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Objective To identify occupations where employees with type 2 diabetes have a high risk of cardiovascular disease (CVD) and mortality, and their prevalence of CVD risk factors. This study can contribute in the creation of targeted interventions at the workplace. Research design and methods This nationwide registry-based study included all employees with type 2 diabetes born in Sweden in 1937–1979 (n = 180,620) and followed up in 2002–2015. We calculated age-standardized incidence (per 100,000 person-years) of all-cause and CVD mortality, ischemic heart disease (IHD) and stroke across the 30 most common occupations. Information on prognostic factors was retrieved from the National Diabetes Register. Results In males with type 2 diabetes, mortality rates were highest in manufacturing workers (1782) and machine operators (1329), and lowest in specialist managers (633). The risk of death at age 61–70 years was 21.8% in manufacturing workers and 8.5% in managers. In females with type 2 diabetes, mortality rates were highest in manufacturing workers (1150) and cleaners (876), and lowest in writers and artists (458); the risk of death at age 61–70 years was 12.4% in manufacturing workers and 4.3% in writers and artists. The same occupations also had relatively high incidences of CVD mortality, IHD and stroke. Occupational groups with poor prognosis had high prevalence of CVD risk factors including poor glycemic control, smoking and obesity. Conclusions Manufacturing workers, machine operators and cleaners with type 2 diabetes have two to three times higher mortality rates than managers, writers and artists with type 2 diabetes. Major health gains would be made if targeted workplace interventions could reduce CVD risk factors in these occupations.

Objectives The aim of the study was to examine the associations between heavy physical workload among middle-aged and older workers and disability pension due to any diagnosis, as well as musculoskeletal, psychiatric, cardiovascular or respiratory diagnoses. The population-based design made it possible to examine dose–response and potential gender differences in the associations. Methods About 1.8 million men and women aged 44–63 years and registered as living in Sweden in 2005 were followed regarding disability pension during 2006–2016, until ages 55–65 years. Mean values of physical workload and job control, estimated through gender-specific job-exposure matrices (JEMs), were assigned to individuals through their occupational titles in 2005. Exposure values were ranked separately for women and men and divided into quintiles. Associations were analyzed with Cox proportional-hazards regression. Results The analyses showed robust, dose–response associations between physical workload and disability pension with a musculoskeletal diagnosis in both genders: the adjusted hazard ratio and 95% confidence interval for those with the heaviest exposure was 2.58 (2.37–2.81) in women and 3.34 (2.83–3.94) in men. Dose–response associations were also seen in relation to disability pension with a cardiovascular or a respiratory diagnosis, though the hazard ratios were smaller. Physical workload was not associated with disability pension with a psychiatric diagnosis after adjustment for job control. Conclusion This study of the entire Swedish population of middle-aged and older workers suggests that higher degrees of physical workload may increase the risk of disability pension overall, and specifically with musculoskeletal, cardiovascular or respiratory diagnosis, in both women and men.

Background and introduction Accurate identification of clinical outcome events is critical to obtaining reliable results in cardiovascular outcomes trials (CVOTs). Current processes for event adjudication are expensive and hampered by delays. As part of a larger project to more reliably identify outcomes, we evaluated the use of machine learning to automate event adjudication using data from the SOCRATES trial (NCT01994720), a large randomized trial comparing ticagrelor and aspirin in reducing risk of major cardiovascular events after acute ischemic stroke or transient ischemic attack (TIA). Purpose We studied whether machine learning algorithms could replicate the outcome of the expert adjudication process for clinical events of ischemic stroke and TIA. Could classification models be trained on historical CVOT data and demonstrate performance comparable to human adjudicators? Methods Using data from the SOCRATES trial, multiple machine learning algorithms were tested using grid search and cross validation. Models tested included Support Vector Machines, Random Forest and XGBoost. Performance was assessed on a validation subset of the adjudication data not used for training or testing in model development. Metrics used to evaluate model performance were Receiver Operating Characteristic (ROC), Matthews Correlation Coefficient, Precision and Recall. The contribution of features, attributes of data used by the algorithm as it is trained to classify an event, that contributed to a classification were examined using both Mutual Information and Recursive Feature Elimination. Results Classification models were trained on historical CVOT data using adjudicator consensus decision as the ground truth. Best performance was observed on models trained to classify ischemic stroke (ROC 0.95) and TIA (ROC 0.97). Top ranked features that contributed to classification of Ischemic Stroke or TIA corresponded to site investigator decision or variables used to define the event in the trial charter, such as duration of symptoms. Model performance was comparable across the different machine learning algorithms tested with XGBoost demonstrating the best ROC on the validation set for correctly classifying both stroke and TIA. Conclusions Our results indicate that machine learning may augment or even replace clinician adjudication in clinical trials, with potential to gain efficiencies, speed up clinical development, and retain reliability. Our current models demonstrate good performance at binary classification of ischemic stroke and TIA within a single CVOT with high consistency and accuracy between automated and clinician adjudication. Further work will focus on harmonizing features between multiple historical clinical trials and training models to classify several different endpoint events across trials. Our aim is to utilize these clinical trial datasets to optimize the delivery of CVOTs in further cardiovascular drug development. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZenca Plc

Background Interest in the application of machine learning (ML) to the design, conduct, and analysis of clinical trials has grown, but the evidence base for such applications has not been surveyed. This manuscript reviews the proceedings of a multi-stakeholder conference to discuss the current and future state of ML for clinical research. Key areas of clinical trial methodology in which ML holds particular promise and priority areas for further investigation are presented alongside a narrative review of evidence supporting the use of ML across the clinical trial spectrum. Results Conference attendees included stakeholders, such as biomedical and ML researchers, representatives from the US Food and Drug Administration (FDA), artificial intelligence technology and data analytics companies, non-profit organizations, patient advocacy groups, and pharmaceutical companies. ML contributions to clinical research were highlighted in the pre-trial phase, cohort selection and participant management, and data collection and analysis. A particular focus was paid to the operational and philosophical barriers to ML in clinical research. Peer-reviewed evidence was noted to be lacking in several areas. Conclusions ML holds great promise for improving the efficiency and quality of clinical research, but substantial barriers remain, the surmounting of which will require addressing significant gaps in evidence.

The scientific debate following the initial formulation of the “bad luck” hypothesis in cancer development highlighted how measures based on analysis of variance are inappropriately used for risk communication. The notion of “explained” variance is not only used to quantify randomness, but also to quantify genetic and environmental contribution to disease in heritability coefficients. In this paper, we demonstrate why such quantifications are generally as problematic as bad luck estimates. We stress the differences in calculation and interpretation between the heritability coefficient and the population attributable fraction, the estimated fraction of all disease events that would not occur if an intervention could successfully prevent the excess genetic risk. We recommend using the population attributable fraction when communicating results regarding the genetic contribution to disease, as this measure is both more relevant from a public health perspective and easier to understand. Electronic supplementary material The online version of this article (10.1007/s10654-019-00573-8) contains supplementary material, which is available to authorized users.

Objective To investigate how weight loss by different diets impacts postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon. Methods In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomised to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP and glucagon measured during an OGTT are described. Results In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34 and 45% after 6 and 24 months in the Paleolithic diet group and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The area under the curve (AUC) for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase. Conclusions Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state.

Background Smoking and use of Swedish smokeless tobacco (snus) are associated with increased risk of type 2 diabetes (T2D). Our aim was to estimate the unique and shared genetic components of these traits and to what extent the association is explained by shared genetic factors. Methods We used twins of the Swedish Twin Registry who responded to a questionnaire between 1998 and 2006 (n = 40 247) and were followed until 2015 in the National Prescription and Patient Registries. We estimated hazard ratios (HRs) and odds ratios (ORs) for the association between smoking/snus use and T2D (n = 2130) and used structural equation models to estimate genetic and environmental variance components and genetic correlations. Results Current smokers [HR 1.69, 95% confidence interval (CI), 1.49–1.92] and snus users (HR 1.19, 95% CI 1.01–1.41) had an increased risk of T2D. In within-pair analyses of monozygotic twins, corresponding ORs were 1.36, 95% CI 0.75–2.46 (smoking) and 1.54, 95% CI 0.80–2.99 (snus). Heritability was 43% (95% CI 36–51) for ever smoking, 58% (95% CI 44– 70) for ever snus use and 66% (95% CI 59–72) for T2D. The genetic correlation with T2D was 18% (95% CI 1–35) for smoking and –6% (95% CI –24 to 4) for snus use, indicating that only a small fraction of the genetic influence is shared. Conclusions We could confirm that consumers of snus and cigarettes are at increased risk of T2D. Both snus use and smoking have strong genetic components, which appears to be attributable primarily to genes that are distinct from those promoting T2D.

Objectives Chronic Obstructive Pulmonary Disease (COPD) is a common respiratory disorder. Next to tobacco smoking, occupational exposure is the most important risk factor for COPD in high-income countries. To enable preventative measures, more knowledge is needed on which specific occupational exposures that are related to risk of developing COPD in men and women. Methods A population-based cohort was formed from subjects responding to the Stockholm Public Health Surveys in 2002, 2006, and 2010, followed up until 2014. The dataset was linked to a quantitative job exposure matrix via occupational titles from the 1990 nation-wide Population and housing census. We identified COPD among subjects having medication for COPD and/or reporting a physician's diagnosis of COPD. The gender-specific risks to develop COPD from occupational particle-exposure were estimated by proportional hazards regression model, adjusted for age and individual data on tobacco-smoking. Results Men exposed to respirable crystalline silica (RCS) (HR 1.46, CI 1.13–1.90), gypsum and insulation material (HR 1.56, CI 1.18–2.05), diesel exhaust (HR 1.18, CI 0.99–1.41) and high levels of particles from asphalt/bitumen (HR 1.71, CI 1.06–2.76) as well as welding fumes (HR 1.57, CI 1.12–2.21) had an increased smoking-adjusted risk for developing COPD. An increased risk was also observed among women highly exposed to various organic particles from soil, leather, plastic, soot, animal, textile, flour (HR 1.53, CI 1.15–2.04). Furthermore, a significant positive exposure-response trend was found among men exposed to RCS, iron dust, gypsum and insulation material, and diesel exhaust. A tendency towards an exposure-response relationship was also seen among both men and women exposed to welding fumes and various organic particles, and among men exposed to particles from asphalt/bitumen. The population attributable fraction for COPD from occupational exposure to particles was 10.6% among men and 6.1% among women. Conclusions This study indicates an increased smoking-adjusted risk of developing of COPD due to occupational exposure to particles. A positive exposure-response relationship was found for RCS, gypsum and insulation, diesel exhaust, and welding fumes. Also, exposure to high levels of asphalt/bitumen and various organic particles was associated with a higher risk for COPD. Reduction of these exposures in the work environment are important to prevent future cases of COPD. More studies are needed to investigate exposure-response relationships further, but this study indicates that the European occupational exposure limit (OEL) for RCS needs to be re-evaluated.

Purpose Red meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes. Methods Analyses were based on Swedish case–control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Multivariable-adjusted ORs in relation to self-reported processed and unprocessed red meat intake were estimated by conditional logistic regression models. Attributable proportion (AP) due to interaction was used to assess departure from additivity of effects. Results Consumption of processed red meat was associated with increased risk of LADA (per one servings/day OR 1.27, 95% CI 1.07–1.52), whereas no association was observed for unprocessed red meat. For T2D, there was no association with red meat intake once BMI was taken into account. The combination of high (> 0.3 servings/day vs. less) processed red meat intake and high-risk HLA-DQB1 and -DRB1 genotypes yielded OR 8.05 (95% CI 4.86–13.34) for LADA, with indications of significant interaction (AP 0.53, 95% CI 0.32–0.73). Results were similar for the combination of FHD-T1D and processed red meat. No interaction between processed red meat intake and FHD-T2D or risk variants of TCF7L2 was seen in relation to LADA or T2D. Conclusion Consumption of processed but not unprocessed red meat may increase the risk of LADA, especially in individuals with FHD-T1D or high-risk HLA genotypes.

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Purpose Sweetened beverage consumption is associated with type 2 diabetes (T2D) and LADA. We investigated to what extent this association is mediated by BMI and whether it is modified by genotypes of HLA, TCF7L2 rs7903146, or FTO rs9939609. Methods Swedish case–control data including incident cases of LADA (n = 386) and T2D (n = 1253) with matched population-based controls (n = 1545) was used. We estimated adjusted ORs of diabetes (95% CI) in relation to sweetened beverage intake (per daily 200 mL serving) and genotypes. The impact of BMI was estimated using causal mediation methodology. Associations with HOMA-IR and HOMA-B were explored through linear regression. Results Sweetened beverage intake was associated with increased risk of LADA (OR 1.15, 95% CI 1.03–1.29) and T2D (OR 1.21, 1.11–1.32). BMI was estimated to mediate 17% (LADA) and 56% (T2D) of the total risk. LADA was associated with risk variants of HLA (3.44, 2.63–4.50) and TCF7L2 (1.27, 1.00–1.61) but not FTO. Only among non-carriers of high-risk HLA genotypes was sweetened beverage intake associated with risk of LADA (OR 1.32, 1.06–1.56) and HOMA-IR (beta = 0.162, p = 0.0047). T2D was associated with TCF7L2 and FTO but not HLA, and the risk conferred by sweetened beverages appeared modified by FTO (OR 1.45, 95% CI 1.21–1.73 in non-carriers). Conclusions Our findings suggest that sweetened beverages are associated with LADA and T2D partly through mediation by excess weight, but possibly also through other mechanisms including adverse effects on insulin sensitivity. These effects seem more pronounced in individuals without genetic susceptibility.

OBJECTIVE Given the increasing attention being paid to potential strategies for sudden unexpected death in epilepsy (SUDEP) prevention, we analyzed the circumstances of SUDEP and its incidence in relation to time of year, week, and day. METHODS Prospective case-series based on persons with an International Classification of Diseases (ICD-10) code for epilepsy in the Swedish Patient Registry 1998-2005, who were alive on June 30, 2006 (n = 60 952). Linkage to the National Cause-of-Death Registry identified all deaths from July 2006 through December 2011, with epilepsy mentioned on death certificate, together with all deaths during 2008 (n = 3166). Death certificates, medical charts, autopsy, and police reports were reviewed to identify SUDEP cases and related circumstances. Autopsied non-SUDEP deaths (n = 60) from the study population served as a reference. RESULTS There were 329 SUDEPs (63% men) of which 167 were definite, 89 probable, and 73 possible. SUDEP cases were younger at death (50.8 years) than non-SUDEP deaths (73.3 years) (P < .001) and more likely to be male (63% vs 55%, P = .0079). Most SUDEP cases died at night (58%), at home (91%), and 65% were found dead in bed. When documented, 70% were found in prone position. In 17%, death was witnessed and in 88% of these, a seizure was observed. Of the 329 SUDEP cases, 71% were living alone and 14% shared a bedroom. Compared to an autopsied non-SUDEP reference group, definite SUDEPs were more likely to die at home, during the night, unwitnessed, in the prone position, to live alone, and more often with a preceding seizure. SIGNIFICANCE SUDEP cases live alone, die unwitnessed at home at night, with indication of a preceding seizure, supporting the critical role of lack of supervision. These facts need to be considered in the development of preventive strategies.

ObjectiveTo study the risk for injuries/accidents in people with newly diagnosed epileptic seizures in relation to comorbidities.MethodsBetween September 1, 2001, and August 31, 2008, individuals in northern Stockholm with incident unprovoked seizures (epilepsy; n = 2,130) were included in a registry. For every epilepsy patient, 8 individuals matched for sex and inclusion year (n = 16,992) were randomly selected as references from the population of the catchment area. Occurrence of injuries/accidents was monitored through the national patient and cause of death registers until December 31, 2013. These registers also provided information on comorbidities (e.g., brain tumor, stroke, psychiatric disease, diabetes mellitus).ResultsInjury/accident was demonstrated in 1,033 epilepsy cases and 6,202 references (hazard ratio [HR] 1.71, 95% confidence interval 1.60–1.83). The excess risk was seen mainly during the first 2 years after diagnosis. Sex and educational status had no significant effect on HR. The risk was normal in children but increased in adults. Highest HR was seen for drowning, poisoning, adverse effect of medication, and severe traumatic brain injury. Compared to references without comorbidities, HR was 1.17 (1.07–1.28) in epilepsy without comorbidities, 4.52 (4.18–4.88) in references with comorbidities, and 7.15 (6.49–7.87) in epilepsy with comorbidities.ConclusionPresence of comorbidities should be considered when counseling patients with newly diagnosed epilepsy concerning risk for injuries/accidents. Early information is important, as the risk is highest during the first 2 years following seizure onset.

Objectives Previous studies on firefighters indicate an increased risk of cancer although findings regarding which cancer sites are in excess have been inconsistent. The aim of this study was to investigate the cancer incidence among Swedish firefighters. Methods This updated cohort study included 1080 men who worked at least 1 year as a firefighter in the city of Stockholm, Sweden during 1931–1983. First-time diagnoses of cancer were identified through the Swedish Cancer Registry from 1958 until 2012. Employment as a firefighter was determined from the annual fire station enrolment records. Standardized incidence ratios were calculated using the Stockholm population as reference. Results Firefighters in Stockholm had a low overall risk of cancer (SIR = 0.81 95% CI 0.71–0.91). However, firefighters were at an increased risk of stomach cancer (SIR = 1.89 95% CI 1.25–2.75). Firefighters had significantly low risks for prostate cancer (SIR = 0.68 95% CI 0.52–0.87) and malignant melanoma of the skin (SIR = 0.30 95% CI 0.06–0.88). There was a statistically significant trend of increasing overall risk of cancer with increasing employment duration, although there was still no excess of cancer overall in any of the categories of employment duration. Conclusion Stockholm firefighters had an increased risk of stomach cancer but a low overall risk of cancer. The trend of increasing overall risk of cancer with increasing employment duration could potentially be related to the carcinogenic exposures at work.

Aim: It has been suggested that experiencing serious life events may promote Type 1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. Methods: Analysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016. Self-reported information on life events including conflicts, divorce, illness/accidents, death and financial problems experienced during the 5 years preceding diagnosis/index year was used. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated by logistic regression and adjusted for age, sex, BMI, family history of diabetes, smoking, physical activity and education. Results: Overall there was no association between experience of any life event and either LADA (OR 0.86, 95% CI 0.68-1.08) or Type 2 diabetes (OR 1.00, 95% CI 0.83-1.21). The results were similar for individual events as well as in separate analysis of men and women. Similar results were seen in more autoimmune LADA (glutamic acid decarboxylase antibodies > median) [OR (any life event) 0.88, 95% CI 0.64-1.21] and in LADA carriers of the high-risk HLADR4-DQ8 genotype (OR 0.89, 95% CI 0.61-1.29). Conclusions: Our findings indicate that experience of a serious life event, including the death of a family member, divorce or financial problems, is not associated with an increased risk of LADA, overall or in genetically susceptible individuals.

Objectives Work in chemical laboratories is associated with exposure to chemicals, of which some are known or suspected carcinogens. A cohort study of laboratory workers in Stockholm followed until 1992 showed an excess of hematolymphatic malignancies in chemical laboratories and an excess of breast cancer among women working for more than 10 years in such laboratories. The follow-up of this cohort has now been extended by 20 years. Methods The cohort comprised 2245 female laboratory workers who are employed for >1 year from 1950 to 1989. Information on employment periods and type of laboratory (‘chemical’ or ‘non-chemical’) was obtained from employee registers. Cancer diagnoses from 1958 to 2012 were obtained from the Swedish Cancer Registry. Results There were 383 cases of cancer (SIR=0.93 (95% CI 0.84 to 1.02)). The risk of breast cancer was elevated, of borderline statistical significance, among those who had worked for at least 10 years in chemical laboratories (SIR=1.41 (95% CI 0.99 to 1.95) 36 cases). The breast cancer risk was especially high in women who had worked for more than 10 years in chemical labs before 1970 (SIR=3.76 (95% CI 1.72 to 7.14), nine cases). There was no excess of breast cancer in non-chemical labs (SIR=0.77 (95% CI 0.54 to 1.07), 35 cases). The number of hematolymphatic cancer was no longer significantly elevated. Conclusions The increased risk of breast cancer, as well as the earlier noted excess of hematolymphatic malignancies, may be related to exposure to carcinogenic chemicals/organic solvents (eg, benzene) used in chemical laboratories, especially during earlier periods.

Objective The population pharmacokinetics of ticagrelor and its active metabolite AR-C124910XX were characterized following ticagrelor 60 mg or 90 mg twice daily oral long-term treatment in 4,426 patients with a history of myocardial infarction. Methods The ticagrelor and AR-C124910XX plasma concentration-time data were described by one-compartment models with first-order absorption or metabolite formation and elimination. Results Systemic exposure to ticagrelor and AR-C124910XX were stable over time. Ticagrelor apparent clearance (CL/F) was 17 L/h for the 60-mg and 15.4 L/h for the 90-mg dose. The CL/F of AR-C124910XX was 11.1 L/h for the 60-mg and 9.95 L/h for the 90-mg dose. Both ticagrelor and AR-C124910XX CL/F were independently influenced by body weight, sex, age, smoking, and Japanese ethnicity. Female sex and age > 75 years were the only categorical covariates, having more than 20% effect on AR-C124910XX CL/F. Ticagrelor CL/F was 6% higher and 11% lower, whereas AR-C124910XX CL/F was 26% higher and 34% lower for patients weighing 110 and 50 kg, respectively, compared with an 83 kg patient. Conclusions The small differences in exposure to both ticagrelor and AR-C124910XX between demographic subgroups were in accordance with the consistent efficacy and safety outcomes observed across the population. The results were similar to those observed previously in patients with acute coronary syndromes. .

Previous research shows how powerful interests outside the media have the upper hand in the relationship between journalists and sources. This conclusion is sometimes challenged by the fact that journalists might control framing, follow-ups, and the packaging of stories. This article seeks to contribute to the field of journalist–source studies by focusing on aspects of the digital media environment, with a focus on the breakthrough of online media and social media. The purpose of the article is to analyze how external sources, such as public authorities, perceive the power relation to the news media in crisis communication. The empirical data used is semi-structured interviews conducted with 26 communication managers, communication staff, and crisis managers at authorities and nationally owned companies during four societal crises in Sweden in 2012–2014. The public authorities perceive that the digital media environment gives them control of the information flow in relation to journalists. Even if there ...

Background and Purpose: Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees’ independence and effectiveness. Methods: An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees. Results and Conclusions: Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee’s independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and experience with trials in general to ensure that the data monitoring committee has access to timely, reliable, and readily interpretable insights about emerging evidence in the clinical trial. Contracts engaging data monitoring committee members for industry-sponsored trials should have language customized to the unique responsibilities of data monitoring committee members rather than use language appropriate to consultants for product development. Regulatory scientists would benefit from experiencing data monitoring committee service that does not conflict with their regulatory responsibilities.

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable. Yet the benefits of relying on real-world data sources must be weighed against difficulties with ensuring data integrity and completeness. Additionally, appropriately monitoring patient safety in randomized trials of new drugs using healthcare system data that might not be available in real time can be quite difficult. Recognizing that these and other concerns are critical to the development and acceptability of PCTs, a group of stakeholders from academia, industry, professional organizations, regulatory bodies, government agencies, and patient advocates discussed a path forward for PCT growth and sustainability at a think tank meeting entitled "Monitoring and Analyzing Data from Pragmatic Streamlined Randomized Clinical Trials," which took place in January 2019 (Washington, DC). The goals of this meeting were to: (1) evaluate study design and methodological options specific to PCTs that have the potential to yield high-quality evidence; (2) discuss best practices to ensure data quality in PCTs; and (3) identify appropriate methods for study monitoring. Proceedings from the think tank meeting are summarized in this manuscript.

ObjectiveWe conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP).MethodsThe study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP).ResultsExperiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP.ConclusionsIndividuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

Objective We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Methods We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). Results The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. Conclusions Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.

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Aims/hypothesis The workplace is a potentially important arena for prevention of type 2 diabetes and the first step is to identify occupations where the disease is common and/or risk is high. Therefore, our aim was to analyse incidence and prevalence of type 2 diabetes across all occupational groups in Sweden. Methods This nationwide study included all Swedish citizens born between 1937 and 1979 and gainfully employed between 2001 and 2013 (N = 4,550,892), and followed for a diagnosis of diabetes from 2006 to 2015 (n = 201,717) through national registers. Prevalence in 2013 (mean age 51 years; range 35–67) and age-standardised incidence (per 1000 person-years) were analysed across the 30 most common occupations among men and women. Information on BMI, physical fitness and smoking was obtained through the National Conscription (mean age 18) and Medical Birth Registers (mean age 29). Results Prevalence of type 2 diabetes was 5.2% in men and 3.2% in women; in men it was highest among motor vehicle drivers (8.8%) and in women it was highest among manufacturing workers (6.4%). Incidence varied dramatically across occupational groups. In men, it was highest among manufacturing workers (9.41) and professional drivers (9.32) and lowest among university teachers (3.44). In women, incidence was highest in manufacturing workers (7.20) and cleaners (6.18) and lowest in physiotherapists (2.20). We found major differences in the prevalence of being overweight and smoking and in the level of physical fitness across these occupational groups even at young ages. Conclusions/interpretation Professional drivers, manufacturing workers and cleaners have a threefold increased risk of type 2 diabetes compared with university teachers and physiotherapists. These differences most likely reflect dramatic differences in the prevalence of lifestyle risk factors. If workplace interventions could reduce weight and increase physical activity among employees in these occupations, major health gains may be made.

The present article investigates two questions: What determines citizens’ use of different media to seek information in a crisis situation, and what influences their evaluation of the information found. The case analysed is a major fire at a chemical storage facility in the harbour of Halmstad in Sweden, where there was a risk of toxic fumes reaching the city and its approximately 60,000 inhabitants. The study is part of a larger project, financed by the Swedish Civil Contingencies Agency, and in this part, focus group interviews are analysed. The results point to an interaction between citizens’ perception of the world, the perceived information, and the development of how the situation is regarded, where sensemaking is the pivotal concept.

OBJECTIVE Smoking is an established risk factor for type 2 diabetes. In contrast, it has been proposed that smoking may reduce the risk of latent autoimmune diabetes in adults (LADA), but studies are scarce. We aimed to study the impact of smoking on LADA and type 2 diabetes risks. RESEARCH DESIGN AND METHODS We used data from a Swedish case-control study including incident case patients with LADA (GAD antibody [GADA] positive, n = 377) and type 2 diabetes (GADA negative, n = 1,188) and control subjects randomly selected from the population (n = 1,472). We calculated odds ratios (ORs) with 95% CIs by logistic regression, adjusted for age, sex, BMI, family history of diabetes, and alcohol consumption. RESULTS There was no indication of reduced risk of LADA in smokers; instead, heavy smoking was associated with an increased risk of LADA (OR 1.37, 95% CI 1.02–1.84). Heavy smokers had higher levels of HOMA of insulin resistance (9.89 vs. 4.38, P = 0.0479) and HOMA of β-cell function (55.7 vs. 42.5, P = 0.0204), but lower levels of GADA (75 vs. 250, P = 0.0445), compared with never smokers. Smokers also displayed an increased risk of type 2 diabetes (OR in ever smokers 1.53, 95% CI 1.25–1.88). CONCLUSIONS In this large population of LADA patients, we did not observe a protective effect of smoking on autoimmunity and the risk of LADA. A protective effect could possibly be masked by a smoking-induced aggravation of insulin resistance, akin to the diabetogenic effect seen in individuals with type 2 diabetes.

Prompted by a recent report on declining incidence of sudden unexpected death in epilepsy (SUDEP) following implantation of a vagus nerve stimulator (VNS), we analyzed SUDEP risk over 6 years in a population-based cohort of 60 952 epilepsy patients in Sweden. All deaths from July 1, 2006 through December 31, 2011, were identified. Those with epilepsy mentioned on the death certificate were adjudicated for SUDEP using medical records and autopsy reports. In all, 292 SUDEP cases were identified. Comparing the first years (2006-2007) with the subsequent 4 years (2008-2011), the crude and standardized (to the US 2000 population) incidence of SUDEP (whether or not possible SUDEP was included) was significantly lower during the second time period; Incidence rate ratios based on standardized rates was estimated at 0.76 (95% confidence interval [CI] 0.60-0.97, P = .027) for SUDEP. The incidence of SUDEP decreased by 7% per year during the 6-year follow-up. Our data thus suggest that, for unknown reasons, incidence of SUDEP decreases with duration of follow-up. This has implications for patient counseling as well as for the design of studies attempting to assess the effectiveness of an intervention against SUDEP, which clearly needs to include a control group.

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide range of possible uses in clinical trials, including assisting with prestudy feasibility assessment, patient recruitment, and data capture in care delivery. To fully appreciate these opportunities, health care stakeholders must come together to face critical challenges in leveraging EHR data, including data quality/completeness, information security, stakeholder engagement, and increasing the scale of research infrastructure and related governance. Leaders from academia, government, industry, and professional societies representing patient, provider, researcher, industry, and regulator perspectives convened the Leveraging EHR for Clinical Research Now! Think Tank in Washington, DC (February 18-19, 2016), to identify barriers to using EHRs in clinical research and to generate potential solutions. Think tank members identified a broad range of issues surrounding the use of EHRs in research and proposed a variety of solutions. Recognizing the challenges, the participants identified the urgent need to look more deeply at previous efforts to use these data, share lessons learned, and develop a multidisciplinary agenda for best practices for using EHRs in clinical research. We report the proceedings from this think tank meeting in the following paper.

Introduction The development of chronic obstructive pulmonary disease (COPD) has previously been linked to occupational exposure. The aim of this register-based study was to assess the risk for being diagnosed with COPD in subjects with occupational exposure to organic and inorganic dust. Methods The study population included 20 069 men and 23 572 women from the Stockholm Public Health Cohort. Information of occupation was derived from 1985 or 1990 censuses. New cases of COPD were identified for the period 1990–2010. COPD cases were defined as either a self-reported COPD diagnosis by a physician or a prescription for anticholinergic drugs. A quantitative job-exposure matrix provided information on organic dust (wood dust, paper dust, textile dust, oil mist, cooking fumes, other organic dust) and inorganic dust (respirable crystalline silica dust, iron dust, other inorganic dust and fibres). Analyses were adjusted for age and smoking. Results Exposure to any organic dust was associated with an increased risk of COPD in men (HR 1.32, 95% CI: 1.12 to 1.56), and in women (HR 1.21, CI: 1.00 to 1.46). Among organic dusts, men exposed to paper dust had a HR of 1.39 (CI: 1.01 to 1.92). In women, paper dust (HR 1.56, CI: 1.08 to 2.26) and other organic dust (HR 1.48, CI: 1.12 to 1.96) were associated with an increased risk. Exposure to any inorganic dust was associated with an increased risk in men (HR 1.39, CI: 1.15 to 1.67) and among these, risks for respirable crystalline silica dust (HR 1.46, CI: 1.13 to 1.90) and other inorganic dust and fibres (HR 1.56, CI: 1.18 to 2.05) were increased. Analysis of women exposed to inorganic dusts were not possible due to too few subjects. Conclusion This study confirms an increased incidence of COPD in Swedish workers exposed to organic and inorganic dusts. Health care personnel should consider not only smoking but also occupational exposure when informing COPD-patients of potential risk exposures.

Background Hip fracture is a common cause of disability and mortality among the elderly. Declining incidence trends have been observed in Sweden. Still, this condition remains a significant public health problem since Sweden has one of the highest incidences worldwide. Yet, no Swedish lifetime risk or survival trends have been presented. By examining how hip fracture incidence, post-fracture survival, as well as lifetime risk have developed between 1995 and 2010 in Sweden, this study aims to establish how the burden hip fractures pose on the elderly changed over time, in order to inform initiatives for improvements of their health. Material and Methods The entire Swedish population 60 years-old and above was followed between 1987 and 2010 in the National Patient Register and the Cause of Death Register. Annual age-specific hip fracture cumulative incidence was estimated using hospital admissions for hip fractures. Three-month and one-year survival after the first hip fracture were also estimated. Period life table was used to assess lifetime risk of hip fractures occurring from age 60 and above, and the expected mean age of the first hip fracture. Results The age-specific hip fracture incidence decreased between 1995 and 2010 in all ages up to 94 years, on average by 1% per year. The lifetime risk remained almost stable, between 9% and 11% for men, and between 18% and 20% for women. The expected mean age of a first hip fracture increased by 2.5 years for men and by 2.2 years for women. No improvements over time were observed for the 3-month survival for men, while for women a 1% decrease per year was observed. The 1-year survival slightly increased over time for men (0.4% per year) while no improvement was observed for women. Conclusions The age-specific hip fracture incidence has decreased over time. Yet the lifetime risk of a hip fracture has not decreased because life expectancy in the population has increased in parallel. Overall, survival after hip fracture has not improved.

Summary Objective To quantify the risk of unprovoked seizures after traumatic brain injury (TBI) Methods We used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case–control study, including 1,885 cases with incident unprovoked seizures from September 1, 2000 through August 31, 2008, together with 15,080 matched controls. Information of prior hospitalizations for TBI was obtained through record linkage with the Swedish National Inpatient Registry for the period 1980–2008. Relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail. Results After hospitalization for mild TBI, the RR was 2.0 (95% confidence interval [CI] 1.5–2.7). The RR was higher after brain contusion (5.9, 95% CI 2.4–15.0) or intracranial hemorrhage (ICH) (4.5, 95% CI 2.2–9.0), whereas a combination of both diagnoses led to a further sevenfold increase in RR (42.6, 95% CI 12.2–148.5). The risk was greatest during the first 6 months after severe TBI (RR 48.9, 95% CI 10.9–218.9) or mild TBI (RR 8.1, 95% CI 3.1–21.7), but was still elevated >10 years after any TBI. Significance Herein we present a large population-based case–control study on TBI as a risk factor for unprovoked epileptic seizures, including cases of all ages with individually validated seizure diagnoses. The risk for epileptic seizures was substantially increased after TBI, especially during the first 6 months after the injury and in patients with a combination of ICH and brain contusion.

Respirable silica dust is a common and serious occupational hazard to workers´ health. Inhalation causes inflammation which is a risk factor for cardiovascular disease, but few studies have confirmed a relationship. In the present study, we have investigated the risk of myocardial infarction in workers exposed to respirable silica dust, as well as differences in sensitivity based on gender. The cohort consists of manual workers in the Swedish National Census in 1980 with information on demography and occupation (1960–1990). Information on hospital admissions for acute myocardial infarction and cause of death were obtained from nation-wide registers. A job-exposure matrix was used to assess lifetime occupational exposure. No smoking data was available. Among manual workers ever exposed to respirable silica dust, the hazard ratio (HR) for acute myocardial infarction was 1.29 (95% Confidence Interval (CI) 1.15–1.46) for women, and 1.02 (95% CI 1.00–1.04) for men, respectively. In the highest quartile of cumulative exposure the HR was 1.66 (95% CI 1.27–2.18) for women, and 1.06 (95% CI 1.03–1.10) for men, respectively. We found a dose-response relationship between exposure and disease. The population etiologic fraction of disease for women was 11%. In absolute numbers this corresponds to 7 extra cases/10000 person years among exposed women in the highest exposed group. In conclusion, occupational exposure to respirable silica dust was in this study related to an increased risk for acute myocardial infarction in women, indicating a slightly increased sensitivity of the exposed women.

Objectives The purpose of this study was to explore the pattern of mortality above the age of 100 years. In particular, we aimed to examine whether Scandinavian data support the theory that mortality reaches a plateau at particularly old ages. Whether the maximum length of life increases with time was also investigated. Methods The analyses were based on individual level data on all Swedish and Danish centenarians born from 1870 to 1901; in total 3006 men and 10 963 women were included. Birth cohort-specific probabilities of dying were calculated. Exact ages were used for calculations of maximum length of life. Whether maximum age changed over time was analysed taking into account increases in cohort size. Results The results confirm that there has not been any improvement in mortality among centenarians in the past 30 years and that the current rise in life expectancy is driven by reductions in mortality below the age of 100 years. The death risks seem to reach a plateau of around 50% at the age 103 years for men and 107 years for women. Despite the rising life expectancy, the maximum age does not appear to increase, in particular after accounting for the increasing number of individuals of advanced age. Conclusion Mortality among centenarians is not changing despite improvements at younger ages. An extension of the maximum life span and a sizeable extension of life expectancy both require reductions in mortality above the age of 100 years. This article is protected by copyright. All rights reserved.

Objectives Firefighters are potentially exposed to carcinogens during work, such as benzene, benso(a)pyrene, arsenic, asbestos and silica dust. There are previous studies indicating an increased cancer risk among firefighters. The aim was to study risk of cancer in Swedish firefighters. Methods We updated a previous cohort study of firefighters in Stockholm, comprising 1 080 men who worked at least 1 year as a firefighter during 1931–1983. They were followed regarding cancer incidence (in the National Cancer Register) from 1958–2012, adding 26 years of follow-up compared to the previous study. We also updated the information of employment duration, by annual records at the fire stations. We calculated standardised incidence ratios (SIR) with the male population in Stockholm as reference. Results The overall cancer incidence was low (SIR=0.81, 95% CI=0.71–0.91), but there was a trend of increasing cancer incidence with increasing employment duration (p=0.03). There was an increased incidence of stomach cancer (SIR=1.89, 95% CI=1.25–2.75). The risk was significantly low for prostate cancer (SIR=0.68, 95% CI=0.52–0.87) and for malignant melanoma of the skin (SIR=0.30, 95% CI=0.06–0.88). Conclusions We found no increased cancer incidence overall in Swedish firefighters, although the increasing incidence with increasing work duration indicates a possible carcinogenic effect of exposures at work. The cause of the increased incidence of stomach cancer is uncertain but could possibly be due to exposure to asbestos or silica dust, although this is quite speculative.

According to Swedish National Board of Health and Welfare statistics, a dramatic decrease in both the incidence of and mortality from acute myo-cardial infarction has been seen in the past two deca...

In 2009, 9108 vulnerable road users (VRUs; pedestrians and bicyclists) died in the EU and 4722 in the US. Active safety systems, that is intelligent systems able to predict and prevent crashes, may significantly help to reduce VRU fatalities and injuries; however, current active safety systems for VRUs are only found on high-end vehicles, only support the host vehicle driver, and do not make use of wireless communication. The scope of this study is to describe the set-up and real-world verification of a platform to enable active safety systems for VRU. This platform is carried by VRUs and may support multiple road users using wireless communication. A simple conceptual application, addressing pedestrian safety at crossings, was developed to test the platform. This application was not cooperative (i.e. did not support multiple road users with wireless communication). The results presented in this study suggest that such a platform can be employed (i) as a logger for naturalistic studies on VRUs, (ii) to better understand VRU behaviour and accident causation and (iii) as a basis for the development of novel active safety applications, running on portable devices, such as future generation smart phones, and possibly enabled by wireless communication.

Night and shift work is common in industry and service that must be functional 24 hour. Night work disrupts the circadian rhythm, and is potentially linked to an excess of cancer (especially breast cancer), cardiovascular disease, pregnancy complications, as well as to psychical effects. Large studies with detailed and objectively collected data on working hours are needed to confirm causal associations and develop practical advice on how shift schedules should be planned in order to minimize negative health effects.Stockholm County Council employs a high number of health care workers of which many are working in shifts. We have formed a cohort of those employed from 2008 to 2016, 45 000 women and 15 000 men. The computerized employment register holds individual records on working hours day by day in retrospect since 2008, and information on night work since year 2000. Information on cancer incidence, hospital discharge diagnoses of cardiovascular disease, pregnancy outcome, and causes of sick-leave have been obtained from national central registers.There were typically three work shifts: morning shifts (07–15), afternoon shifts (14–21), and night shifts (21–07). Non shift-workers typically worked (08–17). So far, we have investigated work shift patterns for those with a high percentage of night work: nurses, assistant nurses and midwives. Among these, 22% worked at least one night per month, and 15% worked at least 5 nights per month in 2009, which increased slightly to 23% and 16% respectively in 2016. It was common to work several nights in a row: in 2009 13.8% worked at least 3 consecutive nights or more per month, which increased to 15.5% in 2016. Only 0.6% worked 5 consecutive nights or more per month.Analyses of cancer, pregnancy outcome, cardiovascular disease and psychical outcomes are planned for 2019.

OBJECTIVE Knowledge on mortality in autoimmune diabetes with adult onset is limited. We compared mortality in adult-onset autoimmune diabetes and type 2 diabetes, taking into account metabolic risk factors, HbA1c, lifestyle, and socioeconomic factors. RESEARCH DESIGN AND METHODS Participants of the population-based HUNT2 Study (second survey of the Norwegian HelseUndersøkelsen i Nord-Trøndelag Study; n = 64,264) were followed up prospectively for mortality in the Cause of Death Registry (1995–2009). Diabetes with onset ≥35 years was classified as autoimmune diabetes in adults if anti-GAD was positive (n = 208) and as type 2 diabetes if anti-GAD was negative (n = 2,425). Hazard ratios (HRs) of mortality from all-causes, cardiovascular disease (CVD), and ischemic heart disease (IHD) were calculated using the Cox proportional hazards model. RESULTS Prevalence of the metabolic syndrome was lower in autoimmune diabetes than in type 2 diabetes (55 vs. 77%, P < 0.001). Still, autoimmune diabetes was associated with an increased risks of mortality from all-causes (HR 1.55 [95% CI 1.25–1.92]), CVD (1.87 [1.40–2.48]), and IHD (2.39 [1.57–3.64]), equally high as in type 2 diabetes in analyses where individuals without diabetes were used as the reference group. The increased risk was not explained by overweight, lifestyle, socioeconomic position, or presence of the metabolic syndrome. Excess mortality was primarily observed in individuals with elevated HbA1c. CONCLUSIONS Mortality in autoimmune diabetes was as high as in type 2 diabetes, despite a more favorable baseline metabolic risk profile. Excess risk was associated with poor glycemic control. The results from this study, the largest so far on mortality in autoimmune diabetes in adults, underscore the importance of optimal treatment modalities to improve survival in adult-onset autoimmune diabetes.

OBJECTIVE To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes. RESEARCH DESIGN AND METHODS We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984–2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models. RESULTS The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30–0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18–0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10–1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23–0.57). CONCLUSIONS In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.

Objective:To identify all cases of sudden unexpected death in epilepsy (SUDEP) among people in Sweden during 1 year and to determine the SUDEP incidence in relation to age, sex, and psychiatric comorbidity.Methods:We included all individuals with a hospital-based ambulatory care or hospital discharge diagnosis of epilepsy in the Swedish National Patient Registry during 1998–2005 who were alive on January 1, 2008. Deaths during 2008 were identified by linkage to the National Cause of Death Registry. Death certificates, medical charts, and police and autopsy reports were extensively reviewed to identify SUDEP cases.Results:Of 57,775 epilepsy patients alive on January 1, 2008, 1,890 died (3.3%) during 2008. Of these, 99 met the Annegers SUDEP criteria (49 definite, 19 probable, and 31 possible). SUDEP accounted for 5.2% of all deaths and 36% of deaths in the 0–15 years age group. The incidence of definite/probable SUDEP was 1.20/1,000 person-years, and higher in men (1.41) than in women (0.96). All SUDEP cases 50 years was 1.11, 1.13, and 1.29, respectively, per 1,000 person-years. The incidence was 5-fold increased among female patients with psychiatric comorbidities compared to those without. Epilepsy was mentioned on the death certificate in only 62 of the 99 (63%) SUDEP cases.Conclusions:Methods relying on death certificates underestimate SUDEP incidence. SUDEP risk has been underestimated especially in boys and in older people regardless of sex. Patients with psychiatric comorbidities, women in particular, are at increased SUDEP risk.

Background. - A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods. - Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age

Work in chemical laboratories may potentially be associated with exposure to carcinogenic chemicals. A previous cohort study of laboratory technicians in Stockholm followed until 1992 showed an excess of hematolymphatic malignancies among workers in chemical laboratories and an excess of breast cancer among women working for more than 10 years in such laboratories. The cohort comprised laboratory technicians employed 1950–1989 at “chemical” (e.g. chemistry, cytology, pathology) or “non-chemical” (e.g. physiology, haematology, fertility) laboratories at Karolinska Hospital and Karolinska Institutet in Stockholm. Follow-up of the 2 247 women in the cohort was extended by 20 years to include the period 1958–2012. Information on employment times and types of laboratory work was obtained from employee registers. Cancer incidence data was obtained from the the Swedish Cancer Registry. There were 389 cases of cancer in the cohort, SIR = 0.94 (95% CI: 0.85–1.04). The risk of breast cancer was increased among those who had worked for at least 10 years in chemical laboratories, SIR = 1.49 (1.05–2.05), 38 cases. There was no excess of breast cancer among those who had worked in non-chemical labs (SIR = 0.77 (0.54–1.07), 35 cases. The number of hematolymphatic cancers was not significantly increased. The increased risk of breast cancer among women who had worked for at least 10 years in chemical labs may be related to exposure to cancerogenic chemicals used in these laboratories. The absence of risk among those working in non-chemical labs makes it less likely that the excess would be caused by diagnostic bias resulting from a higher participation in mammography screening among health care workers, or late or no child-births due to longer education, since these factors would be expected to be similar between chemical and non-chemical labs. Night work, a well-recognised risk factor for breast cancer, is uncommon for lab workers.

Background In Sweden, approximately 50% of the men and 60% of the women entering retirement pension have had other subsistence than paid employment the years before retirement. Associations between heavy physical workload and musculoskeletal disorders are well-documented. This study investigates the role of heavy physical work for reduced work ability and early exits from the labour market. Socioeconomic position (SEP) is a potential confounder as it both influences the choice of occupation and is a determinant of health and work ability. The aim of this study was to investigate the associations between heavy physical workload, awkward work postures and long-term sickness absence, disability pension and long-term unemployment. Methods The study is based on the Stockholm Public Health Cohort, a population-based cohort of randomly selected residents in the Stockholm county. A total of 11 041 employed women and men, who answered a baseline questionnaire in 2002, were followed in national registers on sickness absence, disability pension and unemployment until 2010. The questionnaire contained questions on physical workload, work below knees, work above shoulder height and occupation. Results Heavy physical workload increased the risk of long-term sickness absence (HR 2.21, CI: 95% 1.83–2.68), disability pension (HR 2.06, CI: 95% 1.27–3.35), and long-term unemployment (HR 1.49, CI: 95% 1.15–1.93). Exposure for daily work below knees and above shoulder height were also associated with the three outcomes, with slightly lower hazard ratios. The associations were clearly attenuated after adjustments for SEP. Conclusions The results imply that heavy physical work contribute to reduced work ability and early exits from labour market manifested in long-term sickness absence, disability pension and long-term unemployment. The effects were partly explained by SEP. However, the associations were probably over-adjusted to some extent as SEP is closely related to occupational exposures, and to high physical workload in particular.

The relationships between drug exposure and the composite risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke as well as the risk of TIMI major bleeding were estimated following long-term treatment with ticagrelor 60 or 90 mg twice daily in 20,942 patients with prior MI. These analyses support the primary reported efficacy and safety evaluations by showing that there were clear separations from placebo early in treatment with both doses, regardless of ticagrelor exposure, for both endpoints. In addition, the exposure-response analyses provided new insight into the contribution of individual exposure levels, rather than dose, as a predictor of events and accounted for differences in the baseline risk between patients. The predicted risks of CV death/MI/stroke were similar despite an increase in the median predicted ticagrelor average steady-state concentration from 606 nmol/L with ticagrelor 60 mg to 998 nmol/L with ticagrelor 90 mg (hazard ratios vs placebo of 0.83 and 0.81, respectively). The corresponding predicted risk of TIMI major bleeding slightly increased (hazard ratios vs placebo of 2.4 and 2.6, respectively). Apart from Japanese patients, showing a lower risk of CV death/MI/stroke, the response to ticagrelor was consistent across the study population, as supported by the combination of relatively flat exposure-response relationships in the studied exposure range, similar sensitivity to ticagrelor exposure, and small exposure differences. Consequently, the present analyses support the selection of the 60-mg dose for all demographic subgroups of patients studied.

Aims It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). Method Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case–control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. Results No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). Conclusion The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

Objective Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Design/methods Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Results Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11–3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02–1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00–1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95–1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07–1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. Conclusions High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance.

Diabet. Med. 30, 56–64 (2013) Abstract Aims We investigated the influence of different aspects of alcohol consumption on the risk of Type 2 diabetes and autoimmune diabetes in adults. Methods We used data from the Nord-Trondelag Health Survey (HUNT) study, in which all adults aged ≥ 20 years from Nord-Trondelag County were invited to participate in three surveys in 1984–1986, 1995–1997 and 2006–2008. Patients with diabetes were identified using self-reports, and participants with onset age ≥ 35 years were classified as having Type 2 diabetes if they were negative for anti-glutamic acid decarboxylase (n = 1841) and as having autoimmune diabetes if they were positive for anti-glutamic acid decarboxylase (n = 140). Hazard ratios of amount and frequency of alcohol use, alcoholic beverage choice, and binge drinking and alcohol use disorders were estimated. Results Moderate alcohol consumption (adjusted for confounders) was associated with a reduced risk of Type 2 diabetes in men, but not in women (hazard ratio for men 10–15 g/day 0.48, 95% CI 0.28–0.77; hazard ratio for women ≥ 10 g/day 0.81, 95% CI 0.33–1.96). The reduced risk was primarily linked to consumption of wine [hazard ratio 0.93, 95% CI 0.87–0.99 (per g/day)]. No increased risk was seen in participants reporting binge drinking or in problem drinkers. The results were also compatible with a reduced risk of autoimmune diabetes associated with alcohol consumption [hazard ratio 0.70, 95% CI 0.45–1.08 (frequent consumption) and hazard ratio 0.36, 95% CI 0.13–0.97 (2–7 g/day)]. Conclusions Moderate alcohol consumption associates with reduced risk of both Type 2 diabetes and autoimmune diabetes. A protective effect of alcohol intake may be limited to men. High alcohol consumption does not seem to carry an increased risk of diabetes.

Late retirement is not associated with increased mortality, results based on all Swedish retirements 1991-2007

It is often taken for granted that an ageing population will lead to an increased burden for the health care sector. However, for several diseases of big public health impact the rates have actually come down for a substantial period of time. In this study we investigate how much the incidence rates for myocardial infarction (MI), stroke, and cancer will have to decline in order to counterbalance future demographic changes (changes in population size and age structure) and compare these figures with observed historical trends. Information on incidence rates were obtained from the National Board of Health and Welfare and referred to the total Swedish population. Population projections were obtained from Statistics Sweden. We projected the number of MI events to increase 50-60% between 2010 and 2050. The decline in incidence rates that is required to keep the number of events constant over time is, on average, 1.2%/year for men and 0.9%/year for women, somewhat higher than the trend for the past 10 years. For stroke the corresponding figures were 1.3% (men) and 1% (women), well in line with historical trends. For cancer the results indicate an increasing number of events in the future. Population ageing is more important than population growth when projecting future number of MI, stroke and cancer events. The required changes in incidence rates in order to counterbalance the demographic changes are well in line with historical figures for stroke, almost in line regarding MI, but not in line regarding cancer. For diseases with age dependence similar to these diseases, a reduction of incidence rates in the order of 1-2% is sufficient to offset the challenges of the ageing population. These are changes that have been observed for several diseases indicating that the challenges posed by the ageing population may not be as severe as they may seem when considering the demographic component alone.

Summary Purpose: To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE). Methods: From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records. Results: After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%. Conclusions: We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.