The impact of type 2 diabetes and glycaemic control on mortality and clinical outcomes in hospitalized patients with COVID-19 in the capital region of Denmark.

AIM: To explore the impact of type 2 diabetes (T2D), glycaemic control and use of glucose-lowering medication on clinical outcomes in hospitalized patients with COVID-19. MATERIALS AND METHODS: For all patients admitted to a hospital in the Capital Region of Denmark (1 March 2020 to 1 December 2021) with confirmed COVID-19, we extracted data on mortality, admission to intensive care unit (ICU), demographics, comorbidities, medication use and laboratory tests from the electronic health record system. We compared patients with T2D to patients without diabetes using Cox proportional hazards models adjusted for available confounding variables. Outcomes were 30-day mortality and admission to an ICU. For patients with T2D, we also analysed the association of baseline haemoglobin A1c (HbA1c) levels and use of specific glucose-lowering medications with the outcomes. RESULTS: In total, 4430 patients were analysed, 1236 with T2D and 2194 without diabetes. The overall 30-day mortality was 19% (n = 850) and 10% (n = 421) were admitted to an ICU. Crude analyses showed that patients with T2D both had increased mortality [hazard ratio (HR) 1.37; 95% CI 1.19-1.58] and increased risk of ICU admission (HR 1.28; 95% CI 1.04-1.57). When adjusted for available confounders, this discrepancy was attenuated for both mortality (adjusted HR 1.13; 95% CI 0.95-1.33) and risk of ICU admission (adjusted HR 1.01; 95% CI 0.79-1.29). Neither baseline haemoglobin A1c nor specific glucose-lowering medication use were significantly associated with the outcomes. CONCLUSION: Among those hospitalized for COVID-19, patients with T2D did not have a higher risk of death and ICU admission, when adjusting for confounders.

Fatal drug overdoses in individuals treated pharmacologically for chronic pain: a nationwide register-based study.

INTRODUCTION: Chronic pain patients may be at an increased risk for drug overdoses as a result of comorbid psychiatric disorders and treatment with risk-increasing prescription medications, such as opioids. We aimed to characterise fatal drug overdoses and investigate factors associated with the deaths among individuals who had been treated pharmacologically for chronic pain. METHODS: We included all individuals who received analgesics reimbursed for chronic pain in Norway during 2010-9 (n=569 047). Among this population, we identified all individuals with drug overdoses as cause of death (cases). Extracting data from national registries on diagnoses, filled prescriptions, and socioeconomic variables, we used a nested case-control design to compare the cases with age- and sex-matched controls from the study population. RESULTS: Overall, 623 (0.11%) individuals in the study population died of an overdose. Most, 66.8%, had overdosed accidentally, and 61.9% as a result of pharmaceutically available opioids. Compared with the controls (n=62 245), overdoses overall were associated strongly with substance use disorders (adjusted odds ratio 7.78 [95% confidence interval 6.20-9.77]), use of combinations of opioids, benzodiazepines and related drugs and gabapentinoids (4.60 [3.62-5.85]), previous poisoning with pharmaceuticals (2.78 [2.20-3.51]), and with living alone the last year of life (2.11 [1.75-2.54]). Intentional overdoses had a stronger association with previous poisonings with pharmaceuticals whereas accidental overdoses were strongly associated with substance use disorders. CONCLUSIONS: This study shows the need for better identification of overdose and suicide risk in individuals treated for chronic pain. Extra caution is needed when treating complex comorbid disorders, especially with overdose risk-increasing medications.

Celiac disease and risk of neuropsychiatric disorders: A nationwide cohort study.

INTRODUCTION: Previous studies have indicated that patients with celiac disease (CD) may have an increased risk of developing neuropsychiatric disorders. However, large-scale epidemiologic studies on the topic are still scarce. We aimed to examine the association between CD and development of neuropsychiatric disorders during an 18-year follow-up period. METHODS: We conducted a prospective cohort study. All Danish patients with an incident diagnosis of CD (ICD-10 K90.0) from 2000 to 2018 were identified in nationwide registries and compared with birthdate- and sex-matched controls (variable 1:10 ratio) for the development of a neuropsychiatric disease. Individual neuropsychiatric diseases were also examined. The absolute risk was calculated by the cumulative incidence, and the relative risk was estimated in Cox regression models. RESULTS: We identified a cohort of 6329 patients with CD diagnosed from 2000 to 2018 and 63,287 matches at risk for developing incident neuropsychiatric disorders. The cumulative incidence of development of any neuropsychiatric disorder was 3.9%, 14.9%, 24.8%, 35.9% after 1, 5, 10, and 15 years of follow-up, respectively, in patients with CD compared with 1.8%, 9.3%, 18.3%, and 27.0% in controls. Gray's test for equality p < 0.001. The relative risk was HR = 1.58 (95% confidence interval: 1.49-1.68) in CD patients compared with matches. For the individual outcomes, CD was associated with an increased relative risk of developing anxiety, depression, eating disorders, epilepsy, migraine, and stress. We also found indications of an increased relative risk of ADHD, alcoholism, bipolar disorders, and drug abuse, although the associations were less clear. No associations were found between CD and dementia, Parkinson's disease, and schizophrenia. CONCLUSIONS: In this nationwide study including more than 6000 patients with CD, we found an increased risk of development of a neuropsychiatric disorder compared with age- and sex-matched controls. The causes and the clinical relevance of these associations remain to be elucidated.

Sick leave and disability pension among TMD patients with musculoskeletal diseases, mental and behavioural disorders - a SWEREG-TMD population-based cohort study.

BACKGROUND: Temporomandibular disorders (TMD) are associated with musculoskeletal diseases (MSD), mental and behavioural disorders (MBD), and patients with TMD have been shown to have 2-3 times more days of sick leave (SL) and disability pension (DP) than the general population. MSD and MBD are two of the most common causes for SL and DP, and the association between TMD and the influence of comorbidities on the need for SL and DP among TMD patients need further clarification. This study investigates the impact of MSD and MBD comorbidity on SL and DP among TMD patients diagnosed in a hospital setting and/or surgically treated. METHODS: All incident TMD patients diagnosed or treated in a hospital setting between 1998 and 2016 and aged 23-59 were included. A non-exposed comparison cohort was collected from the general population. The cohorts were grouped based on the presence of comorbidity: No comorbidity (Group I); MSD comorbidity (Group II); MBD comorbidity (Group III); and combined MSD and MBD comorbidity (Group IV). Main outcomes were mean annual days of SL and DP, and statistical analysis was conducted using generalized estimated equations. RESULTS: TMD subjects with no comorbidities (Group I) and with MSD/MBD comorbidity (Group II and III) were 2-3 times more often on SL and DP than the corresponding groups from the general population. However, in the group with both MSD and MBD comorbidity (Group IV), the difference between the TMD subjects and the general population was diminishing, suggesting an additive effect. CONCLUSION: TMD patients are more dependent on SL and DP benefits compared to general population and the difference remains even after considering MSD and MBD comorbidity. In individuals with combined MSD and MBD comorbidity, concurrent TMD has less impact on the need for social insurance benefits. The results accentuate the impact TMD has on the patients' impaired ability to return to work and why TMD should be recognized as having a substantial impact on individual and economic suffering as well as on societal costs, with emphasis on the influence of comorbidities on patient suffering.

Sick leave and disability pension in a cohort of TMD-patients - The Swedish National Registry Studies for Surgically Treated TMD (SWEREG-TMD).

BACKGROUND: Temporomandibular disorders (TMD) are common and affect approximately 10% of the adult population. TMD is usually associated with headache, pain in the masticatory muscles and/or the temporomandibular joint, clicking or crepitations during mandibular movement as well as painful and/or reduced mouth opening. This study aimed to investigate the level TMD-patients use social insurance benefits before and after their first time of diagnosis or first surgical event, compared to the general population. Furthermore, the aim was to investigate the differences in the use of social insurance benefits between surgically and non-surgically treated TMD-patients that were diagnosed in a hospital setting. METHODS: All Swedish citizens aged 23-59 diagnosed with TMD in a hospital setting and/or surgically treated for the condition during 1998-2016 were identified via the Swedish National Board of Health and Welfare. A non-exposed comparison cohort was collected via the Total Population Registry. Outcome and sociodemographic data were collected via Statistics Sweden. Main outcome was annual net days on sick leave and disability pension five years before (-T5) and five years after (T5) diagnosis and/or surgical treatment (T0). Regression analysis was conducted with generalized estimated equations. RESULTS: The study included 219 255 individuals (73% female) - 19 934 in the exposed cohort and 199 321 in the comparison cohort. The exposed group was classified into three subgroups: non-surgical, surgically treated once, and surgically treated twice or more. The mean annual net days of sick leave and disability pension combined during the ten-year follow-up was 61 days in the non-surgical group, 76 days in the surgically treated once group, and 104 days in the surgically treated twice or more subgroup. The corresponding number for the non-exposed comparison cohort was 32 days. CONCLUSION: Patients diagnosed with TMD in a hospital setting are 2-3 times more dependent on the use of social benefits than the general population. The reliance on sick leave and disability pension is seen as early as five years before diagnosis, and the reliance remains after surgical treatment. The reliance is stronger in patients with several surgical interventions. These findings indicate that patients diagnosed with TMD constitute a patient group with a high burden of health issues causing long-term dependence on social security benefits.

Trends of anti-reflux surgery in Denmark 2000-2017: a nationwide registry-based cohort study.

BACKGROUND: The utilisation of laparoscopic fundoplication peaked internationally around 2000. Perioperative morbidity, mortality, and length of stay initially declined as the use of laparoscopic technique increased. Studies indicate that complication rates have increased over time, probably as a consequence of rising age and level of comorbidity. None of these previous studies is nationwide. Therefore, this study aimed to investigate trends in the utilisation of anti-reflux surgery in the entire Danish population from 2000 to 2017. METHODS: Nationwide Danish health registries were utilised to include all Danish patients undergoing anti-reflux surgery 2000-2017. The utilisation of anti-reflux surgery in procedures per 100.000 inhabitants was compared to the utilisation of proton-pump inhibitors for each year. Postoperative complications, mortality, and length of stay per year, including yearly changes, were also calculated. RESULTS: The use of anti-reflux surgery peaked in 2001 with 5.9 procedures per 100,000 inhabitants and reached its lowest point in 2008 with 2.8 procedures per 100,000 inhabitants. The use of proton-pump inhibitors increased from 3,370 users per 100,000 inhabitants in 2000 to 10,284 users per 100,000 inhabitants in 2017. The 30-day and 90-day mortality ranged from 0 to 1.2%. The 30-day hospital-registered complications were 1.3-6.1%, and the 90-day hospital-registered complications were 2.4-8.3%. Length of stay was consistently low, with a median of 2 days in 2000 reduced to a median of 1 day by 2017. CONCLUSION: The utilisation of anti-reflux surgery in Denmark from 2000 to 2017 declined, and the use of PPI increased dramatically. Age, comorbidity, and postoperative complications increased, while the use of laparoscopic technique remained high, and mortality was consistently low.

One size fits none - a qualitative study investigating nine national quality registries' conditions for use in quality improvement, research and interaction with patients.

BACKGROUND: Swedish National Quality Registries (NQRs) are observational clinical registries that have long been seen as an underused resource for research and quality improvement (QI) in health care. In recent years, NQRs have also been recognised as an area where patients can be involved, contributing with self-reported experiences and estimations of health effects. This study aimed to investigate what the registry management perceived as barriers and facilitators for the use of NQRs in QI, research, and interaction with patients, and main activities undertaken to enhance their use for these purposes. The aim was further to identify potential differences between various types of NQRs for their use in these areas. METHODS: In this multiple case study, nine NQRs were purposively selected. Interviews (n = 18) were conducted and analysed iteratively using conventional and directed content analysis. RESULTS: A recent national investment initiative enabled more intensive work with development areas previously identified by the NQR management teams. The recent focus on value-based health care and other contemporary national healthcare investments aiming at QI and public benchmarking were perceived as facilitating factors. Having to perform double registrations due to shortcomings in digital systems was perceived as a barrier, as was the lack of authority on behalf of the registry management to request participation in NQRs and QI activities based on registry outcomes. The registry management teams used three strategies to enhance the use of NQRs: ensuring registering of correct and complete data, ensuring updated and understandable information available for patients, clinicians, researchers and others stakeholders, and intensifying cooperation with them. Varied characteristics of the NQRs influenced their use, and the possibility to reach various end-users was connected to the focus area and context of the NQRs. CONCLUSIONS: The recent national investment initiative contributed to already ongoing work to strengthen the use of NQRs. To further increase the use, the demands of stakeholders and end-users must be in focus, but also an understanding of the NQRs' various characteristics and challenges. The end-users may have in common a need for training in the methodology of registry based research and benchmarking, and how to be more patient-centred.

Long-term survival following out-of-hospital cardiac arrest in women and men: Influence of comorbidities, social characteristics, and resuscitation characteristics.

AIM: We aimed to study sex differences in long-term survival following out-of-hospital cardiac arrest (OHCA) compared to the general population, and determined associations for comorbidities, social characteristics, and resuscitation characteristics with survival in women and men separately. METHODS: We followed 2,452 Danish (530 women and 1,922 men) and 1,255 Dutch (259 women and 996 men) individuals aged ≥25 years, who survived 30 days post-OHCA in 2009-2015, until 2019. Using Poisson regression analyses we assessed sex differences in long-term survival and sex-specific associations of characteristics mutually adjusted, and compared survival with an age- and sex-matched general population. The potential predictive value was assessed with the Concordance-index. RESULTS: Post-OHCA survival was longer in women than men (adjusted incidence rate ratio (IRR) for mortality 0.74, 95%CI 0.61-0.89 in Denmark; 0.86, 95%CI 0.65-1.15 in the Netherlands). Both sexes had a shorter survival than the general population (e.g., IRR for mortality 3.07, 95%CI 2.55-3.70 and IRR 2.15, 95%CI 1.95-2.37 in Danish women and men). Higher age, glucose lowering medication, no dyslipidaemia medication, unemployment, and a non-shockable initial rhythm were associated with shorter survival in both sexes. Cardiovascular medication, depression/anxiety medication, living alone, low household income, and residential OHCA location were associated with shorter survival in men. Not living with children and bystander cardiopulmonary resuscitation provision were associated with shorter survival in women. The Concordance-indexes ranged from 0.51 to 0.63. CONCLUSIONS: Women survived longer than men post-OHCA. Several characteristics were associated with long-term post-OHCA survival, with some sex-specific characteristics. In both sexes, these characteristics had low predictive potential.

Osteoporosis and bone fractures in patients with celiac disease: A nationwide cohort study.

Celiac disease (CD) is an autoimmune disease caused by an abnormal immune response triggered by ingestion of gluten. Treatment of CD is a lifelong gluten-free diet. Both diagnosed and undiagnosed CD has been found to be associated with reduced bone mineral density, which can lead to an increased risk of fractures. We therefore aimed to investigate the association of CD and the risk of fractures and osteoporosis in Denmark in a nationwide registry-based study. We identified all patients with CD (ICD-10 code K90.0) between 2000 and 2018 and included those with at least two contacts with a CD diagnosis. In total, 9397 CD patients and 93,964 randomly selected age- and sex-matched (1:10) references from the general population were identified. The overall hazard ratio (HR) of developing osteoporosis in CD patients compared with matches was 5.39 (95 % confidence interval (CI): 4.89, 5.95), however when excluding events of osteoporosis occurring within 12 months from the date of diagnosis the overall HR was reduced to 3.87 (95 % CI: 3.44, 4.33). The HR for major osteoporotic fractures was 1.37 (95 % CI: 1.25, 1.51) and for any fractures 1.27 (95 % CI: 1.18, 1.36). For osteoporosis, major osteoporotic fractures, and any fracture prior to diagnosis of CD the odds ratios comparing CD patients with matches were 4.32 (95 % CI: 3.64, 4.68), 1.29 (95 % CI: 1.21, 1.37) and 1.34 (95 % CI: 1.27, 1.41), respectively. Thus, this study showed an increased risk of osteoporosis and bone fractures among individuals with CD, both before and after diagnosis of CD. These results underline that the risk of osteoporosis should be considered in the clinical management of patients with CD and that early diagnosis and treatment could be important.

Profiling Bispebjerg Acute Cohort: Database Formation, Acute Contact Characteristics of a Metropolitan Hospital, and Comparisons to Urban and Rural Hospitals in Denmark.

Purpose: To present a metropolitan cohort, Bispebjerg acute cohort (BAC), and compare patient characteristics and outcomes with patients from urban and rural hospitals in Denmark. Patients and Methods: We linked data from seven Danish nationwide registries and included all acute contacts to non-psychiatric hospitals in the years 2016-2018. Acute hospital contacts to Bispebjerg and Frederiksberg Hospital constituted BAC, representing a solely metropolitan/urban catchment area. Patient characteristics and outcomes were compared to the rest of Denmark in an urban cohort (UrC) and a rural cohort (RuC), stratified by visit and hospitalization contact types. Results: We identified 4,063,420 acute hospital contacts in Denmark and BAC constituted 8.4% (n=343,200) of them. BAC had a higher proportion of visits (65.1%) compared with UrC (52.1%) and RuC (45.3%). Patients in BAC more often lived alone (visits: BAC: 34.8%, UrC: 30.6%, RuC: 29.2%; hospitalizations: BAC: 50.8%, UrC: 36.7%, RuC: 37.2%) and had temporary CPR number (visits: BAC: 4.4%, UrC: 1.9%, RuC: 1.6%; hospitalizations: BAC: 1.5%, UrC: 0.9%, RuC: 0.8%). Visit patients in BAC were younger (BAC: 36, UrC: 42, RuC: 45 years, median), more often students (BAC: 18.0%, UrC: 14.0%, RuC: 12.5%), and had more contacts due to infectious diseases (BAC: 19.8%, UrC: 14.1%, RuC: 6.2%) but less due to injuries (BAC: 40.0%, UrC: 43.8%, RuC: 60.7%). Hospitalized patients in BAC had higher median age (BAC: 64, UrC: 61, RuC: 64 years) and fewer were in employment than in UrC (BAC: 26.1%, UrC: 32.1%, RuC: 28.1%). BAC Hospitalizations had a lower death rate within 30 days than in RuC (BAC: 3.0% [2.9-3.1%], UrC: 3.1% [3.0-3.1%], RuC: 3.4% [3.3-3.4%]), but a higher readmission-rate (BAC: 20.5% [20.3-20.8%], UrC: 17.3% [17.2-17.4%], RuC: 17.5% [17.5-17.6%]). Conclusion: Significant differences between BAC, urban, and rural cohorts may be explained by differences in healthcare structure and sociodemographics of the catchment areas.

Scoping Review on ACL Surgery and Registry Data.

PURPOSE OF REVIEW: To present an overview of registry-based anterior cruciate ligament (ACL) research, as well as provide insight into the future of ACL registries. RECENT FINDINGS: During the past decades, the ACL registries have had an important role in increasing our understanding of patients with ACL injuries and their treatment. The registry data has deepened our understanding of factors that have been associated with an increased risk of sustaining an ACL injury and for evaluation of treatment factors and their impact on patient-related outcomes. Recently, registry-based ACL research using artificial intelligence (AI) and machine learning (ML) has shown potential to create clinical decision-making tools and analyzing outcomes. Thus, standardization of collected data between the registries is needed to facilitate the further collaboration between registries and to facilitate the interpretation of results and subsequently improve the possibilities for implementation of AI and ML in the registry-based research. Several studies have been based on the current ACL registries providing an insight into the epidemiology of ACL injuries as well as outcomes following ACL reconstruction. However, the current ACL registries are facing future challenges, and thus, new methods and techniques are needed to ensure further good quality and clinical applicability of study findings based on ACL registry data.

Pheochromocytoma in Denmark during 1977-2016: validating diagnosis codes and creating a national cohort using patterns of health registrations.

BACKGROUND: Pheochromocytoma and catecholamine-secreting paraganglioma (PPGL) are rare but potentially life-threatening tumors. We aimed to validate diagnosis codes for PPGL in the Danish National Patient Registry, the Danish National Pathology Registry, and the Danish Registry of Causes of Death and to create a national cohort of incident PPGL patients by linking these three registries. PATIENTS AND METHODS: We obtained data from the three abovementioned registries for all individuals registered with pheochromocytoma or catecholamine hypersecretion in Denmark during 1977-2016 (average population 5.30 million). We then reviewed health records for all individuals living in the North Denmark Region and Central Denmark Region (average population 1.75 million) to validate the diagnosis of PPGL. We tested a number of algorithms for accurately identifying true cases of PPGL to maximize positive predictive values (PPVs) and completeness. The best algorithm was subsequently validated in an external sample. RESULTS: We identified 2626 individuals with a PPGL diagnosis code in Denmark, including 787 (30.0%) in the North Denmark Region and Central Denmark Region. In this subsample, we retrieved the health records of 771/787 (98.0%) individuals and confirmed 198 incident PPGL patients (25.3%). The PPV of PPGL diagnosis codes was 21.7% in the Danish National Patient Registry, 50.0% in the Danish Registry of Causes of Death, and 79.5% in the Danish National Pathology Registry. By combining patterns of registrations in the three registries, we could increase the PPV to 93.1% (95% confidence interval [CI]: 88.5-96.3) and completeness to 88.9% (95% CI: 83.7-92.9), thus creating a national PPGL cohort of 588 patients. PPV for the optimal algorithm was 95.3% (95% CI: 88.5-98.7) in the external validation sample. CONCLUSION: Diagnosis codes for pheochromocytoma had low PPV in several individual health registries. However, with a combination of registries we were able to identify a near-complete national cohort of PPGL patients in Denmark, as a valuable source for epidemiological research.

The Danish Anaesthesia Database.

AIM OF DATABASE: The aim of the Danish Anaesthesia Database (DAD) is the nationwide collection of data on all patients undergoing anesthesia. Collected data are used for quality assurance, quality development, and serve as a basis for research projects. STUDY POPULATION: The DAD was founded in 2004 as a part of Danish Clinical Registries (Regionernes Kliniske Kvalitetsudviklings Program [RKKP]). Patients undergoing general anesthesia, regional anesthesia with or without combined general anesthesia as well as patients under sedation are registered. Data are retrieved from public and private anesthesia clinics, single-centers as well as multihospital corporations across Denmark. In 2014 a total of 278,679 unique entries representing a national coverage of ~70% were recorded, data completeness is steadily increasing. MAIN VARIABLE: Records are aggregated for determining 13 defined quality indicators and eleven defined complications all covering the anesthetic process from the preoperative assessment through anesthesia and surgery until the end of the postoperative recovery period. DESCRIPTIVE DATA: Registered variables include patients' individual social security number (assigned to all Danes) and both direct patient-related lifestyle factors enabling a quantification of patients' comorbidity as well as variables that are strictly related to the type, duration, and safety of the anesthesia. Data and specific data combinations can be extracted within each department in order to monitor patient treatment. In addition, an annual DAD report is a benchmark for departments nationwide. CONCLUSION: The DAD is covering the anesthetic process for the majority of patients undergoing anesthesia in Denmark. Data in the DAD are increasingly used for both quality and research projects.

Ethical aspects of registry-based research in the Nordic countries.

National health care registries in the Nordic countries share many attributes, but different legal and ethical frameworks represent a challenge to promoting effective joint research. Internationally, there is a lack of knowledge about how ethical matters are considered in Nordic registry-based research, and a lack of knowledge about how Nordic ethics committees operate and what is needed to obtain an approval. In this paper, we review ethical aspects of registry-based research, the legal framework, the role of ethics review boards in the Nordic countries, and the structure of the ethics application. We discuss the role of informed consent in registry-based research and how to safeguard the integrity of study participants, including vulnerable subjects and children. Our review also provides information on the different government agencies that contribute registry-based data, and a list of the major health registries in Denmark, Finland, Iceland, Norway, and Sweden. Both ethical values and conditions for registry-based research are similar in the Nordic countries. While Denmark, Finland, Iceland, Norway, and Sweden have chosen different legal frameworks, these differences can be resolved through mutual recognition of ethical applications and by harmonizing the different systems, likely leading to increased collaboration and enlarged studies.

Existing data sources for clinical epidemiology: Danish registries for studies of medical genetic diseases.

Denmark has an extensive collection of national and regional medical registries. There are many advantages to registry-based research when investigating genetic diseases which, due to their rarity, can be difficult to identify. In this study, we aimed to provide an updated overview of Danish registries for medical genetic conditions and describe how data linkage across registries can be used to collect data on genetic diseases at the individual level and at the family level. We present a list of medical genetic registries in Denmark at the national level, data sources from the departments of clinical genetics and other specialized centers, and project-specific data sources. We also summarize key general registries, such as the Danish National Registry of Patients, the Danish Medical Birth Registry, and the Civil Registration System, which are renowned for their comprehensive and high quality data, and are useful supplemental data sources for genetic epidemiology research. We describe the potential for data linkage across multiple registries, which allows for access to medical histories with follow-up time spanning birth to death. Finally, we provide a brief introduction to the Danish epidemiological research setting and legalities related to data access. The Danish collection of medical registries is a valuable resource for genetic epidemiology research.

Existing data sources for clinical epidemiology: The Danish National Database of Reimbursed Prescriptions.

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.

Existing data sources for clinical epidemiology: Aarhus University Prescription Database.

Population-based prescription databases in Nordic countries have become a mainstay of epidemiologic research. Denmark has both national and regional population-based prescription databases. Aarhus University Prescription Database collects data on reimbursed medications dispensed at all community pharmacies of the North Denmark Region and the Central Denmark Region. The regions have a combined population of 1.8 million inhabitants, or one-third of the Danish population. Denmark's primary health care sector, which includes general practitioners, specialists, and dentists, generates about 96% of the prescription sales, most of which are reimbursable and are dispensed by the community pharmacies. The Aarhus University Prescription Database combines the region's pharmacy records in a single database, maintained and updated for research purposes. Each dispensation record contains patient-, drug-, and prescriber-related data. Dispensation records retain patients' universal personal identifier, which allows for individual-level linkage to all Danish registries and medical databases. The linked data have many applications in clinical epidemiology, including drug utilization studies, safety monitoring, etiologic research, and validation studies.