OBJECTIVE: To describe antibiotic use in patients with inflammatory arthritis (IA) and in the background population (BP) within one year before and after IA diagnosis.
METHODS: Using data from Danish nationwide registries, we identified all adults with a first-time diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis/spondyloarthritis (AS/SpA) from 2010 through 2018. For each IA patient, we randomly sampled ten persons from the BP, matched on sex and birthdate. We calculated the prevalence (n [%]) of any antibiotic dispensing and the total antibiotic dispensing in the year before and after diagnosis.
RESULTS: We identified 28 504 new-onset IA patients (RA, n = 16 130; PsA, n = 5,988; AS/SpA, n = 6,386) and 285 040 BP individuals. The one-year prevalence of any antibiotic dispensing was 42.1% in IA patients before diagnosis vs 30.7% in the BP. The total antibiotic dispensing was higher the one-year before both RA, PsA, and As/SpA compared with BP (prevalence rate ratios [PRR], 1.48 [1.46; 1.51]; 1.67 [1.62; 1.72]; 1.52 [1.47; 1.56], respectively), and increased with 22% in IA patients three months before diagnosis compared with the preceding three-month period. Although the prevalence of any antibiotic dispensing in IA patients decreased in the year following the diagnosis (IA; 40.6%), the total one-year antibiotic dispensing remained constant in RA (PRR 0.99 [0.97; 1.01]), decreased in PsA (0.91 [0.87; 0.94]), and increased in AS/SpA (1.08 [1.04; 1.12]) patients after diagnosis compared with before.
CONCLUSIONS: Antibiotics are more frequently dispensed to individuals developing IA compared with the BP. Antibiotic utilisation patterns change after IA diagnosis with marked differences among IA subgroups.

The human sex ratio at birth (SRB) undergoes temporary changes around a mean proportion of 0.51 male births. SRB has been well studied for historical, geographical, and secular trends, but until now not linked to health outcomes in the total population, e.g. for cardiovascular disease (CVD) or mortality during follow-up of birth cohorts. We used linkage analysis based on national registers in Sweden that cover all births from 1900 to 2016. SRB at birth was calculated by every 10-year birth cohort in all survivors living in 1997 for a follow-up analysis of risk of CVD and mortality with data from national registers. When the highest quartile of SRB was used as reference, a slightly increased risk of fatal CVD (HR 1.03 (95% confidence intervals, CI): 1.02-1.04), non-fatal CVD (HR 1.01; 95%CI: 1.01-1.02) and mortality (HR 1.02; 95%CI, 1.01-1.03) was found after full adjustments in men belonging to the lowest SRB quartile. A similar pattern was also found for fatal CHD in women. in the lowest SBR quartile compared to the highest, HR 1.03 (95%CI: 1.02-1.05). In conclusion, in birth cohorts with a relatively lower than expected number of males born, long-term adverse health effects were observed with slightly increased cardiovascular risk and total mortality at the population level. This could indicate that men belonging to so-called \"culled cohorts\" in a developed country during the 20th century are characterized by a slightly increased risk that could reflect negative early life influences and environmental exposures in pregnant women resulting in selective loss of male embryos or fetuses. In a public health perspective SRB could be of some importance to monitor as an aspect of birth statistics linked to relatively minor population health effects.

UNASSIGNED: The prevalence of occlusive lower extremity artery disease (LEAD) is rising worldwide while European epidemiology data are scarce. We report incidence and mortality of LEAD repair in Denmark from 1996 through 2018, stratified on open aorto-iliac, open peripheral, and endovascular repair.
UNASSIGNED: A nationwide cohort study of prospective data from population-based Danish registers covering 1996 to 2018. Comorbidity was assessed by Charlson\'s Comorbidity Index (CCI). Incidence rate (IR) ratios and mortality rate ratios (MRR) were estimated by multivariable Poisson and Cox regression, respectively.
UNASSIGNED: We identified 41,438 unique patients undergoing 46,236 incident first-time LEAD repairs by either aorto-iliac- (n=5213), peripheral surgery (n=18,665) or percutaneous transluminal angioplasty (PTA, n=22,358). From 1996 to 2018, the age- and sex-standardized IR for primary revascularization declined from 71.8 to 50.2 per 100,000 person-years (IRR, 0.70; 95% CI, 0.66-0.75). Following a 2.5-fold IR increase of PTA from 1996 to 2010, all three repair techniques showed a declining trend after 2010. The declining IR was driven by decreasing LEAD repair due to claudication, and by persons aged below 80 years, while the IR increased in persons aged above 80 years (p interaction<0.001). LEAD repair was more frequent in men (IRRfemale vs male, 0.78; 95% CI, 0.77-0.80), which was consistent over calendar time (p interaction=0.41). Crude mortality decreased following open/surgical repair, and increased following PTA, but all three techniques trended towards lower adjusted mortality comparing the start and the end of the study period (MRRaorto-iliac, 0.71; 95% CI, 0.54-0.93 vs MRRperipheral, 0.76; 95% CI, 0.69-0.83 vs MRRPTA, 0.96; 95% CI, 0.86-1.07). Increasing age and CCI, male sex, smoking, and care dependency associated with increased mortality.
UNASSIGNED: The incidence rate of LEAD repair decreased in Denmark from 1996 to 2018, especially in persons younger than 80 years, and primarily due to reduced revascularization for claudication. Adjusted mortality rates decreased following open surgery, but seemed unaltered following PTA.

UNASSIGNED: Duchenne Muscular Dystrophy (DMD) is a progressive genetic disease with a prevalence of 1 per 3,600-6,000 male births. Individuals with DMD are typically diagnosed at age 4-7 years; median survival is 30 years. They require multidisciplinary care, personal assistance, and often special education.
UNASSIGNED: The aim was to assess the burden of disease in DMD in Denmark. This includes incidence, prevalence, use of healthcare services, labour market participation, educational outcomes, and overall attributable costs due to DMD. Impact on the closest relatives (siblings and parents) was also investigated.
UNASSIGNED: The comprehensive Danish national health and administrative registers were used to assess the burden of disease following individuals with DMD and closest relatives from five years before, and up to 20 years after DMD diagnosis. Individuals with DMD (and relatives) from 1994-2021 were included. All outcomes were compared to matched control groups without the disease drawn from the Danish population.
UNASSIGNED: 213 unique individuals with DMD were identified. They had lower grades in school, required more special education and more healthcare and home care compared to their control group. The extra costs of special education summed to EUR 180,900 over the course of 11 years elementary school. They had an annual average productivity loss of EUR 20,200 between the age of 18 to 30. The extra healthcare costs of DMD in the 20 years after diagnosis were estimated to EUR 1,524,000. If an individual with DMD lives to be 30, total extra costs sum to EUR 2,365,800.
UNASSIGNED: Using national register data this study presented detailed results on the burden of disease of DMD, including impact on closest relatives. With 60 additional hospital admissions and 200 extra outpatient contacts in 20 years healthcare costs, but also costs of home care and special education, increases as disease progresses.

Cardiovascular diseases (CVDs) are prevalent in older people, but few studies focus on developmental patterns in CVD medication directly after transition to statutory retirement. We thus aimed to identify trajectories of CVD medication after retirement, and their sociodemographic, work and health-related determinants.
We used complete register data of former employees of the City of Helsinki, Finland. All who reached their statutory retirement in 2000-2013, with five-year follow-up data (n = 6,505, 73% women), were included. Trajectories of CVD medication were identified with group-based trajectory modelling using data from Finnish Social Insurance Institution\'s reimbursement register. Sociodemographic, work and health-related determinants of trajectory group membership were analysed using multinomial logistic regression.
Six trajectories of CVD medication were distinguished: \"constant low\" (35%), \"late increase\" (6%), \"early increase\" (5%), \"constant high\" (39%), \"high and decreasing \" (8%), and \"low and decreasing\" (7%). The majority (74%) of the retirees fell into the \"constant low\" and \"constant high\" categories. Lower occupational class and increased pre-retirement sickness absence were associated with the \"constant high\" trajectory. Further, those with lower educational attainment were more prone to be in the \"early increase\" trajectory.
Individuals in lower socioeconomic positions or with a higher number of pre-retirement sickness absence may be considered at higher risk and might benefit from early interventions, e.g. lifestyle interventions and interventions targeting working conditions, or more frequent monitoring.

Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.
Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring\'s age as the time scale.
During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20-1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38-1.78) and gestational diabetes (HR=1.37, 95% CI=1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98-1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00-1.88) or preeclampsia (HR=1.62, 95% CI=1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85-5.60) than offspring of mothers with HDP or diabetes alone.
Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

BACKGROUND: Many Western countries have scaled back social and health expenditure, including decreases in the generosity and coverage of unemployment insurance, resulting in negative effects on general health and well-being at the aggregate level. Yet, research has not sufficiently looked into heterogeneity of such effects across different subgroups of the population. In Sweden, the 2006 unemployment insurance reform, implemented on the 1st of January 2007, encompassed a drastic increase of insurance fund membership fees, reduced benefit levels, and stricter eligibility requirements. As this particularly affected already socioeconomically disadvantaged groups in society, such as foreign-born and low-educated individuals, the current study hypothesise that the reform would also have a greater impact on health outcomes in these groups.
METHODS: Based on register data for the total population, we utilise a quasi-experimental approach to investigate heterogeneous health effects of the reform across ethnic background, educational level, employment status, and sex. Due to behaviourally caused diseases having a relatively shorter lag time from exposure, hospitalisation due to alcohol-related disorders serves as the health outcome. A series of regression discontinuity models are used to analyse monthly incidence rates of hospitalisation due to alcohol-related disorders among individuals aged 30-60 during the study period (2001-2012), with the threshold set to the 1st of January 2007.
RESULTS: The results suggest that, in general, there was no adverse effect of the reform on incidence rates of hospitalisation due to alcohol-related disorders. A significant increase is nonetheless detected among the unemployed, largely driven by Swedish-born individuals with Swedish-born or foreign-born parents, low-educated individuals, and men.
CONCLUSIONS: We conclude that the Swedish 2006 unemployment insurance reform generally resulted in increasing incidence rates of hospitalisation due to alcohol-related disorders among unemployed population subgroups known to have higher levels of alcohol consumption.

Atrial fibrillation (AF) is a common heart rhythm disorder and a risk factor of adverse cardiovascular diseases. Established causes do not fully explain the risk of AF and unexplained risk factors might be related to the environment, e.g. magnesium in drinking water. Low magnesium levels in drinking water might be associated with higher risk of cardiovascular diseases including AF. With detailed individual data from nationwide registries and long-term magnesium exposure time series, we had a unique opportunity to investigate the association between magnesium in drinking water and AF.
We evaluated the association between magnesium concentration in drinking water and AF risk.
A nationwide register-based cohort study (2002-2015) was used including individuals aged ≥30 years. Addresses were linked with water supply areas (n = 2418) to obtain time-varying drinking water magnesium exposure at each address. Five exposure groups were defined based on a 5-year rolling time-weighted average magnesium concentration. AF incidence rate ratios (IRRs) between exposure groups were calculated using a Poisson regression of incidence rates, adjusted for sex, age, and socioeconomic position. Robustness of results was investigated with different exposure definitions.
The study included 4,264,809 individuals (44,731,694 person-years) whereof 222,998 experienced an incident AF. Magnesium exposure ranged from 0.5 to 62.0 mg/L (mean = 13.9 mg/L). Estimated IRR (95% CI) compared to the referent exposure group (< 5 mg/L) was 0.98 (0.97-1.00) for the second lowest exposure group (5-10 mg/L), and 1.07 (1.05-1.08) for the two highest exposure groups (15-62 mg/L). Strongest positive associations were observed among those aged ≥80 years and with lowest education group. An inverse association was found among individuals with highest education group.
There might be a small beneficial effect on AF of an increase in magnesium level in drinking water up to 10 mg/L, though an overall positive association was observed. The unexpected positive association and different associations observed for subgroups suggest a potential influence of unaccounted factors, particularly in vulnerable populations. Future research on magnesium in drinking water and cardiovascular diseases needs to focus on contextual risk factors, especially those potentially correlating with magnesium in drinking water.

We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-allergic asthma, accounting for family factors and intermediate variables.
The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables: caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-allergic prevalent asthma at 6 years as a measure of more established asthma.
The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI): 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.78, 95% CI: 1.64, 1.95 for severe pre-eclampsia and asthma at <2 years age. Sibling comparisons attenuated most estimates except for the association between severe pre-eclampsia and asthma at <2 years age (adjHR 1.45, 95% CI: 1.10, 1.90), which also remained when stratifying for the risk of intermediates. Mild/moderate and severe pre-eclampsia were associated with prevalent non-allergic (but not allergic) asthma at 6 years, with adjusted odds ratio (adjOR) 1.17, 95% CI: 1.00, 1.36 and adjOR 1.51, 95% CI: 1.23, 1.84, respectively.
We found evidence that severe, but not mild/moderate, pre-eclampsia is associated with asthma regardless of familial factors and confounders.

OBJECTIVE: We aimed to investigate the associations between maternal diabetes before or during pregnancy and the risk of high refractive error (RE) in offspring until the age of 25 years.
METHODS: This nationwide register-based cohort study comprised 2,470,580 individuals born in 1977-2016. The exposure was maternal diabetes during or before pregnancy (type 1 diabetes, type 2 diabetes and gestational diabetes). Cox regression was used to examine the association between maternal diabetes and the risk of high RE in offspring from birth until the age of 25 years, adjusting for multiple potential confounders.
RESULTS: During up to 25 years of follow-up, 553 offspring of mothers with diabetes and 19,695 offspring of mothers without diabetes were diagnosed with high RE. Prenatal exposure to maternal diabetes was associated with a 39% increased risk of high RE: HR 1.39 (95% CI 1.28, 1.51), p < 0.001; standardised cumulative incidence in unexposed offspring at 25 years of age 1.18% (95% CI 1.16%, 1.19%); cumulative incidence difference 0.72% (95% CI 0.51%, 0.94%). The elevated risks were observed for hypermetropia (HR 1.37 [95% CI 1.24, 1.51], p < 0.001), myopia (HR 1.34 [95% CI 1.08, 1.66], p = 0.007) and astigmatism (HR 1.58 [95% CI 1.29, 1.92], p < 0.001). The increased risks were more pronounced among offspring of mothers with diabetic complications (HR 2.05 [95% CI 1.60, 2.64], p < 0.001), compared with those of mothers with diabetes but no diabetic complications (HR 1.18 [95% CI 1.02, 1.37], p = 0.030).
CONCLUSIONS: Our findings suggest that maternal diabetes during pregnancy is associated with an increased risk of high RE in offspring, in particular among those of mothers with diabetic complications. Early ophthalmological screening should be recommended in offspring of mothers with diabetes diagnosed before or during pregnancy.