The Danish health care system provides partial reimbursement of most prescription medications in Denmark. The dispensation of prescription medications is registered in administrative databases. Each time a prescription is redeemed at a pharmacy, an electronic record is generated with information related to the user, prescriber, the pharmacy, and the dispensed drug. The National Health Service gathers this information for administration of the drug reimbursement plan. Recently, this information became the basis for the establishment of a new research database, the Danish National Database of Reimbursed Prescriptions (DNDRP). In this paper, we review the content, coverage, quality, linkage, access, and research possibilities of this new database. The database encompasses the reimbursement records of all reimbursed drugs sold in community pharmacies and hospital-based outpatient pharmacies in Denmark since 2004. On average, approximately 3.5 million users are recorded in the database each year. During the coverage period, the number of annual prescription redemptions increased by 15%. Most dispensed prescriptions are in the categories “alimentary tract and metabolism”, “cardiovascular system”, “nervous system”, and “respiratory system”. Individuals are identified by the unique central personal registration (CPR) number assigned to all persons born in or immigrating to Denmark. The new database fully complies with Denmark’s Act on Processing of Personal Data, while avoiding additional restrictions imposed on data use at the Danish National Prescription Registry, administered by Statistics Denmark. Most importantly, CPR numbers are reversibly encrypted, which allows re-identification of drug users; furthermore, the data access is possible outside the servers of Statistics Denmark. These features open additional opportunities for international collaboration, validation studies, studies on adverse drug effects requiring review of medical records, studies involving contact to general practitioners, and linkage of prescription data to other clinical and research databases. The DNDRP thus is a valuable data source for pharmacoepidemiological research.

To cite this article: Schmidt M, Cannegieter SC, Johannesdottir SA, Dekkers OM, Horv ath-Puh o E, Sørensen HT. Statin use and venous throm-boembolism recurrence: a combined nationwide cohort and nested case-control study. J Thromb Haemost 2014; 12: 1207-15. See also Rodger M. Is it time to try or to trial statins to prevent recurrent venous thromboembolism?. This issue, pp 1204-6. Summary. Background: Data on statins' effect on venous thromboembolism (VTE) recurrence are conflicting. Objectives: We examined whether statin use was associated with reduced risk of recurrent VTE in a nationwide population-based setting. Patients/Methods: Using the Danish National Patient Registry, we identified first-time and recurrent VTEs between 1 July 2004 and 31 Decem-ber 2012 (n = 27 862). VTE diagnoses were validated by medical record review of a subsample of patients. We ascertained nationwide prescription data and categorized statin use as current (further divided into new and long-term use), former and no use. We identified statin use at baseline (mimicking an intention-to-treat analysis) and in a time-varying manner during follow-up (mimicking per-protocol analysis) and computed hazard ratios (HRs) for recurrent VTE using Cox regression. In a supplementary nested case-control study, we identified statin use at time of VTE recurrence and computed odds ratios as unbiased estimates of the incidence rate ratios (IRRs) using conditional logistic regression. We adjusted for age, sex, year of diagnosis, provoking factors, co-morbidities and co-medications, including time-varying use of aspirin and anticoagulant drugs. Results: The adjusted HR comparing current use with no use was 0.72 (95% confidence interval [CI], 0.59-0.88) for recurrent VTE, with a stronger effect of high (0.40; 95% CI, 0.21-0.78) vs. low potency statins (0.77; 95% CI, 0.63-0.94). Consistently, the recurrence rate was reduced in both the time-varying analysis (HR=0.64; 95% CI, 0.54-0.77) and nested case-control analysis (IRR=0.55; 95% CI, 0.45-0.67). The effect was largest for recurrent deep venous thrombosis. Conclusions: Statin use was associated with reduced VTE recurrence .

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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are involved in carcinogenesis. Therefore, the authors of this report examined the association between NSAID use and the risk of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: From 1991 through 2009, all incident cases of SCC (n ¼ 1974), BCC (n ¼ 13,316), and MM (n ¼ 3242) in northern Denmark were identified. Approximately 10 population controls (n ¼ 178,655) were matched to each case by age, gender, and county of residence. The use of aspirin, other nonselective NSAIDs, or selective COX-2 inhibitors was ascertained through a prescription database. Conditional logistic regression analyses adjusted for potential confounders were used to compute odds ratios as estimates of incidence rate ratios (IRRs). RESULTS: For NSAIDs overall, ever use (>2 prescriptions) compared with nonuse ( 2 prescriptions) was associated with a decreased risk of SCC (IRR, 0.85; 95% confidence interval [CI], 0.76-0.94) and MM (IRR, 0.87; 95% CI, 0.80-0.95), especially for long-term use (!7 years) and high-intensity use (>25% prescription coverage during the total duration of use). NSAID use was not associated with a reduced risk of BCC overall (IRR, 0.97; 95% CI, 0.93-1.01), but the risk of BCC at sites other than the head and neck was reduced in association with long-term use (IRR, 0.85; 95% CI,) and high-intensity use (IRR, 0.79; 95% CI, 0.69-0.91). All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors (diclofenac, etodolac, and meloxicam). CONCLUSIONS: The current results indicated that NSAID use may decrease the risk of SCC and MM.

Health Composite Scores from the 12-item Short-Form Health Survey. Those randomized to the intervention group increased their 6-minute walk distance in meters significantly (357.4 to 399.8 vs 353.3 to 342.2 for those in the control group; mean difference, 53.5; P < .001). There were also increases in maximum treadmill walking time (intervention, 7.91 to 9.44 minutes vs control, 7.56 to 8.09 minutes; mean difference, 1.01 minutes; P ¼ .04). Accelerometer-measured physical activity over 7 days also increased in the intervention group vs the control group (P ¼ .03). There were also significant improvements in the Walking Impairment Questionnaire distance score (P ¼ .003) and Walking Impairment Questionnaire speed score (P ¼ .004). Comment: The study indicates that home-based exercise can be effective in patients with PAD. It does not indicate that home-based exercise has equal effectiveness to supervised exercise programs, because the two were not directly compared. Nevertheless, until supervised exercise becomes a benefit of insurance coverage, the data should encourage physicians to recommend home-based exercise therapy in their patients with PAD.

ObjectivesTo examine the association between body mass index (BMI) in young adulthood and cardiovascular risks, including venous thromboembolism, before 55 years of age.DesignCohort study using population-based medical databases.SettingOutcomes registered from all hospitals in Denmark from 1977 onwards.Participants6502 men born in 1955 and eligible for conscription in Northern Denmark.Main outcome measuresFollow-up began at participants’ 22nd birthday and continued until death, emigration or 55 years of age, whichever came first. Using regression analyses, we calculated the risks and HRs, adjusting for cognitive test score and years of education.Results48% of all obese young men (BMI ≥30 kg/m2) were either diagnosed with type 2 diabetes, hypertension, myocardial infarction, stroke or venous thromboembolism or died before reaching 55 years of age. Comparing obese men with normal weight men (BMI 18.5 to <25.0 kg/m2), the risk difference for any outcome was 28% (95% CI 19% to 38%) and the HR was 3.0 (95% CI 2.3 to 4.0). Compared with normal weight, obesity was associated with an event rate that was increased more than eightfold for type 2 diabetes, fourfold for venous thromboembolism and twofold for hypertension, myocardial infarction and death.ConclusionsIn this cohort of young men, obesity was strongly associated with adverse cardiometabolic events before 55 years of age, including venous thromboembolism. Compared with those of normal weight, young obese men had an absolute risk increase for type 2 diabetes, cardiovascular morbidity or premature death of almost 30%.

BackgroundExperimental data suggest that catecholamine hormones are involved in stimulating the aggressiveness of ovarian cancer, but few population-based studies have examined this association. We therefore conducted a population-based cohort study to examine whether ß-blockers affect mortality following ovarian cancer diagnosis.MethodsWe used the Danish Cancer Registry to identify all patients diagnosed with ovarian cancer in northern Denmark between 1999 and 2010 (n=6,626). Data on medication use, comorbidity, and survival were obtained from medical databases. According to the last redeemed prescription before diagnosis, ß-blocker use was categorized as current (within ≤90 days), previous (>90 days) or never. We used Cox proportional hazards regression to calculate hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) adjusting for confounding factors.ResultsAmong the ovarian cancer patients, 373 (5.6%) were current, 87 (1.3%) previous, and 6,166 (93.1%) were nonusers of ß-blockers. Median duration of use was 19.0 months among current users and 43.0 months among previous users. Median follow-up was 2.55 years (IQR: 0.81-9.23). Nonusers and current users of ß-blockers had similar comorbidity burden whereas previous users had moderate comorbidity more frequently. Compared with nonusers, the adjusted HR was 1.17 (95% CI: 1.02–1.34) for current users and 1.18 (95% CI: 0.90–1.55) for previous users. Secondary analyses stratifying by cancer stage and duration of ß-blocker use supported the overall results.ConclusionsWe found no evidence that ß-blocker use was associated with decreased mortality following ovarian cancer diagnosis.

To cite this article: Johannesdottir SA, Schmidt M, Horvá th-Puhó E, Sørensen HT. Autoimmune skin and connective tissue diseases and risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost 2012; 10: 815-21.Summary. Background: Systemic inflammation is associated with vessel wall damage, upregulation of procoagulants, downregulation of anticoagulants, and suppression of fibrinolysis. Autoimmune diseases may therefore increase the risk of venous thromboembolism (VTE). Objectives: To examine whether autoimmune skin and connective tissue diseases are associated with increased VTE risk. Methods: We conducted this population-based case-control study in northern Denmark, using administrative databases. From 1999 to 2009, we identified 14 721 VTE cases and 147 210 birth year-matched, sex-matched and county-matched population controls. The date of diagnosis/matching was considered to be the index date for cases and controls. For all study subjects, we identified hospital diagnoses of autoimmune skin or connective tissue diseases between 1977 and the index date. We used conditional logistic regression with adjustment for VTE risk factors to calculate odds ratios and 95% confidence intervals (CIs) for patients with vs. without autoimmune disease. Given the riskset sampling design, odds ratios estimate incidence rate ratios (IRRs). Results: Autoimmune skin disease was not associated with VTE (IRR 1.0; 95% CI 0.9-1.2). Patients with connective tissue disease had an increased VTE risk within 90 days (IRR 2.3; 95% CI 1.5-3.7) and 91-365 days (IRR 2.0; 95% CI 1.5-2.8) after diagnosis, but not thereafter (IRR 1.1; 95% CI 1.0-1.2). Among connective tissue diseases, the greatest overall risk increases were found for juvenile rheumatoid arthritis (IRR 3.0; 95% CI 1.4-6.4) and systemic lupus erythematosus (IRR 2.8; 95% CI 1.7-4.7). Conclusions: Autoimmune connective tissue disease was associated with an increased risk of VTE within 1 year after diagnosis, whereas skin diseases were not.