ORCID Profile
0000-0003-0761-9028
Current Organisations
University of Iceland
,
UNSW Sydney
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: BMJ
Date: 12-01-2011
DOI: 10.1136/BMJ.D8012
Abstract: To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Population based cohort study using data from the national health registers. Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. More than 1.6 million infants born after gestational week 33. Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000) adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2021
Publisher: Wiley
Date: 14-11-2014
Abstract: To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. Case-control study using data from national registers. Denmark, Finland, and Norway during the period 1996-2007. A total of 14,902 women were included as cases and 148,929 women were included as controls. Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies.
Publisher: American Medical Association (AMA)
Date: 11-2022
DOI: 10.1001/JAMANEUROL.2022.2977
Abstract: Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown. To assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer. Observational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3 379 171 children after exclusion of 126 711 children because of stillbirth or missing or erroneous values on important covariates. Maternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth. First onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk. The median age at the end of follow-up in the study population of 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46 646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4 absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6% 95% CI, 0.2%-1.3%). Prenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.
Publisher: Wiley
Date: 19-12-2018
DOI: 10.1002/PDS.4702
Abstract: Increased expression of Vacuolar-type H In this population-based case-control study, we identified incident cases of breast cancer (n = 1739), prostate cancer (n = 1897), and malignant melanoma (n = 385) in Iceland between 2005 and 2014 from the Icelandic Cancer Registry. We assessed varying levels of PPI use through record linkages to the Icelandic Medicines Registry. For each case, we selected up to 10 age-matched, sex-matched, and calendar-matched population controls using risk-set s ling. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) controlling for NSAID use. Adjusted ORs associated with ever use of PPIs were 1.03 (95% CI: 0.92-1.16) for breast cancer, 1.12 (95% CI: 1.00-1.25) for prostate cancer, and 0.84 (95% CI: 0.69-1.12) for malignant melanoma. Analyses of high use of PPIs (≥1000 DDDs) yielded ORs of 0.97 (95% CI: 0.78-1.19), 1.20 (0.99-1.47), and 0.59 (0.40-1.13) for breast cancer, prostate cancer, and malignant melanoma, respectively. Analyses of cumulative exposure to PPIs did not support a dose-response relationship for any of the three cancer types. Our findings do not support a chemopreventive effect of PPI use on breast cancer, prostate cancer, or malignant melanoma.
Publisher: Wiley
Date: 23-05-2013
DOI: 10.1002/PDS.3457
Abstract: All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up.
Publisher: SAGE Publications
Date: 23-08-2023
DOI: 10.1177/00048674221114782
Abstract: New therapeutic options such as lisdexamfetamine and guanfacine have recently become available for the treatment of attention deficit hyperactivity disorder. We described contemporary patterns of attention deficit hyperactivity disorder medicine use among children, adolescents and adults in Australia. This population-based study used dispensing data for a 10% random s le of Australian residents between July 2012 and December 2020. We estimated the annual prevalence and incidence of attention deficit hyperactivity disorder medicines, second-line guanfacine use and examined concurrent medicine use of both stimulants and non-stimulants. We followed incident users for up to 5 years and analysed treatment persistence using a novel proportion of people covered method. Analyses were stratified by attention deficit hyperactivity disorder medicine, sex and age group young children (0–5 years), children (6–12 years), adolescents (13–17 years), young adults (18–24 years) and adults (⩾25 years). We observed a twofold increase in the overall prevalence of attention deficit hyperactivity disorder medicine use between 2013 and 2020, from 4.9 to 9.7 per 1000 persons. Incident use also increased across all age groups and both sexes, with the most pronounced increases among adolescent females (from 1.4 to 5.3 per 1000 persons). Stimulant treatment persistence after 5 years was highest among those initiating treatment as young children (64%) and children (69%) and lowest among those initiating treatment in adolescence (19%). Concurrent use of stimulants and non-stimulants was more common among males and younger age groups. Most children (87%) initiating guanfacine had prior dispensings of attention deficit hyperactivity disorder medicines. We observed increasing attention deficit hyperactivity disorder medicine use in Australia, especially among young females. Nevertheless, treatment rates remain lower than the estimated prevalence of attention deficit hyperactivity disorder across all subpopulations. Poor long-term treatment persistence in adolescence may warrant improved clinical monitoring of attention deficit hyperactivity disorder in patients transitioning from paediatric to adult care. Reassuringly, use of newly approved guanfacine appeared to be in accordance with guidelines among children.
Publisher: Wiley
Date: 16-08-2015
DOI: 10.1002/PDS.3852
Abstract: Several survey studies have documented misuse of methylphenidate defined as the use of non-prescribed methylphenidate or use different from what was prescribed. We aimed to identify and characterize adults with deviant patterns of methylphenidate use in Denmark during 2007-2012. Further, we aimed to identify risk factors associated with deviant patterns of use. Based on in idual-level prescription data, new users of methylphenidate were followed for one year after filling their first prescription on methylphenidate. Adult patients were identified with deviant patterns of use if they had ≥4 different prescribers and filled ≥1095 defined daily doses of methylphenidate during the year of follow-up. Risk factors were estimated by using logistic regression. Among 20 829 new users of methylphenidate, we identified 82 (0.39%) patients displaying deviant patterns of use. Characteristics associated with deviant patterns of use included an initial prescription for extended-release methylphenidate (OR2 4.35), age 25-49 years at first prescription (OR2 2.49), general practitioners or hospital doctors as initial prescribers (OR2 3.06 and OR2 4.07) and prior use of drugs used in addictive disorders (OR2 2.08) or opioids (OR2 1.75). Sensitivity analyses revealed that the number of different prescribers alone does not seem to effectively identify deviant users of methylphenidate. We have identified characteristics associated with deviant patterns of methylphenidate use. Our results do not allow us to conclude if deviant users truly represent medical misusers.
Publisher: Wiley
Date: 21-07-2023
DOI: 10.1111/BCP.15821
Abstract: There are increasing concerns about harms related to suboptimal antipsychotic use. Here we describe recent population‐based trends in antipsychotic use and harms in Australia and identify population groups exhibiting patterns of use likely to contribute to these harms. Using population‐based data from the Australian Pharmaceutical Benefits Scheme (2015‐2020), poisoning calls to the New South Wales (NSW) Poisons Information Centre (2015‐2020) and poisoning deaths in all coronial records (2005‐2018) in Australia, we measured trends in the prevalence of antipsychotic use and related deaths and poisonings. We applied latent class analyses to identify patterns of antipsychotic use that may contribute to harms. Quetiapine and olanzapine had the highest prevalence of use between 2015 and 2020. Noteworthy trends included increases of 9.1% and 30.8% in quetiapine use and poisonings, while olanzapine use decreased by 4.5% but poisonings increased by 32.7%. Quetiapine and olanzapine poisonings and related deaths had the highest rates of co‐ingestion of opioids, benzodiazepines and pregabalin compared to other antipsychotics. We identified six distinct population groups using antipsychotics: (i) ongoing high‐dose use with sedatives (8%), (ii) ongoing use (42%), (iii) ongoing use with analgesics and sedatives (11%), (iv) long‐term low‐dose use (9%), (v) sporadic use (20%) and (vi) sporadic use with analgesics (10%). Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for ex le through prescription monitoring systems.
Publisher: SAGE Publications
Date: 2020
Abstract: Proton-pump inhibitors (PPIs) are among the most prescribed medicines worldwide and concern about their long-term use is growing. We used dispensing claims for every person in Australia dispensed publicly subsidized PPIs between 2013 and 2016 to determine the incidence and prevalence of PPI use and to examine the patterns and durations of PPI treatment among in iduals continuing treatment beyond the guideline-recommended maximum 12 weeks. We estimated annual prevalence and incidence per 100 people and duration of treatment for every Australian dispensed publicly subsidized PPIs between 2013 and 2016. We examined patterns of PPI treatment in three patient subgroups using PPIs for more than 12 weeks duration people receiving maintenance, long-term continuous or long-term intermittent treatment. We calculated the proportion in each subgroup stepping down from higher to lower PPI strengths, stepping up from lower to higher PPI strength and discontinuing treatment. PPIs were dispensed to 4,388,586 people 60% were women median age at initiation was 52 years [interquartile range (IQR): 36–65]. Standard and high strength PPIs accounted for 95% of dispensings. Annual incidence and prevalence were 3.9/100 and 12.5/100, respectively, in 2016 and highest among in iduals over 65 years (prevalence range: 33–43/100). Most people (67%) stopped treatment after one dispensing while 25%, 6% and 10% continued on maintenance, long-term continuous and long-term intermittent treatment, respectively. Median duration of treatment in people continuing treatment was 501 days (IQR: 180–not reached) for maintenance treated in iduals and ‘not reached’ for long-term treated in iduals. We observed 35%, 20% and 47% of people stepping down from higher to lower treatment strengths on maintenance, long-term continuous and long-term intermittent treatment, respectively. Longer-term treatment with higher strength PPIs is common. Targeted regulation of PPI prescribing may improve the uptake of lower strength formulations and reduce both harms and costs associated with long-term PPI treatment.
Publisher: American Medical Association (AMA)
Date: 06-2023
DOI: 10.1001/JAMANEUROL.2023.0674
Abstract: Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied. To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy. This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023. Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth. The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 in idual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported. Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM 19 582 [51.3%] male mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03] cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%] cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78 95% CI, 1.03-3.07). Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2016
DOI: 10.1007/S10654-016-0139-5
Abstract: Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preecl sia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preecl sia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preecl sia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery ( 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preecl sia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preecl sia paradox appears to be an ex le of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preecl sia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes.
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.ENVRES.2011.10.010
Abstract: Air pollutants in Iceland's capital area include hydrogen sulfide (H2S) emissions from geothermal power plants, particle pollution (PM10) and traffic-related pollutants. Respiratory health effects of exposure to PM and traffic pollutants are well documented, yet this is one of the first studies to investigate short-term health effects of ambient H2S exposure. The aim of this study was to investigate the associations between daily ambient levels of H2S, PM10, nitrogen dioxide (NO2) and ozone (O3), and the use of drugs for obstructive pulmonary diseases in adults in Iceland's capital area. The study period was 8 March 2006 to 31 December 2009. We used log-linear Poisson generalized additive regression models with cubic splines to estimate relative risks of in idually dispensed drugs by air pollution levels. A three-day moving average of the exposure variables gave the best fit to the data. Final models included significant covariates adjusting for climate and influenza epidemics, as well as time-dependent variables. The three-day moving average of H2S and PM10 levels were positively associated with the number of in iduals who were dispensed drugs at lag 3-5, corresponding to a 2.0% (95% confidence interval [CI] 0.4, 3.6) and 0.9% (95% CI 0.1, 1.8) per 10 μg/m3 pollutant concentration increase, respectively. Our findings indicated that intermittent increases in levels of particle matter from traffic and natural sources and ambient H2S levels were weakly associated with increased dispensing of drugs for obstructive pulmonary disease in Iceland's capital area. These weak associations could be confounded by unevaluated variables hence further studies are needed.
Publisher: Wiley
Date: 16-02-2022
DOI: 10.1111/PPE.12870
Abstract: Medicine prescribing for children is impacted by a lack of paediatric‐specific dosing, efficacy and safety data for many medicines. To estimate the prevalence of medicine use among children and the rate of ‘off‐label’ prescribing according to age at dispensing. We used population‐wide primarily outpatient dispensing claims data for 15% of Australian children (0–17 years), 2013–2017 ( n = 840,190). We estimated prescribed medicine use and ‘off‐label’ medicine use according to the child's age ( year, 1–5 years, 6–11 years, 12–17 years) defined as medicines without age‐appropriate dose recommendations in regulator‐approved product information. Within off‐label medicines, we also identified medicines with and without age‐specific dose recommendations in a national prescribing guide, the Australian Medicines Handbook Children's Dosing Companion (AMH CDC). The overall dispensing rate was 2.0 dispensings per child per year. The medicines with the highest average yearly prevalence were systemic antibiotics (435.3 per 1000 children), greatest in children 1–5 years (546.9 per 1000). Other common medicine classes were systemic corticosteroids (92.7 per 1000), respiratory medicines (91.2 per 1000), acid‐suppressing medicines in children year (47.2 per 1000), antidepressants in children 12–17 years (40.3 per 1000) and psychostimulants in children 6–11 years (27.0 per 1000). We identified 12.2% of dispensings as off‐label based on age, but 66.3% of these had age‐specific dosing recommendations in the AMH CDC. Among children year, off‐label dispensings were commonly acid‐suppressing medicines (35.5%) and topical hydrocortisone (33.1%) in children 6–11 years, off‐label prescribing of clonidine (16.0%) and risperidone (13.1%) was common. Off‐label dispensings were more likely to be prescribed by a specialist (21.7%) than on‐label dispensings (7.5%). Prescribed medicine use is common in children, with off‐label dispensings for medicines without paediatric‐specific dosing guidelines concentrated in classes such as acid‐suppressing medicines and psychotropics. Our findings highlight a need for better evidence to support best‐practice prescribing.
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/BCPT.12243
Abstract: In this study, we leveraged on complete nationwide prescription data for the total adult population in Iceland (N = 227,000) to examine how attention-deficit/hyperactivity disorder (ADHD) drugs have been used over the past decade. In particular, we aimed to describe the prevalence, incidence and duration of use of stimulants and atomoxetine, among adults (≥19 years) in Iceland, with regard to sex, age, type of drug and specialty of the prescribing physician. Our results indicate that the 1-year period prevalence of ADHD drug use rose, from 2.9 to 12.2 per 1000 adults between 2003 and 2012, with the most pronounced increases among young adults (19-24 years). The annual incidence increased 3 times, similarly among men and women. Extended-release methylphenidate formulations were the most commonly used ADHD drugs. Specialists in psychiatry initiated treatment in 79% of new adult ADHD drug users. The proportion of users still receiving treatment after 1 year varied from 43.0% (19-24 years), 57.2% (25-49 years) to 47.5% (50+ years). After 3 years, the corresponding proportions still on treatment were 12.4%, 24.5% and 24.3%, and after 5 years 7.9%, 15.9% and 16.8%. These results of increasing ADHD drug use and short treatment durations call for further investigation of the quality of treatment regimens for adults with ADHD and better follow-up of patients treated with ADHD drugs.
Publisher: MDPI AG
Date: 18-12-2021
Abstract: Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to in iduals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research exemplified by Australia’s limited capacity to contribute to the global effort in real-world studies of vaccine and disease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2010
DOI: 10.1007/S00228-010-0789-2
Abstract: To examine the risk of thromboembolic cardiovascular events in users of coxibs and NSAIDs in a nationwide cohort. Data were synchronised from three nationwide databases, the Icelandic Medicines Registry (IMR), The Icelandic National Patient Registry (INPR) and the Registry for Causes of Death at Statistics Iceland (RCD), for prescriptions for NSAIDs or coxibs with respect to hospitalisation for unstable angina pectoris, myocardial infarction and cerebral infarction over a 3-year period. The Cox proportional hazards model and Poisson regression were used to analyse the data. A total of 108,700 in iduals received prescriptions for NSAIDs or coxibs (ATC code M01A), of whom 78,539 received one drug only (163,406 person-years). Among those receiving only one drug 426 in iduals were discharged from hospital with endpoint diagnoses. In comparison to diclofenac, the incidence ratios, adjusted for age and gender, were significantly higher for cerebral infarction (2.13 95% CI 1.54-2.97 P < 0.001), for myocardial infarction (1.77 95% CI 1.34-2.32 P < 0.001) and for unstable angina pectoris (1.52 95% CI 1.01-2.30 P = 0.047) for patients who used rofecoxib. For naproxen users, the incidence ratio was 1.46 for myocardial infarction (95% CI 1.03-2.07 P = 0.03), but was reduced in ibuprofen users (0.63 95% CI 0.40-1.00 P = 0.05). The youngest users of rofecoxib (< or =39 years) had the highest hazard ratio (HR) for cardiovascular events (8.34 P or =60 years had a lower but still significantly elevated HR (1.35 P = 0.001). This Icelandic nationwide registry-based study amounting to 163,406 patient-years showed increased risk of cardiovascular events, i.e. cerebral infarction, myocardial infarction and unstable angina pectoris, among rofecoxib and naproxen users in comparison to diclofenac users. The added risk was most pronounced in young adults using rofecoxib.
Publisher: American Academy of Pediatrics (AAP)
Date: 07-2012
Abstract: We evaluated the hypothesis that later start of stimulant treatment of attention-deficit/hyperactivity disorder adversely affects academic progress in mathematics and language arts among 9- to 12-year-old children. We linked nationwide data from the Icelandic Medicines Registry and the Database of National Scholastic Examinations. The study population comprised 11 872 children born in 1994–1996 who took standardized tests in both fourth and seventh grade. We estimated the probability of academic decline (drop of ≥5.0 percentile points) according to drug exposure and timing of treatment start between examinations. To limit confounding by indication, we concentrated on children who started treatment either early or later, but at some point between fourth-grade and seventh-grade standardized tests. In contrast with nonmedicated children, children starting stimulant treatment between their fourth- and seventh-grade tests were more likely to decline in test performance. The crude probability of academic decline was 72.9% in mathematics and 42.9% in language arts for children with a treatment start 25 to 36 months after the fourth-grade test. Compared with those starting treatment earlier (≤12 months after tests), the multivariable adjusted risk ratio (RR) for decline was 1.7 (95% confidence interval [CI]: 1.2–2.4) in mathematics and 1.1 (95% CI: 0.7–1.8) in language arts. The adjusted RR of mathematics decline with later treatment was higher among girls (RR, 2.7 95% CI: 1.2–6.0) than boys (RR, 1.4 95% CI: 0.9–2.0). Later start of stimulant drug treatment of attention-deficit/hyperactivity disorder is associated with academic decline in mathematics.
Publisher: SAGE Publications
Date: 17-02-2023
DOI: 10.1177/00048674221079740
Abstract: Depression and anxiety affect 4–14% of Australians every year symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015–2021, which includes the first year of the pandemic. We used national dispensing claims for people aged ⩾10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020–February 2021). In 2019, the annual prevalence of antidepressant use was 170.4 per 1000 women and 101.8 per 1000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10–17 years 46–57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95% CI = [0.3%, 4.2%]) among females, corresponding to a predicted excess of 45,217 (95% CI = [5,819, 84,614]) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95% CI = [4.1%, 20.5%]) and new antidepressant use (+15.6%, 95% CI = [8.5%, 23.7%]). Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.
Publisher: BMJ
Date: 11-2019
DOI: 10.1136/BMJDRC-2019-000759
Abstract: Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed. Data sources included in idually linked data from the nationwide health registers in Denmark (2006–2016), Finland (2006–2016), Iceland (2006–2012), Norway (2006–2015), Sweden (2006–2015), state-wide administrative and claims data for New South Wales, Australia (2006–2012) and two US insurance databases: Medicaid Analytic eXtract (MAX 2006–2012, public) and IBM MarketScan (2012–2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy. Prevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%–62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used. Prevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period.
Publisher: Wiley
Date: 19-05-2016
DOI: 10.1002/PDS.4033
Abstract: Compare analyses of a pooled data set on the in idual level with aggregate meta-analysis in a multi-database study. We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. Country adjusted OR (95%CI) for any cardiovascular birth defect in the in idual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. Results of fixed effects meta-analysis and in idual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the in idual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: American Diabetes Association
Date: 21-06-2023
DOI: 10.2337/DC23-0256
Abstract: To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes. This cohort study used four Nordic countries’ nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs. Adjusted risk ratios (RRs) and 95% CIs were estimated for any and cardiac malformations. Of 3,734,125 infants in the source population, 25,956 were exposed to metformin or insulin in the first trimester, and 4,023 singleton infants were included. A malformation was diagnosed in 147 (4.7%) of 3,145 infants with exposure to any metformin (alone or in addition to insulin) and 50 (5.7%) of 878 infants with exposure to insulin alone (RR 0.84, 95% CI 0.46–1.54). Among 2,852 infants exposed to metformin alone and 293 infants exposed to metformin in addition to insulin 127 (4.4%) and 20 (6.8%), respectively, had a malformation. The adjusted risk was not increased for either metformin alone (0.83, 0.44–1.58) or both metformin and insulin (0.98, 0.56–1.69) versus insulin alone. Corresponding RRs for cardiac malformations were 1.01 (0.55–1.84) for any metformin, 0.92 (0.47–1.81) for metformin alone, and 1.72 (0.76–3.91) for both metformin and insulin. No evidence of an increased malformation risk with metformin versus insulin in the first trimester was found. Results should be interpreted with caution since information on glycemic control was missing.
Publisher: American College of Physicians
Date: 16-10-2018
DOI: 10.7326/M18-0338
Publisher: SAGE Publications
Date: 31-07-2017
Abstract: To examine changes in annual patterns of psychotropic medication use in Australia from 2007 to 2015. We used a 10% s le of in idual-level nationwide dispensing claims for concessional beneficiaries dispensed psychotropic medications (stratified by class, subclass) to investigate annual trends and changes in the incidence and prevalence of use, median annual duration of exposure, proportion of people with single psychotropic dispensing and median defined daily doses per person dispensed each medicine per year. Over the study period, there was a 26.1% decrease in the incidence and a 2.6% increase in the prevalence of all psychotropic medicine use. We observed a decrease in the annual incidence and prevalence of antidepressants (11.6% and 16.8%, respectively) but increases in the median annual duration of exposure (7.4%). Amitriptyline had the highest proportion of single dispensings of all antidepressants throughout the study period (26.5% in 2015) and defined daily doses per person dispensed each medicine per year increased by 20% for antidepressants overall. Benzodiazepine use decreased across all measures over the study period apart from long-term use (exposure for >240 days of the year), which in 2015 was 23.6% of those dispensed a benzodiazepine. We observed a relative increase in the incidence and prevalence of antipsychotic use (14.2% and 26.8%, respectively), and haloperidol had the highest proportion of single dispensings of any antipsychotic throughout the study period (47.5% in 2015). We observed a relative increase in the incidence and prevalence of attention-deficit hyperactivity disorder medication use of 114.0% and 101.8%, respectively, over the study period. Increasing doses and treatment durations of antidepressants warrants further investigation due to concerns about overuse. Single dispensings of amitriptyline and haloperidol may indicate off-label use and long-term use of benzodiazepines remains problematic. Despite increases in attention-deficit hyperactivity disorder medication use, prevalence of use is still much lower than the estimated prevalence of attention-deficit hyperactivity disorder in the adult population.
Publisher: Physicians Postgraduate Press, Inc
Date: 16-01-2023
DOI: 10.4088/JCP.22M14430
Publisher: Public Library of Science (PLoS)
Date: 15-06-2022
DOI: 10.1371/JOURNAL.PONE.0269482
Abstract: Since COVID-19 was first recognised, there has been ever-changing evidence and misinformation around effective use of medicines. Understanding how pandemics impact on medicine use can help policymakers act quickly to prevent harm. We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia. We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidized medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analog). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models and compared characteristics of initiators in 2020 and 2019. In March 2020, we observed a 99% (95%CI: 96%-103%) increase in hydroxychloroquine dispensing (approximately 22% attributable to new users), and a 199% increase (95%CI: 184%-213%) in initiation, with an increase in prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing. There was a small but sustained increase in ivermectin dispensing over multiple months, with an 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no change in the initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin was lower than expected from April through November 2020. While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we observed increases in the initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to the media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harm.
Publisher: Oxford University Press (OUP)
Date: 22-09-2022
DOI: 10.1093/IJE/DYAC180
Abstract: Conflicting evidence suggests a possible association between use of prescribed psychostimulants during pregnancy and adverse perinatal outcomes. We conducted population-based cohort studies including pregnancies conceived between April 2002 and March 2017 (Ontario, Canada N = 554 272) and January 2003 to April 2011 [New South Wales (NSW), Australia N = 139 229]. We evaluated the association between exposure to prescription hetamine, methylphenidate, dextro hetamine or lisdexamfetamine during pregnancy and pre-ecl sia, placental abruption, preterm birth, low birthweight, small for gestational age and neonatal intensive care unit admission. We used inverse probability of treatment weighting based on propensity scores to balance measured confounders between exposed and unexposed pregnancies. Additionally, we restricted the Ontario cohort to social security beneficiaries where supplementary confounder information was available. In Ontario and NSW respectively, 1360 (0.25%) and 146 (0.10%) pregnancies were exposed to psychostimulants. Crude analyses indicated associations between exposure and nearly all outcomes [OR range 1.15–2.16 (Ontario) 0.97–2.20 (NSW)]. Nearly all associations were attenuated after weighting. Pre-ecl sia was the exception: odds remained elevated in the weighted analysis of the Ontario cohort (OR 2.02, 95% CI 1.42–2.88), although some attenuation occurred in NSW (weighted OR 1.50, 95% CI 0.77–2.94) and upon restriction to social security beneficiaries (weighted OR 1.24, 95% CI 0.64–2.40), and confidence intervals were wide. We observed higher rates of outcomes among exposed pregnancies, but the attenuation of associations after adjustment and likelihood of residual confounding suggests psychostimulant exposure is not a major causal factor for most measured outcomes. Our findings for pre-ecl sia were inconclusive exposed pregnancies may benefit from closer monitoring.
Publisher: Wiley
Date: 12-12-2022
DOI: 10.1002/ANA.26561
Abstract: 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. 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. 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. 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 :551–562
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.SRHC.2016.09.006
Abstract: To describe and analyse factors associated with natural birth intentions in a s le of pre-pregnant Icelandic women. An internationally validated tool was used to survey pre-pregnant women about their attitudes towards birth. The online survey was sent to all students at the University of Iceland in November 2014. Log binomial regression was used to calculate crude and adjusted relative risks (RR 410 eligible women completed the cross-sectional survey. Women with low fear of birth were more likely to have natural birth intentions when compared to women with moderate (RR Pre-pregnant women with low fear of birth and high confidence in their birth knowledge are more likely to have natural birth intentions. Addressing concerns about pain, safety, the perceived unpredictability of birth and worries about the physical impact of childbirth may strengthen natural birth intentions.
Publisher: F1000 Research Ltd
Date: 02-02-2021
DOI: 10.12688/WELLCOMEOPENRES.16507.1
Abstract: Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.
Publisher: Wiley
Date: 17-08-2022
DOI: 10.1111/BCP.15000
Abstract: Public health responses to reduce SARS‐CoV‐2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID‐19 restrictions on antibiotic dispensing in Australia. We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face‐to‐face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID‐19 restrictions, we observed a sustained 36% (95% CI: 33–40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51–69%), whereas those recommended for non‐respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April–October 2019 to 37.0 per 1000 for April–October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. In a setting with a low COVID‐19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post‐pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.
Publisher: Wiley
Date: 03-08-2020
DOI: 10.1111/BCPT.13463
Publisher: Public Library of Science (PLoS)
Date: 14-12-2015
Publisher: Wiley
Date: 14-05-2017
DOI: 10.1111/ACPS.12742
Abstract: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. A repeated cross‐sectional design was applied to data extracts (2005–2014) from 17 countries worldwide. In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8–197.2%). In most countries, clozapine use was highest in 40–59‐year‐olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10–19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.
Publisher: Oxford University Press (OUP)
Date: 06-2016
Publisher: BMJ
Date: 22-10-2020
DOI: 10.1136/BMJQS-2019-009897
Abstract: Proton pump inhibitor (PPI) use is widespread. There have been increasing concerns about overuse of high-dose PPIs for durations longer than clinically necessary. To evaluate the impact of national education initiatives on reducing PPI use in Australia. Population-based, controlled interrupted time series analysis of PPI dispensing claims data for Australian adults from July 2012 to June 2018 we used statin dispensing as a control. A year-long educational initiative led by NPS MedicineWise (previously the National Prescribing Service) from April 2015. Simultaneously, Choosing Wisely released recommendations in April 2015 and May 2016. Both promoted review of prolonged PPI use and encouraged stepping down or ceasing treatment, where appropriate. We examined monthly changes in PPI (and statin) dispensing (stratified by high, standard and low tablet strength), rates of switching from higher to lower strength PPIs and rates of PPI (and statin) discontinuation. We observed 12 040 021 PPI dispensings to 579 594 people. We observed a sustained −1.7% (95% CI: −2.7 to −0.7%) decline in monthly dispensing of standard strength PPIs following the initiatives until the end of the study period. There were no significant changes in high or low strength PPI (or statin) dispensings, switching to lower strength PPIs, or PPI (and statin) treatment discontinuation. Our findings suggest that these educational initiatives alone were insufficient in curbing overuse of PPIs on a national level. Concerted efforts with policy levers such as imposing tighter restrictions on subsidised use of PPIs may be more effective. Noting low strength esomeprazole is not publicly subsidised in Australia, availability of these preparations may also facilitate more appropriate practice
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 08-1966
DOI: 10.1302/0301-620X.48B3.514
Abstract: 1. Three cases of Colles's fracture complicated by ulnar nerve paralysis are described. 2. Observation at operation in two cases and studies in a cadaver demonstrated a close relationship of the ulnar nerve to a fracture line at the lower end of the radius when the distal fragment is displaced dorsally and radially. It is surprising that this injury has not been observed and commented on previously.
Publisher: Oxford University Press (OUP)
Date: 26-04-2018
DOI: 10.1093/IJE/DYY066
Publisher: BMJ
Date: 08-09-2021
Publisher: Public Library of Science (PLoS)
Date: 17-09-2015
Publisher: The Sax Institute
Date: 2020
DOI: 10.17061/PHRP3022013
Publisher: Wiley
Date: 16-09-2022
DOI: 10.1111/AOGS.14447
Abstract: Use of labor induction has increased rapidly in most middle‐ and high‐income countries over the past decade. The reasons for the stark rise in labor induction are largely unknown. We aimed to assess the extent to which the rising rate of labor induction is explained by changes in rates of underlying indications over time. The study was based on nationwide data from the Icelandic Medical Birth Register on 85 620 singleton births from 1997 to 2018. The rate of labor induction and indications for induction was calculated for all singleton births in 1997–2018. Change over time was expressed as relative risk (RR), using Poisson regression with 95% confidence intervals (CI) adjusted for maternal characteristics and indications for labor induction. The crude rate of labor induction rose from 12.5% in 1997–2001 to 23.9% in 2014–2018 (crude RR = 1.91, 95% CI 1.81–2.01). While adjusting for maternal characteristics had little impact, adjusting additionally for labor induction indications lowered the RR to 1.43 (95% CI 1.35–1.51). Induction was increasingly indicated from 1997–2001 to 2014–2018 by gestational diabetes (2.4%–16.5%), hypertensive disorders (7.0%–11.1%), prolonged pregnancy (16.2%–23.7%), concerns for maternal wellbeing (3.2%–6.9%) and maternal age (0.5%–1.2%). No indication was registered for 9.2% of inductions in 2014–2018 compared with 16.3% in 1997–2001. Our results show that the increase in labor induction over the study period is largely explained by an increase in various underlying conditions indicating labor induction. However, indications for 9.2% of labor inductions remain unexplained and warrant further investigation.
Publisher: SAGE Publications
Date: 25-04-2023
Publisher: Wiley
Date: 25-02-2016
DOI: 10.1111/TRF.13522
Abstract: Demographic information of blood donors is important to formulate strategies for recruitment and maintenance of the donor group. Factors like aging population, increasingly advanced medical treatments, and growing safety initiatives to protect donors and recipients of blood components are likely to affect the size of the donor group in the future. The purpose of this study was to determine the size of the donor group in Iceland and describe the demographic and donation characteristics. The size of the Icelandic donor group was determined and the demographic and donation characteristics described, particularly of all newly registered and whole blood donors in the country from 2005 to 2013. Overall the prevalence of whole blood donors per population decreased by 24.2% between 2005 and 2013 or by 3.4% per year. Females and males were almost equally represented as newly registered donors (44.7%/55.3%) but males were better represented as whole blood donors (26.7%/73.3%). Only 57.5% of newly registered donors in 2005 to 2006 returned to donate blood in the period 2005-2013. In parallel with a period of decreased demand for red blood cells, the number of whole blood donors and donations declined in Iceland between 2005 and 2013 but still with adequate supply. A smaller retention among females than males gives the opportunity to focus on increasing the share of women among regular blood donors. Strategic work toward effective recruitment and retention of newly registered donors is needed to ensure a sufficiently large group of blood donors in Iceland in the near future.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2013
Abstract: Ambient air pollution has been associated with increased cardiovascular morbidity and mortality. In Reykjavik, Iceland, air pollutant concentrations exceed official health limits several times every year. The aim was to study the association of concentrations of NO 2 , O 3 , PM 10 , and H 2 S in the Reykjavik capital area with the dispensing of anti-angina pectoris medication, glyceryl trinitrate to the inhabitants. Data on daily dispensing of glyceryl trinitrate , were retrieved from the Icelandic Medicines Registry. Data on hourly concentrations of NO 2 , O 3 , PM 10 , and H 2 S were obtained from the Environment Agency of Iceland. A case-crossover design was used, based on the dispensing of glyceryl trinitrate to 5,246 in iduals (≥18 years) between 2005 and 2009. For every 10 μg/m 3 increase of NO 2 and O 3 3-day mean concentrations, the odds ratio (OR) for daily dispensing of glyceryl trinitrates was 1.136 (95% confidence intervals (CI) 1.069-1.207) and 1.094 (95% CI 1.029-1.163) at lag 0, and OR was 1.096 (95% CI 1.029-1.168) and 1.094 (95% CI 1.028-1.166) at lag 1, respectively. These findings suggest that NO 2 and O 3 ambient air concentrations may adversely affect cardiovascular health, as measured by the dispensing of glyceryl trinitrates for angina pectoris. Further, the findings suggest that data on the dispensing of medication may be a valuable health indicator when studying the effect of air pollution on cardiovascular morbidity.
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2012
Abstract: We evaluated whether younger age in class is associated with poorer academic performance and an increased risk of being prescribed stimulants for attention-deficit/hyperactivity disorder (ADHD). This was a nationwide population-based cohort study, linking data from national registries of prescribed drugs and standardized scholastic examinations. The study population comprised all children born in 1994–1996 who took standardized tests in Iceland at ages 9 and 12 (n = 11 785). We estimated risks of receiving low test scores (0–10th percentile) and being prescribed stimulants for ADHD. Comparisons were made according to children’s relative age in class. Mean test scores in mathematics and language arts were lowest among the youngest children in the fourth grade, although the gap attenuated in the seventh grade. Compared with the oldest third, those in the youngest third of class had an increased relative risk of receiving a low test score at age 9 for mathematics (1.9 95% confidence interval [CI] 1.6–2.2) and language arts (1.8 95% CI 1.6–2.1), whereas at age 12, the relative risk was 1.6 in both subjects. Children in the youngest third of class were 50% more likely (1.5 95% CI 1.3–1.8) than those in the oldest third to be prescribed stimulants between ages 7 and 14. Relative age among classmates affects children’s academic performance into puberty, as well as their risk of being prescribed stimulants for ADHD. This should be taken into account when evaluating children’s performance and behavior in school to prevent unnecessary stimulant treatment.
Publisher: Wiley
Date: 15-10-2022
DOI: 10.1111/BCP.15074
Abstract: To examine trends in the prevalence and incidence of prescription opioid analgesic use in Australian women of reproductive age and to estimate the number of calendar months each year that women were dispensed opioids. We conducted a retrospective cross‐sectional study involving women aged 15–44 years using pharmaceutical dispensing claims for a 10% random s le of Australians. For the period 2013–2020, we calculated the annual prevalence and incidence of opioid analgesic dispensing per 100 (%) population by opioid type and age group. We also estimated the total number of calendar months that women were dispensed at least 1 opioid each year. The prevalence of opioid use decreased from 12.8% in 2013 to 11.3% in 2020, representing a relative decrease of 11.6% (95% confidence interval 10.7, 12.6%). The incidence of opioid use decreased from 10.3% in 2014 to 8.3% in 2020, representing a relative decrease of 18.6% (95% confidence interval 17.6, 19.6%). Codeine in combination products, followed by oxycodone and tramadol, were the most prevalent opioids. Prevalence and incidence of opioid use were lowest in women aged 15–19 years and the highest in women 30 years and above. Among all women dispensed opioids, 72.7% were dispensed an opioid in only 1 month each year. Prescription opioid use remains common, although decreasing, among women of reproductive age in Australia. However, it is reassuring that the majority of opioid use in this population is short term.
Publisher: Wiley
Date: 29-01-2016
DOI: 10.1002/PDS.3962
Publisher: American College of Physicians
Date: 18-06-2019
DOI: 10.7326/L19-0157
Publisher: American Medical Association (AMA)
Date: 02-2023
DOI: 10.1001/JAMAPSYCHIATRY.2022.4109
Abstract: Psychiatric disorders are common among female in iduals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps. To evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on in idual drugs and specific malformation subtypes. This cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022. One or more first-trimester dispensing of any atypical, any typical, and in idual antipsychotic drugs. Any major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization. A total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]) however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions. In this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 07-07-2019
DOI: 10.1111/BCP.13976
Publisher: BMJ
Date: 12-2021
DOI: 10.1136/BMJOPHTH-2021-000921
Abstract: Medical therapy can halt or significantly slow the progression of glaucoma if medicines are used in accordance with the guidelines. We used dispensing claims for a 10% s le of all Australians dispensed publicly subsidised glaucoma medicines to determine the prevalence and incidence of glaucoma medicine treatment and to examine treatment persistence between July 2012 and June 2019. We estimated incidence and prevalence per 10 000 population for Australian financial years (1 July to 30 June). We defined prevalence as at least one dispensing of any glaucoma medicine and incidence as a dispensing of any glaucoma medicine with no previous dispensing during the preceding 12 months. We estimated duration of treatment for a cohort initiating glaucoma medicines and used Kaplan-Meier methods to estimate the proportion of people persisting on treatment at 6, 12, 18 and 36 months after initiation. We stratified analyses by the number of repeats prescribed at initiation, age, sex and medicine class. Prevalence remained stable over the study period at around 180/10 000 people/year incidence was also stable around 36/10 000/year. Among 34 900 people initiating glaucoma medicines, 37.0% remained on treatment at 6 months from initiation, 29.8% at 12 months and 19.2% at 36 months. Median duration of treatment was 13.2 months (IQR: 2.5—not reached) for people initiating prostaglandin analogues and less than 3 months for those initiating other medicine classes. Prevalence and incidence of glaucoma treatment have not changed in Australia over the past decade. Persistence to treatment increased with age but remained poor throughout the study period.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
Publisher: Mary Ann Liebert Inc
Date: 12-2009
Abstract: The aim of this study was to investigate psychotropic drug use among children in Iceland between 2003 and 2007. A nationwide population-based drug use study covering the total pediatric population (ages 0-17) in Iceland. Information was obtained from the National Medicines Registry to calculate prevalence of use by year and psychotropic drug group incidence by year, psychotropic drug group, child's age and sex, and medical specialty of prescriber the most commonly used psychotropic chemical substances, off-label and unlicensed use and concomitant psychotropic drug use. The overall prevalence of psychotropic drug use was 48.7 per 1000 Icelandic children in 2007. Stimulants and antidepressants increased in prevalence from 2003 to 2007 and were the two most prevalent psychotropic drug groups, respectively, 28.4 and 23.4 per 1000 children in 2007. A statistically significant trend of declining prevalence (p = 0.00013) and incidence (p = 0.0018) of antidepressant use occurred during the study period. Out of 21,986 psychotropic drugs dispensed in 2007, 25.4% were used off-label. With reference to reports from other European countries, the results indicate extensive psychotropic drug use among children in Iceland between 2003 and 2007. Further scrutiny is needed to assess the rationale behind this widespread use.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 20-04-2018
DOI: 10.1111/BCPT.13003
Abstract: Paracetamol (acetaminophen) is one of the most commonly used analgesics in Europe however, both the safety and efficacy of paracetamol have recently been questioned. Little is known about cross-national differences in the sales of paracetamol. Using national wholesale statistics and nationwide prescription drug registers, we investigated trends in total and prescribed use of paracetamol in the Nordic countries. The total sales of paracetamol (Anatomical Therapeutic Chemical (ATC) classification system code: N02BE01) measured as defined daily doses (DDD) per 1000 inhabitants/day, and the sales by prescription (users per 1000 inhabitants/year), increased in the Nordic countries from 2000 to 2015. The total sales were highest in Denmark throughout the period, with 65 DDD per 1000 inhabitants/day and lowest in Iceland with 30 DDD per 1000 inhabitants/day in 2015. The cross-national difference in total sales of paracetamol was smaller in 2015 than in 2000. The proportion of paracetamol (DDD per 1000 inhabitants/day) sold by prescription was also highest in Denmark (78%), compared with 75% in Finland, 69% in Sweden, 61% in Norway and 38% in Iceland. Paracetamol by prescription was more common at older ages and among women. Total and prescribed sales of paracetamol have increased in all five Nordic countries over time. Cross-national differences exist, with highest sales per capita in Denmark throughout the period.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2014
DOI: 10.1007/S00787-014-0523-1
Abstract: Our objective was to describe the use of selective serotonin reuptake inhibitors (SSRIs) in the entire Danish population of children and adolescents from 1995 to 2011. Data on filled SSRIs were obtained for all children in Denmark aged 5-17 during 1995-2011. The amount and type of SSRIs filled were calculated as well as incidence rates and prevalence proportions. Furthermore, we looked at concurrent use of other psychotropic drug treatment duration. A total of 23,547 children aged 5-17 used SSRIs during the study period, most commonly sertraline followed by citalopram. Overall, the incidence rate increased from 0.57 per 1,000 person years in 1997 to 3.30 in 2010 and fell to 2.55 in 2011, while the prevalence proportion rose from 0.1 per 1,000 children at the end of 1995 to 3.3 at the end of 2011. However, these findings were driven entirely by an increase among adolescents (12-17 years), where the prevalence proportion rose from 0.11 and 0.36 to 4.64 and 8.52 per 1,000 boys and girls, respectively. A significant proportion of SSRI users used other psychotropic drugs concurrently, most notably antipsychotics (12-28 %) and psychostimulants (10-33 %). About 50 % of adolescents and 40 % of children discontinued treatment within 12 months of initiation. We found a marked increase in the use of SSRI drugs among adolescents in Denmark between 1995 and 2011. Whether this increase reflects a true increase in disorder occurrence, an increase in diagnostic intensity or more aggressive treatment remains uncertain.
Publisher: BMJ
Date: 17-04-2015
DOI: 10.1136/BMJ.H1798
Abstract: To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding. Multicountry population based cohort study, including sibling controlled design. Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010. The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects. Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression. Among 36,772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2,266,875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects. In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.
Publisher: Wiley
Date: 03-06-2020
DOI: 10.1002/PDS.5035
Publisher: BMJ
Date: 22-11-2021
DOI: 10.1136/EBMENTAL-2021-300311
Abstract: Antipsychotics are increasingly used among women of childbearing age and during pregnancy. 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. 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. Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.
Publisher: Wiley
Date: 21-12-2021
DOI: 10.1002/PDS.5395
Abstract: In May 2019, Australia's Pharmaceutical Benefits Scheme (PBS) tightened the prescribing restrictions for publicly subsidized high and standard strength proton‐pump inhibitors (PPIs). We aimed to determine the impacts on PPI use in Australia. Population‐based interrupted time series analysis of PBS dispensing claims for a 10% s le of PBS‐eligible Australian residents from January 2017 to December 2020 and national prescription and over‐the‐counter sales to pharmacies from January 2017 to October 2020. We examined trends in monthly PPI dispensings, switches from higher to lower strength formulations, and volume (kg) dispensed and sold. From May 2019, we observed a small, immediate decrease (−7830 [95%CI: −8818 to −6842]) in standard strength PPI dispensings/month, which rebounded to exceed pre‐intervention levels by December 2020. High strength dispensings decreased until the end of the study period to less than half their pre‐intervention average/month low strength dispensings/month increased until the end of the study period to more than double their pre‐intervention average/month. We observed transient increases in switches to lower strength formulations post‐intervention. The kilograms of PPIs sold/month followed a similar pattern to PBS kilograms dispensed/month with the exception of standard strength formulations where PBS dispensings decreased by −74 (95%CI: −93 to −55) but total sales remained unchanged (comprising PBS and private prescriptions, and over‐the‐counter sales). Tightened prescribing restrictions had an immediate and sustained impact on PPI use in Australia, with decreased high strength use and increased low strength use. Some patients likely switched to private market prescriptions for standard strength PPI, given the observed patterns in total volume sold/dispensed.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2023
DOI: 10.1038/S41562-023-01522-Y
Abstract: Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value .0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, .001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
Publisher: SAGE Publications
Date: 15-05-2019
Abstract: To identify distinct trajectories of antipsychotic use prior to and during pregnancy and describe the associated maternal and birth characteristics. We conducted a population-based cohort study of births (2005–2012) using linked administrative data in New South Wales, Australia. We used group-based trajectory modelling to classify trajectories of antipsychotic use in the 450 days prior to pregnancy and during pregnancy. We characterised women with different trajectories according to maternal sociodemographic characteristics, mental health diagnoses and hospitalisations, use of psychotropic medicines and birth outcomes. Of 137,993 women who gave birth, 2741 (2.0%) were exposed to antipsychotics prior to or during pregnancy. We identified six trajectories of antipsychotic use: two involved short-term use of low daily doses prior to pregnancy (51.1%), while three involved long-term use of low (20.9%), moderate (11.0%) and high (2.0%) daily doses throughout pregnancy. One trajectory (15.0%) involved increasing use during pregnancy. Women with long-term use were more likely to have a schizophrenia or bipolar disorder diagnosis, to have used multiple psychotropics and to have a mental health hospitalisation during pregnancy. Overall, women using antipsychotics had elevated rates of adverse birth outcomes compared to unexposed women. Women with the greatest antipsychotic exposure had the highest rates of gestational diabetes and gestational hypertension. Women using antipsychotics around pregnancy are heterogeneous, with varying patterns of use and associated birth outcomes, reflecting underlying differences in the indications for treatment and/or severity of illness. This ersity should be considered when developing clinical guidelines and designing safety studies.
Publisher: BMJ
Date: 05-2022
DOI: 10.1136/BMJOPEN-2021-059375
Abstract: To assess the trends in medication use indicative of physical and psychological morbidity following the 2010 volcanic eruption in Eyjafjallajökull immediately after and during a 3-year period following the eruption. Population-based register study. Eyjafjallajökull eruption in Iceland, 2007–2013. All residents in Iceland who received at least one medication dispensing were identified. Residents of exposed areas were classified into exposure groups (in idual-level data) and residents in other parts of Iceland were included as a non-exposed group (aggregated data). Eyjafjallajökull erupted on 14 April 2010 and continued for 39 days, producing heavy ash fall in South Iceland. Using interrupted time series analysis, we examined annual and quarterly changes in medicine use, measured as number of dispensed defined daily dose (DDD) per 1000 in iduals. We calculated the level shift (immediate change) and change in slope from pre-eruption to post-eruption (long-term change) in medication dispensing. Among exposed residents, there was a 6% decrease (95% CI -7% to -4%) in the annual number of dispensed DDDs 1-year post-eruption in the overall medication class, including analgesics (−5%, 95% CI -6% to -3%), hypnotics and sedatives (−9%, 95% CI -11% to -7%) and respiratory medications (−7%, 95% CI -9% to -5% −8%, 95% CI -11% to -4%). Simultaneously, there was a 9% decrease (95% CI -14% to -4%) in the overall medication class among non-exposed residents. Moreover, among exposed residents, we observed change in slope of −4% (95% CI -7% to -1%) in the overall medication class, including for analgesics (−6%, 95% CI -8% to -3%) and other respiratory drugs (−10%, 95% CI -16% to -4%). Our findings indicate that the eruption did not lead to increases in medication dispensing among residents of exposed areas, rather decreases for some medicine classes. The results should be interpreted with caution since the content of each eruption differs.
Publisher: American Medical Association (AMA)
Date: 02-01-2013
Abstract: Maternal psychiatric disease is associated with adverse pregnancy outcomes. Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown. To study risk of stillbirth and infant mortality associated with use of SSRIs during pregnancy. Population-based cohort study from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The study included women with singleton births. We obtained information on maternal use of SSRIs from prescription registries. Maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries. We used logistic regression to estimate relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization. Among 1,633,877 singleton births in the study, 6054 were stillbirths 3609, neonatal deaths and 1578, postneonatal deaths. A total of 29,228 (1.79%) of mothers had filled a prescription for an SSRI during pregnancy. Women exposed to an SSRI presented with higher rates of stillbirth (4.62 vs 3.69 per 1000, P = .01) and postneonatal death (1.38 vs 0.96 per 1000, P = .03) than those who did not. The rate of neonatal death was similar between groups (2.54 vs 2.21 per 1000, P = .24). Yet in multivariable models, SSRI use was not associated with stillbirth (adjusted odds ratio [OR], 1.17 95% CI, 0.96-1.41 P = .12), neonatal death (adjusted OR, 1.23 95% CI, 0.96-1.57 P = .11), or postneonatal death (adjusted OR, 1.34 95% CI, 0.97-1.86 P = .08). Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease. The adjusted OR for stillbirth in women with a previous hospitalization for psychiatric disease was 0.92 (95% CI, 0.66-1.28 P = .62) and was 1.07 (95% CI, 0.84-1.36 P = .59) for those who had not been previously hospitalized. The corresponding ORs for neonatal death were 0.89 (95% CI, 0.58-1.39 P = .62) for women who were hospitalized and 1.14 (95% CI, 0.84-1.56 P = .39) for women who were not. For postneonatal death, the ORs were 1.02 (95% CI, 0.61-1.69 P = .95) for women who were hospitalized and 1.10 (95% CI, 0.71-1.72 P = .66) for women who were not. Among women with singleton births in Nordic countries, no significant association was found between use of SSRIs during pregnancy and risk of stillbirth, neonatal mortality, or postneonatal mortality. However, decisions about use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness.
Publisher: Wiley
Date: 08-01-2020
DOI: 10.1111/BCPT.13379
Abstract: Proton pump inhibitors (PPIs) are commonly used drugs among cancer patients. Due to conflicting reports on their safety, we aimed to determine whether PPI use is associated with mortality among prostate cancer patients. In this population-based cohort study, we identified incident diagnoses of prostate cancer between 2007 and 2012 (n = 1058). Follow-up was from 12 months after diagnosis until death, emigration or end the of study. Post-diagnosis use was defined as ≥2 filled prescriptions following diagnosis. We used time-dependent Cox proportional hazard regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer-specific and all-cause mortality associated with post-diagnosis use of PPIs. We identified 347 (32.8%) post-diagnosis PPI users and 711 (67.2%) non-users after diagnosis. Of the 347 patients using PPIs after diagnosis, 59 (17.0%) died due to any cause and 22 (6.3%) due to prostate cancer, compared with 144 (20.3%) and 76 (10.7%) among non-users after diagnosis, respectively. Post-diagnosis PPI use was not associated with prostate cancer-specific mortality (HR 0.88 95% CI: 0.52-1.48) or all-cause mortality (HR 1.02 95% CI: 0.73-1.43). Contrary to a previous report, this study did not find evidence of an association between post-diagnosis PPI use and mortality among prostate cancer patients.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: Wiley
Date: 17-11-2014
DOI: 10.1111/JCPP.12361
Publisher: Wiley
Date: 12-05-2014
DOI: 10.1111/JCPP.12243
Publisher: Wiley
Date: 08-11-2022
DOI: 10.1111/BCPT.13811
Abstract: Use of benzodiazepines (BZ) and related drugs is subject to considerable debate due to problems with dependency and adverse events. We aimed to describe and compare their use across the Nordic countries. Data on the use of clonazepam, BZ-sedatives, BZ-hypnotics, and benzodiazepine-related drugs (BZRD) in adults (≥20 years) were obtained from nationwide registers in Denmark, Finland, Iceland, Norway, and Sweden, 2000-2020. Main measures were therapeutic intensity (TI:DDD/1000 inhabitants [inhab.]/day) and annual prevalence (users/1000 inhab./year). Overall, TI of BZ and related drugs decreased in all Nordic countries from 2004 to 2020. However, there were considerable differences between countries in TI. In 2020, the TI of BZ and related drugs ranged from 17 DDD/1000 inhab./day in Denmark to 93 DDD/1000 inhab./day in Iceland. BZRD accounted for 55-78% of BZ use in 2020, followed by BZ sedatives at 20-44%, BZ-hypnotics at <1-5%, and clonazepam at <1-2%. Annual prevalence of BZ use increased with age in all countries, and the highest annual prevalence was observed among people ≥80 years. Overall, the use of BZ and related drugs has decreased in all Nordic countries from 2004 to 2020, however, with considerable differences in their use between countries. The highest prevalence was observed among the oldest age groups-despite warnings against their use in this population.
Publisher: Oxford University Press (OUP)
Date: 30-03-2015
Abstract: The prevalence of smoking during pregnancy in Western societies has decreased in the last decades, whereas prevalence of overweight and obesity has increased. Our objective was to study secular trends and patterns of smoking and body weight among pregnant women in Iceland, during a period of dramatic changes in the nation's economy. On the basis of the Medical Birth Registry, we used a random s le of 1329 births between 1 January 2001 and 31 December 2010. Information on smoking, body mass index and background factors during pregnancy was retrieved from the Medical Birth Register and maternity records. Trends in smoking, overweight, obesity and body mass index were assessed using logistic and linear regression analyses. Logistic regression analysis was used to examine the annual odds of smoking and obesity and by socio-demographic characteristics. We found a decrease in the prevalence of continued smoking during pregnancy from 12.4% in 2001 to 7.9% in 2010 [odds ratio (OR) = 0.94, 95% confidence interval (CI) (0.88-1.00)], particularly among women with Icelandic citizenship [OR = 0.92, 95% CI (0.86-0.98)], whereas no changes in obesity [OR = 1.02, 95% CI (0.96-1.07)] were observed. The highest prevalence of maternal smoking and obesity was observed in 2005-06. Our results indicate that smoking during pregnancy decreased among Icelandic women in 2001-10, whereas an initial increase in obesity prevalence seemed to level off towards the end of the observation period. Interestingly, we found that both of these maternal risk factors reached their highest prevalence in 2005-06, which coincides with a flourishing period in the nation's economy.
Publisher: Wiley
Date: 07-10-2014
DOI: 10.1111/BCPT.12325
Abstract: Knowledge of patterns of treatment discontinuation in attention-deficit/hyperactivity disorder (ADHD) drug treatment is of importance, for both the clinical practice and the study of long-term treatment outcomes. The purpose of this study was to describe early discontinuation of ADHD drug treatment. Using the Danish National Prescription Registry, all first-time users of the ADHD drugs methylphenidate and atomoxetine were identified between 2000 and 2012. Early discontinuation was defined as failing to fill a second prescription for any ADHD drug within 6 months. Analyses were conducted stratified by calendar year, drug formulation, patient sex, age and region of residence. 59,116 first-time users of methylphenidate and atomoxetine with at least 6 months of eligible follow-up were identified. Overall, 12.6% (n = 7441) failed to fill a second prescription within 6 months. This proportion changed over time, dropping from 20.8% in 2000 to 12.5% in 2012. The proportion of early discontinuation was considerably lower among children than among adults. Proportions were comparable when stratifying by index drug. Proportions of early discontinuation were similar between regions of Denmark, except in the capital region, where it remained at around 20% among 18- to 49-year-olds throughout the study period (22.6% in 2012). In conclusion, we found that the proportion of early discontinuation among ADHD drug users in Denmark dropped markedly during the past decade for both sexes, all age groups and all regions, except for adults in the capital region. Overall, early discontinuation was somewhat lower than expected, considering rates of side effects or non-response to ADHD drug treatment.
Publisher: Wiley
Date: 09-08-2020
DOI: 10.1111/AJO.13044
Abstract: Given the potential hazards of teratogenic medicines, to a fetus exposed in utero, monitoring their use around pregnancy is imperative. To measure utilisation of teratogenic medicines (Therapeutic Goods Administration's category D or X) in women who gave birth in New South Wales, Australia, during pregnancy and the 24 months prior. We used linked population-based datasets including dispensing and perinatal data for all deliveries in NSW between 2005 and 2012. We included pregnancies among concessional beneficiaries only, with complete ascertainment of dispensing claims. Pre-pregnancy and during-pregnancy periods were based on birth dates and gestational age. We determined prevalence of exposure using percent of pregnancies in which women had at least one dispensed teratogenic medicine in three-month time periods. The study included 191 588 pregnancies (145 419 women). Prevalence of exposure to D/X medicines anytime during pregnancy was 2.0% (<20 pregnancies category X), decreasing from pre-pregnancy (3.8-6.0%) to first trimester (1.5%), further decreasing in second and third trimesters (0.8% and 0.6% respectively). We observed large reductions in antibiotic prevalence but only modest reductions for psychotropics and antilipidemic agents (all category D). Our results suggest higher use of potentially teratogenic medicines (category D) than those strictly contraindicated for use (category X), during pregnancy. Overall, use was higher in the first trimester than the rest of pregnancy. The high prevalence of potentially contraindicated psychotropics in all three trimesters may suggest a higher benefit-to-risk ratio and warrants future research focusing on the reasons for their prescribing to pregnant women.
Publisher: Wiley
Date: 24-04-2018
DOI: 10.1111/BIRT.12353
Abstract: Population data on obstetric interventions is often limited to cesarean delivery. We aimed to provide a more comprehensive overview of trends in use of several common obstetric interventions over the past 2 decades. The study was based on nationwide data from the Icelandic Medical Birth Register. Incidence of labor induction, epidural analgesia, cesarean, and instrumental delivery was calculated for all births in 1995-2014. Change over time was expressed as relative risk (RR), using Poisson regression with 95% confidence intervals (CI) adjusted for several maternal and pregnancy-related characteristics. Analyses were stratified by women's parity and diagnosis of diabetes or hypertensive disorder. During the study period, there were 81 389 intended vaginal births and 5544 elective cesarean deliveries. Among both primiparous and multiparous women, we observed a marked increase across time for labor induction (RR 1.78 [CI 1.67-1.91] and RR 1.83 [CI 1.73-1.93], respectively) and epidural analgesia (RR 1.40 [CI 1.36-1.45] and RR 1.74 [CI 1.66-1.83], respectively). A similar trend of smaller magnitude was observed among women with hypertensive disorders but no time trend was observed among women with diabetes. Incidence of cesarean and instrumental delivery remained stable across time. The use of labor induction and epidural analgesia increased considerably over time, while the cesarean delivery rate remained low and stable. Increases in labor induction and epidural analgesia were most pronounced for women without a diagnosis of diabetes or hypertensive disorder and were not explained by maternal characteristics such as advanced age.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 20-02-2019
DOI: 10.1002/PDS.4755
Abstract: Countries worldwide are developing a variety of strategies to combat the opioid epidemic, such as restricting access to high-strength opioid formulations. We aimed to examine the dispensing patterns of strong opioids by dose units (DUs), age, and sex. We used Australian population-level dispensing data from January 2003 to December 2015 and categorised strong opioids by DU: very low, low, moderate, and high, corresponding to total daily doses of less than or equal to 25, 26 to 50, 51 to 100, and greater than 100 morphine milligramme equivalents, respectively. We measured trends in strong opioid use as dispensings/1000 population/year and stratified dispensing in 2015 by patient age and sex. From 2003 to 2015, strong opioid dispensing of very low, low, moderate, and high DU increased 6.7-, 6.2-, 2.2-, and 1.8-fold, respectively. The increase in very low and low DU dispensing was driven primarily by oxycodone (5, 10, and 15 mg tablets and capsules) and buprenorphine transdermal patches. In 2015, the number of dispensings/1000 population for very low, low, moderate, and high DU were 180.3, 77.0, 52.7, and 34.8, respectively. Females aged greater than or equal to 85 years had the highest opioid use, ranging from 157.1 dispensings/1000 population for high DU to 2104.5 dispensings/1000 population for very low DU. In contrast, the high DU dispensings in males aged 25 to 64 years exceeded their female counterparts by approximately 1.3-fold. Relative to moderate and high DU strong opioids, dispensing of very low and low DU strong opioids increased dramatically during the study period in Australia. Future studies investigating opioids use and harms in elderly females and males between 25 to 64 years are warranted.
Publisher: Public Library of Science (PLoS)
Date: 21-11-2018
Publisher: Wiley
Date: 24-07-2023
DOI: 10.1111/EPI.17717
Abstract: Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.
Publisher: Cold Spring Harbor Laboratory
Date: 28-09-2021
DOI: 10.1101/2021.09.26.21264150
Abstract: We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia, a country with relatively low COVID-19 incidence in the first year of the pandemic. We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidised medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) and compared characteristics of initiators in 2020 and 2019. In March 2020, we observed a 99% (95%CI 96%-103%) increase in hydroxychloroquine dispensing (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in April through November 2020. While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we did observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.
Publisher: Informa UK Limited
Date: 11-2015
DOI: 10.2147/CLEP.S90589
Publisher: Wiley
Date: 20-02-2014
DOI: 10.1111/APT.12659
Publisher: Elsevier BV
Date: 10-2018
Publisher: Wiley
Date: 28-07-2021
DOI: 10.1111/AOGS.14231
Abstract: Previous evidence has been conflicting regarding the effect of coronavirus disease 2019 (COVID‐19) pandemic lockdowns on obstetric intervention and preterm birth rates. The literature to date suggests potentially differential underlying mechanisms based on country economic setting. We aimed to study these outcomes in an Icelandic population where uniform lockdown measures were implemented across the country. The study included all singleton births ( n = 20 680) during 2016–2020 identified from the population‐based Icelandic Medical Birth Register. We defined two lockdown periods during March–May and October–December in 2020 according to government implemented nationwide lockdown. We compared monthly rates of cesarean section, induction of labor and preterm birth during lockdown with the same time periods in the 4 previous years (2016–2019) using logit binomial regression adjusted for confounders. Our results indicated a reduction in the overall cesarean section rate, which was mainly evident for elective cesarean section, both during the first (adjusted odd ratio [aOR] 0.71, 95% CI 0.51–0.99) and second (aOR 0.72, 95% CI 0.52–0.99) lockdown periods, and not for emergency cesarean section. No change during lockdown was observed in induction of labor. Our results also suggested a reduction in the overall preterm birth rate during the first lockdown (aOR 0.69, 95% CI 0.49–0.97) and in the months immediately following the lockdown (June–September) (aOR 0.67, 95% CI 0.49–0.89). The reduction during the first lockdown was mainly evident for medically indicated preterm birth (although not statistically significant) and the reduction during June–September was mainly evident for spontaneous preterm birth. This study suggested a reduction in elective cesarean section during COVID‐19 lockdown, possibly reflecting changes in prioritization of non‐urgent health care during lockdown. We also found a reduction in overall preterm birth during the first lockdown and spontaneous preterm birth following the first lockdown, but further research is needed to shed light on the underlying mechanisms for these findings.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 23-09-2010
DOI: 10.1111/J.1600-0447.2010.01607.X
Abstract: To compare national use of attention-deficit/hyperactivity disorder (ADHD) drugs between five Nordic countries. A population-based drug utilisation study based on nationwide prescription databases, covering in total 24 919 145 in iduals in 2007. ADHD drugs defined according to the World Health Organization Anatomic Therapeutic Chemical classification system as centrally acting sympathomimetics (N06BA). The 2007 prevalence of ADHD drug use among the total Nordic population was 2.76 per 1000 inhabitants, varying from 1.23 per 1000 in Finland to 12.46 per 1000 in Iceland. Adjusting for age, Icelanders were nearly five times more likely than Swedes to have used ADHD drugs (Prev.Ratio = 4.53, 95% CI: 4.38-4.69). Prevalence among boys (age 7-15) was fourfold the prevalence among girls (Prev.Ratio = 4.28, 95% CI: 3.70-4.96). The gender ratio was diminished among adults (age 21 +) (Prev.Ratio = 1.24, CI: 1.21-1.27). A considerable national variation in use of ADHD drugs exists between the Nordic countries.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2023
DOI: 10.1038/S41398-023-02315-7
Abstract: Serious concerns have been raised about the negative effects of the COVID-19 pandemic on population psychological well-being. However, limited data exist on the long-term effects of the pandemic on incident psychiatric morbidities among in iduals with varying exposure to the pandemic. Leveraging prospective data from the community-based UK Biobank cohort, we included 308,400 participants free of diagnosis of anxiety or depression, as well as 213,757 participants free of anxiolytics or antidepressants prescriptions, to explore the trends in incident diagnoses and drug prescriptions for anxiety and depression from 16 March 2020 to 31 August 2021, compared to the pre-pandemic period (i.e., 1 January 2017 to 31 December 2019) and across populations with different exposure statuses (i.e., not tested for COVID-19, tested negative and tested positive). The age- and sex-standardized incidence ratios (SIRs) were calculated by month which indicated an increase in incident diagnoses of anxiety or depression among in iduals who were tested for COVID-19 (tested negative: SIR 3.05 [95% confidence interval 2.88–3.22] tested positive: 2.03 [1.76–2.34]), especially during the first six months of the pandemic (i.e., March-September 2020). Similar increases were also observed for incident prescriptions of anxiolytics or antidepressants (tested negative: 1.56 [1.47–1.67] tested positive: 1.41 [1.22–1.62]). In contrast, in iduals not tested for COVID-19 had consistently lower incidence rates of both diagnoses of anxiety or depression (0.70 [0.67–0.72]) and prescriptions of respective psychotropic medications (0.70 [0.68–0.72]) during the pandemic period. These data suggest a distinct rise in health care needs for anxiety and depression among in iduals tested for COVID-19, regardless of the test result, in contrast to a reduction in health care consumption for these disorders among in iduals not tested for and, presumably, not directly exposed to the disease.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.EURONEURO.2017.07.001
Abstract: The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
Publisher: American Medical Association (AMA)
Date: 07-2022
DOI: 10.1001/JAMANEUROL.2022.1269
Abstract: Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain. To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders. The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017 analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848). Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth. We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID). A total of 4 494 926 children were included 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7% aHR, 3.5 95% CI, 1.5-8.2 lamotrigine with topiramate: 8-year cumulative incidence, 7.5% aHR, 2.4 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6% aHR, 0.9 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital. In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.PREGHY.2018.09.010
Abstract: Previous research reported greater risk of adverse perinatal outcomes associated with first trimester exposure to angiotensin converting enzyme inhibitors (ACEIs) in comparison to unexposed pregnancies among non-hypertensive women. We examined the relationship between first trimester exposure to ACEIs and angiotensin receptor blockers (ARBs), and maternal and perinatal outcomes, whilst controlling for the underlying hypertension. We performed a population-based cohort study among 130,061 pregnancies resulting in birth in NSW, Australia between 2005 and 2012. Birth data were linked to hospital discharge and pharmaceutical dispensing records. After restricting to women with chronic hypertension, 67 and 73 pregnancies exposed to ACEIs and ARBs respectively during the first trimester were compared with 316 pregnancies exposed to methyldopa. Preterm delivery, caesarean section, low birth weight, small for gestational age and Apgar score <7. Compared to pregnancies exposed to methyldopa, the adjusted odds ratio (aOR) for ACEI exposure was 0.5 (95% CI: 0.2-1.1) for preterm delivery, 1.6 (0.8-3.1) for caesarean section, 0.6 (0.2-1.3) for LBW and 0.8 (0.4-1.9) for SGA. The corresponding aORs and confidence intervals for ARB exposure were 0.7 (0.3-1.5), 1.2 (0.6-2.6), 1.3 (0.7-2.6), and 1.2 (0.6-2.4). No association between early pregnancy exposure to ACEIs and ARBs and perinatal outcomes was observed, however, the possibility of an association cannot be ruled out due to limited power. Nonetheless, this study suggests that the magnitude of risk is smaller than that reported previously.
Publisher: Springer Science and Business Media LLC
Date: 16-05-2022
DOI: 10.1186/S12877-022-03125-0
Abstract: Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on in idual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009–2018. We conducted cross-sectional measurements of opioid utilisation in 2009–2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day. From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation. The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009–2018. We found large cross-national differences despite similarities across the countries’ cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.
Publisher: Public Library of Science (PLoS)
Date: 02-03-2023
DOI: 10.1371/JOURNAL.PONE.0282477
Abstract: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the “therapeutic window” and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national rovincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks’ gestation were included 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
Publisher: American Medical Association (AMA)
Date: 02-2018
Publisher: Mary Ann Liebert Inc
Date: 08-2022
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2021
DOI: 10.1101/2021.11.24.21266837
Abstract: Depression and anxiety affect 4% to 14% of Australians every year symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015 to 2021, which includes the first year of the pandemic. We used national dispensing claims for people aged ≥10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020 to February 2021). In 2019 the annual prevalence of antidepressant use was 170.4 per 1,000 women and 101.8 per 1,000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10-17 years 46%-57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95%CI 0.3%, 4.2%) among females, corresponding to a predicted excess of 45,217 (95%CI 5,819, 84,614) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95%CI 4.1%, 20.5%) and new antidepressant use (+15.6%, 95%CI 8.5%, 23.7%). Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.
Publisher: Public Library of Science (PLoS)
Date: 24-03-2016
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.CTIM.2014.01.008
Abstract: To evaluate the effect of an integrated hatha yoga practice on perceived stress and stress-related symptoms in the aftermath of an earthquake. Inhabitants, aged 20-67 years, from highly exposed earthquake areas of two villages in South Iceland were offered to participate in a yoga program subsequent to an earthquake. Sixty-six in iduals were self-selected into the study and ided by residential convenience into an experimental group (n=31) and a waiting list control group (n=35). The yoga program was conducted twice a week for six weeks, in normal situations among the inhabitants in the community. Several validated questionnaires assessing stress and stress-related symptoms, posttraumatic symptoms, depression, anxiety and health related quality of life were administered at pre- and post-intervention. Multivariate analysis of variance (MANOVA) revealed differences between the experimental group and waiting list control group on sleep quality (p=.03) and social relations (p=.04). These differences did not prevail at Bonferroni correction for multiple testing (at alpha level of .005). Participants in both groups showed significant improvements in stress and some stress-related symptoms such as sleep, concentration, well-being, quality of life, depression and anxiety from pre- to post-intervention. The data from this small study show no statistically significant improvement of an integrated hatha yoga program above and beyond waiting list control, following exposure to an earthquake. However, the observed trend toward improved sleep quality and social relations deserve further exploration in larger effectiveness studies on the impact of Hatha yoga on recovery after natural disaster.
Publisher: SAGE Publications
Date: 2018
Abstract: The use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use of PPIs over the past decade in an entire national population. This was a nationwide population-based drug-utilization study. Patterns of outpatient PPI use among adults in Iceland between 2003 and 2015 were investigated, including annual incidence and prevalence, duration of use, and dose of tablet used (lower versus higher), as well as the proportion of PPI use attributable to gastroprotection. We observed 1,372,790 prescription fills over the entire study period, of which 95% were for higher-dose PPIs. Annual incidence remained stable across time (3.3–4.1 per 100 persons per year), while the annual prevalence increased from 8.5 per 100 persons to 15.5 per 100 persons. Prevalence increased with patient age and was higher among women than men. Duration of treatment increased with patients’ age (36% of users over 80 years remained on treatment after 1 year compared with 13% of users aged 19–39 years), and was longer among those initiating on a higher dose compared with a lower dose. The proportion of PPI users concurrently using nonsteroidal anti-inflammatory drugs decreased over the study period, while the proportion concurrently using acetylsalicylic acid, oral anticoagulants, or platelet inhibitors increased. In this nationwide study, a considerable increase in overall outpatient use of PPIs over a 13-year period was observed, particularly among older adults. Patients were increasingly treated for longer durations than recommended by clinical guidelines and mainly with higher doses.
Publisher: Wiley
Date: 02-2019
DOI: 10.1002/PHAR.2217
Abstract: Evidence on the cardiotoxicity of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), particularly diclofenac and the newer selective cyclooxygenase (COX)-2 inhibitors, has accumulated over the last decade. Our objective was to examine whether the use of NSAIDs in the Nordic countries changed with the emerging evidence, regulatory statements, and clinical guidelines advocating caution for the use of specific NSAIDs. Drug utilization study. Nationwide wholesale statistics and prescription registries in Denmark, Finland, Iceland, Norway, and Sweden (2000-2016). Our main outcome measures were yearly total sales, expressed as number of sold defined daily doses (DDDs)/1000 inhabitants/day, and yearly prevalence of prescription use, expressed as number of prescription users per 1000 inhabitants. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. Total sales of NSAIDs increased in all countries and were highest in Iceland, with 74.3 DDDs/1000 inhabitants/day sold in 2016, followed by Finland (73.9), Sweden (54.4), Norway (43.8), and Denmark (31.8). Diclofenac use declined after 2008 in all countries but remained the most widely prescribed NSAID in Norway, with 63 prescription users/1000 inhabitants in 2016. Diclofenac sales also remained high in Iceland (12.7 DDD/1000 inhabitants/day), Norway (8.1), and Sweden (7.8). Since its introduction in 2003, the use of etoricoxib, a newer selective COX-2 inhibitor, increased in all countries except Denmark, with highest sales in Finland (6.7 DDD/1000 inhabitants/day in 2016). Sales and prescription patterns of NSAIDs in the Nordic countries has changed along with the accumulating evidence for the cardiovascular risks of specific NSAIDs. However, given existing evidence on the cardiovascular risks associated with the use of diclofenac and etoricoxib, the persistent high use of diclofenac in Iceland, Norway, and Sweden, the persistent over-the-counter availability of diclofenac in Norway and Sweden, and the increasing use of etoricoxib in most of the Nordic countries pose a cardiovascular health concern.
Publisher: Elsevier BV
Date: 2023
DOI: 10.2139/SSRN.4549178
Location: United States of America
No related grants have been discovered for Helga Zoega.