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Autism spectrum disorder (ASD) is a lifelong disorder. In the UK, risperidone is the only psychotropic medication approved for the management of the behavioural symptoms that may accompany autism. This is a population-based study aimed to provide an evaluation of the changing trend in the incidence and prevalence of ASD and to analyse the pattern of psychotropic medication prescribing in the UK. 20,194 patients with ASD were identified. The prevalence increased 3.3-fold from 0.109 per 100 persons in 2009 to 0.355 per 100 persons in 2016. Approximately one-third of the identified cohort was prescribed at least one psychotropic medication. Although the medications approved to manage the symptoms of ASD are limited, the prescribing of such medications is increasing.

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. [ABSTRACT FROM AUTHOR]

Background: Low‐dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear. Objective: Among individuals with T2DM taking metformin, we sought to evaluate the association between low‐dose aspirin versus no aspirin and the risk of CRC. Methods: A multiple‐database new‐user cohort study of patients with T2DM taking metformin was conducted between 2007 and 2010 (Clinical Data Analysis and Reporting System [CDARS], Hong Kong) and 2007–2016 (The Health Improvement Network [THIN], UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until 31 December 2019. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using I2. Results: After one‐to‐one propensity‐score matching, 57,534 patients were included (CDARS = 16,276; THIN = 41,258). The median (IQR) follow‐up was 9.3 (6.5–10.7) years in CDARS and 3.2 (1.1–5.8) years in THIN. The concurrent use of low‐dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR = 0.89, 95% CI 0.75–1.05, I2 = 0%). Conclusion: Low‐dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low‐dose aspirin in this population. [ABSTRACT FROM AUTHOR]

Background: Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the 'high risk of relapse' group for whom longer antidepressant treatment durations are recommended. Aims: In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment. Method: This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures. Results: We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32–3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased – individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25–2.48). We found no interaction between polypharmacy and previous antidepressant duration. Conclusions: Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment. [ABSTRACT FROM AUTHOR]

Background Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends. Objective To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom. Design Multinational, retrospective, time-trend, observational study using a common study protocol. Setting Outpatient and community settings. Subjects All individuals aged ≥ 65 years between 2013 and 2016. Methods We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends. Results A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, −4.9%; the United Kingdom, −1.1%). Conclusions Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies. [ABSTRACT FROM AUTHOR]

Background: Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes. Methods and results: A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n = 170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: [SR1] optimal SR & low risk; [SR2] sub-optimal SR & low risk; [SR3] optimal SR & high risk; [SR4] sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE). Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval [CI] 0.70–0.71; UK) and 0.68 (95% CI 0.67–0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35–1.43, p<0.001; UK) and 1.14 (95% CI 1.11–1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32–1.40, p<0.001: HK HR 1.25, 95% CI 1.21–1.28, p<0.001). Conclusions: Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment. [ABSTRACT FROM AUTHOR]

Background: Re‐designing services and processes to meet growing demands in chemotherapy services is necessary with increasing treatments. There is little evidence guiding the timing and thresholds to be attained of pre‐chemotherapy blood assessments, namely neutrophils. Methods: A survey was developed and distributed to health professionals in the United Kingdom (UK) to examine current practice in timing and threshold values of neutrophils and platelets before treatment administration. This was followed by a retrospective cohort study, using data from electronic patient record systems; including patients initiating treatment between January 2013 and December 2018, to determine a safe timeframe for blood assessments; comparing neutrophil, platelet, creatinine and bilirubin levels at different time points. Results: The survey captured 25% of hospitals in the UK and variations were apparent in both the timing of assessments and thresholds needed, particularly for neutrophils. 616 (6.5%) of 4007 patients included had neutrophil levels measured twice within 7 days of treatment (with the first level taken beyond 3 days and the second test being within 3 days of treatment‐ the UK standard). Of the patients that attained an acceptable neutrophil level at their first test, five of the 616 (0.8%) became ineligible for administration from the test 2 level. 23% of patients improved their grade and became eligible for treatment. Little difference was observed for platelets. Conclusions: We have demonstrated that extending the timeframe for blood tests can be safe, however, this practice may cause unnecessary delays for patients if only an early test is relied on for eligibility. [ABSTRACT FROM AUTHOR]

Background: Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function.Methods: We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set. We included all patients aged ≥ 16 with bipolar disorder prescribed lithium. To be included patients had to have ≥ 1 year of follow-up before lithium initiation, ≥ 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥ 60 mL/min/1.73 m2) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients. We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model. We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group).Results: The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898).Conclusions: Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory. [ABSTRACT FROM AUTHOR]

Background: The development and rapid uptake of immune checkpoint inhibitors (CPI) has changed the outlook for patients with cancer. However, CPIs have different adverse event (AE) profiles to other systemic therapies, and prompt AE management is essential to assure optimal outcomes. In order to understand what and when adverse events are experienced, reported and managed during CPI treatment, a mixed methods study was conducted, including a case note review of patients who were receiving immunotherapy and semi-structured interviews with patients to understand their experience, management and reporting of AEs after receiving immune CPI treatment.Methods: This mixed methods study was conducted at a large cancer hospital in the United Kingdom. A case note review identified how and where patients reported AEs. Data relating to patients with lung, bladder, prostate and head & neck cancers who received CPI treatment between 01/04/2015 and 31/07/2018 were extracted from e-prescribing databases and clinical data were included for analysis at a single time point (31 July 2018). Semi-structured interviews were conducted with patients receiving CPI treatment, exploring experience of AEs and reasons for delays in AE reporting and management.Results: Sixty-two patients were included in the case note review, with 78 AEs being experienced by 36 patients (58%), including one patient experiencing 10 AEs. Serious AEs were experienced by 12 patients (19%) and ten AEs (17%) required oral steroids as treatment. The majority of AEs were reported to clinicians prior to further dosing, although milder AEs were often not addressed until subsequent clinic appointments. Interviews with 13 patients yielded major themes: variability, causality, decision making and impact.Conclusion: Most CPI-associated AEs are manageable if reported and treated promptly. Both the case note review and interviews found that reporting of non-serious AEs is often left until routine clinic visits, despite impacting patient experience, leaving the opportunity for AEs to be left unreported and implying a potential benefit for real time monitoring. Our study highlights a need to provide patients with reminders around AEs and their timely reporting even when apparently innocuous; patients must understand that AEs can occur at any cycle and even following treatment completion. [ABSTRACT FROM AUTHOR]

PURPOSE The growth in understanding of molecular biology and genomics has augmented the development of targeted cancer treatments; however, challenges exist in access to molecular testing, an essential precursor to treatment decision-making. We used data from a cross-sectional survey to evaluate the differences in uptake of molecular testing, METHODS Using the aggregated results of a questionnaire developed and distributed to clinicians by IQVIA, including treatment details and investigations undertaken for patients, we compared proportions of patients receiving molecular testing and targeted treatment by cancer type for the United Kingdom, France, Italy, Germany, Spain, South Korea, Japan, and China. We used multivariable logistic regression methods to understand the effect of country on the odds of receiving a molecular test. RESULTS There was a total of 61,491 cases. Across countries and cancer types, uptake rates for molecular testing ranged between 2% and 98%, with the greatest differences seen in gastric cancers (range, 23% to 70%), and significant variations were observed for both European and Asian countries. China consistently demonstrated a significantly reduced uptake for all molecular tests assessed; however; uptake of drug treatment in gastric cancers after testing positive for the human epidermal growth factor receptor 2 gene was higher than in some European countries (China, 85%; European range, 8% to 66%). The uptake of epidermal growth factor receptor gene testing was greater in some Asian countries relative to the United Kingdom, where incidence of lung cancer is higher (Japan: odds ratio, 3.1 [95% CI, 2.6 to 3.8]; South Korea: odds ratio, 2.7 [95% CI, 2 to 3.4]). CONCLUSION We have highlighted inequity in access to molecular testing and subsequent treatments across countries, which warrants improvements. [ABSTRACT FROM AUTHOR]

Introduction: Hypoglycaemia and hyperglycaemia are common adverse events associated with antidiabetic medications. They are also a common cause of hospital admissions for people with diabetes. The objective of the study was to explore the trends in hospital admissions due to hypoglycaemia and hyperglycaemia and in the prescriptions of antidiabetic medications in England and Wales.Methods: We conducted an observational study during the period 1999–2016. Hospital admission data for patients from all age groups were extracted from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Data on prescriptions of antidiabetic medications were extracted from the Prescription Cost Analysis database from 2004 to 2016.Results: Between 1999 and 2016, the hospital admission rate increased by 173.0% [from 17.2 (95% CI 16.9–17.6) to 47.1 (95% CI 46.5–47.6) per 100,000 persons] for hypoglycaemia and by 147.0% [from 22.8 (95% CI 22.4–23.2) to 56.3 (95% CI 55.7–56.9) per 100,000 persons] for hyperglycaemia. The prescription rate for all antidiabetic medications increased between 2004 and 2016 by 116.0% [from 373.0 (95% CI 373.0–373.0) to 806.0 (95% CI 806.0–806.0) prescriptions per 1000 persons]. There was a parallel increase in the rate of antidiabetic medication prescriptions during the same study period, with correlation coefficients of 0.94 for hypoglycaemia and 0.98 for hyperglycaemia, respectively.Conclusions: There have been parallel increases in the rate of admissions due to dysglycaemia and the rate of antidiabetic prescriptions in England and Wales. Further analytical studies are required to investigate whether increased admission for dysglycaemia is associated with increased use of antidiabetic medications. [ABSTRACT FROM AUTHOR]

Background: Compared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood. Methods: Patients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs. GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics. Results: Overall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed. Conclusion: This study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made [ABSTRACT FROM AUTHOR]

Objectives The WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) methodology is a standardized method of comparing antimicrobial use. The ATC/DDD is defined as the average maintenance daily dose of a drug used in a 70 kg adult, ignoring the considerable differences in body weight of neonates and children. The aim of this study was to develop a new standardized way of comparing rates of antimicrobial prescribing between European children's hospitals. Methods This pilot study at four European children's hospitals (in the UK, Greece and Italy) collected data including demographics, antibiotic use, dosing and indication in children and neonates over a 14 day period. Results A total of 1217 antibiotic prescriptions were issued with 47 different antibiotics used. Approximately half of all children and a third of all neonates received antibiotics, with wide variation between centres in the type and dose of antibiotic used. We propose a new pragmatic three-step algorithm. The first step includes a simple comparison of the proportion of hospitalized children on antibiotics by weight bands and the number of antimicrobials that account for 90% of total DDD drug usage (DU90%). The second step is a comparison of the dosing used (mg/kg/day). The third step is to compare overall drug exposure using DDD/100 bed days for standardized weight bands between centres. Conclusions This novel method has the potential to be a useful tool to provide antibiotic use comparator data and requires validation in a large prospective point prevalence study. [ABSTRACT FROM PUBLISHER]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Metformin is licensed for type 2 diabetes mellitus (DM) treatment in the UK. • Evidence has shown the moderate efficacy of metformin treatment for polycystic ovarian syndrome (PCOS) and obesity. WHAT THIS STUDY ADDS • Metformin prescribing increased in children and adolescents between 2000 and 2010, in particular in girls aged 16-18 years. • PCOS and obesity were the main, but unlicensed, indications for metformin prescribing amongst female adolescents. AIM Metformin is the most commonly prescribed oral anti-diabetic drug in young people. It is also prescribed for polycystic ovarian syndrome (PCOS) and obesity treatment in adults in an unlicensed fashion. Little is known as to the extent metformin has been used in young people. We investigated the use of metformin in children and adolescents aged 0-18 years in the UK. METHODS Population-based prescribing data were obtained from the UK IMS Disease Analyzer between January 2000 and December 2010. RESULTS A total of 2674 metformin prescriptions were issued to 337 patients (80% female) between 2000 and 2010. The prevalence of metformin prescribing increased from 0.03 per 1000 person-years [95% confidence interval (CI) 0.02, 0.05] to 0.16 per 1000 person-years (95% CI 0.12, 0.20) ( P= 0.001). There was a steady increase in metformin prescribing in girls aged 16-18 years. There were 290 metformin treated patients (81% female; n= 235) who had at least one diagnosis of diabetes, PCOS or obesity. Among these patients, PCOS was the most common indication for metformin prescribing in girls ( n= 120) followed by diabetes. There were 22 patients (7.6%) who received metformin for obesity treatment only. CONCLUSIONS Prescribing of metformin increased between 2000 and 2010, in particular amongst girls aged 16-18 years. The main indication for metformin prescribing was PCOS. At present, metformin is not licensed for PCOS and obesity treatment in adults or children. As there is a steady increase in the prescribing of metformin in young people, further studies are required to investigate the efficacy and safety of these prescriptions. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Increasing antidiabetic drugs use in youths has been reported in the USA, however there is a lack of epidemiological evidence in the UK. • There is an increase in the prevalence of both type 1 and 2 diabetes, but precise estimates are difficult to obtain and as such are uninformative for future health services planning. WHAT THIS STUDY ADDS • The prevalence of children receiving insulin and oral antidiabetic drugs has increased twofold and eightfold, respectively, between 1998 and 2005. • The data reflect the prevalence of both type 1 and type 2 diabetes rapidly increase in recent years. • The prevalence of antidiabetic drug use increases with increasing age, especially among those aged 12–18 years. • Consideration needs to be given to the funding and design of future services for children and particularly adolescents with diabetes to take account of these epidemiological findings. AIMS Despite evidence of an increase in the incidence of both type 1 and type 2 diabetes in youths, there are few data on the prevalence of either type in children and adolescents. The aim of this study was to investigate the prevalence of childhood diabetes over an 8-year period in the UK. METHODS This was a retrospective cohort study that covered 8 years (January 1998 to December 2005) of UK IMS Disease Analyzer (IMS DA) data. The cohort comprised all children and adolescents aged 0–18 years who received at least one antidiabetic drug prescription during the study period. The prevalence of antidiabetic drug prescribing was used as a proxy for diabetes itself. RESULTS Data were available on 505 754 children aged 0–18 years and a total of 37 225 antidiabetic prescriptions were issued. Insulin use increased significantly from 1.08 per 1000 children [95% confidence interval (CI) 0.96, 1.20] in 1998 to 1.98 (95% CI 1.80, 2.10) in 2005 ( P < 0.001), more markedly in those aged 12 and 18 years. The use of oral antidiabetic drugs for diabetes treatment rose significantly from 0.006 per 1000 children in 1998 (95% CI 0.0043, 0.017) to 0.05 (95% CI 0.025, 0.080) ( P < 0.001) in 2005. CONCLUSIONS This study indicates a significant increase in prevalence on both type 1 and type 2 diabetes treatment in children and adolescents in the UK. Thus, this supporting evidence from other sources that the prevalence of childhood diabetes is rising rapidly. Further epidemiological studies are required to investigate the aetiology and risk factors. [ABSTRACT FROM AUTHOR]

Background: Psychotropic medication prescribing for children and adolescents rose significantly between 2000 and 2002, including antidepressant prescribing. In 2003, the Committee on Safety of Medicines (CSM) advised against using venlafaxine or any selective serotonin receptor inhibitor (SSRI), with the exception of fluoxetine, for childhood and adolescent depression. The aim of this study was to compare the prevalence and incidence of children and adolescents who were prescribed antidepressants in UK primary care, before and after the CSM advice on antidepressant prescribing. We also compared paediatric antidepressant prescribing trends from Mediplus data with national antidepressant prescribing trends in England from the Prescription Pricing Authority (PPA).Methods: The Disease Analyzer-Mediplus database contains anonymised primary care records for about 3 million patients. Eligible patients were aged or=1 antidepressant prescription between 2000 and 2004. Antidepressants were grouped according to the CSM advice and the British National Formulary. Prevalence and incidence were calculated. The prevalences of 2000, 2002 and 2004 were compared using a Chi-squared test. PPA data on antidepressant prescribing rates were compared with paediatric antidepressant prescribing rates from Mediplus.Results: 5,718 children and adolescents received a total of 25,542 prescriptions between 2000 and 2004. The median number of prescriptions per patient was two (interquartile range 1-5). Common indications included depression and anxiety. Antidepressant prevalence increased from 2000 to 2002 (from 5.4 to 6.6 patients per 1,000 people), with a rise in the number of patients prescribed venlafaxine and SSRIs. However, between 2002 and 2004 there was a decrease in antidepressant prevalence (from 6.6 to 5.7 per 1,000). The prevalence of CSM-contraindicated antidepressants (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline and venlafaxine) declined by a third (from 3.1 to 2.0 per 1,000), but there was no change in fluoxetine prevalence (from 2.1 to 2.3 per 1,000). The number of patients prescribed tricyclic antidepressants dropped marginally (from 2.0 to 1.7 per 1,000). Incidences followed the same trends as the prevalences, but there was a 48% reduction in the incidence of CSM-contraindicated antidepressants between 2002 and 2004. National antidepressant prescribing trends increased; paediatric prescribing trends were similar to national trends between 2000 and 2003; however, there was a 27% reduction in the paediatric prescribing rate of CSM-contraindicated antidepressants between 2002 and 2004.Conclusion: Since 2003, fewer children and adolescents have been prescribed antidepressants in primary care. However, fluoxetine and non-SSRI antidepressant prevalences have not risen, implying that they are not prescribed as alternative treatments. This study shows that the CSM advice has had a significant effect in reversing the rising prevalence of antidepressant prescribing to children and adolescents in primary care. [ABSTRACT FROM AUTHOR]

The research potential of many UK clinical databases is not being realized. A recent report published by the Royal College of Paediatrics&Child Health stated that there is a need to build research capacity and support in the area of paediatric pharmacology, with specific emphasis on the use of clinical databases. This article presents the databases available in the UK for medication research and gives some examples of paediatric studies conducted. The databases discussed include the Prescription Pricing Authority database, the General Practice Research Database, IMS Health databases (Medical Data Index, MIDAS Prescribing Insights, Disease-Analyser-Mediplus) and the Yellow Card Scheme. Other databases such as the Medicines Monitoring Unit (MEMO) and the Scottish Primary Care Computer System also have research potential in paediatric pharmacoepidemiology, but their population sizes are relatively small. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To identify prognostic factors for freedom from seizures and long-term retention of treatment in patients receiving lamotrigine (LTG). Methods: A multicenter, retrospective, case record study of 1,050 patients with chronic epilepsy was carried out. Logistic regression and Cox regression analyses were used to identify clinical features associated with freedom from seizures and retention of treatment, respectively. Long-term retention rates of LTG therapy were estimated using Kaplan–Meier survival analysis. Results: The 1,050 patients with chronic epilepsy were included in the study. Patients with generalized epilepsy (p = 0.01), who were not receiving carbamazepine (CBZ; p = 0.02) were more likely to become seizure-free. Sixty percent of patients continued on LTG therapy >1 year and estimated retention at 8 years was 38%. Patients with generalized epilepsy (p = 0.002), patients receiving concurrent sodium valproate (VPA; p < 0.0001), those not previously exposed to gabapentin and vigabatrin (p < 0.0001), and those in whom the starting dose was lower (p < 0.0012), were more likely to remain on long-term treatment with LTG. The relationships with exposure to other antiepileptic drugs remained significant in patients with focal and with generalized epilepsy when considered separately. Conclusions: The best results from LTG treatment in terms of freedom from seizures and long-term retention of treatment were obtained in patients with generalized epilepsy. Retention of treatment was enhanced by VPA not only in generalized but also in focal epilepsy. The importance of a low starting dose of LTG was again confirmed. The apparent negative effect of CBZ in patients taking LTG merits further investigation. [ABSTRACT FROM AUTHOR]

In the original publication, the fifth author’s name was incorrectly published as Simon J. Bell. The correct name should read as ‘J. Simon Bell’. [ABSTRACT FROM AUTHOR]

Focuses on the rise in psychotropic drug prescription in children in Great Britain. Warnings issued by the UK Committee on Safety of Medicines on two new antidepressants; Examination of the trends for prescribing psychotropic medications in different age groups for the period of 2000-2004; Call for funding bodies and pharmaceutical companies to put pediatric psychotropic medications research as a higher priority.

Background: The 2017 WHO Model List of Essential Medicines for Children (EMLc) groups antibiotics as Access, Watch, or Reserve, based on recommendations of their use as first-choice and second-choice empirical treatment for the most common infections. This grouping provides an opportunity to review country-level antibiotic consumption and a potential for stewardship. Therefore, we aimed to review 2015 levels of oral antibiotic consumption by young children globally.Methods: We analysed wholesale antibiotic sales in 70 middle-income and high-income countries in 2015. We identified oral antibiotic formulations appropriate for use in young children (defined as child-appropriate formulations [CAFs]) using wholesale data from the IQVIA-Multinational Integrated Data Analysis System database, and we estimated 2015 antibiotic consumption in reference to the 2017 WHO EMLc Access, Watch, Reserve (AWaRe) antibiotic groups. We used three metrics for assessment of intra-country patterns: access percentage, defined as the number of CAF standard units of Access antibiotics divided by the total number of CAF standard units; amoxicillin index, defined as the number of amoxicillin CAF standard units divided by the total number of CAF standard units; and access-to-watch index, defined as the ratio of Access-to-Watch CAF standard units.Findings: The overall median volume of CAF antibiotic standard units sold in 2015 per country was 74·5 million (IQR 12·4-210·7 million). The median access percentage among the 70 countries was 76·3% (IQR 62·6-84·2). The amoxicillin index was low (median 30·7%, IQR 14·3-47·3). The median access-to-watch index was 6·0 (IQR 3·1-9·8). CAF antibiotic consumption patterns were highly variable between the 70 countries, without a clear difference between high-income and middle-income countries.Interpretation: Antibiotics in the Access group have a key role in treating young children globally. A simple combination of metrics based on the AWaRe groups can be informative on individual countries' patterns of antibiotic consumption and stewardship opportunities. These metrics could support countries in the development of programmes to improve access to core Access antibiotics, particularly amoxicillin.Funding: Global Antibiotic R&D Partnership (German Federal Ministry of Health, Médecins Sans Frontières, Netherlands Ministry of Health, Welfare and Sport, and UK Department for International Development). [ABSTRACT FROM AUTHOR]

OBJECTIVE. The goal was to investigate the epidemiologic features of antipsychotic prescribing to children and adolescents in general practice in the United Kingdom. METHODS. A total of 384 participating general practices from the United Kingdom General Practice Research Database were used to identify patients 0 to 18 years of age Who were prescribed ≥1 antipsychotic medication between January 1, 1992, and December 31, 2005. Annual age-specific prevalences and incidences of antipsychotic prescribing were calculated. RESULTS. The overall prevalence of use of all antipsychotics increased from 1992 (0.39 users per 1000 patient-years) to 2005 (0.77 users per 1000 patient-years). The prescribing prevalence for patients 7 to 12 years of age almost tripled between 1992 (0.23 users per 1000 patient-years) and 2005 (0.61 users per 1000 patient-years). Atypical antipsychotic prescribing increased 60-fold from 1994 (0.01 users per 1000 patient-years) to 2005 (0.61 users per 1000 patient-years). However, typical antipsychotic prescribing decreased significantly from 2000 (0.44 users per 1000 patient-years) to 2005 (0.18 users per 1000 patient-years). The incidences for typical and atypical antipsychotics showed trends similar to those of the respective prevalences. However, the overall incidence (number of new starters) for all antipsychotics was relatively stable between 1992 and 2005, which suggests that patients remain on treatment longer. CONCLUSIONS. The overall prevalence of antipsychotics almost doubled between 1992 and 2005; however, the rate of increase was much lower than the reported figures in the United States. The prescribing of atypical antipsychotic drugs has increased despite the lack of conclusive evidence showing their superiority over older conventional antipsychotics. Additional investigation is required to evaluate their efficacy and safety in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: People with mental health conditions were potentially more vulnerable than others to the neuropsychiatric effects of the COVID-19 pandemic and the global efforts taken to contain it. The aim of this multinational study was to examine the changes in psychotropic drug prescribing during the pandemic among people with depressive and anxiety disorders., Methods: This study included electronic medical records and claims data from nine databases in six countries (France, Germany, Italy, the UK, South Korea, and the USA) of patients with a diagnosis of depressive or anxiety disorders between 2016 and 2021. The outcomes were monthly prevalence rates of antidepressant, antipsychotic, and anxiolytic drug prescribing. The associations between the pandemic and psychotropic drug prescribing were examined with interrupted time series analyses for the total sample and stratified by sex and age group. People with lived experience were not involved in the research and writing process., Findings: Between Jan 1, 2016 and Dec 31, 2020, an average of 16 567 914 patients with depressive disorders (10 820 956 females [65·31%] and 5 746 958 males [34·69%]) and 15 988 451 patients with anxiety disorders (10 688 788 females [66·85%] and 5 299 663 males [33·15%]) were identified annually. Most patients with depressive disorders and anxiety disorders were aged 45-64 years. Ethnicity data were not available. Two distinct trends in prescribing rates were identified. The first pattern shows an initial surge at the start of the pandemic (eg, antipsychotics among patients with depressive disorders in MDCD&#95;US (rate ratio [RR] 1·077, 95% CI 1·055-1·100), followed by a gradual decline towards the counterfactual level (RR 0·990, 95% CI 0·988-0·992). The second pattern, observed in four databases for anxiolytics among patients with depressive disorders and two for antipsychotics among patients with anxiety disorders, shows an immediate increase (eg, antipsychotics among patients with anxiety disorders in IQVIA&#95;UK: RR 1·467, 95% CI 1·282-1·675) without a subsequent change in slope (RR 0·985, 95% CI 0·969-1·003). In MDCD&#95;US and IQVIA&#95;US, the anxiolytic prescribing rate continued to increase among patients younger than 25 years for both disorders., Interpretation: The study reveals persistently elevated rates of psychotropic drug prescriptions beyond the initial phase of the pandemic. These findings underscore the importance of enhanced mental health support and emphasise the need for regular review of psychotropic drug use among this patient group in the post-pandemic era., Funding: University Grants Committee, Research Grants Council, The Government of the Hong Kong Special Administrative Region., Competing Interests: Declaration of interests HL reports grants from Research Grants Council of Hong Kong, outside the submitted work. WCYL reports research grants from AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. JH reports grants from UKRI, Consultancy Fees from Wellcome Trust and Juli Health, and patents pending and stock from Juli Health, outside the submitted work. COT reports stock or stock options and other financial or non-financial interests from Roche Pharmaceutical as an employee, outside the submitted work. XL reports grants from IQVIA, outside the submitted work. SF and DMK report stock or stock options and other financial or non-financial interests from Johnson and Johnson as employees, outside the submitted work. JL reports stock or stock options and other financial or non-financial interests from IQVIA as an employee, outside the submitted work. KKCM reports grants from the CW Maplethorpe Fellowship, National Institute of Health Research, UK, Hong Kong Research Grant Council, and the European Commission Horizon 2020 Framework, outside the submitted work. ICKW reports grants from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK and Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia, consulting fees from IQVIA, payment for expert testimony and a role as an independent non-executive director of Jacobson Medical, Hong Kong, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures., Competing Interests: Declaration of competing interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research (United Kingdom), the European Union Horizon 2020 Framework, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K.Wong received research grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer and Bristol-Myers Squibb and Takeda, Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, The European Union's Seventh Framework Programme for research, technological development, Research Grants Council Hong Kong and Health and Medical Research Fund Hong Kong; consulting fee from IQVIA and WHO; payment for expert testimony for Appeal Court in Hong Kong; serves on advisory committees for Member of Pharmacy and Poisons Board; Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization; Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government; is the non-executive director of Jacobson Medical in Hong Kong; is the Founder and Director of Therakind Limited (UK), Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK). Ching-Lung Cheung received research grants and the honorarium from Amgen, research grant support from HMRF, and the honorarium from Abbott. Wallis C.Y. Lau reports grant from Diabetes UK, AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Vanessa W.S. Ng, Miriam T.Y. Leung, and David P.J. Osborn declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: To investigate the association between antidepressant prescribing and the rate of insulin initiation in type 2 diabetes., Methods: Using UK primary care records we completed a nested-case control study in a individuals with comorbid depression and type 2 diabetes. Cases were defined as individuals initiating insulin, controls were individuals remaining on oral antidiabetic medication. We used conditional logistic regression to estimate incident rate ratios (IRR) and the 95% confidence intervals (CI) for the association between antidepressant prescribing and initiating insulin. We adjusted for demographic characteristics, comorbidities, health service and previous medication use., Results: We included 11,862 cases who initiated insulin, and 43,452 controls. Increased rates of insulin initiation were associated with any antidepressant prescription (IRR 3.78, 95% CI 3.53-4.04), longer (24+ months) durations of antidepressant treatment (IRR 5.61, 95% CI 5.23-6.03), and higher numbers (3+) of different antidepressant agents prescribed (IRR 5.72, 95% CI 5.25-6.24). There was no difference between recent and non-recent antidepressant prescriptions, or between different antidepressant agents., Conclusions: Antidepressant prescribing was highly associated with the initiation of insulin therapy. However, this may not indicate a direct causal effect of the antidepressant medication itself, and may be a marker of more severe depression influencing diabetic control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Type 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease 'risk equivalent' for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to determine the risk of all-cause mortality of patients with cardiovascular disease (CVD) and T2DM in UK and Hong Kong, with stratifications for hemoglobin A1 (HbA1c) concentrations, compared with those without CVD and diabetes mellitus., Research Design and Methods: This is a retrospective cohort study of 3 839 391 adults from Hong Kong and a prospective cohort study of 497 779 adults from the UK Biobank. Individuals were divided into seven disease groups: (1) no T2DM and CVD, (2) T2DM only with HbA1c <7%, (3) T2DM only with HbA1c 7%-7.9%, (4) T2DM only with HbA1c 8%-8.9%, (5) T2DM only with HbA1c ≥9%, (6) CVD only, and (7) T2DM and CVD. Differences in all-cause mortality between groups were examined using Cox regression., Results: After around 10 years of median follow-up, 423 818 and 19 844 deaths were identified in the Hong Kong cohort and UK Biobank, respectively. Compared with individuals without T2DM and CVD, the adjusted HR for all-cause mortality in the other six disease groups for the Hong Kong cohort was 1.25 (95% CI 1.23 to 1.27) for T2DM only with HbA1c <7%, 1.21 (95% CI 1.19 to 1.23) for T2DM only with HbA1c 7%-7.9%, 1.36 (95% CI 1.33 to 1.39) for T2DM only with HbA1c 8%-8.9%, 1.82 (95% CI 1.78 to 1.85) for T2DM only with HbA1c ≥9%, 1.37 (95% CI 1.36 to 1.38) for CVD only, and 1.83 (95% CI 1.81 to 1.85) for T2DM and CVD, and for the UK Biobank the HR was 1.45 (95% CI 1.33 to 1.58), 1.50 (95% CI 1.32 to 1.70), 1.72 (95% CI 1.43 to 2.08), 2.51 (95% CI 2.05 to 3.08), 1.67 (95% CI 1.59 to 1.75) and 2.62 (95% CI 2.42 to 2.83), respectively. This indicates that patients with T2DM had an increased risk of mortality compared with those without T2DM and CVD, and in those with HbA1c ≥9% an even higher risk than people with CVD., Conclusions: Patients with T2DM with poor HbA1c control (8%-8.9% and ≥9%) were associated with similar and higher risk of mortality compared with patients with CVD, respectively. Optimal HbA1c, controlled for risk reduction and prevention of mortality and complications in diabetes management, remains important., Competing Interests: Competing interests: EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR and the Hong Kong Research Grant Council, outside the submitted work. CLKL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians and Kerry Group Kuok Foundation, outside the submitted work. EYTY has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. EWYC has received research grants from the Hong Kong Research Grant Council, Narcotics Division of the Security Bureau of the Government of the Hong Kong SAR, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, National Health and Medical Research Council in Australia, Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen and Takeda, outside the submitted work. ICKW has received research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Hong Kong Research Grant Council and Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK., Method: A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK., Results: The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK., Conclusion: The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Aims: Oral anticoagulant (OAC) is recommended for preventing stroke in atrial fibrillation (AF). However, the OAC utilisation in AF patients with dementia or cognitive impairment (CI) is limited. This study aimed to examine the prevalence of OAC prescriptions in AF patients with dementia/CI and to identify factors associated with OAC treatment within 180 days after dementia/CI diagnosis., Methods: Using The Health Improvement Network database, the annual trends of OAC between 2000 and 2015 were calculated. Multivariable logistic regression was performed to identify factors associated with OAC treatment., Results: The prevalence rate of OAC prescriptions increased from 6.1% in 2000 to 45.9% in 2015. Among OAC users, the proportion of direct oral anticoagulants (DOACs) use increased significantly from 0.1% in 2011 to 33.8% in 2015 (P-trend < 0.001), while the proportion of vitamin K antagonist use decreased by 28.6% from 100% in 2000 to 71.4% in 2015 (P-trend < 0.001). In the multivariable analysis, younger age, very old age, female sex, higher Charlson Comorbidity Index, having a HAS-BLED score ≥3, a history of intracranial bleeding, falls and polypharmacy were significantly associated with lower odds of receiving OAC., Conclusions: In UK primary care, OAC use increased from 2000 to 2015 in AF patients with dementia/CI, with a substantial increase in use of DOACs. Characteristics related to frailty are associated with lower odds of OAC prescription. Given the increasing use of DOACs in patients with dementia/CI, further studies are needed to investigate the safety and effectiveness of DOACs in this important patient group., (© 2020 The British Pharmacological Society.)

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., Competing Interests: Declaration of competing interest IW has received grants from The Research Grants Council (Hong Kong), National Institute of Health Research in the UK, Innovative Medicines Initiative, Amgen, Shire, Janssen-Cilag, Eli-Lily, Pfizer, GSK, Bayer and Novartis outside the submitted work. KM and RB are recipients of the UCL CW Maplethorpe Fellowship. KM has received personal fees from IQVIA Ltd., outside the submitted work. LMH is an NIHR Senior Investigator and receives salary support from the South London and Maudsley NHS Foundation Trust/King's College London NIHR Biomedical Research Centre, and the NIHR South London Applied Research Collaboration. ZW, TM and LW have no other competing interests. No other relationships or activities could appear to have influenced the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Patients with Type 2 diabetes mellitus (T2DM) have an increased risk of atrial fibrillation (AF). The current study aimed to investigate the prevalence and treatment of AF in patients with T2DM, assess the impact of direct oral anticoagulants (DOACs) introduction on oral anticoagulant (OACs) prescribing rates, and factors associated with OAC initiations in patients with T2DM and AF. The Health Improvement Network (THIN) database (2001-2016), was used to examine the annual prevalence and treatment of AF in T2DM. The impact of DOACs introduction on OAC prescribing rates were investigated using interrupted time series analysis (ITS). Factors associated with OAC initiations were also identified using multivariate logistic regression. The prevalence of AF increased from 2.7 [95% confidence intervals (CI) 2.5-2.8] in 2001 to 5.0 (4.9-5.1) in 2016 per 100 persons. OACs prescribing within 30-days of AF diagnosis increased from 21.5% in 2001 to 56.8% in 2016. ITS analysis showed that OAC prescribing increased after DOAC introduction (P < 0.001), however, no immediate change was observed (P = 0.29). T2DM patients with AF, aged 60-79, male gender and BMI ≥ 25 were more likely to receive OAC, adjusted OR 1.3 (1.2-1.5) for aged 60-79, 1.3 (1.2-1.4) for male gender and 2.0 (1.9-2.2) for BMI ≥ 25, respectively. This study highlighted an increase in prevalence of AF in patients with T2DM during the study period. Further studies are warranted to investigate factors contributing to the underuse of OAC in patients with T2DM and AF.

Objective: To evaluate oral anticoagulant (OAC) prescribing trends in type 2 diabetes mellitus (T2DM) in the UK from 2001 to 2015., Design: A cross-sectional drug utilisation study., Setting: Electronic health records from The Health Improvement Network primary care database in the UK., Participants: Individuals with T2DM who received a record of OAC prescription., Outcome Measures: The prescribing trends of OAC medications in individuals with T2DM were examined from 2001 to 2015, stratified by age, gender and therapeutic classifications., Results: A total of 361 635 individuals with T2DM were identified, of whom 36 570 were prescribed OAC from 2001 to 2015. The prevalence of OAC prescribing increased by 50.0%, from 1781 individuals receiving OAC prescriptions (IROACP) (4.4 (95% CI 4.2 to 4.6) per 100 persons) in 2001, to 17 070 IROACP (6.6 (95% CI 6.5 to 6.7) per 100 persons) in 2015. The prevalence of warfarin prescribing decreased by 14.0%, from 1761 individuals receiving warfarin prescriptions (IRWP) (98.9 (95% CI 98.4 to 99.4) per 100 persons) in 2001, to 14 533 IRWP (85.1 (95% CI 84.6 to 85.7) per 100 persons) in 2015. This corresponded with increased prescribing of direct oral anticoagulants (DOACs), from 18 individuals receiving DOAC prescriptions (IRDOACP) (0.1 (95% CI 0.08 to 0.23) per 100 persons) in 2010, to 3016 IRDOACP (17.6 (95% CI 17.1 to 18.2) per 100 persons) in 2015, during the same period., Conclusions: Prescribing of OACs in individuals with T2DM increased from 2001 to 2015. Since the introduction of DOACs, there has been a clear shift in prescribing towards these agents. Future studies are needed to assess the safety of coadministration of OAC medications and antidiabetic therapy with T2DM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Few studies have shown that an increased risk of dementia is associated with diabetes mellitus., Objective: To estimate the prevalence and incidence of dementia in people with diabetes in primary care in the UK., Methods: We conducted a descriptive study using the UK The Health Improvement Network (THIN) database. People diagnosed with diabetes from 2000 to 2016 were included in the study. Prevalence and incidence rates of dementia were calculated annually, stratified by age and gender., Results: The prevalence of dementia was 0.424% [95% CI (0.420%-0.427%)] in 2000 and 2.508% [95% CI (2.501%-2.515%)] in 2016. The highest prevalence was in those aged 85+ from 2.9% [95% CI (2.890%-2.974%)] in 2000 to 11.3% [95% CI (11.285%-11.384%)] in 2016. The incidence of dementia increased 3.7 times, from 0.181 cases per 100 persons [95% CI (0.179-0.183)] in 2000 to 0.683 cases per 100 persons [95% CI (0.679-0.686)] in 2016, respectively. Women had a higher prevalence and incidence of dementia than men 3.138% [95% CI (3.127%-3.150%)] versus 2.014% [95% CI (2.006%-2.022%)] and 0.820 [95% CI (0.814-0.826)] versus 0.576 cases per 100 persons [95% CI (0.571-0.580)] in 2016, respectively., Conclusion: There was a trend of increasing prevalence and incidence of dementia in people with diabetes over the period of 2000 to 2016. This study adds to the evidence on dementia prevalence and incidence, particularly in the diabetic population.

Purpose: To explore the impact of pneumococcal conjugate vaccines (PCVs) in preventing childhood pneumonia in the United Kingdom., Methods: We carried out a population-based study to assess the trend of all-cause pneumonia in children aged under 10 years between 2002 and 2012. Data were obtained from the IMS Disease Analyser, a primary care database in the United Kingdom. Three time periods were defined to estimate monthly incidence: pre-PCV7 (January 2002 to August 2006), post-PCV7 (September 2006 to March 2010), and post-PCV13 (April 2010 to December 2012). Interrupted time series analysis (ITS) was performed to assess any immediate change or gradual change in the monthly incidence of pneumonia between prevaccination and postvaccination introduction., Results: A total of 4228 children with at least one all-cause pneumonia episode were identified. The overall annual incidence rate of all-cause pneumonia declined by 37% from 3.8 episodes/1000 person-years in 2002 to 2.4 episodes/1000 person-years in 2012. Results of ITS analyses indicated that the incidence did not decline immediately after the introduction of PCV7 and PCV13. The incidence declined gradually in children aged under 2 years (IRR = 0.98; 95% CI, 0.97-0.99) post PCV7 and levelled off during post PCV13 (IRR = 1.00; 95% CI, 0.99-1.02). No significant changes in incidence trend was observed in children aged 2 to 4 years (IRR = 0.86; 95% CI, 0.68-1.07) and 5 to 9 years (IRR = 0.92; 95% CI, 0.73-1.15) after PCV13 introduction., Conclusions: In the United Kingdom, the incidence of all-cause pneumonia in children under 2 years declined after the introduction of PCV7 and levelled off in the first 2 years of introduction of PCV13. Continual monitoring is warranted to assess the population impact of PCV13 in preventing childhood pneumonia in the long term., (© 2019 John Wiley & Sons, Ltd.)

Background: In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice., Methods and Findings: The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding., Conclusions: In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: ICKW has received research funding from Bristol-Myers Squibb, Pfizer, Janssen, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund outside the submitted work. KKCM has received personal fees from IQVIA outside the submitted work. JK is an employee of IQVIA. There are no other relationships or activities that could appear to have influenced the submitted work.