Conditional Logistic Regression Research Articles

Association of Antithrombotic Drug Use With Incident Intracerebral Hemorrhage Location.

Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.

Hydroxychloroquine Dose and Hospitalizations for Active Lupus.

We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE). We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥ 1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assessed during each 6-month case or control period. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use and other immunosuppressant use. Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight-based dose (≤5 vs. >5 mg/kg/day) and non-weight-based dose (<400 vs. 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20 [95% CI 1.45-12.19] and 3.39 [95% CI 1.31-8.81]). The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long-term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short-term and cumulative risks of increased SLE activity.

Red Blood Cell Polyunsaturated Fatty Acids and Mortality Following Breast Cancer.

Intake of polyunsaturated fatty acids (PUFAs) may impact mortality following breast cancer (BC); however, epidemiological studies have relied on self-reported assessment of PUFA intake. Herein, we examined the associations between red blood cell (RBC) PUFAs and mortality. This nested case-control study included 1,104 women from, the Women's Healthy Eating and Living Study, a multi-site randomized controlled trial. Cases (n=290) were women who died from 1995-2006. Matched controls (n=814) were women who were alive at the end of follow-up. PUFAs were measured in baseline RBC samples and included four ω-3 and seven ω-6 PUFAs. We examined each PUFA individually and Principal Components Factor Analysis (PCFA)-derived scores in association with all-cause mortality (ACM) and BC-specific mortality (BCM) using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In fully-adjusted models, ACM ORs were elevated among women with PUFAs >median (versus ≤median) for α-linolenic acid (ALA, OR=1.63, 95%CI=1.18-2.24) and for linolenic acid (LA, OR=1.56, 95%CI=1.16-2.09), and BCM ORs were elevated for ALA (OR=1.83, 95%CI=1.27-2.63), LA (OR=1.70, 95%CI=1.23-2.37), and γ-linolenic acid (GLA, OR=1.50; 95%CI=1.04-2.16). PCFA-Factor 1 [arachidonic acid/adrenic acid/docosapentaenoic acid] scores >median (versus ≤median) were associated with lower odds of ACM (OR=0.71; 95%CI=0.52-0.97) and BCM (OR=0.69; 95%CI=0.49-0.97), and PCFA-Factor 4 [ALA/GLA] scores >median (versus ≤median) were associated with increased odds of BCM (OR=1.47; 95%CI=1.04-2.09). RBC ALA, LA, and GLA may be prognostic indicators among BC survivors. These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors.

Complementary acupuncture treatment and reduced risk of sudden sensorineural hearing loss in nasopharyngeal carcinoma patients: a retrospective, nested case-control study.

Hearing loss is a frequently observed comorbidity in patients with nasopharyngeal carcinoma (NPC). Accumulating evidence demonstrated that acupuncture can safely manage cancer and its treatment-related symptoms, but its effect in minimizing the likelihood of experiencing sudden sensorineural hearing loss (SSHL) has not been established. So this work aimed to determine the risk of SSHL among NPC persons with or without acupuncture use. One population-level, nested case-control design within a cohort study is employed. Relevant information on persons aged 20-80years who were afflicted with NPC between 2000 and 2010 was extracted from a nationwide health claims database. From them, we identified the cases who had the first SSHL diagnosis occurring after NPC, and all of them were randomly matched to two controls without SSHL. Conditional logistic regression was employed to calculate odds ratios (OR) and its respective 95% confidence intervals (CI) for incident SSHL in relation to acupuncture treatment. Eight hundred eleven SSHL cases were randomly matched to 1452 controls. Those receiving conventional care plus acupuncture use had a reduced adjusted OR of 0.39 (95% CI, 0.25-0.60) for SSHL. We further discovered that the longer usage of acupuncture remarkably correlated with reduction of SSHL risk in a dose-dependent manner. Delineation of the benefit from integration of acupuncture into conventional care may be a reference in instituting more appropriate care for NPC subjects. Patients living with NPC may benefit from a timely integration of acupuncture into routine care to lessen SSHL risk.

Analysis of Antipsychotic Dosage in Patients With Tardive Dyskinesia: A Case-Control Study Using the Claims Database of the Corporate Health Insurance Association.

This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020. The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age. The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively. In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.

THE PREDICTIVE VALUE OF VASCULAR CALCIFICATION ON PLAIN RADIOGRAPHS OF THE FOOT TO DIAGNOSE DIABETES MELLITUS

IntroductionThere are nearly 500,000 people with undiagnosed diabetes mellitus in the UK. The incidental finding vascular calcification on plain radiographs in patients with undiagnosed diabetes has the potential to alter patient management in those presenting with pathology. We hypothesised that the presence of vascular calcification on plain radiographs of the foot may predict the diagnosis of diabetes. The primary aim of this case control study was to determine the positive predictive value of vascular calcification to diagnose diabetes. Secondary aims were to determine the odds of having diabetes dependent on other known risk factors for calcification.MethodsA retrospective case control study of 130 diabetic patients were compared to 130 non-diabetic patients that were matched for age and gender. The presence of vascular calcification in anterior, posterior or plantar vessels, and length of calcification were measured on plain radiographs. McNemar's Chi-squared test and positive predictive values were calculated. Conditional logistic regression models were used to estimate the association between calcification and diabetes.Results28 patients had type I diabetes and 102 had type II diabetes. The mean age was 58.0 in both groups and 31.5% were females. 89.2% of those with diabetes had calcification present, and 23.1% in those without (p &lt; 0.0001). Calcification in two vessels predicts diabetes with a positive predictive value of 91.2% (95% CI 82.1%–100%). The odds ratio for having diabetes is 78 (95% CI: 7.8 – 784) times higher in a person who has calcification in the blood vessels of their foot than in a person without calcification after adjusting for confounders.ConclusionThis study has demonstrated that vascular calcification in 2 vessels is over 90% predictive of a diagnosis of diabetes. This screening test could be used in future clinics when interpreting radiographs, aiding in the diagnosis of diabetes and altering patient management.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition

BackgroundCirculating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.MethodsWe analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.ResultsCirculating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.ConclusionsEstimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Association between BCL11B gene polymorphisms and age-related hearing loss in the elderly: A case-control study in Qingdao, China.

Age-related hearing loss is a complex disease caused by a combination of genetic and environmental factors, and a study have conducted animal experiments to explore the association between BCL11B heterozygosity and age-related hearing loss. The present study used established genetic models to examine the association between BCL11B gene polymorphisms and age-related hearing loss. A total of 410 older adults from two communities in Qingdao, China, participated in this study. The case group comprised individuals aged ≥ 60 years with age-related hearing loss, and the control group comprised individuals without age-related hearing loss from the same communities. The groups were matched 1:1 for age and sex. The individual characteristics of the participants were analyzed descriptively using the Mann-Whitney U test and the chi-square test. To explore the association between BCL11B gene polymorphisms and age-related hearing loss, conditional logistic regression was performed to construct genetic models for two single-nucleotide-polymorphisms (SNPs) of BCL11B, and haplotype analysis was conducted to construct their haplotype domains. Two SNP sites of the BCL11B gene, four genetic models of rs1152781 (additive, dominant, recessive, and codominant), and five genetic models of rs1152783 (additive, dominant, recessive, codominant, and over dominant) were significantly associated with age-related hearing loss in the models both unadjusted and adjusted for all covariates (P < 0.05). Additionally, a linkage disequilibrium between rs1152781 and rs1152783 was revealed through haplotype analysis. Our study revealed that BCL11B gene polymorphisms were significantly associated with age-related hearing loss.

The UF-5000 Atyp.C parameter is an independent risk factor for bladder cancer

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The “Atyp.C” parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case–control study identified clinical primary or newly recurrent BC (study period, 2022–2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman’s rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.

Hydroxychloroquine Improves Low Complement Levels.

Low complement is associated with clinical systemic lupus erythematosus (SLE) disease activity and future organ damage. We studied the association of hydroxychloroquine (HCQ) whole blood levels with changes in complement. We performed two analyses on data prospectively collected from an SLE cohort. In the first (a "new starts on HCQ" analysis), we compared changes in complement between those starting hydroxychloroquine and those who did not.The second analysis evaluated the association between hydroxychloroquine whole blood levels and low complement in all cohort visits using conditional logistic regression. In the "new starts on HCQ" analysis, a higher percentage of patients starting hydroxychloroquine (as reflected in HCQ blood levels>50) experienced a normalization of C4 compared to those who did not (23/57 (40%) vs. 9/56 (13%), p=0.011), as well as a significantly greater increase in both C3 and C4 (p=0.048 and p=0.017 respectively). In the "all cohort visits" analysis, there was a statistically significant higher probability of having normal C4 levels in visits with higher hydroxychloroquine whole blood levels (OR 1.8 to 2.6 depending on the levels). This relationship was most pronounced for whole blood hydroxychloroquine levels of 200ng/ml or more. We observed significant improvement in complement levels when hydroxychloroquine was started and among those with higher whole blood levels of hydroxychloroquine, particularly with respect to C4. Modulating the pathogenic mechanisms that lead to complement consumption may be one mode by which hydroxychloroquine prevents poor outcomes in SLE.

Broad-spectrum antibiotic use and risk of early-onset colorectal cancer.

e15653 Background: The incidence of early-onset colorectal cancer (eoCRC) diagnosed under age 50 is rising in the United States, but the underlying causes are largely unknown. Use of broad-spectrum antibiotics can induce intense gut dysbiosis, which is strongly implicated in CRC carcinogenesis. Emerging evidence supports a link between broad-spectrum antibiotic use and CRC. We evaluated the associations between oral broad-spectrum antibiotic use and risk of eoCRC. Methods: We conducted a nested case-control study within Kaiser Permanente Southern California (KPSC). Cases were persons aged 15-49 years with invasive colorectal adenocarcinoma diagnosis between 2009-2021; controls were matched at 10:1 ratio on age, sex at birth, and length of KPSC membership. Those with less than 15 years of prior membership at diagnosis date or controls’ index date were excluded to allow evaluation of exposure up to 15 years prior. We extracted all study data, including use of antibiotics by drug type and days of prescriptions, from KSPC’s electronic medical records. Conditional logistic regression was used to evaluate antibiotic use from three etiologic periods: 10-15, 5-10, and 2-5 years prior to diagnosis/index date, adjusting for potential confounders (narrow-spectrum antibiotics use, clinical and lifestyle risk factors, race/ethnicity, body mass index) with a crude p-value &lt; 0.10. Analyses were conducted overall and separately for colon cancer. Results: A total of 310 cases (mean age at diagnosis 44.5 years, 52% female, 33% non-Hispanic White) and 2,976 controls were included. In the 10-15 years prior to diagnosis/index date, 65% of cases and 62% of controls used broad-spectrum antibiotics. Broad-spectrum antibiotic use was not associated with eoCRC overall [OR = 1.15 (95% CI: 0.88-1.49)]. An increased risk was suggested for &gt; 3 months of cumulative use: OR = 1.07 (0.81-1.42) for ≤1 month; 1.26 (0.87-1.84) for 1-3 months; and 1.59 (0.95-2.65) for &gt; 3 months. The association between exposure and colon adenocarcinoma was: OR = 1.26 (0.91-1.72) for any use; OR = 1.17 (0.83-1.64) for ≤1 month; and OR = 1.50 (0.99-2.27) for &gt; 1 month. No association was observed between broad-spectrum antibiotic use within 5-9.9 years or 2-4.9 years prior to diagnosis and risk of eoCRC overall or for the colon site. Conclusions: Our findings suggest a possible association between cumulative longer-term use of broad-spectrum antibiotics and increased risk of eoCRC. The etiologic window for assessing antibiotic exposure appears to be relevant. Larger studies with long-term follow-up are needed to confirm these findings.

Association of Psychiatric Emergency Visits and Warm Ambient Temperature during Pregnancy: A Time-Stratified Case-Crossover Study.

Acute exposure to high ambient temperature and heat waves during the warm season has been linked with psychiatric disorders. Emerging research has shown that pregnant people, due to physiological and psychological changes, may be more sensitive to extreme heat, and acute exposure has been linked to increased risk of pregnancy complications; however, few studies have examined psychiatric complications. Our objective was to examine the association between acute exposure to warm ambient temperatures and emergency department (ED) visits for mental disorders during pregnancy. A time-stratified case-crossover design with conditional logistic regression was performed on psychiatric ED visits for pregnant patients in North Carolina, from May to September 2016 to 2019. Daily average ambient temperature was the main exposure and was linked to daily visits by maternal zip code of residence for prenatal mood and anxiety disorders (PMAD), severe mental illness (SMI), mental disorder of pregnancy (MDP), suicidal thoughts (SUIC), and any psychiatric disorder (Any). Effect modification by trimester, residential segregation, economic segregation, urbanicity, and availability of greenspace was also investigated. Each increase in same-day exposure to warm ambient temperature on case days was associated with an increase in incidence rate ratio (IRR) for any psychiatric disorder [IRR = 1.07; 95% confidence interval (CI): 1.01, 1.14] including anxiety (IRR = 1.14; 95% CI: 1.00, 1.30), bipolar disorder (IRR = 1.28; 95% CI: 0.98, 1.67), and suicidal thoughts (IRR = 1.28; 95% CI: 1.00, 1.65) compared to control days. In general, the associations were strongest for warm season temperatures on the same day of exposure or for temperatures averaged over the 3 or 6 d preceding the ED visit. The greatest risk of an incident ED admission for PMAD (RR = 1.20; 95% CI: 1.04, 1.39), particularly for anxiety (RR = 1.30; 95% CI: 1.07, 1.59), and any psychiatric disorder (RR = 1.17; 95% CI: 1.07, 1.28) occurred following cumulative exposure to hot temperatures the week before admission. Higher psychiatric burden from temperature was observed in urban areas and on extreme heat days. For this pregnant population in the southeastern United States, short-term exposure to high ambient temperatures during the warm season was associated with a greater risk of ED visits for an array of psychiatric disorders. Findings show that climate-related increases in ambient temperature may contribute to psychiatric morbidity in pregnant people. https://doi.org/10.1289/EHP13293.

Statin use and the risk of Parkinson's disease in persons with diabetes: A nested case-control study.

Persons with diabetes may have an elevated risk of Parkinson's disease (PD). Statin use could also modify the progression of PD. The aim was to study whether there is an association between statin exposure and risk of PD in persons with diabetes. A nationwide, nested case-control study restricted to people with diabetes was performed as part of nationwide register-based Finnish study on PD (FINPARK). Study included 2017 PD cases and their 7934 matched controls without PD. Persons with PD were diagnosed between 1999 and 2015, and statin use (1995-2015) was determined from Prescription Register. In the main analysis, exposure at least 3 years before outcome was considered. Cumulative exposure was categorized into tertiles, and associations were analysed with conditional logistic regression (adjusted with comorbidities and number of antidiabetic drugs). Prevalence of statin use was similar in PD cases and controls, with 54.2% of cases and 54.4% controls exposed before the lag time (adjusted odds ratio [aOR] =1.03; 95% confidence interval [CI]: 0.92-1.15). Those in the highest cumulative statin exposure tertile had higher risk of PD than statin nonusers (aOR =1.22; 95% CI: 1.04-1.43), or those in the lowest cumulative statin exposure tertile (aOR =1.29; 95% CI: 1.07-1.57). Our nationwide study that controlled for diabetes duration and used 3-year lag between exposure and outcome to account for reverse causality does not provide support for the hypothesis that statin use decreases the risk of PD.

The role of familial factors and neuroticism in the association between exposure to offensive behaviors at work and long-term sickness absence due to common mental disorders - a prospective twin study

ObjectivesThe aim of this study was to investigate associations between exposure to work-related violence/threats and harassment, and future sickness absence (SA) due to common mental disorders (CMDs), taking familial factors (shared genetics and early-life environment) and neuroticism into account.MethodsThe study sample included 8795 twin individuals from the Swedish Twin Project of Disability Pension and Sickness Absence (STODS), including survey data from the Study of Twin Adults: Genes and Environment (STAGE). Self-reported work-related violence and/or threats as well as work-related harassment (including bullying) and national register data on SA due to CMDs were analyzed using standard logistic regression, and conditional logistic regression among complete twin pairs discordant on exposures. Individuals were followed for a maximum of 13 years. Interactions between neuroticism and exposures were assessed using both multiplicative and additive interaction analyses.ResultsExposure to work-related violence/threats was associated with higher odds of SA due to CMDs when adjusting for age, sex, marital status, children, education, type of living area, work characteristics, and symptoms of depression and burnout (OR 2.11, 95% CI 1.52–2.95). Higher odds of SA due to CMDs were also found for exposure to harassment (OR 1.52, 95% CI 1.10–2.11) and a combined indicator of exposure to violence/threats and/or harassment (OR 1.98, 95% CI 1.52–2.59), compared with the unexposed. Analyses of twins discordant on exposure, using the unexposed co-twin as reference, showed reduced ORs. These ORs were still elevated but no longer statistically significant, potentially due to a lack of statistical power. No multiplicative interaction was found between neuroticism and exposure to work-related violence/threats, or harassment. However, a statistically significant additive interaction was found between neuroticism and exposure to violence/threats, indicating higher odds of SA due to CMDs in the group scoring lower on neuroticism.ConclusionsExposure to work-related offensive behaviors was associated with SA due to CMDs. However, the results indicated that these associations may be partly confounded by familial factors. In addition, an interaction between exposure and neuroticism was suggested. Thus, when possible, future studies investigating associations and causality between offensive behaviors at work and mental health-related outcomes, should consider familial factors and neuroticism.

Genetic drivers of severe skin toxicity with immune checkpoint inhibitors (ICIs) in Asian patients.

2667 Background: ICIs may cause severe skin toxicity associated with significant patient (pt) impact. Published data suggests Asian pts might be at higher risk of skin immune-related adverse events (SirAEs). Variation in human leukocyte antigen (HLA) is known to predispose to autoimmune (AI) conditions, but there is limited data to understand genetic drivers of severe SirAEs. Methods: The incidence of severe SirAEs was correlated with 30 HLA alleles of interest in 2 cohorts totaling 18 Asian pts (Dermatitis bullous n=4, Erythema multiforme n=10, Stevens-Johnson syndrome n=3, Toxic skin eruption n=1) treated with atezolizumab (A) across tumor types as monotherapy or as part of combinations- 8 Japanese pts received A in a non-interventional study (trial ID: UMIN000048702) and 10 Asian pts were enrolled in Roche trials with A. Data from the 18 cases was compared to 3 different controls of Asian pts identified from Roche trials with A (i.e. pts without any irAEs n=148, pts without SirAEs n=225, pts without severe SirAEs n=390). For each HLA allele, positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, (unadjusted) odds ratio (OR) and corresponding 95%-confidence interval (CI) were evaluated. Case-control populations were obtained by risk-set sampling with exact matching on indication, treatment arm and sex, and used in age-adjusted conditional logistic regression models to assess associations between each HLA allele and severe SirAEs. Results: There was an association between some HLA alleles and severe SirAEs, but sensitivity was low (&lt;30%) and 1-NPV was only slightly smaller than background prevalence. Results for five HLA alleles with OR&gt;1.5 in either the unadjusted or adjusted analysis compared to controls without severe SirAEs are presented in table. Results were consistent across the three control populations. Conclusions: Five HLA alleles previously reported in AI disorders were associated with severe SirAEs in Asian pts receiving A. Although the effect size is insufficient to be considered clinically relevant, further research is warranted to better characterize the pt-level drivers of severe SirAEs in Asians pts. Clinical trial information: UMIN000048702 . [Table: see text]

Metabolomics signatures of air pollution mixtures and lung cancer risk: A large-scale metabolome-wide association study in the Cancer Prevention Study cohorts.

10571 Background: Despite the well-established link between air pollution exposure and lung carcinogenesis, the underlying mechanism remains underexplored. While metabolomics has provided valuable molecular insights, existing air pollution metabolomics studies only assess biological changes to single air pollutants, without examining the join effects of air pollutant mixtures. We sought to identify metabolic signatures mediating the association between ambient air pollution mixtures and lung cancer risk. Methods: A total of 603 matched lung cancer case-control pairs were selected from the Cancer Prevention Study cohorts. Controls were matched to cases on age at blood draw, sex, race/ethnicity, and blood draw date. Plasma metabolomics was conducted using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Air pollution mixtures include carbon monoxide, nitrogen dioxide, particulate matter, sulfur dioxide, and ozone, matched to subjects’ residential address at blood draw. We conducted an untargeted metabolome-wide association study with multivariable-adjusted linear and conditional logistic regression models to assess associations between metabolites and individual air pollutants and lung cancer risk, respectively, adjusting for individual and lifestyle-related covariates. We used a meet-in-the-middle (MITM) approach to identify potential mediators. Quantile g-computation was used to examine the effects of air pollution mixtures on metabolome perturbations to analyze the collective effects of multiple air pollutants concurrently. Results: Among 1,138 extracted metabolic features, 162 were significantly associated with the combined mixture (false discovery rate &lt; 0.2). Using MITM, no metabolites were associated with both air pollution mixture and lung cancer risk at FDR &lt; 0.2. At raw p &lt; 0.05, 16 metabolites were identified as potential mediators of the air pollution mixture and lung cancer risk. These metabolites, including 4-hydroxyphenylacetylglutamine, glutamate, and 3-aminoisobutyrate, were also significantly associated with the mixture at FDR &lt; 0.2. Conclusions: Findings from this analysis demonstrate the feasibility of considering multiple air pollutants as mixtures when conducting air pollution-related metabolomics investigations. Future exploration of the underlying biological mechanisms will be critical for validating pathways that participate in air pollution carcinogenicity. As lung cancer cases in never smokers continue to increase, it is pertinent to study air pollution and other environmental risk factors on cancer incidence.

Antidepressant drugs and risk of developing glioma: a national registry-based case control study and a meta-analysis.

The aim of the present study was to investigate if use of antidepressants is related to the risk of developing lower (WHO grade 2-3) and higher grade (WHO grade 4) glioma. A registry-based case-control study was performed using 1283 glioma cases and 6400 age-, sex- and geographically matched controls, diagnosed in Sweden 2009-2013. Conditional logistic regression was used to analyze whether Selective Serotonin Reuptake Inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the dataset from the present study was combined with results from two previous epidemiological studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (OR 0.90 [95% CI 0.83-0.97]), when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.

Re-emergence and influencing factors of mountain-type zoonotic visceral leishmaniasis in the extension region of Loess Plateau, China.

To understand the epidemiological distribution characteristics of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in Yangquan City, Shanxi Province, China, from 2006 to 2021, to explore the influencing factors leading to the re-emergence of the epidemic, and to provide a basis for the formulation of targeted control strategies. Case information spanning from 2006 to 2021 in Yangquan City was collected for a retrospective case-control study conducted from June to September 2022. A 1:3 matched ratio was employed. A questionnaire was utilized to gather data on basic information, demographic characteristics, awareness of MT-ZVL knowledge, residence, and dog breeding and living habits. The study employed a multifactorial conditional stepwise logistic regression model to analyze the influencing factors. A total of 508 subjects was analyzed. Risk factors for MT-ZVL included the use of soil/stone/concrete as building materials (OR = 3.932), presence of nearby empty/stone stack houses (OR = 2.515), dog breeding (OR = 4.215), presence of stray dogs (OR = 2.767), and neighbor's dog breeding (OR = 1.953). Protective factors comprised knowledge of MT-ZVL (OR = 0.113) and using mosquito repellents (OR = 0.388). The findings indicate significant associations between environmental and behavioral factors and MT-ZVL incidence in Yangquan City, Shanxi Province, China, from 2006 to 2021. These results underscore the importance of public awareness campaigns and targeted interventions aimed at reducing exposure to risk factors and promoting protective measures to mitigate the re-emergence of MT-ZVL outbreaks. House building materials, presence of neighboring empty houses, breeding domestic dogs and distribution of stray dogs surrounding the home are risk factors for MT-ZVL. Awareness of MT-ZVL and implementation of preventive measures during outdoor activities in summer and autumn are protective and may reduce the risk of MT-ZVL.

Self-injurious unnatural death among Veterans with HIV: a nested case-control study.

People living with HIV (PWH) are at increased risk of suicide and death from unintentional causes compared with people living without HIV. Broadening the categorization of death from suicide to self-injurious unnatural death (SIUD) may better identify a more complete set of modifiable risk factors that could be targeted for prevention efforts among PWH. We conducted a nested case-control study using data from the Veterans Aging Cohort Study (VACS), a longitudinal, observational cohort of Veterans from 2006-2015. A total of 5,036 Veterans with HIV, of whom 461 died by SIUD, were included in the sample. SIUD was defined using the International Classification of Disease 10th revision cause of death codes. Cases (n = 461) included individuals who died by SIUD (intentional, unintentional, and undetermined causes of death). Controls (n = 4,575) were selected using incidence density sampling, matching on date of birth ± one year, race, sex, and HIV status. SIUD and suicide was estimated using conditional logistic regression. A previous suicide attempt, a diagnosis of an affective disorder, recent use of benzodiazepines, psychiatric hospitalization, and living in the western US significantly increased the risk of suicide and SIUD. Risk factors that appear more important for SIUD than for suicide included a drug use disorder, alcohol use disorder, Hepatitis C, VACS Index 2.0, current smoking, and high pain levels (7-10). Limiting studies to known suicides obscures the larger public health burden of excess deaths from self-injurious behavior. Our findings demonstrate the benefit of expanding the focus to SIUD for the identification of modifiable risk factors that could be targeted for treatment.

Daily temperature variability and mental health-related hospital visits in New York State

BackgroundDespite plausible behavioral and physiological pathways, limited evidence exists on how daily temperature variability is associated with acute mental health-related episodes. ObjectivesWe aimed to explore associations between daily temperature range (DTR) and mental health-related hospital visits using data of all hospital records in New York State during 1995–2014. We further examined factors that may modify these associations, including age, sex, hospital visit type and season. MethodsUsing a case-crossover design with distributed lag non-linear DTR terms (0–6 days), we estimated associations between ZIP Code-level DTR and hospital visits for mood (4.6 million hospital visits), anxiety (2.4 million), adjustment (∼368,000), and schizophrenia disorders (∼211,000), controlling for daily mean temperature, via conditional logistic regression models. We assessed potential heterogeneity by age, sex, hospital visit type (in-patient vs. out-patient), and season (summer, winter, and transition seasons). ResultsFor all included outcomes, we observed positive associations from period minimum DTR (0.1 °C) until 25th percentile (5.2 °C) and between mean DTR (7.7 °C) and 90th percentile (12.2 °C), beyond which we observed negative associations. For mood disorders, an increase in DTR from 0.1 °C to 12.2 °C was associated with a cumulative 16.0% increase (95% confidence interval [CI]: 12.8, 19.2%) in hospital visit rates. This increase was highest during transition seasons (32.5%; 95%CI: 26.4, 39.0%) compared with summer (10.7%; 95%CI: 4.8, 16.8%) and winter (−1.6%; 95%CI: −7.6, 4.7%). For adjustment and schizophrenia disorders, the strongest associations were seen among the youngest group (0–24 years) with almost no association in the oldest group (65+ years). We observed no evidence for modification by sex and hospital visit type. DiscussionDaily temperature variability was positively associated with mental health-related hospital visits within specific DTR ranges in New York State, after controlling for daily mean temperature. Given uncertainty on how climate change modifies temperature variability, additional research is crucial to comprehend the implications of these findings, particularly under different scenarios of future temperature variability.