Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

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

Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

Socioeconomic differences in use of antiseizure medication in pregnancies with maternal epilepsy: A population-based study from Nordic universal health care systems.

OBJECTIVE: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. METHODS: We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. RESULTS: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). SIGNIFICANCE: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.

Prevalence and Persistence of Prescription Opioid Use Following Hospital Discharge After Childbirth: An Australian Population-Based Cohort Study.

BACKGROUND: Opioid analgesics are used for acute postpartum pain relief but carry risks, including persistent long-term opioid use. Our primary objective was to estimate the prevalence of persistent use following hospital discharge after childbirth. METHODS: We conducted a population-based cohort study of women discharged from public or private hospitals in New South Wales, Australia, between 2012 and 2018 following vaginal birth (VB) or cesarean delivery (CD). We used linked hospitalization and medicine dispensing data to calculate the prevalence of opioid use within 14 days of hospital discharge for childbirth using an external estimate of the total number of hospital admissions for childbirth per year as the denominator. Among women dispensed an opioid postdischarge, we estimated the prevalence of persistent use defined as ≥3 dispensings between 30- and 365-days postdischarge. To calculate the odds of persistent opioid use, we performed a series of logistic regressions each including a single characteristic of interest. Included characteristics were maternal and birth characteristics, maternal medical conditions, prior use of certain medicines, and the initial opioid dispensed following discharge for childbirth. RESULTS: The final cohort comprised of 38,832 women who were dispensed an opioid in the 14 days following discharge after childbirth. Between 2012 and 2018, the prevalence of opioid use was increased following CD (public hospital 16.6%-21.0%; private hospital 9.8%-19.5%) compared with VB (public hospital 1.5%-1.5%; private hospital 1.2%-1.4%) and was higher following discharge from public hospitals compared with private. The most commonly dispensed opioids following discharge for childbirth were oxycodone (44.8%; 95% confidence interval [CI], 44.3-45.3), codeine (42.1%; 95% CI, 41.6-42.6), and tramadol (12.9%; 95% CI, 12.6-13.2). Among women dispensed an opioid, the prevalence of persistent opioid use was 5.4% (95% CI, 5.1-5.6). This prevalence was 11.4% (95% CI, 10.5-12.3) following a VB as compared with 4.3% (95% CI, 4.1-4.6) among those who underwent a CD ( P < .001). Characteristics associated with persistent opioid use included smoking during pregnancy, age <25 years, living in remote areas, discharged from a public hospital, history of opioid use disorder, other substance use disorder, mental health diagnosis, or prior use of prescription opioids, nonopioid analgesics, or benzodiazepines. CONCLUSIONS: The results of this cohort study indicate that Australian women have a higher prevalence of opioid use following CD compared to VB. One in 19 women dispensed an opioid postdischarge used opioids persistently. Careful monitoring of opioid therapy following childbirth is warranted, particularly among women with characteristics we identified as high risk for persistent opioid use.

Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta-analysis†.

BACKGROUND: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta-analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. METHODS: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first-trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non-Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random-effects meta-analysis. RESULTS: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98-1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96-1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92-1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38-5.16) and cleft palate (relative risk 1.57, 95%CI 0.48-5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05-1.36) following codeine exposure. CONCLUSIONS: Although the meta-analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.

Mental health-related service and medicine use among a cohort of urban Aboriginal children and young people: Data linkage study.

OBJECTIVE: The objective was to describe mental health service and psychotropic medicine use among a cohort of Aboriginal young people and quantify their relation to sociodemographic, family and health factors. METHODS: In a prospective cohort study with data linkage, 892 Aboriginal children aged 0-17 years living in urban and regional areas of New South Wales, Australia, were included. We assessed mental health-related service use, paediatric service use and psychotropic medicine dispensing claims covered by the Australian Government Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme from July 2012 to June 2017. RESULTS: Most children (71%) did not have a record of mental health service or psychotropic medication use. 18.7% had ⩾1 mental health-related service claim; 26.7% had ⩾1 paediatric service claim; and 20.3% had ⩾1 psychotropic medicine dispensing claim. General practitioner services were the most accessed mental health-related service (17.4%) and 12.7% had been dispensed attention-deficit hyperactivity disorder medicines. Child characteristics associated with treatment included emotional and behavioural problems (prevalence ratio: 1.97, 95% confidence interval = [1.46, 2.64] for mental health services; prevalence ratio: 2.87, 95% confidence interval = [2.07, 3.96] for medicines) and risky behaviour (prevalence ratio: 1.56, 95% confidence interval = [1.12, 2.16] for mental health services; prevalence ratio: 2.28, 95% confidence interval = [1.54, 3.37] for medicines). Parent-related factors included chronic illness (prevalence ratio: 1.42, 95% confidence interval = [1.03, 1.95] for mental health services; prevalence ratio: 2.00, 95% confidence interval = [1.49, 2.69] for medicines) and functional limitations (prevalence ratio: 1.61, 95% confidence interval = [1.16, 2.24] for mental health services; prevalence ratio: 1.86, 95% confidence interval = [1.34, 2.59] for medicines). CONCLUSIONS: Most Aboriginal children and young people did not have claims for mental health services or medicines. Aboriginal children with emotional and behavioural problems, or parents with health problems were more likely to have mental health service or medicine claims.

Trends of perceived disruption in healthcare services during the pandemic: findings from the COVID-19 National Resilience Cohort in Iceland.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused major disruptions in healthcare services worldwide. Yet, little is known about the association between perceived disruption in healthcare services and socio-demographic factors, pre-existing health conditions as well as concurrent physical and psychological symptoms. METHODS: Leveraging data from the Icelandic COVID-19 National Resilience Cohort, we performed a repeated measure analysis among 15 754 participants who responded to the question on perceived disruption in healthcare services from December 2020 to July 2021, to explore its association with socio-demographic factors, health indicators and conditions. Furthermore, we performed a longitudinal analysis among 7848 participants with two repeated measures to explore the association between timing and duration of perceived disruption in healthcare services and changes in depression, anxiety, sleep quality and somatic symptoms. RESULTS: The prevalence of perceived disruption in healthcare services slightly decreased over time (P < 0.01). Perceived disruption in healthcare services was more prevalent among individuals with pre-existing health conditions, i.e. history of psychiatric disorders (prevalence ratio = 1.59, 95% confidence interval 1.48-1.72) and chronic somatic conditions [1.40 (1.30-1.52)]. However, no increase in the prevalence of perceived disruption in healthcare services was observed among individuals diagnosed with COVID-19 [0.99 (0.84-1.18)]. Moreover, we found that emerging perceived disruption in healthcare services was associated with an increase in symptoms of mental illness during the pandemic (ßs 0.06-0.68). CONCLUSIONS: A disruption in healthcare services during the COVID-19 pandemic was reported by vulnerable groups, while the Icelandic healthcare system managed to maintain accessible services to individuals with COVID-19.

Prescription retinoid and contraception use in women in Australia: A population-based study.

BACKGROUND/OBECTIVES: Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly. METHODS: This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level. RESULTS: There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021. CONCLUSIONS: Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Psychiatric comorbidities in women with cardiometabolic conditions with and without ADHD: a population-based study.

BACKGROUND: Leveraging a large nationwide study of Icelandic women, we aimed to narrow the evidence gap around female attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic comorbidities by determining the prevalence of obesity, hypertension, type 2 diabetes, and cardiovascular diseases among women with ADHD and examine the association between cardiometabolic conditions and co-occurring ADHD with anxiety and mood disorders, alcoholism/substance use disorder (SUD), self-harm, and suicide attempts. METHODS: We conducted a cross-sectional analysis of the nationwide, all-female, population-based SAGA Cohort Study (n = 26,668). To ascertain diagnoses and symptoms, we used self-reported history of ADHD diagnoses, selected cardiometabolic conditions and psychiatric disorders, and measured current depressive, anxiety, and PTSD symptoms through appropriate questionnaires (PHQ-9, GAD-7, and PCL-5). We calculated age-adjusted prevalences of cardiometabolic conditions by women's ADHD status and estimated adjusted prevalence ratios (PR) and 95% confidence intervals (CI), using modified Poisson regression models. Similarly, we assessed the association of cardiometabolic conditions and co-occurring ADHD with current psychiatric symptoms and psychiatric disorders, using adjusted PRs and 95% CIs. RESULTS: We identified 2299 (8.6%) women with a history of ADHD diagnosis. The age-adjusted prevalence of having at least one cardiometabolic condition was higher among women with ADHD (49.5%) than those without (41.7%), (PR = 1.19, 95% CI 1.14-1.25), with higher prevalence of all measured cardiometabolic conditions (myocardial infarctions (PR = 2.53, 95% CI 1.83--3.49), type 2 diabetes (PR = 2.08, 95% CI 1.66-2.61), hypertension (PR = 1.23, 95% CI 1.12-1.34), and obesity (PR = 1.18, 95% CI 1.11-1.25)). Women with cardiometabolic conditions and co-occurring ADHD had, compared with those without ADHD, substantially increased prevalence of (a) all measured mood and anxiety disorders, e.g., depression (PR = 2.38, 95% CI 2.19-2.58), bipolar disorder (PR = 4.81, 95% CI 3.65-6.35), posttraumatic stress disorder (PR = 2.78, 95% CI 2.52-3.07), social phobia (PR = 2.96, 95% CI 2.64-3.32); (b) moderate/severe depressive, anxiety, and PTSD symptoms with PR = 1.76 (95% CI 1.67-1.85), PR = 1.97 (95% CI 1.82-2.12), and PR = 2.01 (95% CI 1.88-2.15), respectively; (c) alcoholism/SUD, PR = 4.79 (95% CI 3.90-5.89); and (d) self-harm, PR = 1.47 (95% CI 1.29-1.67) and suicide attempts, PR = 2.37 (95% CI 2.05-2.73). CONCLUSIONS: ADHD is overrepresented among women with cardiometabolic conditions and contributes substantially to other psychiatric comorbidities among women with cardiometabolic conditions.

High-dose folic acid and cancer risk; unjustified concerns by von Wrede and colleagues regarding our paper.

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.

Patterns of suboptimal antipsychotic use and misuse in Australia: What can routinely collected data tell us?

AIMS: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for example through prescription monitoring systems.

Changes in antidepressant use in Australia: A nationwide analysis (2015-2021).

BACKGROUND: 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. METHODS: 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). RESULTS: 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%]). CONCLUSION: 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.

Patterns of attention deficit hyperactivity disorder medicine use in the era of new non-stimulant medicines: A population-based study among Australian children and adults (2013-2020).

BACKGROUND AND AIMS: 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. METHODS: This population-based study used dispensing data for a 10% random sample 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). RESULTS: 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. CONCLUSION: 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.

Prescription opioid use in Australian women of reproductive age: Implications for unplanned pregnancies.

AIMS: 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. METHODS: We conducted a retrospective cross-sectional study involving women aged 15-44 years using pharmaceutical dispensing claims for a 10% random sample 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. RESULTS: 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. CONCLUSION: 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.

Changes in antibiotic prescribing following COVID-19 restrictions: Lessons for post-pandemic antibiotic stewardship.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prescribed medicine use and extent of off-label use according to age in a nationwide sample of Australian children.

BACKGROUND: Medicine prescribing for children is impacted by a lack of paediatric-specific dosing, efficacy and safety data for many medicines. OBJECTIVES: To estimate the prevalence of medicine use among children and the rate of 'off-label' prescribing according to age at dispensing. METHODS: 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 (<1 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). RESULTS: 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 <1 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 <1 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%). CONCLUSIONS: 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.

The impact of tightened prescribing restrictions on proton pump inhibitor use in Australia: An evaluation using interrupted time series analysis.

AIM: 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. METHODS: Population-based interrupted time series analysis of PBS dispensing claims for a 10% sample 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. RESULTS: 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). CONCLUSIONS: 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.

Trends in labor induction indications: A 20-year population-based study.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality. METHODS: We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with ≥1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure. RESULTS: Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality. CONCLUSION: PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.

Changes in obstetric interventions and preterm birth during COVID-19: A nationwide study from Iceland.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.