Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

OBJECTIVE: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. METHODS: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. RESULTS: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. INTERPRETATION: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562.

Pharmacological treatment of obesity in adults in Norway 2004-2022.

AIMS: To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022. MATERIALS AND METHODS: We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017. RESULTS: The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. CONCLUSIONS: The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.

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.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer - A nationwide cohort study.

OBJECTIVES: To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer. DESIGN: A prospective study. SETTING: Population-based registries. POPULATION: 1.76 million women, including 17 500 women with gynaecological cancers. METHODS: Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases. MAIN OUTCOME MEASURES: Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log-binomial and Cox regression, respectively, with cancer-free women as reference. RESULTS: For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer-free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18-30 and PR = 29, 95% CI 15-38, respectively), but low in cancer-free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0-21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers. CONCLUSIONS: Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long-term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010-2019.

PURPOSE: This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use. METHODS: We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester. RESULTS: ADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden). CONCLUSION: ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.

Trajectories of ADHD medication use before, during, and after pregnancy: A population-based study from Norway and Sweden.

PURPOSE: To describe ADHD medication use trajectories around pregnancy in Norway and Sweden. METHODS: We identified pregnancies resulting in births using linked data from birth and prescribed drug registers of Norway (2006-2019, N = 813 107) and Sweden (2007-2018, N = 1 269 146). We restricted to women who filled prescriptions for ADHD medication during pregnancy or in the year before or after. We described exposure as use versus no use, and total amount of drug dispensed in defined daily doses (DDDs). Group-based trajectory modeling was used to identify distinct medication use trajectories. RESULTS: In total, 13 286 women (0.64%) filled a prescription for ADHD medication. We identified four trajectory groups: continuers (5.7%), interrupters (23.8%), discontinuers (49.5%), and late initiators (21.0%). Discontinuers were younger, continuers were older on average. More women continued medication in recent years (2014-2019). Most discontinuers (60.7%) were nulliparous; more initiators and continuers had one or multiple previous births, respectively. Continuers were least likely to live with a partner (65.8%). Discontinuers were least likely (24.7%) and continuers most likely (37.6%) to smoke at the beginning of pregnancy. More continuers used amphetamine derivatives and were most likely to use other psychotropics. On modeling continuers, we identified three dose-trajectory groups which suggested that most women reduced medication dose during pregnancy. CONCLUSIONS: Most pregnant women discontinued or interrupted their ADHD medication during pregnancy, but more continued in recent years. Continuers were more likely to have had previous births, less likely to have lived with a partner, and may have had additional comorbidities warranting the use of other psychotropics.

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.

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.

Prescribed drugs in 27 000 individuals after diagnosis of colorectal cancer: A population-based cohort study.

BACKGROUND: The prevalence of prescribed drugs in survivors of colorectal cancer (CRC) was evaluated. METHODS: Data from the Cancer Registry of Norway were linked to the Norwegian Prescription Database for a study population of 3.52 million individuals. Prevalence ratios (PRs) with 95% confidence intervals (CIs) of prescribed drugs in CRC-survivors compared to the cancer-free population, were estimated by log-binomial regression, adjusting for age and education. RESULTS: Almost 27 000 individuals, aged 20 to 84, were diagnosed with CRC during 2005 to 2014. The first year after diagnosis, the prevalence of prescribed drugs was higher in CRC-survivors compared with the cancer-free population, especially drugs for anxiety and tension, and steroid-responsive conditions. PRs for several drugs, especially drugs used for mental and behavioural disorders, decreased with time since diagnosis. The prevalence of drugs used for anxiety and tension was elevated 10 years after diagnosis; PRs the first year after diagnosis were 20 (95% CI: 18-22) in males and 17 (16-18) in females. Ten years after diagnosis PRs were 5.0 (3.1-7.9) and 2.0 (1.0-3.8), respectively. In absolute numbers, the largest increase, compared to the cancer-free population, was in drugs used for gastric acid disorders and pain. The prevalence of neuromodulatory drugs was higher in CRC-survivors. CONCLUSIONS: The prevalence of several drugs was higher in CRC-survivors than in the cancer-free population 10 years after diagnosis. The largest absolute excess in prevalence was for gastric acid disorder and pain medications, while the relative prevalence of drugs used for anxiety and tension was high in CRC-survivors. Long persisting neuropathia was indicated.

ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.

N(6)-methyladenosine (m(6)A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. The discovery of this RNA demethylase strongly suggests that the reversible m(6)A modification has fundamental and broad functions in mammalian cells.

Use of sildenafil and other phosphodiesterase type 5 inhibitors among pregnant women in Scandinavia.

INTRODUCTION: For phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, the only approved indication in women is for pulmonary arterial hypertension. These drugs are increasingly being proposed and tested for treatment of female infertility and complications in pregnancy. However, the extent of use of PDE5 inhibitors in the general pregnant population over the last decades is unknown. Therefore, we conducted a descriptive cohort study using data from the population health registers in the Scandinavian countries. MATERIAL AND METHODS: By linking the Medical Birth Registers and the Prescribed Drug Registers in Denmark (1997-2017), Norway (2004-2017), and Sweden (2006-2016), women with filled prescriptions of PDE5 inhibitors in outpatient settings in the 90 days before the date of last menstrual period and/or during pregnancies were identified. With additional linkage to the National Patient Registers, information on maternal, pregnancy, and infant characteristics, co-morbidities, and co-medication was collected and described. RESULTS: Among over 3 million singleton pregnancies, only 77 were pregnancies in women who had at least one filled prescription of a PDE5 inhibitor within the 90 days before the start of pregnancy to delivery. Prescription fills most often occurred before the last menstrual period and in the first trimester, with very few occurring later in pregnancy. Sildenafil was the most used PDE5 inhibitor. Among pregnant women using PDE5 inhibitors, 44% were 35 years of age or older, eight had a cardiovascular diagnosis, and three specifically had a diagnosis of pulmonary arterial hypertension. Among the infants born to mothers using PDE5 inhibitors, nine were born preterm, six were small-for-gestational age, five had an Apgar score at 5 minutes below 8, 18 were admitted to the Neonatal Intensive Care Unit, and eight had respiratory and cardiovascular conditions. CONCLUSIONS: Few women used PDE5 inhibitors in outpatient settings before or during pregnancy in the Scandinavian countries in the last decades. Only a small proportion had a diagnosis for pulmonary arterial hypertension, suggesting off-label use in the remaining users. Use was predominantly in mothers over age 35 years. The safety of fetal exposure to sildenafil and other PDE5 inhibitors in pregnancy has not been established. As maternal age continues to increase and additional uses of PDE5 inhibitors are investigated, the safety of these drugs in pregnancy should be thoroughly evaluated.

Validation of Assisted Reproductive Technology in the Medical Birth Registry of Norway Versus the Norwegian Prescription Database.

BACKGROUND: Increasing attention has been given to the long-term effects of assisted reproductive technology (ART). This study assessed the validity and completeness of ART as registered in the Medical Birth Registry of Norway (MBRN) using drug prescription data from the Norwegian Prescription Database (NorPD) as reference. METHODS: In this nationwide registry validation study, we included all pregnancies recorded in the MBRN between 2005 and 2017. We estimated sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the MBRN, using data from the NorPD as reference. We obtained the total percentage of ART pregnancies that could be identified (completeness) from both registries using the capture-recapture method. We analyzed subgroups by maternal age, gestational length, mode of ART treatment, health region, and mode of registration of ART (ART institution or birth notification form). RESULTS: Twenty-three thousand seven hundred eighteen of a total 765,789 pregnancies were registered as ART pregnancies through the MBRN and 20,807 as ART pregnancies through the NorPD. The sensitivity of the MBRN was 85.1% (95% confidence interval [CI] = 84.7, 85.6) and the PPV was 74.7% (74.1-75.2). Sensitivity declined with increasing maternal age: 71.5% (69.4-73.7) in the age group 40-44 years, and 40.7% (22.2-59.3) in the ages above 45 years. Completeness when combining data was 96.2% (96.0-96.5). CONCLUSIONS: Our analysis shows that, when identifying women pregnant through ART, NorPD data complemented MBRN data to obtain a more complete count of all women giving birth after ART in Norway.

Interrupted time series analysis to assess changes in prescription filling around conception and implications for exposure misclassification.

PURPOSE: Medication exposures in pregnancy are often defined by one or more prescription fills. Harmful effects could be underestimated if rapid discontinuation of use after pregnancy recognition is common. We used conception, a critical biological period, as an intervention in a novel application of interrupted time series analysis (ITSA). METHODS: Among 645 049 pregnancies from the Medical Birth Registry (2005-2015) linked to the Norwegian Prescription Database, we modeled the total number of prescription fills in the 12 weeks before and after estimated conception date with ITSA. We examined psychostimulants, antidepressants, antipsychotics, and antiepileptics (AEDs; separated by use for epilepsy or other indications). We used relative measures (%) to compare model coefficients. We also compared number of pregnancies defined as exposed when the earliest fill considered was 30 days before the last menstrual period (LMP -30 days), LMP, or estimated conception date (LMP +14 days). RESULTS: We observed a sudden decline in prescription fills from 2 weeks after conception and decreasing fills thereafter for psychostimulants, antidepressants, AEDs for other indications, and antipsychotics excluding incident users. Fills for AEDs for epilepsy did not fall after conception. Only 77% of pregnancies with fills for psychostimulants from LMP and 58% with fills from LMP -30 days had fills from conception. Similar figures for AEDs for epilepsy were 99% and 96%. CONCLUSIONS: This application shows that ITSA can help researchers understand rapid changes in patient behavior around conception that have consequences for exposure misclassification in pregnancy drug safety studies. ITSA results can help pharmacoepidemiologists guide study exposure definitions.

Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006-2016: A study in the five Nordic countries, United States, and Australia.

PURPOSE: To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching. METHODS: We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester. RESULTS: Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%). CONCLUSIONS: Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED.

Adjusting for unmeasured confounding using validation data: Simplified two-stage calibration for survival and dichotomous outcomes.

In epidemiology, one typically wants to estimate the risk of an outcome associated with an exposure after adjusting for confounders. Sometimes, outcome and exposure and maybe some confounders are available in a large data set, whereas some important confounders are only available in a validation data set that is typically a subset of the main data set. A generally applicable method in this situation is the two-stage calibration (TSC) method. We present a simplified easy-to-implement version of the TSC for the case where the validation data are a subset of the main data. We compared the simplified version to the standard TSC version for incidence rate ratios, odds ratios, relative risks, and hazard ratios using simulated data, and the simplified version performed better than our implementation of the standard version. The simplified version was also tested on real data and performed well.

ß-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

Background: ß-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to ß-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to ß-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to ß-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with ß-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of ß-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Risk factors for stroke and choice of oral anticoagulant in atrial fibrillation.

PURPOSE: To investigate risk factors for stroke in patients initiating oral anticoagulants for atrial fibrillation in Norway and their association with receiving DOACs versus warfarin. METHODS: From nationwide registries, we identified naïve users initiating treatment with warfarin, dabigatran, rivaroxaban, or apixaban for atrial fibrillation from 2010 to 2015 in Norway. We studied temporal changes in the CHA2DS2-VASc score and its component risk factors. We used multiple logistic regressions to identify CHA2DS2-VASc risk factors associated with receiving DOACs versus warfarin in 2015. RESULTS: From 2010 to 2015, the yearly number of new oral anticoagulant users increased from 7588 to 13,344. All new users initiated warfarin in 2010, while 86% initiated a DOAC in 2015. The mean CHA2DS2-VASc score decreased from 3.2 (SD 1.7) to 3.1 (SD 1.6) in the same period. Vascular disease (0.56 [0.49-0.63]), congestive heart failure (OR 0.65 [95% CI 0.58-0.72]), and diabetes (0.83 [0.73-0.95]) decreased the odds of receiving DOACs instead of warfarin, and ischemic stroke/transient ischemic attack/arterial thromboembolism (1.31 [1.12-1.54]), age 65-74 (1.23 [1.06-1.43]), and female sex (1.22 [1.10-1.36]) increased it. Age ≥ 75 (reference age < 65) and hypertension had no impact. CONCLUSIONS: The uptake of DOACs was rapid and spurred an increase in new users of oral anticoagulants for atrial fibrillation from 2010 to 2015 in Norway. The mean CHA2DS2-VASc score did not change substantially during this period. Vascular disease, heart failure, and diabetes were associated with initiation of warfarin, and previous stroke, age 65-74 and female sex with initiation of DOACs.

Trends in prescription drug use during pregnancy and postpartum in Norway, 2005 to 2015.

PURPOSE: To explore trends in use of maternal medication 3 months prior to, during and 3 months after pregnancy. METHODS: Data on births from the Medical Birth Registry of Norway were linked to the Norwegian Prescription Database, identifying women's use of medications around pregnancy. All women giving birth in Norway during 2005 to 2015 (638 532 singleton births to 414 567 women) were included. Proportions of pregnant women using different medications in association with pregnancy, and annual relative change in medication use during 2005 to 2015, were calculated. RESULTS: In Norway, 60% of pregnant women used prescription medications during pregnancy (2005-15), increasing from 57% in 2005 to 62% in 2015. The annual relative increase was 0.9% (95% CI: 0.8-1.0). In the first trimester, approximately 17% of the women used medications regarded as potentially teratogenic during 2005 to 2015, increasing from 15% to 19%. Overall, this proportion was higher in the first than in the second (8.9%) and third (8.0%) trimesters, and higher than in the 3 months after pregnancy (14%). The annual relative increase of medications regarded as potentially teratogenic in the first trimester was 2.5% (95% CI: 2.3-2.7). CONCLUSIONS: The proportion of women using potentially teratogenic medications in the first trimester of pregnancy have increased during the last decade. Clinicians need to be aware of the possibility of pregnancy when prescribing potentially teratogenic medication to women of fertile age and focus this in the consultations. The increasing trends call for the need of routine surveillance of adverse birth outcomes linked to medication use in pregnancy.

Prescribing of asthma drugs for children 2004-2015. / Forskrivning av legemidler mot astma til barn i perioden 2004­15.

BAKGRUNN: Astma kan være vanskelig å diagnostisere hos barn. For barn under skolealder finnes det få tilgjengelige objektive diagnostiske undersøkelser, og retningslinjene for diagnose og behandling er basert på sykehistorie og klinisk undersøkelse. Dette kan gi rom for varierende behandlingspraksis. MATERIALE OG METODE: Data fra Reseptregisteret ble brukt til å studere forskrivning av legemidler mot astma til barn i aldersgruppene 0-4 år og 5-9 år fordelt på fylker fra 2004-15. RESULTATER: Det var stor variasjon mellom fylkene i andelen per 1 000 barn som fikk forskrevet legemidler mot astma i perioden 2012-14 (aldersgruppen 0-4 år: median: 104/1 000; ekstremverdier: 64-147, aldersgruppen 5-9 år: 68/1000; 46-86). Inhalasjonssteroider var hyppigst forskrevet, og det var her variasjonen mellom fylkene var størst i begge aldersgruppene (aldersgruppen 0-4 år: 85/1 000; 42-116, aldersgruppen 5-9 år: 51/1 000; 31-70). De fleste fikk kun en eller få forskrivninger med inhalasjonssteroider over en treårsperiode. Endring i forskrivningen av inhalasjonssteroider fra 2004 til 2015 varierte betydelig mellom fylkene, mest for aldersgruppen 0-4 år. FORTOLKNING: Stor forskjell i forskrivning av legemidler mot astma fylkene imellom, høy andel sporadisk bruk og endring over tid, særlig i den yngste aldersgruppen, kan tyde på en unaturlig variasjon i behandlingen som ikke kan forklares av forskjeller i astmaforekomst. Uklare retningslinjer som ikke er tilstrekkelig innarbeidet i klinisk praksis kan være én årsak.

Diagnosis of hyperkinetic disorder among children in Norway. / Diagnostikk av hyperkinetisk forstyrrelse hos barn i Norge.

BACKGROUND: Hyperkinetic disorder is one of the most frequently used psychiatric diagnoses among children and adolescents in Norway. It has previously been shown that use of the diagnosis varies widely by county. MATERIAL AND METHOD: We estimated the proportion of children with hyperkinetic disorder using patient data from the Norwegian Patient Registry and population data from the Norwegian Population Registry. The estimations were made for both Norway as a whole and by county. Assessment and documentation of the diagnosis were surveyed by linking the Norwegian Patient Registry and the Norwegian Mother and Child Cohort Study. We reviewed medical records from specialist mental health services for children and adolescents and assessed whether the diagnoses met the research criteria for hyperkinetic disorder. RESULTS: At 12 years of age, 5.4 % of Norwegian boys and 2.1 % of Norwegian girls had been diagnosed with hyperkinetic disorder by specialist health services. The proportion of children varied between 1.4 % and 5.5 % among the counties. A review of medical records for 549 children showed that 49 % of the diagnoses were reliably documented in the records. The main reasons that the diagnosis was not documented were a discrepancy between the information in the medical record and diagnostic criteria (38 %) and inadequate differential diagnostic assessment (46 %). INTERPRETATION: There was considerable geographic variation in the proportions of children and adolescents with hyperkinetic disorder. A large percentage of the diagnoses were not reliably documented in medical records. The guideline for evaluation, diagnostics and medical recordkeeping should be reviewed.