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Introduction: Both suicide and self‐harm are disproportionately common in autistic people. Sex differences in risk of self‐harm and suicide are observed in the general population, but findings are mixed for autistic people. Self‐cutting may be a particularly risky self‐harm behaviour for suicide in autistic people. We aimed to explore sex differences and differences in method of self‐harm in the association between self‐harm and suicide in autistic and non‐autistic adolescents and young adults. Methods: We used a total population register of 2.8 million Swedish residents. Participants were followed from age 12 until December 2021 for medical treatment because of self‐harm, and death from suicide. We used Cox proportional hazard regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of death from suicide following self‐harm, and Relative Excessive Risk due to Interaction (RERI) to explore the interaction between self‐harm and autism in females and males. Results: We identified 85,143 autistic individuals (31,288 female; 53,855 male) and 2,628,382 non‐autistic individuals (1,286,481 female; 1,341,901 male) aged 12–37 years. Incidence of suicide following self‐harm was higher in autistic males (incidence per 100,000 risk‐years = 169.0 [95% CI 135.1, 211.3]) than females (125.4 [99.4, 158.3]). The relative risk was higher for autistic females (HR 26.1 [95% CI 20.2, 33.7]) than autistic males (12.5 [9.9, 15.8]). An additive effect of both autism and self‐harm was observed in both females (RERI = 9.8) and males (2.0). Autistic individuals who self‐harmed through cutting were at greatest risk of death from suicide (HR 25.1 [17.9, 35.2]), compared to other methods. Conclusion: Autistic males and females are at increased risk of death from suicide following severe self‐harm, particularly self‐cutting. [ABSTRACT FROM AUTHOR]

Purpose: Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication‐based sampling ensures that the exposed and unexposed are exchangeable on the indication—limiting the potential for confounding by indication. However, indication‐based sampling has received little scrutiny, despite the hazards of exposure‐related covariate control. Methods: Using simulations of varying levels of confounding and applied examples we describe bias amplification under indication‐based sampling. Results: We demonstrate that indication‐based sampling in the presence of unobserved confounding can give rise to bias amplification, a self‐inflicted phenomenon where one inflates pre‐existing bias through inappropriate covariate control. Additionally, we show that indication‐based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication exist (effect‐heterogeneity). Conclusion: We conclude that studies using indication‐based sampling should have robust justification ‐ and that it should by no means be considered unbiased to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications. [ABSTRACT FROM AUTHOR]

Objective: Self‐harm among young autistic individuals is a clinical challenge, and the risk of premature death by suicide is strongly increased in this group. Using the advantage of total‐population and family‐based data, we investigated whether autism per se is a risk factor for self‐harm independently of psychiatric comorbidities and how it differs from self‐harm in non‐autistic individuals. Methods: We used The Stockholm Youth Cohort, a total‐population register study, including all residents in Stockholm County aged 0–17 years between 2001 and 2011.Study participants were followed from age 10 to 27 for hospital admissions because of self‐harm. We used modified Poisson regression to calculate relative risks (RR) using robust standard error to derive 95% confidence intervals (CI). Results: In all, 410,732 individuals were included in the cohort (9,070 with a diagnosis of autism). Autistic individuals had a fivefold increased adjusted relative risk of self‐harm (RR 5.0 [95% CI 4.4–5.6]). The risk increase was more pronounced for autism without intellectual disability and particularly high for self‐cutting 10.2 [7.1–14.7] and more violent methods 8.9 [5.2–15.4]. The association between autism and self‐harm was independent of, but clearly exacerbated by comorbid psychiatric conditions. It was of similar magnitude as risks linked to these conditions per se, and not explained by shared familial factors. Conclusion: Self‐harm severe enough to present to medical services is as common in autistic youth as in those with depression or ADHD. Potentially more lethal methods are more likely to be used of autistic self‐harmers. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether parental migration, parental region of origin, timing of child's birth in relation to maternal migration and parental reason for migration are associated with intellectual disability (ID) with and without autism. Methods: We used a register‐based cohort of all individuals aged 0–17 years in Stockholm County during 2001–2011. General estimating equation logistic model and additionally sibling comparison were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The models were adjusted for child's sex and birth year and parental age at child's birth, and additionally for migrant‐specific variables in the analyses including only children with migrant parent(s). Results: Within the eligible sample of 670,098 individuals, 3781 (0.6%) had ID with autism, and 5076 (0.8%) had ID without autism. Compared with children with Swedish‐born parents, children with both parents born abroad had an increased risk of ID with autism (OR = 1.6, CI 1.5–1.8) and ID without autism (OR = 1.9, CI 1.7–2.0). Among these children with both parents born abroad, it was protective of ID with autism when the child's birth occurred before and later than four years after maternal migration, which was replicated in the sibling comparison. The associations with both conditions were more pronounced with parental origin in regions comprising low‐ and middle‐income countries and with reasons other than work or study. Conclusions: Parental migration is associated with ID regardless of co‐occurrence of autism. Our results indicate an association between environmental factors during pregnancy related to migration and offspring ID with autism, although further confirmative studies are needed. [ABSTRACT FROM AUTHOR]

While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83-1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer. [ABSTRACT FROM AUTHOR]

Previous studies indicate that the increasing educational level in many post-industrial nations may imply that subgroups of the population work in occupations for which they are overeducated. We aimed to investigate whether overeducation is associated with future self-rated health and psychological distress. The analytical sample consisted of 21,159 participants from the Stockholm Public Health Cohort. Individuals with upper secondary or university education, who in 2006 or 2007 had occupations requiring less education, were considered overeducated. The outcomes were self-rated health ( SRH) and psychological distress in 2010. Overeducated women had an increased risk of less than good SRH, compared to university-educated women in matching occupations (adjusted odds ratios ( OR): 2.44 confidence intervals ( CI): 1.32-4.51 for overeducated women with secondary school education), but not compared to less educated women in the same occupational class (adjusted OR: 0.87 CI:0.32-2.38 for overeducated women with secondary school education). We found no increased risk of less than good SRH for overeducated men, and no association between overeducation and psychological distress for either sex. The results indicate that overeducation is not per se associated with onset of less than good SRH or psychological distress in a short-term perspective, and the findings support education expansion as a means of improving public health. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drug–drug interactions (DDIs) may have a profound impact on the individual drug response, for instance by reducing the clearance of involved drugs and thereby causing adverse drug reactions at supratherapeutic drug exposure. • In specific cases, such a risk with specific drug combinations is stated in the drug label, including specific recommendations on the choice of drug and/or dose. • Less frequently, DDIs that reduce the drug effectiveness may have been recognized as well. • The clinical adherence to these recommendations is today unknown. WHAT THIS ADDS • The results from this study on specific drug combinations related to cytochrome P450-dependent drug metabolism indicate that Swedish doctors avoid prescribing strong inhibitors of drug metabolism together with drugs at risk of accumulation and exposure-dependent adverse drug reactions. • However, ‘silent’ DDIs that impact on effectiveness appear to be neglected, pointing out an area for continued medical education of drug prescribers about such DDIs. AIMS The study aimed to investigate the clinical adherence to drug label recommendations on important drug–drug interactions (DDIs). Dispensing data on drug combinations involving selective serotonin reuptake inhibitor (SSRI) antidepressants could help to identify areas for intensified medical education. METHODS This was a retrospective, cross-sectional analysis of individual dispensing data regarding all individuals ≥15 years old in Sweden. The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole). Odds were calculated between each CYP2D6 drug and the corresponding comparator drug in patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline, respectively. The odds ratio (OR) was calculated by dividing the obtained odds in patients on fluoxetine/paroxetine by the corresponding odds in patients on citalopram/escitalopram/sertraline. RESULTS Compared with patients that were dispensed citalopram/escitalopram/sertraline, patients dispensed fluoxetine/paroxetine had lower prescribing rates of metoprolol (adjusted OR 0.80; 95% confidence interval 0.76, 0.85), donepezil (0.65; 0.49, 0.86) and galantamine (0.58; 0.41, 0.81). In contrast, the use of prodrugs codeine (compared woth propoxyphene) or tamoxifen (compared with anastrozole) was similar among patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline (adjusted OR 1.03; 0.94, 1.12 and 1.29; 0.96, 1.73, respectively). CONCLUSIONS Clinically important DDIs that are associated with impaired bioactivation of prodrugs might be more easily neglected in clinical practice compared with DDIs that cause drug accumulation and symptomatic adverse drug reactions. [ABSTRACT FROM AUTHOR]