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.

Utilization of etoricoxib in dental patients in the Nordic countries: a population-based register study.

Background: Etoricoxib is a second-generation cyclooxygenase-2-inhibitor approved in 2012 for short-term treatment of pain associated with dental surgery. Objectives: To evaluate etoricoxib utilization in dental patients in the Nordic countries, including its off-label use. Methods: The entire populations of Denmark, Finland, Sweden and Norway with etoricoxib prescriptions written by dentists and dispensed in 2012-2014 were evaluated using national register data. Nationwide estimates of etoricoxib utilization were generated according to year, gender, age, dose and package size. Off-label use in paediatric patients, prescribed doses >90 mg/day or for dental contacts not associated with surgical procedures, and concomitant administration with anticoagulants were evaluated. Results: Utilization of etoricoxib for dental pain was low (1615 prescriptions: Finland, 907; Sweden, 359; Norway, 337; Denmark, 12). Overall, 70% of the prescriptions were without an associated dental procedure. Moreover, 58%, 55%, 10% and 58% of the prescriptions in Denmark, Finland, Sweden and Norway, respectively, were for >90 mg/day doses. Few paediatric prescriptions were dispensed (n < 10), and only a small overlap (n = 21) was observed between etoricoxib and anticoagulant prescriptions. Conclusions: Given the low overall number of prescriptions, it is unlikely that off-label use of etoricoxib within dentistry in the Nordic countries is an important public health concern.

Effect of screening for type 2 diabetes on healthcare costs: a register-based study among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009.

AIMS/HYPOTHESIS: Trials have not demonstrated benefits to the population of screening for type 2 diabetes. However, there may be cost savings for those found to have diabetes. We therefore aimed to compare healthcare costs among individuals with incident type 2 diabetes in a screened group with those in an unscreened group. METHODS: In this register-based, non-randomised controlled trial, eligible individuals were men and women aged 40-69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk-score questionnaire. Individuals with a moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other practices in Denmark constituted the retrospectively constructed no-screening (control) group. In this post hoc analysis, we identified individuals from the screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 (n = 139,075). Using national registry data, we quantified the cost of healthcare services in these two groups between 2001 and 2012. From a healthcare sector perspective, we estimated the potential healthcare cost savings for individuals with diabetes that were attributable to the screening programme. RESULTS: In the screening group, 27,177 of 153,107 individuals (18% of those sent a risk-score questionnaire) attended for screening, 1533 of whom were diagnosed with diabetes. Between 2001 and 2009, 13,992 people were newly diagnosed with diabetes in the screening group (including those diagnosed by screening) and 125,083 in the no-screening group. Healthcare costs were significantly lower in the screening group compared with the no-screening group (difference in mean total annual healthcare costs -€889 per individual with incident diabetes; 95% CI -€1196, -€581). The screening programme was associated with a cost saving per person with incident diabetes over a 5-year period of €2688 (95% CI €1421, €3995). CONCLUSIONS/INTERPRETATION: Healthcare costs were lower among individuals with incident type 2 diabetes in the screened group compared with the unscreened group. The relatively modest cost of screening per person discovered to have developed diabetes was offset within 2 years by savings in the healthcare system.

Social inequality in diabetes patients' morbidity patterns from diagnosis to death - A Danish register-based investigation.

AIM: Measuring socioeconomic inequalities in health and health care, and understanding determinants of such inequalities, are critical for achieving higher equity in health. Equity in health is a prerequisite for public health and welfare. The aim of the paper is (1) to quantify inequality in diabetes morbidity patterns over patients' entire life span, and (2) to compare levels of inequality measured through income and educational level, respectively, as proxies for socioeconomic status (SES). METHOD: Historic individual register data on the entire Danish diabetes population alive in 2011 were gathered. Cox survival analysis and a concentration index decomposition approach were applied to analyse relevant morbidity indicators reflecting patients' health state at diagnosis and throughout their lives with diabetes. RESULTS: Patients with high education have approximately 26% lower mortality hazard when diagnosed with diabetes and 10-15% lower hazard of developing complications as compared with patients with short education. The outcome variables: 'severe complications at diagnosis' and 'years with severe complications' inhibit the highest negative concentration index value, indicating that morbidity is concentrated among the lower SES groups, whereas the outcome variables 'years without complications' and 'duration of diabetes' concentrate among the socioeconomically better-off patients. CONCLUSIONS: Significant differences in diabetes patients' morbidity patterns and survival indicate that diabetes impacts harder on patients of lower SES; these patients experience more severe complications and die earlier. Hence to reduce inequality in health, it is important to invest in efforts targeted towards socially vulnerable groups.

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.

Large impact of antidiabetic drug treatment and hospitalizations on economic burden of diabetes mellitus in The Netherlands during 2000 to 2004.

OBJECTIVE: To estimate the burden of diabetes mellitus (DM) and its complications in The Netherlands. METHODS: The PHARMO Record Linkage System comprised among others linked drug dispensing, hospital and clinical laboratory data from approximately 2.5 million individuals in The Netherlands. Patients with DM (type 1 and type 2) were included in the study cohort from 2000 to 2004 if they used antidiabetic drugs or had HbA1c >or= 6.5 mmol/L or had a hospitalization for DM or a diabetic complication in the measurement year or in the preceding year. Controls, defined as subjects without a diagnosis of DM and/or subjects not prescribed glucose-lowering medication, were 1:1 matched to patients with diabetes, on birth year, zip code, and gender. Complications (hospitalizations and dispensings for cardiovascular disease/eye problems/amputations) were classified into stages. Complications attributed to DM were estimated as complication stages 1 and 2 among patients minus those among controls. Drug costs were extrapolated to The Netherlands by direct standardization. RESULTS: Among the total population in The Netherlands, the prevalence of DM increased from 2.8% in 2000 to 4.0% in 2004. Severe cardiovascular complications attributed to DM increased from 18,000 to 39,000 patients. Per DM patient the cost of direct treatment attributed to DM increased from Euro 974 in 2000 to Euro 1283 in 2004. Per 100 members of the total population, this increase was from Euro 2764 in 2000 to Euro 5140 in 2004. Most of these costs (65% in 2004) were because of hospitalizations. CONCLUSION: Drug treatment, hospitalizations, and cost attributed to diabetes mellitus have almost doubled between 2000 and 2004, but so did the "background" costs in the general population, perhaps because of preventive efforts.

Electronic Health Lifestyle Coaching Among Diabetes Patients in a Real-Life Municipality Setting: Observational Study.

BACKGROUND: Internet and mobile interventions aiming to promote healthy lifestyle have attracted much attention because of their scalability and accessibility, low costs, privacy and user control, potential for use in real-life settings, as well as opportunities for real-time modifications and interactive advices. A real-life electronic health (eHealth) lifestyle coaching intervention was implemented in 8 Danish municipalities between summer 2016 and summer 2018. OBJECTIVE: The aim of this study was to assess the effects associated with the eHealth intervention among diabetes patients in a real-life municipal setting. The eHealth intervention is based on an initial meeting, establishing a strong empathic relationship, followed by digital lifestyle coaching and collaboration supported by a Web-based community among patients. METHODS: We conducted an observational study examining the effect of an eHealth intervention on self-reported weight change among 103 obese diabetes patients in a real-life municipal setting. The patients in the study participated in the eHealth intervention between 3 and 12 months. A weight change was observed at 6, 9, and 12 months. We used regression methods to estimate the impacts of the intervention on weight change. RESULTS: We found that the eHealth intervention significantly reduced weight among diabetes patients, on average 4.3% of the initial body mass, which corresponds to 4.8 kg over a mean period of 7.3 months. Patients who were in intervention for more than 9 months achieved a weight reduction of 6.3% or 6.8 kg. CONCLUSIONS: This study brings forward evidence of a positive effect of a real-life eHealth lifestyle intervention on diabetes patients' lifestyle in a municipal setting. Future research is needed to show if the effect is sustainable from a long-term perspective.

Finasteride Use and Risk of Male Breast Cancer: A Case-Control Study Using Individual-Level Registry Data from Denmark, Finland, and Sweden.

BACKGROUND: In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders. METHODS: The source population consisted of all men (≥35 years) from Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). Cases with incident male breast cancer were identified in the cancer registries and matched with 50 density-sampled, age, and country-matched male population controls per case. Exposure information on finasteride use was derived from the prescription registries. Potential confounders were identified using the directed acyclic graph methodology and measured by use of information from nation-wide registries. RESULTS: The study population comprised 1,005 male breast cancer cases and 43,058 controls. Confounder-adjusted odds of finasteride exposure were not statistically significantly increased [OR, 1.09; 95% confidence interval (CI), 0.77-1.54] in breast cancer cases relative to controls. There was no evidence of a dose-response relationship, as the group with greatest exposure to finasteride was associated with lowest OR of male breast cancer [OR, 0.72 (95% CI, 0.40-1.30)]. Sensitivity analyses did not reveal marked changes in results with different exposure definitions or for specific subgroups. CONCLUSIONS: Results from this study provided no evidence that finasteride use was associated with male breast cancer. IMPACT: This large confounder-adjusted study supports the view that exposure to finasteride is not associated materially with male breast cancer risk.

Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries.

A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess the potential association between dispensed finasteride and MBC. A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual-level register data included country, dates of dispensed finasteride, MBC diagnosis, and death. Incidence rate ratios (IRRs) were estimated using a generalized linear model with a Poisson distribution. An increased risk of MBC was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers. The IRR increased to 1.60 (95% CI = 1.20-2.13) when users in Norway and Sweden with short follow-up time were excluded. The highest IRR was seen among men with medium duration of dispensed finasteride, medium accumulated consumption of finasteride, and among men with first dispensed finasteride prescription 1-3 years prior to diagnosis. The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and MBC. In conclusion, a significant association between dispensed finasteride and MBC was identified. However, due to limited data for adjustment of potential confounding and surveillance bias in the present study, further research is needed to confirm these results.

Socioeconomic inequality of diabetes patients' health care utilization in Denmark.

Understanding socioeconomic inequalities in health care is critical for achieving health equity. The aim of this paper is threefold: 1) to quantify inequality in diabetes health care service utilization; 2) to understand determinants of these inequalities in relation to socio-demographic and clinical morbidity factors; and 3) to compare the empirical outcome of using income level and educational level as proxies for Socio Economic Status (SES).Data on the entire Danish population of diabetes patients in 2011 (N = 318,729) were applied. Patients' unique personal identification number enabled individual patient data from several national registers to be linked. A concentration index approach with decomposition into contributing factors was applied. Differences in diabetes patients' health care utilization patterns suggest that use of services differ among patients of lower and higher SES, despite the Danish universal health care system. Especially, out-patient services, rehabilitation and specialists in primary care show different utilization patterns according to SES. Comparison of the empirical outcome from using educational level and income level as proxy for patients' SES indicate important differences in inequality estimates. While income, alike other measures of labor market attachment, to a certain extent is explained by morbidity and thus endogenous, education is more decisive for patients' ability to take advantage of the more specialized services provided in a universal health care system.

Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction: a Danish nationwide population-based cohort study.

OBJECTIVES: The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. DESIGN: A registry-based observational cohort study was performed using antecedent data. SETTING: This study linked morbidity, mortality and medication data from Danish national registries. PARTICIPANTS: All 28 449 patients admitted to a Danish hospital with a first-time MI and alive at discharge from 2009 through 2012 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was initiation of DAPT and secondary outcomes comprised persistence in DAPT treatment and switches between DAPT treatments. RESULTS: The overall proportion of patients prescribed DAPT increased from 68% (CL 95% 67-69%) to 73% (CL 95% 72-74%) from 2009 to 2012. For treatment of patients with and without percutaneous coronary intervention (PCI), the corresponding numbers were from 87% (CL 95% 86-88%) to 91% (CL 95% 90-92%) and from 49% (CL 95% 47-50%) to 52% (CL 95% 51-54%), respectively. Non-PCI patients had a higher cardiovascular risk compared with PCI patients. Among PCI patients, age>75 years, atrial fibrillation, diabetes and peripheral arterial disease were associated with a higher risk of treatment breaks for DAPT. Among patients without PCI, ticagrelor treatment was associated with an increased risk of treatment breaks during the first 12 months compared with clopidogrel treatment. CONCLUSIONS: From 2009 to 2012, there was an increase in the proportion of patients with MI receiving DAPT, and a longer duration of DAPT. Still, a large proportion of patients without PCI are discharged either without DAPT or with a short DAPT duration. These findings may indicate the need for more careful attention to DAPT for patients with MI not undergoing PCI in Denmark.

Incidence, morbidity, mortality, and prevalence of diabetes in Denmark, 2000-2011: results from the Diabetes Impact Study 2013.

PURPOSE: As part of the Danish Diabetes Impact Study 2013, we present trends in the incidence, morbidity, mortality, and prevalence of diabetes in Denmark for the period 2000 through 2011. PATIENTS AND METHODS: The Danish National Diabetes Register was established in 2006 and is assumed to cover all patients with diabetes, alive as of the end of 1996, and all subsequent new cases. The present study is based on the content of the register as of July 3, 2013 (n=497,232 patients). Using the personal identification code assigned to all Danish inhabitants, all available supplementary information from the Danish National Patient Register and the Danish Civil Registration Service was used to define the date of diagnosis of diabetes and the first date of experiencing complications (grouped according to impact and severity). RESULTS: During the period of 2000 to 2011, the incidence rate of diabetes increased approximately 5% annually. During the same period, decreasing trends were observed for both the rates of progression in complications and of the complication-specific mortality. During the same period, the prevalence of diabetes doubled. CONCLUSION: The increasing prevalence of diabetes in Denmark is driven by increasing incidence combined with decreasing morbidity and mortality in the population of patients with diabetes. These mechanisms will be explored further as part of the Diabetes Impact Study 2013, together with investigations into the socioeconomic and health economic aspects of diabetes.

Validation of the danish national diabetes register.

The Danish National Diabetes Register (NDR) was established in 2006 and builds on data from Danish health registers. We validated the content of NDR, using full information from the Danish National Patient Register and data from the literature. Our study indicates that the completeness in NDR is ≥95% concerning ascertainment from data sources specific for diabetes, ie, prescriptions with antidiabetic drugs and diagnoses of diabetes in the National Patient Register. Since the NDR algorithm ignores diabetes-related hospital contacts terminated before 1990, the establishment of the date of inclusion is systematically delayed for ≥10% of the registrants in general and for ≥30% of the inclusions before 1997 in particular. This bias is enhanced for ascertainment by chiropody services and by frequent measurements of blood glucose because the date of reimbursement of services, rather than the date of encounter, has been taken as the date of inclusion in NDR. We also find that some 20% of the registrations in NDR may represent false positive inclusions of persons with frequent measurements of blood glucose without having diabetes. We conclude that NDR is a novel initiative to support research in the epidemiological and public health aspects of diabetes in Denmark, but we also present a list of recommended changes for improving validity, by reducing the impact of current sources of bias and misclassifications.

Incidence of cancer and mortality in patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial.

The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.