Considerable paediatric drug dispensing - A nationwide study of more than 2 million Swedish children.

AIM: The aim of the nationwide study was to describe paediatric drug utilisation in Sweden. METHODS: Drug prescriptions dispensed to all children aged 0-17 years in 2019 were analysed using data from the Swedish National Prescribed Drug Register. RESULTS: We retrieved data on 2 180 508 unique children. Nearly 4.6 million prescriptions were dispensed to children aged 0-17 years, and 52% of these were to boys. Just under half of the children (47%) were dispensed at least one drug: 48% of girls and 45% of boys (p < 0.01). More than a third (34%) were dispensed three or more different drugs during 2019. The number of dispensed prescriptions per 1000 children was higher in boys than girls up to 12 years of age (p < 0.01), and the opposite trend was observed from 13 years and above, even when we excluded contraceptives (p < 0.01). The most common therapeutic areas were drugs for the respiratory tract (25%), namely antihistamines, antiasthmatics and cough medication. These were followed by psychoanaleptics and melatonin for the nervous system (19%) and dermatologicals (16%), namely cortisone creams and emollients. CONCLUSION: Paediatric drug use was common, and a considerable proportion of children were dispensed multiple drugs.

New users of anxiolytics and sedatives in Sweden-Drug type, doses, prescribers' characteristics, and psychiatric comorbidity in more than 750,000 patients.

OBJECTIVES: Anxiety and sleep disorders are common in the population and anxiolytics and sedatives are widely used. Our aim was to describe the drug utilization of new users of anxiolytics and sedatives in adults including type of drug, doses, prescribers' characteristics, and psychiatric comorbidity. METHODS: A register-based cohort study of new users (18-64 years) of anxiolytics and sedatives in 2015-2019, free of any such drug 5 years prior to inclusion. The individuals were linked to national registers on dispensed drugs and recorded diagnoses. RESULTS: In total, 764,432 new users of anxiolytics and sedatives were identified, which corresponds to an incidence of 26/1000 inhabitants and year. The proportion of new users of benzodiazepines (including both anxiolytics and sedatives) decreased, whereas the proportion of sedative antihistamines and melatonin increased. The most common drug dispensed was hydroxizin (33%) followed by benzodiazepine related drugs (zopiclone and zolpidem; 20%), propiomazine (14%) and benzodiazepines (13%). The majority (68%) of the prescriptions were from primary care. Most new users were prescribed 1-30DDDs and 52% among women and 49% among men were dispensed their drug only once during the first year. Half of the new users had a previous comorbid psychiatric disorder. CONCLUSIONS: The findings are well reflecting the recommendations in national guidelines.

Melatonin Prescription in Children and Adolescents in Relation to Body Weight and Age.

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution.

Defined daily doses in pediatric dosing- a theoretical example.

A defined daily dose for children (cDDD) taking body weight into account, was proposed as a better measure of drug utilization in children than the World Health Organization's DDD. There is no global definition of DDDs for children, and it is unclear which standard doses should be used for children when conducting drug utilization studies. We used doses according to the authorized medical product information and body weight according to national pediatric growth curves to calculate theoretical cDDD for three common medicines in children in a Swedish setting. These examples demonstrate that the concept of cDDD may not be optimal for drug utilization studies in children, especially not for younger children and when dosing is done according to weight is crucial. Validation of cDDD in real-world data is warranted. When conducting pediatric drug utilization studies, accessibility to individual-level data on body weight and age combined with dosing information is needed.

The effect of absent or deferred antibiotic treatment on complications of common infections in primary care.

OBJECTIVES: The objective of this study was to compare the incidence rate for complications to upper respiratory tract infections (URTIs), including acute bronchitis and lower urinary tract infections (UTIs), for those treated with antibiotics compared to those who were not. METHODS: This was a population-based retrospective cohort study in Sweden. Patients diagnosed with otitis, pharyngotonsillitis, sinusitis, acute bronchitis, and lower UTI in primary care between 2014 and 2020 were included. Data on prescribed and dispensed antibiotics and comorbidities for each subject were collected. The outcome we investigated was the number of infectious complications within 30 days and if antibiotic treatment had any effect on risk reduction. RESULTS: There were 202,995 episodes of otitis, 388,158 pharyngotonsillitis, 125,792 sinusitis, 220,960 bronchitis, and 377,954 lower UTIs in our cohort. No increased risk for complications was seen for untreated compared with treated cases with URTI. For lower UTI, the adjusted odds ratio for febrile UTI or bloodstream infection was 1.53 (95% confidence interval 1.39-1.68). CONCLUSION: The risk for infectious complications from common URTIs is low and not modified by antibiotic treatment. On the contrary, patients diagnosed with UTI in whom antibiotics were withheld had an increased 30 days risk for severe infections.

Non-adherence and sub-optimal treatment with asthma medications in young adults: a population-based cohort study.

OBJECTIVE: Pharmacological treatment plays a key role in the management of asthma, but medication adherence is generally low. Our aim was to assess factors associated with dispensing patterns of, and adherence to, asthma medication in young adults with asthma. METHODS: The study included young adults (age 22-24 years) from the Swedish population-based birth cohort BAMSE (n = 3,064) with linkage to register data on dispensed asthma medications and recorded diagnosis. Dispensing information was collected in January 2014-June 2019 (the study period) to cover the period of questionnaire data. Adherence to asthma medication was defined as refilling a prescription within 18 months. RESULTS: In total, 234 individuals (7.6%) had asthma (doctor's diagnosis of asthma in combination with respiratory symptoms) and had been dispensed at least one prescription of asthma medication during the study period. Among them, 77% were dispensed a controller medication. The mean number of prescriptions dispensed per individual was higher in males than females (11.0 vs. 7.2; p < 0.01). The proportion of asthmatics with only a short-acting ß2-agonist (SABA) dispensed was 22%, of which 33% were classified as having uncontrolled asthma. Adherence to controller medication was 60% and higher among those with an asthma diagnosis from specialized care than those diagnosed in primary care (RR 1.32 95% CI 1.03-1.69). Sex, socioeconomic status, and non-allergic comorbidity did not affect adherence. CONCLUSION: Young adults with asthma had few prescriptions of asthma medication dispensed, indicating sub-optimal treatment. A considerable proportion was dispensed only SABA. Furthermore, adherence to controller medication was relatively low.

Sibship and dispensing patterns of asthma medication in young children-a population-based study.

PURPOSE: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings' medication into account. METHODS: A register-based cohort study including all children (n = 50 546) born in Stockholm, Sweden 2006 to 2007, followed up during 2006 to 2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4 and 18 months) in a refill sequence model including siblings' and unrelated control children's medication. RESULTS: After 1 year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95% CI 0.80-0.90) among children with siblings compared with singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings' controller medication, the estimated proportion was 8.8% (4 months) and 7.8% for control children (relative risk (RR) 0.89, 95% CI 0.81-0.98). The persistence was lower for those with siblings compared with singletons (adj. RR 0.72, 95% CI 0.62-0.85 for 4 months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. CONCLUSIONS: Siblings have different dispensing patterns of asthma medications compared with singletons regardless of asthma diagnoses. After including the siblings' asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.

Eliminated patient fee and changes in dispensing patterns of asthma medication in children-An interrupted time series analysis.

In 2016, all prescription drugs included in the reimbursement system in Sweden were made available for children (age 0-17 years) without any patient fees. Our aim was to estimate the association between this intervention and the dispensing patterns of asthma medications among children. Dispensing data on asthma medications for all children living in Stockholm County during 2014-2017 were selected to include two years before (January 2014-December 2015) and after (January 2016-December 2017) the intervention. In an uncontrolled before and after study, the measures of utilization were as follows: the proportion of children with at least one dispensed asthma medication (prevalence); the number of children initiated on treatment after an 18-month drug-free period (incidence); the number of defined daily doses (DDDs) dispensed per child; and the number of children with at least two prescriptions with controller medication (inhaled corticosteroid or leukotriene receptor antagonist) dispensed during 18 months (persistence). In an interrupted time series (ITS) analysis, all measures were included except for persistence. Socio-economic status was defined using Mosaic data. The prevalence increased after the intervention (from 11.9% to 13.0%). However, the ITS analysis showed a positive trend already before the intervention, and consequently, the increase was not attributable to the intervention. For incidence, similar patterns were observed. There was an increase in dispensed volumes related to the intervention, 46.3 DDDs/child/month before and 51.1 after the intervention (P-value 0.01). The proportion of children with persistent asthma medication increased from 46.0% to 51.9% in children with low socio-economic status. In conclusion, the intervention was only modestly associated with changes in the dispensing patterns of asthma medication, with the volume dispensed per child increasing slightly, particularly in children with low socio-economic status.

Agreement between asthma questionnaire and health care register data.

PURPOSE: Risk factors and consequences of asthma can be studied by using validated questionnaires. The overall objective of this study was to assess the agreement of parental-reported asthma-related questions regarding their children against Swedish health care registers. METHODS: We linked a population-based twin cohort of 27 055 children aged 9 to 12 years to the Swedish Prescribed Drug Register, National Patient Register, and the primary care register. Parent-reported asthma was obtained from questionnaires, and diagnoses and medication were retrieved from the registers. For the agreement between the questionnaire and the registers, Cohen's kappa was estimated. RESULTS: The kappa of the "reported ever asthma" against a "register-based ever asthma" was 0.69 and 0.57 between the parental-"reported doctor's diagnosis" and "register-based doctor's diagnosis." The highest agreement between "reported current asthma" and "register-based current asthma" with at least 1 dispensed medication or a diagnosis applied to different time windows was seen for an 18-month window (kappa = 0.70). CONCLUSIONS: We found that parent-reported asthma-related questions showed on average good agreement with the Swedish health care registers. This implies that in-depth questionnaires with rich information on phenotypes are suitable proxies for asthma in general and can be used for health care research purposes.

Medicine use and disease control among adolescents with asthma.

PURPOSE: Pharmacological treatment is a cornerstone in asthma management, but there is limited evidence on how adolescents use their medication and to what extent their asthma is under control. Therefore, the aim of this study was to compare self-reported and register-based medicine use in asthmatic adolescents. Furthermore, we investigated the association between medicine use, patient characteristics, and degree of asthma control. METHODS: Cross-sectional analyses of 331 adolescents with asthma from a population-based birth cohort linked to data from the Swedish Prescribed Drug Register. Adolescents' asthma medicine use was assessed with three approaches: self-reported medicine use, self-reported use of someone else's medicines, and dispensed medicines from pharmacies during an 18-month period. Medicine use in adolescents with and without asthma control were compared. RESULTS: In total, 82% reported use of asthma medicines, 10 % reported use of someone else's medicines, and 62% were dispensed asthma medicines from pharmacies. Among adolescents with self-reported medicine use, 22% (n = 60) were neither dispensed medicines nor using someone else's medicines. The majority of those using someone else's medicines had also been dispensed asthma medicine (22 out of 33). Among adolescents with asthma, 176 were fully controlled and 155 were uncontrolled. Also, boys had higher odds of having asthma control than girls. CONCLUSION: Most adolescents with asthma reported use of asthma medicines, but a considerable proportion were neither dispensed any medicines nor using someone else's medicines. Girls were less likely to achieve asthma control. It is important to combine data sources to understand medicine use among adolescents with asthma.

Factors associated with concordance between parental-reported use and dispensed asthma drugs in adolescents: findings from the BAMSE birth cohort.

PURPOSE: Pharmacological treatment is important in asthma care, but there are methodological challenges in measuring how drugs are used by patients. The aim of this study was to investigate the concordance between register data on dispensed drugs and parental-reported use of asthma drugs in adolescents. METHODS: A cross-sectional study comparing data on dispensed drugs from the Swedish Prescribed Drug Register with data on parental-reported use of asthma drugs among 3 316 adolescents (age 11-14 years) in a population-based birth cohort in Sweden. Sensitivity, specificity, and positive predicted value for different time windows (3, 6, 12, 18, and 24 months) for dispensing in the register were computed. Logistic regression was used to explore factors associated with concordance. RESULTS: The prevalence of parental-reported use of asthma drugs in the past year was 10.7% (n = 356) compared with 8.1% (n = 269) for dispensed drugs according to the register (p ≤ 0.001). The sensitivity increased with an extended time window in the register, whereas the specificity remained high up to 18 months. Although 90% of the adolescents with asthma had parental-reported use of asthma drugs, 30% of them had no such drugs dispensed in the preceding 18 months. The highest concordance was seen for adolescents with severe asthma (OR 4.6, CI 1.2-17.6). CONCLUSIONS: An 18-month window is preferable when using dispensing data to study the use of asthma drugs. Still, many adolescents with reported drug use had not purchased any asthma drug in this period. The concordance between parental-reported use and dispensed drugs is higher for adolescents with severe asthma.

Socioeconomic status and the quality of prescribing asthma drugs in Sweden.

INTRODUCTION: Socioeconomic status (SES) is strongly associated with morbidity as well as with health care utilization and expenditure. The association between SES and quality of prescribing of asthma drugs is less studied. OBJECTIVES: The aim of this study was to examine the association between socioeconomic factors, i.e. education, income and country of birth, and the prevalence, incidence and adherence to guidelines for antiasthmatic drugs. METHODS: This registry study includes all Swedish citizens aged 25-44 years who redeemed at least one prescription of an antiasthmatic drug during 2010. Incidence and prevalence was calculated. The adherence to guidelines was studied using two defined quality indicators. Heavy users were also assessed. RESULTS: Incidence for antiasthmatic drugs was 18.4 per 1000 person-years and the prevalence 50.9 per 1000 inhabitants. Previously untreated patients who redeemed fixed combination ranged from 45% to 49%. Patients who purchase long-acting beta-2-adrenoceptor agonists (LABA) without inhaled corticosteroid ranged from 43% to 59%. Six percent of the population was classified as heavy users. CONCLUSION: The study showed a high incidence and prevalence of asthma drug use with a poor adherence to guidelines for rational drug prescribing. Fixed combination as first line asthma treatment as well as purchasing LABA without concomitant ICS was more common in patients born outside Scandinavia. Heavy users of short-acting bronchodilators were associated with male sex, high age, low income levels and low levels of education.