Swedish Population-based Cohort Research Articles

Increased risk of bacterial pneumonia before and after respiratory syncytial virus infection in young children.

The burden of respiratory disease is great among children. This study aimed to examine the temporal relationship between hospitalisation for respiratory syncytial virus (RSV) and bacterial pneumonia. A Swedish population-based cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Children born between 1998 and 2015 were included and followed for 2 years. We examined the temporal relationship between RSV hospitalisation and bacterial pneumonia using piecewise exponential models. The final cohort comprised 1 641 747 children, 48.5% were females. There were 23 632 RSV and 4722 bacterial pneumonia hospitalisations, with mean age of 137.8 and 424.2 days, respectively. RSV hospitalisation was associated with bacterial pneumonia with an adjusted incidence rate ratio (aIRR) of 3.18. The risk was highest in the first month after RSV hospitalisation, aIRR 11.19. The risk of bacterial pneumonia was elevated for 4 months after RSV hospitalisation and before RSV hospitalisation. We found an increased risk for bacterial pneumonia hospitalisation in children hospitalised for RSV both before and after RSV hospitalisation, indicating a bidirectional relationship.

Seroprevalence of Helicobacter pylori and incident myocardial infarction - A population-based Swedish nested case-control study.

Helicobacter pylori (H. pylori) and its Cytotoxin associated gene A (CagA) have been associated with myocardial infarction (MI), but existing data are conflicting possibly due to limitations in study designs and lack of data on important confounders. The aim of this study was to determine whether H. pylori or CagA seropositivity are associated with incident MI, including MI phenotypes, and to describe temporal trends. We used the Northern Sweden Health and Disease study, a prospective biobank with data from residents enrolled in a population-based cohort from health examinations between 1986 and 2006. A total of 826 first time MI cases with available blood samples from their index health examination were identified up to 2006. Each case was 1:2 matched with controls by age, sex, sample date and geographical area. Blood samples were analysed using ELISA to determine seroprevalence of H. pylori and CagA, which were then used to study the association with incident MI. The median age at baseline was 50 years, and 71% of participants were male. Seroprevalence of H. pylori and CagA was 46.5% and 32.1% in cases, respectively, compared to 43.7% and 30.6% in controls. Overall, H. pylori prevalence decreased over the study period. After multivariable adjustments, no significant association was observed between H. pylori seropositivity and incident MI (odds ratio 1.15, 95% CI 0.94-1.42) nor between CagA-positive H. pylori and incident MI. In a Swedish population-based cohort, no significant association was observed between H. pylori or CagA seropositivity and incidence of MI.

Vascular ageing in relation to chronological and self-perceived age in the general Swedish population

Background. Aortic stiffness is a marker of vascular ageing. Non-conventional risk markers reflecting vascular ageing are largely unexplored. We aimed to investigate the relationship between self-perceived age (SPA) and self-rated health (SRH) with aortic stiffness in the general population. Methods. Cross-sectional assessment of 3760 participants from two Swedish population-based cohorts (mean age 43.5 ± 14.5 years, 53.4% women). Participants completed two self-administered questions about SPA (SPA-self referring to SPA perceived by oneself, and SPA-others referring to SPA perceived by others) graded as: younger, no difference, or older than same-aged/sex peers. SRH was graded as poor versus good. Aortic stiffness (vascular ageing) was assessed by carotid–femoral pulse wave velocity (PWV). Linear regression was performed stratified by the median age of 45 years. Results. Chronologically younger men and women ≤45 years with older SPA-others had unexpectedly lower PWV (β − 0.39, p < .001 and β − 0.40, p < .001, respectively), independently of cardiovascular risk factors and social health determinants, compared with subjects with younger SPA-others. Lower PWV was also observed in women ≤45 years with older SPA-self (β − 0.24 m/s, p = .005) compared with younger SPA-self, but not in men. A similar pattern between SPA-self, SPA-others and PWV was found in chronologically younger subjects ≤45 years reporting good SRH. On the contrary, chronologically older subjects >45 years reporting poor SRH, with older SPA-others had increased vascular ageing (PWV β 2.57, p = .03). Conclusions. Self-perceived age is a subjective cognitive variable inversely associated with vascular ageing particularly among chronologically younger adults ≤45 years.

Pancreatic cancer risk after benign gallbladder disease: A Swedish population-based cohort study

AimThe purpose of this nationwide registry-based cohort study was to outline pancreatic cancer risk after benign gallbladder disease (GBD). Anatomically adjacent cancers were investigated to address incidental findings. MethodsWe included all Swedes aged 20–79 years with histologically confirmed GBD (cholecystitis and/or cholecystectomy) in 1992–2016 and five matched non-exposed population comparators. Follow-up started one month after GBD and incidence rates (IR) and hazard ratios (HR) with 95 % confidence intervals (CI) up to 15 years after GBD were estimated using Poisson and Cox regression, respectively. Fully adjusted models included sex, age, year, education, type 2 diabetes, obesity, smoking-, and alcohol-related disorders. Analyses were stratified by follow-up and flexible parametric models applied to assess time-varying effects. Interaction models were used to identify patient groups at risk. Results680 and 1890 incident pancreatic cancers were detected over 15 years in 130907 GBD exposed and 571618 non-exposed, respectively. An excess pancreatic cancer risk was mainly seen within the first 2 years; IR: 84 [95 % CI 73,95] versus 31 [95 % CI 27,34] per 100000 person-years corresponding to an HR of 2.74 [95 % CI 2.31,3.25]. The same pattern was noted for duodenal cancer while primary liver cancer risk was elevated across follow-up. An initial extrahepatic biliary cancer risk elevation shifted to a reduction over time. The 2-year pancreatic cancer risk was augmented in younger (age 20–49) individuals, HR 7.64 [95 % CI 3.73,15.65]. ConclusionOur findings urge more studies on the clinical follow-up the first years after cholecystitis to detect early pancreatic cancer.

Glycemic Control and Adult Height: A Nationwide Swedish Cohort Study on Childhood Type 1 Diabetes

Abstract Context Normal growth throughout childhood and adolescence is considered an indicator of adequate glycaemic control in patients with type 1 diabetes. While it has been suggested that growth in type 1 diabetes is reduced, the literature is conflicting and differences in final adult height and the risk of short stature depending on glycaemic control remain largely unexplored. Objective This work aims to assess adult height outcomes across levels of glycemic control in children and adolescents with type 1 diabetes, as well as to investigate the effect of sex, age at disease onset, and timing of glycemic control in relation to puberty. Methods In this population-based Swedish cohort study, we collected data on glycemic control and height from specialist health-care visits of all individuals with childhood-onset type 1 diabetes in the National Diabetes Register. Using linear and logistic regression, we compared suboptimal (glycated hemoglobin A1c [HbA1c] 53-75 mmol/mol [7.0-9.0%]) and poor (HbA1c &amp;gt; 75 mmol/mol [&amp;gt;9.0%]) to optimal (HbA1c &amp;lt; 53 mmol/mol [&amp;lt;7.0%]) glycemic control in relation to final adult height and the risk of short stature. Results Poor glycemic control was associated with lower final adult height (−2.91 cm [95% CI, –3.48 to −2.33] for males, −1.83 cm [−2.42 to −1.23] for females) as well as a higher risk of short stature in males (odds ratio 1.90 [1.07-3.35]) but not in females (0.73 [0.36-1.51]). For females, adult height was lower only among those with type 1 diabetes since before puberty and if the poor glycemic control occurred before puberty. For males, adult height was lower irrespective of their age at diabetes onset, but only if they had poor glycemic control during or after puberty. Conclusion Poor glycemic control after the onset of type 1 diabetes, compared to optimal control, is associated with lower adult height in males and females. The prepubertal period seems to be more critical for females than males.

Sleeping habits and aortic stiffness in middle-aged men and women from the general population: insights from the SCAPIS study

Background The relationship between sleeping habits and aortic stiffness remains inconclusive and is not fully explored in the European general population. Methods We examined cross-sectionally 8659 participants from the Swedish population-based cohort Swedish CArdioPulmonary bioImage Study (SCAPIS), mean age 57.5 years, 52.1% women. A self-administered questionnaire on sleeping habits (duration, quality, insomnia, and daytime sleepiness) was administered. Aortic stiffness was examined by the gold-standard method, carotid-femoral pulse wave velocity (c-f PWV) using Sphygmocor® XCEL, continuously and stratified by cut-off of >10 m/s. Multivariable linear and logistic regression were performed stratified by sex. Results Out of 8659 subjects (mean c-f PWV of 9.4 ± 1.9 m/s), 32.3% had c-f PWV >10 m/s, defined as aortic stiffness. Compared with subjects with c-f PWV ≤10 m/s, individuals with aortic stiffness reported more insomnia (p = 0.01) but less daytime sleepiness (p = 0.008). Men and women with poor sleep quality had 0.2 m/s lower mean c-f PWV compared with subjects with good sleep quality (p = 0.004). No difference in mean PWV was found in men and women with shorter/longer sleep duration (p > 0.05). In the multivariable regression models, no significant association was found between poor sleep quality, shorter (≤6 h) or longer (≥9 h) sleep duration and aortic stiffness in the total population, neither among men nor women (all p > 0.05), independently of cardiovascular risk factors. Conclusions Short and long sleep duration and poor sleep quality are not associated with aortic stiffness, measured with the gold-standard method c-f-PWV, in middle-aged men and women from the Swedish general population, independently of cardiovascular risk factors.

Longitudinal assessment of the impact of prevalent diabetes on hospital admissions and mortality in the general population: a prospective population-based study with 19 years of follow-up

BackgroundHospitalization indicates the presence of severe disease and constitutes a leading cost in health care. We aimed to prospectively assess if prevalent diabetes mellitus contributes to excess all-cause and cause-specific hospital admissions and mortality at the population level.MethodsWe used a Swedish prospective population-based cohort, including 25,642 individuals of whom 4.2% had prevalent diabetes at baseline (mean age 61.2 ± 6.8 years, age range 44.8–73.4 years). We compared the number of hospitalizations and mortality classified according to the main chapters of the 10th revision of the International Classification of Diseases (ICD-10) during follow-up using nationwide inpatient registries, comparing individuals with and without prevalent diabetes, using multivariate adjusted negative binomial regression (incidence rate ratio, IRR) and Cox regression, respectively.ResultsDuring a median follow-up of 19 years, 18,904 subjects were hospitalized at least once [median 3 (IQR 2–6)] and 6767 (26.4%) individuals died. Overall, subjects with diabetes were hospitalized (IRR 1.83, p < 0.001) more often, and had a higher incidence rate of hospital admissions due to endocrine diseases (IRR 14.6, p < 0.001), dermatological diseases (IRR 3.7, p < 0.001), injuries and poisoning (IRR 2.7, p < 0.001), infectious diseases (IRR 2.5, p < 0.001), psychiatric diseases (IRR 2.0, p < 0.001), but also cardiovascular, hematological, genitourinary, neurologic and respiratory diseases compared with non-diabetic individuals. No difference was observed for hospital admissions due to cancer or musculoskeletal disorders. All-cause mortality was higher (HR 1.77, p < 0.001) in individuals with diabetes, with disease-specific mortality being significant only for cardiovascular and endocrine disease-related death.ConclusionsAt the population level, prevalent diabetes increased the hospitalization burden longitudinally due to diseases of most of the ICD-10 main chapters, except for cancer and musculoskeletal disorders. These novel findings challenge the current view on the spectrum of prevalent diabetes-related conditions and may have implications for screening and treatment strategies in diabetes.Permission of graphical illustrationsSource: Pixabay.com. No permission or acknowledgement is required.

Cardiovascular disease in pregnancy: Prevalence and obstetric outcomes in a Swedish population-based cohort study between 2000 and 2019.

The prevalence of cardiovascular disease during pregnancy (cardiovascular disease diagnosed before, during or up to 6 months after childbirth) and the risk of adverse outcomes associated with it have not been previously described in Sweden. This study examined trends in prevalence of cardiovascular disease and its association with maternal and perinatal outcomes, overall and by timing of diagnosis in relation to pregnancy. This population-based observational retrospective cohort study consisted of women aged 15-49 years who were registered in the Swedish Medical Birth Register 2000-2019. Prevalence was defined as annual diagnosis of cardiovascular disease per pregnant woman as numerator and all pregnant women per year as denominator. Adverse maternal and perinatal outcomes were analyzed using time-dependent Cox regression and Poisson regression models. Outcomes were obtained during and after childbirth up to 1 year postpartum, depending on the outcome. There were 2 069 107 births to 1 186 137 women (911 101 primiparous). The prevalence of cardiovascular disease among pregnant women in Sweden during 2000-2019 increased from 0.31% to 1.34%, for non-congenital cardiovascular disease, this was primarily driven by arrythmia (0.11%-0.58%). Primiparous women with cardiovascular disease had a higher risk of eclampsia over-all (aHR 4.50, 95% CI 2.01-10.05) and when diagnosed during pregnancy (aHR 3.22, 95% CI 1.21-8.61); admission to psychiatric ward overall (aHR 2.51, 95% CI 1.30-4.83), and when diagnosed during pregnancy (aHR 2.54, 95% CI 1.21-5.34); and one-year mortality when diagnosed before pregnancy (aHR 1.67, 95% CI 1.16-2.42) and when diagnosed postpartum (aHR 6.59, 95% CI 3.38-12.84), compared to those without cardiovascular disease. Children born to women with cardiovascular disease diagnosed both overall and in relation to timing of diagnosis had an increased risk of being born preterm and small for gestational age. Cardiovascular disease prevalence among pregnant women in Sweden increased during 2000-2019, primarily driven by arrhythmias. In primiparous women, the timing of diagnosis of cardiovascular disease is important for maternal and perinatal outcomes, including when diagnosed postpartum. This calls for awareness among all staff when planning pregnancy and monitoring women with cardiovascular disease throughout pregnancy and in the postpartum period.

Asthma and allergy trajectories in children based on combined parental report and register data.

Trajectories of asthma and allergy in children are heterogeneous and commonly derived from parental report of disease or clinical records. This study combined parental-reported and register-based dispensed medication data to characterize childhood trajectories of co-existing asthma, allergic rhinitis, and eczema. From a Swedish population-based birth cohort (N = 5654), survey responses collected at the age of 1, 4.5, 8, and 12 years were linked to dispensed medication register data for the period of 2-13 years. Trajectories were identified with latent class analysis. Statistical metrics and clinical interpretability guided the model selection. Nine distinct trajectories were identified: three asthma-dominated (early-onset remitting [n = 189, 3.3%], late-onset [n = 117, 2.1%], and persistent [n = 149, 2.6%]), two eczema-dominated (persistent [n = 190, 3.4%] and remitting [n = 432, 7.6%]), one allergic rhinitis-dominated (late-onset [n = 259, 4.6%]), two multimorbidity (mid-childhood asthma and late-onset allergic rhinitis [n = 144, 2.5%], and persistent eczema and late-onset allergic rhinitis [n = 90, 1.6%]), and one low-disease burden trajectory (n = 4084, 72.2%). Differences were seen across the trajectories in the proportion of parental report of disease and dispensed medication as well as by class and quantity of medication dispensed. Combined parental-reported and dispensed medication data enriches characterization of longitudinal trajectories of asthma and allergy in children by merging subjective experience of disease with healthcare utilization. The identified trajectories were characterized by distinct disease development and prescription patterns suggesting clinically differential morbidity burden.

Adverse pregnancy outcomes attributable to overweight and obesity across maternal birth regions: a Swedish population-based cohort study

Whether there are differences in the contribution of overweight and obesity to adverse pregnancy outcomes between migrant and non-migrant women in high-income countries, which might increase health inequalities, remains unclear. Therefore, in this study, we aimed to estimate the contribution (including the proportion and number of attributable cases) of overweight and obesity to a wide range of adverse pregnancy outcomes in Swedish-born and migrant women. This population-based cohort study used nationwide population registries in Sweden. All outcomes and covariates were collected from the Medical Birth Register (delivery and maternal characteristics), National Patient Register (inpatient and specialised outpatient care), the Cause of Death Register (all deaths in Sweden), the Longitudinal Integrated Database for Health Insurance and Labour Market Studies (socioeconomic data), and the Total Population Register (maternal birth country data). Women with missing records of BMI at the first antenatal visit, country of birth, or covariates, were excluded from the study. BMI was measured during the first antenatal visit. Maternal country of birth was categorised into Sweden and seven super-regions. The proportion (ie, population attributable fractions [PAFs]) and the number of adverse pregnancy outcomes attributable to overweight and obesity were calculated, adjusting for maternal age, gestational age at first antenatal visit, maternal parity, smoking status, maternal somatic conditions, child's sex, socioeconomic and demographic variables. We identified 2 228 416 singleton pregnancies between Jan 1, 2000, and Dec 31, 2020 of 1 245 273 women. 254 778 (11·4%) pregnancies with missing records of BMI at the first antenatal visit, country of birth, or covariates were excluded, which resulted in a final analytical cohort of 1 973 638 pregnancies carried by 1 164 783 women. The overall mean maternal age of the study population was 30·8 years (SD 5·1). As estimated by PAFs, overweight and obesity contributed to a large proportion of adverse pregnancy outcomes: gestational diabetes (52·1% [95% CI 51·0-53·2]), large-for-gestational age (36·9% [36·2-37·6]), pre-eclampsia (26·5% [25·7-27·3]), low Apgar score (14·7% [13·5-15·9]), infant mortality (12·7% [9·8-15·7]), severe maternal morbidity (henceforth referred to as a near-miss event; 8·5% [6·0-11·0]), and preterm birth (5·0% [4·4-5·7]) in the total study population. PAFs varied between maternal birth regions. Interventions to reduce overweight and obesity have the potential to mitigate the burden of adverse pregnancy outcomes and possibly reduce inequalities in reproductive health. Therefore, public health practice and policy should prioritise efforts to prevent overweight and obesity among women of childbearing age. Swedish Research Council.

Early clinical outcomes in men and women undergoing proximal thoracic aortic surgery: A Swedish population-based cohort study

ObjectiveThe study objective was to investigate the association between female sex and 30-day mortality and postoperative complications in patients undergoing scheduled proximal thoracic aortic surgery in Sweden. MethodsIn a nationwide population-based cohort study, all patients who underwent scheduled proximal thoracic aortic surgery in Sweden between 2016 and 2020 were included. The primary outcome measure was 30-day mortality. Secondary outcome measures included a combined end point including 30-day all-cause mortality, postoperative new-onset dialysis, perioperative stroke, or a prolonged need of postoperative ventilation (>48 hours). Logistic regression models and propensity score matching were used to estimate the association between female sex and primary and secondary outcomes adjusted for differences in baseline characteristics. ResultsA total of 2000 patients (29% women) were analyzed. The crude 30-day all-cause mortality rate was higher in women compared with men (3.1% vs 1.4%, P < .001). Women were older at the time of surgery (65.6 vs 60.2 years, P < .001) and had more comorbidities and a larger maximum indexed aortic diameter (cm/m body height) at the time of surgery (3.4 ± 0.56 vs 3.0 ± 0.48, P < .001). The adjusted risk for 30-day mortality for women compared with men was not significant (odds ratio, 1.41; 95% CI, 0.70-2.83), and neither was the secondary composite end point (odds ratio, 0.89; 95% CI, 0.62-1.27). The propensity score–matched analysis showed similar results. ConclusionsWomen who underwent proximal thoracic aortic surgery had a 2-fold higher unadjusted 30-day mortality risk, but the mortality risk was not significantly higher when age and comorbidities was taken into consideration.

Prediction of suicide attempt in a Swedish population-based cohort.

Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts. Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982-1990 with information on genetic liability and environmental exposures from birth to age 16: perinatal variables, parental psychopathology (suicide attempt, substance use disorder, major depression), family status, socioeconomic difficulties, peers' psychopathology, and school grades. We conducted sex-specific analysis and developed data-driven predictive models including risk factors that occurred between ages 0 and 16 using structural equation modeling. In both females and males, the best-fitting models reveal a complex risk pathway to suicide attempt. In females, the model indicates four direct effects on suicide attempt risk: the occurrence of suicide attempt in parents during childhood (β = 0.159, 95% CI: 0.118; 0.199) and adolescence (β = 0.115, 95% CI: 0.077; 0.153), suicide attempt in peers (β = 0.068, 95% CI: 0.057; 0.079), and low academic achievement (β = 0.166, 95% CI: 0.156; 0.175). In males, aggregate genetic liability for suicide attempt (β = 0.130, 95% CI: 0.111; 0.148), suicide attempt in parents during adolescence (β = 0.099, 95% CI: 0.074; 0.124), suicide attempt in peers (β = 0.118, 95% CI: 0.108; 0.129), and low academic achievement (β = 0.61, 95% CI: 0.152; 0.171) were related to later suicide attempt. These factors also acted as mediators to explain the association between environmental exposures in childhood and later suicide attempt. These findings illustrate sex-specific pathways to suicide attempt by including risk factors that occur during the development. Results highlight the importance of genetic and family environment but also the prominent role of academic achievement.

Potential of a Second Screening Test for Alloimmunization in Pregnancies of Rhesus-positive Women: A Swedish Population-based Cohort Study.

There is lack of consensus regarding whether a second screening in rhesus-positive pregnant women is worthwhile, with different guidelines, recommendations, and practices. We aimed to estimate the number and timing of missed alloimmunizations in rhesus-positive pregnancies screened once and weigh the relative burden of additional screening and monitoring versus the estimated reduction in adverse pregnancy outcomes. We extracted information on maternal, pregnancy, and screening results for 682,126 pregnancies for 2003-2012 from Swedish national registers. We used data from counties with a routine second screening to develop and validate a logistic model for a positive second test after an earlier negative. We used this model to predict the number of missed alloimmunizations in counties offering only one screening. Interval-censored survival analysis identified an optimal time window for a second test. We compared the burden of additional screening with estimated adverse pregnancy outcomes avoided. The model provided an accurate estimate of positive tests at the second screening. For counties with the lowest screening rates, we estimated that a second screening would increase the alloimmunization prevalence by 33% (from 0.19% to 0.25%), detecting the 25% (304/1222) of cases that are currently missed. The suggested timing of a second screen was gestational week 28. For pregnancies currently screened once, the estimated cost of a second test followed by maternal monitoring was approximately 10% of the cost incurred by the excess adverse pregnancy outcomes. Investment in routine second screening can identify many alloimmunizations that currently go undetected or are detected late, with the potential for cost savings.

Parental substance use disorders and psychiatric conditions in offspring: A Swedish population-based cohort study with over 1,000,000 individuals

BackgroundExposure to parental substance use problems has been associated with offsprings poor health and adverse social outcomes. In this study, we examined the association between exposure to parental substance use disorder (SUD) during childhood, and adolescence and offspring psychiatric conditions in young adulthood. MethodThis was a register-based cohort study comprising 562,095 males and 531,130 females born between 1981 and 1990 in Sweden. Parental SUD was captured between the offspring's birth and eighteenth birthday. Cox regression models were used to estimate the Hazard Ratio (HR) of psychiatric conditions from age 18 years to a maximum age of 35 years, from January 1, 1999 to December 31, 2016. ResultsAbout 4% of the study population was exposed to parental SUD during childhood and adolescence. The HR of psychiatric diagnosis was higher in males (1.80, 95% CI = 1.77–1.85) and females (1.56, 95% CI = 1.51–1.60) who were exposed to parental SUD, compared to those who were not; after adjusting for year of birth, domicile, origin, relative poverty, and other parental psychiatric diagnoses. The risks of psychiatric conditions were higher among males and females exposed to parental SUD during childhood compared to during adolescence. ConclusionExposure to parental SUD during childhood and adolescence was associated with an increased risk of psychiatric conditions in early adulthood for both males and females. Neither origin, poverty, municipality, or other parental psychiatric diagnoses fully explained the association. These risks seemed to be somewhat higher among males, and among those exposed during childhood when compared to during adolescence.

Associations between physical activity and ankle-brachial index: the Swedish CArdioPulmonary bioImage Study (SCAPIS)

BackgroundThe ankle–brachial index (ABI) is the ratio of the ankle and brachial systolic blood pressures. In the clinical setting, low ABI (< 0.9) is an indicator of peripheral atherosclerosis, while high ABI (> 1.4) is a sign of arterial stiffness and calcification. The purpose of the current study was to investigate the association between ABI and physical activity levels, measured by accelerometer.MethodsThe Swedish CArdioPulmonary bioImage Study (SCAPIS) is a Swedish nationwide population-based cross-sectional cohort for the study of cardiovascular and pulmonary diseases, in which individuals aged 50–64 years were randomly invited from the general population. The study population with data on ABI, physical activity, and sedentary time based on accelerometry was 27,737. Differences between ABI categories and associations to sedentary behavior, moderate to vigorous physical activity (MVPA), and other metabolic characteristics were compared. ABI was categorized as low, ABI ≤ 0.9, borderline, ABI 0.91–0.99, normal, ABI 1.0-1.39, and high, ABI ≥ 1.4.ResultsPrevalence of low ABI was higher in the most sedentary quartiles compared to the least sedentary (0.6% vs. 0.1%, p < 0.001). The most sedentary individuals also exhibited higher BMI, higher prevalence of diabetes and hypertension. The proportion of wake time spent in MVPA was lowest in those with low ABI (0.033 ± 0.004; p < 0.001) and highest in those with ABI > 1.4 (0.069 ± 0.001; p < 0.001) compared to those with normal ABI. Compared to normal ABI, the proportion of sedentary time was highest in those with low ABI (0.597 ± 0.012; p < 0.001) and lowest in those with ABI > 1.4 (0.534 ± 0.002; p = 0.004).ConclusionThis population-based study shows that middle-aged individuals with ABI > 1.4 have the highest level of physical activity, while individuals with a lower ABI, especially those with ABI < 0.9, are less active and spend more time sedentary. Future studies are needed to understand the relationships between ABI, physical activity, and the risk of peripheral arterial and cardiovascular disease in the general population.

Peer Social Genetic Effects and the Etiology of Substance Use Disorders, Major Depression, and Anxiety Disorder in a Swedish National Sample.

There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder. Cox models were used with data from a population-based Swedish cohort (N=655,327). Outcomes were drug use disorder, AUD, major depression, and anxiety disorder registrations between ages 17 and 30 from medical, criminal, and pharmacy registries. The authors indexed peer social genetic effects with peers' family genetic risk scores (FGRSs) for the same disorders, which are personalized measures of genetic risk inferred from diagnoses in first- to fifth-degree relatives. Across disorders, peer FGRSs predicted increased risks of proband registration (hazard ratio range, 1.01-1.59), with stronger effects for drug use disorder and AUD than for major depression and anxiety disorder. Peer social genetic effects were stronger for school classmates than for geographically proximal peers, and for peers from upper secondary school (ages 16-19) versus peers from lower secondary school (ages 7-16). Peer social genetic effects remained significant following statistical control for sociodemographic confounders, whether peers were affected, and peers' FGRS for educational attainment. Peer social genetic effects were more pronounced for probands at higher genetic risk. The genetic makeup of adolescents' peers has long-reaching consequences on risks for drug use disorder, AUD, major depression, and anxiety disorder. Individuals at high genetic risk are more sensitive to social genetic effects. Alternative hypotheses such as sociodemographic stratification, exposure to affected peers, and genetic predispositions for educational attainment did not explain the risk associated with peer social genetic effects for substance use and psychiatric disorders.

Applicability of STOPP/START prescribing criteria in integrated Swedish administrative health registries and a Swedish population-based cohort.

The STOPP/START criteria are frequently applied in observational studies to assess potentially inappropriate prescribing in older adults. This study aimed to assess the applicability of the three available STOPP/START versions in two distinct data sources. To evaluate the applicability of the three versions of STOPP/START criteria, we used two observational data sources: (i) Integrated Swedish administrative health registries (ISHR) encompassing routinely collected health data and (ii) the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K), based on health professional-led clinical assessments. The Anatomical Therapeutic Classification code (ATC) was used to categorise medications. Diseases were categorised using the international classification of diseases version 10 (ICD10). The first STOPP/START version demonstrated an applicability rate of 80% in ISHR and 84% in SNAC-K. The second version demonstrated an applicability of 64% in ISHR and 74% in SNAC-K. The third version showed an applicability of 66% in ISHR and 77% in SNAC-K. Challenges in applicability included broad definitions, vague terminology, and the lack of information on disease severity, symptomatic traits, and stability of certain conditions. The applicability of the STOPP/START criteria in observational studies seems to have decreased in more recent versions of the tool. Population-based studies with comprehensive clinical assessments may offer higher applicability compared to studies based on administrative data. Future versions of the STOPP/START criteria should prioritise clear and unambiguous definitions to improve their applicability in research and promote result generalisability and comparability.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort

BackgroundThe prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth.MethodsWe analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features.ResultsWe detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e − 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels.ConclusionsCyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Impact of lower-respiratory tract infections on healthcare utilization and mortality in older adults: a Swedish population-based cohort study

BackgroundLower respiratory tract infections (LRTIs) have an immediate significant impact on morbidity and mortality among older adults. However, the impact following the infectious period of LRTI remains understudied. We aimed to assess the short- to long-term impact of LRTIs on hospitalization, mortality, and healthcare utilization in older adults.MethodsData from the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K) was analyzed, with data from 2001 to 2019 for mortality and 2001–2016 for healthcare utilization. LRTI-exposed participants were identified and matched with LRTI-nonexposed based on sociodemographics, lifestyle factors, and functional and clinical characteristics. Statistical models evaluated post-LRTI hospitalization risk, days of inpatient hospital admissions, healthcare visits, and mortality.Results567 LRTIs-exposed participants during the study period and were matched with 1.701 unexposed individuals. LRTI-exposed individuals exhibited increased risk of hospitalization at 1-year (HR 2.14, CI 1.74, 2.63), 3-years (HR 1.74, CI 1.46, 2.07), and 5-years (HR 1.59, CI 1.33, 1.89). They also experienced longer post-LRTI hospital stays (IRR 1.40, CI 1.18, 1.66), more healthcare visits (IRR 1.47, CI 1.26, 1.71), specialist-care visits (IRR 1.46, CI 1.24, 1.73), and hospital admissions (IRR 1.57, CI 1.34, 1.83) compared to nonexposed participants over 16-years of potential follow-up. Additionally, the 19-year risk of mortality was higher among LRTI-exposed participants (HR 1.45, CI 1.24, 1.70). Men exhibited stronger associations with these risks compared to women.ConclusionsLRTIs pose both short- and long-term risks for older adults, including increased risks of mortality, hospitalization, and healthcare visits that transpire beyond the acute infection period, although these effects diminish over time. Men exhibit higher risks across these outcomes compared to women. Given the potential preventability of LRTIs, further public health measures to mitigate infection risk are warranted.

O-200 Association between proton pump inhibitors use and the risk of maternal infections during pregnancy and postpartum: a Swedish population-based cohort study

Abstract Study question Is there an association between use of proton pump inhibitors (PPIs) and maternal infection during or after pregnancy and subsequent pregnancy complications? Summary answer Use of PPIs in the 3 months before pregnancy or during the first trimester was associated with an elevated risk of maternal infection. What is known already PPIs alter gastric acidity and the gut microbiome, which may increase infection risks in the general population, but their impact on pregnant women is unknown. Study design, size, duration We conducted a Nationwide population-based cohort study using data from Swedish healthcare registers. PPIs use was defined as ≥ 1 prescription fill of a PPI in the 90 days before the first day of the last menstrual period (LMP) to the end of the 1st trimester (LMP+97 days). Maternal infections were identified from the start of the 2nd trimester to 90 days postpartum and classified as mild, moderate/ severe infections, and infection-related pregnancy complications. Participants/materials, setting, methods All pregnancies resulting in live or stillbirths between 2006 to 2019 in Sweden, identified using the Medical Birth Register. Log-binomial regression was used to estimate associations (relative risk (RR) and 95% confidence intervals (CI)) between PPIs and maternal infection, adjusting for potential confounders including birth year, maternal age at delivery, early pregnancy BMI, comorbidities, smoking in early pregnancy, maternal country of birth, maternal education, and parity. Main results and the role of chance Among 1,510,560 pregnant women, 42,599 (2.8%) used PPIs, and use increased over the study period time from 1.5% in 2006 to 3.44% in 2019. Compared to pregnant women without PPI use, those with PPI use had higher rates and risks of any infection (49.7% vs 36.8%; adjusted RR 1.30, 95%CI 1.29-1.32), mild infection (20.9% vs 16.1%; adjusted RR 1.30, 95%CI 1.28-1.33), moderate to severe infection (23.4% vs 15%; adjusted RR 1.47, 95%CI 1.45-1.50), and infection-related pregnancy complications (11.2% vs 9.2; adjusted RR 1.12, 95%CI 1.09-1.15). Conclusion Our results show an association between PPI use and an elevated risk of infection in pregnant women. Next steps include the further investigation into the infection types. PPI therapy has benefits and drawbacks that should be carefully weighed, especially in patients who are prone to infections. While our study highlights potential concerns, it does not imply that all pregnant women are at increased risk. More research is needed to understand the underlying mechanisms and assess potential preventive measures. Prescribing PPIs during pregnancy should be determined on a case-by-case basis, considering the patient’s individual health state. We acknowledge the necessity for caution, particularly in vulnerable populations, and more research is needed to demonstrate clinical correlations. Limitations, reasons for caution Potential confounding by indication due to underlying morbidities cannot be fully accounted for. Further research is required to establish clinical connections. Wider implications of the findings Clinicians should carefully weigh the benefits of PPI therapy during pregnancy, particularly in patients prone to infections. Trial registration number not applicable