Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis.

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. RESULTS: We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. CONCLUSIONS: In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.

Frequency and impact of medication reviews for people aged 65 years or above in UK primary care: an observational study using electronic health records.

BACKGROUND: Medication reviews in primary care provide an opportunity to review and discuss the safety and appropriateness of a person's medicines. However, there is limited evidence about access to and the impact of routine medication reviews for older adults in the general population, particularly in the UK. We aimed to quantify the proportion of people aged 65 years and over with a medication review recorded in 2019 and describe changes in the numbers and types of medicines prescribed following a review. METHODS: We used anonymised primary care electronic health records from the UK's Clinical Practice Research Datalink (CPRD GOLD) to define a population of people aged 65 years or over in 2019. We counted people with a medication review record in 2019 and used Cox regression to estimate associations between demographic characteristics, diagnoses, and prescribed medicines and having a medication review. We used linear regression to compare the number of medicines prescribed as repeat prescriptions in the three months before and after a medication review. Specifically, we compared the 'prescription count' - the maximum number of different medicines with overlapping prescriptions people had in each period. RESULTS: Of 591,726 people prescribed one or more medicines at baseline, 305,526 (51.6%) had a recorded medication review in 2019. Living in a care home (hazard ratio 1.51, 95% confidence interval 1.40-1.62), medication review in the previous year (1.83, 1.69-1.98), and baseline prescription count (e.g. 5-9 vs 1 medicine 1.41, 1.37-1.46) were strongly associated with having a medication review in 2019. Overall, the prescription count tended to increase after a review (mean change 0.13 medicines, 95% CI 0.12-0.14). CONCLUSIONS: Although medication reviews were commonly recorded for people aged 65 years or over, there was little change overall in the numbers and types of medicines prescribed following a review. This study did not examine whether the prescriptions were appropriate or other metrics, such as dose or medicine changes within the same class. However, by examining the impact of medication reviews before the introduction of structured medication review requirements in England in 2020, it provides a useful benchmark which these new reviews can be compared with.

Sex, Age, and Socioeconomic Differences in Nonfatal Stroke Incidence and Subsequent Major Adverse Outcomes.

BACKGROUND AND PURPOSE: Data about variations in stroke incidence and subsequent major adverse outcomes are essential to inform secondary prevention and prioritizing resources to those at the greatest risk of major adverse end points. We aimed to describe the age, sex, and socioeconomic differences in the rates of first nonfatal stroke and subsequent major adverse outcomes. METHODS: The cohort study used linked Clinical Practice Research Datalink and Hospital Episode Statistics data from the United Kingdom. The incidence rate (IR) ratio of first nonfatal stroke and subsequent major adverse outcomes (composite major adverse cardiovascular events, recurrent stroke, cardiovascular disease-related, and all-cause mortality) were calculated and presented by year, sex, age group, and socioeconomic status based on an individual's location of residence, in adults with incident nonfatal stroke diagnosis between 1998 and 2017. RESULTS: A total of 82 774 first nonfatal stroke events were recorded in either primary care or hospital data-an IR of 109.20 per 100 000 person-years (95% CI, 108.46-109.95). Incidence was significantly higher in women compared with men (IR ratio, 1.13 [95% CI, 1.12-1.15]; P<0.001). Rates adjusted for age and sex were higher in the lowest compared with the highest socioeconomic status group (IR ratio, 1.10 [95% CI, 1.08-1.13]; P<0.001). For subsequent major adverse outcomes, the overall incidence for major adverse cardiovascular event was 38.05 per 100 person-years (95% CI, 37.71-38.39) with a slightly higher incidence in women compared with men (38.42 versus 37.62; IR ratio, 1.02 [95% CI, 1.00-1.04]; P=0.0229). Age and socioeconomic status largely accounted for the observed higher incidence of adverse outcomes in women. CONCLUSIONS: In the United Kingdom, incidence of initial stroke and subsequent major adverse outcomes are higher in women, older populations, and people living in socially deprived areas.

Long-term body mass index changes in overweight and obese adults and the risk of heart failure, cardiovascular disease and mortality: a cohort study of over 260,000 adults in the UK.

BACKGROUND: Although obesity is a well-recognised risk factor for cardiovascular disease (CVD), the impact of long-term body mass index (BMI) changes in overweight or obese adults, on the risk of heart failure, CVD and mortality has not been quantified. METHODS: This population-based cohort study used routine UK primary care electronic health data linked to secondary care and death-registry records. We identified adults who were overweight or obese, free from CVD and who had repeated BMI measures. Using group-based trajectory modelling, we examined the BMI trajectories of these individuals and then determined incidence rates of CVD, heart failure and mortality associated with the different trajectories. Cox-proportional hazards regression determined hazards ratios for incident outcomes. RESULTS: 264,230 individuals (mean age 49.5 years (SD 12.7) and mean BMI 33.8 kg/m2 (SD 6.1)) were followed-up for a median duration of 10.9 years. Four BMI trajectories were identified, corresponding at baseline, with World Health Organisation BMI classifications for overweight, class-1, class-2 and class-3 obesity respectively. In all four groups, there was a small, stable upwards trajectory in BMI (mean BMI increase of 1.06 kg/m2 (± 3.8)). Compared with overweight individuals, class-3 obese individuals had hazards ratios (HR) of 3.26 (95% CI 2.98-3.57) for heart failure, HR of 2.72 (2.58-2.87) for all-cause mortality and HR of 3.31 (2.84-3.86) for CVD-related mortality, after adjusting for baseline demographic and cardiovascular risk factors. CONCLUSION: The majority of adults who are overweight or obese retain their degree of overweight or obesity over the long term. Individuals with stable severe obesity experience the worst heart failure, CVD and mortality outcomes. These findings highlight the high cardiovascular toll exacted by continuing failure to tackle obesity.

Mental health conditions and COVID-19 vaccine outcomes: A scoping review.

OBJECTIVE: Research shows that people with a history of mental health conditions were at increased risk of COVID-19 infection, hospitalisation, and mortality. However, the relationship between mental health conditions and COVID-19 vaccine outcomes such as vaccine intention, uptake and vaccine breakthrough is not yet well-understood. METHODS: We conducted a systematic search on the topics of COVID-19 vaccine intentions, vaccine uptake, and vaccine breakthrough, in relation to mental health conditions (e.g., depression, schizophrenia), in four databases: PubMed, MEDLINE, SCOPUS, and PsychINFO, and the publication lists of Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), OpenSAFELY, and QResearch. Inclusion criteria focussed on studies reporting any of the aforementioned COVID-19 vaccine outcomes among people with mental health conditions. RESULTS: Of 251 publications initially identified, 32 met our inclusion criteria. Overall, the evidence is inconclusive regarding the levels of intention to accept COVID-19 vaccines among people with mental health conditions. People with mental health conditions were more likely to have lower uptake of COVID-19 vaccines, compared to people without. Common barriers to COVID-19 vaccine uptake included concerns about the safety, effectiveness, and side effects of the vaccines. Limited evidence also suggests that vaccine breakthrough may be a particular risk for those with substance use disorder. CONCLUSIONS: Evidence for the association between COVID-19 vaccine intentions and mental health conditions is mixed. Vaccine uptake might be lower in people with mental health conditions compared to people without, yielding interventions to encourage vaccine uptake in this population. Our understanding of COVID-19 vaccine breakthrough in this population also needs enhancing.

Factors affecting shared decision-making concerning menopausal hormone therapy.

Menopausal hormone therapy (MHT) is an effective treatment for menopause-related symptoms. Menopause management guidelines recommend a personalized approach to menopause care, including MHT use. Decision-making around menopause care is a complex, iterative process influenced by multiple factors framed by perspectives from both women and healthcare providers (HCPs). This narrative review aims to summarize evidence around factors affecting decision-making regarding menopause-related care. For HCPs, the provision of individualized risk estimates is challenging in practice given the number of potential benefits and risks to consider, and the complexity of the data available, especially within time-limited consultations. Women seeking menopause care have the difficult task of making sense of the benefit versus risk profiles to make choices in line with their decisional needs influenced by sociocultural/economic, educational, demographic, and personal characteristics. The press, social media, and influential celebrities also impact the perception of menopause and decision-making around it. Understanding these factors can lead to improved participation in shared decision-making, satisfaction with the decision and decision-making process, adherence to treatment, reduced decisional regret, efficient use of resources, and ultimately long-term satisfaction with care.

Recovery from injury: the UK burden of injury multicentre longitudinal study.

OBJECTIVES: To estimate the likelihood of recovery at 1, 4 and 12 months post injury and investigate predictors of recovery in injured people attending an emergency department (ED) or admitted to hospital in the UK. METHODS: Participants completed questionnaires at recruitment and 1, 4 and 12 months post injury or until recovered. Data were collected on injury details, sociodemographic characteristics, general health prior to injury and recovery. We compared three age groups: 5-17, 18-64 and 65 years and above. Modified Poisson regression estimated the relative risk of recovery. Multivariable models were built using backward stepwise regression. Sensitivity analyses assessed the effect of missing data. RESULTS: We recruited 1517 participants, 55% (n=836) ED attenders and 44% (n=661) hospital admissions. By 1 month after injury, 28% (285/968) had fully recovered, 54% (440/820) at 4 months and 71% (523/738) at 12 months. Recovery was independently associated with gender, admission status, injury severity, body region injured and place of injury for 5-17 year olds and 18-64 year olds and with gender, admission status, injury severity and long-term illness for those aged 65+. Injury severity and hospital admission were associated with recovery across all age groups, but not at every time point in each age group. Other factors varied between age groups or time points. Results were generally robust to imputing missing data. CONCLUSIONS: A range of factors was found to predict recovery among injured people. These could be used to identify those at risk of delayed recovery and to inform the design of interventions to maximise recovery.

Efficacy and safety of intensive versus conventional glucose targets in people with type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. METHODS: We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA1clevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5--0.87), microalbuminuria (0.67, 0.52-0.85), major amputation (0.6, 0.38-0.96), retinopathy (0.75 ,0.63-0.9), and nephropathy (0.78, 0.63-0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34-3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57-0.95). CONCLUSION: Targeting HbA1c levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D.

Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study.

Background: Heavy menstrual bleeding is a common problem that can significantly affect women's lives until menopause. There is a lack of evidence on longer-term outcomes after seeking health care and treatment for heavy menstrual bleeding. Objectives: To assess the continuation rates of medical treatments and the rates of ablative and surgical interventions among women who had participated in the ECLIPSE trial (ISRCTN86566246) 10 years after initial management for heavy menstrual bleeding in primary care. To explore experiences of heavy menstrual bleeding and influences on treatment for women. Design: This was a prospective observational cohort study, with a parallel qualitative study. Setting: Primary care. Participants: A total of 206 women with heavy menstrual bleeding who had participated in the ECLIPSE trial consented to providing outcome data via a questionnaire approximately 10 years after original randomisation. Their mean age at follow-up was 54 years (standard deviation 5 years). A purposeful sample of 36 women also participated in semistructured qualitative interviews. Interventions: The ECLIPSE trial randomised participants to either the levonorgestrel-releasing intrauterine system (52 mg) or the usual medical treatment (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone, chosen as clinically appropriate by general practitioners and women). Women could subsequently swap or cease their allocated treatment. Main outcome measures: The main outcome measures were rates of ablative and surgical treatments; the rate of continuation of medical treatments; and quality of life using the Short Form questionnaire-36 items and EuroQol-5 Dimensions; women's experiences of heavy menstrual bleeding; and the influences on their decisions around treatment. Results: Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, n = 34 (17%); endometrial ablation, n = 26 (13%)]. Between 5 and 10 years post trial intervention, 89 women (43%) had ceased all medical treatments and 88 (43%) were using the levonorgestrel-releasing intrauterine system alone or in combination with other oral treatments. More women in the usual medical treatment group had also used the levonorgestrel-releasing intrauterine system than women in the levonorgestrel-releasing intrauterine system group. Fifty-six women (28%) used the levonorgestrel-releasing intrauterine system at 10 years. There was no statistically significant difference in generic quality-of-life scores between the two original trial groups, although small improvements in the majority of domains were seen in both groups across time. Women reported wide-ranging impacts on their quality of life and normalisation of their heavy menstrual bleeding experience as a result of the taboo around menstruation. Women's treatment decisions and experiences were influenced by the perceived quality of health-care interactions with clinicians and their climacteric status. Limitations: Fewer than half of the original 571 participants participated; however, the cohort was clinically and demographically representative of the original trial population. Conclusions: Medical treatments for women with heavy menstrual bleeding can be initiated in primary care, with low rates of surgical intervention and improvement in quality of life observed 10 years later. Clinicians should be aware of the considerable challenges that women with heavy menstrual bleeding experience at presentation and subsequently over time, and the importance and value to women of patient-centred communication in this context. Future work: Any further evaluation of treatments for heavy menstrual bleeding should include long-term evaluation of outcomes and adherence. Trial registration: The original ECLIPSE trial was registered as ISRCTN86566246. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 17. See the NIHR Journals Library website for further project information.

Heavy menstrual bleeding is a common problem that can significantly affect women's lives, yet many women do not seek medical help. Medical treatments, such as tablets and a hormonal coil inserted in the womb, were shown to help women with heavy menstrual bleeding in a previous clinical trial that we conducted, called ECLIPSE. In the ECLIPSE trial, women provided information for 5 years after their treatment started. We planned to continue to ask these women about their periods, their symptoms and quality of life, and the treatments that they chose about 10 years after they first joined the trial. We did this using questionnaires and by interviewing women. We received questionnaires from 206 out of the 490 women (42%) who had participated in the ECLIPSE trial 10 years earlier. Responders were, on average, 54 years old, and half reported that they had reached the menopause. About 3 in 10 women overall had either received a hysterectomy or undergone destruction of the womb lining. Just over one-quarter of women were using the hormonal coil. Quality of life remained improved and was generally higher than that before treatment. There was no big difference in quality of life or in the numbers of women having surgery between those who first used tablets and those who received the coil. Women described the wide-ranging impact of heavy bleeding on their lives and the taboo around periods. Women's experience of good or poor communication with their doctors, and thoughts about fertility and menopause, influenced the treatment choices that they made. Women's quality of life was improved by medical treatments for heavy menstrual bleeding, even as menopause approached, and this shows the importance of these treatments. This research can help doctors and women to make more informed decisions about medical and surgical treatments.

Getting back to work after injury: the UK Burden of Injury multicentre longitudinal study.

BACKGROUND: Injuries to working age adults are common and place a considerable burden on health services accounting for more than 10% of GP sick notes and 14% of those claiming benefits because they are unable to work in the UK. General practitioners (GPs) currently assess fitness to work and provide care and referral to other services to facilitate return to work (RTW). Recent UK recommendations suggest replacing GP sickness certification with independent assessments of fitness to work after four weeks sick leave. The impact of a wide range of injuries on RTW and subsequent need for independent fitness to work assessments has not been well studied in the UK. The aim of this study was to quantify RTW and factors predicting RTW following a wide range of injuries. METHODS: We used a multicentre longitudinal study, set in four acute NHS Trusts in the UK which recruited emergency department (ED) attenders and hospital admissions for injury and included those aged 16-65years that were employed or self-employed before the injury. Participants were followed up by postal questionnaire at 1, 4 and 12 months post injury to measure health status (EQ-5D), recovery, use of health and social services, time off work in the preceding month and work problems amongst those who had RTW. Multivariable Poisson regression with a robust variance estimator was used to estimate relative risks for factors associated with RTW. RESULTS: One month after injury 35% of ED attenders had fully RTW. The self employed were more likely (RR 1.70, 95% CI 1.17 to 2.47 compared with employed) and the moderate/severely injured less likely to RTW (RR 0.48, 95% CI 0.32 to 0.72 compared with minor injuries). At four months, 83% of ED attenders had RTW and self employment and injury severity remained significant predictors of RTW (self employment RR 1.15, 95% CI 1.03 to 1.30; moderate/severe injury RR 0.79, 95% CI 0.68 to 0.92). At four months 57% of hospital admissions had RTW. Men were more likely than women to RTW (RR 1.94, 95% CI 1.34 to 2.82), whilst those injured at work (RR 0.49, 95% CI 0.27 to 0.87 compared with at home) and those living in deprived areas (most deprived tertile RR 0.59, 95% CI 0.40 to 0.85 and middle tertile RR 0.61, 95% CI 0.40 to 0.93) were less likely to RTW. Health status was significantly poorer at one and four months after injury than before the injury and was significantly poorer amongst those that had not RTW compared to those that had. Problems with pain control, undertaking usual activities, mobility and anxiety and depression were common and persisted in a considerable proportion of participants up to four months post injury. CONCLUSIONS: Injuries have a large impact on time off work, including amongst those whose injuries did not warrant hospital admission. The majority of injured people would require an in-depth fitness for work assessment if recent UK recommendations are implemented. Many people will have on-going pain, mobility problems, anxiety and depression at the point of assessment and it is important that patients are encouraged to use primary care services to address these problems. A range of factors may be useful for identifying those at risk of a slower recovery and a delayed RTW so that appropriate interventions can be provided to this group.

Risk of breast cancer with HRT depends on therapy type and duration.

The studyVinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ 2020;371:m3873. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/risk-of-breast-cancer-with-hrt-depends-therapy-type-and-duration/.

Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ≥60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies.

INTRODUCTION: Guidelines for type 2 diabetes (T2D) recommend individualized HbA1c targets to take into account patient age or frailty. We synthesized evidence from randomized controlled trials and observational studies for intensive glycemic control (HbA1c target ≤58 mmol/mol) versus standard care, in elderly (age ≥60 years) or frail adults with T2D. METHODS: Searches were performed utilizing recognized terms for T2D, frailty, older age, and HbA1c control and outcomes of interest. Meta-analysis was performed where possible. Primary outcomes included all-cause mortality, severe hypoglycemia, and hospital admission rates. Vascular complications, cognitive decline, and falls/fractures were secondary outcomes. RESULTS: 7,528 studies were identified of which 15 different clinical studies were selected. No difference was noted in all-cause mortality with intensive control (pooled hazard ratio 0.96, 95% confidence interval 0.90-1.03), but risk of severe hypoglycemia increased (2.45, 2.22-2.72). Intensive control was associated reductions in microvascular (0.73, 0.68-0.79) and macrovascular complications (0.84, 0.79-0.89). Outcome data for risk of hospitalization, cognition, and falls/fractures were limited. CONCLUSION: Intensive glycemic control was associated with reduced rates of complications but increased severe hypoglycemia. Significant heterogeneity exists and the impact of different drug regimens is unclear. Caution is needed when setting glycemic targets in elderly or frail individuals.

Medical treatment for heavy menstrual bleeding in primary care: 10-year data from the ECLIPSE trial.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem that can significantly affect women's lives. There is a lack of evidence on long-term outcomes after seeking treatment. AIM: To assess continuation rates of medical treatments and rates of surgery in women 10 years after initial management for HMB in primary care. DESIGN AND SETTING: This was a prospective observational cohort study. METHOD: Women with HMB who participated in the ECLIPSE primary care trial (ISRCTN86566246) completed questionnaires 10 years after randomisation to the levonorgestrel-releasing intrauterine system (LNG-IUS) or other usual medical treatments (oral tranexamic acid, mefenamic acid, combined oestrogen-progestogen; or progesterone alone). Outcomes were rates of surgery, medical treatments, and quality of life using the 36-item Short-Form Health Survey (SF-36) and EuroQoL EQ-5D. RESULTS: The responding cohort of 206 women was demographically and clinically representative of the original trial population. Mean age at baseline was 41.9 years (SD 4.9) and 53.7 years (SD 5.1) at follow-up. Over the 10-year follow-up, 60 of 206 (29.1%) women had surgery (hysterectomy n = 34, 16.5%; endometrial ablation n = 26, 12.6%). Between 5 and 10 years, 89 women (43.2%) ceased all medical treatments and 88 (42.7%) used LNG-IUS alone or in combination with other treatments. Fifty-six women (27.2%) were using LNG-IUS at 10 years. There were improvements over time in quality-of-life scores, with no evidence of differences in these or other outcomes between the two groups. CONCLUSION: Medical treatments for women with HMB can be successfully initiated in primary care, with low rates of surgery and improvement in quality of life observed a decade later.

Exposure to statins and risk of common cancers: a series of nested case-control studies.

BACKGROUND: Many studies and meta-analyses have investigated the effects of statins on cancer incidence but without showing consistent effects. METHODS: A series of nested case-control studies was conducted covering 574 UK general practices within the QResearch database. Cases were patients with primary cancers diagnosed between 1998 and 2008. The associations between statin use and risk of ten site-specific cancers were estimated with conditional logistic regression adjusted for co-morbidities, smoking status, socio-economic status, and use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors and aspirin. RESULTS: 88125 cases and 362254 matched controls were analysed. The adjusted odds ratio for any statin use and cancer at any site were 1.01 (95%CI 0.99 to 1.04). For haematological malignancies there was a significant reduced risk associated with any statin use (odds ratio 0.78, 95%CI 0.71 to 0.86). Prolonged (more than 4 years) use of statins was associated with a significantly increased risk of colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to 1.34). There were no significant associations with any other cancers. CONCLUSION: In this large population-based case-control study, prolonged use of statins was not associated with an increased risk of cancer at any of the most common sites except for colorectal cancer, bladder cancer and lung cancer, while there was a reduced risk of haematological malignancies.

Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases.

OBJECTIVE: To assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy. DESIGN: Two nested case-control studies. SETTING: UK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data. PARTICIPANTS: 118 501 women aged 55 and older with a primary diagnosis of dementia between 1998 and 2020, matched by age, general practice, and index date to 497 416 female controls. MAIN OUTCOME MEASURES: Dementia diagnoses from general practice, mortality, and hospital records; odds ratios for menopausal hormone treatments adjusted for demographics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. RESULTS: Overall, 16 291 (14%) women with a diagnosis of dementia and 68 726 (14%) controls had used menopausal hormone therapy more than three years before the index date. Overall, no increased risks of developing dementia associated with menopausal hormone therapy were observed. A decreased global risk of dementia was found among cases and controls younger than 80 years who had been taking oestrogen-only therapy for 10 years or more (adjusted odds ratio 0.85, 95% confidence interval 0.76 to 0.94). Increased risks of developing specifically Alzheimer's disease were found among women who had used oestrogen-progestogen therapy for between five and nine years (1.11, 1.04 to 1.20) and for 10 years or more (1.19, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10 000 woman years. Detailed risk associations for the specific progestogens studied are also provided. CONCLUSION: This study gives estimates for risks of developing dementia and Alzheimer's disease in women exposed to different types of menopausal hormone therapy for different durations and has shown no increased risks of developing dementia overall. It has shown a slightly increased risk of developing Alzheimer's disease among long term users of oestrogen-progestogen therapies.

Long-term oral prednisolone exposure in primary care for bullous pemphigoid: population-based study.

BACKGROUND: Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. AIM: To describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017. DESIGN AND SETTING: A prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK. METHOD: Oral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone. RESULTS: In total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4-24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059-6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%. CONCLUSION: A high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place.

Effects of severe mental illness on survival of people with diabetes.

BACKGROUND: People with mental health problems are more likely to die prematurely than the general population but no study has examined this in individuals with diabetes. AIMS: To compare survival rates in people with diabetes with and without schizophrenia or bipolar disorder. METHOD: A total of 43,992 people with diabetes were drawn from the QRESEARCH database population of over 9 million patients. Survival rates during the study period, between 1 April 2000 and 1 April 2005, and hazard ratios for deaths associated with schizophrenia and bipolar disorder were adjusted by age and gender and additionally for socioeconomic status, obesity, smoking and use of statins. RESULTS: Among the participants, we identified 257 people diagnosed with schizophrenia, 159 with bipolar disorder and 14 with both conditions. Although crude survival rates did not show significant differences between the groups during the study period, people with schizophrenia or bipolar disorder and diabetes, compared with those with diabetes alone, had a significantly increased risk of death after adjusting for age and gender, with hazard ratios for schizophrenia of 1.84 (95% CI 1.42-2.40) and for bipolar disorder of 1.51 (95% CI 1.10-2.07). After adjusting for the other factors, hazard ratios were 1.52 (95 CI 1.17-1.97) for schizophrenia and 1.47 (95% CI 1.07-2.02) for bipolar disorder. CONCLUSIONS: People with schizophrenia or bipolar disorder in addition to diabetes have a relatively higher mortality rate. This suggests that diabetes either progresses more rapidly or is more poorly controlled in these individuals, or that they have higher levels of comorbidity and so are more likely to die of other causes.

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.

OBJECTIVE: To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). DESIGN: Two nested case-control studies. SETTING: UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. PARTICIPANTS: 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 female controls. MAIN OUTCOME MEASURES: Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. RESULTS: Overall, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 women years. CONCLUSION: This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.

Validation study of bullous pemphigoid and pemphigus vulgaris recording in routinely collected electronic primary healthcare records in England.

OBJECTIVES: The validity of bullous pemphigoid and pemphigus vulgaris recording in routinely collected healthcare data in the UK is unknown. We assessed the positive predictive value (PPV) for bullous pemphigoid and pemphigus vulgaris primary care Read codes in the Clinical Practice Research Datalink (CPRD) using linked inpatient data (Hospital Episode Statistics (HES)) as the diagnostic benchmark. SETTING: Adult participants with bullous pemphigoid or pemphigus vulgaris registered with HES-linked general practices in England between January 1998 and December 2017. Code-based algorithms were used to identify patients from the CPRD and extract their benchmark blistering disease diagnosis from HES. PRIMARY OUTCOME MEASURE: The PPVs of Read codes for bullous pemphigoid and pemphigus vulgaris. RESULTS: Of 2468 incident cases of bullous pemphigoid and 431 of pemphigus vulgaris, 797 (32.3%) and 85 (19.7%) patients, respectively, had a hospitalisation record for a blistering disease. The PPV for bullous pemphigoid Read codes was 93.2% (95% CI 91.3% to 94.8%). Of the bullous pemphigoid cases, 3.0% had an HES diagnosis of pemphigus vulgaris and 3.8% of another blistering disease. The PPV for pemphigus vulgaris Read codes was 58.5% (95% CI 48.0% to 68.9%). Of the pemphigus vulgaris cases, 24.7% had an HES diagnosis of bullous pemphigoid and 16.5% of another blistering disease. CONCLUSIONS: The CPRD can be used to study bullous pemphigoid, but recording of pemphigus vulgaris needs to improve in primary care.

Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases.

OBJECTIVE: To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. DESIGN: Two nested case-control studies. SETTING: UK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data. PARTICIPANTS: 80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls. MAIN OUTCOME MEASURES: Venous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs. RESULTS: Overall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiol had a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01). CONCLUSIONS: In the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.