Large Population-based Cohort Research Articles

Perineal tear and childbirth-related posttraumatic stress: A prospective cohort study.

Quantitative studies examining the occurrence of childbirth-related posttraumatic stress disorder (CB-PTSD) following severe perineal rupture are lacking. The objective of this population-based study was to investigate the prospective associations between the degree of perineal tear during childbirth and CB-PTSD symptoms, when adjusting for known covariates (maternal age, years of school education, premature birth, and parity). We hypothesized that women with different degrees of perineal tear will differ regarding (1) the level of CB-PTSD symptoms at 8 weeks and 2 years postpartum and (2) the rate of change in CB-PTSD symptoms from 8 weeks to 2 years postpartum. Secondary data analysis from the Akershus Birth Cohort, a large population-based prospective cohort study using self-report questionnaires and hospital record data. The degree of perineal tear was significantly associated with CB-PTSD symptoms at 8 weeks and 2 years postpartum. However, the degree of perineal tear was not significantly associated with the change in CB-PTSD symptoms over time. Similar patterns were found for both total CB-PTSD symptoms as well as for avoidance and intrusion symptoms only. Results seem to support a dose-response model, suggesting that the higher the severity of the perineal tear, the higher the posttraumatic morbidity.

Development and validation of a risk prediction model for post-polypectomy colorectal cancer in the USA: a prospective cohort study

Effective risk stratification tools for post-polypectomy colorectal cancer (PPCRC) are lacking. We aimed to develop an effective risk stratification tool for the prediction of PPCRC in three large population-based cohorts and to validate the tool in a clinical cohort. Leveraging the integrated endoscopic, histopathologic and epidemiologic data in three U.S population-based cohorts of health professional (the Nurses' Health Study (NHS) I, II and Health Professionals Follow-up Study (HPFS)), we developed a risk score to predict incident PPCRC among 26,741 patients with a polypectomy between 1986 and 2017. We validated the PPCRC score in the Mass General Brigham (MGB) Colonoscopy Cohort (Boston, Massachusetts, U.S) of 76,603 patients with a polypectomy between 2007 and 2018. In all four cohorts, we collected detailed data on patients' demographics, endoscopic history, polyp features, and lifestyle factors at polypectomy. The outcome, incidence of PPCRC, was assessed by biennial follow-up questionnaires in the NHS/HPFS cohorts, and through linkage to the Massachusetts Cancer Registry in the MGB cohort. In all four cohorts, individuals who were diagnosed with CRC or died before baseline or within six months after baseline were excluded. We used Cox regression to calculate the hazard ratio (HR), 95% confidence interval (CI) and assessed the discrimination using C-statistics and reclassification using the Net Reclassification Improvement (NRI). During a median follow-up of 12.8 years (interquartile range (IQR): 9.3, 16.7) and 5.1 years (IQR: 2.7, 7.8) in the NHS/HPFS and MGB cohorts, we documented 220 and 241 PPCRC cases, respectively. We identified a PPCRC risk score based on 11 predictors. In the validation cohort, the PPCRC risk score showed a strong association with PPCRC risk (HR for high vs. low, 3.55, 95% CI, 2.59-4.88) and demonstrated a C-statistic (95% CI) of 0.75 (0.70-0.79), and was discriminatory even within the low- and high-risk polyp groups (C-statistic, 0.73 and 0.71, respectively) defined by the current colonoscopy surveillance recommendations, leading to a NRI of 45% (95% CI, 36-54%) for patients with PPCRC. We developed and validated a risk stratification model for PPCRC that may be useful to guide tailored colonoscopy surveillance. Further work is needed to determine the optimal surveillance interval and test the added value of other predictors of PPCRC beyond those included in the current study, along with implementation studies. USNational Institutes of Health, the American Cancer Society, the South-Eastern Norway Regional Health Authority, the Deutsche Forschungsgemeinschaft.

Quantifying postprandial glucose responses using a hybrid modeling approach: Combining mechanistic and data-driven models in The Maastricht Study.

Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored. Here, we propose a sequential combination of a mechanistic and a data-driven modeling approach to quantify individuals' glucose and insulin responses to an oral glucose tolerance test, using cross sectional data from 2968 individuals from a large observational prospective population-based cohort, the Maastricht Study. The best predictive performance, measured by R2 and mean squared error of prediction, was achieved with personalized mechanistic models alone. The addition of a data-driven model did not improve predictive performance. The personalized mechanistic models consistently outperformed the data-driven and the combined model approaches, demonstrating the strength and suitability of bottom-up mechanistic models in describing the dynamic glucose and insulin response to oral glucose tolerance tests.

Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.

The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.

Association of psychological distress, smoking and genetic risk with the incidence of lung cancer: a large prospective population-based cohort study.

Emerging evidence suggests a potential link between psychological distress (anxiety and depression) and lung cancer risk, however, it is unclear whether other factors such as tobacco smoking and genetic susceptibility modify the association. We included 405,892 UK Biobank participants free of cancer at baseline. Psychological distress was measured using the Patient Health Questionnaire-4 (PHQ-4). A polygenic risk score (PRS) was calculated using 18 lung cancer-associated genetic loci. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 7.13 years, 1754 lung cancer cases were documented. The higher score of psychological distress was associated with an increased risk of lung cancer (HRper 1-SD= 1.07, 95% CI: 1.02-1.11) after adjustment for smoking and other confounders. Mediation analysis revealed that 16.8% (95% CI: 13.0%-20.6%) of the distress-lung cancer association was mediated by smoking. Compared with never smokers with no distress, participants with heavy smoking and high distress had the highest risk of lung cancer (HR=18.57, 95% CI: 14.51-23.76). Both multiplicative and additive interactions were observed between smoking and psychological distress in lung cancer. Furthermore, the greatest relative increase in risk was observed among those with high genetic risk and high distress (HR=1.87, 95%CI: 1.50-2.33), and there was a significant additive interaction between the PRS and psychological distress. Our results indicate that psychological distress was associated with an elevated risk of incident lung cancer, and such relation was modified by tobacco smoking and genetic susceptibility.

Echocardiography protocol and cardiometabolic phenotyping in Indian birth cohorts-the IndEcho study.

Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. 13432279.

Effects of Pre- and Postnatal Early-Life Stress on Internalizing, Adiposity, and Their Comorbidity

Depression and obesity are 2 highly prevalent and often comorbid conditions. Exposure to early-life stress (ELS) has been associated with both depression and obesity in adulthood, as well as their preclinical manifestations during development. However, it remains unclear whether (1) associations differ depending on the timing of stress exposure (prenatal vs postnatal), and whether (2) ELS is a shared risk factor underlying the comorbidity between the 2 conditions. Leveraging data from 2 large population-based birth cohorts (ALSPAC: n= 8,428 [52% male participants]; Generation R: n= 4,268 [48% male participants]), we constructed comprehensive cumulative measures of prenatal (in utero) and postnatal (from birth to 10 years) ELS. At age 13.5 years, we assessed the following: internalizing symptoms (using maternal reports); fat mass percentage (using dual-energy X-ray absorptiometry); and their comorbidity, defined as the co-occurrence of high internalizing and high adiposity. Both prenatal (total effect [95% CI]= 0.20 [0.16; 0.22]) and postnatal stress (β [95%CI]= 0.22 [0.17; 0.25]) were associated with higher internalizing symptoms, with evidence of a more prominent role of postnatal stress. A weaker association (driven primarily by prenatal stress) was observed between stress and adiposity (prenatal: 0.07 [0.05; 0.09]; postnatal: 0.04 [0.01; 0.07]). Both prenatal (odds ratio [95%CI]= 1.70 [1.47; 1.97]) and postnatal (1.87 [1.61; 2.17]) stress were associated with an increased risk of developing comorbidity. We found evidence of timing and shared causal effects of ELS on psycho-cardiometabolic health in adolescence; however, future research is warranted to clarify how these associations may unfold over time. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group.

Association Between Frequency of Social Contact and Brain Atrophy in Community-Dwelling Older People Without Dementia: The JPSC-AD Study.

Epidemiologic evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association between low frequency of social contact and the volumes of various brain regions and to assess the extent to which depressive symptoms mediate these relationships from a large population-based multisite cohort study. Dementia-free community-dwelling Japanese aged 65 years or older underwent brain MRI scans and a comprehensive health examination. Frequency of contact with noncohabiting relatives and friends was determined by asking a single question with 4 categories: everyday, several times a week, several times a month, and seldom. Total and regional brain volumes, intracranial volume (ICV), and white matter lesion volume were estimated using FreeSurfer software. The associations between frequency of social contact and brain volumes per ICV were examined using analyses of covariance. Mediation analyses were conducted to calculate the proportion of the associations explained by depressive symptoms. We included 8,896 participants. The multivariable-adjusted mean of the total brain volume in the group with the lowest frequency of social contact was significantly lower compared with that in the group with the highest frequency of social contact (67.3% vs 67.8%), with a significant increasing trend across the groups (p value for trend <0.001). The white matter lesion volume increased significantly with lower frequency of social contact (0.30% in the lowest frequency group vs 0.26% in the highest frequency group, p value for trend <0.001). Lower frequency of social contact was associated with smaller volumes in the temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala (all q values of false discovery rate correction <0.05). The relationships seemed to be partly mediated by depressive symptoms, which accounted for 15%-29% of the observed associations. Lower frequency of social contact was associated with decreased total and cognitive function-related regional brain volumes. In addition, depressive symptoms partially explained the association in community-dwelling older people without dementia in Japan.

Pre-pregnancy obesity is associated with greater systemic inflammation and increased risk of antenatal depression

BackgroundPre-pregnancy obesity is an emerging risk factor for perinatal depression. However, the underlying mechanisms remain unclear. We investigated the association between pre-pregnancy body mass index (BMI) and perinatal depressive symptoms in a large population-based pre-birth cohort, the Barwon Infant Study. We also assessed whether the levels of circulating inflammatory markers during pregnancy mediated this relationship. MethodsDepressive symptoms were assessed in 883 women using the Edinburgh Postnatal Depression Scale (EPDS) and psychological stress using the Perceived Stress Scale (PSS) at 28 weeks gestation and 4 weeks postpartum. Glycoprotein acetyls (GlycA), high-sensitivity C-reactive protein (hsCRP) and cytokines were assessed at 28 weeks gestation. We performed regression analyses, adjusted for potential confounders, and investigated mediation using nested counterfactual models. ResultsThe estimated effect of pre-pregnancy obesity (BMI ≥ 30 kg/m2) on antenatal EPDS scores was 1.05 points per kg/m2 increase in BMI (95% CI: 0.20, 1.90; p = 0.02). GlycA, hsCRP, interleukin (IL) −1ra and IL-6 were higher in women with obesity, compared to healthy weight women, while eotaxin and IL-4 were lower. Higher GlycA was associated with higher EPDS and PSS scores and partially mediated the association between pre-pregnancy obesity and EPDS/PSS scores in unadjusted models, but this association attenuated upon adjustment for socioeconomic adversity. IL-6 and eotaxin were negatively associated with EPDS/PSS scores, however there was no evidence for mediation. ConclusionsPre-pregnancy obesity increases the risk of antenatal depressive symptoms and is also associated with systemic inflammation during pregnancy. While discrete inflammatory markers are associated with antenatal depressive symptoms and perceived stress, their role in mediating the effects of pre-pregnancy obesity on antenatal depression requires further investigation.

Midlife intake of the isoflavone genistein and soy, and the risk of late-life cognitive impairment: the JPHC Saku Mental Health Study.

The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR=1.51; 95% CI, 1.02-2.24; p for trend=0.03) in the final multivariable analysis. High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Two novel clinical tools to predict the risk of bone metastasis and overall survival in esophageal cancer patients: a large population-based retrospective cohort study.

The aim of this study was to construct two web-based nomograms to predict the probability of bone metastasis (BM) in esophageal cancer (EC) patients and the prognostic of EC patients with BM (ECBM). We collected the data of EC and ECBM patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015. Independent risk variables for the development of BM in EC patients were identified using univariate and multivariate logistic regression analyses. Univariate and multivariate Cox regression analyses were used to assess independent prognostic variables in ECBM patients. And then, constructed two nomograms to predict the risk of bone metastases and overall survival (OS) of ECBM patients. Survival differences were studied by Kaplan-Meier (K-M) survival analysis. The predictive efficacy and clinical applicability of these two nomograms were assessed by using receiver operating characteristic (ROC) curve, the area under curve (AUC), calibration curve and decision curve analysis (DCA). We selected a total of 6839 patients with EC, of which 326 (4.77%) had BM at the time of initial diagnosis. The results of K-M survival and Cox regression analysis showed significant effects of BM on the OS in EC patients. Age, N stage, tumor size and brain/liver/lung organ metastasis were identified as BM-related risk variables. Chemotherapy and brain/liver organ metastasis were identified as ECBM-related prognostic variables. The ROC, AUC, calibration curves and DCA of two nomograms all showed excellent predictive efficacy and clinical applicability. These two nomograms were constructed and validated, which could objectively predict the risk of BM in EC patients and the prognostic in ECBM patients. These tools are expected to make valuable contributions in clinical work, informing surgeons in making decisions about patient care.

Distinct cardiovascular and cancer burdens associated with social position, work environment and unemployment: a cross-sectional and retrospective study in a large population-based French cohort

ObjectivesDistinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks.DesignA cross-sectional and retrospective observational study.SettingA population-based French cohort (CONSTANCES).Participants130 197 adults enrolled between 2012...

Iron deficiency is related to lower muscle mass in community-dwelling individuals and impairs myoblast proliferation.

Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population-based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes. In a population-based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24-h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5-bromo-2'-deoxy-uridine ELISA assay. Myocyte differentiation was assessed using Myh7-stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence-activated cell sorting. RNA sequencing (RNAseq) was used to identify ID-related gene and pathway enrichment in myoblasts and myocytes. Participants in the lowest age- and sex-specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25-2.10, P<0.001) or transferrin saturation (OR 1.34, 95% CI 1.03-1.75, P=0.03) had a significantly higher risk of being in the lowest age- and sex-specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs-CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine-induced ID reduced myoblast proliferation rate (P-trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (-52%, P<0.001) and tended to reduce mitochondrial oxygen consumption capacity (-28%, P=0.10). Deferoxamine induced gene expression of cellular atrophy markers Trim63 (+20%, P=0.002) and Fbxo32 (+27%, P=0.048), which was reversed by ferric citrate (-31%, P=0.04 and -26%, P=0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in glycolytic energy metabolism, cell cycle regulation and apoptosis; co-treatment with ferric citrate reversed these effects. In population-dwelling individuals, ID is related to lower muscle mass, independent of haemoglobin levels and potential confounders. ID impaired myoblast proliferation and aerobic glycolytic capacity, and induced markers of myocyte atrophy and apoptosis. These findings suggest that ID contributes to loss of muscle mass.

Associations of long-term joint exposure to various ambient air pollutants with all-cause and cause-specific mortality: evidence from a large population-based cohort study.

The association between long-term joint exposure to all kinds of ambient air pollutants and the risk of mortality is not known. Our study prospectively assessed the joint associations of various air pollutants with cause-specific and all-cause mortality risk and identified potential modifying factors affecting these associations. A total of 400,259 individuals aged 40-70 years were included in this study. Information on PM10, PM2.5-10, PM2.5, NO2, and NOx was collected. A weighted air pollution score was calculated to assess joint exposure to the above air pollutants. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During a median of 12.0 years (4,733,495 person-years) of follow-up, 21,612 deaths were recorded, including 7097 deaths from cardiovascular disease and 11,557 deaths from cancer. The adjusted HRs of all-cause mortality were 1.39 (95% CI: 1.29-1.50), 1.86 (95% CI: 1.63-2.13), 1.12 (95% CI: 1.10-1.14), and 1.04 (95% CI: 1.03-1.05) for every 10-ug/m3 increase in PM10, PM2.5, NO2, and NOx, respectively. The adjusted HRs associated with the air pollution score (the highest quintile versus the lowest quintile) were 1.24 (95% CI: 1.19-1.30) for all-cause mortality, 1.33 (95% CI: 1.23-1.43) for cardiovascular mortality, and 1.16 (95% CI: 1.09-1.23) for cancer mortality. Furthermore, we found that the air pollution score was associated with a linear dose-response increase in mortality risk (all P for linearity < 0.001). The findings highlight the importance of a comprehensive assessment of various air pollutants.

Influence of Gestational Diabetes Mellitus on Diabetes Risk and Glycemic Control in a Retrospective Population-Based Cohort.

Racial/ethnic-specific estimates of the influence of gestational diabetes mellitus (GDM) on type 2 diabetes remain underexplored in large population-based cohorts. We estimated racial/ethnic differences in the influence of GDM on diabetes risk and glycemic control in a multiethnic, population-based cohort of postpartum women. Hospital discharge and vital registry data for New York City (NYC) births between 2009 and 2011 were linked with NYC A1C Registry data between 2009 and 2017. Women with baseline diabetes (n = 2,810) were excluded for a final birth cohort of 336,276. GDM on time to diabetes onset (two A1C tests of ≥6.5% from 12 weeks postpartum onward) or glucose control (first test of A1C <7.0% following diagnosis) was assessed using Cox regression with a time-varying exposure. Models were adjusted for sociodemographic and clinical factors and stratified by race/ethnicity. The cumulative incidence for diabetes was 11.8% and 0.6% among women with and without GDM, respectively. The adjusted hazard ratio (aHR) of GDM status on diabetes risk was 11.5 (95% CI 10.8, 12.3) overall, with slight differences by race/ethnicity. GDM was associated with a lower likelihood of glycemic control (aHR 0.85; 95% CI 0.79, 0.92), with the largest negative influence among Black (aHR 0.77; 95% CI 0.68, 0.88) and Hispanic (aHR 0.84; 95% CI 0.74, 0.95) women. Adjustment for screening bias and loss to follow-up modestly attenuated racial/ethnic differences in diabetes risk but had little influence on glycemic control. Understanding racial/ethnic differences in the influence of GDM on diabetes progression is critical to disrupt life course cardiometabolic disparities.

1023-P: Current Practices in Racial Equity—Findings from the T1D Exchange Quality Improvement Collaborative (T1DX-QI) in 2022

Background: Medical racism contributes to adverse health outcomes. T1DX-QI is a large population-based cohort engaged in data sharing and quality improvement to drive system changes in type 1 diabetes care. The annual T1DX-QI survey included questions to evaluate racial equity in diabetes care and practices to promote equity. Methods: The annual T1DX-QI survey was administered to participating clinics fall 2022 and had a 94 % response rate. There were 50 responses consisting of 66% pediatric (P) and 34% adult (A) institutions. Questions concerned clinic resources, LGBTQ+ practices, racial equity, patient transition, and reproductive health. Response data were aggregated, summarized and stratified by P/A institutions. Results: Only 21% P and 33% A institutions felt all their team members can articulate how medical racism contributes to adverse diabetes outcomes. Pediatric institutions reported more strategies to address medical racism than adult (3.6 vs 3.1). Organizational strategies to decrease racial discrimination included employee trainings, DEI offices/committees, patient resources and hiring practices. Patient resources include interpreter services, transportation, insurance navigation, and housing and food assistance. Hiring practices included changing prior protocols, hiring from the community, and diversifying workforces. Majority of institutions have offered anti-racism training in the last year (P 85%, A 72%) and annually (P 64%, A 56%). Pediatric teams felt that their anti-racism training was effective more often (P 60%, A 45%) and more commonly were provided resources (67% P vs 47% A) to help address inequities. Conclusion: Despite increased offering in anti-racism training, insufficient institutional support and perceived subeffective training still represent obstacles especially in adult institutions. Sharing effective strategies to address medical racism will help institutions take steps to mitigate inequities. Disclosure J.Sanchez: None. M.Zupa: None. O.Ebekozien: Advisory Panel; Medtronic, Research Support; Eli Lilly and Company, Dexcom, Inc. T1dx-qi collaborative: n/a. J.Cases-villablanca: None. A.Addala: None. A.Mungmode: None. T.Wright: None. R.M.Wolf: Research Support; Dexcom, Inc., Boehringer Ingelheim Inc. A.Ahmann: Advisory Panel; Medtronic. N.N.Mathioudakis: None. J.Ng: Research Support; Sanofi-Aventis U.S. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Work productivity and activity impairment in disorders of gut-brain interaction: Data from the Rome Foundation Global Epidemiology Study.

Disorders of Gut-Brain Interaction (DGBI) are highly prevalent worldwide, but their effect on work productivity has not gained much attention. We aimed to compare work productivity and activity impairment (WPAI) in persons with and without DGBI in a large population-based cohort and identify factors independently associated with WPAI in subjects with DGBI. Data were collected from Germany, Israel, Italy, Japan, the Netherlands, Poland, Spain and Sweden via Internet surveys as part of the Rome Foundation Global Epidemiology Study. Apart from the Rome IV diagnostic questionnaire, questionnaires evaluating WPAI related to general health (WPAI:GH), psychological distress (PHQ-4), somatic symptom severity (PHQ-15) and other factors were assessed. Of the 16,820 subjects, 7111 met the criteria for DGBI according to the Rome IV diagnostic questionnaire. Subjects with DGBI were younger (median (interquartile range) age 43 (31-58) vs. 47 (33-62)) and more often female (59.0% vs. 43.7%) compared to subjects without DGBI. Subjects with DGBI had higher absenteeism, presenteeism (poor work productivity due to illness), overall work impairment and activity impairment (p<0.001) compared with subjects without. For subjects with DGBI affecting more than one anatomical region, WPAI was incrementally higher for each additional region. There were significant differences in WPAI for subjects with DGBI in different countries. Subjects from Sweden had the highest overall work impairment and from Poland the lowest. Using multiple linear regression, male sex, fatigue, psychological distress, somatic symptom severity and number of anatomical regions were independently associated with overall work impairment (p<0.05 for all). In the general population, people with DGBI have substantial WPAI compared with those without DGBI. The reasons for these findings should be explored further, but having multiple DGBI, psychological distress, fatigue and somatic symptom severity seem to contribute to this impairment associated with DGBI.

Stage 2 Registered Report: The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach

Youth with symptoms of emotion dysregulation are at risk for a multitude of psychiatric diagnoses later in life. However, few studies have focused on the underlying neurobiology of emotion dysregulation. This study assessed the bidirectional relationship between emotion dysregulation symptoms and brain morphology throughout childhood and adolescence. A combined total of 8,235 children and adolescents drawn from 2 large population-based cohorts, the Generation R Study and Adolescent Brain Cognitive Development (ABCD) Study, were included. Data were acquired in 3 waves in Generation R (mean [SD] age= 7.8 [1.0] wave 1 [W1]; 10.1 [0.6] W2; 13.9 [0.5] W3) and in 2 waves in ABCD (mean [SD] age= 9.9 [0.6] W1; 11.9 [0.6] W2). Cross-lagged panel models were used to determine the bidirectional relationships between emotion dysregulation symptoms and brain morphology. The study was preregistered before performing analyses. In the Generation R sample, emotion dysregulation symptoms at W1 preceded lower hippocampal (β=-.07, SE= 0.03, p= .017) and temporal pole (β=-.19, SE= 0.07, p= .006) volumes at W2. Emotion dysregulation symptoms at W2 preceded lower fractional anisotropy in the uncinate fasciculus (β=-.11, SE= 0.05, p= .017) and corticospinal tract (β=-.12, SE= 0.05, p= .012). In the ABCD sample, emotion dysregulation symptoms preceded posterior cingulate (β= .01, SE= 0.003, p= .014) and nucleus accumbens volumes (left hemisphere: β=-.02, SE= 0.01, p= .014; right hemisphere: β=-.02, SE= 0.01, p= .003). In population-based samples, with relatively low psychopathology symptoms in the majority of children, symptoms of emotion dysregulation can precede differential development of brain morphology. This provides the foundation for future work to assess to what extent optimal brain development can be promoted through early intervention. The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach; https://doi.org/10.1016/j.jaac.2022.03.008. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population.

Although tranexamic acid (TXA) has occasionally been used to prevent postoperative recurrence of chronic subdural hematoma (CSDH) after burr hole craniotomy (BC), robust evidence of its efficacy has been lacking. To assess the efficacy and safety of postoperative oral administration of TXA after BC for CSDH among the elderly. This retrospective, propensity score-matched cohort study was carried out with a large Japanese local population-based longitudinal cohort in the Shizuoka Kokuho Database between April 2012 and September 2020. Patients included were age 60 years or older and had undergone BC for CSDH but were not undergoing dialysis. Covariates were collected from records of the preceding 12 months from the month of first BC, and patients were followed up for 6 months after surgery. The primary outcome was repeat surgery, and the secondary outcome was death or the onset of thrombosis. Data on postoperative TXA administration were collected and compared with controls using propensity score matching. Of the 8544 patients who underwent BC for CSDH, 6647 were included, with 473 placed in the TXA group and 6174 placed in the control group. After 1:1 matching, repeated BC was found to have been performed in 30 of 465 patients (6.5%) in the TXA group and in 78 of 465 patients (16.8%) in the control group (relative risk, 0.38; 95% CI, 0.26-0.56). No significant difference was observed for death or the onset of thrombosis. Oral administration of TXA reduced the occurrence of repeat surgery after BC for CSDH.

Modifiable Risk Factors for Accelerated Decline in Processing Speed: Results from Three Dutch Population Cohorts

BackgroundSeveral lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up.MethodsWe used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages.ResultsLatent growth curves showed that decline in processing speed accelerated with age. Smoking, not drinking alcohol and depressive symptoms were associated with a lower level of processing speed in all cohorts. In two of the cohorts, more physical activity, drinking more than two glasses of alcohol per day, higher BMI and diabetes were associated with a lower level of processing speed. Depressive symptoms and diabetes were also associated with faster decline in processing speed.ConclusionSeveral modifiable risk factors are associated with the level of processing speed in older age, while few are also related to the rate of decline.