Geographical inequalities in the decreasing 28-day mortality following incident acute myocardial infarction: a Danish register-based cohort study, 1987-2016.

BACKGROUND: Mortality following acute myocardial infarction (AMI) has decreased in western countries for decades; however, it remains unknown whether the decrease is distributed equally across the population independently of residential location. This study investigated whether the observed decreasing 28-day mortality following an incident AMI in Denmark from 1987 to 2016 varied geographically at municipality level after accounting for sociodemographic characteristics. METHODS: A register-based cohort study design was used to investigate 28-day mortality among individuals with an incident AMI. Global spatial autocorrelation (within sub-periods) was analysed at municipality level using Moran's I. Analysis of spatio-temporal autocorrelation before and after adjusting for sociodemographic characteristics was performed using logistic regression and conditional autoregressive models with inference in a Bayesian setting. RESULTS: In total, 368,839 individuals with incident AMI were registered between 1987 and 2016 in Denmark; 128,957 incident AMIs were fatal. The 28-day mortality decreased over time at national level with an odds ratio of 0.788 (95% credible interval (0.784, 0.792)) per 5-year period after adjusting for sociodemographic characteristics. The decrease in the 28-day mortality was geographically unequally distributed across the country and in a geographical region in northern Jutland, the 28-day mortality decreased significantly slower (4-12%) than at national level. CONCLUSIONS: During the period from 1987 to 2016, the 28-day mortality following an incident AMI decreased substantially in Denmark. However, in a local geographical region, the 28-day mortality decreased significantly slower than in the rest of the country both before and after adjusting for sociodemographic differences. Efforts should be made to keep geographical trend inequalities in the 28-day mortality to a minimum.

Characteristics of finasteride users in comparison with nonusers: A Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden.

PURPOSE: Published epidemiological studies on the association between finasteride use and the risk of male breast cancer have been inconclusive due to methodological limitations including a few male breast cancer cases included. Determinants of male breast cancer have been studied, but it remains unexplored whether these are also related to finasteride use and thereby constitute potential confounders. This study aimed to assess whether there are differences between finasteride users and nonusers with regard to numerous potential confounders. METHODS: In total, 246 508 finasteride users (≥35 years) were identified in the prescription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). An equal number of nonusers were sampled. The directed acyclic graph (DAG) methodology was used to identify potential confounders for the association between finasteride and male breast cancer. A logistic regression model compared finasteride users and nonusers with regard to potential confounders that were measurable in registries and population surveys. RESULTS: Finasteride users had higher odds of testicular abnormalities (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exogenous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabetes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry or in high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), living in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70; 0.50-0.99) compared to nonusers. CONCLUSIONS: Systematic differences between finasteride users and nonusers were found emphasizing the importance of confounder adjustment of associations between finasteride and male breast cancer.

Association between travel distance and face-to-face consultations with general practitioners before an incident acute myocardial infarction: a nationwide register-based spatial epidemiological study.

OBJECTIVES: This study examined the association between travel distance to the general practitioner's (GP) office and no face-to-face GP consultation within 1 year before an incident acute myocardial infarction (AMI). DESIGN: A prospective cohort study using multilevel spatial logistic regression analysis of nationwide register data. SETTING: Nationwide study including contacts to GPs in Denmark prior to an incident AMI in 2005-2017. PARTICIPANTS: 121 232 adults (≥30 years) with incident AMI were included in the study. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome was odds of not having a face-to-face GP consultation within 1 year before an incident AMI. RESULTS: In total, 13 108 (10.8%) of the 121 232 individuals with incident AMI had no face-to-face consultation with the GP within 1 year before the AMI. Population density modified the association between travel distance and no face-to-face GP consultation. Increased odds of no face-to-face GP consultation was observed for medium (25th-75th percentile/1123-5449 m) and long (>75th percentile/5449 m) compared with short travel distance (<25th percentile/1123 m) among individuals living in small cities (OR (95% credible intervals) of 1.19 (1.10 to 1.29) and 1.19 (1.06 to 1.33), respectively) and rural areas (1.46 (1.26 to 1.68) and 1.48 (1.29 to 1.68), respectively). No association was observed for individuals living in large cities and the capital. CONCLUSIONS: Travel distance above approximately 1 km was significantly associated with no face-to-face GP consultation before an incident AMI among individuals living in small cities and rural areas. The structure of the healthcare system should consider the importance of geographical distance between citizens and the GP in remote areas.

Helicopter emergency medical services missions to islands and the mainland during a 3-year period in Denmark: a population-based study on patient and sociodemographic characteristics, comorbidity, and use of healthcare services.

BACKGROUND: The Danish Helicopter Emergency Medical Services (HEMS) is part of the Danish Emergency Medical Services System serving 5.7 million citizens with 1% living on islands not connected to the mainland by road. HEMS is dispatched based on pre-defined criteria including severity and urgency, and moreover to islands for less urgent cases, when rapid transport to further care is needed. The study aim was to characterize patient and sociodemographic factors, comorbidity and use of healthcare services for patients with HEMS missions to islands versus mainland. METHODS: Descriptive study of data from the HEMS database in a three-year period from 1 October 2014 to 30 September 2017. All missions in which a patient was either treated on scene or transported by HEMS were included. RESULTS: Of 5776 included HEMS missions, 1023 (17.7%) were island missions. In total, 90.2% of island missions resulted in patient transport by HEMS compared with 62.1% of missions to the mainland. Disease severity was serious or life-threatening in 34.7% of missions to islands compared with 65.1% of missions to mainland and less interventions were performed by HEMS on island missions. The disease pattern differed with more "Other diseases" registered on islands compared with the mainland where cardiovascular diseases and trauma were the leading causes of contact. Patients from islands were older than patients from the mainland. Sociodemographic characteristics varied between inhabiting island patients and mainland patients: more island patients lived alone, less were employed, more were retired, and more had low income. In addition, residing island patients had to a higher extend severe comorbidity and more contacts to general practitioners and hospitals compared with the mainland patients. CONCLUSIONS: HEMS missions to islands count for 17.7% of HEMS missions and 90.2% of island missions result in patient transport. The island patients encountered by HEMS are less severely diseased or injured and interventions are less frequently performed. Residing island patients are older than mainland patients and have lower socioeconomic position, more comorbidities and a higher use of health care services. Whether these socio-economic differences result in longer hospital stay or higher mortality is still to be investigated.

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

INTRODUCTION: A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure. OBJECTIVE: The aim was to study the association between DL exposure and incidence of first seizure. METHODS: A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001-2015 was conducted. DL exposure was defined as days' supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure. RESULTS: A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0-5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34-1.59). The aIRR ranged from 1.85 (95% CI 1.65-2.08) in children aged 0-5 years to 1.01 in adults aged 20 years or more (95% CI 0.85-1.19). CONCLUSION: This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.

Geographical inequalities in acute myocardial infarction beyond neighbourhood-level and individual-level sociodemographic characteristics: a Danish 10-year nationwide population-based cohort study.

OBJECTIVE: This study examined whether geographical patterns in incident acute myocardial infarction (AMI) were explained by neighbourhood-level and individual-level sociodemographic characteristics. DESIGN: An open cohort study design of AMI-free adults (age ≥30 years) with a residential location in Denmark in 2005-2014 was used based on nationwide administrative population and health register data linked by the unique personal identification number. Poisson regression of AMI incidence rates (IRs) with a geographical random effect component was performed using a Bayesian approach. The analysis included neighbourhood-level variables on income, ethnic composition, population density and population turnover and accounted for individual-level age, sex, calendar year, cohabitation status, income and education. SETTING: Residents in Denmark (2005-2014). PARTICIPANTS: The study population included 4 128 079 persons (33 907 796 person-years at risk) out of whom 98 265 experienced an incident AMI. OUTCOME MEASURE: Incident AMI registered in the National Patient Register or the Register of Causes of Death. RESULTS: Including individual and neighbourhood sociodemographic characteristics in the model decreased the variation in IRs of AMI. However, living in certain areas was associated with up to 40% increased IRs of AMI in the adjusted model and accounting for sociodemographic characteristics only moderately changed the geographical disease patterns. CONCLUSIONS: Differences in sociodemographic characteristics of the neighbourhood and individuals explained part, but not all of the geographical inequalities in incident AMI. Prevention strategies should address the confirmed social inequalities in incident AMI, but also target the areas with a heavy disease burden to enable efficient allocation of prevention resources.

Acute myocardial infarction: Does survival depend on geographical location and social background?

AIMS: This study described the interplay between geographical and social inequalities in survival after incident acute myocardial infarction (AMI) and examined whether geographical variation in survival exists when accounting for sociodemographic characteristics of the patients and their neighbourhood. METHODS: Ringmap visualization and generalized linear models were performed to study post-AMI mortality. Three individual-level analyses were conducted: immediate case fatality, mortality between days 1 and 28 after admission and 365-day survival among patients who survived 28 days after admission. RESULTS: In total, 99,013 incident AMI cases were registered between 2005 and 2014 in Denmark. Survival after AMI tended to correlate with sociodemographic indicators at the municipality level. In individual-level models, geographical inequality in immediate case fatality was observed with high mortality in northern parts of Jutland after accounting for sociodemographic characteristics. In contrast, no geographical variation in survival was observed among patients who survived 28 days. In all three analyses, odds and rates of mortality were higher among patients with low educational level (odds ratio (OR) (95% credible intervals) of 1.20 (1.12-1.29), OR of 1.12 (1.01-1.24) and mortality rate ratio of 1.45 (1.30-1.61)) and low income (OR of 1.24 (1.15-1.33), OR of 1.33 (1.20-1.48) and mortality rate ratio of 1.25 (1.13-1.38)). CONCLUSION: Marked geographical inequality was observed in immediate case fatality. However, no geographically unequal distribution of survival was found among patients who survived 28 days after AMI. Results additionally showed social inequality in survival following AMI.

The Influence of Antidepressants on the Disease Course Among Patients With Crohn's Disease and Ulcerative Colitis-A Danish Nationwide Register-Based Cohort Study.

BACKGROUND: Psychiatric comorbidity might modify the disease course adversely in patients with inflammatory bowel disease (IBD). Treatment options include antidepressants, which, apart from improving mood, have anti-inflammatory properties that might modify the disease course. This nationwide study aimed to examine the influence of antidepressants on the disease course among patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Patients registered with an incident diagnosis of CD or UC in the Danish National Patient Register (2000-2017) were included. Information on antidepressant use and proxy measures of disease activity (health care and drug utilization) was extracted from national population registers. Poisson regression was performed to estimate disease activity rates by antidepressant use adjusted for confounders. Furthermore, the analyses were performed stratified by IBD subtype and type of antidepressants. RESULTS: A total of 42,890 patients were included (UC: 69.5%; CD: 30.5%). When adjusted for confounders, a lower incidence rate of disease activity was found among antidepressant users compared with nonusers in both CD (incidence rate ratio [IRR], 0.75; 95% confidence interval [CI], 0.68-0.82) and UC (IRR, 0.90; 95% CI, 0.84-0.95) patients. Further, markedly lower rates of disease activity were found among CD (IRR, 0.51; 95% CI, 0.43-0.62) and UC (IRR, 0.67; 95% CI, 0.59-0.75) patients with no use of antidepressants before IBD onset. CONCLUSIONS: In this nationwide study, antidepressant use was found to be beneficial on the disease course among patients with UC and CD, particularly in patients with no use of antidepressants before IBD onset. Randomized controlled trials are warranted to investigate the potential of antidepressants being an adjunct treatment to conventional IBD therapy.

The difficult medical emergency call: A register-based study of predictors and outcomes.

BACKGROUND: Pre-hospital emergency care requires proper categorization of emergency calls and assessment of emergency priority levels by the medical dispatchers. We investigated predictors for emergency call categorization as "unclear problem" in contrast to "symptom-specific" categories and the effect of categorization on mortality. METHODS: Register-based study in a 2-year period based on emergency call data from the emergency medical dispatch center in Copenhagen combined with nationwide register data. Logistic regression analysis (N = 78,040 individuals) was used for identification of predictors of emergency call categorization as "unclear problem". Poisson regression analysis (N = 97,293 calls) was used for examining the effect of categorization as "unclear problem" on mortality. RESULTS: "Unclear problem" was the registered category in 18% of calls. Significant predictors for "unclear problem" categorization were: age (odds ratio (OR) 1.34 for age group 76+ versus 18-30 years), ethnicity (OR 1.27 for non-Danish vs. Danish), day of week (OR 0.92 for weekend vs. weekday), and time of day (OR 0.79 for night vs. day). Emergency call categorization had no effect on mortality for emergency priority level A calls, incidence rate ratio (IRR) 0.99 (95% confidence interval (CI) 0.90-1.09). For emergency priority level B calls, an association was observed, IRR 1.26 (95% CI 1.18-1.36). DISCUSSIONS: The results shed light on the complexity of emergency call handling, but also implicate a need for further improvement. Educational interventions at the dispatch centers may improve the call handling, but also the underlying supportive tools are modifiable. The higher mortality rate for patients with emergency priority level B calls with "unclear problem categorization" could imply lowering the threshold for dispatching a high level ambulance response when the call is considered unclear. On the other hand a "benefit of the doubt" approach could hinder the adequate response to other patients in need for an ambulance as there is an increasing demand and limited resources for ambulance services. CONCLUSIONS: Age, ethnicity, day of week and time of day were significant predictors of emergency call categorization as "unclear problem". "Unclear problem" categorization was not associated with mortality for emergency priority level A calls, but a higher mortality was observed for emergency priority level B calls.

Geographical clustering of incident acute myocardial infarction in Denmark: A spatial analysis approach.

OBJECTIVES: To examine the geographical patterns in AMI and characterize individual and neighborhood sociodemographic factors for persons living inside versus outside AMI clusters. METHODS: The study population comprised 3,515,670 adults out of whom 74,126 persons experienced an incident AMI (2005-2011). Kernel density estimation and global and local clustering methods were used to examine the geographical patterns in AMI. Median differences and frequency distributions of sociodemographic factors were calculated for persons living inside versus outside AMI clusters. RESULTS: Global clustering of AMI occurred in Denmark. Throughout the country, 112 significant clusters with high risk of incident AMI were identified. The relative risk of AMI in significant clusters ranged from 1.45 to 47.43 (median=4.84). Individual and neighborhood socioeconomic position was markedly lower for persons living inside versus outside AMI clusters. CONCLUSIONS: AMI is geographically unequally distributed throughout Denmark and determinants of these geographical patterns might include individual- and neighborhood-level sociodemographic factors.

Geographical variation in a fatal outcome of acute myocardial infarction and association with contact to a general practitioner.

BACKGROUND: Geographical variation in incidence and mortality of acute myocardial infarction (AMI) is present in Denmark. We aimed at examining the association between contact to a general practitioner (GP) the year before AMI and a fatal outcome of AMI. METHODS: Register-based data and individual-level addresses including 69,608 individuals with AMI in 2006-2011. A Bayesian hierarchical logistic regression model was used to examine the association. RESULTS: A fatal outcome of AMI was seen among 12.0% (78%) of individuals with (without) contact to a GP the year before AMI. A significant association was estimated. CONCLUSIONS: A fatal outcome of AMI was significantly associated with contact to a GP. A high population to GP ratio and long distance to GP could not explain the increased odds of a fatal outcome of AMI for individuals with no contact to a GP.

Body water distribution and risk of cardiovascular morbidity and mortality in a healthy population: a prospective cohort study.

BACKGROUND: Early alterations in the cardiovascular structure and function may change normal body water distribution. The resulting fluid shifts may thus serve as an early marker for cardiovascular disease. However, studies examining this in healthy populations are absent. OBJECTIVE: This study examined the association between the proportion of total body water that is extracellular water and subsequent development of non-fatal or fatal cardiovascular disease in a healthy population. METHOD: Bioelectrical impedance spectroscopy is an easy-to-use, non-invasive and relatively inexpensive technique to evaluate changes in body water distribution. A random subset (n = 2120) of Danes aged 41-71 years, examined in 1993-1994 for body water distribution by bioelectrical impedance spectroscopy was included. Cox-proportional hazard models and linear splines were performed. The ratio between resistance estimates from an infinite-frequency and from no-frequency (R∞/R0) was used as a surrogate measure of ratio between extracellular water and total body water. The outcome was 13.5 years of follow-up for cardiovascular morbidity and mortality. RESULTS: A high proportion of total body water that is extracellular water was associated with increased risk of incident cardiovascular disease. A threshold effect was evident, with greatly increased risk of cardiovascular morbidity and mortality above R∞/R0 = 0.68. Below the threshold there seemed to be no additional benefit of having a low ratio. CONCLUSION: Our findings suggest that non-clinically evident oedema, measured as an increased proportion of total body water that is extracellular, above a threshold of 0.68, may be an early marker of pre-clinical cardiovascular disease. This simple, safe, cheap and easily obtainable measure of R∞/R0 from bioelectrical impedance may help the early identification of these otherwise clinically healthy individuals who are at an increased risk of future cardiovascular disease. However, more studies are needed before it can be concluded that bioelectrical impedance spectroscopy improves clinical risk prediction.