In a nationwide, population-based, matched cohort study, we observed an association between a diagnosis of acute pancreatitis and long-term risk of pancreatic cancer.

Background: Patients with atrial fibrillation generally require anticoagulant therapy and, at times, therapy with additional platelet aggregation inhibitors. Data are scarce on bleeding rates in high-risk groups receiving combination therapy, such as the elderly or patients with a high CHA 2 DS 2 -VASc score. Methods: We conducted a nationwide cohort study of Danish patients with atrial fibrillation ≥50 years of age. Treatments were ascertained from a prescription database. These included no anticoagulant treatment, and treatment with vitamin K antagonists, direct oral anticoagulants, platelet inhibitors, and combinations of antithrombotic drugs. Incidence rates (IRs) of major bleeding and hazard ratios were estimated overall, and also stratified by treatment modality, age, CHA 2 DS 2 -VASc score, and comorbidity. Major bleeding was defined as bleeding requiring hospitalization or causing death. Results: We identified 272 315 patients with atrial fibrillation. Median age was 75 years (interquartile range, 67–83) and 47% were women. Over a total follow-up period of 1 373 131 patient-years (PYs), 31 459 major bleeds occurred (IR 2.3/100 PYs; 95% CI, 2.3–2.3/100 PYs). In comparison with vitamin K antagonist monotherapy, adjusted hazard ratios of major bleeding were 1.13 (95% CI, 1.06–1.19) for dual antiplatelet therapy, 1.82 (95% CI, 1.76–1.89) for therapy with a vitamin K antagonist and an antiplatelet drug, 1.28 (95% CI, 1.13–1.44) for therapy of a direct oral anticoagulant with an antiplatelet drug, 3.73 (95% CI, 3.23–4.31) for vitamin K antagonist triple therapy, and 2.28 (95% CI, 1.67–3.12) for direct oral anticoagulant triple therapy. Subgroup analyses showed similar patterns. The IR for major bleeding was 10.2/100 PYs among patients receiving triple therapy. Very high major bleeding rates occurred among patients on triple therapy aged >90 years (IR 22.8/100 PYs) or with a CHA 2 DS 2 -VASc score >6 (IR 17.6/100 PYs) or with a history of major bleeding (IR 17.5/100 PYs). Conclusions: Patients with atrial fibrillation on triple therapy experienced high rates of major bleeding in comparison with patients on dual therapy or monotherapy. The high bleeding rates observed in patients on triple therapy >90 years of age or with a CHA 2 DS 2 -VASc score >6 or with a history of a major bleeding warrants careful consideration of such therapy in these patients.

Objective: We aimed to investigate the impact of hyponatremia severity on mortality risk and assess any evidence of a dose-response relation, utilizing prospectively collected data from population-based registries. Design: Cohort study of 279 508 first-time acute admissions to Departments of Internal Medicine in the North and Central Denmark Regions from 2006 to 2011. Methods: We used the Kaplan-Meier method (1 -survival function) to compute 30-day and 1-year mortality in patients with normonatremia and categories of increasing hyponatremia severity. Relative risks (RRs) with 95% CIs, adjusted for age, gender and previous morbidities, and stratified by clinical subgroups were estimated by the pseudo-value approach. The probability of death was estimated treating serum sodium as a continuous variable. Results: The prevalence of admission hyponatremia was 15% (41 803 patients). Thirty-day mortality was 3.6% in normonatremic patients compared to 7.3, 10.0, 10.4 and 9.6% in patients with serum sodium levels of 130-134.9, 125-129.9, 120-124.9 and !120 mmol/l, resulting in adjusted RRs of 1.4 (95% CI: 1.3-1.4), 1.7 (95% CI: 1.6-1.8), 1.7 (95% CI: 1.4-1.9) and 1.3 (95% CI: 1.1-1.5) respectively. Mortality risk was increased across virtually all clinical subgroups, and remained increased by 30-40% 1 year after admission. The probability of death increased when serum sodium decreased from 139 to 132 mmol/l. No clear increase in mortality was observed for lower concentrations. Conclusions: Hyponatremia is highly prevalent among patients admitted to Departments of Internal Medicine and is associated with increased 30-day and 1-year mortality risk, regardless of underlying disease. This risk seems independent of hyponatremia severity.

BACKGROUNDFew population-based data exist on birth outcomes in women who received opioid maintenance treatment during pregnancy. We therefore examined adverse birth outcomes in women exposed to methadone or buprenorphine during pregnancy and the risk of neonatal abstinence syndrome (NAS) among neonates exposed to buprenorphine, methadone, and/or heroin in utero.PATIENTS AND METHODSThis study included all female Danish residents with a live birth or a stillbirth from 1997 to 2011. We identified the study population, use of opioids and opioid substitution treatment, birth outcomes, and NAS through medical registers. Birth outcomes included preterm birth (born before 38th gestational week), low-birth weight (LBW) (<2,500 g, restricted to term births), small for gestational age (SGA) (weight <2 standard deviations from the sex- and gestational-week-specific mean), congenital malformations, and stillbirths. We used log-binomial regression to estimate the prevalence ratio (PR) for birth outcomes.RESULTSAmong 950,172 pregnancies in a total of 571,823 women, we identified 557 pregnancies exposed to buprenorphine, methadone, and/or heroin (167 to buprenorphine, 197 to methadone, 28 to self-reported heroin, and 165 to combinations). Compared with nonexposed pregnancies, prenatal opioid use was associated with greater prevalence of preterm birth (PR of 2.8 (95% confidence interval (CI), 2.3–3.4)), LBW among infants born at term (PR of 4.3 (95% CI, 3.0–6.1)), and being SGA (PR of 2.7 (95% CI, 1.9–4.3)). Restricting the analyses to women who smoked slightly lowered these estimates. The prevalence of congenital malformations was 8.3% in opioid-exposed women compared with 4.2% in nonexposed women (PR of 2.0 (95% CI, 1.5–2.6)). The risk of NAS ranged from 7% in neonates exposed to buprenorphine only to 55% in neonates exposed to methadone only or to opioid combinations.CONCLUSIONThe maternal use of buprenorphine and methadone during pregnancy was associated with increased prevalence of adverse birth outcomes, and this increase could only be explained to a smaller extent by increased prevalence of smoking. The risk of NAS was eight-fold higher in methadone-exposed neonates than that in buprenorphine-exposed neonates, but this difference may at least partly be explained by differences in underlying indications (analgesic versus opioid maintenance treatment) between the two groups.

ESBL E. coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage due to their widespread use.