The risk and development of work disability among individuals with gambling disorder: a longitudinal case-cohort study in Sweden.

BACKGROUND: This longitudinal register study aimed to investigate the association between gambling disorder (GD) and work disability and to map work disability in subgroups of individuals with GD, three years before and three years after diagnosis. METHODS: We included individuals aged 19-62 with GD between 2005 and 2018 (n = 2830; 71.1% men, mean age: 35.1) and a matched comparison cohort (n = 28 300). Work disability was operationalized as the aggregated net days of sickness absence and disability pension. Generalized estimating equation models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the risk of long-term work disability (>90 days of work disability/year). Secondly, we conducted Group-based Trajectory Models on days of work disability. RESULTS: Individuals with GD showed a four-year increased risk of long-term work disability compared to the matched cohort, peaking at the time of diagnosis (AOR = 1.89; CI 1.67-2.13). Four trajectory groups of work disability days were identified: constant low (60.3%, 5.6-11.2 days), low and increasing (11.4%, 11.8-152.5 days), medium-high and decreasing (11.1%, 65.1-110 days), and constant high (17.1%, 264-331 days). Individuals who were females, older, with prior psychiatric diagnosis, and had been dispensed a psychotropic medication, particularly antidepressants, were more likely to be assigned to groups other than the constant low. CONCLUSION: Individuals with GD have an increased risk of work disability which may add financial and social pressure and is an additional incentive for earlier detection and prevention of GD.

Sex ratio at birth across 100 years in Sweden and risk of cardiovascular disease and all-cause mortality - a national register study.

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.

The Danish Nationwide Electrocardiogram (ECG) Cohort.

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th-75th percentiles, 40-71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up.

Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

PURPOSE: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. METHODS: We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. RESULTS: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. CONCLUSIONS: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Prevalence of diabetes and hospitalization due to poor glycemic control in people with bladder cancer or renal cell carcinoma in Sweden.

BACKGROUND: Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. METHODS: This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. RESULTS: We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. CONCLUSION: The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes.

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 - December 2022.

BACKGROUND: Due to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25-64-years-old) in Norway. METHODS: We performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported. RESULTS: We included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2-7 days after vaccination for both sick leave (0.25; 95%CI 0.24-0.26 and 0.26; 95% CI 0.24-0.29) and infection ( 0.16; 95% CI 0.15-0.17 and 0.18; 95% CI 0.16-0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2-7 weeks after receiving the second (0.61; 95% CI 0.59-0.64) or third dose (0.63; 95% CI 0.62-0.64). CONCLUSION: Our results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

Nationwide evidence that education disrupts the intergenerational transmission of disadvantage.

Despite overall improvements in health and living standards in the Western world, health and social disadvantages persist across generations. Using nationwide administrative databases linked for 2.1 million Danish citizens, we leveraged a three-generation approach to test whether multiple, different health and social disadvantages-poor physical health, poor mental health, social welfare dependency, criminal offending, and Child Protective Services involvement-were transmitted within families and whether education disrupted these statistical associations. Health and social disadvantages concentrated, aggregated, and accumulated within a small, high-need segment of families: Adults who relied disproportionately on multiple, different health and social services tended to have parents who relied disproportionately on multiple, different health and social services and tended to have children who evidenced risk for disadvantage at an early age, through appearance in protective services records. Intra- and intergenerational comparisons were consistent with the possibility that education disrupted this transmission. Within families, siblings who obtained more education were at a reduced risk for later-life disadvantage compared with their cosiblings who obtained less education, despite shared family background. Supporting the education potential of the most vulnerable citizens might mitigate the multigenerational transmission of multiple disadvantages and reduce health and social disparities.

Development of application and surgical technique of total knee arthroplasties: a systematic comparative analysis using worldwide registers.

PURPOSE: The aim was to compare total knee arthroplasty (TKA) between countries with regard to epidemiologic data and surgical technique by the use of worldwide registers and compare findings with a previous report after one decade. METHODS: A systematic search was carried out in November 2022 and compared to previous reports from 2010. We extracted data regarding implanted TKAs, patients' age distribution, procedure types, fixation and revision rates. After identification of 28 national arthroplasty registers, 8of them, namely Australia, Canada, Denmark, England and Wales, New Zealand, Norway, Scotland and Sweden, offered sufficient data and were included in final analysis. RESULTS: A large variation was found in the annual number of implantations per 100,000 inhabitants with a range from 77 to 210.2 (mean 132.8). The fixation type varied strongly as well, e.g. over 95% of totally cemented TKAs in Sweden versus 61.2% cemented fixation in Denmark. Another significant difference was the use of patellar resurfacing in TKA, ranging from 47.3% (Canada) using a patellar button in TKA to less than 5% (Sweden). Within the period of one decade, the mean overall number of annual implantations increased (10%), whilst relative number of revisions decreased, the use of cemented TKA decreased from 87 to 74%, and the use of patella button remained largely inhomogeneous. CONCLUSION: Comparison of arthroplasty registers revealed large differences regarding the annual number of primary TKAs per inhabitant as well as primary TKA procedure types with an increase of annual implantations, decrease of relative number of revisions, and a decrease of the use of cemented systems over the period of one decade.

The Impact of Hip Fracture on Geriatric Care and Mortality Among Older Swedes: Mapping Care Trajectories and Their Determinants.

In this study, we examined the impact of hip fractures on trajectories of home care, nursing home residence, and mortality among individuals aged 65 years or more and explored the impacts of living arrangements, cohabitation, frailty, and socioeconomic position on these trajectories. Based on a linkage of nationwide Swedish population registers, our study included 20,573 individuals with first hip fracture in 2014-2015. Care trajectories during the 2 years following the fracture were visualized and compared with those of 2 hip-fracture-free control groups drawn from the general population: age- and sex-matched controls and health-matched controls identified through propensity score matching. Multistate modeling was employed to identify sociodemographic and health-related factors associated with care trajectories among hip fracture patients. We found that hip fracture patients already had worse health than the general population before their fracture. However, when controlling for prefracture health, hip fractures still had a considerable impact on use of elder-care services and mortality. Comparisons with the health-matched controls suggest that hip fractures have an immediate, yet short-term, impact on care trajectories. Long-term care needs are largely attributable to poorer health profiles independent of the fracture itself. This emphasizes the importance of adequate comparison groups when examining the consequences of diseases which are often accompanied by other underlying health problems.

Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood: a nationwide population-based cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The complexities of suicide: a multilevel survival analysis examining individual, familial and neighbourhood determinants of suicide risk using Danish register-based data.

BACKGROUND: Suicide risk is complex and nuanced, and how place impacts suicide risk when considered alongside detailed individual risk factors remains uncertain. We aimed to examine suicide risk in Denmark with both individual and neighbourhood level risk factors. METHODS: We used Danish register-based data to identify individuals born in Denmark from 1972, with full parental information and psychiatric diagnosis history. We fitted a two-level survival model to estimate individual and neighbourhood determinants on suicide risk. RESULTS: We identified 1723 cases of suicide in Denmark during the follow-up period from 1982 to 2015. Suicide risk was explained mainly by individual determinants. Parental comorbidities, particularly maternal schizophrenia [incidence rate ratio (IRR): 2.29, 95% CI 1.56-3.16] and paternal death (2.29, 95% CI 1.31-3.72) partly explained suicide risk when adjusted for all other determinants. The general contextual effect of suicide risk across neighbourhoods showed a median incidence rate ratio (MRR) of 1.13 (1.01-1.28), which was further reduced with full adjustment. Suicide risk increased in neighbourhoods with a higher proportion of manual workers (IRR: 1.08; 1.03-1.14), and decreased with a higher population density (IRR: 0.89; 0.83-0.96). CONCLUSION: Suicide risk varies mainly between individuals, with parental comorbidities having the largest effect on suicide risk. Suicide risk was less impacted by neighbourhood, though, albeit to a lesser extent than individual determinants, some characteristics were associated with suicide risk. Suicide prevention policies might consider targeting interventions towards individuals more vulnerable due to particular parental comorbidities, whilst taking into account that some neighbourhood characteristics might exacerbate this risk further.

Epidemiology and clinical outcomes of light-chain amyloidosis in Sweden: A nationwide population-based study.

OBJECTIVES: This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis. METHODS: Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. RESULTS: 846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group. CONCLUSION: The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.

Incidence and outcomes of head injuries in people with and without Parkinson disease.

BACKGROUND AND PURPOSE: Fall-related injuries are a major health concern among people with Parkinson disease (PD). We compared the incidence and postinjury mortality of head injuries and traumatic brain injury (TBI) among persons with and without PD. METHODS: This register-based study was conducted on the FINPARK cohort, which includes 22,189 persons who were diagnosed with PD in Finland during 1996-2015. We excluded persons with a previous head injury, leaving 20,514 persons with PD. For each person with PD, 1-7 matching persons without PD and previous head injury were identified with respect to age, sex, and residence. The Cox proportional hazard model was used to estimate hazard ratios for head injury. A logistic regression model was used to compare mortality. RESULTS: Persons with PD had 2.16-fold (95% confidence interval [CI] = 2.06-2.26) risk of all head injuries and 1.97-fold (95% CI = 1.84-2.10) risk of TBI after adjustment for age, sex, and comorbidities. Persons with PD had higher 1-year mortality after any type of head injury (adjusted odds ratio [aOR] = 1.44, 95% CI = 1.28-1.62), TBI (aOR = 1.33, 95% CI = 1.14-1.57), or non-TBI head injury (aOR = 1.72, 95% CI = 1.42-2.07) than persons without PD. The higher risk of mortality was observed 6 months after TBI and 1 month after non-TBI injury in persons with PD. Persons with PD and head injury also had higher 1-year mortality than persons with PD and without head injury. CONCLUSIONS: Persons with PD have a higher risk of head injury and higher postinjury mortality than persons without PD.

Severity of preterm birth and the risk of pulmonary hypertension in childhood: A population-based cohort study in Sweden.

BACKGROUND: Preterm birth (<37 completed gestational weeks) has been linked to pulmonary hypertension (PH), but the relationship to severity of preterm birth has not been studied. OBJECTIVES: We investigated associations between extremely (<28 weeks), very (28-31 weeks), moderately (32-36 weeks) preterm birth, early-term birth (37-38 weeks) and later PH. Additionally, we explored associations between birthweight for gestational age and PH. METHODS: This registry-based cohort study followed 3.1 million individuals born in Sweden (1987-2016) from 1 up to a maximum of 30 years of age. The outcome was diagnosis or death from PH in national health registers. Adjusted hazard ratios (HR) were estimated using Cox regression analysis. Unadjusted and confounder-adjusted incidence rate differences were also calculated. RESULTS: Of 3,142,812 individuals, there were 543 cases of PH (1.2 per 100,000 person-years), 153 of which in individuals without malformations. Compared with individuals born at 39 weeks, adjusted HRs with 95% confidence interval (CI) for PH for extremely, moderately, and very preterm birth were 68.78 (95% CI 49.49, 95.57), 13.86 (95% CI 9.27, 20.72) and 3.42 (95% CI 2.46, 4.74), respectively, and for early-term birth 1.74 (1.31, 2.32). HRs were higher in subjects without malformations. There were 90 additional cases of PH per 100,000 person-years in the extremely preterm group (50 after excluding malformations). Very small for gestational age (below 2 SD from estimated birthweight for gestational age and sex) was also associated with increased risk of PH (adjusted HR 2.02, 95% CI 1.14, 3.57). CONCLUSIONS: We found an inverse association between gestational age and later PH, but the incidence and absolute risks are low. The severity of preterm birth adds clinically relevant information to the assessment of cardiovascular risks in childhood.

Experience-based health state valuation using the EQ VAS: a register-based study of the EQ-5D-3L among nine patient groups in Sweden.

BACKGROUND: The EQ VAS component of the EQ-5D questionnaire has been used to assess patients' valuation of their own health besides its use for self-reporting of overall health status. The objective of the present study was to identify patients' valuation of EQ-5D-3L health states using the EQ VAS in different patient groups over time and in comparison to the general population. METHODS: Data were obtained from patients from nine National Quality Registers (n = 172,070 patients) at baseline and at 1-year follow-up and compared with data from the general population (n = 41,761 participants). The correlation between EQ VAS scores and EQ-5D-3L index based on the Swedish experience-based VAS value set was assessed. Ordinary least squares (OLS) regression models were used to determine the association between EQ-5D-3L dimensions and EQ VAS valuation. RESULTS: EQ VAS scores showed consistency with severity of health states both at baseline and at 1-year follow-up in the nine selected EQ-5D-3L health states. The regression models showed mostly consistent decrements by severity levels in each dimension at both time points and similar to the general population. The dimension mainly associated with inconsistency was the self-care severity level three. Problems in the anxiety/depression dimension had the largest impact on overall health status in most of the patient groups and the general population. CONCLUSION: The study has demonstrated the important role EQ VAS can play in revealing patients' valuation of their health and showed the variation in valuation of EQ-5D-3L dimensions and levels of severity across different patient groups.

Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010-2019.

PURPOSE: This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use. METHODS: We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester. RESULTS: ADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden). CONCLUSION: ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.

Federated analyses of multiple data sources in drug safety studies.

PURPOSE: Studies of rare side effects of new drugs with limited exposure may require pooling of multiple data sources. Federated Analyses (FA) allow real-time, interactive, centralized statistical processing of individual-level data from different data sets without transfer of sensitive personal data. METHODS: We review IT-architecture, legal considerations, and statistical methods in FA, based on a Swedish Medical Products Agency methodological development project. RESULTS: In a review of all post-authorisation safety studies assessed by the EMA during 2019, 74% (20/27 studies) reported issues with lack of precision in spite of mean study periods of 9.3 years. FA could potentially improve precision in such studies. Depending on the statistical model, the federated approach can generate identical results to a standard analysis. FA may be particularly attractive for repeated collaborative projects where data is regularly updated. There are also important limitations. Detailed agreements between involved parties are strongly recommended to anticipate potential issues and conflicts, document a shared understanding of the project, and fully comply with legal obligations regarding ethics and data protection. FA do not remove the data harmonisation step, which remains essential and often cumbersome. Reliable support for technical integration with the local server architecture and security solutions is required. Common statistical methods are available, but adaptations may be required. CONCLUSIONS: Federated Analyses require competent and active involvement of all collaborating parties but have the potential to facilitate collaboration across institutional and national borders and improve the precision of postmarketing drug safety studies.

A short length of hospital stay is not associated with risk of readmission among hip fracture patients - a Swedish national register-based cohort study.

BACKGROUND: Hospital length of stay (LoS) after a hip fracture likely mirrors health status; however, a too short hospitalization might increase the risk of readmission. In this national register-based study, we investigated the association between LoS after a hip fracture and the risk of readmissions. METHODS: 73,551 patients with a first hip fracture between 2012 and 2019 were followed for 4 months after discharge. LoS was categorized by cubic splines and the association with readmissions was analyzed with Cox regression models. RESULTS: The mean LoS was 11 ± 6 days and 25% of the study population had at least one readmission. Compared to the mean LoS of 9-12 days, there was a 18% decreased risk of readmission for LoS of 2-4 days (HR 0.82 [95% CI 0.77-0.87]) and 13% decrease for 5-8 days (HR 0.87 [95% CI 0.83-0.91]), when adjusting for sex, age, walking ability, ASA score, CCI, complications during hospitalization and living arrangements. For longer LoS, risk of readmission increased (13-23 days: HR 1.09 [95% CI 1.05-1.13] and 24 + days: HR 1.19 [95% CI 1.11-1.28]). The results were robust across sex, age, and living arrangements. The most common specific reasons for readmission were trauma/injury, cardiovascular and complications, and the proportions did not differ considerably between short and long LoS-categories. CONCLUSIONS: While a long LoS can be explained by the care need of the patient, a short LoS - compared to the average stay - does not increase the risk of readmission regardless of health status and hospital complications in a Swedish setting.

Trajectories of CVD medication after statutory retirement: contributions of pre-retirement sociodemographic, work and health-related factors: a register study in Finland.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Perspectives on environment and health research in Denmark.

AIMS: We provide an overview of nationwide environmental data available for Denmark and its linkage potentials to individual-level records with the aim of promoting research on the potential impact of the local surrounding environment on human health. BACKGROUND: Researchers in Denmark have unique opportunities for conducting large population-based studies treating the entire Danish population as one big, open and dynamic cohort based on nationally complete population and health registries. So far, most research in this area has utilised individual- and family-level information to study the clustering of disease in families, comorbidities, risk of, and prognosis after, disease onset, and social gradients in disease risk. Linking environmental data in time and space to individuals enables novel possibilities for studying the health effects of the social, built and physical environment. METHODS: We describe the possible linkage between individuals and their local surrounding environment to establish the exposome - that is, the total environmental exposure of an individual over their life course. CONCLUSIONS: The currently available nationwide longitudinal environmental data in Denmark constitutes a valuable and globally rare asset that can help explore the impact of the exposome on human health.