Conditional Logistic Regression Models Research Articles

Physical activity, metabolites, and breast cancer associations.

The effects of usual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites, and breast cancer risk. Physical activity levels were assessed using doubly labeled water, accelerometers, and 24-hr recalls in the IDATA study (N = 707 participants, ages 50-74 years, 51% women), with 1-6 assessments over 12 months and two blood sample collections. Partial Spearman correlations were used to estimate associations between physical activity and 843 serum metabolites, corrected for multiple testing. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolites with postmenopausal breast cancer in a nested case-control study (621 cases, 621 controls), all statistical tests were 2-sided. Physical activity was associated with 164 metabolites spanning numerous pathways, including amino acid and fatty acid metabolism. Twelve of these metabolites were also associated with breast cancer risk, ten of which supported a protective role of physical activity. Notably, higher physical activity was associated with lower 16alpha-hydroxy DHEA 3-sulfate (androgen) and adipoylcarnitine (fatty acid), both of which were associated with increased breast cancer risk (OR per 1 standard deviation (SD)=1.34, 95% CI = 1.16-1.55 and 1.26,1.11-1.42, respectively). Higher physical activity energy expenditure was also associated with lower sphingomyelin (d18:1/20:1, d18:2/20:0), which was associated with a reduced breast cancer risk (0.82,0.73-0.93). Physical activity is associated with a broad range of metabolites, many of which are consistent with a protective effect against breast cancer. Our findings highlight potential metabolic pathways for cancer prevention.

Risk Factors for Late-Onset Psychosis: A Case-Control Study.

The onset of schizophrenia occurs after the age of 40 in up to 20% of cases. We aim to depict risk factors for first-episode psychosis after the age of 40 by comparing late-onset psychosis (LOP) patients to healthy age-matched controls. In this case-control study using electronic health records, 142 individuals aged 40-65 years with an encounter for a first episode of psychosis between 2013 and 2021 were included. Four controls (N = 568) were matched to each case on age, sex, race, and year of encounter. Potential risk factors for the primary analysis were captured via structured data and text-mining of medical notes. Conditional logistic regression models were used to assess the odds of LOP with potential risk factors. After adjusting for all variables in the main analysis, odds for LOP were increased by immigration (OR 3.30, 95% CI, 1.56-6.98), depression (OR 3.58, 95% CI, 2.01-6.38), anxiety (OR 2.12, 95% CI, 1.20-3.75), cannabis use (OR 3.00, 95% CI, 1.36-6.61), alcohol use disorder (OR 5.46, 95% CI, 2.41-12.36), polysubstance use (OR 4.22, 95% CI, 1.30-13.7), severe trauma (OR 2.29, 95% CI, 1.08-4.48), and caregiver burden (OR 15.26, 95% CI, 3.85-60.48). Life stressors along with the effects of substance use and other psychiatric conditions may confer some risk to the development of LOP. Replication is required in independent prospective studies. Further research is necessary to truly parse out which of these factors belong on the causal pathway.

12374 A Prospective Study Of Plasma Levels Of Asprosin And Incident Type 2 Diabetes Among Postmenopausal Women In The Women’s Health Initiative

Abstract Disclosure: B. Yang: None. J. Li: None. E.S. Silva: None. L.S. Phillips: None. J.E. Manson: None. A.P. Reiner: None. A.R. Chopra: None. S. Liu: None. Background: Asprosin, a 30-kDa hormone identified from white adipose tissue, has been shown to play key roles in regulating hepatic glucose release and appetite stimulation. Despite an increasing body of experimental studies demonstrating asprosin as a promising therapeutic target, little is known about its distribution in the general population particularly concerning its association with incident type 2 diabetes (T2D). Objectives: To evaluate whether higher plasma levels of asprosin are associated with incident T2D among postmenopausal women independently of known risk factors for T2D. Methods: We conducted a case-control study nested in the Women’s Health Initiative (WHI), including 5,198 participants free of diabetes, cardiovascular diseases, and cancer at baseline (2,602 incident T2D cases and 2,596 controls). Plasma levels of asprosin were measured using a sandwich enzyme-linked immunosorbent (ELISA) assay. We used conditional logistic regression models to estimate the association between asprosin and T2D risk with adjustment for matching variables (age, race, sampling batch), education, body mass index (BMI), physical activity, tobacco smoking, alcohol drinking, family history of diabetes, age at menopause, total energy intake, the Alternate Healthy Eating Index (AHEI), and multivitamin use. Results: Approximately 43% of participants were white and the mean age at baseline was 63 years. The median plasma levels of asprosin were 38 (IQR: 30, 50) pmoL/L in the controls and 39 (IQR: 31, 50) pmoL/L among those who developed T2D during follow-up. Compared with the participants in the lowest quintile of plasma levels of asprosin at baseline, those in the highest quintile had a 26% increased risk of T2D (adjusted odds ratio: OR: 1.26 [95% CIs, 1.01, 1.57], p for trend=0.03) in the fully adjusted model. The OR estimates exhibited a large variation across race and BMI, although there was a linear dose-response relation between levels of asprosin and T2D risk (p for nonlinear=0.44). Genetic analysis revealed that women with the heterozygous allele (CG) at single nucleotide polymorphisms (SNP) rs56407701 had higher levels of asprosin compared to women with the homozygous reference allele (CC). Further, Mendelian Randomization analysis revealed that genetically predicted asprosin levels were associated with higher T2D risk. Conclusion: Among postmenopausal women, higher plasma levels of asprosin were prospectively associated with elevated T2D risk independent of known T2D risk factors. Further work is needed to confirm the potential causal role of this peptide hormone in the clinical risk stratification and potential prevention of T2D. Presentation: 6/2/2024

Ambient Air Pollution and Hospitalizations for Schizophrenia in China

Schizophrenia episodes may be triggered by short-term environmental stimuli. Short-term increases in ambient air pollution levels may elevate the risk of schizophrenia episodes, yet few epidemiologic studies have examined this association. To investigate whether short-term increases in air pollution levels are associated with an additional risk of schizophrenia episodes, independent of absolute air pollution concentrations, and whether sustained increases in air pollution levels for several days are associated with more pronounced risks of schizophrenia episodes. This nationwide, population-based, time-stratified case-crossover study was performed based on hospitalization records for schizophrenia across 295 administrative divisions of prefecture-level or above cities in China. Records were extracted from 2 major health insurance systems from January 1, 2013, to December 31, 2017. Thirty-six cities with a small number of schizophrenia hospitalizations (n < 50) were excluded. Data analysis for this study was performed from January to March 2024. Daily absolute concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were collected. Air pollution increases between neighboring days (APINs) were generated as the differences in absolute air pollution concentrations on the current day minus that on the previous day. Sustained increases (APIN ≥5 μg/m3 for PM2.5 and PM10, APIN ≥1 μg/m3 for nitrogen dioxide and sulfur dioxide, and APIN ≥0.05 mg/m3 for carbon monoxide) lasting for 1 or more to 4 or more days were defined for different air pollutants. Patients with schizophrenia episodes were identified by principal discharge diagnoses of schizophrenia. A conditional logistic regression model was used to capture the associations of absolute concentrations, APINs, and sustained increase events for different air pollutants with risks of schizophrenia hospitalizations. The study included 817 296 hospitalization records for schizophrenia across 259 Chinese cities (30.6% aged 0-39 years, 56.4% aged 40-64 years, and 13.0% aged ≥65 years; 55.04% male). After adjusting for the absolute concentrations of respective air pollutants, per-IQR increases in 6-day moving average (lag0-5) APINs of PM2.5, PM10, nitrogen dioxide, sulfur dioxide, and carbon monoxide were associated with increases of 2.37% (95% CI, 0.88%-3.88%), 2.95% (95% CI, 1.46%-4.47%), 4.61% (95% CI, 2.93%-6.32%), 2.16% (95% CI, 0.59%-3.76%), and 2.02% (95% CI, 0.39%-3.68%) in schizophrenia hospitalizations, respectively. Greater risks of schizophrenia hospitalizations were associated with sustained increases in air pollutants lasting for longer durations up to 4 or more days. This case-crossover study of the association between ambient air pollution increases and schizophrenia hospitalizations provides novel evidence that short-term increases in ambient air pollution levels were positively associated with an elevated risk of schizophrenia episodes. Future schizophrenia prevention practices should pay additional attention to APINs, especially sustained increases in air pollution levels for longer durations, besides the absolute air pollution concentrations.

Short-term exposure to PM2.5 constituents, extreme temperature events and stroke mortality

BackgroundFine particulate matter (PM2.5) pollution and extreme temperature events (ETEs) are main environmental threats to human health. Elevated stroke mortality has been growingly linked to PM2.5 mass exposure, while its relationship with PM2.5 constituents was extensively unstudied across the globe. Additionally, no prior assessments have investigated the interactive effects of PM2.5 constituents and ETEs on stroke mortality. MethodsProvince-wide records of 320,372 stroke deaths collected in eastern China during 2016–2019 were analyzed using an individual-level time-stratified case-crossover design. Daily gridded estimates of PM2.5 mass and its major constituents (i.e., black carbon [BC], organic matter [OM], ammonium [NH4+], sulfate [SO42‐], and nitrate [NO3‐]) were assigned to stroke cases on case days and control days at the residential address. We assessed 12 ETEs defined by multiple combinations of air temperature thresholds (2.5–10th percentiles for cold spell, 90–97.5th percentiles for heat wave) and durations (2–4 days). Conditional logistic regression model was applied to investigate associations of short-term exposure to PM2.5 constituents and ETEs with stroke mortality. Odds ratio and its 95% confidence interval (CI) were assessed for an interquartile range (IQR) increase in each PM2.5 constituent and on ETEs days compared with non-ETEs days. Additive interactive effects were quantitatively evaluated via relative excess odds due to interaction (REOI), attributable proportion due to interaction (AP), and synergy index (SI). ResultsElevated overall stroke mortality was significantly related to PM2.5 constituents, with the largest odds observed for NO3‐ (1.04, 95% CI: 1.03–1.04, IQR = 11.25 μg/m3), followed by OM (1.03, 1.03–1.04, IQR = 7.97 μg/m3), NH4+ (1.03, 1.02–1.04, IQR = 6.66 μg/m3), BC (1.03, 1.02–1.03, IQR = 1.41 μg/m3), and SO42‐ (1.03, 1.02–1.03, IQR = 6.67 μg/m3). Overall, higher risks of stroke mortality were identified in analyses using more rigorous thresholds and lengthened durations of ETEs definitions, ranging from 1.19 (1.17–1.21) to 1.55 (1.51–1.60) for heat wave, and 1.03 (1.02–1.05) to 1.11 (1.08–1.15) for cold spell, respectively. We observed consistent evidence for the synergistic effects of heat wave and PM2.5 constituents on both ischemic and hemorrhagic stroke mortality, where compound exposures to heat wave and secondary inorganic aerosols (i.e., NO3‐, SO42‐, and NH4+) posed greater increases in risk (0.23< REOI <0.81, 0.16< AP <0.39, and 2.63< SI <8.19). ConclusionsShort-term exposure to both PM2.5 constituents and ETEs were associated with heightened stroke mortality, and heat wave may interact synergistically with PM2.5 constituents to trigger stroke deaths.

Abstract PR001: A comparison of modeling approaches to assess the interplay of social, behavioral, and environmental factors on lung cancer racial disparities

Abstract Purpose: While risk factors for lung cancer incidence are well established, our understanding of factors driving an increased risk of lung cancer among Black/African American populations remains incomplete. Methods: We assembled data from five U.S. lung cancer case-control studies matched on race, gender and age: the Southern Community Cohort Study, the Inflammation, Health, Ancestry and Lung Epidemiology study, the Northern California Lung Cancer Study, three Detroit area lung studies, and the NCI-Maryland Lung Cancer Study. Incident lung cancers were ascertained from state and regional cancer registries or National Death Index mortality records. Social, behavioral, and environmental factors were ascertained by in-person interviews or mailed-in questionnaires. Participant's residential addresses were geocoded and area-level area deprivation and environmental justice variables were linked at the census block. We evaluated interactions between known lung cancer risk factors and race using multilevel logistic regression analyses and novel tree-based approaches to identify potential factors contributing to racial disparities. Tree-based approaches included a conditional matched classification tree analysis designed to detect complex interactions, as well as a specialized partially recursively induced structured moderation (PRISM) analysis to study variation in disparity in lung cancer risk across levels of educational status. Results: Among 5,829 lung cancer cases and 10,671 controls (64% self-identified Black/African American and 36% White), the average age was 60 years, 50% were female, and 24% had less than a high school education. Conditional logistic regression models fit after imputation of missing data identified increased risk of lung cancer associated with personal history of cancer, family history of lung cancer, current smoking status, smoking duration, smoking pack-years, and higher neighborhood deprivation; whereas, reduced lung cancer risk was associated with higher education and increased BMI. Similar patterns were observed among Black/African Americans only, with the addition of secondhand smoke exposure. Assessment for interactions with race identified significant interactions between race and body mass index (BMI) (p-value &amp;lt; 0.0001), PM2.5 (p= 0.010) and gender (p=0.001) and lung cancer risk. A conditional matched classification tree analysis identified both increased and decreased risk subgroups defined by multi-way interactions of similar variables that were identified as significant main effects in the conditional logistic regression analysis. Smoking pack-years and BMI were identified as the most important determinants of heterogeneity of disparity in lung cancer risk across educational levels in our study population. Conclusions: The use of both traditional and novel tree-based based approaches provide approaches for identifying factors contributing to racial disparities. Future studies should assess the interplay of lung cancer risk factors to inform development of targeted interventions. Citation Format: Melinda C. Aldrich, Chen Zhao, Christine M Lusk, Lucie McCoy, James Jaworski, Michael Mumma, Catherine Pichardo, Michael Betti, John K Wiencke, Brid Ryan, Ann G Schwartz, Sunil Rao. A comparison of modeling approaches to assess the interplay of social, behavioral, and environmental factors on lung cancer racial disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR001.

Abstract B020: DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members

Abstract Introduction: Pancreatic cancer (PC) is a devastating disease, its etiology is not fully understood, and there is a paucity of non-invasive biomarkers for early diagnosis. While DNA methylation (DNAm) holds promise, associations between DNAm and PC risk are poorly understood, especially regarding temporal changes in associations. Therefore, we aimed to evaluate potential associations between DNAm in pre-diagnostic serum on 9 genes (BNIP3, CDKN1C, CLDN4, LCN2, p16, RASSF1, SFN, SPARC, and TFPI-2) and 2 repetitive elements (Alu and LINE-1) and PC risk in a US Department of Defense cohort. Methods : The study population included 82 PC cases, diagnosed 1991 - 2007, and 229 controls individually- matched on age (within 5 years), sex, race, and serum draw time period. Cases had up to 3 pre- diagnostic serum samples. Controls had 1 serum sample collected 0-10 years before their selection date (date of case diagnosis). DNA was extracted from serum and the percentage of cytosines at a given CpG site that were methylated was quantified via Pyrosequencing. For serum samples within a time window (&amp;lt;2, 2-&amp;lt;5, and 5-10 years pre-diagnosis), we computed odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of each CpG site with PC risk (66 sites in total across all genes and repetitive elements) with conditional logistic regression models. DNAm was evaluated as both a binary variable and a continuous variable. Results : In samples collected 5-10 years before diagnosis, those with no DNAm (0% DNAm) had increased odds of PC compared to those with DNAm (&amp;gt;0% DNAm) in the promoter region of BNIP3 (Chr10:131982293 OR, 95% CI: 5.63, 1.16 – 27.28) and those with lower DNAm (&amp;lt;median) had increased odds of PC compared to those with higher DNAm (≥median) in the promoter regions of CDKN1C (Chr11:2886398 OR, 95% CI: 4.07, 1.16 – 14.31; Chr11:2886388 OR, 95% CI: 3.51, 1.24 – 9.96) and RASSF1 (Chr3:50340841 OR, 95% CI: 3.98, 1.15 – 17.45). Similarly, in samples collected 2 - &amp;lt;5 years before diagnosis, lower DNAm (&amp;lt;median) was associated with increased odds of PC compared to those with higher DNAm (≥median) in the promoter region of TFPI-2 (Chr7:93890717 OR, 95% CI: 3.82, 1.20 – 12.15). In models with DNAm as a continuous measure and in samples collected &amp;lt;2 years before diagnosis, a 1% increase in DNAm in the promoter region of SFN was associated with increased odds of PC (Chr1:26863188 OR, 95% CI: 1.23, 1.01 – 1.51). There was no evidence of associations between DNAm on Alu, CLDN4, LCN2, LINE-1, p16, or SPARC and PC risk. Conclusions : Our findings of increased risk of PC associated with lower DNAm on BNIP3, CDKN1C and TFPI-2 and higher DNAm on SFN genes suggest there may be molecular patterns occurring prior to PC diagnosis that could be considered further for developing non-invasive biomarkers for early diagnosis of this aggressive carcinoma. The opinions and assertions expressed herein do not reflect the official policy or position of the Uniformed Services University, the Department of Defense, or the National Cancer Institute. Citation Format: Jordan McAdam, Ruth M Pfeiffer, Alexander P Keil, Ann Meyer, Anwar E Ahmed, Dechang Chen, Jennifer Rusiecki. DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B020.

No Association Between Growth Hormone Therapy and Upper Extremity Physeal Tension Injuries: A Matched Case-control Study.

Recent evidence has identified a strong association between growth hormone therapy and physeal injuries in the lower extremity; however, few studies have investigated this association in the upper extremity. (1) Do pediatric patients with physeal tension injuries of the shoulder and elbow have higher odds of having exposure to recombinant growth hormone therapy than matched controls? (2) Are the odds of having exposure to recombinant growth hormone therapy in physeal tension injuries different when stratified by shoulder and elbow injuries? Using a matched case-control study design, patients between 4 and 18 years of age treated at a large, urban, academic center from February 1, 2016, to November 6, 2023, were identified by ICD-10 codes using EPIC SlicerDicer, an electronic medical record-based data mining tool. Patients diagnosed with physeal tension injuries in the shoulder or elbow were included in the case group, and those with midshaft radius, metaphyseal radius, or both-bone forearm fractures were included in the control group. A total of 618 patients with physeal injuries and 1244 with non-physeal fractures were identified and screened for inclusion. After further chart review to confirm diagnoses, 46% (283) of patients with physeal injuries and 54% (670) of patients with non-physeal fractures were included. A further 6% (16) of patients with physeal injuries and 2% (15) of patients with non-physeal injuries were excluded due concomitant dislocations or missing data, resulting in 267 eligible patients with physeal injuries and 655 eligible patients with non-physeal fractures. Two patients with concurrent elbow and shoulder physeal injuries were additionally excluded from stratified analyses. Patients with physeal injuries and non-physeal fractures were 1:1 matched by age ± 0.5 years, sex, and BMI ± 2 kg/m2. In all, 522 patients were included in the analysis, including 261 patients with physeal injuries and 261 with non-physeal fractures. The mean ± SD ages for both patient groups was 13 ± 2 years (p = 0.44), 88% (229 of 261) of all participants were male, and the mean BMIs were 19.9 ± 3.0 kg/m2 and 19.4 ± 3.0 kg/m2 (p = 0.11), respectively. Growth hormone exposure was compared between patients with physeal injuries and non-physeal fractures using a conditional logistic regression model. Overall, 4% (10 of 261) of patients with physeal injuries had exposure to growth hormone therapy as compared with 2% (4 of 261) of patients with non-physeal fractures (OR 2.5 [95% confidence interval 0.8 to 8.0]). Subgroup analyses of shoulder and elbow injuries demonstrated no difference in growth hormone exposure between patients with physeal injuries and non-physeal fractures (OR 2 [95% CI 0.4 to 10.2] and OR 3 [95% CI 0.6 to 14.9], respectively). In light of these results, clinicians may not need to advise precaution against sports or other activities that put the upper extremity physes under stress when treating patients with growth hormone supplementation therapy. Future multicenter studies, however, are indicated to further investigate for the existence of any subtle association between growth hormone therapy and upper extremity physeal injuries relative to the large association previously noted in the lower extremity in pediatric and adolescent patients. Level III, therapeutic study.

Associations between long-term exposures to environmental factors and the development of amyotrophic lateral sclerosis: A matched case-control study

ObjectiveAmyotrophic lateral sclerosis (ALS) is a motor neuron disease in which the causes remain unclear, particularly the contribution of environmental factors. Thus, we created a multifactorial database to investigate the association between long-term exposure to urbanization, air pollution, water pollution, and the development of ALS. ApproachA matched case-control study was conducted in New Brunswick, Canada from January 2003 to February 2021. Study population included 304 ALS patients and 1207 controls with their historical postal codes from the New Brunswick Citizen Database linked to medical records and spatial environmental datasets from the Canadian Urban Environmental Heath Research Consortium. We compared their environmental exposures at place of residence prior to disease onset via conditional logistic regression models. ResultsOf the common air pollutants investigated, odds of ALS was significantly higher with increased SO2 exposure (OR = 4.369, 1.190-16.044 [95% CI], per 1 ppb increase of SO2) in adjusted models. No significant associations were observed for the investigated urbanization and water pollution-related exposures. ConclusionsThis is the first study to rigorously identify a potential environmental cause of ALS. Our findings suggest an association between long-term exposure to air pollutants, particularly SO2, and the development of ALS. Revision of SO2 emission regulations may be required. ImplicationsThe identification of SO2 exposure as an ALS environmental risk factor opens new prospects for identifying ALS therapeutic targets. Utilizing a similar data linking workflow to pre-existing disease registries found within data centres should be conducted to further investigate environmental influences on complex diseases.

Association of free fatty acid in first trimester with the risk of gestational diabetes mellitus: a nested case-control study

BackgroundAccumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA.ObjectiveThis study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM.MethodsThe participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography–Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM.ResultsNine FFAs were respectively associated with an increased risk of GDM (P < 0.05), and four FFAs were respectively associated with a decreased risk of GDM (P < 0.05). SFA risk score was associated with a greater risk of GDM (OR = 1.34, 95% CI: 1.12–1.60), as well as UFA risk score (OR = 1.26, 95% CI: 1.11–1.44), MUFA risk score (OR = 1.70, 95%CI: 1.27–2.26), PUFA risk score (OR = 1.32, 95%CI: 1.09–1.59) and TFA risk score (OR = 2.51, 95%CI: 1.23–5.13). Moreover, joint effects between different types of FFA risk scores on GDM were detected. For instance, compared with those with low risk scores of SFA and UFA, women with high risk scores of SFA and UFA had the highest risk of GDM (OR = 8.53, 95%CI: 2.41–30.24), while the Odds ratio in those with a low risk score of SFA and high risk score of UFA and those with a high risk score of SFA and low risk score of UFA was 6.37 (95%CI:1.33– 30.53) and 4.25 (95%CI: 0.97–18.70), respectively.ConclusionMaternal FFAs during the first trimester were positively associated with the risk of GDM. Additionally, there were joint effects between FFAs on GDM risk.CondensationElevated FFA levels in the first trimester increased the risk of GDM.

Post-Traumatic Stress Disorder and Risk of Parkinson's Disease in a Veteran Cohort.

Post-traumatic stress disorder (PTSD) may be a risk factor for Parkinson's disease (PD). We examined the relation between PTSD and PD in a cohort of 158,122 Veterans who had any Veterans Health Administration (VHA) or Medicare health care utilization between 10/1/1999- 2/17/2021. Using a nested case-control design we matched 10 controls to each Veteran with PD by sex, race, and rank. In conditional logistic regression models adjusted for camp and smoking, a PTSD diagnosis was significantly associated with PD (OR = 1.35; p = 0.0002); odds were higher if PTSD was coded before PD (OR = 1.53, p < 0.0001). PTSD may be a risk factor for PD.

Use of systemic hormonal contraception and risk of attempted suicide: a nested case-control study.

Evidence regarding the role of hormonal contraception (HC) as a risk factor for attempted suicide is inconclusive. Thus, this study aimed to assess the associations of use of different types of systemic HC with the risk of attempted suicide in women aged 15-49years. Data on a population-based cohort (n = 587,823) of HC users and non-users in 2017 was derived from national registers in Finland. In a nested case-control design we examined the risk of attempted suicide in relation to current HC use (past six months) via multivariable conditional logistic regression models. During the follow-up (from 2018 to 2019) there were 1.174,346 million person-years of which 818 cases of suicide attempts were observed (incidence rate: 0.70 per 1000 person-years). Use of HC, especially combined hormonal contraceptives, was not associated with a higher risk of attempted suicide compared to non-use (OR 0.68, 95% CI 0.45-1.02) after controlling for marital status, socioeconomic status, education, chronic diseases, recent delivery, recent psychiatric hospitalizations, and current use of psychotropic medications. In women without psychiatric history, current HC use (OR 0.73, 95% CI 0.58-0.91), especially ethinylestradiol-containing preparations (OR 0.54, 95% CI 0.40-0.73), was associated with a lower risk of attempted suicide. After adjusting for recent psychiatric hospitalizations and use of psychotropic medications, current use of progestin-only preparations was not associated with attempted suicide. In conclusion, current HC use was not associated with an increased risk of attempted suicide in fertile-aged women.

Age and Hair Cortisol Levels as Predictors of SARS-CoV-2 Infection.

Chronic psychosocial stress is known to adversely impact immune function. During the SARS-CoV-2 pandemic, occupational stress among workers in healthcare was at an unprecedented level due to risks of infection and work demands. We performed a nested case-control study to investigate the associations between chronic stress and the risks of contracting SARS-CoV-2. We collected 3 cm of hair from employees at an academic medical center who tested positive for SARS-CoV-2 (N = 49) and controls who tested negative (N = 49), matched for age, race, and sex. The diagnosis of SARS-CoV-2 was based on polymerase chain reaction or antibody tests. As a proxy for chronic stress, we segmented hair into 1 cm sections each representing one month and measured cortisol levels using a cortisol enzyme-linked immunosorbent assay. For cases, we used cortisol concentrations measured in hair segments from the month prior to a positive SARS-CoV-2 test, and for controls, we used time-matched hair segments. We fitted conditional logistic regression models adjusted for sex, age, race, body mass index, and healthcare worker status, and stratified models by older vs. younger age (cutoff = 41 years). African Americans had higher hair cortisol levels relative to participants of other races and ethnicities. In adjusted models, higher hair cortisol concentrations were associated with an increased odds of infection with SARS-CoV-2 (OR = 1.84; CI: 1.10-3.07) among older, but not younger, participants. The results suggest that psychosocial stress may be a risk factor for SARS-CoV-2 infection; stress management may be an important part of a comprehensive approach to protect against SARS-CoV-2 infection.

The association between dietary patterns before pregnancy and gestational diabetes mellitus: a matched case-control study in China.

We aimed to explore the relationship between dietary patterns and gestational diabetes mellitus (GDM) during pre-pregnancy six months using principal component analysis (PCA) and the geometric framework for nutrition (GFN). We conducted a case-control study that included 210 GDM pregnant women and 210 controls. The dietary intake of all participants was assessed by a validated semi-quantitative food frequency questionnaire (FFQ). Major dietary patterns were extracted by PCA. A conditional logistic regression model was used to determine whether specific dietary patterns are associated with the risk of GDM. Meanwhile, the relationship between dietary patterns and GDM was visualized using GFN. Four major dietary patterns were identified: "protein-rich pattern," "plant-based pattern," "oil-pickles-desserts pattern," and "cereals-nuts pattern." After adjustment for confounders, the "plant-based pattern" was associated with decreased risk of GDM (Q4 vs. Q1: OR = 0.01, 95% CI: 0.00-0.08), whereas no significant association was found in other dietary patterns. Moreover, there was no dietary intake of ice cream cones and deep-fried dough sticks for the population, which would produce fewer patients with GDM. Deep-fried dough sticks had statistically significant differences in the case and control groups (p < 0.001), while ice cream cones had the opposite result. The "plant-based pattern" may reduce the risk of GDM. Besides, although the "cereals-nuts pattern" had no association with GDM risk, avoiding the intake of deep-fried dough sticks could decrease GDM risk.

Influenza Epidemiology and Vaccine Effectiveness Following Funded Influenza Vaccine in Queensland, Australia, 2022.

In 2022, publicly funded influenza vaccine was made available to all residents of Queensland, Australia. This study compared influenza epidemiology in 2022 with previous years (2017-2021) and estimated influenza vaccine effectiveness (VE) during 2022. The study involved a descriptive analysis of influenza notifications and a case-control study to estimate VE. Cases were notifications of laboratory-confirmed influenza, and controls were individuals who were test negative for COVID-19. Cases and controls were matched on age, postcode and specimen collection date. VE against hospitalisation was investigated by matching hospitalised cases to controls. Conditional logistic regression models were adjusted for sex. In 2022, Queensland experienced an early influenza season onset (April-May) and high case numbers (n = 45,311), compared to the previous 5 years (annual average: 29,364) and 2020-2021 (2020:6047; 2021:301) during the COVID-19 pandemic. Adjusted VE (VEadj) against laboratory-confirmed influenza was 39% (95% confidence interval [CI]: 37-41), highest for children aged 30 months to < 5 years (61%, 95% CI: 49-70) and lowest for adults aged ≥ 65 years (24%, 95% CI: 17-30). VEadj against influenza-associated hospitalisation was 54% (95% CI: 48-59). Among children < 9 years of age, VEadj against laboratory-confirmed influenza (55%, 95% CI: 49-61) and hospitalisation (67%, 95% CI: 39-82) was higher in those who received a complete dose schedule. In Queensland, the 2022 influenza season started earlier than the previous 5 years. VE against influenza notifications varied across age groups. VE estimates against influenza-associated hospitalisation were higher than those against laboratory-confirmed influenza.

Risk Factors Associated with Cervical Cancer: A Matched Case-control Study

Background: One of the most effective ways to prevent cervical cancer is to identify the risk factors for the disease. Objective: The purpose of this research was to determine the risk factors for cervical cancer in women in Iran. Methods: This was a matched case-control study. 105 participants (35 patients with cervical cancer and 70 healthy women) were selected from the registered patients and women attending a women’s specialized hospital in Hamadan, Iran. One case was matched to 2 controls by age (±3 years). Demographic and clinical data were collected using a semi-structured questionnaire. Conditional multivariate logistic regression model and STATA 11 software were used for data analysis. Results: The mean age of women in the case and control group were 58.02(12.32) and 58.11(12.25) years (P = 0.486), respectively. Patients had lower education levels (P = 0.037), lower economic status (P˂0.001), and lower spouse education levels (P = 0.009). The results showed OCP users were 8.79 times more likely to develop cervical cancer than women who do not use OCP (P = 0.007), and the probability of cervical cancer in women increased by 8.33 times (&lt;0.001) with decreasing each level of socio-economic status. Conclusion: The results of the present study showed low economic status, and a history of using oral contraceptive pills are risk factors for cervical cancer.

Short-Term Effects of Lower Air Temperature and Cold Spells on Myocardial Infarction Hospitalizations in Sweden

BackgroundLower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood. ObjectivesThe purpose of this study was to investigate the short-term effects of lower air temperature and cold spells on the risk of hospitalization for MI in Sweden. MethodsThis population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature (1 km2 resolution) was estimated using machine learning, and percentiles of daily temperatures experienced by individuals in the same municipality were used as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least 2 consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating conditional logistic regression models with distributed lag nonlinear models using lag 0 to 1 (immediate) and 2 to 6 days (delayed) was used to evaluate the short-term effects of lower air temperature and cold spells on total MI, non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). ResultsA decrease of 1-U in percentile temperature at a lag of 2 to 6 days was significantly associated with increased risks of total MI, NSTEMI, and STEMI, with ORs of 1.099 (95% CI: 1.057-1.142), 1.110 (95% CI: 1.060-1.164), and 1.076 (95% CI: 1.004-1.153), respectively. Additionally, cold spells at a lag of 2 to 6 days were significantly associated with increased risks for total MI, NSTEMI, and STEMI, with ORs of 1.077 (95% CI: 1.037-1.120), 1.069 (95% CI: 1.020-1.119), and 1.095 (95% CI: 1.023-1.172), respectively. Conversely, lower air temperature and cold spells at a lag of 0 to 1 days were associated with decreased risks for MI. ConclusionsThis nationwide case-crossover study reveals that short-term exposures to lower air temperature and cold spells are associated with an increased risk of hospitalization for MI at lag 2 to 6 days.

Oral issues and childhood stress in eight-to-ten-year-old schoolchildren: a case-control study.

The aim of the present study was to investigate whether oral problems, harmful oral habits, and sociodemographic factors are associated with the occurrence of stress in schoolchildren. A case-control study nested within a cross-sectional study was conducted with a sample of 375 schoolchildren eight to ten years of age in the city of Diamantina, Brazil. The case group (with childhood stress) and control group (without childhood stress) were matched for age and sex at a 1:4 ratio (75 cases to 300 controls). Data collection involved the self-administration of a questionnaire by parents/caregivers addressing sociodemographic characteristics and the child's history of harmful oral habits. The children answered the Child Stress Scale (CSS) and underwent a clinical oral examination to determine the presence/absence of dental caries, malocclusion, and traumatic dental injuries. Data analysis involved the calculation of frequencies, the chi-square test, and conditional logistic regression (95% CI; p ≤ 0.05). The final adjusted conditional logistic regression model showed that dental caries (OR = 1.78, 95% CI: 1.01 - 3.14, p = 0.044) and biting objects (OR = 1.81, 95% CI: 1.02 - 3.22, p = 0.041) remained associated with stress in the schoolchildren analysed. The present results showed that children with dental caries and the habit of biting objects were more likely to have childhood stress. The study allows paediatric dentists to expand their knowledge with regards to the influence of oral problems and harmful habits on the occurrence of childhood stress and serves as a guide for decision-making related to oral problems in schoolchildren.

Ambient temperature and the risk of childhood epilepsy hospitalizations: Potentially neglected risk of temperature extremes and modifying effects of air pollution

PurposeExtreme temperatures and air pollution are increasingly important risk factors for human health in the background of climate change, with limited evidence available for neurological disorders. This study intended to investigate the short-term effects of extreme temperatures on childhood epilepsy and explore the potential modifying effect of air pollution. MethodsDaily childhood epilepsy hospitalization, meteorological and air pollution data were collected from 10 cities in Anhui Province of China during 2016–2018. We firstly employed a space–time-stratified case-crossover design and conditional logistic regression model to fit the short-term relationship between temperature and epilepsy. Then, we conducted stratified analyses by the level of air pollution and individual characteristics. ResultsBoth extreme heat and extreme cold increased the risk of hospitalization for childhood epilepsy. The effect of extreme heat [97.5th vs. minimum hospitalization temperature (MHT)] on hospitalization was acute and emerged at lag0 [OR: 1.229 (95 %CI: 1.035 to 1.459)], while the effect of extreme cold (2.5th vs. MHT) was delayed and appeared at lag5 [OR: 1.098 (95 %CI: 1.043 to 1.156)]. We also found children aged 6–18 years were more susceptible to extreme cold than children aged 0–5 years. Besides, extreme heat and cold effects differed by the level of air pollutants. ConclusionThis study suggests that extreme temperatures might be the novel but currently neglected risk factor for childhood epilepsy, and air pollution could further amplify the adverse effect of temperature.

First-Generation Antihistamines and Seizures in Young Children

The widespread use of antihistamines in children for treatment of common cold symptoms and their central nervous system effects, like drowsiness, underscore the importance of being aware of the associated risks. To assess associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset. This cohort study used a self-controlled case-crossover design. Data were obtained from the National Health Insurance Service database in Korea. Children born between January 1, 2002, and December 31, 2005, who visited the emergency department for seizure events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes R56.8, G40, and G41) during the follow-up period were included. Follow-up was completed on December 31, 2019, and data were analyzed from June 3, 2023, to January 30, 2024. First-generation antihistamine prescription. Primary outcome consisted of an index seizure event. Odds ratios (ORs) for seizure events were estimated using a conditional logistic regression model, comparing first-generation antihistamine prescription 1 to 15 days before seizure (hazard period) against control period 1 (31-45 days before the event) and control period 2 (61-75 days before the event) using the same period windows. Stratified analyses were conducted to examine the association with individual participant characteristics. Of 11 729 children who had a seizure event, 3178 (1776 [55.9%] boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both. Seizure events were predominantly observed in children aged 6 to 24 months (985 [31.0%]) and 25 months to 6 years (1445 [45.5%]). During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively. After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) than children aged 25 months to 6 years (AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction). Furthermore, sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk. In this cohort study, prescriptions for first-generation antihistamines were associated with a 22.0% higher seizure risk in children, especially in those aged 6 to 24 months. These findings emphasize the need for careful and judicious prescription of first-generation antihistamines in young children and underline the need for further research to elucidate associations between antihistamine prescriptions and seizure risk.