Exposure Odds Ratio Research Articles

A single mutation G454A in the P450 CYP9K1 drives pyrethroid resistance in the major malaria vector Anopheles funestus reducing bed net efficacy.

Metabolic mechanisms conferring pyrethroid resistance in malaria vectors are jeopardizing the effectiveness of insecticide-based interventions, and identification of their markers is a key requirement for robust resistance management. Here, using a field-lab-field approach, we demonstrated that a single mutation G454A in the P450 CYP9K1 is driving pyrethroid resistance in the major malaria vector Anopheles funestus in East and Central Africa. Drastic reduction in CYP9K1 diversity was observed in Ugandan samples collected in 2014, with selection of a predominant haplotype (G454A mutation at 90%), which was completely absent in the other African regions. However, six years later (2020) the Ugandan 454A-CYP9K1 haplotype was found predominant in Cameroon (84.6%), but absent in Malawi (Southern Africa) and Ghana (West Africa). Comparative in vitro heterologous expression and metabolism assays revealed that the mutant 454A-CYP9K1 (R) allele significantly metabolises more type II pyrethroid (deltamethrin) compared with the wild G454-CYP9K1 (S) allele. Transgenic Drosophila melanogaster flies expressing 454A-CYP9K1 (R) allele exhibited significantly higher type I and II pyrethroids resistance compared to flies expressing the wild G454-CYP9K1 (S) allele. Furthermore, laboratory testing and field experimental hut trials in Cameroon demonstrated that mosquitoes harbouring the resistant 454A-CYP9K1 allele significantly survived to pyrethroids exposure (Odds ratio = 567, p < 0.0001). This study highlights the rapid spread of pyrethroid resistant CYP9K1 allele, under directional selection in East and Central Africa, contributing to reduced bed net efficacy. The newly designed DNA-based assay here will add to the toolbox of resistance monitoring and improving its management strategies.

A co-created citizen science project on the short term effects of outdoor residential woodsmoke on the respiratory health of adults in the Netherlands

Background and aimWoodsmoke from household fireplaces contributes significantly to outdoor air pollution in the Netherlands. The current understanding of the respiratory health effects of exposure to smoke from residential wood burning is limited. This study investigated the association between short-term changes in outdoor woodsmoke exposure and lung function, respiratory symptoms, and medication use in adults in the Netherlands.MethodsThis study was co-created with citizen scientists and other relevant stakeholders. A panel study was conducted with repeated observations in 46 adults between February and May 2021 in four Dutch towns. Participants recorded their symptoms and medication use in daily diaries, and conducted morning and evening home spirometry measurements. Woodsmoke exposure was characterized by measuring levoglucosan (most specific marker for woodsmoke exposure), black/brown carbon, fine and ultrafine particulate matter at central monitoring sites. Individual woodsmoke perception (smell) was recorded in daily diaries. Linear and logistic regression models were used to investigate the association between respiratory health and woodsmoke exposure. Models were adjusted for time-varying confounders and accounted for repeated observations within participants.ResultsConsistent positive associations were found between levoglucosan and shortness of breath (SOB) during rest and extra respiratory medication use. Odds ratios for current day exposure to levoglucosan were 1.12 (95% CI: 0.97, 1.30) for SOB during rest and 1.19 (95% CI: 1.07, 1.33) for extra medication use, expressed per interquartile range of levoglucosan concentrations (69.16 ng/m3). Positive non-significant associations were found between levoglucosan and nasal symptoms, cough and waking up with SOB. No consistent association was found between levoglucosan and lung function. Associations found between woodsmoke markers, SOB during rest and extra medication use remained after the inclusion of PM2.5 and UFP in two-pollutant models.ConclusionsAdults experienced more SOB during rest, nasal symptoms and used more medication to treat respiratory symptoms on days with higher levels of outdoor woodsmoke concentrations.

Sweetened Areca Nut, A Risk in Dental Caries among Adolescents in Pune, Maharashtra? A Case-Control Study

Abstract Introduction: Smokeless tobacco (SLT) causes dental caries and so does chewing of areca nut (sweetened supari) due to the presence of sugar. Since conflicting views exist about whether areca nut causes dental caries or not, and since studies are undertaken in adults and data on adolescents are not available, this study was carried out. Since those were cross-sectional or longitudinal studies, this case-control study was undertaken to understand if flavored/sweetened areca nut is a risk factor for dental caries. Material and Method: This unmatched case-control study was conducted among the male students of 8th to 10th standard in the age group of 12–16 of four Madhyamik Vidyalaya’s (MVs) in Pimpri–Chinchwad (urban area), Pune. A directed acyclic graph (DAG) was drawn to determine the independent variables to be selected for the study and minimal variables to be adjusted during data analysis. Selection of cases was based on diagnostic and eligibility criteria. The data on the use of sweetened areca nuts and the presence of caries were collected through oral examination and a semistructured questionnaire administered by the principal investigator on a one-to-one basis between August 2022 and October 2022. Data were analyzed using epiinfoTM 7.2.5.0. Results: This study of 146 males in the age group of 13 to 16 years had 61 students as cases and 85 as controls. No significant difference was observed between the group with (cases) and without (controls) dental caries for areca nut use (pack years) whether consumed daily or less frequently for 1 year or more. While the exposure rate to areca nut among cases was 44.26%, for the control group it was 36.47%. The odds ratio of sweetened areca nut as being the risk factor for dental caries was 1.38 at 95% CI (0.70–2.71) with P = 0.44. Conclusion: This study revealed that the adolescent users of sweetened areca nuts studying in government schools had a higher exposure odds ratio for dental caries. However, it was not significant statistically. Information bias including recall may have influenced the outcome.

Trace Element Concentrations of Arsenic and Selenium in Toenails and Risk of Prostate Cancer among Pesticide Applicators.

Prostate cancer is a common cancer among males in the US, but little is known about its risk factors, including trace elements. The primary aim of this study was to examine prostate cancer and its association with arsenic and selenium in toenails. We conducted a small, nested case-control study of men residing in Iowa within the Agricultural Health Study cohort, where we also collected toenail samples to test for arsenic and other trace elements. Toenail samples were sent for neutron activation analysis aimed at long-lived trace elements, including arsenic. Logistic regression was used to estimate odds ratios (ORs) for trace element exposures and prostate cancer. A total of 66 prostate cancer cases and 173 healthy controls returned questionnaires, over 99% of which included toenail samples. An increased risk was seen for the highest levels of arsenic (OR = 3.4 confidence interval (CI) of 1.3-8.6 and OR = 2.2, 95% CI of 0.9-5.6) and the highest level of selenium (2.0, 95% CI of 1.0-4.0). These data also show detectable levels of over 50% for 14 of 22 elements detected in the toenails. The association seen here with arsenic and prostate cancer further supports ecological studies finding an association with community levels of arsenic and prostate cancer incidence and mortality.

Concomitant Use of Oral Anticoagulants with Oral Dipeptidyl Peptidase-4 Inhibitors and Serious Bleeding Events.

In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020. For the SCCS, we used conditional Poisson regression to estimate adjusted rate ratios (RRs) between each co-exposure (vs. not) and serious bleeding and divided the RR by the adjusted RR for the corresponding lisinopril + precipitant pair to obtain ratios of RRs (RRRs). For the CCO, we estimated the adjusted odds ratios (ORs) of exposure to the precipitant in the focal window vs. referent window using multivariable conditional logistic regression and divided the ORs in the object drug-exposed cases over the ORs in negative object drug-exposed cases to obtain the ratios of ORs (RORs). The adjusted RRRs for serious bleeding ranged from 0.32 (0.05-1.91) for apixaban/lisinopril + saxagliptin to 3.49 (1.29-9.48) for warfarin/lisinopril + linagliptin. The adjusted RORs ranged from 0.01 (0.00-0.20) for rivaroxaban/lisinopril + saxagliptin to 2.99 (0.74-12.11) for apixaban/lisinopril + linagliptin. While we could not confirm previously identified signals because of statistical imprecision, several numerically elevated estimates still warrant caution in concomitant use and further examination.

The risk of sleep-related death in an inclined sleep environment

BackgroundUnsafe sleep environments are the primary modifiable risk factor for sudden unexpected infant death (SUID). Despite this knowledge, products that deviate from the American Academy of Pediatrics (AAP) safe sleep recommendations continue to be commonplace, such as inclined sleepers. Analyses to estimate risk among these products are lacking, perpetuating their presence in the marketplace. We present a method of comparing risk of SUID in an inclined sleeper to an AAP-recommended sleep environment.MethodsA case-control analysis using publicly available and previously published survey data was conducted for SUID events occurring between January 1, 2018 and April 12, 2019 (the date of the first inclined sleeper recall). SUID deaths were categorized as occurring in an AAP-recommended sleep environments or in an inclined sleeper. Exposure Odds Ratios (OR) are reported as the risk of SUID among infants using inclined sleepers relative to an AAP-recommended sleep environment.ResultsDuring the study period, 4,900,573 births and 4,363 SUID deaths occurred in the US. Control characteristics were similar between previous night users of an AAP-recommended sleep environment (24%) and inclined sleepers (3.8%). Inclined sleepers were associated with a 5-fold (OR: 5.1; 95% CI: 3.2, 7.9) increased risk of SUID among infants < 12 months compared to infants in an AAP-recommended sleep environment. This risk was greatest among infants ≥ 4 months (RR: 10.4; 95% CI: 5.1, 21.5).ConclusionsThis novel analysis fills a longstanding gap in risk assessments of inclined infant sleep products. More timely risk analyses may improve the safety of the marketplace.

The role of proactive therapeutic drug monitoring in guiding infliximab therapeutic optimization in pediatric patients with Crohn's disease: A retrospective study

AbstractTherapeutic drug monitoring (TDM) plays an important role in guiding treatment plan adjustments and clinical outcomes in Crohn's disease. To evaluate the role of TDM‐guided optimization of infliximab dosage in patients with pediatric Crohn's disease. Medical records of patients with pediatric Crohn's disease who were treated with infliximab and had proactive TDM from June 2020 to June 2022 at the Children's Hospital of Chongqing Medical University were included. Baseline influencing factors for infliximab trough concentration (TC) and clinical outcomes before and after the treatment change were analyzed to assess the value of adjusting treatment in the patients. Forty‐six patients (male‐to‐female ratio = 1.55:1, age &lt;18 years) were included. Univariate and multivariate analyses showed that hormone exposure (odds ratio: 0.042, 95% confidence interval: 0.002–0.924, p = 0.044), perianal lesions (5.813, 0.984–34.349, p = 0.052), simplified endoscopic score for Crohn's disease (1.656, 1.065–2.577, p = 0.025), and total protein (TP) (0.851, 0.749–0.967, p = 0.014) were correlated with infliximab TC. Shortening the treatment interval increased the infliximab TC (pre vs. post = 1.69 ± 0.8 vs. 12.03 ± 6.64, p = 0.001, n = 12) after 93.9 ± 37.47 days, decreased the pediatric Crohn's disease activity index and simplified endoscopic score for Crohn's disease, and increased the biochemical remission, clinical remission, endoscopic remission, and endoscopic response rates; however, there was no statistical significance. Hormone exposure, perianal lesions, simplified endoscopic score for Crohn's disease, and TP levels before the first infliximab use affected the infliximab TC. Shortening the treatment interval can improve infliximab TC levels and clinical outcomes.

Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.

Metformin is the most used oral antidiabetic medication. Despite its established safety profile, it has known antiandrogenic and epigenetic modifying effects. This raised concerns about possible adverse developmental effects caused by genomic alterations related to paternal use of metformin during the spermatogenesis period preceding conception. To assess the potential adverse intergenerational effect of metformin by examining the association between paternal metformin use during spermatogenesis and major congenital malformations (MCMs) in newborns. Nationally representative cohort study. A large Israeli health fund. 383 851 live births linked to fathers and mothers that occurred in 1999 to 2020. MCMs and parental cardiometabolic conditions were ascertained using clinical diagnoses, medication dispensing information, and laboratory test results. The effect of metformin use on MCMs was estimated using general estimating equations, accounting for concurrent use of other antidiabetic medications and parental cardiometabolic morbidity. Compared with unexposed fathers, the prevalence of cardiometabolic morbidity was substantially higher among fathers who used metformin during spermatogenesis, and their spouses. Whereas the crude odds ratio (OR) for paternal metformin exposure in all formulations and MCMs was 1.28 (95% CI, 1.01 to 1.64), the adjusted OR was 1.00 (CI, 0.76 to 1.31). Within specific treatment regimens, the adjusted OR was 0.86 (CI, 0.60 to 1.23) for metformin in monotherapy and 1.36 (CI, 1.00 to 1.85) for metformin in polytherapy, a treatment that was more common in patients with more poorly controlled diabetes. Laboratory test results for hemoglobin A1c to assess underlying diabetes severity were available only for a subset of the cohort. Paternal use of metformin in monotherapy does not increase the risk for MCMs. Association for metformin in polytherapy could potentially be explained by worse underlying parental cardiometabolic risk profile. None.

Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

Metformin exposure and the incidence of lactic acidosis in critically ill patients with T2DM: A retrospective cohort study.

The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients. The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort. In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.

Risk of fibromyalgia following antibiotic prescriptions: Apopulation-based case-control study.

The health of the gut microbiome is now recognized to be an important component of the gut-brain axis which itself appears to be implicated in pain perception. Antibiotics are known to create dysbiosis in the microbiome, so whether fibromyalgia is more commonly diagnosed after antibiotic prescriptions provides a means of exploring the role of the microbiome in the experience of chronic pain. A case-control study was carried out using electronic health records collected in the UK's Clinical Practice Research Datalink (CPRD), a comprehensive database of primary care consultations. For each case of diagnosed fibromyalgia, three controls were identified and matched by age, gender and GP practice. The exposure variable was the number and timing of antibiotic prescriptions over previous years. The analysis involved adjusting for a wide range of co-variates that might be possible confounders. A total of 44,674 cases of fibromyalgia were identified together with 133,513 controls. After adjusting for co-variates, it was found that both the total number of prescriptions and their timing was associated with an FM diagnosis. For example, the quartile with the highest number of prescriptions and that with the longest exposure had a greater than three-fold increase in FM diagnoses (number of prescriptions: odds ratio 3.92; 95% CIs: 3.71-4.13; exposure odds ratio 3.28; CIs: 3.13-3.43). Some antibiotics (such as tetracyclines and metronidazole) seemed to confer greater risk than others. The results lend support for prior antibiotics being an important risk factor for a diagnosis of FM. This study shows an association between the volume as well as timing of prior antibiotic prescriptions and of a subsequent diagnosis of fibromyalgia in primary care.

Cardiometabolic diseases according to the type and degree of hearing loss in noise-exposed workers.

This study aimed to determine the association between cardiometabolic diseases, including metabolic syndrome, hypertension, and diabetes, and the type and degree of hearing loss in noise-exposed workers. A total of 237,028 workers underwent air conduction pure tone audiometry in 2015 to assess their health and diagnose cardiometabolic diseases. The study defined metabolic syndrome, hypertension, and diabetes using blood pressure, fasting blood sugar, cholesterol, and triglyceride levels. Mid-frequency hearing loss was defined as ≥ 30 dB at 2,000 Hz, whereas high-frequency hearing loss was ≥ 40 dB at 4,000 Hz. The average air conduction hearing thresholds at these frequencies were used to determine hearing loss degrees. The odds ratio (OR) of combined exposure to noise and night-shift work in all cardiometabolic diseases was higher than that of noise exposure alone. The risk of cardiometabolic diseases was dose-response, with higher hearing loss causing higher ORs. The ORs of hypertension compared with the normal group were 1.147 (1.098-1.198), 1.196 (1.127-1.270), and 1.212 (1.124-1.306), and those of diabetes were 1.177 (1.119-1.239), 1.234 (1.154-1.319), and 1.346 (1.241-1.459) for mild, moderate, and moderate-severe hearing loss, respectively. Workers who are exposed to noise tend to demonstrate high risks of hearing loss and cardiometabolic diseases; thus, bio-monitoring of cardiometabolic diseases, as well as auditory observation, is necessary.

Associations of maternal exposure to multiple plasma trace elements with the prevalence of fetal congenital heart defects: A nested case-control study

BackgroundScanty knowledge prevails regarding the combined impact of multiple plasma trace elements and main contributors on the prevalence of congenital heart defects (CHDs) in offspring. Thus, we performed a nested case-control analysis in a neonates cohort to investigate this important public health issue. MethodsWe selected 164 pairs of cases and non-malformed controls from live births registered in the parent cohort (n = 11,578) at the same hospital. Plasma levels of 14 trace elements were determined by inductively coupled plasma-mass spectrometry. The odds ratios (ORs) of exposure were compared between cases and controls. Bayesian Kernel Machine Regression (BKMR) and Quantile g-Computation (QgC) models were employed to assess the cumulative effect of exposure to trace elements. ResultsWe found positive associations and linear dose-response relationships between plasma Pb and Sn and CHD. BKMR models indicated that the overall effect of the trace element mixture was associated with CHDs below the 45th percentile or above the 50th percentile, and the combined effect was primarily attributed to Sn and Pb. The QgC model indicated significantly increased odds of CHD with simultaneous exposure to all studied trace elements (OR: 2.19, 95%CI: 1.44–3.33). ConclusionsThis study is the first to report an association between elevated levels of mixed trace elements in maternal plasma with an increased prevalence of fetal CHDs, particularly in the case of Pb and Sn. Findings from this study provide further evidence of the important of heavy metal pollution to human health, and can help stakeholders prioritize policies and develop interventions to target the leading contributors to human exposure.

Associations of maternal exposure to multiple plasma metals with the risk of fetal congenital heart defects: a prospective nested case-control study

Abstract Background Congenital heart defects (CHDs) are the most common congenital anomalies with complex etiologies. There is knowledge gap with respect to the association between single and combined exposures to multiple heavy metals during pregnancy and the risk of CHDs in the fetus. Thus, we aimed to examine the association between maternal plasma heavy metal concentrations in mid-pregnancy and the risk of CHDs in the fetus. Methods A prospective nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios (ORs) were compared between 164 CHD cases and 164 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 21 metals were determined in maternal peripheral blood plasma via an ultra-performance liquid chromatography inductively coupled to mass spectrometry (ICP-MS). Single- and multiple-metal logistic regressions, the adaptive least absolute shrinkage and selection operator (LASSO) penalized regression analysis and restricted cubic spline (RCS) analysis were applied to explore the associations and dose-response relationships of plasma metals with CHD. We also applied Bayesian Kernel Machine Regression (BKMR) model to evaluate the cumulative effect of the exposure metals. Results Median (interquartile range, IQR) Vanadium (V) [0.3 (0.3-0.4) vs. 0.3 (0.3-0.4) μg/L, P = 0.027] and cadmium (Cd) [0.1 (0.0-0.1) vs. 0.1 (0.0-0.1) μg/L, P = 0.036] levels were different between the CHDs and control groups. Compared with the first quartile, the Directed acyclic graph(DAG) model-adjusted ORs (95% CI) were 3.12 (1.72-5.64) for kalium (K), 2.21 (1.23-3.94) for manganese (Mn), 0.55 (0.33-0.94) for cerium (Ce), 1.96 (1.06-3.64) for lead (Pb) in the second quartile, and ORs (95%CIs) were 1.88 (1.08-3.26) for V, 0.53 (0.30-0.93) for Cr, 1.92 (1.10-3.35) for copper (Cu), 2.09 (1.18-3.70) for Cd, 2.14 (1.24-3.70) for stannum (Sn) and 3.05 (1.69-5.49) for Pb in the third quartile. In the multi-metal model, compared to the lowest quartile, the ORs for Sn and Pb in the second quartile were 1.32 (95% CI: 0.69-2.55) and 1.94 (95% CI: 0.98-3.84), respectively, and the ORs for both metals in the third quartiles were 2.15 (95% CI: 1.16-3.98) and 3.32 (OR=0.66, 95% CI: 1.68-6.55), suggesting that Sn and Pb had relatively stable positive results with a linear dose progression. BKMR models with 2 cluster for 9 metals showed that the overall effect of metal mixture was not statistically significant at or below 35th percentile and at or above the 70th percentile, compared to their median levels. Pb was the major contributor to the combined effect. Conclusions Elevated level of plasma plumbum was associated with increased risk of CHDs. Further investigations in larger perspective cohorts are needed to confirm our findings.fig 1fig 2

Abstract 15227: Venous Thromboembolism and Effects of Statin and Hormone Therapy: A Case-Control Study of 250,000 Women Aged 50-64

Background: Post-menopausal hormone therapy (HT) may elevate the risk of venous thromboembolism (VTE), while statin therapy may lower risk. Purpose. To estimate VTE risk from HT exposure with/without statin therapy in women 50-64 years of age. Methods: This was a case-control study in a large database of commercially insured subjects. We matched cases of VTE diagnoses (1:10) to controls without VTE on age, +/- 2 years. Conditional logistic regression estimated odds ratios (ORs) for recent HT exposure (any estrogen and/or progestogen within 60 days) and current statin therapy ( &gt; 90 days continuous exposure) controlling for VTE risk factors, comorbidities, and coronary artery disease. We assessed risk by current exposure to a statin of any intensity (Model 1) and then by increasing intensity (Model 2). Results: In a comparison of cases (n=20,359) and matched controls (n=203,590), 9% (n=19,558) had recent HT exposure and 16% (n=36,238) had current/continuous statin exposure. After adjustment for all covariates, the OR for any recent HT exposure (regardless of statin exposure) was 1.51 (95% CI: 1.43, 1.60) compared to no HT exposure. The OR for current statin therapy (regardless of HT exposure) was 0.88 (95% CI: 0.84, 0.93). For those with HT exposure without statin therapy the OR was 1.53 (95% CI: 1.44, 1.63), for those with HT exposure with statin therapy the OR was 1.25 (95% CI: 1.10, 1.43), and for those exposed to statin therapy without HT exposure the OR was 0.89 (95% CI: 0.85, 0.94), compared those not exposed to either statin or HT. HT with statin therapy had a 18% significantly lower odds ratio than HT without statin therapy (OR=0.82, 95% CI: 0.71, 0.94). Exposure to high intensity statin therapy trended towards greater risk reduction for VTE compared to low/moderate exposure. Conclusion: Statin therapy may reduce VTE risk associated with HT.

Atherosclerosis as a Risk Factor of Inflammatory Bowel Disease: A Population-Based Case-Control Study.

Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing. In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD. There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even ≥5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition. A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals.

The directed acyclic graph helped identify confounders in the association between coronary heart disease and pesticide exposure among greenhouse vegetable farmers.

To explore the causal pathways associated with coronary heart disease (CHD) and pesticide exposure using a directed acyclic graph (DAG) analysis and to investigate the potential benefits of DAG by comparing it with logistic regression. This cross-sectional study enrolled 1368 participants from April 2015 to May 2017. Trained research investigators interviewed farmers using a self-administered questionnaire. Logistic regression and DAG models were used to identify the associations between CHD and chronic pesticide exposure. A total of 150 (11.0%) of the 1368 participants are characterized as having CHD. High pesticide exposure (odds ratio = 2.852, 95% confidence intervals: 1.951-4.171) is associated with CHD when compare with low pesticide exposure by both DAG and logistic analyses. After adjusting for the additional potential influence of factors identified by the DAG analysis, there is no significant association, such as the results in logistic regression: ethnicity, education level, settlement time, and mixed pesticide status. Specifically, age, meal frequency, and consumption of fresh fruit, according to the DAG analysis, are independent factors for CHD. High pesticide exposure is a risk factor for CHD as indicated by both DAG and logistic regression analyses. DAG can be a preferable improvement over traditional regression methods to identify sources of bias and causal inference in observational studies, especially for complex research questions.

Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study.

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and ASPearly were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DSearly odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASPearly odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DSearly OR = 2.7 (95% CI: 0.9, 8.4); ASPearly OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.

Association Between Proton Pump Inhibitor Use and Extended-Spectrum Beta-Lactamase Urinary Tract Infection in Adults: A Retrospective Study.

To study the association between proton pump inhibitor (PPI) use and the risk of urinary tract infection (UTI) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL). A retrospective cross-sectional study was conducted between October 2018 and September 2019. Adults with ESBL-UTIs were compared to adults with UTIs caused by gram-negative bacteria (GNB) and those with UTIs caused by miscellaneous organisms. The association between ESBL infection and PPI use was assessed. A total of 117 of 277 ESBL cases, 229 of 679 non-ESBL GNB controls, and 57 of 144 non-ESBL miscellaneous controls were exposed to PPIs within 3 months prior to admission. The univariate analysis indicated unadjusted odds ratio for PPI exposure with ESBL infection versus the GNB controls was 1.43 (95% CI 1.07-1.90, P = 0.015) while the odds ratio for PPI exposure with ESBL infection versus miscellaneous organisms was 1.10 (95% CI 0.73-1.67, P = 0.633) indicating positive association (PPI exposure increases risk of ESBL infection). Multivariate analysis revealed a positive association between ESBL infection and PPI use versus the GNB controls with an odds ratio of 1.74 (95% CI 0.91-3.31). While Esomeprazole was positively associated with ESBL infection, particularly compared with the miscellaneous group (adjusted OR 1.35, 95% CI 0.47-3.88), Lansoprazole was inversely associated (adjusted OR 0.48, 95% CI 0.18-1.24 and adjusted OR 0.40, 95% CI 0.11-1.41 for ESBL versus GNB controls and ESBL versus miscellaneous organisms, respectively). Exposure to PPIs in the preceding 3 months showed an association with increased risk of ESBL-UTI. While Esomeprazole showed a positive association, Lansoprazole had an inverse association for ESBL-UTI. Restricting the use of PPIs may be beneficial in the fight against antimicrobial resistance.

Risk of type 2 diabetes after diagnosed gestational diabetes is enhanced by exposure to PM2.5.

Air pollution and gestational diabetes mellitus (GDM) are both associated with increased diabetes mellitus (DM) occurrence. However, whether air pollutants modify the effects of GDM on the occurrence of DM has been unknown. This study aims to determine whether the effect of GDM on DM development can be modified by exposure to ambient air pollutants. Women with one singleton birth delivery during 2004-14 according to the Taiwan Birth Certificate Database (TBCD) were included as the study cohort. Those newly diagnosed as having DM 1 year or later after childbirth were identified as DM cases. Controls were selected among women without DM diagnosis during follow-up. Personal residence was geocoded and linked with interpolated concentrations of air pollutants into township levels. Conditional logistic regression was used to determine the odds ratio (OR) of pollutant exposure and GDM, adjusting for age, smoking and meteorological variables. There were 9846 women who were newly diagnosed as having DM over a mean follow-up period of 10.2 years. We involved them and the 10-fold matching controls involved in our final analysis. The OR (odds ratio) (95% confidence interval, 95% CI) of DM occurrence per interquartile range increased in particulate matter (PM) smaller than or equal to 2.5 µm (PM2.5) and ozone (O3) was 1.31 (1.22-1.41) and 1.20 (1.16-1.25), respectively. The effects of PM exposure on DM development were significantly higher in the GDM group (OR: 2.46, 95% CI: 1.84-3.30) than in the non-GDM group (OR: 1.30, 95% CI: 1.21-1.40). Exposure to high levels of PM2.5 and O3 elevates the risk of DM. GDM acted synergistically in DM development with exposure to PM2.5 but not with that to O3.