Lotte Rasmussen

Comparison of the Five Danish Regions Regarding Demographic Characteristics, Healthcare Utilization, and Medication Use—A Descriptive Cross-Sectional Study

Background While Denmark is well known for its plethora of registers. Many studies are conducted on research databases that only cover parts of Denmark, and regional differences could potentially threaten these studies’ external validity. The aim of this study was to assess sociodemographic and health related homogeneity of the five Danish regions. Methods We obtained descriptive data for the five Danish regions, using publicly available data sources: Statbank Denmark, the Danish Ministry of Economic Affairs, and Medstat.dk. These data sources comprise aggregate data from four different nationwide registers: The Danish National Patient Register, The Danish Civil Registration System, The Danish Register of Medicinal Product Statistics, and The Danish National Health Service Register for Primary Care. We compared the Danish regions regarding demographic and socioeconomic characteristics, health care utilization, and use of medication. For each characteristic, one-year prevalence was obtained and analyses were performed for 2013 and 2008 to account for possible change over time. Results In 2013, 5,602,628 persons were living in Denmark. The mean age was 40.7 years in the entire Danish population and ranged between 39.6 to 42.4 years in the five regions (coefficient of variation between regions [CV] = 0.028). The proportion of women in Denmark was 50.4% (CV = 0.009). The proportion of residents with low education level was 28.7% (CV = 0.051). The annual number of GP contacts was 7.1 (range: 6.7–7.4, CV = 0.040), and 114 per 1,000 residents were admitted to the hospital (range: 101–131, CV = 0.107). The annual number of persons redeeming a prescription of any medication was 723 per 1,000 residents (range: 718–743, CV = 0.016). Analyses for 2008 showed comparable levels of homogeneity as for 2013. Conclusions We found substantial homogeneity between all of the five Danish regions with regard to sociodemographic and health related characteristics. Epidemiologic studies conducted on regional subsets of Danish citizens have a high degree of generalizability.

Treatment Changes among Users of Non‐Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real‐life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non‐VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one‐third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA2DS2‐VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA2DS2‐VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.

Cardiovascular drugs and erectile dysfunction – a symmetry analysis

AIM Erectile dysfunction is a common problem among patients with cardiovascular diseases and the influence of cardiovascular drugs is much debated. The aim of this study was to evaluate the short term potential for different cardiovascular drugs to affect the risk of being prescribed a drug against erectile dysfunction. METHODS We employed a symmetry analysis design and included all Danish male individuals born before 1950 who filled their first ever prescription for a cardiovascular drug and a 5-phosphodiesterase inhibitor within a 6 month interval during 2002-2012. If the cardiovascular drug induces erectile dysfunction, this would manifest as a non-symmetrical distribution of subjects being prescribed the cardiovascular drug first vs. persons following the opposite pattern. Furthermore, we calculated the number of patients needed to treat for one additional patient to be treated for erectile dysfunction (NNTH). RESULTS We identified 20 072 males with a median age of 64 years (IQR 60-70) who initiated a cardiovascular drug and a 5-phosphodiesterase inhibitor within a 6 month interval. Sequence ratios showed minor asymmetry in prescription orders after adjustment for trends in prescribing. This asymmetry was most profound for thiazides (1.28, 95% CI 1.20, 1.38), calcium channel blockers (1.29, 95% CI 1.21, 1.38) and ACE inhibitors (1.29, 95% CI 1.21, 1.37), suggesting a small liability of these drugs to provoke erectile dysfunction. NNTH values were generally large, in the range of 330-6400, corresponding to small absolute effects. CONCLUSION Our study does not suggest that cardiovascular drugs strongly affect the risk of being prescribed a drug against erectile dysfunction on a short term basis.

The potential drug–drug interaction between proton pump inhibitors and warfarin

Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug–drug interaction is sparsely investigated in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values.

Clinical events preceding switching and discontinuation of oral anticoagulant treatment in patients with atrial fibrillation

Abstract Aims Switching between oral anticoagulants and treatment discontinuation are common events related to therapy with non-vitamin K antagonist oral anticoagulants (NOACs). However, knowledge on the reasons leading to these treatment changes is scarce. The aim of this study was to identify clinical events preceding anticoagulant switching and NOAC discontinuation during oral anticoagulant therapy in patients with atrial fibrillation. Methods and results We performed a nationwide register-based study including Danish atrial fibrillation patients initiating a NOAC between August 2011 and February 2016 (n = 50 623). We explored potential reasons leading to changes in anticoagulant treatment by identifying clinical events preceding switches from vitamin K antagonists (VKA) to NOAC, switches from NOAC to VKA, and discontinuations of NOACs. Among 23 531 anticoagulant users changing treatment, we identified 13 295 switches from VKA to NOAC, 5206 switches from NOAC to VKA, and 8995 discontinuations of NOACs. Approximately half of all treatment changes were preceded by a hospitalization. A relevant specific clinical event or procedure was identified prior to 18.3% of switches from VKA to NOAC, prior to 23.0% of switches from NOAC to VKA, and prior to 26.6% of discontinuations. Switches from VKA to NOAC were most often preceded by thromboembolic events (7.0%), whereas cardioversion was the most common specific event prior to a switch from NOAC to VKA (11.4%). Discontinuations were most often preceded by bleeding events (7.6%). Conclusion For about one in five patients, treatment changes during anticoagulant therapy were preceded by a major clinical event. However, the majority of patients changed treatment for reasons not recorded in health registries.

Use of tricyclic antidepressants and risk of glioma: a nationwide case–control study

Background:A protective effect of tricyclic antidepressants (TCAs) against gliomas has been suggested by a small number of studies. We investigated this putative association in a nationwide setting.Methods:Using a case–control design, we identified all patients with histologically verified glioma (cases) in Denmark between 2000 and 2012 and matched these 1 : 20 to population controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) for glioma associated with long-term (⩾3 years) use of TCAs. Similar analyses were performed for selective serotonin reuptake inhibitors (SSRIs).Results:We identified 3767 glioma cases and 75 340 population controls. Long-term use of TCAs was inversely associated with risk of glioma (OR 0.72, 95% CI: 0.41–1.25). Long-term SSRI use was not associated with glioma risk (OR 0.93, 95% CI: 0.75–1.16).Conclusions:Our study indicated that long-term use of TCAs may be associated with a reduced risk of glioma, however, the statistical precision was limited. A similar pattern was not observed for use of SSRIs.

Deviant patterns of methylphenidate use in adults: a Danish nationwide registry‐based drug utilization study

Several survey studies have documented misuse of methylphenidate defined as the use of non‐prescribed methylphenidate or use different from what was prescribed. We aimed to identify and characterize adults with deviant patterns of methylphenidate use in Denmark during 2007–2012. Further, we aimed to identify risk factors associated with deviant patterns of use.

Trends in Off-Label Prescribing of Sedatives, Hypnotics and Antidepressants among Children and Adolescents - A Danish, Nationwide Register-based Study.

In recent years, psychotropic drug use among children and adolescents in Europe and USA has increased. However, the majority of psychotropic drugs are not formally approved for use in children and adolescents, and consequently, use is often off‐label. The objectives were to describe time trends in off‐label prescribing rates and the most commonly used types of psychotropic drugs by age and gender in Danish children and adolescents. Using the Register of Medicinal Product Statistics, we identified all prescriptions for sedatives, hypnotics and antidepressants filled for children and adolescents in 2006–2012. Information on diagnoses was obtained from the Danish National Registry of Patients and allowed classification of prescriptions as either on‐ or off‐label. We identified 186,831 prescriptions filled for 29,851 children and adolescents: 88.0% of these were classified as off‐label. During 2006–2012, off‐label rates for sedatives and hypnotics increased significantly, except for prescriptions for girls aged 15–17 years [range 24.1–98.2% (girls), 31.9% to 99.0% (boys)]. In the same period, the number of registered melatonin prescriptions (all off‐label) increased expansively. For antidepressants, we found decreasing trends in off‐label rates over time [range 94.5–65.6% (girls), 93.8–71.2% (boys)]. Off‐label prescribing of psychotropic drugs to Danish children and adolescents is common. Off‐label rates for sedatives and hypnotics increased in the period of 2006–2012, whereas off‐label rates for antidepressants declined. Off‐label rates might be underestimated and should be considered a conservative estimate.

Validity of the Prescriber Information in the Danish National Prescription Registry

The aim of this study was to measure the validity of the prescriber information recorded in the Danish National Prescription Registry (DNPR). The prescriber information recorded in the pharmacies’ electronic dispensing system was considered to represent the prescriber information recorded in the DNPR. Further, the problem of validity of the prescriber information pertains only to non‐electronic prescriptions, as these are manually entered into the dispensing system. The recorded prescriber information was thus validated against information from a total of 2000 non‐electronic prescriptions at five Danish community pharmacies. The validity of the recorded prescriber information was measured at the level of the individual prescriber and the prescriber type, respectively. The proportion of non‐electronic prescriptions with incorrect registrations was 22.4% (95% confidence interval (CI): 20.6–24.3) when considering individual prescriber identifiers and 17.8% (95% CI: 16.1–19.5) when considering prescriber type. When excluding prescriptions specifically registered as ‘missing prescriber identifier’, the proportions decreased to 9.5% (95% CI: 8.2–11.0) and 4.1% (95% CI: 3.2–5.1), respectively. The positive predictive values for the classification of prescriber types were in the range of 94.0–99.2%, while the sensitivity ranged between 64.6% and 91.8%. With a maximum of 14% non‐electronic prescriptions of all prescriptions in the DNPR in 2015, this corresponds to correct classification of prescriber types in the DNPR of at least 97.5%. In conclusion, the prescriber information in the DNPR was found to be valid, especially in recent years. Researchers should be aware of the low sensitivity towards prescriptions from private practicing specialists.

Drug use among complete responders, partial responders and non-responders in a longitudinal survey of nonagenarians: analysis of prescription register data

In observational studies, non‐response can limit representativity and introduce bias. We aimed to investigate the longitudinal changes in the number of used drugs among complete responders, partial responders, and non‐responders in a whole birth cohort of Danish nonagenarians participating in a longitudinal survey.