer OS (HR 1.27; 95% CI 1.08-1.49). CONCLUSIONS: Findings suggest that in a healthcare system designed for equal access, disparities in OS among men diagnosed with CaP may not exist.

Serially measured pre-diagnostic levels of serum cytokines and risk of brain cancer in active component military personnel.

BACKGROUND: There is growing evidence that history of allergic or autoimmune disease is associated with reduced risk of glioma, but few prospective studies have explored the biological basis. To assess associations with immune conditions and levels of 14 cytokines in serial prediagnostic serum samples, we conducted a study of glioma/brain cancer nested in a cohort of active component military personnel. METHODS: A total of 457 case-control sets were ascertained from the Department of Defense (DoD) Automated Central Tumour Registry, Defense Medical Surveillance System (DMSS) database, and DoD Serum Repository. These were individually matched on sex, race/ethnicity, birth year, number of serum samples (1, 2 or 3), and date(s) of sample collection. We obtained diagnoses of pre-existing immune-related conditions from the DMSS database and measured cytokines using Meso Scale Discovery assays. Statistical analyses included conditional logistic regression. RESULTS: Overall association between glioma and prior immune-related conditions was null. Higher levels of IL-15 and IL-16 were independently associated with lower glioma risks (Ptrend = 0.002 and Ptrend = 0.001); both associations were more pronounced in individuals with prior immune conditions (Pheterogeneity = 0.0009 and Pheterogeneity = 0.031). CONCLUSIONS: Associations with pre-diagnostic levels of IL-15 and IL-16 and their modification by diagnosis of immune-related conditions support the importance of immune alterations in glioma aetiology years before diagnosis.

The Deepwater Horizon Oil Spill Coast Guard Cohort study.

OBJECTIVES: Long-term studies of oil spill responders are urgently needed as oil spills continue to occur. To this end, we established the prospective Deepwater Horizon (DWH) Oil Spill Coast Guard Cohort study. METHODS: DWH oil spill responders (n=8696) and non-responders (n=44 823) who were members of the US Coast Guard (20 April-17 December 2010) were included. This cohort uses both prospective, objective health data from military medical encounters and cross-sectional survey data. Here, we describe the cohort, present adjusted prevalence ratios (PRs) estimating cross-sectional associations between crude oil exposure (none, low/medium, high) and acute physical symptoms, and present adjusted relative risks (RRs) based on longitudinal medical encounter data (2010-2012) for responders/non-responders and responders exposed/not exposed to crude oil. RESULTS: Responders and non-responders in this large cohort (n=53 519) have similar characteristics. Crude oil exposure was reported by >50% of responders. We found statistically significant associations for crude oil exposure with coughing (PRhigh=1.78), shortness of breath (PRhigh=2.30), wheezing (PRhigh=2.32), headaches (PRhigh=1.46), light-headedness/dizziness (PRhigh=1.96), skin rash/itching (PRhigh=1.87), diarrhoea (PRhigh=1.76), stomach pain (PRhigh=1.67), nausea/vomiting (PRhigh=1.48) and painful/burning urination (PRhigh=2.89) during deployment. Longitudinal analyses revealed that responders had elevated RRs for dermal conditions (RR=1.09), as did oil-exposed responders for chronic respiratory conditions (RR=1.32), asthma (RR=1.83) and dermal conditions (RR=1.21). CONCLUSIONS: We found positive associations between crude oil exposure and various acute physical symptoms among responders, as well as longer term health effects. This cohort is well positioned to evaluate both short-term and long-term effects of oil spill exposures using both self-reported and clinical health data.

The deepwater horizon oil spill coast guard cohort study: A cross-sectional study of acute respiratory health symptoms.

INTRODUCTION: Over 8500 United States Coast Guard (USCG) personnel were deployed in response to the Deepwater Horizon (DWH) oil spill; however, human respiratory effects as a result of spill-related exposures are relatively unknown. METHODS: USCG personnel who responded to the DWH oil spill were queried via survey on exposures to crude oil and oil dispersant, and acute respiratory symptoms experienced during deployment. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and respiratory symptoms. RESULTS: 4855 USCG personnel completed the survey. More than half (54.6%) and almost one-fourth (22.0%) of responders were exposed to crude oil and oil dispersants, respectively. Coughing was the most prevalent symptom (19.4%), followed by shortness of breath (5.5%), and wheezing (3.6%). Adjusted analyses showed an exposure-response relationship between increasing deployment duration and likelihood of coughing, shortness of breath, and wheezing in the pre-capping period. A similar pattern was observed in the post-capping period for coughing and wheezing. Adjusted analyses revealed increased PRs for coughing (PR=1.92), shortness of breath (PR=2.60), and wheezing (PR=2.68) for any oil exposure. Increasing frequency of inhalation of oil was associated with increased likelihood of all three respiratory symptoms. A similar pattern was observed for contact with oil dispersants for coughing and shortness of breath. The combination of both oil and oil dispersants presented associations that were much greater in magnitude than oil alone for coughing (PR=2.72), shortness of breath (PR=4.65), and wheezing (PR=5.06). CONCLUSIONS: Results from the present study suggested strong relationships between oil and oil dispersant exposures and acute respiratory symptoms among disaster responders. Future prospective studies will be needed to confirm these findings.