Epidemiology of asthma drug use in children, adolescents and young adults in Norway

Background Asthma is one of the most common chronic diseases among children, adolescents and young adults. The use of drugs to treat asthma has not been widely investigated in the Norwegian population and there has been a lack of longitudinal data. Most studies have been conducted in confined age groups and geographic regions. The occurrence of additional health problems in the young population with asthma has important implications for the management of asthma and needs investigation. Asthma is a clinical diagnosis that is not easily captured in population-based studies and there is no agreement on a gold standard for measuring asthma in epidemiology. Prescription data on asthma drug use may be a useful proxy measure for identifying individuals with current asthma in the population. Objectives The main objectives of this thesis were to study issues related to asthma in the Norwegian population of children, adolescents and young adults. Three areas have been studied: Asthma drug use, asthma drug use as a proxy measure of asthma, and selected additional diseases and drug treatments occurring in individuals with asthma. Materials and methods This thesis rests on data from population-based databases and questionnaires: 1) The Norwegian Prescription Database, 2) The Norwegian Mother and Child cohort study questionnaire for seven years old participants, 3) The Youth Health Surveys in five counties, 4) The Population and Housing Census from 2001, and 5) The Central Population Register. Data on filled prescriptions from the Norwegian Prescription Database is the central source for information and provided the outcome variables in all papers of this thesis. Main findings Mother-reported use of asthma drugs in children had high validity, compared to prescription data of asthma drug use. Furthermore, the prescription data on asthma drugs corresponded well with maternal reports of current physician-diagnosed asthma, and few individuals with no reported asthma had filled prescriptions. Filled prescriptions were used as a proxy measure in the other papers in this thesis to identify individuals with current asthma in the study populations. The prevalence and incidence of asthma drug use in the Norwegian population 2-29 years old was highest in preschool children and lowest in young adults. Males had higher levels than females at a young age, but this changed from about 15 years of age to higher levels in females. The persistence to asthma drugs over time was relatively low, with less than half of asthma drug users receiving drugs in three consecutive years. The type of asthma drugs used varied substantially by age but not by gender, and there were indications of suboptimal pharmacotherapy. The occurrence of chronic diseases in individuals with asthma was assessed by utilizing diagnostic codes provided by physician on reimbursed prescriptions. Several diseases occurred more frequently in children, adolescents and young adults with asthma than in the Norwegian general population. A majority of the asthma population had one of the nine comorbid diseases examined, while few had more than one of the comorbidities. In another study, young adults with asthma were at an increased risk for initiating use of hypnotic drugs. The risk was highest among individuals who recently had received asthma drugs, indicating that they had currently active asthma disease. Conclusions The findings in this thesis indicate that prescription data may serve as a proxy for current asthma in the population. It is important to carefully consider the length of the capture period for prescription data and possible overlapping conditions treated with the same drugs in different age groups. The relatively low persistence to asthma drug use may reflect the variability of asthma within and between patients, and illustrate the challenges encountered in defining asthma in epidemiologic studies. Several diseases and drug treatments occurred more frequently in the asthma population. The presence of comorbidities may influence and complicate several aspects of asthma and both the causes and consequences of comorbidities need further investigation

Psychotropic drug use among 0-17 year olds during 2004-2014: a nationwide prescription database study

This is an Open Access article licensed under the Creative Commons Attribution License 3.0 (CC BY 3.0) and originally published in BMC Psychiatry. You can access the article by following this link: http://dx.doi.org/10.1186/s12876-016-0446-zDette er en vitenskapelig, fagfellevurdert artikkel som opprinnelig ble publisert i BMC Psychiatry. Artikkelen er publisert under lisensen Creative Commons Attribution License 3.0 (CC BY 3.0). Du kan også få tilgang til artikkelen ved å følge denne lenken: http://dx.doi.org/10.1186/s12876-016-0446-zBackground Time-trend studies on psychotropic drugs among children and adolescents are scarce, and most of them are outdated. The purpose of this study was to study prevalences of psychotropic drug use during 2004–2014 among Norwegians aged <18 years, overall and in psychotropic sub-groups. Methods Data were obtained from the Norwegian Prescription Database, which covers all dispensed prescription drugs in Norway from 2004 and onwards. Psychotropic drugs included: antipsychotics (ATC-group N05A), anxiolytics (N05B), hypnotic/sedatives (N05C), antidepressants (N06A), stimulants (N06BA), and alimemazine (R06AD01). Period (1-year) prevalence of use, overall and in subgroups of psychotropic drugs, was estimated by identifying individuals <18 years who had at least one psychotropic drug dispensed during each year. Results Psychotropic drug use increased in 0–17 year olds over an 11-year period, in which the main contributing drugs were stimulants (boys overall; 15.0 to 20.8/1000, girls overall; 3.8 to 8.5/1000), hypnotic/sedative drugs in adolescents (boys overall; 4.2 to 10.8/1000, girls overall; 2.6 to 8.8/1000) and to some extent antidepressants among adolescent girls (girls overall from 3.1 to 4.0/1000). Psychotropic drug use was, however, reduced by half in the youngest children, attributed to reduction of alimemazine only (1-year olds: boys; from 36.6 to 10.2/1000, girls; 26.9 to 7.2/1000). A higher level of psychotropic drug use was observed among younger boys, but there is a shift towards girls using more psychotropic drugs than boys during adolescence for all psychotropic drugs except for stimulants. Conclusion Different trends in psychotropic drug use exist in age and gender subgroups. Psychotropic drug use has decreased among the youngest children, attributed to alimemazine, and increased in older children and adolescents, attributed mainly to stimulants and hypnotics/sedatives

Airway symptoms and atopy in young children prescribed asthma medications:A large-scale cohort study

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age‐intervals (0‐6, 6‐18, 18‐36 months, and 3‐7 years). Primary outcomes were dispensed asthma medications (no medication, short‐acting β‐2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0‐6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups.publishedVersio

Maternal history of miscarriages and measures of fertility in relation to childhood asthma

Background: it remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (art). Objective: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between art and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. Methods: We used data from national norwegian health registries (n=474 402) and the norwegian Mother and child cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. Results: ART offspring had greater asthma risk, the adjusted relative risk (arr) was 1.20 (95% ci 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% ci 1.14 to 1.76) in MoBa. the sibling analysis yielded similar associations, although the ci included the null value. the elevated asthma risk among art offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, arr 1.22 (95% ci 0.95 to 1.57). asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an arr of 1.07 (95% ci 1.03 to 1.11) for one, arr 1.18 (95% ci 1.10 to 1.26) for two and arr 1.24 (95% ci 1.12 to 1.37) for three or more. Conclusion: Our findings indicate that both parental subfertility and characteristics related to the art procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis

Antipsychotic use in pregnancy and risk of attention/ deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study

Background Antipsychotics are increasingly used among women of childbearing age and during pregnancy. Objective To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors. Findings Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD. Discussion Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. Clinical implications Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.publishedVersio

Cancer risk among insulin users : comparing analogues with human insulin in the CARING five-country cohort study

Aims/hypothesis The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. Methods National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. Results A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for 6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. Conclusions/interpretation The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.Peer reviewe

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study

AIMS: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant. METHODS AND RESULTS: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94). CONCLUSION: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial

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

Publisher's version (útgefin grein)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.This study was funded by NordForsk as part of the Nordic Pregnancy Drug Safety Studies (NorPreSS) (Project No: 83539) and the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS) (Project No: 273366). Linkage of Danish data was supported by the Danish Council for Independent Research (Project No: DFF‐6110‐00019) and Karen Elise Jensens Fond (2016), and grant NNF18OC0052029 from Novo Nordisk Fonden (Li). Linkage of the Australian data was supported by an Australian National Health and Medical Research Council Project grant (No. 1028543). We thank Anders Engeland (Norwegian Institute of Public Health, University of Bergen, Norway), Anna Heino (National Institute for Health and Welfare, Finland), Mette Nørgaard (Aarhus University, Denmark), Pär Karlsson (Karolinska Institutet, Sweden), Jennifer Yland (Harvard T.H. Chan School of Public Health, USA), Gregory Brill and Helen Mogun (Brigham and Women's Hospital & Harvard Medical School, USA) for providing assistance with analyses. The authors would like to thank the NSW Ministry of Health, the Australian Government Department of Health and Ageing and the Department of Human Services for providing data. The authors also thank the Centre for Health Record Linkage (CHeReL) and the Australian Institute for Health and Welfare for conducting the linkage of records.Peer Reviewe

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder : a Nordic cohort study

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND: Antipsychotics are increasingly used among women of childbearing age and during pregnancy. OBJECTIVE: To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors. FINDINGS: Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD. DISCUSSION: Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. CLINICAL IMPLICATIONS: Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.Peer reviewe

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder : a Nordic cohort study

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND: Antipsychotics are increasingly used among women of childbearing age and during pregnancy. OBJECTIVE: To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors. FINDINGS: Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD. DISCUSSION: Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. CLINICAL IMPLICATIONS: Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.Peer reviewe