Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons. CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

Risk of prostate cancer with increasing years of night shift work: A two-stage dose-response meta-analysis with duration of night shift work as exposure dose.

Introduction: Night shift work could be a modifiable risk factor for prostate cancer. However, the epidemiological evidence is inconsistent. To summarize the existing evidence on this topic, we conducted a two-stage dose-response meta-analysis. Methods: Medical librarians searched PubMed, EMBASE, and the Cochrane Library on December 30, 2022. Seven criteria were used to determine the inclusion of each study in the present analysis. Results: Eleven cohort studies (12 cohort reports; total cases: 9366; and total person-years: 88,238,009) and seven case-control studies (seven case-control reports; total cases: 5593; and total controls: 6876) were included. This study estimated that the risk of prostate cancer increased by 1, 12, 24, and 39% after 1, 10, 20, and 30 years of night shift work exposure, respectively, according to four cohort and five case-control studies. Discussion: Seven inclusion criteria were used to determine which studies were eligible for this analysis. Risk ratios from cohort studies and odds ratios from case-control studies were analyzed separately. However, all odds ratios from the case-control studies were excluded because of a high likelihood of publication bias. Moreover, exposure, measured in years of night shift work, was defined based on the information provided by individual studies. Finally, we utilized a recently reported two-stage dose-response meta-analysis method. This study provides evidence that night shift work contributes to the risk of prostate cancer in a dose-dependent manner.

Former smoking, but not active smoking, is associated with delirium in postoperative ICU patients: a matched case-control study.

Objective: To examine the relationship between current and former smoking and the occurrence of delirium in surgical Intensive Care Unit (ICU) patients. Methods: We conducted a single center, case-control study involving 244 delirious and 251 non-delirious patients that were admitted to our ICU between 2018 and 2022. Using propensity score analysis, we obtained 115 pairs of delirious and non-delirious patients matched for age and Simplified Acute Physiology Score II (SAPS II). Both groups of patients were further stratified into non-smokers, active smokers and former smokers, and logistic regression was performed to further investigate potential confounders. Results: Our study revealed a significant association between former smoking and the incidence of delirium in ICU patients, both in unmatched (adjusted odds ratio (OR): 1.82, 95% confidence interval (CI): 1.17-2.83) and matched cohorts (OR: 3.0, CI: 1.53-5.89). Active smoking did not demonstrate a significant difference in delirium incidence compared to non-smokers (unmatched OR = 0.98, CI: 0.62-1.53, matched OR = 1.05, CI: 0.55-2.0). Logistic regression analysis of the matched group confirmed former smoking as an independent risk factor for delirium, irrespective of other variables like surgical history (p = 0.010). Notably, also respiratory and vascular surgeries were associated with increased odds of delirium (respiratory: OR: 4.13, CI: 1.73-9.83; vascular: OR: 2.18, CI: 1.03-4.59). Medication analysis showed that while Ketamine and Midazolam usage did not significantly correlate with delirium, Morphine use was linked to a decreased likelihood (OR: 0.27, 95% CI: 0.13-0.55). Discussion: Nicotine's complex neuropharmacological impact on the brain is still not fully understood, especially its short-term and long-term implications for critically ill patients. Although our retrospective study cannot establish causality, our findings suggest that smoking may induce structural changes in the brain, potentially heightening the risk of postoperative delirium. Intriguingly, this effect seems to be obscured in active smokers, potentially due to the recognized neuroprotective properties of nicotine. Our results motivate future prospective studies, the results of which hold the potential to substantially impact risk assessment procedures for surgeries.

Association between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis.

Among patients with pathologically-proven infective endocarditis, the association of pathogen with occurrence of infection-related glomerulonephritis (IRGN) was examined in 48 cases of IRGN and 192 propensity score-matched controls. Bartonella was very strongly associated with IRGN (OR 38.2, 95% C.I. 6.7-718.8, p-value <.001); other microorganisms were not.

Quality of life in long-term cervical cancer survivors compared with healthy women and women with benign gynecological disorders.

OBJECTIVE: The impact of cervical cancer treatment on the quality of life of long-term survivors compared with the general female population is controversial, and no studies have been conducted comparing patients with benign gynecological diseases. The aim of this study was to compare the quality of life of cervical cancer survivors with that of healthy controls. STUDY DESIGN: A case-control study was conducted to compare the quality of life of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a healthy woman check-up (n 46) or for a benign gynecological disorder (symptomatic, n 113; asymptomatic, n 26). To measure quality of life, self-administered questionnaires, such as the Functional Assessment Cancer Therapy-cervix and World Health Organization quality of life-brief version, were employed. Baseline scores were collected when patients first reported, and further evaluations were completed at 0-6, 7-12, 13-24, 25-60, and more than 60 months. For the contrastive analysis hypothesis, we employed R statistical software. RESULTS: Except for the environment domain at 0-6, 7-12, and 13-24 months (51.52 vs. 60.73, p < 0.0001; 52 vs. 60.73, p < 0.0001; 49.81 vs. 60.73, p < 0.0001, respectively), we found no statistically significant differences in the quality of life between cervical cancer survivors and controls. We did find differences in the physical health domain scores at 0-6 months (60.22 vs. 72.42, p = 0.039) and the social relationships domain scores at 13-24 months (54 vs. 71.42, p = 0.017) between cases and asymptomatic controls. CONCLUSION: Except for physical well-being, environment and social relationships, which were substantially better for controls, especially in the asymptomatic, long-term cervical cancer survivorsquality of life did not vary from that of controls.

Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Corrigendum: Associations between omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fnut.2022.1016943.].

Feasibility and limitations of using commercial databases to evaluate residential mobility in registry-based research on childhood cancer.

BACKGROUND: Researchers have used commercial databases containing residential addresses to reduce exposure misclassification in case-control studies. Our objective is to evaluate the potential systematic bias regarding case status when reconstructing residential locations from commercial databases. METHODS: Our study population of 3640 Colorado-born children includes 520 children diagnosed with acute lymphocytic leukemia between 2002 and 2019. We aligned addresses and date ranges obtained from LexisNexis with registry dates to determine three dichotomous outcomes: Found in LexisNexis, conception date found in LexisNexis, and reference date/diagnosis date found in LexisNexis. We applied logistic regression to determine whether outcomes differed by case status. RESULTS: Mothers of cases were 39% more likely to be found in LexisNexis than mothers of controls (OR = 1.39, 95% CI: 0.97, 2). Of the mothers found in LexisNexis, a conception address was 33% more likely (OR= 1.33, 95% CI: 1.06, 1.66) and a reference/diagnosis address was 60% more likely (OR= 1.60, 95% CI: 1.21, 2.12) to be found for mothers of cases than mothers of controls. CONCLUSION: This study indicates that use of commercial databases to reconstruct residential locations may systematically bias results in case-control studies of childhood cancers.

Association between osteoarthritis and cardiovascular disease in elderly in Japan: an administrative claims database analysis.

OBJECTIVE: To investigate whether osteoarthritis (OA) is a risk factor for cardiovascular disease (CVD); whether there are differences concerning ischaemic heart disease (IHD), congestive heart failure (CHF) and stroke; and whether there are differences between OA sites (hips, knees and hand) in predicting CVD onset. DESIGN: Population-based matched case-control study. SETTING: Health insurance claims data among Japanese patients. PARTICIPANTS: Japanese patients aged ≥65 years with newly diagnosed CVD and hospitalised between January 2015 and December 2020 (cases) and age-matched and sex-matched 1:1 individuals (controls). MAIN OUTCOME MEASURES: A conditional logistic regression model was used to estimate the adjusted ORs and their 95% CIs for CVD, IHD, CHF and stroke risk, adjusting for covariates. RESULTS: A total of 79 296 patients were included, with respect to CVD (39 648 patients with newly diagnosed CVD and 39 648 controls). After adjustment for covariates, the exposure odds of knee OA (KOA), hip OA (HipOA) and hand OA (HandOA) for CVD were 1.192 (95% CI 1.115 to 1.274), 1.057 (95% CI 0.919 to 1.215) and 1.035 (95% CI 0.684 to 1.566), respectively, showing an association only for KOA. The exposure odds of KOA, HipOA and HandOA for IHD were 1.187 (95% CI 1.086 to 1.297), 1.078 (95% CI 0.891 to 1.306) and 1.099 (95% CI 0.677 to 1.784), respectively. The exposure odds of KOA, HipOA and HandOA for stroke were 1.221 (95% CI 1.099 to 1.356), 0.918 (95% CI 0.723 to 1.165) and 1.169 (95% CI 0.635 to 2.151), respectively. Similar to CVD, only KOA was associated with both. For CHF, neither KOA nor HipOA and HandOA were associated with CHF development. CONCLUSION: This study confirms the association of KOA with CVD, particularly IHD and stroke, in the Japanese population. The finding that patients with KOA have a higher CVD risk can potentially assist in guiding future treatment strategies.

CT comparison of the nasal airway anterior and posterior to the piriform aperture in patients with and without nasal obstruction.

BACKGROUND: Nasal airway stenosis may lie anterior and/or posterior to the piriform aperture. We intended to compare the nasal airway anterior and posterior to the piriform aperture in patients with and without nasal obstruction. METHODS: Segmented computed tomography cross-sectional areas of the nasal airway anterior (CT-CSAant) and posterior to the piriform aperture (at the level of the head of the inferior turbinate; CT-CSApost) were compared between patients with nasal obstruction (cases) and trauma controls. CT-CSA were approximately perpendicular to the direction of the nasal airflow. Anterior to the piriform aperture, they were tilted about 30o, 60o and 90o to the nasal floor. Posterior to the piriform aperture, they were tilted about 50o, 80o and 100o to the nasal floor. In cases, we examined the Pearson's correlation of active anterior rhinomanometry with CT-CSAant and CT-CSApost. RESULTS: Narrow and bilateral CT-CSApost were similarly large between 56 cases and 56 controls (all p > 0.2). On the contrary, narrow and bilateral CT-CSAant were significantly smaller in cases than in controls (all p < 0.001). The ratio of the size of CT-CSAant-30 to that of CT-CSApost-80 was significantly lower in cases (median: 0.84; lower to upper quartile: 0.55-1.13) than in controls (1.0; 0.88-1.16; Mann-Whitney U test; p = 0.006). Bilateral CT-CSAant correlated significantly with total inspiratory flow (all p < 0.026) in contrast to bilateral CT-CSApost (all p > 0.056). CONCLUSIONS: The nasal airway anterior to the piriform aperture was smaller in patients with nasal obstruction due to skeletal nasal stenosis than that in controls. On the contrary, the nasal airway posterior to the piriform aperture was similarly large between patients with and without nasal obstruction. Furthermore, in patients with nasal obstruction, the anterior nasal airway was narrower compared to that located posterior to it. On the contrary, control patients' anterior nasal airway was as large as the posterior one.

Dietary Patterns and Lifestyle Factors Associated with the Risk of Colorectal Cancer: A Hospital-Based Case-Control Study among Malaysians.

Background: This study aimed to examine the association between dietary patterns, lifestyle factors, and colorectal cancer (CRC) risk among the Malaysian population. Methods: We recruited 100 patients and 100 controls from two selected government hospitals. Principal component analysis was used to identify dietary patterns using a 123-item semiquantitative food frequency questionnaire. Tobacco smoking and alcohol consumption questionnaires were modified from the WHO STEPS Survey questionnaire. Physical activity levels were assessed using the revised Global Physical Activity questionnaire. Associations between dietary patterns, lifestyle factors and CRC risk were assessed using logistic regression with SPSS version 24.0. Results: Three dietary patterns were derived from factor analysis: i) vegetables; ii) meat, seafood and processed food; and iii) grains and legumes. High vegetable diet intake was independently and significantly associated with an 81% decreased risk of CRC (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.08, 0.46). Both recreational-related physical activity (OR: 2.04; 95% CI: 1.14, 3.64) and vigorous physical activity (OR: 2.06; 95% CI: 1.13, 3.74) are significantly associated with decreased risk of CRC. Increasing the number of cigarettes smoked (≥ 16 cigarettes) per day significantly increased the odds of developing CRC (OR: 2.58; 95% CI: 1.95, 6.75). The duration of alcohol consumption cessation was inversely associated with CRC risk (OR: 2.52; 95% CI: 2.30, 10.57). Conclusion: The protective effects of a fruit and vegetable diet, and a healthy lifestyle can be used to develop interventions that help reduce the risk of CRC in the Malaysian population.

Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

Immune thrombocytopenia in systemic lupus erythematosus: Prevalence, risk factors, and a novel predictive model for risk assessment.

INTRODUCTION: Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality. OBJECTIVES: To describe which factors are associated with the presence of ITP in SLE patients. METHODS: Retrospective case-control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP. RESULTS: ITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-ß2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-ß2GP1 antibodies. CONCLUSION: SLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP.

Identifying prior signals of bipolar disorder using primary care electronic health records: a nested case-control study.

BACKGROUND: Bipolar disorders are serious mental illnesses, yet evidence suggests that the diagnosis and treatment of bipolar disorder can be delayed by around 6 years. AIM: To identify signals of undiagnosed bipolar disorder using routinely collected electronic health records. DESIGN AND SETTING: A nested case-control study conducted using the UK Clinical Practice Research Datalink (CPRD) GOLD dataset, an anonymised electronic primary care patient database linked with hospital records. 'Cases' were adult patients with incident bipolar disorder diagnoses between 1 January 2010 and 31 July 2017. METHOD: The patients with bipolar disorder (the bipolar disorder group) were matched by age, sex, and registered general practice to 20 'controls' without recorded bipolar disorder (the control group). Annual episode incidence rates were estimated and odds ratios from conditional logistic regression models were reported for recorded health events before the index (diagnosis) date. RESULTS: There were 2366 patients with incident bipolar disorder diagnoses and 47 138 matched control patients (median age 40 years and 60.4% female: n = 1430/2366 with bipolar disorder and n = 28 471/47 138 without). Compared with the control group, the bipolar disorder group had a higher incidence of diagnosed depressive, psychotic, anxiety, and personality disorders and escalating self-harm up to 10 years before a bipolar disorder diagnosis. Sleep disturbance, substance misuse, and mood swings were more frequent among the bipolar disorder group than the control group. The bipolar disorder group had more frequent face-to-face consultations, and were more likely to miss multiple scheduled appointments and to be prescribed ≥3 different psychotropic medication classes in a given year. CONCLUSION: Psychiatric diagnoses, psychotropic prescriptions, and health service use patterns might be signals of unreported bipolar disorder. Recognising these signals could prompt further investigation for undiagnosed significant psychopathology, leading to timely referral, assessment, and initiation of appropriate treatments.

Occupational exposure to endotoxins and small cell lung cancer: a systematic review with meta-analysis.

The relationship of occupational exposure to endotoxins with different histologic subtypes of lung cancer has not been established. Our objective was to conduct a systematic review with meta-analysis to assess the effect of exposure to endotoxins on the development of small cell lung cancer (SCLC). A bibliographic search was conducted using MEDLINE, Embase, CENTRAL, and Web of Science databases until December 2022, including all cohort and/or case-control studies that examined occupational exposure to endotoxins and SCLC. Risk of bias was assessed using the U.S. Office of Health Assessment and Translation tool. A random effects model was applied, publication bias were assessed, and a sensitivity analysis was conducted. Four papers were selected for meta-analysis purposes. A total of 144 incident cases of SCLC and 897 population or hospital controls were included. Occupational exposure to endotoxins was considered for textile/leather industry and agricultural sector workers exposed to endotoxins originating from wool, cotton, or leather dust. Except for one study, all investigations were classified as having a low probability of risk of biases. The results of the meta-analysis were not statistically significant (pooled OR: 0.86; 95% CI:0.69-1.08). In addition, neither between-study heterogeneity (I2=0%;p=0.92) nor publication bias was observed (p=0.49). The results of the sensitivity analysis, after including five studies that assessed the risk of SCLC among textile industry and crop/livestock farm workers (not specifically exposed to endotoxins), showed a negative statistically non-significant association and low between-study heterogeneity (pooled OR: 0.90; 95% CI:0.79-1.02; I2=22%;p=0.23). Subjects exposed to occupational exposure to endotoxins seem to exhibit a negative association with the development of SCLC, although the results are not conclusive.

Use of machine learning to identify characteristics associated with severe hypoglycemia in older adults with type 1 diabetes: a post-hoc analysis of a case-control study.

INTRODUCTION: Severe hypoglycemia (SH) in older adults (OAs) with type 1 diabetes is associated with profound morbidity and mortality, yet its etiology can be complex and multifactorial. Enhanced tools to identify OAs who are at high risk for SH are needed. This study used machine learning to identify characteristics that distinguish those with and without recent SH, selecting from a range of demographic and clinical, behavioral and lifestyle, and neurocognitive characteristics, along with continuous glucose monitoring (CGM) measures. RESEARCH DESIGN AND METHODS: Data from a case-control study involving OAs recruited from the T1D Exchange Clinical Network were analyzed. The random forest machine learning algorithm was used to elucidate the characteristics associated with case versus control status and their relative importance. Models with successively rich characteristic sets were examined to systematically incorporate each domain of possible risk characteristics. RESULTS: Data from 191 OAs with type 1 diabetes (47.1% female, 92.1% non-Hispanic white) were analyzed. Across models, hypoglycemia unawareness was the top characteristic associated with SH history. For the model with the richest input data, the most important characteristics, in descending order, were hypoglycemia unawareness, hypoglycemia fear, coefficient of variation from CGM, % time blood glucose below 70 mg/dL, and trail making test B score. CONCLUSIONS: Machine learning may augment risk stratification for OAs by identifying key characteristics associated with SH. Prospective studies are needed to identify the predictive performance of these risk characteristics.

Comparison of the microvascular anastomotic Coupler™ system with hand-sewn suture for end to end veno-venous anastomosis for head and neck reconstruction with free flap transfer: Medico-economic retrospective case-control study.

The aim of this study was to assess the medico-economic impact of the MACD Coupler™ system in comparison with HSA for end to end veno-venous anastomosis during free flap transfer. A retrospective case-control study was performed in an academic institution, from March 2019 through July 2021, to analyze medical and economic outcomes of patients managed for head and neck reconstruction with free flap transfer. 43 patients per group were analyzed. Rates of initial success, re-intervention, complications and flap transfer failure were not different between groups. Use of MACD increased the cost of medical devices between Coupler and Control groups with respectively K€ 0.7 [0.5; 0.8] and K€ 0.1 [0.5; 0.8] (p = 0.001) and decreased the cost for operating staff with respectively K€ 4.0 [3.4; 5.2] and K€ 5.1 [3.8; 5.4] (p = 0.03). The total management costs were not different between groups with respectively a total median cost of K€ 18.4 [14.3; 27.2] and K€ 17.3 [14.1; 23.7] (p = 0.03). In conclusion, the cost of the Coupler™ is significant but is partly offset by the decrease in operating staff costs. The choice of one or the other technique can be left to the discretion of the surgeon.

Association between the Use of Proton Pump Inhibitors and Cardiovascular Diseases: A Nested Case-Control Study Using a National Health Screening Cohort.

We investigated the association of proton pump inhibitor (PPI) use with the risk of stroke and ischemic heart disease (IHD). The Korean National Health Insurance Service-Health Screening cohort from 2002 to 2003, the participants of which were followed up until 2019, was used. In study I, 45,905 participants who were diagnosed with stroke were matched with 91,810 control I participants. The history of PPI medication was examined. In study II, 40,928 participants who were diagnosed with IHD were matched with 81,856 control II participants. In both study I and study II, the previous history of PPI medication was examined. A propensity score overlap-weighted multivariable logistic regression analysis was conducted to estimate the overlap-weighted odds ratios (ORs) of PPI use for stroke (study I) and IHD (study II). Current PPI use was linked with higher odds for stroke in study I. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 0.96 [95% CI = 0.92-1.00] < 1.55 [1.50-1.61] < 1.62 [1.57-1.68] for < 30 days, 30 to 180 days, and ≥180 days of PPI use). Previous PPI use was linked with higher odds for IHD in study II. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 1.13 [95% CI = 1.08-1.18] < 2.12 [2.04-2.21] < 2.60 [2.51-2.69] for <30 days, 30 to 180 days, and ≥180 days of PPI use). Current PPI medication is associated with a high risk of stroke and IHD. A longer duration of PPI medication was related to a higher risk of stroke and IHD. However, a prior history of PPI medication was not linked with a high risk of stroke or IHD.

Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway.

OBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group. DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway. PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls. PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group. RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8). CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic.

Drug Exposure During Pregnancy: A Case-Control Study from a Primary Care Database.

Objective: Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births. Materials and Methods: Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure. Results: Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p < 0.001), smoking (4.5% vs. 3.6%, p < 0.001), and previous abortions (9.9% vs. 7.8%, p < 0.001). Anxiety (30.3% and 25.1%, p < 0.001), respiratory diseases (10.6% and 9.2%, p < 0.001), and migraine (8.2% and 7.3%, p < 0.001), for cases and controls, respectively, were the most frequent baseline conditions. Cases had lower rate of drug exposure, 40,148 (66.5%) versus 80,449 (68.1%), p < 0.001. Association with abortion was found for systemic antihistamines (adjusted odds ratio [ORadj] 1.23, 95% confidence interval [CI] 1.19-1.27), antidepressants (ORadj 1.11, 95% CI 1.06-1.17), anxiolytics (ORadj 1.31, 95% CI 1.26-1.73), and nonsteroidal anti-inflammatory drugs (ORadj 1. 63, 95% CI 1.59-1.67). Conclusions: These high rates of drug exposures during the first trimester of pregnancy highlights the relevance of informed prescription to women with childbearing potential.