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.

An interrupted time-series analysis of the effects of withdrawal of financial incentives on diagnosis of atrial fibrillation as resolved. Does withdrawal of an incentive reverse its unintended effects?

BACKGROUND: The UK introduced financial incentives for management of atrial fibrillation (AF) in 2006, after which there was an increase in the proportion of patients with AF diagnosed as resolved. Removal of incentives in Scotland provides a natural experiment to investigate the effects of withdrawal of an incentive on diagnosis of resolved AF. AIM: To investigate the effects of introduction and withdrawal of financial incentives on the diagnosis of resolved AF. DESIGN & SETTING: Cohort study in a large database of UK primary care records, before and after introduction of incentives in April 2006 in Scotland, England, and Northern Ireland, and their withdrawal in April 2016 in Scotland. METHOD: Interrupted time-series analysis of monthly rates of resolved AF from January 2000-September 2019. RESULTS: A total of 251 526 adult patients with AF were included, of whom 14 674 were diagnosed as resolved AF. In April 2006 there were similar shift-changes in rates of resolved AF per 1000 in England 1.55 (95% confidence interval [CI] = 1.11 to 2.00) and Northern Ireland 1.54 (95% CI = 0.91 to 2.18), and a smaller increase in Scotland 0.79 (95% CI = 0.04 to 1.53). There were modest downward post-introduction trends in all countries. After Scotland's withdrawal of the incentive in April 2016 there was a small, statistically non-significant, downward shift in rate of resolved AF per 1000 (0.39 [95% CI = -3.21 to 2.42]) and no change in post-removal trend. CONCLUSION: Introduction of a financial incentive coincided with an increase in resolved AF but no evidence was found that its withdrawal led to a reduction.

Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study.

BACKGROUND AND OBJECTIVES: Physician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared to matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared to population controls. METHODS: We performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from 1st January 1995 to 25th September 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: 3411 women with IIH, 13,966 migraine controls and 33,495 population controls were included. The adjusted hazard ratio (aHR) for new onset headache in IIH compared to population controls was 3.09 (95%CI 2.78-3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after six years, compared to 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared to migraine controls and three times as many women with IIH were prescribed opiates compared to population controls. Women with IIH were also prescribed more headache preventative medications compared to migraine controls. DISCUSSION: Women with IIH were more likely to be prescribed opiate and simple analgesics compared to both migraine and population controls. Women with IIH trialled more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.

The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.

INTRODUCTION: To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes. METHODS: Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. RESULTS: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively. CONCLUSIONS: Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.

Trends in the pharmacological management of atrial fibrillation in UK general practice 2008-2018.

OBJECTIVE: The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018. METHODS: Eleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure. RESULTS: Between 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%). CONCLUSIONS: There has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.

Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK.

OBJECTIVES: The objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of comorbidities and to examine the associations between these clusters and mortality. METHODS: Longitudinal analysis of electronic health records in the health improvement network (THIN), a UK primary care database including 92 186 men and women aged ≥18 years with IHD and a median of 2 (IQR 1-3) comorbidities. RESULTS: Latent class analysis revealed five clusters with half categorised as a low-burden comorbidity group. After a median follow-up of 3.2 (IQR 1.4-5.8) years, 17 645 patients died. Compared with the low-burden comorbidity group, two groups of patients with a high-burden of comorbidities had the highest adjusted HR for mortality: those with vascular and musculoskeletal conditions, HR 2.38 (95% CI 2.28 to 2.49) and those with respiratory and musculoskeletal conditions, HR 2.62 (95% CI 2.45 to 2.79). Hazards of mortality in two other groups of patients characterised by cardiometabolic and mental health comorbidities were also higher than the low-burden comorbidity group; HR 1.46 (95% CI 1.39 to 1.52) and 1.55 (95% CI 1.46 to 1.64), respectively. CONCLUSIONS: This analysis has identified five distinct comorbidity clusters in patients with IHD that were differentially associated with risk of mortality. These analyses should be replicated in other large datasets, and this may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.

Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016.

OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important risk factor for stroke. Treatment with anticoagulants substantially reduces risk of stroke. Current prevalence and treatment rates of AF in the UK as well as changes in recent years are not known. The aim of this analysis was to determine trends in age-sex specific prevalence and treatment of AF in the UK from 2000 to 2016. METHODS: 17 sequential cross-sectional analyses were carried out between 2000 and 2016 using a large database of electronic primary care records of patients registered with UK general practitioners. These determined the prevalence of patients diagnosed with AF, the stroke risk of those with AF and the proportion of AF patients currently receiving anticoagulants. Stroke risk was assessed using CHA2DS2-VASc score. RESULTS: Age-sex standardised AF prevalence increased from 2.14% (95% CI 2.11% to 2.17%) in 2000 to 3.29% (95% CI 3.27% to 3.32%) in 2016. Between 2000 and 2016, the proportion of patients with AF prescribed anticoagulants increased from 35.4% (95% CI 34.7% to 36.1%) to 75.5% (95% CI 75.1% to 75.8%) in those with high stroke risk (p for change over time <0.001) and from 32.8% (95% CI 30.5% to 35.2%) to 47.1% (95% CI 45.4% to 48.7%) in those with moderate stroke risk (p<0.001). In patients with low risk of stroke, the proportion decreased from 19.9% (95% CI 17.8% to 22.2%) to 9.7% (95% CI 8.4% to 11.1%) (p<0.001). Anticoagulant prescribing performance varied between practices; in 2016, the proportion of eligible patients treated was 82.9% (95% CI 82.2% to 83.7%) and 62.0% (95% CI 61.0% to 63.0%) in the highest-performing and lowest-performing practice quintiles, respectively. There was poor agreement in individual practice performance over time from 2006 to 2016: linear-weighted κ=0.10 (95% CI 0.02 to 0.19). CONCLUSIONS: From 2000 to 2016, the prevalence of recorded AF has increased in all age groups and both sexes. Anticoagulant treatment of eligible patients with AF has more than doubled, with marked improvements since 2011, alongside a reduction in the use of anticoagulants in ineligible patients with AF.

The treatment of paroxysmal atrial fibrillation in UK primary care.

OBJECTIVE: To determine whether patients with paroxysmal atrial fibrillation (AF) are less likely to be treated with anticoagulants than patients with persistent/permanent AF and to investigate trends in treatment between 2000 and 2015. UK and European guidelines recommend that anticoagulants are offered to all patients with AF at increased risk of stroke, irrespective of AF type. METHODS: Sixteen sequential cross-sectional analyses from 2000 to 2015 were carried out with index dates on 1st of May each year. The data source was primary care data from 648 practices across the UK contributing to The Health Improvement Network database. All patients with a diagnosis of AF aged ≥35 years and registered for at least 1 year were included. The main outcome measure was prescription of anticoagulant medication. RESULTS: The proportion of patients with AF with a diagnosis of paroxysmal AF increased from 7.4% (95% CI 7.0 to 7.8) in 2000 to 14.0% (95% CI 13.7 to 14.3) in 2015. Among patients with a CHADS2 score of ≥1, between 2000 and 2015 the proportion prescribed anticoagulants increased from 18.8% (95% CI 16.4 to 21.4) to 56.2% (95% CI 55.0 to 57.3) and from 34.2% (95% CI 33.3 to 35.0) to 69.4% (95% CI 68.9 to 69.8) in patients with paroxysmal and other (persistent/permanent) AF, respectively; RR for treatment of patients with paroxysmal AF compared with patients with other AF increased from 0.48 (95% CI 0.42 to 0.55) to 0.76 (95% CI 0.74 to 0.77). Adjusting for age, sex, Townsend score and presence or absence of contraindications had little effect on the results. CONCLUSIONS: In 2000, eligible patients with paroxysmal AF were half as likely to be treated with anticoagulants as patients with other AF; this has improved over time, but in 2015, eligible patients with paroxysmal AF were still around 20% less likely to be prescribed anticoagulant medication.