Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study.

BACKGROUND: Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. METHODS: This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. FINDINGS: 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). INTERPRETATION: Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. FUNDING: Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice.

Type, Etiology, and Duration of Epilepsy as Risk Factors for SUDEP: Further Analyses of a Population-Based Case-Control Study.

BACKGROUND AND OBJECTIVES: We conducted a nationwide case-control study in Sweden to investigate the risk of sudden unexpected death in epilepsy (SUDEP) in relation to epilepsy duration, epilepsy type, and etiology in combination with occurrence and frequency of tonic-clonic seizures (TCS) and nocturnal TCS. METHODS: The study comprised 255 SUDEP cases and 1,148 epilepsy controls. Clinical information was obtained from medical records. The association between SUDEP and risk factors was estimated by odds ratios (ORs) with 95% CIs calculated by conditional logistic regression to account for matching by sex and calendar time. RESULTS: The risk of SUDEP was elevated in people with focal (OR 1.48, 95% CI 1.00-2.20), generalized and focal (OR 3.51, 95% CI 1.55-7.96), or unknown (OR 2.43, 95% CI 1.29-4.57) vs generalized epilepsy type. Increased risk of SUDEP was also observed in relation to epilepsy with traumatic causes (OR 2.27, 95% CI 1.33-3.89 vs genetic etiology) or short duration (OR 1.71, 95% CI 1.01-2.87 for 0-5 vs 6-15 years duration). Among those with 1-3 TCS during the preceding year, structural epilepsy etiology was associated with a more than 10-fold increase 10.84 (4.85-24.27) in SUDEP risk compared with people with genetic epilepsy without TCS. The risk with ≥4 TCS the preceding year was similar among those with generalized and focal epilepsies. Those with ≥4 TCS had an OR of 210.73 (95% CI 28.40-∞) during years 0-5 compared with those free from TCS and an epilepsy duration of 6-15 years. The combination of short epilepsy duration (0-5 years) and nocturnal TCS conferred an OR of 45.99 (95% CI 12.19-173.61) compared with having longer duration (6-15 years) and being free from nocturnal TCS. DISCUSSION: Although certain etiologies, such as post-traumatic epilepsy, seem to entail a higher SUDEP risk, our data indicate that frequent and nocturnal TCS carry a similar level of risk whether focal or generalized from onset. The tonic-clonic part of the seizure seems to be decisive for the fatal outcome. SUDEP risk associated with TCS is highest during the first years after the epilepsy diagnosis which calls for effective TCS treatment and vigilance from the onset of diagnosis.

All-Cause Mortality and Cardiovascular and Microvascular Diseases in Latent Autoimmune Diabetes in Adults.

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) is a heterogenous, slowly progressing autoimmune diabetes. We aim to contribute new knowledge on the long-term prognosis of LADA with varying degrees of autoimmunity by comparing it to type 2 diabetes and adult-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: This Swedish population-based study included newly diagnosed LADA (n = 550, stratified into LADAlow and LADAhigh by median autoimmunity level), type 2 diabetes (n = 2,001), adult-onset type 1 diabetes (n = 1,573), and control subjects without diabetes (n = 2,355) in 2007-2019. Register linkages provided information on all-cause mortality, cardiovascular diseases (CVDs), diabetic retinopathy, nephropathy, and clinical characteristics during follow-up. RESULTS: Mortality was higher in LADA (hazard ratio [HR] 1.44; 95% CI 1.03, 2.02), type 1 (2.31 [1.75, 3.05]), and type 2 diabetes (1.31 [1.03, 1.67]) than in control subjects. CVD incidence was elevated in LADAhigh (HR 1.67; 95% CI 1.04, 2.69) and type 2 diabetes (1.53 [1.17, 2.00]), but not in LADAlow or type 1 diabetes. Incidence of retinopathy but not nephropathy was higher in LADA (HR 2.25; 95% CI 1.64, 3.09), including LADAhigh and LADAlow than in type 2 diabetes (unavailable in type 1 diabetes). More favorable blood pressure and lipid profiles, but higher HbA1c levels, were seen in LADA than type 2 diabetes at baseline and throughout follow-up, especially in LADAhigh, which resembled type 1 diabetes in this respect. CONCLUSIONS: Despite having fewer metabolic risk factors than type 2 diabetes, LADA has equal to higher risks of death, CVD, and retinopathy. Poorer glycemic control, particularly in LADAhigh, highlights the need for improved LADA management.

"Click and mortar" opportunities for digitization and consumerism in trials.

BACKGROUND: Digitization (using novel digital tools and strategies) and consumerism (taking a consumer-oriented approach) are increasingly commonplace in clinical trials, but the implications of these changes are not well described. METHODS: We assembled a group of trial experts from academia, industry, non-profit, and government to discuss implications of this changing trial landscape and provide guidance. RESULTS: Digitization and consumerism can increase the volume and diversity of trial participants and expedite recruitment. However, downstream bottlenecks, challenges with retention, and serious issues with equity, ethics, and security can result. A "click and mortar" approach, combining approaches from novel and traditional trials with the thoughtful use of technology, may optimally balance opportunities and challenges facing many trials. CONCLUSION: We offer expert guidance and three "click and mortar" approaches to digital, consumer-oriented trials. More guidance and research are needed to navigate the associated opportunities and challenges.

Night and shift work patterns and incidence of type 2 diabetes and hypertension in a prospective cohort study of healthcare employees.

OBJECTIVES: This study aimed to evaluate effects of night and shift work patterns on type 2 diabetes (T2D) and hypertension in a longitudinal study, with detailed information on working hours. METHODS: The cohort comprised about 28 000 nurses and nursing assistants employed for more than one year 2008-2016 in Stockholm, Sweden. The employee register held detailed individual information on daily working hours. Information on diagnoses came from national and regional registers. Hazard ratios (HR) and confidence intervals (CI) were estimated by discrete-time proportional hazard models, adjusting for sex, age, country of birth, and profession. RESULTS: During follow-up in 2013-2017, we identified 232 cases of T2D and 875 of hypertension. We observed an increased risk of T2D, but not hypertension, among employees who worked only night shifts the previous year (HR 1.59, 95% CI 1.02-2.43) and those with intensive shift work (>120 afternoon and/or night shifts the previous year: HR 1.67, 95% CI 1.11-2.48) compared to only day work. There was a non-significantly increased risk of T2D related to mixed day and afternoon shifts (HR 1.34, 95% CI 0.97-1.88). We observed tendencies in increased risk of T2D related to frequent spells of ≥3 consecutive night shifts and with number of years with exclusive (but not mixed) night work. CONCLUSIONS: Permanent night work and frequent afternoon and/or night shifts were associated with an increased risk of T2D the following year, but not hypertension. The T2D risk was, to some extent, affected by frequent spells of several night shifts in a row and by cumulative years with permanent night work.

Geographical Variation in the Use of Oral Anticoagulation and Clinical Outcomes among Patients with Atrial Fibrillation in Denmark, Sweden, and Finland.

Background Geographical mapping of variations in the treatment and outcomes of a disease is a valuable tool for identifying inequity. We examined international and intranational variations in initiating oral anticoagulation (OAC) therapy and clinical outcomes among patients with atrial fibrillation (AF) in Nordic countries. We also tracked real-world trends in initiating OAC and the clinical outcomes. Methods We conducted a registry-based multinational cohort study of OAC-naive patients with an incident hospital diagnosis of AF in Denmark ( N = 61,345), Sweden ( N = 124,120), and Finland ( N = 59,855) and a CHA 2 DS 2 -VASc score of ≥1 in men and ≥2 in women between 2012 and 2017. Initiation of OAC therapy was defined as dispensing at least one prescription between 90 days before and 90 days after the AF diagnosis. Clinical outcomes included ischemic stroke, intracerebral hemorrhage, intracranial bleeding, other major bleeding, and all-cause mortality. Results The proportion of patients initiating OAC therapy ranged from 67.7% (95% CI: 67.5-68.0) in Sweden to 69.6% (95% CI: 69.2-70.0) in Finland, with intranational variation. The 1-year risk of stroke varied from 1.9% (95% CI: 1.8-2.0) in Sweden and Finland to 2.3% (95% CI: 2.2-2.4) in Denmark, with intranational variation. The initiation of OAC therapy increased with a preference for direct oral anticoagulants over warfarin. The risk of ischemic stroke decreased with no increase in intracranial and intracerebral bleeding. Conclusion We documented inter- and intranational variation in initiating OAC therapy and clinical outcomes across Nordic countries. Adherence to structured care of patients with AF could reduce future variation.

Recurrent myocardial infarction and emergency department visits: a retrospective study on the Stockholm Area Chest Pain Cohort.

BACKGROUND: Patients who experience acute myocardial infarction (AMI) are at risk of recurrent AMI. Contemporary data on recurrent AMI and its association with return emergency department (ED) visits for chest pain are needed. METHODS: This Swedish retrospective cohort study linked patient-level data from six participating hospitals to four national registers to construct the Stockholm Area Chest Pain Cohort (SACPC). The AMI cohort included SACPC participants visiting the ED for chest pain diagnosed with AMI and discharged alive (first primary diagnosis of AMI during the study period not necessarily the patient's first AMI). The rate and timing of recurrent AMI events, return ED visits for chest pain and all-cause mortality were determined during the year following index AMI discharge. RESULTS: Among 1 37 706 patients presenting to the ED with chest pain as principal complaint from 2011 to 2016, 5.5% (7579/137 706) were hospitalised with AMI. In total, 98.5% (7467/7579) of patients were discharged alive. In the year following index AMI discharge, 5.8% (432/7467) of AMI patients experienced ≥1 recurrent AMI event. Return ED visits for chest pain occurred in 27.0% (2017/7467) of index AMI survivors. During a return ED visit, recurrent AMI was diagnosed in 13.6% (274/2017) of patients. One-year all-cause mortality was 3.1% in the AMI cohort and 11.6% in the recurrent AMI cohort. CONCLUSIONS: In this AMI population, 3 in 10 AMI survivors returned to the ED for chest pain in the year following AMI discharge. Furthermore, over 10% of patients with return ED visits were diagnosed with recurrent AMI during that visit. This study confirms the high residual ischaemic risk and associated mortality among AMI survivors.

Geographical variation in persistence to oral anticoagulation therapy and clinical outcomes among patients with atrial fibrillation initiating therapy in Denmark, Sweden, Norway and Finland.

AIM: To examine inter-national and regional variations in persistence of oral anticoagulation (OAC) therapy and incidence of clinical outcomes and mortality, among patients with incident atrial fibrillation (AF) in the Nordic countries. METHODS: We conducted a registry-based multinational cohort study of OAC-naïve patients diagnosed with AF that redeemed at least one prescription of OAC after AF in Denmark (N = 25 585), Sweden (N = 59 455), Norway (N = 40 046) and Finland (N = 22 415). Persistence was dispensing at least one prescription of OAC from Day 365 after the first prescription and 90 days forward. RESULTS: Persistence was 73.6% (95% confidence interval 73.0-74.1) in Denmark, 71.1% (70.7-71.4) in Sweden, 89.3% (88.2-90.1) in Norway and 68.6% (68.0-69.3) in Finland. One-year risk of ischemic stroke varied between 2.0% (1.8-2.1) in Norway and 1.5% (1.4-1.6) in Sweden and 1.5% (1.3-1.6) in Finland. One-year risk of major bleeding other than intracranial bleeding varied between 2.1% (1.9-2.2) in Norway and 5.9% (5.6-6.2) in Denmark. One-year mortality risk varied between 9.3% (8.9-9.6) in Denmark and 4.2% (4.0-4.4) in Norway. CONCLUSION: In OAC-naïve patients with incident AF, persistence of OAC therapy and clinical outcomes vary across Denmark, Sweden, Norway and Finland. Initiation of real-time efforts are warranted to ensure uniform high-quality care across nations and regions.

Night work and breast cancer risk in a cohort of female healthcare employees in Stockholm, Sweden.

OBJECTIVES: Night work has been classified as probably carcinogenic to humans by the International Agency for Research on Cancer, but epidemiological evidence was considered limited due to variability in findings and potential bias. This study aimed to investigate the risk of breast cancer in a cohort with detailed and registry-based data on night work. METHODS: The cohort comprised 25 585 women (nurses and nursing assistants) employed 1 year or more between 2008 and 2016 in the healthcare sector in Stockholm. Information on work schedules was obtained from employment records. Breast cancer cases were identified from the national cancer register. HRs were estimated by a discrete time proportional hazards model, adjusting for age, country of birth, profession and childbirth. RESULTS: There were 299 cases of breast cancer, 147 in premenopausal and 152 in postmenopausal women. The adjusted HR of postmenopausal breast cancer in association with ever versus never working nights was 1.31 (95% CI 0.91 to 1.85). Eight or more years of night work was associated with an increased risk of postmenopausal breast cancer, HR=4.33 (95% CI 1.45 to 10.57), based on five cases only, though. CONCLUSIONS: This study is limited by a short period of follow-up and a lack of information on night work before 2008. Most exposure metrics showed no association with breast cancer risk, but there was an elevated risk of postmenopausal breast cancer in women after 8 or more years of night work.

Reperfusion by endovascular thrombectomy and early cerebral edema in anterior circulation stroke: Results from the SITS-International Stroke Thrombectomy Registry.

BACKGROUND: A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. AIM: To investigate the association of reperfusion with development of early CED after stroke thrombectomy. METHODS: From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. RESULTS: In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. CONCLUSION: In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Optimizing outcomes in heart failure: 2022 and beyond.

Although the development of therapies and tools for the improved management of heart failure (HF) continues apace, day-to-day management in clinical practice is often far from ideal. A Cardiovascular Round Table workshop was convened by the European Society of Cardiology (ESC) to identify barriers to the optimal implementation of therapies and guidelines and to consider mitigation strategies to improve patient outcomes in the future. Key challenges identified included the complexity of HF itself and its treatment, financial constraints and the perception of HF treatments as costly, failure to meet the needs of patients, suboptimal outpatient management, and the fragmented nature of healthcare systems. It was discussed that ongoing initiatives may help to address some of these barriers, such as changes incorporated into the 2021 ESC HF guideline, ESC Heart Failure Association quality indicators, quality improvement registries (e.g. EuroHeart), new ESC guidelines for patients, and the universal definition of HF. Additional priority action points discussed to promote further improvements included revised definitions of HF 'phenotypes' based on trial data, the development of implementation strategies, improved affordability, greater regulator/payer involvement, increased patient education, further development of patient-reported outcomes, better incorporation of guidelines into primary care systems, and targeted education for primary care practitioners. Finally, it was concluded that overarching changes are needed to improve current HF care models, such as the development of a standardized pathway, with a common adaptable digital backbone, decision-making support, and data integration, to ensure that the model 'learns' as the management of HF continues to evolve.

Admission glucose as a prognostic marker for all-cause mortality and cardiovascular disease.

BACKGROUND: Diabetes and prediabetes are known risk factors for cardiovascular disease and associated with increased mortality risk. Whether patients with a random elevated blood glucose level but no history of diabetes are at a higher mortality and cardiovascular risk is not entirely known. METHODS: A retrospective cohort study where patients (18-80 years) with no history of diabetes between 2006 and 2016 attending the emergency department (ED) in Sweden were included. Based on the first (index) blood glucose level patients were categorized into four groups: hypoglycemia (< 3.9 mmol/L), normal glucose tolerance (NGT) (3.9-7.8 mmol/L), dysglycemia (7.8-11.1 mmol/L), and hyperglycemia (> 11.1 mmol/L). Data was collected from four nationwide registers (National Patient Register, National Cause of Death Register, Prescribed Drug Register and Statistics Sweden). Cox regression was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality and cardiovascular outcomes using NGT as reference. RESULTS: 618,694 patients were included during a mean follow-up time of 3.9 years. According to the index blood glucose level: 1871 (0.3%) had hypoglycemia, 525,636 (85%) had NGT, 77,442 (13%) had dysglycemia, and 13,745 (2%) patients had hyperglycemia, respectively. During follow-up 44,532 (7.2%) deaths occurred. After multiple adjustments, mortality risk was highest in patients with hypoglycemia HR 2.58 (2.26-2.96) followed by patients with hyperglycemia HR 1.69 (1.63-1.76) and dysglycemia HR 1.16 (1.13-1.19). Risk for cardiovascular events: i.e., myocardial infarction, stroke and heart failure, were highest among patients with hyperglycemia HR 2.28 (2.13-2.44), HR 1.62 (1.51-1.74) and HR 1.60 (1.46-1.75), respectively. CONCLUSION: Patients with disturbed blood glucose level at ED admission have a higher mortality risk than patients with NGT. Patients with hyperglycemia have almost a two folded increased long-term mortality risk and more than a doubled risk for cardiovascular events compared to patients with NGT.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: a nationwide register-based study with family-based designs.

BACKGROUND: Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. METHODS: We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case-control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used. RESULTS: A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75-0.82). The corresponding odds ratio was 0.78 (95% CI 0.69-0.88) in the sibling and 0.72 (95% CI 0.66-0.79) in the cousin comparison analysis. CONCLUSIONS: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Perinatal risk factors for SUDEP: A population-based case-control study.

Sudden unexpected death in epilepsy (SUDEP) is a leading epilepsy-related cause of death. Researchers have highlighted the similarities between SUDEP and sudden infant death syndrome (SIDS), but perinatal risk factors such as those identified for SIDS have not been assessed previously for SUDEP. We conducted a population-based case-control study of 58 SUDEP individuals and 384 living epilepsy controls born after 1982, utilizing the Swedish Medical Birth Register together with other national health registers and individual medical records to examine if prenatal and perinatal factors are associated with SUDEP risk. We observed a 3-fold SUDEP risk increase for infants who were small for gestational age (SGA) (odds ratio [OR] 3.13; 95% confidence interval [CI] 1.05-9.30) and for those with an Apgar score of 0-6 compared to 9-10 at 10 min (OR 3.22; 95% CI 1.05-9.87). After adjusting for a number of known SUDEP risk factors, we observed that the Apgar score between 0 and 6 after 10 min had a 10-fold increased risk for SUDEP OR 10.37 (95% CI 1.49-72.01) and over a 2-fold risk for those born after the 40th gestational week (OR 2.42; 95% CI 1.03-5.65). The potential mechanisms linking low Apgar score, gestational age, and SGA to SUDEP risk remain to be explored.

Job control, job demands and job strain and suicidal behaviour among three million workers in Sweden.

OBJECTIVE: To investigate the association between job control, job demands and their combination (job strain) and suicide attempts and deaths among male and female workers in Sweden. METHODS: Job control and demands were measured separately for men and women using a job exposure matrix, which was linked to around three million individuals based on their occupational title in 2005. Suicide attempts and deaths were measured in the hospital and cause of death registers from 2006 to 2016. HRs were estimated using discrete proportional hazards models with annually updated age as the time axis. Models were adjusted for sociodemographic, family, health, labour market and childhood factors, as well as the time-varying effects of unemployment, sick leave and family factors during follow-up. RESULTS: Low job control was associated with an increased risk of suicide attempts and deaths among both men and women while high job demands tended to be associated with a decreased risk. The combination of job control and job demands (job strain) reflected the increased risk of low control jobs and the decreased risk of high demand jobs. Associations were attenuated but still present after adjustments. CONCLUSIONS: Low job control is related to suicide attempts and deaths, and this is only partially explained by important covariates measured both prebaseline and during follow-up. Attempts to increase job control among workers may be beneficial in preventing suicide.

Night and shift work characteristics and incident ischemic heart disease and atrial fibrillation among healthcare employees - a prospective cohort study.

OBJECTIVE: This study aimed to examine the effects of various aspects of night and shift work on the risk of incident ischemic heart disease (IHD) and atrial fibrillation (AF) using detailed and registry-based exposure data. METHODS: This prospective cohort study included >30 300 healthcare employees (eg, nurses, nursing assistants) employed for at least one year in Region Stockholm 2008-2016. Information on daily working hours was obtained from a computerized administrative employee register and outcomes from national and regional registers. Using discrete-time proportional hazard models, we analyzed the outcomes as functions of working hour characteristics the preceding year, adjusted for sex, age, country of birth, education, and profession. RESULTS: We observed 223 cases of IHD and 281 cases of AF during follow-up 2009-2016. The risk of IHD was increased among employees who the preceding year had permanent night shifts compared to those with permanent day work [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.06-2.43] and among employees working night shifts >120 times per year compared to those who never worked night (HR 1.53, 95% CI 1.05-2.21). When restricted to non-night workers, the risk of IHD was increased for employees having frequent quick returns from afternoon shifts. No increased risks were observed for AF. CONCLUSIONS: Night work, especially working permanent night shifts and frequent night shifts, is associated with an increased risk of incident IHD but not AF. Moreover, frequent quick returns from afternoon shifts (among non-night workers) increased IHD risk. Organizing work schedules to minimize these exposures may reduce IHD risk.

Outcome at age 7 of epilepsy presenting in the first 2 years of life. A population-based study.

OBJECTIVE: Existing data suggest that epilepsy presenting in the first few years of life carries a worse prognosis than later onset. However, studies are few and methods differ, making interpretations of data uncertain. This study analyzes outcome at age 7 and potential prognostic factors in a well-characterized population-based cohort with epilepsy onset during the first 2 years of life. METHODS: An incidence cohort of 116 prospectively identified cases of epilepsy with seizure onset before age 2 years was described in Stödberg et al. (2020). Cases were originally retrieved from the Stockholm Incidence Registry of Epilepsy (SIRE), which registered all cases with a first unprovoked epileptic seizure from September 1, 2001, in Northern Stockholm. Data on treatment and outcome at age 7 years were collected from electronic medical records and through interviews with parents. Outcome and potential prognostic factors were analyzed with descriptive statistics and multivariable log binomial regression analysis. RESULTS: Eleven children (9.5%) died before age 7. Polytherapy was common. Epilepsy surgery was performed in two children. At age 7 years, 61 of 116 children (53%) had been seizure-free for the last 2 years or longer. Intellectual disability was diagnosed in 57 of 116 children (49%), autism spectrum disorder in 13 (11%), and cerebral palsy in 28 (24%). West syndrome had a similar seizure remission rate but a worse cognitive outcome. There was no difference in outcome between first and second year onset. Six predictors, including etiology, remained associated with two or more outcome variables after regression analysis. SIGNIFICANCE: About half of children with infantile-onset epilepsy will become seizure-free and half of them will have intellectual disability. Etiology was confirmed as a major independent predictor of outcome. Our study contributes to a more firm knowledge base when counseling parents of infants diagnosed with epilepsy.