BACKGROUND:U.S. military veterans deployed to the Persian Gulf to serve in the 1990-1991 Gulf War (GWVs) have expressed concerns about potential increased risk of experiencing adverse COVID-related health outcomes given broad near-unique exposure to multiple diverse toxic agents during deployment and ongoing ~30% prevalence of Gulf War Illness (GWI+), a chronic, medically unexplained multi-symptom disorder associated with inflammation and immune dysregulation. METHODS:We conducted a retrospective study in the largest nationwide research cohort of 1990-1991Gulf War era veterans (GWEVs) enrolled in the VA's nationwide Million Veteran Program (MVP) to interrogate: 1) if deployed GWVs had increased risk for testing positive for novel SARS-CoV-2 infection (COVID+), COVID-related hospitalization, ICU admission, or death in 2020 (pre-vaccine period); and 2) if deployed GWVs with GWI+ had particularly increased susceptibility. COVID outcomes ascertained using VA's COVID Data Resource; GWI+ determined using CDC severe criteria in surveyed GWV subcohort. FINDINGS:Our overall GWEV cohort (N = 136,868) had mean age 60.7 years, with 84% male, 27% African-American, and 22% deployed; n = 26,141 COVID-tested in 2020. COVID test-positivity (COVID+) was slightly higher in deployed GWVs (18.8% vs. 17.2% in non-deployed GWEVs, p = 0.005). In multivariable logistic models, there were neither strong nor significant associations between deployment and testing COVID+, COVID-related hospitalization or ICU admission (adjusted [adj] ORs ranged from 0.90-1.06, all p-values >0.05), nor significant differences in COVID-related mortality. Preliminary analysis in our pre-pandemic surveyed deployed GWV subcohort (N = 1,643 COVID-tested, 39% GWI+, 18.4% testing-COVID+, 10.6% COVID+ hospitalized) suggested GWI+ potentially associated with significantly increased COVID-hospitalization risk (adjOR=2.21, 95%CI: 1.02-4.81, p = 0.04); though no significant excess was observed for COVID-related ICU admission or mortality. CONCLUSIONS:Our findings demonstrated that overall deployment to serve in the 1990-1991 Gulf War was not associated with increased COVID-related health risks among Gulf War era veterans using VA healthcare system in early pre-vaccine pandemic era. Preliminary findings suggesting association between Gulf War Illness and potential increased COVID-related hospitalization risk among deployed Gulf War veterans in the early pandemic era warrants replication and ongoing evaluation to assess if it persists in the era of COVID vaccination, oral anti-COVID medications and new viral variants.

BACKGROUND:US service members are often exposed to a range of service-related hazards. To date, there has been limited synthesis of the existing research conducted on military environmental exposures and subsequent psychiatric conditions and symptoms. OBJECTIVE:To systematically review and characterize the main features of studies examining associations between military exposures and mental health outcomes. METHODS:We used evidence mapping methodology to systematically search MEDLINE, Embase, PsycINFO, and PTSDpubs for studies of toxic exposure during military service and psychiatric outcomes, which included psychiatric diagnoses, psychiatric symptoms, and neurocognitive functioning. RESULTS:We identified 49 studies; most were comprised of predominantly White, male veteran samples. Chemical exposures, including chemical munitions from the Gulf War era and Agent Orange from the Vietnam War era, were the most frequently examined military toxic exposures. Symptoms of depression, PTSD, and anxiety were the most commonly examined psychiatric outcomes. Only 9 studies assessed neurocognitive functioning. We found extensive variation in how exposures and outcomes were defined and measured. Most exposure and symptom data were based on self-reports. Overall, available evidence suggests that veterans reporting environmental toxic exposures may report relatively high levels of mental health needs. CONCLUSIONS:We found broad evidence that toxic exposure was associated with poorer mental health outcomes, though the ability to draw stronger conclusions is limited by the quality of the current literature. Future research should focus on longitudinal studies of toxic exposure and mental health that include more broadly representative military populations, including diverse samples and more recent service cohorts.

OBJECTIVE:Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care. METHODS:This cross-sectional study analysed GWVs referred to a Veterans Health Administration clinical War-Related Illness and Injury Study Center (2008-2020). Symptoms, demographics, military service and clinical history were obtained from self-reported intake packets. GWI was defined by the Centers for Disease Control and Prevention criteria requiring moderate-to-severe symptoms in at least two of three domains: fatigue, musculoskeletal and mood cognition. UGI symptoms were analysed individually as a composite variable and additively (0-5). Logistic regression models estimated ORs for associations between UGI symptoms, GWI and GI specialty care. RESULTS:The cohort included 596 GWVs (mean age 49.3 years, 88% men). Most (93.5%) reported at least one UGI symptom, with a mean of 2.8 symptoms. GWI was identified in 413 (69%). Veterans with GWI were more likely to report UGI symptoms (98.3% vs 82.5%) and had a higher mean symptom count (3.1 vs 2.1). Adjusted ORs for UGI symptoms in GWI ranged from 1.79 (dysphagia) to 3.57 (nausea/vomiting). CONCLUSION:UGI symptoms are common among GWVs and strongly associated with GWI. Clinicians should screen for UGI symptoms and follow standard protocols for treatment and referral.

INTRODUCTION:Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. MATERIALS AND METHODS:We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. RESULTS:Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). CONCLUSIONS:More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

British Journal of HaematologyEarly View LETTER TO THE EDITOR Paediatric patients with suspected immune thrombotic thrombocytopenic purpura also experience treatment delays Alexandre Soares Ferreira Junior, Alexandre Soares Ferreira Junior orcid.org/0000-0002-1256-1249 Department of Medicine, Faculdade de Medicina de São José do Rio Preto, São Paulo, São José do Rio Preto, BrazilSearch for more papers by this authorMorgana Pinheiro Maux Lessa, Morgana Pinheiro Maux Lessa Department of Medicine, Faculdade de Medicina de São José do Rio Preto, São Paulo, São José do Rio Preto, BrazilSearch for more papers by this authorStephen H. Boyle, Stephen H. Boyle Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorKate Sanborn, Kate Sanborn Duke Biostatistics, Epidemiology and Research Design Core, Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorMaragatha Kuchibhatla, Maragatha Kuchibhatla Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorOluwatoyosi A. Onwuemene, Corresponding Author Oluwatoyosi A. Onwuemene [email protected] orcid.org/0000-0001-7266-7101 Division of Hematology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Correspondence Oluwatoyosi A. Onwuemene, 40 Duke Medicine Circle, DUMC Box 3422, Durham, NC 27710, USA. Email: [email protected]Search for more papers by this author Alexandre Soares Ferreira Junior, Alexandre Soares Ferreira Junior orcid.org/0000-0002-1256-1249 Department of Medicine, Faculdade de Medicina de São José do Rio Preto, São Paulo, São José do Rio Preto, BrazilSearch for more papers by this authorMorgana Pinheiro Maux Lessa, Morgana Pinheiro Maux Lessa Department of Medicine, Faculdade de Medicina de São José do Rio Preto, São Paulo, São José do Rio Preto, BrazilSearch for more papers by this authorStephen H. Boyle, Stephen H. Boyle Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorKate Sanborn, Kate Sanborn Duke Biostatistics, Epidemiology and Research Design Core, Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorMaragatha Kuchibhatla, Maragatha Kuchibhatla Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USASearch for more papers by this authorOluwatoyosi A. Onwuemene, Corresponding Author Oluwatoyosi A. Onwuemene [email protected] orcid.org/0000-0001-7266-7101 Division of Hematology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Correspondence Oluwatoyosi A. Onwuemene, 40 Duke Medicine Circle, DUMC Box 3422, Durham, NC 27710, USA. Email: [email protected]Search for more papers by this author First published: 04 January 2024 https://doi.org/10.1111/bjh.19290Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1Joly BS, Coppo P, Veyradier A. Pediatric thrombotic thrombocytopenic purpura. Eur J Haematol. 2018; 101(4): 425–434. 10.1111/ejh.13107 PubMedWeb of Science®Google Scholar 2Joly BS, Stepanian A, Leblanc T, Hajage D, Chambost H, Harambat J, et al. 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Objectives: To examine whether severe Gulf War illness (SGWI) case status was associated with longitudinal multimorbidity patterns. Methods: Participants were users of the Veteran Health Administration Health Care System drawn from the Gulf War Era Cohort and Biorepository (n = 840). Longitudinal measures of multimorbidity were constructed using (1) electronic health records (Charlson Comorbidity Index; Elixhauser; and Veterans Affairs Frailty Index) from 10/1/1999 to 6/30/2023 and (2) self-reported medical conditions (Deficit Accumulation Index) since the war until the survey date. Accelerated failure time models examined SGWI case status as a predictor of time until threshold level of multimorbidity was reached, adjusted for age and sociodemographic and military characteristics. Results: Models, adjusted for covariates, revealed that (1) relative to the SWGI- group, the SGWI+ group was associated with an accelerated time for reaching each threshold and (2) the relationship between SGWI and each threshold was not moderated by age. Discussion: Findings suggest that veterans with SGWI experienced accelerated aging.

Gulf War illness (GWI) is a chronic multisymptom disorder of unknown etiology that is believed to be caused by neurotoxicant exposure experienced during deployment to the Gulf War. Posttraumatic stress disorder (PTSD) covaries with GWI and is believed to play a role in GWI symptoms. The present study examined the association between self-reported military exposures and GWI, stratified by PTSD status, in veterans from the Gulf War Era Cohort and Biorepository who were deployed to the Persian Gulf during the war. Participants self-reported current GWI and PTSD symptoms as well as military exposures (e.g., pyridostigmine [PB] pills, pesticides/insecticides, combat, chemical attacks, and oil well fires) experienced during the Gulf War. Deployed veterans' (N = 921) GWI status was ascertained using the Centers for Disease Control and Prevention definition. Individuals who met the GWI criteria were stratified by PTSD status, yielding three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression, adjusted for covariates, was used to examine associations between GWI/PTSD groups and military exposures. Apart from insect bait use, the GWI+/PTSD+ group had higher odds of reporting military exposures than the GWI+/PTSD- group, adjusted odds ratio (aOR) = 2.15, 95% CI [1.30, 3.56]-aOR = 6.91, 95% CI [3.39, 14.08]. Except for PB pills, the GWI+/PTSD- group had a higher likelihood of reporting military exposures than the GWI- group, aOR = 2.03, 95% CI [1.26, 3.26]-aOR = 4.01, 95% CI [1.57, 10.25]. These findings are consistent with roles for both PTSD and military exposures in the etiology of GWI.

Introduction: When immune thrombotic thrombocytopenic purpura (TTP) is suspected, outcomes are impacted by time to therapeutic plasma exchange (TPE). We evaluated the impact of time to TPE on outcomes in suspected TTP cases admitted through the Emergency Department (ED) vs. transferred from another facility (Transfer). Materials and methods: In a retrospective analysis of the National Inpatient Sample, we examined the association between TTP outcomes and admission source (ED vs. Transfer) for the primary outcome of time to TPE. A second stratified analyses within each analytic group examined the association of time to TPE ( 1 day, 1 day, 2 days, and 2 days) and outcomes for the composite outcome of mortality, major bleeding and thrombosis. Results: Of 1195 cases, 793 (66 %) were admitted through the ED and 402 (34 %) were transferred. Compared to ED cases, Transfers had a longer hospital length of stay (14.69 vs. 16.65 days, p = 0.0060). For ED cases, TPE after >2 days was associated with higher odds of the composite outcome (OR = 1.68 95 % CI: 1.11-2.54; p = 0.0150) and mortality (OR = 3.01 95 % CI: 1.38-6.57; p = 0.0056). For Transfers, TPE on day 2 was associated with higher odds of the composite outcome (OR = 3.00 95 % CI: 1.31-6.89; p = 0.0096) and mortality (OR = 4.95 95 % CI: 1.12-21.88; p = 0.0350). Conclusions: In suspected TTP admitted through the ED or transferred, there was no significant difference in time to TPE. A longer time to TPE was associated with worse outcomes. Future studies should evaluate strategies to decrease initial time to TPE.

This study examines how health-related quality of life (HRQOL) and related indices vary by Gulf War illness (GWI) case status. The study population included veterans from the Gulf War Era Cohort and Biorepository (n = 1116). Outcomes were physical and mental health from the Veterans RAND 12 and depression, post-traumatic stress (PTSD), sleep disturbance, and pain. Kansas (KS) and Centers for Disease Control and Prevention (CDC) GWI definitions were used. Kansas GWI derived subtypes included GWI (met symptom criteria; no exclusionary conditions (KS GWI: Sym+/Dx−)) and those without GWI: KS noncase (1): Sym+/Dx+, KS noncase (2): Sym−/Dx+, and noncase (3): Sym−/Dx−. CDC-derived subtypes included CDC GWI severe, CDC GWI mild-to-moderate and CDC noncases. Case status and outcomes were examined using multivariable regression adjusted for sociodemographic and military-related characteristics. Logistic regression analysis was used to examine associations between GWI case status and binary measures for depression, PTSD, and severe pain. The KS GWI: Sym+/Dx− and KS noncase (1): Sym+/Dx+ groups had worse mental and physical HRQOL outcomes than veterans in the KS noncase (2): Sym−/Dx+ and KS noncase (3): Sym−/Dx− groups (ps < 0.001). Individuals who met the CDC GWI severe criteria had worse mental and physical HRQOL outcomes than those meeting the CDC GWI mild-to-moderate or CDC noncases (ps < 0.001). For other outcomes, results followed a similar pattern. Relative to the less symptomatic comparison subtypes, veterans who met the Kansas symptom criteria, regardless of exclusionary conditions, and those who met the CDC GWI severe criteria experienced lower HRQOL and higher rates of depression, PTSD, and severe pain.

Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990–1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans’ reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans’ severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78–9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02–5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01–5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of chronic symptoms, many of which were associated with reported neurotoxicant exposures during the war.

BACKGROUND:For inpatients undergoing therapeutic plasma exchange (TPE) in the United States, the primary mode of venous access is the central venous catheter (CVC). To evaluate the impact of CVC on thrombosis outcomes of patients undergoing TPE, we analyzed the National Inpatient Sample (NIS) database. STUDY DESIGN AND METHODS:In a cross-sectional analysis of the NIS, we identified hospital discharges of adult patients treated with TPE. Cases were classified into two groups based on CVC status. The primary outcome was thrombosis. Secondary outcomes were major bleeding, packed red blood cell (PRBC) transfusion, in-hospital mortality, hospital length of stay (LOS), and charges. RESULTS:Among 9863 TPE-treated discharges, CVC was used in 5988 (60%). These numbers correspond to weighted national estimates of 49 315 and 29 940, respectively. There was a positive and significant association between CVC and thrombosis (OR = 1.23, 95% 1.04-1.46, P = 0.0174), PRBC transfusion (OR = 1.15, 95% 1.03-1.29, P = 0.0121), in-hospital mortality (OR = 1.36, 95% 1.10-1.68, P = 0.0043), hospital LOS (15.63 vs 12.45 days, P < 0.0001) and hospital charges ($166 387 vs. $132 655, P < 0.0001). CONCLUSION:In hospitalized patients undergoing TPE, CVC use is associated with increased rates of thrombosis. Future studies are needed to investigate strategies to decrease CVC use and/or prevent CVC-associated complications in TPE-treated inpatients.

Abstract Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are used in select cases with heparin‐induced thrombocytopenia (HIT). In a cross‐sectional analysis, a propensity matched sample was generated by IVIG or TPE treatment status to assess the primary outcome of mortality. In 500 HIT cases, IVIG or TPE was not associated with increased mortality (OR = 1.46; 95% CI: 0.81–2.63, p = 0.2052) but was associated with a higher likelihood of major bleeding (OR = 1.75; 95% CI: 1.03–2.96, p = 0.0376). The use of IVIG or TPE in HIT cases with bleeding contraindications to standard therapies should be further investigated.

About 25–35% of United States veterans who fought in the 1990–1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness (GWI). Thirty years later, there is little consensus on the causes or biological underpinnings of GWI. The Gulf War Era Cohort and Biorepository (GWECB) was designed to investigate genetic and environmental associations with GWI and consists of 1343 veterans. We investigate candidate gene–toxicant interactions that may be associated with GWI based on prior associations found in human and animal model studies, focusing on SNPs in or near ACHE, BCHE, and PON1 genes to replicate results from prior studies. SOD1 was also considered as a candidate gene. CDC Severe GWI, the primary outcome, was observed in 26% of the 810 deployed veterans included in this study. The interaction between the candidate SNP rs662 and pyridostigmine bromide (PB) pills was found to be associated with CDC Severe GWI. Interactions between PB pill exposure and rs3917545, rs3917550, and rs2299255, all in high linkage disequilibrium in PON1, were also associated with respiratory symptoms. These SNPs could point toward biological pathways through which GWI may develop, which could lead to biomarkers to detect GWI or to better treatment options for veterans with GWI.

BACKGROUND:Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE.STUDY DESIGN AND METHODS:In a cross-sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE-treated conditions. A 1:3 propensity-matched analysis of TPE- to non-TPE-treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes.RESULTS:The study population was 15,964 discharges, of which 3991 were TPE- treated. The prevalence of major bleeding was low (5.4%). When compared to non-TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16-1.63, p = .0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42-1.94, p < .0001), in-hospital mortality (OR = 1.45, 95% CI: 1.10-1.90, p = .0008), hospital length of stay (12.45 [95% CI: 11.95-12.97] vs. 7.38 [95% CI: 7.12-7.65] days, p < .0001) and total charges, ($125,123 [95% CI: $119,220-$131,317] vs. $61,953 [95% CI: $59,391-$64,625], p < .0001), and disposition to non-self-care (OR = 1.29, 95% CI: 1.19-1.39, p < .0001).DISCUSSION:The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE-associated bleeding.

Introduction: In heparin-induced thrombocytopenia (HIT), selected patients are treated with therapies directed at the immune response, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). To determine IVIG and TPE characteristics and outcomes in HIT, we analyzed the National Inpatient Sample (NIS) database. Methods: In a population-based analysis of the NIS, we identified hospital discharges of adult patients with a HIT diagnosis. A two-level statistical analysis was performed comparing cases as follows 1) IVIG or TPE vs. none; and 2) IVIG vs. TPE. For each analysis, the primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, infections, hospital length of stay, and total charges. Results: Among 22,152 discharges with a HIT diagnosis, 77 (0.34%) and 52 (0.23%) received TPE and IVIG, respectively. In the first level analysis of TPE or IVIG vs. no treatment, TPE or IVIG treatment was associated with a higher likelihood of in-hospital mortality (OR = 1.85; 95%CI: 1.13?3.03, p = 0.0104), major bleeding (OR = 1.91; 95%CI: 1.25?2.93, p = 0.0030), gastrointestinal bleeding (OR = 1.89; 95%CI: 1.08?3.30, p = 0.0259), and infection (OR = 1.65; 95% CI:1.13?2.41, p = 0.0095). In the second-level analysis comparing IVIG vs. TPE, there were no significant differences in patient characteristics or outcomes in both unadjusted and adjusted analyses. Conclusions: In this population-based analysis of HIT, we found similar outcomes of IVIG and TPE-treated cases. Given the small sample size, future studies are needed to confirm this observation.

Background Heparin-induced thrombocytopenia (HIT) is characterized by anti-heparin/platelet factor 4 immune complexes, which are removed by therapeutic plasma exchange (TPE). Our main objective was to study TPE outcomes in HIT using a large administrative claims database. Study design and methods We used the National Inpatient Sample (NIS) to identify hospital discharges of adult patients (>= 18) with a primary or secondary diagnosis of HIT. Cases were classified into two groups based on TPE use. The primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, hospital length of stay (LOS), and charges. Multivariable regression analysis, controlling for age and medical comorbidities, was used to examine the association of TPE with study outcomes. Results A HIT diagnosis was made in 22 165 discharges, of which 90 (0.4%) received TPE. Corresponding national estimates are 106 435 and 439, respectively. TPE was not associated with decreased in-hospital mortality (OR = 1.72; 95%CI: 0.93-3.17, P = .085). However, TPE was associated with a higher likelihood of major bleeding (OR = 2.35; 95%CI: 1.40-3.68, P = .0009), primarily driven by gastrointestinal bleeding (OR = 2.21; 95%CI: 1.17-4.17, P = .015). TPE was also associated with higher hospital LOS (20.5 vs 10 day, P < .0001) and charges (USD 211181 vs USD 81654, P < .0001). Conclusion TPE's association with increased bleeding and a prolonged hospital course indicates that it is being used in HIT cases with a severe clinical phenotype. Future studies are needed to better characterize the HIT phenotype that will most benefit from TPE.

A correction to this paper has been published: https://doi.org/10.1007/s11306-021-01809-z

The short (s) variant of the serotonin transporter (5-HTT) gene linked functional polymorphic region (5-HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. We examined the relationship between 5-HTTLPR genotype and symptoms of depression in two samples. Study 1 = 288 participants from a study of caregiver stress; and Study 2 = 142 participants from a study examining psychosocial stressors, genetics, and health. Main effects of 5-HTTLPR on symptoms of depression were examined, along with moderation by stress (caregiving status or low childhood socioeconomic status (SES), gender, and race. The 5-HTTLPR x stress group x gender interaction was significant in both samples (P < 0.003, and P < 0.008, respectively). For females, the s allele, combined with caregiving stress (Study 1) or low childhood SES (Study 2), was associated with higher depression scores as compared to participants in the non-stressor group and those with the long (l) allele; whereas, in males, the l allele, combined with a stressor, was associated with higher depression scores as compared to those in the non-stressor group and those with the s allele. Findings from two independent samples suggest that the association of 5-HTTLPR with depression varies according to gender and stressful life events.