No abstract

Background:The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. Methods: We performed a population-based cohort study consisting of 974,304 statin initiators ≥40 years of age and 1,948,606 matched general population comparators identified from Danish, nationwide registries . We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. Results: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (11.4 [95% CI = 10.9, 12.0] events per 100,000 person years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI = 1.00, 1.23]. In the first year after initiation, the HR was 1.40 (95% CI = 1.09, 1.79) for both sexes combined, 1.00 (95% CI = 0.70, 1.42) for men, and 1.92 (95% CI = 1.30, 2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. Conclusions: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.

Socioeconomic deprivation can limit access to healthcare. Important gaps persist in the understanding of how individual indicators of socioeconomic disadvantage may affect clinical outcomes after heart transplantation. We sought to examine the impact of individual-level socioeconomic position (SEP) on prognosis of heart-transplant recipients. A population-based study including all Danish first-time heart-transplant recipients (n = 649) was conducted. Data were linked across complete national health registers. Associations were evaluated between SEP and all-cause mortality and first-time major adverse cardiovascular event (MACE) during follow-up periods. The half-time survival was 15.6 years (20-year period). In total, 330 (51%) of recipients experienced a first-time cardiovascular event and the most frequent was graft failure (42%). Both acute myocardial infarction and cardiac arrest occurred in ≤5 of recipients. Low educational level was associated with increased all-cause mortality 10–20 years post-transplant (adjusted hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.19–3.19). During 1–10 years post-transplant, low educational level (adjusted HR 1.66, 95% CI 1.14–2.43) and low income (adjusted HR 1.81, 95% CI 1.02–3.22) were associated with a first-time MACE. In a country with free access to multidisciplinary team management, low levels of education and income were associated with a poorer prognosis after heart transplantation.

Background: Existing evidence on the link between smoking and appendicitis is scarce and ambiguous. We therefore conducted a population-based cohort study in Denmark to investigate whether smoking during pregnancy is associated with an increased risk of appendicitis in offspring. Methods: We used the Danish Birth Registry to include all singletons born during 1991–2017 and to identify maternal smoking status during pregnancy. We followed the children from birth until date of appendicitis, emigration, death, or administrative end of study (31 December 2018), whichever came first. We calculated crude and adjusted hazard ratios (HRs) of appendicitis with 95% confidence intervals (CIs) comparing children of mothers who smoked during pregnancy to children of nonsmokers. Further, we conducted a bias analysis and sibling analysis. Results: We included 1,659,526 singletons of whom 19% were born to mothers who smoked during pregnancy. After maximum 28 years of follow-up, hazard rates for children of smokers were slightly higher than for children of nonsmokers [adjusted HR: 1.07 (95% CI = 1.04, 1.10)]. Stratification by sex revealed no association for males [adjusted HR: 1.02 (95% CI = 0.99, 1.06)], but a higher HR for females [adjusted HR: 1.13 (95% CI = 1.09, 1.18)]. This association increased with increasing length of follow-up, indicating that the association may be mediated by later-life exposures. The bias analysis indicated that misclassification of maternal smoking could attenuate a true association, while the sibling analysis showed no association. Conclusions: Maternal smoking during pregnancy and appendicitis in the offspring may be associated.