Sex ratio of newborn infants born to pregnant women with severe chronic constipation

There was a significant male excess in the newborns of pregnant women with severe chronic constipation during pregnancy compared to pregnant women without constipation and pregnant women with new onset severe constipation, during pregnancy

Socioeconomic status and risk of incident venous thromboembolism

Background: Although venous thromboembolism (VTE) is a leading cause of morbidity and mortality, and socioeconomic status (SES) affects human health and health behavior, few studies have examined the association between SES and VTE. Objectives: We aimed to investigate the association between SES, assessed individually and in a composite score by levels of education, income, and employment status, and incident VTE. Methods: We used Danish national registries to identify 51 350 persons aged 25– 65 years with incident VTE during 1995–2016. For each case, we used incidence density sampling to select five age-, sex-, and index-year-matched controls from the general Danish population (n = 256 750). SES indicators, including education, income, and employment status, were assessed 1 and 5 years before the VTE. We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to individual SES indicators and a composite SES score in analyses adjusted for age, sex, and comorbidities. Results: Compared with low levels, high educational level (OR 0.74; 95% CI 0.71– 0.77), high income (OR 0.70; 95% CI 0.68–0.72), and high employment status (OR 0.66; 95% CI 0.64–0.68) were associated with decreased risk of VTE, even after adjusting for comorbidities. A composite SES score was superior to the individual indicators in assessing VTE risk (OR for high vs. low score: 0.61; 95% CI 0.59–0.63). In sensitivity analysis with SES indicators measured 5 years before the VTE, the risk estimates remained essentially the same. Conclusion: High levels of both individual SES indicators and a composite SES score were associated with decreased VTE risk

Estimated lifetime risk of venous thromboembolism in men and women in a Danish nationwide cohort: impact of competing risk of death

Incidence of venous thromboembolism (VTE) risk varies by age and sex. Some studies have reported overall higher risk in men, especially when VTEs triggered by female reproductive factors are excluded. However, higher mortality rates in men may have led to overestimation of lifetime VTE risk in men compared with women. Therefore, we estimated the lifetime risk of VTE in men and women in a Danish, nationwide cohort, taking into account the competing risk of death. Within the population of Denmark (> 5 million persons), all first-time VTEs occurring in 1995–2016 were identified from the Danish National Patient Registry covering all Danish hospitals. The cumulative incidences of VTE were estimated in men and women with age as timescale, taking into account the competing risk of death. Estimated lifetime risk was defined as cumulative incidence at age 100. In a simulation study, we excluded the proportion of female cases that could be attributed to reproductive risk factors and re-estimated the cumulative incidence. We identified 123,543 incident VTEs. The cumulative incidence of VTE was 1.9% in women and 1.3% in men at age 50, 4.3% in women and 4.4% in men at age 70, and 9.3% in women and 8.1% in men at age 100. After accounting for VTEs attributed to reproductive factors, the corresponding incidences in women were 1.2% at age 50, 3.2% at age 70, and 8.2% at age 100. In conclusion, the estimated lifetime risk of VTE was slightly higher in women than in men when accounting for competing risk of death. Our simulation study suggested that reproductive risk factors contribute modestly to the estimated lifetime VTE risk in women

Conditioning on future exposure to define study cohorts can induce bias: the case of low-dose acetylsalicylic acid and risk of major bleeding

A principle of cohort studies is that cohort membership is defined by current rather than future exposure information. Pharmacoepidemiologic studies using existing databases are vulnerable to violation of this principle. We evaluated the impact of using data on future redemption of prescriptions to determine cohort membership, motivated by a published example seeking to emulate a “per-protocol” association between continuous versus never use of low-dose acetylsalicylic acid (ASA) and major bleeding (e.g., cerebral hemorrhage or gastrointestinal bleeding)

Long-term Risk of Epilepsy Following Invasive Group B Streptococcus Disease in Neonates in Denmark

IMPORTANCE: The risk of epilepsy after neonatal invasive Group B Streptococcus (iGBS) disease, particularly iGBS sepsis, is poorly understood. OBJECTIVE: To examine the association between neonatal iGBS (sepsis or meningitis) and long-term risk of epilepsy, stratified by sex, prematurity, and maternal socioeconomic position (SEP). DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted in Denmark with an inclusion period from 1997 through 2017 and follow-up until the end of 2018. A general population comparison cohort was randomly sampled and matched up to 10:1 to the exposed cohort. Linkage between Danish national registers were applied for data collection. Participants were infants aged 0 to 89 days. The general population comparison cohort was matched by sex, the child's year and month of birth, and gestational age. SEP was defined by maternal income and education. EXPOSURE: Hospital-diagnosed iGBS (sepsis or meningitis) during the first 89 days after birth. OUTCOMES AND MEASURES: Epilepsy was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and/or prescription codes for antiepileptic drugs using Danish medical registry data. Cumulative risk (CR) of epilepsy was calculated by treating death as a competing event. Cox proportional hazards regression was used to estimate hazard ratios with 95% CIs. Effect modification by sex, prematurity, and maternal SEP was assessed on an additive scale. RESULTS: A total of 1432 children (792 [55.3%] boys; 1126 [78.6%] with gestational age ≥37 weeks) were identified with iGBS disease: 1264 with sepsis and 168 with meningitis. In the comparison cohort, there were 14 211 children (7869 [55.4%] boys; 11 260 [79.2%] with gestational age ≥37 weeks). The overall (0 to 22 years) CR of epilepsy was 3.6% (95% CI, 2.6%-5.0%) in children with iGBS disease and 2.3% (95% CI, 1.9%-2.7%) in the comparison cohort. The overall CR of epilepsy for iGBS meningitis was 15.1% (95% CI, 8.9%-22.8%) and 2.2% (95% CI, 1.4%-3.4%) for iGBS sepsis. The adjusted hazard ratio for epilepsy in children with iGBS disease was 2.04 (95% CI, 1.46-2.85). Being a boy, born premature, or born to a mother belonging to a low SEP group was associated with an increased risk of epilepsy in later childhood. CONCLUSION: In this population-based cohort study of 1432 neonates, iGBS disease was associated with a higher incidence of epilepsy in later childhood, notably after meningitis. Premature birth, sex, and low maternal SEP modified the association

Irritable bowel syndrome and risk of glaucoma: An analysis of two independent population-based cohort studies

Objective: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome–host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma. Design: Two prospective cohort studies. Subjects: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members). Methods: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database. Main Outcome Measure: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674). Results: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26–15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16–1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06–1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03–1.38). Conclusions: In two large European cohort studies, IBS is a risk factor for glaucoma

Registry-Based Cohort Study of Alpha-1 Antitrypsin Deficiency Prevalence, Incidence and Mortality in Denmark 2000-2018

OBJECTIVE: To estimate the prevalence of diagnosed alpha-1 antitrypsin deficiency (dAATD) in Denmark as of 31 December 2018, and dAATD incidence and mortality from 1 January 2000 to 31 December 2018. STUDY DESIGN AND SETTING: We used the Danish National Patient Registry to identify patients with dAATD based on the International Classification of Diseases, 10th Revision (ICD-10) code E88.0A and the Danish Civil Registration System (CRS) for population counts and vital status. We estimated dAATD prevalence, incidence and mortality. We compared mortality among patients with dAATD and an age-matched and sex-matched cohort extracted from the Danish CRS. We conducted a sensitivity analysis to examine whether coding changes during 2000-2018, from a general to a more specific ICD-10 code for AATD, and left truncation affected results appreciably. RESULTS: The prevalence of dAATD was 12.9 (95% CI 11.9 to 13.8) per 100 000 persons. The age distribution was bimodal, with peaks at ages ≤12 and ≥45 years. The incidence rate per 100 000 person-years was 0.90 (95% CI 0.85 to 0.96), again with a bimodal age distribution. Mortality was higher for patients with dAATD than for the general population (mortality rate ratio (mRR) 4.7, 95% CI 4.1 to 5.3), especially for children (mRR 33.8, 95% CI 6.8 to 167.4). The sensitivity analysis indicated that dAATD prevalence might have been as high as 19.7 per 100 000 persons due to less specific ICD-10 coding for AATD early in the study period or 21.4 per 100 000 persons correcting for left truncation. CONCLUSION: Diagnosed AATD was associated with increased mortality, especially for children. The finding for children was based on few deaths and had very wide 95% CIs

Effect of comorbidity on risk of venous thromboembolism in patients with renal cell carcinoma

AbstractPurposeVenous thromboembolism (VTE) is associated with renal cell carcinoma (RCC), but data on the effect of comorbidities are limited. Therefore, our purpose was to determine the effect of comorbidity on VTE risk among patients with RCC.Materials and methodsA population-based cohort of all patients with RCC (n = 8,633) diagnosed in Denmark between 1995 and 2010 and a comparison cohort selected from the general population and matched on age, sex, and comorbidities (n = 83,055) were identified. Risk of subsequent VTE was estimated with 95% CI for the first 3 months, 1 year, and 5 years following cancer diagnosis. We stratified by Charlson comorbidity index (CCI) scores to estimate excess risk in patients with RCC vs. the comparison cohort within comorbidity strata. We also performed subanalyses for postoperative VTE and metastases.ResultsVTE risk was higher in the RCC compared with comparison cohort, particularly during the initial year following diagnosis (risk difference=9.9 per 1,000 persons [95% CI: 7.7–12.2]). After stratifying by CCI, excess risk declined with increasing comorbidities. The risk difference was 12.3 per 1,000 persons (95% CI: 9.1–15.5) for CCI=0 and 0.5 (95% CI: 6.0–7.0) for CCI=4. Excess risk also declined with increasing comorbidities among patients with postoperative VTE and among those with metastases.ConclusionsRCC is associated with increased risk of VTE when compared with a matched general population cohort. Risk did not appear to increase with added comorbidity burden. Clinical attention to VTE risk in patients with RCC is appropriate regardless of the presence or absence of comorbidities