Antipsychotic drug use in pregnancy: A multinational study from ten countries

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents. Methods: Individually linked health data in Denmark (2000−2012), Finland (2005–2014), Iceland (2004–2017), Norway (2005–2015), Sweden (2006–2015), Germany (2006–2015), Australia (New South Wales, 2004–2012), Hong Kong (2001–2015), UK (2006–2016), and the US (Medicaid, 2000–2013, and IBM MarketScan, 2012–2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics. Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries. Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population

Antipsychotic drug use in pregnancy: A multinational study from ten countries

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents

Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Publisher Copyright: © 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and TherapeuticsThis study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.Peer reviewe

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance.

The purpose of the study is to develop an algorithm to identify pregnancies in administrative databases and apply it to assess pregnancy rates and outcomes in women prescribed isotretinoin or tretinoin. Using the 2011 to 2015 Truven Health MarketScan Database, we identified pregnancies, including losses and terminations. In a cohort design, nonpregnant women filling a prescription for isotretinoin or tretinoin were matched to five women without either prescription. Women were followed for 365 days or until conception, medication discontinuation, or enrollment discontinuation ("prescription episode"). Rates of pregnancy, risks of pregnancy losses, and prevalence of infant malformations at birth were assessed by exposure. We identified 2 179 192 livebirths, 8434 stillbirths, 2521 mixed births, 415 110 spontaneous abortions, 124 556 elective terminations, and 8974 unspecified abortions. There were 86 834 isotretinoin and 973 587 tretinoin episodes, matched to 5 302 105 unexposed women. Pregnancy rates were 3 (isotretinoin), 19 (tretinoin), and 34 (unexposed) per 1000 person-years. Risk of spontaneous pregnancy losses were similar; however, terminations were more common in the isotretinoin-exposed (28% [95% CI: 21%-36%]) than the tretinoin-exposed (10% [95% CI: 9%-11%]) or unexposed pregnancies (6%). Malformations occurred in 4.5% (95% CI: 3.5%-5.6%) of the tretinoin-exposed pregnancies and 4.2% of the unexposed pregnancies (adjusted odds ratio: 1.16 [95% CI: 0.85-1.58]); isotretinoin-exposed births were too few to assess malformations. Administrative databases can complement risk evaluation and mitigation strategies (REMS) for known teratogens and contribute to safety surveillance for other medications. Here, isotretinoin-exposed pregnancy rates were low, but existent, and many pregnancies were terminated. Tretinoin exposure was not associated with a meaningfully elevated risk of losses or malformations as compared with unexposed pregnancies

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

INTRODUCTION: Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. AIM: The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. METHODS: A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. RESULTS: The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. CONCLUSION: Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors