Use of molnupiravir: A Danish nationwide drug utilization study.

PURPOSE: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild-to-moderate COVID-19. METHODS: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs-CoV-2 test. Patient characteristics were compared to matched, untreated SARS-CoV-2 positive reference groups. RESULTS: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT-PCR SARS-CoV-2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT-PCR SARS-CoV-2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS-CoV-2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%). CONCLUSIONS: Molnupiravir was mainly prescribed by general practitioners to RT-PCR SARS-CoV-2 positive individuals who had a potentially increased risk of severe COVID-19. Though some off-label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines.

Treatment patterns of antidepressants in children and adolescents in Scandinavia.

The aim of this study was to examine variations in use of antidepressants among children and adolescents in the three Scandinavian countries (Sweden, Norway, and Denmark). We identified new users of antidepressants (5-17 years) during 2007-2018 and described the annual incidence rate, treatment duration, concomitant psychotropic drug use, and the clinical setting of the prescribing physician (in Sweden and Denmark). Incident use of antidepressants increased by a factor 1.9 in Sweden, 1.3 in Norway and decreased by a factor 0.6 in Denmark during the study period. In Sweden, 58% of antidepressant users were covered by a prescription 12 months after initiation compared to 40% in Norway and 49% in Denmark. Also, 34% of Swedish antidepressant users were in continuous treatment after 12 months compared to 26% in Norway and 31% in Denmark. Concomitant use of other psychotropics was more common in Sweden (57%) than in Norway (37%) and Denmark (27%). During 2007-2018, clinicians from psychiatry settings initiated 75% of antidepressant treatments in Sweden, while this was the case for 50% of prescriptions in Denmark, although the proportion increased over time. The number of new antidepressant users is high and still rising in Sweden compared to Norway and Denmark. Swedish antidepressant users are more likely to use other psychotropics and to be covered by an antidepressant prescription after one year. Most antidepressants in Sweden are prescribed by physicians within psychiatric settings suggesting that they are based on specialized psychiatric evaluation.

Opioid prescriber responsibility: A Danish drug utilization study.

AIMS: We describe the distribution of prescribers responsible for opioid initiation and maintenance (general practice, hospital prescribers and other prescribers) in Denmark. METHODS: We leveraged data on opioid fills from a 20% sample of all Danes alive during 2000-2021. RESULTS: Overall, general practitioners were responsible for most treatment initiation (74% during 2000-2021) and maintenance treatment (92%). However, while hospital prescribers initiated ≈20% of treatments during 2001-2012, this increased to 35% in 2021. Similarly, hospital prescriber's share of maintenance treatment increased from 5.9% during 2000-2012 to 13% in 2021. This change was particularly pronounced for morphine initiation (48% hospital prescribers in 2021 up from 38% during 2000-2010) and oxycodone initiation (78% up from 41%). Regarding choice of opioids, codeine use dropped markedly, in particular among hospital prescribers. Tramadol was consistently the most common first choice opioid in general practice (33% in 2021), whereas its use among hospital prescribers decreased (54% during 2000-2015 to 15% in 2021). Conversely, the proportion of treatment initiation by hospital prescribers composed of morphine and oxycodone increased to 38% and 42% in 2021, respectively. CONCLUSIONS: General practice prescribes most opioids; however, hospital prescribers are increasingly responsible for opioid prescribing, in particular initiation of morphine and oxycodone.

Melatonin use among children, adolescents, and young adults: a Danish nationwide drug utilization study.

We aimed to provide a detailed description of the use of melatonin in Danish children, adolescents, and young adults during 2012-2019. We identified melatonin users 0-24 years of age (n = 43,652; median age 16 years) via the Danish nationwide health registers. Melatonin is a prescription drug in Denmark. The incidence of melatonin use increased from 2.4 to 3.9/1000 person-years during 2012 to 2019. Among 6,557 incident users in 2019, 53% filled only a single prescription within the first 6 months. Long-term use was most common among the younger age groups, with 17% of 5-9-year-olds and 14% of 10-13-year-olds being in continued treatment (no treatment breaks) 12 months after their first melatonin prescription. Disregarding treatment breaks, 3 in 10 were using melatonin 12 months after their first melatonin prescription and this proportion was also highest among 5-9-year-olds (63%) and 10-13-year-olds (51%). Psychopathology was common among melatonin users with 75% registered with either a psychiatric disorder diagnosis (54%), a filled prescription for another psychotropic (58%), or a contact to a private practice psychiatrist (15%) within ± 12 months of treatment initiation. General practitioners authorized melatonin prescriptions to almost half of all new users (48%), while psychiatric specialists authorized 37% of first prescriptions. In conclusion, the incidence of melatonin use increased in Denmark from 2012 to 2019. A substantial proportion of users had concurrent psychopathology most likely explaining their use of melatonin. Long-term melatonin use was more common among the youngest age groups, which should be a focus of interest due to limited safety data.

Trends in use of attention deficit hyperactivity disorder medication among children and adolescents in Scandinavia in 2010-2020.

The objective of the study was to compare the use of attention deficit hyperactivity disorder (ADHD) medication among children and adolescents in Scandinavia 2010-2020. Using aggregated prescription data for individuals aged 5-19 years, we calculated annual prevalence proportions of ADHD medication (users/1000 inhabitants) for each country, overall and stratified by age and sex. Overall, use of ADHD medication increased during 2010-2020 in all countries. The increase was pronounced in Sweden reaching 35 users/1000 inhabitants in 2020 (119% increase), whereas it reached 22/1000 in Denmark and Norway (equivalent to a 38% and 16% increase, respectively). Methylphenidate was the most frequently used drug and Sweden had the highest use reaching 25/1000 in 2020 compared to 16/1000 and 18/1000 in Denmark and Norway, respectively. Lisdexamfetamine use increased steadily and was also highest in Sweden (13/1000 in 2020). In 2020, atomoxetine use was higher in Sweden (4.6/1000) and Denmark (4.5/1000) compared to Norway (2.2/1000). From 2015, use of guanfacine increased in Sweden reaching 4.4/1000 in 2020 but remained low in Denmark (0.4/1000) and Norway (0.7/1000). Use of dexamphetamine was low (ranging from 0.47 to 0.75/1000 in 2020) in the three countries. ADHD medication use was highest in Sweden across all age groups. In all countries, the prevalence was higher in males compared to females. In conclusion, use of ADHD medication among children and adolescents in Scandinavia is increasing. The prevalence of use is higher in Sweden for all drug groups compared to Norway and Denmark.

Who prescribes quetiapine in Denmark?

The second-generation antipsychotic quetiapine is commonly used off-label for its anxiolytic and hypnotic properties. However, quetiapine is associated with problematic side-effects. We used Danish Medicinal Product Statistics and a 20% random sample of the Danish population's prescription fills (2001-2020) to describe the utilization of quetiapine and proportion of various prescriber types (general practitioner [GP], specialist in private practice, hospital physician and other prescribers) both in connection to first-time and subsequent prescriptions. In 2020, 92% of all quetiapine was dispensed outside hospitals and the average daily dispensed quantity of quetiapine per user corresponded to 100 mg/user/d. A GP issued 53% of first-time prescriptions and 75% of subsequent prescriptions for quetiapine in 2020. The proportion of quetiapine prescriptions issued by GPs varied by age group-from 14% among 0-17-year-olds to 93% among the ≥80-year-olds. Future initiatives on the rational use of quetiapine and related drugs, especially among adults, should target GPs.

Core concepts in pharmacoepidemiology: Measures of drug utilization based on individual-level drug dispensing data.

BACKGROUND: Drug utilization studies are essential to facilitate rational drug use in the society. AIM: In this review, we provide an overview of drug utilization measures that can be used with individual-level drug dispensing data, referencing additional reading on the individual analysis. This is intended to serve as a primer for those new to drug utilization research and a shortlist from which researchers can identify useful analytical approaches when designing their drug utilization study. RESULTS AND DISCUSSION: We provide an overview of: (1) basic measures of drug utilization which are used to describe changes in drug use over time or compare drug use in different populations; (2) treatment adherence measures with specific focus on persistence and implementation; (3) how to measure drug combinations which is useful when assessing drug-drug interactions, concomitant treatment, and polypharmacy; (4) prescribing quality indicators and measures to assess variations in drug use which are useful tools to assess appropriate use of drugs; (5) proxies of prescription drug misuse and skewness in drug use; and (6) considerations when describing the characteristics of drug users or prescribers.

Changing characteristics over time of individuals receiving COVID-19 vaccines in Denmark: A population-based descriptive study of vaccine uptake.

AIMS: The Danish authorities implemented a differential rollout of the COVID-19 vaccines where individuals at high risk of COVID-19 were prioritized. We describe the temporal uptake and characteristics of COVID-19 vaccine recipients in Denmark. METHODS: Using nationwide healthcare registries, we identified all Danish residents ⩾5 years of age who received at least one dose of a COVID-19 vaccine from 27 December 2020-29 January 2022. We charted the daily number of newly vaccinated individuals and the cumulative vaccine coverage over time, stratified by vaccine type, age groups and vaccination priority groups, and described characteristics of vaccine recipients during two-month-intervals and in vaccination priority groups. RESULTS: By 29 January 2022, 88%, 86% and 64% of Danish residents ⩾5 years (n=5,562,008) had received a first, second and third dose, respectively, of a COVID-19 vaccine, most commonly the BNT162b2 vaccine (84%). Uptake ranged from 48% in 5-11-year-olds to 98% in 65-74-year-olds. Individuals vaccinated before June 2021 were older (median age 61-70 years vs 10-35 years in later periods) and had more comorbidities such as hypertension (22-28% vs 0.77-2.8% in later periods), chronic lung disease (9.4-15% vs 3.7-4.6% in later periods) and diabetes (9.3-12% vs 0.91-2.4% in later periods). CONCLUSIONS: We document substantial changes over time in, for example, age, sex and medical history of COVID-19 vaccine recipients. Though these results are related to the differential vaccine rollout in Denmark, similar findings are probable in other countries and should be considered when designing and interpreting studies on the effectiveness and safety of COVID-19 vaccines.

Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.

Who prescribes drugs to patients: A Danish register-based study.

We describe the distribution of prescriber types responsible for issuing prescriptions in Denmark. Using a 20% random sample of all Danes alive during 2000-2018 (n = 1 515 025) and all their prescriptions filled at community pharmacies (n = 182 143 707), we found that general practitioners issued 88% of all prescriptions, followed by hospital physicians (7.4%) and private practicing specialists (4.2%). These values were stable over the study period. With increasing patient age, general practitioners were responsible for a larger proportion of prescriptions (e.g. 68% for patients aged 0-17 y and 89% for patients ≥51 y). General practitioners were responsible for 84% of all treatment initiation (first prescription) and 90% of all maintenance treatment. Corresponding values for hospital physicians were 9.5 and 6.3%, and for private practicing specialists 5.3 and 3.6%. In conclusion, general practitioners are responsible for the vast majority of prescribing in Denmark, including both treatment initiation and continuation, in particular among the elderly.

Use of non-insulin antidiabetic drugs in children and young adults - A Scandinavian drug utilization study from 2010-2019.

Knowledge on utilization patterns of non-insulin antidiabetic drugs in childhood and youth is limited. Therefore, we conducted a population-based drug utilization study using publicly available aggregate data on use of non-insulin antidiabetics from 2010 to 2019 in Scandinavia (Denmark, Norway and Sweden) in individuals aged up to 24 years. For each non-insulin antidiabetic drug, we calculated the annual prevalence proportion of users, overall and for specific age groups. From 2010 to 2019, the prevalence of non-insulin antidiabetic users in Scandinavia increased 37% from 0.43 to 0.59/1000 individuals. The prevalence proportions were highest among female adolescents and young adults, but the largest relative increase in use was seen among 10-14-year-olds (78%). Metformin was by far the most widely used non-insulin antidiabetic drug with a prevalence proportion of 0.51/1000 in 2019, followed by glucagon-like peptide-1 (GLP-1) analogues, which, however, showed an eight-fold relative increase during the study period.

Use of hypnotic drugs among children, adolescents, and young adults in Scandinavia.

BACKGROUND: Hypnotic use in children and adolescents is controversial. OBJECTIVE: To describe the use of hypnotic drugs (melatonin, z-drugs, and sedating antihistamines) among 5- to 24-year-old Scandinavians during 2012 to 2018. METHODS: Aggregate-level data were obtained from public data sources in Sweden, Norway, and Denmark. We calculated annual prevalence (users/1000 inhabitants) stratified by age group, sex, and country. Quantity of use (Defined Daily Dose (DDD)/user/day) was estimated for Norway and Denmark. RESULTS: Melatonin was the most commonly used hypnotic, and its use increased markedly from 2012 to 2018, particularly among females and 15- to 24-year-old individuals. Sweden had the highest increase in use (6.5 to 25/1000) compared with Norway (10-20/1000) and Denmark (5.7-12/1000). The annual prevalence of sedating antihistamine use was also highest in Sweden, reaching 13/1000 in 2018 in comparison to 7.5/1000 in Norway and 2.5/1000 in Denmark. Z-drug use decreased in all countries toward 2018, dropping to 3.5/1000 in Sweden, 4.4/1000 in Norway, and 1.7/1000 in Denmark. The quantity of hypnotic use in Norway and Denmark was 0.8-1.0 DDD/user/day for melatonin in 2018, as compared to 0.1-0.3 for z-drugs and antihistamines. CONCLUSION: The use of melatonin and sedating antihistamines increased among young Scandinavians during 2012-2018, and the increase was twice as high in Sweden compared with Norway and Denmark. In addition, Sweden had the highest use of sedating antihistamines. The Scandinavian variation of hypnotic use could reflect differences in frequency of sleep problems between populations or variation of healthcare access or clinical practice between countries.

Use of tramadol and other analgesics following media attention and risk minimization actions from regulators: a Danish nationwide drug utilization study.

PURPOSE: To describe the use of tramadol and other analgesics in Denmark focusing on the impact of media attention (June and December 2017) and regulatory actions (September 2017 and January 2018) on the use of tramadol. METHODS: Using nationwide registries, we identified all adults who filled a prescription for tramadol and other analgesics from 2014 to 2019. We described incidence rates, prevalence proportions, and total use of tramadol and other analgesics over time. We also described switching between analgesics, treatment duration, skewness in drug use, and doctor-shopping. RESULTS: From early 2017 until the end of 2019, total tramadol use decreased markedly while the use of morphine and oxycodone decreased slightly. The quarterly prevalence of tramadol use decreased from 32/1000 individuals in 2014 to 18/1000 at the end of 2019, dropping mainly at the time of media attention. Concomitantly, the quarterly prevalence increased for oxycodone (from 5.1 to 8.2) and morphine (from 8.5 to 9.8), mainly due to more short-term and sporadic users, and decreased for codeine (14 to 9.6). From 2014 to mid-2017, the incidence of tramadol use was stable (around 2.2/1000 person-months) but dropped in June 2017 to 1.7/1000, coinciding with the media attention. The incidence of tramadol use continued to decrease (to 1.1/1000 at the end of 2019). CONCLUSION: We identified a decline in tramadol use coinciding with the media attention in 2017 and continuing during regulatory actions. There was generally no evidence of unintended effects on the utilization of opioids related to the media attention and regulatory actions.

Use of attention-deficit/hyperactivity disorder medication among older adults in Denmark.

AIMS: Knowledge on the use of attention-deficit/hyperactivity disorder (ADHD) medication among older adults is limited. We hypothesized that ADHD medication is used off-label in adults aged ≥50 years as part of palliative care in e.g. cancer patients. The aim of this study was to describe the use of ADHD medication among adults aged ≥50 years in Denmark. METHODS: Using the Danish health registries, we identified new users ≥50 years of ADHD medication during 2000-2012. We estimated the annual incidence of ADHD medication use and ADHD diagnoses. We described new users of ADHD medication according to co-medication, comorbidities and assessed the 1-year cumulative mortality rate. A posthoc analysis allowed us to include new users until 2015. RESULTS: We identified 6690 new users of ADHD medication from 2000 to 2012. From 2000 to 2015 we observed an increase in the incidence of ADHD medication use from 12.5 to 30.3 per 100 000 person-years. However, the incidence rate decreased from 2010 to 2015. Throughout the study period, the incidence rate of ADHD diagnoses was low (overall prevalence among new users ≤2%). Opioids were the most frequent comedication used (used by 54%), while cancer was the most frequent diagnosis preceding treatment (prevalence of 52%). The 1-year cumulative mortality was 50%, primarily driven by patients with a preceding cancer diagnosis. CONCLUSION: There was an increase in the incidence of ADHD medication use in adults aged ≥50 years from 2000-2010 and a decreasing incidence from 2010-2015. Our results suggest that ADHD medication is used off-label in older adults as part of palliative care.

Using the "proportion of patients covered" and the Kaplan-Meier survival analysis to describe treatment persistence.

PURPOSE: Standard Kaplan-Meier (KM) survival analysis is often used to study treatment persistence estimating the proportion of patients who have not yet experienced a treatment break by a given day after treatment initiation. This method only allows patients to be studied until their first treatment break. The "proportion of patients covered" (PPC) method is another approach to study treatment persistence. It measures the proportion of live patients currently covered by treatment. We aimed to describe the PPC method, show how the KM survival analysis and the PPC method can describe treatment persistence, and discuss the interpretation/application of the methods. METHODS: We identified new users of statins, selective serotonin reuptake inhibitors, hormone replacement therapy, and ibuprofen. We used KM estimates and the PPC to describe persistence in the 3 years post treatment initiation, using a grace period of 90 days to define a treatment break. RESULTS: Three years after statin initiation, approximately 40% of patients were still in continuous treatment (KM survival) and 60% of patients still alive were in current treatment (PPC). Corresponding numbers were 12% and 25% for selective serotonin reuptake inhibitors and 9% and 29% for hormone replacement therapy. At 1 year, numbers were 5% and 10% for ibuprofen. The PPC showed markedly less variability than the KM survival analysis with different choices of grace periods. CONCLUSIONS: The KM survival analysis and the PPC method can be used to study different aspects of treatment persistence. Together, they provide a more complete picture of treatment persistence and drug use patterns.

Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe.

PURPOSE: To report and discuss estimated prevalence of potential off-label use and associated methodological challenges using a case study of dabigatran. METHODS: Observational, cross-sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients). STUDY PERIOD: August 2011 to August 2015. Two definitions were used to estimate potential off-label use: a broad definition of on-label prescribing using codes for disease indication (eg, atrial fibrillation [AF]), and a restrictive definition excluding patients with conditions for which dabigatran is not indicated (eg, valvular AF). RESULTS: Prevalence estimates under the broad definition ranged from 5.7% (CPRD-HES) to 34.0% (CSD-LPD) and, under the restrictive definition, from 17.4% (CPRD-HES) to 44.1% (CSD-LPD). For the majority of potential off-label users, no diagnosis potentially related to anticoagulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off-label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources. CONCLUSIONS: Estimates of potential off-label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES-linkable estimates are likely to be the most accurate.

Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.

With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.

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

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.

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

PURPOSE: 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. METHODS: We obtained prescription data on all individuals born in 1905 and living in Denmark when the Danish 1905 cohort study was initiated in 1998 (n = 3600) using the Danish National Prescription Registry. Drug use was assessed for complete responders, non-responders at baseline, and partial responders (i.e., dropouts) in the 4-month period preceding each wave of the study (1998, 2000, 2003, and 2005), that is, as the cohort aged from 92-93 to 99-100 years. RESULTS: Complete responders, non-responders, and partial responders used a similar number of drugs at baseline, on average 4.4, increasing to 5.6 at the age of 99-100 years. In all groups, the number of used drugs increased over time; partial responders had the largest increase of 0.39 drugs per year (95% confidence interval (CI): 0.33-0.44) compared with 0.32 (95%CI: 0.27-0.37) and 0.30 (95%CI: 0.25-0.35) in the other groups. Furthermore, the most frequently used drug classes (e.g., loop diuretics and paracetamol) and the drug classes with the largest change (e.g., increase: laxatives and paracetamol; decrease: benzodiazepines) were similar across response groups. CONCLUSIONS: The number of used drugs increased in all response groups between the age of 92 and 100 years. In this study, drug use among complete responders was representative of the general drug use in the entire cohort. Copyright © 2016 John Wiley & Sons, Ltd.