Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk.

The prevention of thromboembolism in atrial fibrillation (AF) is typically restricted to patients with specific risk factors and ignores outcomes such as vascular dementia. This population-based cohort study used electronic healthcare records from 5,199,994 primary care patients (UK; 2005-2020). A total of 290,525 (5.6%) had a diagnosis of AF and were aged 40-75 years, of which 36,340 had no history of stroke, a low perceived risk of stroke based on clinical risk factors and no oral anticoagulant prescription. Matching was performed for age, sex and region to 117,298 controls without AF. During 5 years median follow-up (831,005 person-years), incident stroke occurred in 3.8% with AF versus 1.5% control (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.91-2.21; P < 0.001), arterial thromboembolism 0.3% versus 0.1% (HR 2.39, 95% CI 1.83-3.11; P < 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38-1.50; P < 0.001). AF was associated with all-cause dementia (HR 1.17, 95% CI 1.04-1.32; P = 0.010), driven by vascular dementia (HR 1.68, 95% CI 1.33-2.12; P < 0.001) rather than Alzheimer's disease (HR 0.85, 95% CI 0.70-1.03; P = 0.09). Death and thromboembolic outcomes, including vascular dementia, are substantially increased in patients with AF despite a lack of conventional stroke risk factors.

Association of sildenafil use with age-related macular degeneration: a retrospective cohort study.

OBJECTIVE: Despite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)-a major cause of global blindness-lacks effective treatment to prevent the irreversible degeneration of photoreceptors leading to central vision loss. Limited studies suggest phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may prevent AMD by increasing retinal blood flow. This study explores the potential association between sildenafil use and AMD risk in men with erectile dysfunction using UK data. METHODS AND ANALYSIS: Using the UK's IQVIA Medical Research Data, the study analysed 31 575 men prescribed sildenafil for erectile dysfunction and no AMD history from 2007 to 2015, matched with a comparator group of 62 155 non-sildenafil users in a 1:2 ratio, over a median follow-up of approximately three years. RESULTS: The primary outcome was the incidence of AMD in the two groups. The study found no significant difference in AMD incidence between the sildenafil users and the non-users, with an adjusted hazard ratio (HR) of 0.99 (95% CI 0.84 to 1.16), after accounting for confounders such as age, ethnicity, Townsend deprivation quintile, body mass index category, and diagnosis of hypertension and type 2 diabetes. CONCLUSION: The study results indicated no significant association between sildenafil use and AMD prevention in UK men with erectile dysfunction, suggesting sildenafil's protective effect on AMD is likely insignificant.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. METHODS: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). CONCLUSIONS: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. CITATION: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data.

BACKGROUND: The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. METHODS: Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. RESULTS: Based on an analysis of 472,173 patients with COVID-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and reporting of longer-term symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. CONCLUSIONS: The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Cardiometabolic screening and monitoring in patients prescribed antipsychotic drugs in primary care: A population-based cohort study.

BACKGROUND: This study aimed to investigate the level of guideline adherence for cardiometabolic health monitoring for patients prescribed antipsychotic medicines in UK primary care. METHODS: In this population-based retrospective open cohort study, we used dataset of patients from the IQVIA Medical Research Data (IMRD) database between 1st January 2003 to 31st December 2018. Clinical Read codes were used to identify a cohort of adult patients with a diagnosis of Schizophrenia and at least four prescriptions of an anti-psychotic medication within 12 months of diagnosis. We then extracted data in relation to monitoring of cardiometabolic parameters (body compositions, lipids, and glucose outcomes) at baseline, then at six weeks, 12 weeks, and then 12 months. The frequency of outcome monitoring was described using descriptive statistics. FINDINGS: A total of 11,435 patients were eligible and of them (n = 9707; 84·8%) were prescribed second-generation antipsychotics (SGAs). Only a small portion of the cohort (≈2·0%) received complete monitoring (at time points) for certain outcomes. Just over half the patients (n = 6599, 52%) had evidence of any cardiometabolic baseline testing for any of the study outcomes and the high majority had at least one abnormal lab value at baseline (n = 4627, 96·7%). INTERPRETATION: In UK primary care, cardiometabolic monitoring practices among patients prescribed antipsychotics remain suboptimal. There is a need to promote guideline adherence to prevent adverse outcomes in antipsychotic users.

Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care.

BACKGROUND: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs). METHODS: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. RESULTS: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42). CONCLUSIONS: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.

Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.

BACKGROUND: Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes. AIMS: To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis. METHODS: We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis. RESULTS: We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression. CONCLUSIONS: Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.

Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.

BACKGROUND: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). METHODS AND RESULTS: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. CONCLUSION: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

The development of a core outcome set for studies of pregnant women with multimorbidity.

BACKGROUND: Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity. METHODS: We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations. RESULTS: Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs. CONCLUSIONS: Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.

Considerations for patient and public involvement and engagement in health research.

Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.

The risk of all-cause mortality associated with anxiety: a retrospective cohort study using 'The Health Improvement Network' database.

BACKGROUND: Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety. METHODS: We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk. RESULTS: During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety. CONCLUSION: A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.

Prevalence of polypharmacy in pregnancy: a systematic review.

OBJECTIVES: The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes. DESIGN: MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included.Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed. RESULTS: Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%-5.5%) to 62.4% (61.3%-63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%-5.14%) to 33.7% (32.2%-35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy. CONCLUSION: There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms. TWEETABLE ABSTRACT: Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown. PROSPERO REGISTRATION NUMBER: CRD42021223966.

Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.

INTRODUCTION: One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions). METHODS AND ANALYSIS: Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses. ETHICS AND DISSEMINATION: Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Emotional and psychosexual well-being is influenced by ethnicity and birthplace in women and individuals with polycystic ovary syndrome in the UK and India.

OBJECTIVE: To assess the association of ethnicity and birthplace on emotional and psychosexual well-being in women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Community recruitment via social media campaigns. POPULATION: Women with PCOS completing an online questionnaire in September-October 2020 (UK) and May-June 2021 (India). METHODS: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). MAIN OUTCOME MEASURES: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). RESULTS: A total of 1008 women with PCOS were included. Women of non-white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41-2.73) and lower BDD (OR 0.57, 95% CI 0.41-0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00-2.46) and depression (OR 2.20, 95% CI 1.52-3.18) but lower BDD rates (OR 0.42, 95% CI 0.29-0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non-white women and women born in India. CONCLUSIONS: Non-white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care.

Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial Hypertension.

The link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.

Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study.

OBJECTIVE: To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls. BACKGROUND: Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study. METHODS: We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls). RESULTS: A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20-1.58; and aHR 1.40, 95% CI 1.19-1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86-1.13; and aHR 0.98, 95% CI 0.83-1.14, respectively). CONCLUSION: Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.

Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.

BACKGROUND: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. METHODS: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. RESULTS: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. CONCLUSIONS: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

BACKGROUND: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. METHODS: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. FINDINGS: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. INTERPRETATION: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.