A Comparison of Sodium-Glucose Co-Transporter 2 Inhibitor Kidney Outcome Trial Participants with a Real-World Chronic Kidney Disease Primary Care Population.

BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. METHODS: A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. RESULTS: Of 6,670,829 adults, 516,491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared to less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. CONCLUSION: SGLT2 inhibitor kidney outcome trials represent a sub-group of people with CKD at high risk of adverse kidney events. Out study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD.

Sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Are clinical trial benefits for heart failure reflected in real-world clinical practice? A systematic review and meta-analysis of observational studies.

AIM: To determine the absolute risk reduction (ARR) of heart failure events in people treated with sodium-glucose co-transporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS: We searched PubMed, EMBASE, CINAHL and ISI Web of Science for observational studies published to 9 May 2022 that explored the association between SGLT2 inhibitors and any indication for heart failure (including new diagnosis or hospitalization for heart failure) in type 2 diabetes. Identified studies were independently screened by two reviewers and assessed for bias using the Newcastle-Ottawa scale. Eligible studies with comparable outcome data were pooled for meta-analysis using random-effects models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). The ARR per 100 person-years was determined overall, and in subgroups with and without baseline cardiovascular disease (CVD). RESULTS: From 43 eligible studies, with a total of 4 818 242 participants from 17 countries, 21 were included for meta-analysis. SGLT2 inhibitors were associated with a reduced risk of hospitalization for heart failure (HR 0.65, 95% CI 0.59-0.72) overall and both in those with CVD (HR 0.78, 95% CI 0.68-0.89) and without CVD (HR 0.53, 95% CI 0.39-0.71). Risk reduction for hospitalization for heart failure in people with a history of CVD (ARR 1.17, 95% CI 0.78-1.55) was significantly greater than for those without CVD (ARR 0.39, 95% CI 0.32-0.47). The number-needed-to-treat to prevent one event of hospitalization for heart failure was 86 (95% CI 65-128) person-years of treatment for the CVD group and 256 (95% CI 215-316) person-years for those without CVD. CONCLUSIONS: Real-world SGLT2 inhibitor use supports randomized trial data for the size effect of reduced hospitalization for heart failure in type 2 diabetes, although with a much lower ARR in people without CVD.

Early and ongoing stable glycaemic control is associated with a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study.

AIM: To determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE). MATERIALS AND METHODS: A retrospective cohort analysis from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database-a large, English primary care network-was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%-9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time-varying Cox proportional hazards models, which included the first-year transition and the glycaemic variability score. RESULTS: From 26 180 patients, there were 2300 MACE. Compared with group A->A transition over 1 year, those with C->A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60-0.94; P = .014), whereas group C->C had HR 1.21 (0.81-1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11-2.06; P = .0096). CONCLUSION: Early control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.

Authoritarian Regime Legitimacy and Health Care Provision: Survey Evidence from Contemporary China.

CONTEXT: Over the last two decades a growing body of research has shown that authoritarian regimes are trying to increase their legitimacy by providing public goods. But there has so far been very little research on whether or not these regimes are successful. METHODS: This article analyzes data from a 2012-2013 nationally representative survey in China to examine whether health care provision bolsters the Communist regime's legitimacy. Using multivariate ordinal logistic regression, we test whether having public health insurance and being satisfied with the health care system are associated with separate measures of the People's Republic of China's regime legitimacy: support for "our form of government" (which we call "system support") and political trust. FINDINGS: Having public health insurance is positively associated with trust in the Chinese central government. Health care system satisfaction is positively associated with system support and trust in local government. CONCLUSIONS: Health care provision may bolster the legitimacy of authoritarian regimes, with the clearest evidence showing that concrete benefits may translate into trust in the central government. Further research is needed to understand the relationship between trends in health care provision and legitimacy over time and in other types of authoritarian regime.

Prescribing sodium-glucose co-transporter-2 inhibitors for type 2 diabetes in primary care: influence of renal function and heart failure diagnosis.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are licenced for initiation for glucose lowering in people with type 2 diabetes (T2DM) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2). However, recent trial data have shown that these medications have renal and cardio-protective effects, even for impaired kidney function. The extent to which trial evidence and updated guidelines have influenced real-world prescribing of SGLT-2is is not known, particularly with co-administration of diuretics. METHODS: We performed a cross-sectional analysis of people with T2DM registered with practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database on the 31st July 2019. We calculated the percentage of people prescribed SGLT-2is according to eGFR categories (< 45, 45-59, and ≥ 60 mL/min/1.73m2), with a heart failure diagnosis and stratified by body mass index categories (underweight, normal weight, overweight, obese), and with concomitant prescription of a diuretic. Multilevel logistic regression analysis was performed to determine whether heart failure diagnosis and renal function were associated with SGLT-2i prescribing. RESULTS: From a population of 242,624 people with T2DM across 419 practices, 11.0% (n = 26,700) had been prescribed SGLT-2is. The majority of people initiated SGLT-2is had an eGFR ≥ 60 mL/min/1.73m2 (93.2%), and 4.3% had a heart failure diagnosis. 9,226 (3.8%) people were prescribed SGLT-2is as an add-on to their diuretic prescription. People in the highest eGFR category (≥ 60 mL/min/1.73m2) were more likely to be prescribed SGLT-2is than those in eGFR lower categories. Overweight (OR 2.05, 95% CI 1.841-2.274) and obese people (OR 3.84, 95% CI 3.472-4.250) were also more likely to be prescribed these medications, whilst use of diuretics (OR 0.74, 95% CI 0.682-0.804) and heart failure (OR 0.81, 95% CI 0.653-0.998) were associated with lower odds of being prescribed SGLT-2is. CONCLUSIONS: Prescribing patterns of SGLT-2is for glucose lowering in T2DM in primary care generally concur with licenced indications according to recommended renal thresholds. A small percentage of people with heart failure were prescribed SGLT-2is for T2DM. An updated analysis is merited should UK National Institute for Health Care and Excellence prescribing guidelines for T2DM be revised to incorporate new data on the benefits for those with reduced renal function or with heart failure.

Effect of type 1 diabetes and type 2 diabetes on the risk of venous thromboembolism.

AIMS: Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk. METHODS: Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE. RESULTS: There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14). CONCLUSIONS: Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.

Disparities in glycaemic control, monitoring, and treatment of type 2 diabetes in England: A retrospective cohort analysis.

BACKGROUND: Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D. METHODS AND FINDINGS: A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation. CONCLUSIONS: Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups.

Real-world prevalence of the inclusion criteria for the LEADER trial: Data from a national general practice network.

AIMS: To explore the prevalence and describe the clinical characteristics of people with type 2 diabetes with a similar cardiovascular (CV) profile to that of the LEADER trial participants in a primary care setting in England. MATERIALS AND METHODS: In this cross-sectional analysis, using the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, we identified people with type 2 diabetes meeting the LEADER inclusion criteria. We identified people's CV risk factors using computerized medical records. Additionally, we assessed the prescription pattern of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this cohort. RESULTS: Of 1 275 461 adults, we identified 84 394 with type 2 diabetes, of whom 14 000 (16.6%) met the LEADER inclusion criteria for established or high-risk CV disease (RCGP RSC-CVD group). The LEADER cohort was younger than the RCGP RSC-CVD group (64.2 vs 73.2 years), had higher mean glycated haemoglobin (71.6 vs 67.1 mmol/mol) and blood pressure (BP) values (systolic BP: 135.9 vs 132.9 mmHg; diastolic BP: 77.2 vs 72.7 mmHg), and a higher mean body mass index (32.5 vs 30.9 kg/m2 ). In the RCGP RSC-CVD group, only 1215 people (8.7%) had ever been prescribed a GLP-1RA and 760 (5.4%) had ever received liraglutide. CONCLUSIONS: In a cohort of English general practice patients, one in six people with type 2 diabetes met the LEADER inclusion criteria, and less than one in 10 of these received liraglutide, a drug which has demonstrated CV benefits amongst others. There is scope to improve the outlook in people with type 2 diabetes and high CV risk through evidence-based use of specific GLP-1RAs.

Intensification to injectable therapy in type 2 diabetes: mixed methods study (protocol).

BACKGROUND: In the UK, type 2 diabetes mellitus (T2D) is largely managed in primary care. Delay in the intensification to injectable therapy, a form of clinical inertia, is associated with worse glycaemic control. UK general practice is highly computerised, with care being recorded on computerised medical record systems; this allows for quantitative analysis of clinical care but not of the underpinning decision-making process. The aim of this study is to investigate perceptions of patients and clinicians in primary care on the initiation of injectable therapies in T2D, and the context within which those decisions are made. METHODS: This is a mixed methods study, taking a "realist evaluation" approach. The qualitative components comprise focus groups, interviews, and video recordings of simulated surgeries; the quantitative analysis: an overview of participating practices, elements of the video recording, and an online survey. We will recruit primary care clinicians (general practitioners and nurses) and patients from a representative sample of practices within the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. Participants will be patients with T2D, and primary care clinicians. Focus groups and semi-structured interviews will be recorded, transcribed verbatim and analysed using Framework Analysis. The simulated surgeries will include cases that might be escalated to injectable therapy. The consultation will be reviewed using the Calgary-Cambridge model to assess communication and determination of adherence to national prescribing guidelines. We will conduct multi-channel video recording including screen capture, clinician and patient facial expressions, wide angle view of the consultation, and the computerised medical record screen. This allows annotation and qualitative analysis of the video recordings, and statistical analyses for the quantitative data. We will also conduct an online survey of primary care clinicians' attitudes to, and perceptions of, initiation of injectable therapies, which will be analysed using summary statistics. DISCUSSION: Results aim to provide a detailed insight into the dynamic two-way decision-making process underpinning use of injectable therapy for T2D. The study will provide insights into clinical practice and enable the development of training, interventions and guidelines that may facilitate, where appropriate, the intensification to injectable therapy.

Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis.

Limited medication adherence and persistence with treatment are barriers to successful management of type 2 diabetes (T2D). We searched MEDLINE, EMBASE, the Cochrane Library, the Register of Controlled Trials, PsychINFO and CINAHL for observational and interventional studies that compared the adherence or persistence associated with 2 or more glucose-lowering medications in people with T2D. Where 5 or more studies provided the same comparison, a random-effects meta-analysis was performed, reporting mean difference (MD) or odds ratio (OR) for adherence or persistence, depending on the pooled study outcomes. We included a total of 48 studies. Compared with metformin, adherence (%) was better for sulphonylureas (5 studies; MD 10.6%, 95% confidence interval [CI] 6.5-14.7) and thiazolidinediones (TZDs; 6 studies; MD 11.3%, 95% CI 2.7%-20.0%). Adherence to TZDs was marginally better than adherence to sulphonylureas (5 studies; MD 1.5%, 95% CI 0.1-2.9). Dipeptidyl peptidase-4 inhibitors had better adherence than sulphonylureas and TZDs. Glucagon-like peptide-1 receptor agonists had higher rates of discontinuation than long-acting analogue insulins (6 studies; OR 1.95; 95% CI 1.17-3.27). Long-acting insulin analogues had better persistence than human insulins (5 studies; MD 43.1 days; 95% CI 22.0-64.2). The methods used to define adherence and persistence were highly variable.

Explaining public satisfaction with health-care systems: findings from a nationwide survey in China.

OBJECTIVE: To identify factors associated with health-care system satisfaction in China. CONTEXT: Recent research suggests that socio-demographic characteristics, self-reported health, income and insurance, ideological beliefs, health-care utilization, media use and perceptions of services may affect health-care system satisfaction, but the relative importance of these factors is poorly understood. New data from China offer the opportunity to test theories about the sources of health-care system satisfaction. DESIGN: Stratified nationwide survey sample analysed using multilevel logistic regression. SETTING AND PARTICIPANTS: 3680 Chinese adults residing in family dwellings between 1 November 2012 and 17 January 2013. MAIN OUTCOME MEASURE: Satisfaction with the way the health-care system in China is run. RESULTS: We find only weak associations between satisfaction and socio-demographic characteristics, self-reported health and income. We do, however, find that satisfaction is strongly associated with having insurance and belief in personal responsibility for meeting health-care costs. We also find it is negatively associated with utilization, social media use, perceptions of access as unequal and perceptions of service providers as unethical. CONCLUSIONS: To improve satisfaction, Chinese policymakers - and their counterparts in countries with similar health-care system characteristics - should improve insurance coverage and the quality of health services, and tackle unethical medical practices.

Impact of Information Technology-Based Interventions for Type 2 Diabetes Mellitus on Glycemic Control: A Systematic Review and Meta-Analysis.

BACKGROUND: Information technology-based interventions are increasingly being used to manage health care. However, there is conflicting evidence regarding whether these interventions improve outcomes in people with type 2 diabetes. OBJECTIVE: The objective of this study was to conduct a systematic review and meta-analysis of clinical trials, assessing the impact of information technology on changes in the levels of hemoglobin A1c (HbA1c) and mapping the interventions with chronic care model (CCM) elements. METHODS: Electronic databases PubMed and EMBASE were searched to identify relevant studies that were published up until July 2016, a method that was supplemented by identifying articles from the references of the articles already selected using the electronic search tools. The study search and selection were performed by independent reviewers. Of the 1082 articles retrieved, 32 trials (focusing on a total of 40,454 patients) were included. A random-effects model was applied to estimate the pooled results. RESULTS: Information technology-based interventions were associated with a statistically significant reduction in HbA1c levels (mean difference -0.33%, 95% CI -0.40 to -0.26, P<.001). Studies focusing on electronic self-management systems demonstrated the largest reduction in HbA1c (0.50%), followed by those with electronic medical records (0.17%), an electronic decision support system (0.15%), and a diabetes registry (0.05%). In addition, the more CCM-incorporated the information technology-based interventions were, the more improvements there were in HbA1c levels. CONCLUSIONS: Information technology strategies combined with the other elements of chronic care models are associated with improved glycemic control in people with diabetes. No clinically relevant impact was observed on low-density lipoprotein levels and blood pressure, but there was evidence that the cost of care was lower.

Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes: Protocol for a Kidney End Points Real-world Study (COMBi-KID Study).

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are both considered to be part of standard care in the management of glycemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary kidney end points for individual drugs within each medication class. Despite the potential benefits of combining SGLT2is and GLP-1RAs for glycemia management, according to national and international guideline recommendations, there is currently limited data on kidney end points for this drug combination. OBJECTIVE: The aims of the study are to assess the real-world effects of combination SGLT2i and GLP-1RA therapies for diabetes management on kidney end points, glycemic control, and weight in people with type 2 diabetes who are being treated with renin-angiotensin system blockade medication. METHODS: This retrospective cohort study will use the electronic health records of people with type 2 diabetes that are registered with general practices covering over 15 million people in England and Wales and are included in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network. A propensity score-matched cohort of prevalent new users of SGLT2is and GLP-1RAs and those who have been prescribed SGLT2is and GLP-1RAs in combination will be identified. They will be matched based on drug histories, comorbidities, and demographics. A repeated-measures, multilevel, linear regression analysis will be performed to compare the mean change (from baseline) in estimated glomerular filtration rate at 12 and 24 months between those who switched to combined therapy and those continuing monotherapy with an SGLT2i or GLP-1RA. The secondary end points will be albuminuria, serum creatinine level, glycated hemoglobin level, and BMI. These will also be assessed for change at the 12- and 24-month follow-ups. RESULTS: The study is due to commence in March 2022 and is expected to be complete by September 2022. CONCLUSIONS: Our study will be the first to assess the impact of combination SGLT2i and GLP-1RA therapy in type 2 diabetes on primary kidney end points from a real-world perspective. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34206.

Barriers and Facilitators to the Initiation of Injectable Therapies for Type 2 Diabetes Mellitus: A Mixed Methods Study.

INTRODUCTION: Initiation of injectable therapies in type 2 diabetes (T2D) is often delayed, however the reasons why are not fully understood. METHODS: A mixed methods study performed in sequential phases. Phase 1: focus groups with people with T2D (injectable naïve [n = 12] and experienced [n = 5]) and healthcare professionals (HCPs; nurses [n = 5] and general practitioners (GPs) [n = 7]) to understand their perceptions of factors affecting initiation of injectables. Phase 2: video-captured GP consultations (n = 18) with actor-portrayed patient scenarios requiring T2D treatment escalation to observe the initiation in the clinical setting. Phase 3: HCP surveys (n = 87) to explore external validity of the themes identified in a larger sample. RESULTS: Focus groups identified patients' barriers to initiation; fear, lack of knowledge and misconceptions about diabetes and treatment aims, concerns regarding lifestyle restrictions and social stigma, and feelings of failure. Facilitators included education, good communication, clinician support and competence. HCP barriers included concerns about weight gain and hypoglycaemia, and limited consultation time. In simulated consultations, GPs performed high-quality consultations and recognised the need for injectable initiation in 9/12 consultations where this was the expert recommended option but did not provide support for initiation themselves. Survey results demonstrated HCPs believe injectable initiation should be performed in primary care, although many practitioners reported inability to do so or difficulty in maintaining skills. CONCLUSION: People with T2D have varied concerns and educational needs regarding injectables. GPs recognise the need to initiate injectables but lack practical skills and time to address patient concerns and provide education. Primary care nurses also report difficulties in maintaining these skills. Primary care HCPs initiating injectables require additional training to provide practical demonstrations, patient education and how to identify and address concerns. These skills should be concentrated in the hands of a small number of primary care providers to ensure they can maintain their skills.

Canomad presenting without ophthalmoplegia and responding to intravenous immunoglobulin.

The acronym CANOMAD encompasses chronic ataxic neuropathy combined with ophthalmoplegia, M protein, cold agglutinins, and anti-disialosyl antibodies.Herein we describe 2 patients presenting with progressive ataxic neuropathy who only developed ophthalmoplegia after a significant delay post-presentation, which in 1 case had features indicative of brainstem dysfunction. Both patients were found to have an IgM paraprotein and anti-disialosyl antibodies. They responded to treatment with intravenous immunoglobulin, thus illustrating the importance of diagnosing this condition.

Diabetic retinopathy in newly diagnosed Type 2 diabetes mellitus: Prevalence and predictors of progression; a national primary network study.

AIMS: To determine, inreal-world primary care settings, the prevalence of, and risk factors for, retinopathy atType 2 diabetes mellitus diagnosis and report cumulative incidence and progression of retinopathy seven years after diabetes diagnosis. METHODS: Retrospective cohort analysis of people with newly diagnosed Type 2 diabetesrecorded bythe Royal College of General Practitioners Research and Surveillance Centre(between 2005 and 2009, n=11,399).Outcomes included; retinopathy prevalence atdiabetesdiagnosis (baseline) and cumulative incidence or progression of retinopathy at seven years. Retinopathy prevalence was compared with the United Kingdom Prospective Diabetes Study (UKPDS-1998). Factors influencing retinopathy incidence and progression were analysed using logistic regression. RESULTS: Baseline retinopathy prevalencewas 18% (n=2,048) versus 37% in UKPDS. At seven years, 11.6% (n=237) of those with baseline retinopathyhad progression of retinopathy. In those without baseline retinopathy, 46.4% (n=4,337/9,351) developed retinopathy by seven years. Retinopathy development (OR: 1.05 [95%CI: 1.02-1.07] per mmol/mol increase) and progression (OR: 1.05 [1.04-1.06]) at seven years was associated with higher HbA1catdiabetesdiagnosis. Obesity (OR: 0.88 [0.79-0.98]) and high socioeconomic status (OR: 0.63 [0.53-0.74]) were negatively associated with retinopathy development at seven years. CONCLUSIONS: Baseline retinopathy prevalence has declined since UKPDS. Additionally, HbA1c at diabetes diagnosis remains important for retinopathy development and progression.

Dashboards to reduce inappropriate prescribing of metformin and aspirin: A quality assurance programme in a primary care sentinel network.

AIMS: To pilot two dashboards to monitor prescribing of metformin and aspirin according to the National Institute for Health and Care Excellence (NICE) 'Do-Not-Do' recommendations. METHODS: This quality assurance programme was conducted in twelve general practices of the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. We developed dashboards to flag inappropriate prescribing of metformin and aspirin to people with type 2 diabetes mellitus (T2DM). In Phase 1, six practices (Group A) received a dashboard flagging suboptimal metformin prescriptions in people with reduced renal function. The other six practices (Group B) were controls. In Phase 2, Group B were provided a dashboard to flag inappropriate aspirin prescribing and Group A were controls. We used logistic regression to explore associations between dashboard exposure and inappropriate prescribing. RESULTS: The cohort comprised 5644 individuals (Group A, n = 2656; Group B, n = 2988). Half (51.6%, n = 2991) were prescribed metformin of which 15 (0.5%) were inappropriate (Group A, n = 10; Group B, n = 5). A fifth (17.6%, n = 986) were prescribed aspirin of which 828 (84.0%) were inappropriate. During Phase 1, metformin was stopped in 50% (n = 5) of people in Group A, compared with 20% (n = 1) in the control group (Group B); in Phase 2, the odds ratio of inappropriate aspirin prescribing was significantly lower in practices that received the dashboard versus control (0.44, 95%CI 0.27-0.72). CONCLUSIONS: It was feasible to use a dashboard to flag inappropriate prescribing. Whilst underpowered to report a change in metformin, we demonstrated a reduction in inappropriate aspirin prescribing.

Alcohol and Parasomnias: The Statistical Evaluation of the Parasomnia Defense in Sexual Assault, Where Alcohol is Involved.

Sleep sex may be a defense for alleged sexual assault. The International Classification of Sleep Disorders (ICSD3) states: "Disorders of arousal should not be diagnosed in the presence of alcohol intoxication… The former [alcohol blackouts] are exponentially more prevalent." A panel member of ICSD3, quoting ICSD3 asserts: "alcohol intoxication should rule out a sleep-walking defense". This implies extremely strong support for a prosecution hypothesis (Hp ) over a defense hypothesis (Hd ). I use Bayesian methodology to evaluate the evidential probity of alcohol intoxication. The likelihood ratio, LR, measures the amplification of prior odds of guilt, LR = Posterior odds of guilt after considering alcohol intoxication /Prior odds of guilt before considering alcohol intoxication . By Bayes' theorem, LR = p ( alcohol intoxication, given H p ) / p ( alcohol intoxication, given H d ) . I use data from cross-sectional studies of sexual assault and prevalence of alcohol use, in college students, with data from longitudinal studies, and data from the epidemiology of parasomnias to evaluate LR (alcohol). LR ~1.5 or 5, depending whether alcohol does, or does not, increase the risk of parasomnias. The proposition of extremely strong support for Hp implies a LR ~1,000,000, so the proposition in ICSD3 is not supported by formal analysis. The statistical reasoning in ICSD3 is unclear. There appears to be inversion of the Bayesian conditional (confusing intoxication given assault, and assault given intoxication) and failure to evaluate alcohol intoxication in Hd . Similar statistical errors in R. v Sally Clark are discussed. The American Academy of Sleep Medicine should review the statistical methodology in ICSD3.

Does Renal Function or Heart Failure Diagnosis Affect Primary Care Prescribing for Sodium-Glucose Co-Transporter 2 Inhibitors in Type 2 Diabetes?

INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are a unique class of drugs currently used in the management of type 2 diabetes (T2D). There are emerging data from cardiovascular outcome trials confirming renal and heart failure benefits of these drugs independent of glucose lowering. By contrast, the current licencing indications of these drugs are mainly limited to their glucose-lowering effects, and not to renal or heart failure benefits. It is therefore timely to ascertain whether the presence of these clinical conditions may influence prescribing choices for patients with T2D. Our aims are to report prescribing of SGLT2is in people with T2D according to their renal function and presence of heart failure. Co-prescribing with diuretics will also be explored. METHODS: We will perform a cross-sectional analysis of people with T2D in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. The RCGP RSC includes more than 1500 volunteer practices throughout England and parts of Wales, and a representative sample of over 10 million patients. The proportion of adults with T2D ever prescribed an SGLT2i will be determined. Within this cohort, we will calculate the percentage of SGLT2is prescribed according to renal function, and the proportion of prescriptions in people with co-morbid heart failure, stratified by body mass index categories. The percentage of SGLT2is prescribed as an add-on to a diuretic or following discontinuation of prescribing for a diuretic will also be reported. Multilevel logistic regression will be performed to explore the association between heart failure and renal function, and propensity to prescribe SGLT2is. PLANNED OUTPUTS: The study findings will be submitted to a primary care/diabetes-focused conference, and for publication in a peer reviewed journal.

Improving the Management of Atrial Fibrillation in General Practice: Protocol for a Mixed Methods Study.

BACKGROUND: Atrial fibrillation (AF) is one of the commonest arrhythmias observed in general practice. The thromboembolic complications of AF include transient ischemic attack, stroke, and pulmonary embolism. Early recognition of AF can lead to early intervention with managing the risks of these complications. OBJECTIVE: The primary aim of this study is to investigate if patients are managed in general practice according to current national guidelines. In addition, the study will evaluate the impact of direct oral anticoagulant use with respect to AF complications in a real-world dataset. The secondary aims of the study are to develop a dashboard that will allow monitoring the management of AF in general practice and evaluate the usability of the dashboard. METHODS: The study was conducted in 2 phases. The initial phase was a quantitative analysis of routinely collected primary care data from the Oxford Royal College of General Practitioners Research and Surveillance Center (RCGP RSC) sentinel network database. AF cases from 2009 to 2019 were identified. The study investigated the impact of the use of anticoagulants on complications of AF over this time period. We used this dataset to examine how AF was managed in primary care during the last decade. The second phase involved development of an online dashboard for monitoring management of AF in general practice. We conducted a usability evaluation for the dashboard to identify usability issues and performed enhancements to improve usability. RESULTS: We received funding for both phases in January 2019 and received approval from the RCGP RSC research committee in March 2019. We completed data extraction for phase 1 in May 2019 and completed analysis in December 2019. We completed building the AF dashboard in May 2019. We started recruiting participants for phase 1 in May 2019 and concluded data collection in July 2019. We completed data analysis for phase 2 in October 2019. The results are expected to be published in the second half of 2020. As of October 2020, the publications reporting the results are under review. CONCLUSIONS: Results of this study will provide an insight into the current trends in management of AF using real-world data from the Oxford RCGP RSC database. We anticipate that the outcomes of this study will be used to guide the development and implementation of an audit-based intervention tool to assist practitioners in identifying and managing AF in primary care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/21259.