Trends in the Use of Medications for Secondary Ischemic Stroke Prevention in Denmark, 2005-2021.

BACKGROUND AND OBJECTIVES: Understanding trends in the use of medications for secondary stroke prevention is crucial for identifying areas for improvement in stroke care. We examined the use of lipid-lowering, antihypertensive, glucose-lowering, oral anticoagulant, and antiplatelet medications after ischemic stroke hospitalization, from 2005 to 2021. METHODS: Using nationwide registries in Denmark, we identified a cohort of patients discharged from hospital with a first-time or recurrent ischemic stroke (N = 150,744). Stratified by calendar year, we ascertained the 180-day probability of filling a prescription for the abovementioned medications after discharge. We further assessed factors associated with medication use. RESULTS: From 2005 to 2021, lipid-lowering medication use increased from 58.3% to 82.0%; atorvastatin use rose from 2.1% to 64.8% and simvastatin use decreased from 55.7% to 8.6%. Antihypertensive medication use remained stable, at approximately 89%, and various antihypertensive classes were used comparably. Glucose-lowering medication use increased from 71.5% in 2005 to 84.1% in 2021, driven primarily by an increase in metformin use (from 28.0% to 59.5%). Use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors continually increased (from 1.7% to 17.5% and from 0.5% to 17.3%, respectively) between 2015 and 2021. Anticoagulant medication use rose from 45.9% in 2005 to 87.0% in 2021, primarily because of increased use of direct oral anticoagulant medications starting around 2010 and a decline in warfarin use. Antiplatelet use remained consistently high, at approximately 95%. Trends were consistent across subgroups of interest; however, overall medication use was lower in older patients (65 years and older), patients with severe stroke, and patients with neurologic and psychiatric comorbidities. DISCUSSION: Despite increasing trends in the use of 3 of 5 medication classes, the overall use of lipid-lowering, glucose-lowering, and oral anticoagulant medications was somewhat lower than expected according to clinical guidelines, particularly among older patients with more severe stroke and other comorbidities. The relatively low use in these subgroups may signify appropriate clinical decision making in consideration of frequent contraindications and reduced life expectancy or highlight potential areas of improvement for the care of patients with recent ischemic stroke.

Mental Health Conditions in Partners and Adult Children of Stroke Survivors.

Importance: Family caregiving after critical illness has been associated with several adverse health outcomes, including various aspects of mental health, but research focusing specifically on family members of stroke survivors is limited. Objectives: To examine the associations of stroke in a partner or parent with the risk of depression, substance use disorders, anxiety disorders, and self-harm or suicide. Design, Setting, and Participants: This nationwide, population-based cohort study used data from Danish nationwide administrative and clinical registries (2004-2021). Participants included partners and adult children of survivors of stroke. Data analysis was performed from March to December 2023. Exposure: Having a partner or parent who survived stroke. Main Outcomes and Measures: The Aalen-Johansen estimator was used to compute propensity score-weighted 3-year absolute risks, risk differences, and risk ratios for depression, substance use disorders, anxiety disorders, and self-harm or suicide among partners or children of survivors of stroke compared with partners or children of survivors of myocardial infarction (MI) and matched individuals from the general population. Results: The study included a total of 1 923 732 individuals: 70 917 partners of stroke survivors (median [IQR] age, 68 [59-76] years; 46 369 women [65%]), 70 664 partners of MI survivors (median [IQR] age, 65 [55-73] years; 51 849 women [73%]), 354 570 partners of individuals from the general population (median [IQR] age, 68 [59-76] years; 231 833 women [65%]), 207 386 adult children of stroke survivors (median [IQR] age, 45 [36-52] years; 99 382 women [48%]), 183 309 adult children of MI survivors (median [IQR] age, 42 [33-49] years; 88 078 women [48%]), and 1 036 886 adult children of individuals from the general population (median [IQR] age, 45 [36-52] years; 496 875 women [48%]). Baseline characteristics were well balanced across cohorts after propensity score weighting. Among partners of stroke survivors, the 3-year absolute risk was 1.0% for depression, 0.7% for substance use disorders, 0.3% for anxiety disorders, and 0.04% for self-harm or suicide. Risk ratio point estimates for the assessed outcomes ranged from 1.14 to 1.42 compared with the general population and from 1.04 to 1.09 compared with partners of MI survivors. The elevated risk of depression in partners of stroke survivors was more pronounced after severe or moderate stroke than after mild stroke. Among adult children of stroke survivors, the 3-year absolute risk was 0.6% for depression, 0.6% for substance use disorders, 0.2% for anxiety disorders, and 0.05% for self-harm or suicide. Both absolute risks and risk ratios for adult children of stroke survivors were smaller than those reported in the partner analyses. Conclusions and Relevance: In this cohort study of partners and adult children of stroke survivors, risks of several mental health conditions and self-harm or suicide were moderately higher compared with the general population and, to a lesser extent, partners and adult children of MI survivors. These findings highlight the potential consequences of stroke among family members, particularly partners, and its findings may possibly serve as a quantitative foundation for the development of future stroke rehabilitation services.

Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Comorbidities and mortality among patients with chronic obstructive pulmonary disease.

INTRODUCTION: Comorbidities are common in patients with chronic obstructive pulmonary disease (COPD). Estimates of prevalence, incidence and prognostic impact of comorbidities provide foundational knowledge of COPD epidemiology. We examined the prevalence, incidence and prognostic impact of 21 comorbidities among patients with COPD compared with the Danish general population. METHODS: We conducted a nationwide, population-based cohort study based on longitudinal Danish registry data, covering all Danish hospitals (2010-2021). The cohorts comprised 142 973 patients with a first-time hospital-based diagnosis of COPD and 428 917 age-matched and sex-matched comparators from the general population. During follow-up, we estimated the 5-year risk and risk difference, using competing risk methods when applicable. RESULTS: At time of diagnosis, the comorbidities with the highest prevalence were mood, stress-related or anxiety disorders (25.2% for patients with COPD vs 13.1% for comparators), osteoporosis/hip fractures (17.4% vs 9.9%), diabetes (15.6% vs 10.5%), peripheral arterial disease (13.5% vs 4.9%) and heart failure (13.3% vs 4.0%). During follow-up, the risk of most incident comorbidities was markedly elevated among patients with COPD. The five comorbidities associated with the highest 5-year absolute risk difference with respect to the risk in the general population were mood, stress-related or anxiety disorders (5.7%), osteoporosis/hip fractures (5.6%), heart failure (4.2%), smoking-related cancers (2.8%) and peripheral arterial disease (2.7%). The 5-year mortality risk was 43% vs 17.7%. Among patients with COPD, the 5-year mortality risk markedly increased with the number of comorbidities present. CONCLUSIONS: Our population-based findings underscore the importance of considering comorbidities in the management of COPD.

High-intensity versus moderate-intensity statin treatment for patients with ischemic stroke: Nationwide cohort study.

PURPOSE: Guidelines recommend high-intensity statin treatment after ischemic stroke, but evidence is sparse on the effectiveness and safety of different statin treatment intensities. We examined effectiveness and safety outcomes among patients initiating high-intensity versus moderate-intensity statins after ischemic stroke. METHODS: In this population-based new-user active-comparator cohort study, we used the Danish Stroke Registry, covering all Danish hospitals, to identify patients with a first-time ischemic stroke during 2012-2021. Using multiple Danish registries, patients who redeemed a statin prescription within 21 days after stroke admission were classified as high-intensity statin initiators or moderate-intensity statin initiators. Propensity score inverse probability of treatment weighting was used to balance patient characteristics. We used competing risk methods to compute 5 year risk differences (RDs) and Cox proportional hazards regression to compute 5 year hazard ratios (HRs) of stroke recurrence, myocardial infarction, heart failure, venous thromboembolism, and all-cause mortality (effectiveness outcomes) and diabetes, liver disease, and kidney disease (safety outcomes). RESULTS: High-intensity (n = 13,032) and moderate-intensity (n = 14,355) statin initiators were identified. Risks of most examined effectiveness outcomes were comparable between statin intensities. There was no clear association between statin intensity and stroke recurrence (RD: 0.8% [95% CI: 0.1, 1.4], HR: 1.08 [95% CI: 0.96, 1.22]). All-cause mortality was slightly reduced among high-intensity statin initiators (RD: -1.1% [95% CI: -0.1, -2.1], HR: 0.93 [95% CI: 0.85, 1.01]. Risks of most safety outcomes were comparable between statin intensities, but high-intensity statin use was associated with an increased risk of diabetes (RD: 1.2% [95% CI: 0.4, 1.9], HR: 1.10 [95% CI: 1.00, 1.21]). DISCUSSION AND CONCLUSION: Compared with initiation of moderate-intensity statins, initiation of high-intensity statins after ischemic stroke was associated with similar risks of most effectiveness and safety outcomes. However, mortality risk was reduced, and diabetes risk was increased.

Risk and Prognosis of Cancer in Patients With Cerebral Venous Thrombosis Compared With the Danish General Population.

BACKGROUND: Whether cerebral venous thrombosis (CVT) is a marker of cancer in clinical practice remains unknown. Little is known about the prognosis of cancer detected subsequent to CVT. METHODS: We used Danish nationwide registries (1996-2019) to identify patients with a first-time primary inpatient diagnosis of CVT without a history of cancer (N=811, 65% women, median age 42 years). We assessed the risk of an incident cancer diagnosis using standardized incidence ratios (SIRs). This measure contrasts the number of observed cancers among patients with CVT to the number of expected cancers where patients with CVT have the same cancer risk as the general population. We used Kaplan-Meier survival analysis and Cox regression to compare the survival of patients with both cancer and CVT with the survival of patients with cancer but without CVT, matched on cancer site, sex, age, and year of cancer diagnosis. RESULTS: Observing 43 incident cancer cases during follow-up, the overall SIR was unity (SIR, 1.04 [95% CI, 0.75-1.40]). However, the risk was ≈7-fold the expected level in the first 3 months following CVT diagnosis (SIR, 7.00 [95% CI, 3.02-13.80]) and ≈2-fold the expected level from 3 to 12 months following CVT diagnosis (SIR, 2.21 [95% CI, 0.89-4.56]). By 12 months following CVT diagnosis, the risk resembled the expected level (SIR, 0.76 [95% CI, 0.50-1.09]). Survival among cancer patients with prior CVT versus cancer patients without prior CVT was 91% versus 87% after 6 months and 65% versus 70% after 5 years. The adjusted hazard ratio of death was 0.78 (95% CI, 0.44-1.38). CONCLUSIONS: Patients with CVT were not at overall increased risk of a cancer diagnosis, except in the first 3 months after diagnosis during which period the risk was elevated ≈7-fold. The estimate from this early period, however, was based on only a few cancer diagnoses. Unlike other forms of venous thrombosis, a prior diagnosis of CVT did not negatively impact cancer survival.

Type 2 diabetes, obesity, and risk of amyotrophic lateral sclerosis: A population-based cohort study.

BACKGROUND: Type 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial. METHODS: Using Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities. RESULTS: We observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6-0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9-1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72-1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62-0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78-1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59-0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4-0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5-0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70-1.11). CONCLUSIONS: Diagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small.

A Review of Major Danish Biobanks: Advantages and Possibilities of Health Research in Denmark.

Biobank research may lead to an improved understanding of disease etiology and advance personalized medicine. Denmark (population ~5.9 million) provides a unique setting for population-based health research. The country is a rich source of biobanks and the universal, tax-funded healthcare system delivers routinely collected data to numerous registries and databases. By virtue of the civil registration number (assigned uniquely to all Danish citizens), biological specimens stored in biobanks can be combined with clinical and demographic data from these population-based health registries and databases. In this review, we aim to provide an understanding of advantages and possibilities of biobank research in Denmark. As knowledge about the Danish setting is needed to grasp the full potential, we first introduce the Danish healthcare system, the Civil Registration System, the population-based registries, and the interface with biobanks. We then describe the biobank infrastructures, comprising the Danish National Biobank Initiative, the Bio- and Genome Bank Denmark, and the Danish National Genome Center. Further, we briefly provide an overview of fourteen selected biobanks, including: The Danish Newborn Screening Biobank; The Danish National Birth Cohort; The Danish Twin Registry Biobank; Diet, Cancer and Health; Diet, Cancer and Health - Next generations; Danish Centre for Strategic Research in Type 2 Diabetes; Vejle Diabetes Biobank; The Copenhagen Hospital Biobank; The Copenhagen City Heart Study; The Copenhagen General Population Study; The Danish Cancer Biobank; The Danish Rheumatological Biobank; The Danish Blood Donor Study; and The Danish Pathology Databank. Last, we inform on practical aspects, such as data access, and discuss future implications.

Labour market participation and retirement after stroke in Denmark: registry based cohort study.

OBJECTIVE: To examine labour market participation and retirement among patients with stroke and matched people in the general population according to stroke subtype. DESIGN: Nationwide, population based, matched cohort study. SETTING: Danish Stroke Registry, covering all Danish hospitals, and other nationwide registries (2005-18). PARTICIPANTS: Patients (aged 18-60 years and active in the labour market) with a first time diagnosis of ischaemic stroke (n=16 577), intracerebral haemorrhage (n=2025), or subarachnoid haemorrhage (n=4305), and individuals from the general population, matched on age, sex, and calendar year (n=134 428). The median Scandinavian stroke scale score was 55. MAIN OUTCOME MEASURES: Unweighted prevalences of labour market participation, receipt of sick leave benefits, receipt of disability pension, voluntary early retirement, state pension, and death were computed for each week and up to five years after stroke diagnosis. A log-linear Poisson model was used to obtain exact prevalence estimates as well as propensity score weighted prevalence differences and prevalence ratios at six months, one year, two years, and five years after stroke diagnosis. RESULTS: Most patients (62% of those with ischaemic stroke, 69% of those with intracerebral haemorrhage, and 52% of those with subarachnoid haemorrhage) went on sick leave within three weeks of diagnosis. Prevalence of labour market participation among patients with ischaemic stroke compared with matched individuals from the general population was 56.6% versus 96.6% at six months, and 63.9% versus 91.6% at two years. Prevalence of sick leave was 39.8% versus 2.6% at six months, and 15.8% versus 3.8% at two years. Prevalence of receipt of a disability pension was 0.9% versus 0.2% at six months, and 12.2% versus 0.6% at two years. Adjusting for socioeconomic and comorbidity differences between patients and matched individuals from the general population using propensity score weighting methods had little impact on contrasts. Patients with intracerebral haemorrhage had higher prevalences of sick leave and receipt of a disability pension and thus a lower prevalence of labour market participation, while prevalences for patients with subarachnoid haemorrhage were similar in magnitude to those for patients with ischaemic stroke. CONCLUSIONS: In a highly resourced country, about two thirds of working age adults with ischaemic stroke of primarily mild severity participated in the labour market two years after diagnosis. Sick leave and receipt of a disability pension were the most common reasons for non-participation. Patients with intracerebral haemorrhage were less likely to return to the labour market than patients with ischaemic stroke and subarachnoid haemorrhage.

Thromboembolic events, bleeding, and mortality in patients with cerebral venous thrombosis: a nationwide cohort study.

Cerebral venous thrombosis (CVT) predominantly affects young to middle-aged women. Scarce data exist regarding the long-term prognosis. We examined the clinical course of patients with CVT overall and according to their age and sex. Using Danish registries, we identified all patients with a first-time primary inpatient diagnosis of CVT from 1996-2018 (N = 653; median age, 41 years; 67% women) and individuals from the general population matched for age, sex, and calendar year (N = 65 300). Patients with CVT were at an increased risk of venous thromboembolism (VTE) at other sites, ischemic stroke, major bleeding, and mortality. For both sexes, the increased risks of VTE at other sites were most prominent among younger patients (18-54 years), whereas the increased risks of ischemic stroke, major bleeding, and mortality were most prominent among older patients (≥55 years). Among young women, the 10-year risks of VTE at other sites for patients with CVT compared with members of the matched cohort were 2.2% vs 0.4% (risk difference, 1.8%; 95% confidence interval [CI], 0.0-3.6). Among older women, compared with members of the matched cohort, the 10-year risks were 12.8% vs 3.1% (risk difference, 9.7%; 95% CI, 1.6-17.9) for ischemic stroke, 11.1% vs 4.6% (risk difference, 6.5%; 95% CI, -1.0 to 14.1) for major bleeding, and 43.1% vs 26.7% (risk difference, 16.4%; 95% CI, 3.7-29.1) for all-cause mortality. The risk of myocardial infarction was not elevated. Clinicians should be aware of the importance of age and sex heterogeneity in the prognosis of CVT.

Venous Thromboembolism and Risk of Cancer in Users of Low-Dose Aspirin: A Danish Population-Based Cohort Study.

Background Aspirin may reduce the risk of cancer, particularly gastrointestinal cancer, and venous thromboembolism (VTE). VTE can be the first symptom of occult cancer, but whether it is also a marker of occult cancer in aspirin users remains unknown. Therefore, we investigated the risk of cancer subsequent to VTE among users of low-dose aspirin. Methods We conducted a population-based cohort study using data from Danish health registries for the years 2001 to 2018. We identified all patients with a first-time diagnosis of VTE who also redeemed a prescription for low-dose aspirin (75-150mg) within 90 days prior to the first-time VTE. We categorized aspirin users by the number of prescriptions filled as new users (<5 prescriptions), short-term users (5-19 prescriptions), and long-term users (>19 prescriptions). We computed the absolute cancer risks and standardized incidence ratios (SIRs) for cancer using national cancer incidence rates. Results We followed-up 11,759 users of low-dose aspirin with VTE. Long-term users comprised 50% of aspirin users. The 1-year absolute risk of cancer was 6.0% for new users and 6.7% for short-term and long-term users, with corresponding SIRs of 3.3 (95% confidence interval [CI]: 2.8-4.0), 3.2 (95% CI: 2.9-3.7), and 2.8 (95% CI: 2.6-3.2), respectively. After the first year of follow-up, the SIR decreased to 1.2 (95% CI: 1.1-1.4) for new users, 1.1 (95% CI: 1.1-1.3) for short-term users, and 1.1 (95% CI: 1.0-1.2) for long-term users. Conclusion VTE may be a harbinger of cancer, even in users of low-dose aspirin, regardless of duration of use.

Trends in Antibiotic Use in Danish, Finnish, Norwegian and Swedish Children.

Objective: To compare the use of antibiotics in children in four Northern European countries. Methods: We conducted a register-based study based on individual-level prescription data from national prescription registers. We identified all redeemed outpatient prescriptions for systemic antibiotics in children aged 0-14 years from July 2006 to June 2017 in Denmark, Finland, Norway, and Sweden. We computed incidence rates and incidence rate ratios of treatment episodes with any antibiotic and different antibiotic classes. Results: In 2016/2017, the rates of antibiotic treatment episodes per 1000 person-years in children aged 0-14 years were 429, 284, 219, and 184 in Finland, Denmark, Sweden, and Norway, respectively, and the rate ratios (95% confidence intervals) compared with Norway were 2.33 (2.33-2.34), 1.54 (1.54-1.55), and 1.19 (1.19-1.20) in Finland, Denmark, and Sweden, respectively. The rate of antibiotic treatment episodes declined over time in all countries. The relative reductions in 2016/2017 compared with 2006/2007 were 36% in Finland, 40% in Denmark, 49% in Sweden, and 29% in Norway. Treatment episodes peaked between age 12 and 18 months. The most used antibiotic class was beta-lactamase sensitive penicillins among all children in Norway and Sweden and among children above two years in Denmark, while penicillins with extended spectrum were most used in Finland and among the youngest children in Denmark. Conclusion: In all countries, the use of antibiotics in children declined between 2006 and 2017. However, there were still considerable differences in antibiotic use between otherwise quite similar Nordic countries, with a more than 2-fold difference between the countries with the lowest and highest rates. Interventions to reduce the number of antibiotic treatment episodes in the countries with higher rates could reduce the total antibiotic use.

Cancer Diagnosis and Prognosis After Guillain-Barré Syndrome: A Population-Based Cohort Study.

Introduction: It is unclear whether Guillain-Barré syndrome (GBS) can be a marker of a paraneoplastic syndrome. We examined whether GBS is associated with cancer and whether the prognosis of GBS patients with cancer differs from that of other cancer patients. Materials and Methods: We conducted a population-based cohort study of patients diagnosed with GBS between 1978 and 2017 using Danish registry-data. Main outcome measures were cancer incidence and mortality after cancer diagnosis. We calculated absolute risks of a cancer diagnosis, treating death as competing risk, and standardized incidence ratios (SIRs) as measures of relative risk. We matched each GBS cancer patient with up to 10 cancer patients without a GBS diagnosis and examined the six-month survival after cancer diagnosis using Cox regression analysis. Results: We identified 7897 patients (58% male, median age 57 years) with GBS. During a median follow-up of 9.5 years, the one-year risk of cancer was 2.7% (95% confidence interval (CI), 2.4-3.1). The SIR was increased throughout follow-up, but most noticeably during the first year after diagnosis (SIR: 3.35, 2.92-3.83). SIRs were particularly elevated for hematologic cancers (SIR: 8.67, 6.49-11.34), smoking-related cancers (SIR: 3.57, 2.81-4.47), and cancers of neurological origin (SIR: 8.60, 5.01-13.77). Lung cancer was the main contributor to the overall excess risk, which persisted after 36 months of follow-up (SIR: 1.17, 1.09-1.25). The mortality rate ratio comparing patients diagnosed with any cancer within one year of their GBS diagnosis and matched GBS-free cancer cohort members was 1.56 (95% CI, 1.27-1.90). Conclusion: GBS patients had a three-fold increased risk of cancer diagnosis in the first year of follow-up. The absolute cancer risk was almost 3.0%. A GBS diagnosis was an adverse prognostic marker for survival following cancer diagnosis. Clinicians should consider occult cancer in patients hospitalized with GBS.

Stroke and Risk of Mental Disorders Compared With Matched General Population and Myocardial Infarction Comparators.

BACKGROUND: Accurate estimates of risks of poststroke outcomes from large population-based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage. METHODS: During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year-matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity. RESULTS: Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0-7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3-1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7-0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4-0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but -0.2% (95% CI, -0.2 to -0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders. CONCLUSIONS: The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke.

Cancer Risk in Pulmonary Hypertension Patients.

BACKGROUND: Strong evidence indicates that venous thromboembolism is a presenting symptom of cancer. Cancer is a known cause of pulmonary hypertension; however, it remains unknown whether pulmonary hypertension is a marker of occult cancer. We examined the association between a pulmonary hypertension diagnosis and cancer risk in a cohort study using population-based data from the Danish health system. PATIENTS AND METHODS: Using Danish nationwide registries, we identified 6335 patients with a pulmonary hypertension diagnosis and without a previous cancer diagnosis between 1995 and 2017. We computed the age-, sex-, and calendar year-standardized incidence ratio (SIR) as the ratio of observed to expected number of cancers using national incidence rates as the reference. We performed a subgroup analysis among patients with chronic thromboembolic pulmonary hypertension in the period in which a specific ICD-10 code was available (2006-2017). RESULTS: We identified 212 cancers within the first year of follow-up and 796 cancers thereafter. The one-year risk of cancer was 3.3% and the one-year SIR was 1.96 (95% confidence interval [CI]: 1.70-2.23). In the second and subsequent years, the SIR remained elevated (SIR: 1.15 [95% CI: 1.08-1.24]). In patients with chronic thromboembolic pulmonary hypertension, the one-year SIR was 1.41 (95% CI: 0.82-2.25). CONCLUSION: Cancer risk was clearly higher in patients with pulmonary hypertension compared with the general population. The association was particularly strong in the first year of follow-up, but remained elevated thereafter. However, absolute risks were low, limiting the clinical relevance of pursuing early cancer detection in these patients.

Type 2 diabetes and risk of diverticular disease: a Danish cohort study.

OBJECTIVES: To investigate the association between type 2 diabetes and risk of diverticular disease. Unlike previous studies, which have found conflicting results, we aimed to distinguish between diabetes types and adjust for modifiable risk factors. DESIGN: Observational cohort study. SETTING: Population-based Danish medical databases, covering the period 2005-2018. PARTICIPANTS: Respondents of the 2010 or the 2013 Danish National Health Survey, of which there were 15 047 patients with type 2 diabetes and 210 606 patients without diabetes. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazard ratios (HRs) for incident hospital diagnosis of diverticular disease adjusted for survey year, sex, age, body mass index (BMI), physical activity intensity, smoking behaviour, diet and education based on Cox regression analysis. As latency may affect the association between type 2 diabetes and diverticular disease, patients with type 2 diabetes were stratified into those with <2.5, 2.5-4.9 and ≥5 years duration of diabetes prior to cohort entry. RESULTS: For patients with and without diabetes the incidence rates of diverticular disease were 0.76 and 0.54 events per 1000 person years, corresponding to a crude HR of 1.08 (95% CI 1.00 to 1.16) and an adjusted HR of 0.88 (95% CI 0.80 to 0.96). The HR was lower among patients with ≥5 years duration of diabetes (adjusted HR: 0.76, 95% CI 0.67 to 0.87) than among those with 2.5-4.9 years or <2.5 years duration. CONCLUSION: We found that patients with type 2 diabetes had a higher incidence rate of diverticular disease compared with patients without diabetes. However, after adjustment for modifiable risk factors, driven by BMI, type 2 diabetes appeared to be associated with a slightly lower risk of diverticular disease. Lack of adjustment for BMI may partially explain the conflicting findings of previous studies.

Cancer risk in patients with migraine: A population-based cohort study in Denmark.

OBJECTIVE: The purpose of this study was to examine overall and site-specific cancer risk among individuals diagnosed with migraine compared with the general population. BACKGROUND: Current evidence regarding migraine and risk of cancer is sparse and inconclusive. METHODS: We conducted a nationwide population-based cohort study with data collected routinely and prospectively from Danish population-based registries from 1995 to 2017. We computed the age- and sex-standardized incidence ratio (SIR) as the ratio of observed to expected cancers among patients diagnosed with migraine in the study population overall, and by encounter type of first diagnosis (inpatient, outpatient specialty clinic, and emergency department). Site-specific cancers were grouped according to etiology. RESULTS: We identified 72,826 patients with a first-time hospital migraine diagnosis. There were 3090 observed overall cancer cases among individuals diagnosed with migraine as compared with 3108 expected cases (SIR 0.99, 95% confidence interval [CI]: 0.96-1.03). The cumulative incidence of all cancers combined from 1995 to 2017 among those with a first-time migraine diagnosis was 9.47% (95% CI: 9.08-9.87). The SIRs for most cancers were consistent with absence of an association: 1.00 (95% CI: 0.94-1.06) for hormone-related cancers, 0.96 (95% CI: 0.88-1.03) for smoking-related cancers, 1.10 (95% CI: 0.98-1.24) for hematologic cancers, and 0.95 (95% CI: 0.85-1.06) for immune-related cancers. Exceptions were SIRs for gastrointestinal cancers (0.78, 95% CI: 0.70-0.87) and for cancers of neurological origin (1.57, 95% CI: 1.40-1.76). CONCLUSIONS: For most cancer groups, our results did not support an association with migraine. The exceptions were an increased risk for cancers of neurological origin and a decreased risk for gastrointestinal cancers. These findings may reflect a true difference in risk among individuals with migraine, or more plausibly they reflect other forces, such as differences in medication use, detection bias and reverse causation, or shared risk factors.

Risks of Stroke Recurrence and Mortality After First and Recurrent Strokes in Denmark: A Nationwide Registry Study.

BACKGROUND AND OBJECTIVES: To examine risks of stroke recurrence and mortality after first and recurrent stroke. METHODS: Using Danish nationwide health registries, we included patients (age ≥18 years) with first-time ischemic stroke (N = 105,397) or intracerebral hemorrhage (N = 13,350) during 2004-2018. Accounting for the competing risk of death, absolute risks of stroke recurrence were computed separately for each stroke subtype and within strata of age groups, sex, stroke severity, body mass index, smoking, alcohol, the Essen stroke risk score, and atrial fibrillation. Mortality risks were computed after first and recurrent stroke. RESULTS: After adjusting for competing risks, the overall 1-year and 10-year risks of recurrence were 4% and 13% following first-time ischemic stroke and 3% and 12% following first-time intracerebral hemorrhage. For ischemic stroke, the risk of recurrence increased with age, was higher for men and following mild than more severe stroke. The most marked differences were across Essen risk scores, for which recurrence risks increased with increasing scores. For intracerebral hemorrhage, risks were similar for both sexes and did not increase with Essen risk score. For ischemic stroke, the 1-year and 10-year risks of all-cause mortality were 17% and 56% after a first-time stroke and 25% and 70% after a recurrent stroke; corresponding estimates for intracerebral hemorrhage were 37% and 70% after a first-time event and 31% and 75% after a recurrent event. CONCLUSION: The risk of stroke recurrence was substantial following both subtypes, but risks differed markedly among patient subgroups. The risk of mortality was higher after a recurrent than first-time stroke.

Venous Thromboembolism and Risk of Cancer in Patients with Diverticular Disease: A Danish Population-Based Cohort Study.

PURPOSE: Venous thromboembolism may be a harbinger of cancer. Patients with diverticular disease are suggested to have an increased risk of developing venous thromboembolism compared with the general population, but it remains unclear whether venous thromboembolism is also a marker of occult cancer in these patients. We investigated the risk of cancer after venous thromboembolism among patients with diverticular disease. PATIENTS AND METHODS: We used Danish health registries to conduct a nationwide, population-based cohort study during 1996-2017. We identified all venous thromboembolism patients with a diagnosis of diverticular disease and calculated absolute risks of cancer and standardized incidence ratios (SIRs) by comparing observed and expected cancer incidence based on national cancer incidence in the Danish population. RESULTS: We followed 3406 patients with venous thromboembolism and diverticular disease for a median of 3.0 years (interquartile range: 1.0-6.0). During the first year of follow-up, we observed 212 cancer cases. The corresponding one-year risk of cancer was 6.2% (95% confidence interval [CI]: 5.5-7.1) with a SIR of 2.9 (95% CI: 2.5-3.3). The SIRs were particularly elevated for cancers of the stomach, pancreas, ovary, and kidney. During the second and subsequent years of follow-up, 337 cancers were diagnosed with a SIR of 1.1 (95% CI: 1.0-1.3). CONCLUSION: Venous thromboembolism is a harbinger of occult cancer in patients with diverticular disease.

Statin Initiation and Risk of Amyotrophic Lateral Sclerosis: A Danish Population-based Cohort Study.

BACKGROUND: The evidence of an association between statins and amyotrophic lateral sclerosis (ALS) is heterogeneous and inconclusive. METHODS: We performed a population-based cohort study consisting of 974,304 statin initiators ≥40 years of age and 1,948,606 matched general population comparators identified from Danish, nationwide registries (1996-2016). We computed incidence rates and hazard ratios (HRs) of a first-time hospital-based diagnosis of ALS. HRs were controlled for sex, birth year, calendar year, medically diagnosed comorbidities, and concomitant medications. RESULTS: During a median follow-up of 7.7 years, 852 ALS events occurred among statin initiators (11.3 [95% confidence interval (CI) = 10.6, 12.1] events per 100,000 person-years) and 1,679 among noninitiators (11.4 [95% CI = 10.9, 12.0] events per 100,000 person years). The overall adjusted HR indicated a slight association between statin initiation and ALS (1.11 [95% CI = 1.00, 1.23]. In the first year after initiation, the HR was 1.40 (95% CI = 1.09, 1.79) for both sexes combined, 1.00 (95% CI = 0.70, 1.42) for men, and 1.92 (95% CI = 1.30, 2.82) for women. The associations diminished to approximately null after the first year of follow-up for both sexes combined and for men, but point estimates were above 1 for women until 10 years after initiation. CONCLUSIONS: Statin initiation was largely unassociated with ALS diagnosis but was associated with an elevated risk of ALS in women, especially in the first year after initiation. The association could be explained by reverse causation, detection bias, early neurotoxic effects of statins that affect women more than men, or a combination thereof.