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Abstract Background Childhood maltreatment (CM) has been indicated in adverse health outcomes across the lifespan, including severe infection-related outcomes. Yet, data are scarce on the potential role of CM in severe COVID-19-related outcomes as well as on mechanisms underlying this association. Methods We included 151,427 individuals in the UK Biobank who responded to questions on the history of CM in 2016 and 2017 and were alive on January 31, 2020. Binomial logistic regression models were performed to estimate the association between a history of CM and severe COVID-19 outcomes (i.e. hospitalization or death due to COVID-19), as well as COVID-19 diagnosis and vaccination as secondary outcomes. We then explored the potential mediating roles of socio-economic status, lifestyle and pre-pandemic comorbidities, and the effect modification by polygenic risk score for severe COVID-19 outcomes. Results The mean age of the study population at the start of the pandemic was 67.7 (SD = 7.72) years, and 56.5% were female. We found the number of CM types was associated with the risk of severe COVID-19 outcomes in a graded manner (p for trend 0.05). Mediation analysis revealed that 50.9% of the association between CM and severe COVID-19 outcomes was explained by suboptimal socio-economic status, lifestyle, and pre-pandemic diagnosis of psychiatric disorders or other chronic medical conditions. In contrast, any CM exposure was only weakly associated with COVID-19 diagnosis (1.06 [1.01–1.12]) while significantly associated with not being vaccinated for COVID-19 (1.21 [1.13–1.29]). Conclusions Our results add to the growing knowledge base indicating the role of childhood maltreatment in negative health outcomes across the lifespan, including severe COVID-19-related outcomes. The identified factors underlying this association represent potential intervention targets for mitigating the harmful effects of childhood maltreatment in COVID-19 and similar future pandemics.

Introduction While changes in the prevalence of depressive symptoms during the COVID-19 pandemic have been described across populations, few studies have incorporated multidimensional variables to characterise the varying effects of the pandemic on the population’s mental health.Methods This cohort study included 6423 participants aged ≥18 years from the Icelandic COVID-19 National Resilience Cohort. Data on depressive symptoms and pandemic-related and non-pandemic-related factors were obtained during three pandemic assessment periods (baseline, follow-up wave 1 and follow-up wave 2; April 2020–December 2021), while health outcomes were obtained during the post-pandemic assessment period (follow-up wave 3; September 2022–February 2023). We used latent growth mixture models to identify variation in depressive symptom trajectories during the pandemic. We then used XGBoost models with 37 pandemic-related and non-pandemic-related factors to characterise these trajectories. Moreover, we performed linear regression to assess the association between the identified trajectories and post-pandemic health outcomes.Results Of the included participants, we identified four depressive symptom trajectories, including consistently low (83.7%), consistently high (5.3%), initially high (5.1%) and late-onset high (5.9%) symptom trajectories. Individuals who exercised frequently (≥3 days/week) and enjoyed social and family support were more likely to experience a consistently low symptom trajectory. In contrast, individuals with a history of psychiatric disorders, women and young adults (18–39 years) were less likely to follow the consistently low symptom trajectory. Moreover, compared with the consistently low symptom trajectory, the other trajectories were associated with significantly higher levels of depressive, anxiety and somatic symptoms and cognitive problems during the post-pandemic period.Conclusions Our results underscore the long-lasting impact of the COVID-19 pandemic on population mental health. Interventions focusing on exercise, social support and family support may mitigate the adverse mental health effects of future pandemics.

Abstract 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.

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 individuals 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 individuals 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, individuals 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 individuals tested for COVID-19, regardless of the test result, in contrast to a reduction in health care consumption for these disorders among individuals not tested for and, presumably, not directly exposed to the disease.

Background 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. Methods 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/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. Results and discussion 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.

BackgroundAntenatal 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.MethodsThe 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/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.Results and discussionThe 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.

Objectives 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.Design Population-based register study.Setting Eyjafjallajökull eruption in Iceland, 2007–2013.Participants All residents in Iceland who received at least one medication dispensing were identified. Residents of exposed areas were classified into exposure groups (individual-level data) and residents in other parts of Iceland were included as a non-exposed group (aggregated data).Intervention/exposure Eyjafjallajökull erupted on 14 April 2010 and continued for 39 days, producing heavy ash fall in South Iceland.Main outcome measures 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 individuals. We calculated the level shift (immediate change) and change in slope from pre-eruption to post-eruption (long-term change) in medication dispensing.Results 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%).Conclusion 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.

Background 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. Methods 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. Results 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. Conclusions 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.

BackgroundSince 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.MethodsWe 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.ResultsIn 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.ConclusionsWhile 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.

Objective 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% sample 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.Methods 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.Results 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.Conclusion 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.

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.

Introduction Recent evidence from the USA and Nordic countries suggests a possible association between psychostimulant use during gestation and adverse pregnancy and birth outcomes. Objectives and Approach We employed a distributed cohort analysis using linked administrative data for women who gave birth in New South Wales (NSW; Australia) and Ontario (Canada), whereby a common protocol was implemented separately in each jurisdiction. The study population comprised women who were hospitalized for a singleton delivery over an 8 (NSW) and 4 (Ontario) year period, respectively, with the NSW cohort restricted to social security beneficiaries. Psychostimulant exposure was defined as at least one dispensing of methylphenidate, amphetamine, dextroamphetamine or lisdexamfetamine during pregnancy. We examined the risk of maternal and neonatal outcomes among psychostimulant exposed mothers compared with unexposed mothers. Results There were 140,356 eligible deliveries in NSW and 449,499 in Ontario during the respective study periods. Fewer than 1% of these pregnancies were exposed to psychostimulants during gestation, although use was higher in Ontario (0.30% vs 0.11% in NSW). Preliminary unadjusted analyses indicated possible associations between psychostimulant use in pregnancy and higher risks of pre-term birth (relative risk [RR] 1.7, 95% confidence interval [CI] 1.4-2.0 (Ontario); RR 1.8, 95% CI 1.2-2.6 (NSW)) and pre-eclampsia (RR 2.0, 95% CI 1.5-2.6 (Ontario); RR 2.0, 95% CI 1.2-3.5 (NSW)). Similarly, psychostimulant use was associated with higher risks of low birthweight (RR 1.6, 95% CI 1.3-1.9 (Ontario); RR 2.0, 95% CI 1.3-3.0 (NSW)) and admission to neonatal intensive care (RR 2.1, 95% CI 1.9-2.3 (Ontario); RR 1.5, 95% CI 1.1-1.9 (NSW)). Conclusion / Implications Unadjusted analyses indicate an increased risk of adverse maternal and birth outcomes associated with psychostimulant exposure during pregnancy, potentially representing a placental effect. We are currently refining the analyses, employing propensity score methods to adjust for confounding.

Introduction HCTZ is first-line treatment for hypertension and among the most commonly used medicines in Australia. Recent evidence suggests increased risks of lip and skin cancers in association with HCTZ use. Objectives and Approach To determine the risk of SCC of the lip and melanoma among people prescribed HCTZ in Australia we conducted a case-control study nested within a cohort of Department of Veterans’ Affairs clients 65 years and older in 2004-2015. We identified incident cases of SCC of the lip (lip cancer) and of cutaneous melanoma (malignant melanoma), each matched by sex and age with up to 20 controls through risk-set sampling. We ascertained HCTZ use from dispensing data and classified use according to ever/never use and cumulative use. We estimated odds ratios (ORs) associating HCTZ use with lip cancer and malignant melanoma using conditional logistic regression, adjusting for predefined confounders obtained from dispensing and hospitalisation data. Results For lip cancer (45 cases) ever-use of HCTZ yielded an OR of 2.6 (95%CI: 1.4–5.0) and high HCTZ use (>25,000mg) an OR of 4.7 (1.61–13.7). For malignant melanoma (659 cases) ever-use of HCTZ resulted in an OR of 1.2 (1.0–1.5) and high HCTZ use in an OR of 1.2 (0.8–1.8). Conclusion / Implications Our study provides further evidence that the photosensitising properties of HCTZ may promote SCC carcinogenesis, and possibly melanoma, in susceptible sun-exposed tissues. Our findings are the first from the Australian population—already at elevated risk of developing skin cancer—and add to the growing body of data supporting the need for skin cancer prevention advice and behaviours, and potentially heightened surveillance, for individuals prescribed this medication.

Background: 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 individuals continuing treatment beyond the guideline-recommended maximum 12 weeks. Methods: 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. Results: 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 individuals 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 individuals and ‘not reached’ for long-term treated individuals. 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. Conclusions: 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.

Abstract Background The global Choosing Wisely campaign has identified the following psychotropic prescribing as low-value (harmful or wasteful): (1) benzodiazepine use in the elderly, (2) antipsychotic use in dementia and (3) prescribing two or more antipsychotics concurrently. We aimed to quantify the extent of these prescribing practices in the Australian population. Methods We applied indicators to dispensing claims of a 10% random sample of Australian Pharmaceutical Benefits Scheme beneficiaries to quantify annual rates of each low-value practice from 2013 to 2016. We also assessed patient factors and direct medicine costs (extrapolated to the entire Australian population) associated with each practice in 2016. Results We observed little change in the rates of the three practices between 2013 and 2016. In 2016, 15.3% of people aged ≥65 years were prescribed a benzodiazepine, 0.5% were prescribed antipsychotics in the context of dementia and 0.2% of people aged ≥18 years received two or more antipsychotics concurrently. The likelihood of elderly people receiving benzodiazepines or antipsychotics in the context of dementia increased with age and the likelihood of receiving all three practices increased with comorbidity burden. In 2016, direct medicine costs to the government of all three practices combined, extrapolated to national figures, were > $21 million AUD. Conclusions Our indicators suggest that the frequency of these three practices has not changed appreciably in recent years and that they incur significant costs. Worryingly, people with the greatest risk of harm from these prescribing practices are often the most likely to receive them.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

BACKGROUND:Hypertensive disorders complicate up to 10% of pregnancies. Evidence suggests a potential association between maternal hypertensive disorders during pregnancy, particularly preeclampsia, and adverse neurodevelopment in the offspring, but existing studies are subject to limitations. We aimed to assess whether in-utero exposure to preeclampsia/eclampsia negatively impacts academic performance at ages 9, 12 and 15 years. METHODS:Using individually linked, nationwide data from the Icelandic registries we followed all children born in 1989-2004 (N = 68,580), from birth until the end of 2014, thereof 63,014 (91.9%) took at least one standardized test. Using a stepwise, mixed-effects approach, we modelled the hypothesized relationship while adjusting for maternal, perinatal and childhood variables of interest. We compared test scores, measured on a normalized scale ranging from 0-60 with a mean of 30 and a standard deviation of 10, in the 4th, 7th, and 10th grades, between children exposed to preeclampsia or eclampsia in-utero versus children from normotensive pregnancies in the population. RESULTS:Children exposed to preeclampsia/eclampsia scored lower than those unexposed in mathematics across all grade levels, corresponding to a difference of 0.44 points (95% CI: 0.00, 0.89), 0.59 points (95% CI: 0.13, 1.06) and 0.59 points (95% CI: 0.08, 1.10), respectively. No differences were observed in the language arts. CONCLUSIONS:Our findings suggest a minimal effect of maternal preeclampsia/eclampsia on children's academic performance at ages 9, 12 and 15 years. The differences observed in mathematic scores between exposed and unexposed children were minimal, less than one tenth of a standard deviation per measurement occasion.

While obesity is an indicated risk factor for hypertensive disorders of pregnancy, smoking during pregnancy has been shown to be inversely associated with the development of preeclampsia and gestational hypertension. The purpose of this study was to investigate the combined effects of high body mass index and smoking on hypertensive disorders during pregnancy. This was a case-control study based on national registers, nested within all pregnancies in Iceland 1989-2004, resulting in birth at the Landspitali University Hospital. Cases (n = 500) were matched 1:2 with women without a hypertensive diagnosis who gave birth in the same year. Body mass index (kg/m2) was based on height and weight at 10-15 weeks of pregnancy. We used logistic regression models to calculate odds ratios and corresponding 95% confidence intervals as measures of association, adjusting for potential confounders and tested for additive and multiplicative interactions of body mass index and smoking. Women's body mass index during early pregnancy was positively associated with each hypertensive outcome. Compared with normal weight women, the multivariable adjusted odds ratio for any hypertensive disorder was 1.8 (95% confidence interval, 1.3-2.3) for overweight women and 3.1 (95% confidence interval, 2.2-4.3) for obese women. The odds ratio for any hypertensive disorder with obesity was 3.9 (95% confidence interval 1.8-8.6) among smokers and 3.0 (95% confidence interval 2.1-4.3) among non-smokers. The effect estimates for hypertensive disorders with high body mass index appeared more pronounced among smokers than non-smokers, although the observed difference was not statistically significant. Our findings may help elucidate the complicated interplay of these lifestyle-related factors with the hypertensive disorders during pregnancy.

BACKGROUND:The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries. METHODS:A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. RESULTS:A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives. CONCLUSION:Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women.

Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008.Women whose pregnancies resulted in live singleton births in Iceland in 2005-2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including β-blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13-1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74-1.47). Similarly, there was an increase in prescription fills of β-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07-1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72-1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods.Our data suggest a transient increased risk of gestational hypertension and use of β-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession.