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.

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.

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.

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.

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.

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.

Trazodone use and risk of dementia: A population-based cohort study.

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.

Evaluation of the risk of cardiovascular events with clarithromycin using both propensity score and self-controlled study designs.

AIM: Some previous studies suggest a long term association between clarithromycin use and cardiovascular events. This study investigates this association for clarithromycin given as part of Helicobacter pylori treatment (HPT). METHODS: Our source population was the Clinical Practice Research Datalink (CPRD), a UK primary care database. We conducted a self-controlled case series (SCCS), a case-time-control study (CTC) and a propensity score adjusted cohort study comparing the rate of cardiovascular events in the 3 years after exposure to HPT containing clarithromycin with exposure to clarithromycin free HPT. Outcomes were first incident diagnosis of myocardial infarction (MI), arrhythmia and stroke. For the cohort analysis we included secondary outcomes all cause and cardiovascular mortality. RESULTS: Twenty-eight thousand five hundred and fifty-two patients were included in the cohort. The incidence rate ratio of first MI within 1 year of exposure to HPT containing clarithromycin was 1.07 (95% CI 0.85, 1.34, P = 0.58) and within 90 days was 1.43 (95% CI 0.99, 2.09 P = 0.057) in the SCCS analysis. CTC and cohort results were consistent with these findings. CONCLUSIONS: There was some evidence for a short term association for first MI but none for a long term association for any outcome.

The risk of acute liver injury among users of antibiotic medications: a comparison of case-only studies.

PURPOSE: The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies. METHODS: For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments. RESULTS: Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53). CONCLUSION: An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations.

The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project.

PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk. METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses. RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates. CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.

PURPOSE: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. METHODS: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. RESULTS: The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.

Prevalence of antibiotic use: a comparison across various European health care data sources.

PURPOSE: There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries. METHODS: Seven European healthcare databases with access to primary care data from Denmark, Germany, the Netherlands, Spain and the UK were used to measure and compare the point and 1-year-period prevalence of antibiotic use between 2004 and 2009. Descriptive analyses were stratified by gender, age and type of antibiotic. Separate analyses were performed to measure the most common underlying indications leading to the prescription of an antibiotic. RESULTS: The average yearly period prevalence of antibiotic use varied from 15 (Netherlands) to 30 (Spain) users per 100 patients. A higher prevalence of antibiotic use by female patients, the very young (0-9 years) and old (80+ years), was observed in all databases. The lowest point prevalence was recorded in June and September and ranged from 0.51 (Netherlands) to 1.47 (UK) per 100 patients per day. Twelve percent (Netherlands) to forty-nine (Spain) percent of all users were diagnosed with a respiratory tract infection, and the most common type of antibiotic prescribed were penicillin. CONCLUSION: Using identical methodology in seven EU databases to assess antibiotic use allowed us to compare drug usage patterns across Europe. Our results contribute quantitatively to the true understanding of similarities and differences in the use of antibiotic agents in different EU countries.

Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study.

AIM: Antipsychotics increase the risk of stroke. Their effect on myocardial infarction remains uncertain because people prescribed and not prescribed antipsychotic drugs differ in their underlying vascular risk making between-person comparisons difficult to interpret. The aim of our study was to investigate this association using the self-controlled case series design that eliminates between-person confounding effects. METHODS AND RESULTS: All the patients with a first recorded myocardial infarction and prescription for an antipsychotic identified in the Clinical Practice Research Datalink linked to the Myocardial Ischaemia National Audit Project were selected for the self-controlled case series. The incidence ratio of myocardial infarction during risk periods following the initiation of antipsychotic use relative to unexposed periods was estimated within individuals. A classical case-control study was undertaken for comparative purposes comparing antipsychotic exposure among cases and matched controls. We identified 1546 exposed cases for the self-controlled case series and found evidence of an association during the first 30 days after the first prescription of an antipsychotic, for first-generation agents [incidence rate ratio (IRR) 2.82, 95% confidence interval (CI) 2.0-3.99] and second-generation agents (IRR: 2.5, 95% CI: 1.18-5.32). Similar results were found for the case-control study for new users of first- (OR: 3.19, 95% CI: 1.9-5.37) and second-generation agents (OR: 2.55, 95% CI: 0.93-7.01) within 30 days of their myocardial infarction. CONCLUSION: We found an increased risk of myocardial infarction in the period following the initiation of antipsychotics that was not attributable to differences between people prescribed and not prescribed antipsychotics.

Glitazone Treatment and Incidence of Parkinson's Disease among People with Diabetes: A Retrospective Cohort Study.

BACKGROUND: Recent in vitro and animal experiments suggest that peroxisome proliferation-activated receptor gamma (PPARÉ£) agonist medications, such as antidiabetic glitazone (GTZ) drugs, are neuroprotective in models of Parkinson's disease (PD). These findings have not been tested in humans. We hypothesized that individuals prescribed GTZ drugs would have a lower incidence of PD compared to individuals prescribed other treatments for diabetes. METHODS AND FINDINGS: Using primary care data from the United Kingdom Clinical Practice Research Datalink (CPRD), we conducted a retrospective cohort study in which individuals with diabetes who were newly prescribed GTZ (GTZ-exposed group) were matched by age, sex, practice, and diabetes treatment stage with up to five individuals prescribed other diabetes treatments (other antidiabetic drug-exposed group). Patients were followed up from 1999 until the first recording of a PD diagnosis, end of observation in the database, or end of the study (1 August 2013). An incidence rate ratio (IRR) was calculated using conditional Poisson regression, adjusted for possible confounders. 44,597 GTZ exposed individuals were matched to 120,373 other antidiabetic users. 175 GTZ-exposed individuals were diagnosed with PD compared to 517 individuals in the other antidiabetic drug-exposed group. The incidence rate (IR) of PD in the GTZ-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 patient years in those prescribed other antidiabetic treatments (IRR 0.72, 95% confidence interval [CI] 0.60-0.87). Adjustments for potential confounding variables, including smoking, other medications, head injury, and disease severity, had no material impact (fully adjusted IRR 0.75, 0.59-0.94). The risk was reduced in those with current GTZ prescriptions (current GTZ-exposed IRR 0.59, 0.46-0.77) but not reduced among those with past prescriptions (past GTZ-exposed IRR 0.85, 0.65-1.10). Our study only included patients with diabetes who did not have a PD diagnosis when they were first prescribed GTZ, and thus, it cannot establish whether GTZ use prevents or slows the progression of PD. CONCLUSIONS: In patients with diabetes, a current prescription for GTZ is associated with a reduction in incidence of PD. This suggests PPAR gamma pathways may be a fruitful drug target in PD.

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

BACKGROUND: Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. METHODS AND FINDINGS: The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. CONCLUSIONS: Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events.

The prescribing of opioids for chronic noncancer pain in the menopausal and postmenopausal population: a drug utilisation study in the United Kingdom.

BACKGROUND: Opioid use for chronic noncancer pain (CNCP) is consistently higher in menopausal/postmenopausal women than in younger women or men, elevating their risk of opioid-related adverse health outcomes. Since pain severity increases with hormonal changes accompanying menopause, these women should be a focus of opioid stewardship efforts. AIM: To examine opioid prescribing trends for CNCP in menopausal/postmenopausal women diagnosed with a musculoskeletal condition. DESIGN & SETTING: Population-based drug utilisation study using IQVIA Medical Research Data UK. METHOD: Annual opioid prescribing incidence, prevalence, and average duration of use were calculated for a cohort of women aged 50-79 with musculoskeletal conditions newly diagnosed between 2010-2021. Specific results were stratified by age, pain indication, and Townsend score. RESULTS: From 2010 to 2021, incident prescribing rates of opioids increased in women aged 50-54 (161.4 [95% CI 149.7-174.0] per 1000 PYAR in 2010 to 239.6 [95% CI 211.7-271.2] per 1000 PYAR in 2021); these women discontinued opioid use faster (~1 year) than older age groups (~2 years). Overall, opioid prescribing prevalence decreased from 23% in 2010 to 14% in 2021, and average opioid use duration decreased from 3 years to 1 year (2010 - post-2017) in women aged 50-79. CONCLUSION: The overall observed decrease in prevalence and average duration of opioid use is encouraging. Incident prescriptions are rising in women aged 50-54 and those with fibromyalgia while remaining steady in women aged 55-79. Understanding the impact of menopause/post-menopause on opioid use trends is important for effective opioid stewardship.

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.

Risk of osteoporotic fractures in menopausal women with common mental health diagnoses prescribed SSRIs/SNRIs: cohort and self-controlled case series analyses.

In a population-based cohort study of menopausal women with common mental health diagnoses, SSRIs/SNRIs were associated with a 32% increased risk of osteoporotic fractures. The risk of osteoporotic fractures was particularly increased for longer periods of treatment with SSRIs/SNRIs (> 5 years) and in younger menopausal women (< 50 years old). PURPOSE: To investigate the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of osteoporotic fractures (OF) in menopausal women with common mental health diagnoses (CMHD). METHODS: We conducted the study with two designs (cohort and self-controlled case series [SCCS]), using the IQVIA Medical Research Database (IMRD) UK. The source population comprised women aged ≥ 50 years and women with a record indicating menopause (< 50 years). All women had a recorded CMHD. For the cohort analysis, the risk of OFs was estimated by comparing women prescribed SSRIs/SNRIs (exposed) to those not exposed. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). For the SCCS, women acted as their own controls; periods of exposure to SSRIs/SNRIs were compared to periods of non-exposure using conditional Poisson regression to estimate incidence rate ratios (IRR) with 95% CIs. RESULTS: We identified 292,848 women, of whom 35,222 experienced OFs within a median follow-up of 6.01 years. We found strong evidence of an association between SSRIs/SNRIs and the risk of OFs (adjusted HR = 1.32, 95% CI:1.29-1.35). Compared to periods of no exposure, SSRIs/SNRIs increased the risk of OFs during the first 30 days (IRR = 1.38, 95% CI:1.26-1.51), during the first 90 days (IRR = 1.58, 95% CI: 1.48-1.69), and the remaining exposure (IRR = 1.42, 95% CI:1.37-1.48). CONCLUSIONS: In a population of menopausal women with CMHDs, the prescribing of SSRIs/SNRIs antidepressants was associated with a higher risk of OFs. Careful assessment of osteoporosis risk needs to be considered when treating menopausal women with SSRIs/SNRIs antidepressants.

Cardiovascular risk of hormone replacement therapy in menopausal women with diabetes: a systematic review and meta-analysis of clinical trials and observational studies.

INTRODUCTION: Studies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population. Evidence on women with diabetes remains scarce. We aimed to investigate the risk of cardiovascular disease (CVD) in menopausal women with diabetes who use HRT compared to non-users. METHODS: Search across Medline, Embase, Web of Sciences, and Cochrane databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CVD outcomes. Non-English studies, observational studies other than cohort and case-control, reviews, and conference abstracts were excluded. Bias was checked using validated risk-of-bias tools. Random-effects model was used to calculate pooled relative risks (RR) for similar outcomes. RESULTS: Out of 7625 identified articles, 19 (6 clinical trials and 13 observational studies) were included, primarily from Europe and the U.S.A. Most studies had moderate risk of bias. Meta-analysis of myocardial infarction (MI) risk from nine observational studies (n = ~34,626) showed a pooled RR of 0.83 (95% CI 0.62-1.12). Limited data precluded meta-analysis for the clinical trials and other outcomes from observational studies. CONCLUSIONS: Observational studies do not suggest an increased risk of MI in menopausal women with diabetes prescribed HRT. Further research with a more robust method is warranted to validate this finding. PROSPERO REGISTRATION NUMBER: CRD42023479335.