Common mental health diagnoses arising from or coinciding with menopausal transition and prescribing of SSRIs/SNRIs medications and other psychotropic medications.

BACKGROUND: Women with menopausal transition (MT) have an elevated risk of experiencing common mental health diagnoses (CMHD: depression or anxiety). There is no recent data comparing the rate, and treatment, of CMHD between men and women. METHODS: In this population-based study, incidence rates (IR) per 100 person-years-at-risk (PYAR) for men and women ≥45 years registered with an UK primary care practice between 2010 and 2021 were estimated. Incidence rate ratios (IRR) with 95 % confidence intervals (CIs) of CMHD were estimated using men as a reference. We measured first prescriptions for psychotropic medications received within 12 months after CMHD. For selective serotonin reuptake inhibitors (SSRIs) /selective norepinephrine reuptake inhibitors (SNRIs), we measured the IR of prescribing per 100 PYAR, by 10-year bands. Proportion of SSRIs/SNRIs prescribing was estimated per 100 persons. RESULTS: Rates of anxiety and depressive disorders were 1.68 and 1.69 per 100 PYAR in women aged 45-54 years-old compared to 0.91 and 1.20 per 100 PYAR in men, with IRR of 1.84 (95 % CI 1.72-1.97) and 1.44 (1.35-1.53) respectively. SSRIs/SNRIs were the most prescribed medication; in 2021, IRs for SSRIs/SNRIs were 13.4 per 100 PYAR in both sexes. In 2021, the proportion of SSRIs/SNRIs prescribing was 50.67 per 100 women and 41.91 per 100 men. LIMITATIONS: MT is assumed based on women's age as menopause onset is rarely recorded in primary care databases. CONCLUSIONS: Women ≥45 years experienced more CMHD compared to men, especially 45-54 years-olds, which coincides with MT. The proportion of SSRIs/SNRIs prescribing was higher in women.

Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study.

AIMS: We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs). METHODS AND RESULTS: We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12 months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR = 1.51, 95% CI = 1.35-1.68; beta-blockers: OR = 1.22, 95% CI = 1.08-1.37; MRAs: OR = 1.31, 95% CI = 1.08-1.59) and poor persistence (RASIs: OR = 2.04, 95% CI = 1.75-2.37; beta-blockers: OR = 1.35, 95% CI = 1.12-1.63; MRAs: OR = 1.49, 95% CI = 1.16-1.93), and higher risks for dose down-titration for RASIs (OR = 1.69, 95% CI = 1.40-2.04) and beta-blockers (OR = 1.31, 95% CI = 1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs. CONCLUSIONS: Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF.

Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study.

BACKGROUND AND OBJECTIVES: Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). METHODS: Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. RESULTS: The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). DISCUSSION: PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Trends in the incidence of dementia in people with hypertension in the UK 2000 to 2021.

INTRODUCTION: We investigated trends in the incidence of dementia in UK adults with hypertension. METHODS: Primary care electronic health records from IQVIA Medical Research Data UK, previously known as THIN, were used to identify 2,133,118 adults aged ≥40 years with hypertension over 2000 to 2021. The annual incidence rate and average annual percentage change in recorded dementia diagnoses were estimated and stratified by sex, 10-year age bands, Townsend deprivation quintiles and dementia subtype. RESULTS: The crude incidence rate of dementia in people with hypertension increased from 1.98 (95% confidence internal [CI] 1.89-2.07) per 1000 person-years at risk (PYAR) in 2000 to 5.29 per 1000 PYAR (95% CI 5.07-5.53) in 2021, corresponding to an average annual increase of 4.1% (95% CI 3.3-5.0). Those aged ≥80 years, the most economically deprived (Townsend = 5), and Alzheimer's disease subtype reported the highest incidence rate within their respective categories. DISCUSSION: The annual incidence rate of dementia in the hypertensive population has increased over the last 22 years. Highlights: New dementia diagnosis in the hypertensive population has increased over 22 years.The Alzheimer's disease subtype reported the highest incidence rate in people with hypertension.Difference in dementia incidence between hypertensive females and males has reduced.Difference in dementia incidence among deprivation categories has reduced in recent years.

Hormone replacement therapy prescribing in menopausal women in the UK: a descriptive study.

BACKGROUND: Recent studies on the prescribing of hormone replacement therapy (HRT) medicines to treat symptoms of menopause are lacking. AIM: To describe the prescribing of HRT in a cohort of UK menopausal women. DESIGN & SETTING: Population-based drug utilisation study using IQVIA Medical Research Database (IMRD-UK). METHOD: Primary care data of women with recorded menopause and/or aged ≥50 years between January 2010 and November 2021 were extracted from the database. The incidence rate of women who received their first prescription for HRT was calculated annually using person-years-at-risk (PYAR) as the denominator. Incidence rates of HRT were estimated by type and route of administration. Relative changes in annual incidence rates were expressed as percentages and the average percentage change was assessed using linear regression. Annual prescribing prevalence per 100 women was calculated using mid-year menopausal population estimates. RESULTS: The incidence rate of prescribing of HRT increased from 5.01 in 2010 to 18.16 per 1000 PYAR in 2021, a relative increase of 13.64% (95% confidence interval [CI] = 6.97 to 20.30) per year. The incidence rate of fixed combinations of HRT increased from 3.33 to 12.23 per 1000 PYAR in 2010 and 2021, respectively. Transdermal formulations of HRT increased from 1.48 to 14.55 per 1000 PYAR in 2010 and 2021, respectively. The overall proportion of women in receipt of a prescription for HRT changed from 7.89% in 2010 to 6.86% in 2020. CONCLUSION: This study shows a steady increase in the number of women receiving their first prescription for HRT during the study period, which suggests regained acceptance of HRT medicines.

Global, regional, and national trends in opioid analgesic consumption from 2015 to 2019: a longitudinal study.

BACKGROUND: Previous studies have reported an extremely unbalanced global access to opioid analgesics. We aimed to determine contemporary trends and patterns of opioid analgesic consumption at the global, regional, and national levels. METHODS: We analysed the global pharmaceutical sales data of 66 countries or regions from the IQVIA-Multinational Integrated Data Analysis System database on opioid analgesics between 2015 and 2019. Opioid analgesic consumption was measured in milligram morphine equivalent per 1000 inhabitants per day (MME per 1000/day). The global, regional, and national trend changes were estimated using linear regressions. Factors associated with consumption patterns and trend changes were explored in multivariable linear regression analyses. FINDINGS: Overall opioid analgesic sales in the 66 countries or regions increased from 27·52 MME per 1000/day (16·63-45·54) in 2015 to 29·51 MME per 1000/day (17·85-48·79) in 2019 (difference per year 3·96%, 95% CI 0·26 to 7·80). Sales reduced yearly in North America (-12·84%; 95% CI -15·34 to -10·27) and Oceania (-2·96%; -4·20 to -1·70); increased in South America (28·69%; 7·18 to 54·53), eastern Europe (7·68%; 3·99 to 11·49), Asia (5·74%; 0·61 to 11·14), and western and central Europe (1·64%; 0·52 to 2·78); and did not differ in Africa or central America and the Caribbean. The global opioid consumption patterns were associated with country-level Human Development Index (p=0·040), cancer death rate excluding leukaemia (p=0·0072), and geographical location (p<0·0001). In 2019, opioid analgesic consumption ranged from 0·01 MME per 1000/day to 5·40 MME per 1000/day in the 17 countries and regions in the lowest consumption quartile, despite high income levels and cancer death rates in some of them. INTERPRETATION: Global opioid analgesic consumption increased from 2015 to 2019. The trend changes were distinctive across regions, which could reflect the different actions in response to known issues of opioid use and misuse. Disparities in opioid analgesic consumption remained, indicating potential inadequate access to essential pain relief in countries with low consumption. FUNDING: None.

Stakeholders' views on the use of psychotropic medication in older people: a systematic review.

BACKGROUND: psychotropic medication use has been shown to increase with age and has been associated with increased risk of falls, strokes and mortality. Various guidelines, regulations and tools have been developed to reduce inappropriate prescribing, but this remains high. In order to understand the reasons for this, we aimed to systematically review healthcare professionals', patients' and family caregivers' attitudes towards the use of psychotropic medication in older people. METHODS: a systematic literature search was carried out from inception to September 2020 using PUBMED, EMBASE, PsycINFO and CINAHL and hand-searching of reference lists. Included studies investigated stakeholder views on psychotropic in adults over the age of 65. Findings were thematically synthesised. RESULTS: overall, there was an acceptance of long-term psychotropic medication for older people both living in the community and in residential care. While healthcare professionals were aware of guidelines for the use of benzodiazepines and psychotropic medicines, they identified barriers to following them on individual, team and organisational levels. Alternative non-pharmacological approaches were not always available or accepted by patients. CONCLUSION: psychotropic medicine use in older adults remains a complex issue, which needs to be addressed on a broad level. Attitudes of older people and healthcare professionals encourage long-term use. Meanwhile, various internal and external factors act as barriers to the use of non-drug alternatives in this population. In order to reduce overprescribing of psychotropics, there is a need to increase the acceptability and accessibility of alternative interventions in both care homes and the community.

Antipsychotic Medication and Risk of Incident Seizure in People with Autism Spectrum Disorder: Analyses with Cohort and Within Individual Study Designs.

There are many case reports of seizures apparently associated with the prescription of antipsychotics. This study aimed to examine whether there is an association between the prescription of antipsychotics and incident seizures in individuals with autism spectrum disorder using retrospective data based on patients' chart review. A cohort study was conducted to compare the rate of incident seizure between 3923 users of antipsychotics with 10,086 users of other psychotropics. This was followed by a self-controlled case series (SCCS) analysis of 149 patients to eliminate the effect of time-invariant confounders. The results showed no evidence of increased risk of seizure after exposure to antipsychotic agents (Hazard Ratio 1.28, 95% CI 0.74-2.19) compared to other psychotropics.

Psychotropic medicine consumption in 65 countries and regions, 2008-19: a longitudinal study.

BACKGROUND: The WHO Comprehensive Mental Health Action Plan 2013-2030 encourages routine collection and reporting of a set of essential mental health indicators, including the availability of psychotropic medicines. The global monitoring of country-level psychotropic medicine consumption trends can provide information on the extent of the availability of psychotropic medicines. The primary objective of this study was to investigate global trends in psychotropic medicines consumption from 2008 to 2019 across 65 countries and regions according to country income level and geographical region. METHODS: In this longitudinal trends study, we used pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS). We analysed monthly sales data of psychotropic medicines between Jan 1, 2008, and Dec 31, 2019. Total psychotropic medicine consumption included sales of antidepressants, antipsychotics, tranquilisers, sedatives or hypnotics, and mood stabilisers. Population estimates of each country or region (eight lower-middle-income countries, 19 upper-middle-income countries, and 38 high-income countries) were based on the UN World Population Prospects 2019 report. Average annual sales trends of psychotropic medicines, expressed as defined daily dose (DDD) per 1000 inhabitants per day, were estimated using a random-effects model adjusted for income level and region. Relative changes in the annual consumption of psychotropic medicines by income, expressed as DDD per 1000 inhabitants per day, were assessed as percentage change for each medicine class. FINDINGS: Psychotropic medicine sales increased from 28·54 DDD per 1000 inhabitants per day in 2008 to 34·77 DDD per 1000 inhabitants per day in 2019, corresponding to a 4·08% (95% CI 2·96-5·21) relative average increase annually. The absolute annual increase was greater in high-income countries (3·31 DDD per 1000 inhabitants per day, 95% CI 3·01-3·61) compared with upper-middle-income countries (1·94 DDD per 1000 inhabitants per day, 1·45-2·44) and low-middle-income countries (0·88 DDD per 1000 inhabitants per day, 0·62-1·13; p<0·0001). The relative average annual increase in psychotropic medicine sales from 2008 to 2019 was greater in upper-middle-income countries (7·88%, 95% CI 6·99-8·77) than in lower-middle-income countries (2·90%, 2·40-3·39) and high-income countries (1·02%, 0·80-1·24). In 2019, the regional consumption of psychotropic medicines varied greatly, with the highest sales of all psychotropic medicine classes reported in northern America (167·54 DDD per 1000 inhabitants per day) and lowest sales reported in Asia (5·59 DDD per 1000 inhabitants per day). 17 countries had very low consumption of psychotropic medicines in 2019, including high-income countries and countries with a high prevalence of mental disorders. INTERPRETATION: The consumption of psychotropic medicines has increased over a 12-year period, and although the absolute growth rate was highest in high-income countries, the relative growth is highest in middle-income countries and especially upper-middle-income countries. Disparities in psychotropic medicine consumption of countries can only partly be explained by geographical location and income. Greater efforts are needed to increase the availability of psychotropic medicines in countries with very low consumption, which is probably due to financial or cultural reasons as well as scarcity of trained health-care professionals to prescribe psychotropic medicines. FUNDING: None.

Global trends in symptomatic medication use against dementia in 66 countries/regions from 2008 to 2018.

BACKGROUND AND PURPOSE: The aim was to determine trends and patterns of symptomatic medication used against dementia in 66 countries and regions. METHODS: This was a cross-sectional study that used the wholesale data from the IQVIA Multinational Integrated Data Analysis System database. Sale data for symptomatic medication against dementia from 66 countries and regions from 2008 to 2018 were analysed and stratified by income level (low/middle-income countries [LMICs], n = 27; high-income countries [HICs], n = 37; regions, n = 2). The medication use volume was estimated by defined daily dose (DDD) per 1000 inhabitants per day (World Health Organization DDD harmonized the size, strength and form of each pack and reflects average dosing). Changes in medication use over time were quantified as percentage changes in compound annual growth rates (CAGRs). RESULTS: Total symptomatic medication against dementia sales increased from 0.85 to 1.33 DDD per 1000 inhabitants per day between 2008 and 2018 (LMICs 0.094-0.396; HICs 3.88-5.04), which is an increase of CAGR of 4.53% per year. The increase was mainly driven by the LMICs (CAGR = 15.42%) in comparison to the HICs (CAGR = 2.65%). The overall medication use from 2008 to 2018 increased for all four agents: memantine (CAGR = 8.51%), rivastigmine (CAGR = 6.91%), donepezil (CAGR = 2.72%) and galantamine (CAGR = 0.695%). In 2018, the most commonly used medication globally was donepezil, contributing to 49.8% of total use volume, followed by memantine (32.7%), rivastigmine (11.24%) and galantamine (6.36%). CONCLUSION: There was an increasing trend in the use of symptomatic medications against dementia globally, but the use remained low in LMICs. Interventions may be needed to support the medication use in some countries.

Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age.

Importance: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. Objective: To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. Design, Setting, and Participants: This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication. Exposures: Prenatal antipsychotic exposure. Main Outcomes and Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. Results: The cohorts included 333 749 mother-child pairs for ADHD (mean [SD] maternal age at delivery, 31.46 [5.03] years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean [SD] maternal age at delivery, 31.56 [5.01] years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (ADHD: wHR, 0.99; 95% CI, 0.60-1.61; ASD: wHR, 1.10; 95% CI, 0.58-2.08; preterm birth: wOR, 0.93; 95% CI, 0.70-1.24; small for gestational age: wOR, 1.21; 95% CI, 0.66-2.20) and in a sibling-matched analysis (ADHD: wHR, 0.41; 95% CI, 0.04-4.93; ASD: wHR, 0.90; 95% CI, 0.40-2.01; preterm birth: wOR, 1.25; 95% CI, 0.85-1.82; small for gestational age: wOR, 0.86, 95% CI, 0.32-2.31). Conclusions and Relevance: In this cohort study, the findings did not suggest that prenatal antipsychotics exposure increased the risk of ADHD, ASD, or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to discontinue receipt of their regular antipsychotic treatment during pregnancy.

Trends in lipid-modifying agent use in 83 countries.

BACKGROUND AND AIMS: Lipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations. METHODS: This cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018 for 83 countries from the IQVIA Multinational Integrated Data Analysis System and total and non-high-density lipoprotein (non-HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. Compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. RESULTS: From 2008 to 2018, use of LMAs increased from 7468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). An estimated 173 million people used LMAs in 2018. Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and mean total and non-HDL cholesterol concentrations in 2008 versus 2018. CONCLUSIONS: Since 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non-HDL cholesterol varied considerably.

Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between antipsychotic use in pregnancy and the risk of congenital malformations in children. DATA SOURCES: Searches of PubMed, EMBASE, PsycINFO and Cochrane Library were conducted from inception to 06 January 2020 using keywords: antipsychotics, pregnancy, pregnancy complication and congenital abnormalities. STUDY SELECTION: Of 38 reports initially identified as being of potential interest, 13 studies met our inclusion criteria: English observational studies that examined the association between gestational antipsychotic use and congenital malformations in children. DATA EXTRACTION: Data were extracted independently by 2 investigators including the publication year, study site, study period, data source, study design, sample size, medication exposure, exposure period and pregnancy definition, exposure as well as outcome ascertainment, selection of study and comparison group, confounding adjustment, statistical analysis, and method of linkage between mother and children. Risk estimates were pooled using a random-effect model and the I2 statistic was used to evaluate the degree of heterogeneity. RESULTS: Thirteen studies met our systematic review inclusion criteria. Six studies with a total of 2 515 272 pregnancy episodes were included in our meta-analysis, which provided a pooled adjusted risk ratio of 1.23, 95% confidence interval: 0.96-1.58. The I2 result showed moderate heterogeneity between studies (I2  = 35.2%, P = .173). CONCLUSION: We did not find strong evidence of an association between prenatal exposure to antipsychotic medications and the risk of congenital malformations in children. We recommend further studies investigate this association, focusing on specific medication classes and dose responses, which would help clinicians decide whether to prescribe certain antipsychotics during pregnancy.

Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack.

BACKGROUND: To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)). METHODS: This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model. RESULTS: During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75-0.89) for two medications, 0.65 (0.59-0.70) for three medications, 0.61 (0.56-0.67) for four medications, 0.60 (0.54-0.66) for five medications and 0.66 (0.59-0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46-0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53-68%) lower risk of mortality compared with APAs alone. CONCLUSION: Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study.

Initial cardiovascular treatment patterns during the first 90 days following an incident cardiovascular event.

AIMS: The aim of this study was to investigate the initial cardiovascular prescription patterns in patients after their first cardiovascular events, and to identify factors associated with cardiovascular polypharmacy. METHODS: This was a cross-sectional study including patients aged ≥ 45 years with the first record of coronary heart disease (CHD) or stroke between 2007 and 2016 using The Health Improvement Network database. This study investigated the patterns of cardiovascular drugs prescribed during the first 90 days after the first cardiovascular events. Logistic regression was used to examine the association between patients' baseline characteristics and cardiovascular polypharmacy (≥5 cardiovascular drugs). RESULTS: A total of 121,600 (59,843 CHD and 61,757 stroke) patients were included in the study. The mean age was 69.5 ± 11.9 years. The proportion of patients who were prescribed 0-1, 2-3, 4-5 drugs and ≥6 drugs were 11.0%, 29.8%, 38.6% and 20.5%, respectively. Factors associated with cardiovascular polypharmacy were sex (female: OR 0.74, 95% CI 0.72-0.76 vs male), age (75-84 years old: OR 0.50, 0.47-0.53 vs 45-54 years old), smoking status (current smoking: OR 1.29, 1.15-1.24 vs never), body mass index (obesity: OR 1.38, 1.34-1.43 vs normal), deprivation status (most deprived: OR 1.09, 1.04-1.14 vs least deprived) and Charlson comorbidity index (index ≥5: OR 1.25, 1.16-1.35 vs index 0). CONCLUSION: Multiple cardiovascular drugs treatment was common in patients with CVD in the UK. High-risk factors of CVD were also associated with cardiovascular polypharmacy. Further studies are warranted to assess the impact of cardiovascular polypharmacy and its interaction on CVD recurrence and mortality.

Association between antipsychotic use in pregnancy and the risk of gestational diabetes: Population-based cohort studies from the United Kingdom and Hong Kong and an updated meta-analysis.

AIMS: To investigate whether exposure to antipsychotic medications during pregnancy is associated with gestational diabetes mellitus (GDM) in United Kingdom (UK) and Hong Kong (HK) population cohorts. METHODS: Two population-based cohort studies were conducted using data from the UK The Health Improvement Network (THIN) and HK Clinical Data Analysis and Reporting System (CDARS). Nondiabetic women who received any type of antipsychotic medicine before their first pregnancy were included in our cohorts. The exposed group comprised women who continued using antipsychotics from the start of pregnancy to delivery (continuers), while the comparison group included women who were prescribed antipsychotics before the start of pregnancy but stopped during pregnancy (discontinuers). GDM was identified using GDM diagnosis and/or clinicians reported GDM. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between antipsychotic use during pregnancy and GDM. Propensity Score fine-stratification weighting was used to adjust for potential confounding factors. RESULTS: 3114 women with registered first pregnancies (2351 in THIN and 763 in CDARS) were included. 5.49% (2.55% in THIN and 14.55% in CDARS) were diagnosed with GDM. The adjusted OR of GDM in continuers was 0.73 (95% CI: 0.43-1.25) in THIN and 1.16 (95% CI: 0.78-1.73) in CDARS compared with discontinuers. CONCLUSIONS: Our results do not suggest an increased risk of GDM in women who continued using antipsychotics during pregnancy compared to women who stopped. Based on these results, women should not stop their regular antipsychotics prescriptions in pregnancy due to the fear of GDM.

Diabetes medications and risk of Parkinson's disease: a cohort study of patients with diabetes.

The elevated risk of Parkinson's disease in patients with diabetes might be mitigated depending on the type of drugs prescribed to treat diabetes. Population data for risk of Parkinson's disease in users of the newer types of drugs used in diabetes are scarce. We compared the risk of Parkinson's disease in patients with diabetes exposed to thiazolidinediones (glitazones), glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, with the risk of Parkinson's disease of users of any other oral glucose lowering drugs. A population-based, longitudinal, cohort study was conducted using historic primary care data from The Health Improvement Network. Patients with a diagnosis of diabetes and a minimum of two prescriptions for diabetes medications between January 2006 and January 2019 were included in our study. The primary outcome was the first recording of a diagnosis of Parkinson's disease after the index date, identified from clinical records. We compared the risk of Parkinson's disease in individuals treated with glitazones or DPP4 inhibitors and/or GLP-1 receptor agonists to individuals treated with other antidiabetic agents using a Cox regression with inverse probability of treatment weighting based on propensity scores. Results were analysed separately for insulin users. Among 100 288 patients [mean age 62.8 years (standard deviation 12.6)], 329 (0.3%) were diagnosed with Parkinson's disease during the median follow-up of 3.33 years. The incidence of Parkinson's disease was 8 per 10 000 person-years in 21 175 patients using glitazones, 5 per 10 000 person-years in 36 897 patients using DPP4 inhibitors and 4 per 10 000 person-years in 10 684 using GLP-1 mimetics, 6861 of whom were prescribed GTZ and/or DPP4 inhibitors prior to using GLP-1 mimetics. Compared with the incidence of Parkinson's disease in the comparison group (10 per 10 000 person-years), adjusted results showed no evidence of any association between the use of glitazones and Parkinson's disease [incidence rate ratio (IRR) 1.17; 95% confidence interval (CI) 0.76-1.63; P = 0.467], but there was strong evidence of an inverse association between use of DPP4 inhibitors and GLP-1 mimetics and the onset of Parkinson's disease (IRR 0.64; 95% CI 0.43-0.88; P < 0.01 and IRR 0.38; 95% CI 0.17-0.60; P < 0.01, respectively). Results for insulin users were in the same direction, but the overall size of this group was small. The incidence of Parkinson's disease in patients diagnosed with diabetes varies substantially depending on the treatment for diabetes received. The use of DPP4 inhibitors and/or GLP-1 mimetics is associated with a lower rate of Parkinson's disease compared to the use of other oral antidiabetic drugs.