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 cotransporter-2 inhibitors and kidney outcomes in real-world type 2 diabetes populations: A systematic review and meta-analysis of observational studies.

AIM: To conduct a systematic review of observational studies to explore the real-world kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in a large and diverse population of adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We searched MEDLINE, EMBASE and Web of Science for observational studies that investigated kidney disease progression in adults with T2D treated with SGLT2 inhibitors compared to other glucose-lowering therapies. Studies published from database inception to July 2022 were independently reviewed by two authors and evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. A random-effects meta-analysis was performed on studies with comparable outcome data, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: We identified 34 studies performed across 15 countries with a total population of 1 494 373 for inclusion. In the meta-analysis of 20 studies, SGLT2 inhibitors were associated with a 46% lower risk of kidney failure events compared with other glucose-lowering drugs (HR 0.54, 95% CI 0.47-0.63). This finding was consistent across multiple sensitivity analyses and was independent of baseline estimated glomerular filtration rate (eGFR) or albuminuria status. SGLT2 inhibitors were associated with a lower risk of kidney failure when compared with dipeptidyl peptidase-4 inhibitors and a combination of other glucose-lowering drug classes (HR 0.50, 95% CI 0.38-0.67 and HR 0.51, 95% CI 0.44-0.59, respectively). However, when compared to glucagon-like peptide 1 receptor agonists there was no statistically significant difference in the risk of kidney failure (HR 0.93, 95% CI 0.80-1.09). CONCLUSIONS: The reno-protective benefits of SGLT2 inhibitors apply to a broad population of adults with T2D treated in routine clinical practice, including those at lower risk of kidney events with normal eGFR and without albuminuria. These findings support the early use of SGLT2 inhibitors in T2D for preservation of kidney health.

A preliminary investigation of digital media supplements for head and neck anatomy: Does production format matter?

From cassettes to digital, use of video in education has evolved. Supplemental digital media is a common educational adjunct within gross anatomy courses. As these aids have advanced technologically, so has production cost. Traditional lecture (T-lect) productions tend to be more efficient. Traditional gross anatomy laboratory (T-lab) productions requiring cadaver dissection and high-definition video are comparatively less efficient. This preliminary study pragmatically assessed T-lect and T-lab supplemental learning tools in a head and neck anatomy course for first-year dental students. Two videos of similar length were developed for different anatomical regions. Learning objectives were similar while format differed. A carotid triangle supplement was created using a T-lab production format and an infratemporal fossa aid was created using a T-lect format. Both incorporated recommended elements for facilitating learning. Development time and costs were documented. Student exam performance on topic specific questions was collected along with survey data. Group mean exam score comparisons between students who viewed (n = 74 T-lect, n = 70 T-lab) versus did not view (n = 27 T-lect, n = 30 T-lab) each aid revealed higher scores for the "viewed" group. The T-lab production cost ($15,190 versus $10,003) and time (19 hr. versus 18 hr) were greater than T-lect. Descriptive survey data did not reveal a format preference. Students valued previews/summaries and structure highlighting/labeling within the supplements. Students appreciated the supplemental learning aids and mean exam scores were higher for users. Since production format did not noticeably alter exam performance and satisfaction was similar, production efficiency should take precedence.

Pheochromocytoma presenting as a mimic of acute coronary syndrome.

Chest pain with elevated serum troponin is a common clinical presentation and is normally managed as suspected myocardial infarction or acute coronary syndrome (ACS). We report a 49 year old man who presented with central chest pain sweating and breathlessness. He had a significantly elevated serum troponin I level and a subsequent angiogram showed near normal coronary arteries. He was subsequently investigated for fever and found to have a 3cm right sided adrenal mass consistent with a pheochromocytoma. After confirmation and appropriate blockade laparoscopic adrenalectomy was performed. Pheochromocytoma may present as a mimic of acute coronary syndrome but this is often unrecognized and leaves the patient at risk of future pheo crisis events which may be fatal.

Speaking of sex workers: How suppression of research has distorted the United States' domestic HIV response.

Sex workers remain a vulnerable population at risk for HIV acquisition and transmission. Research suggests that interventions at the individual level, such as condom distribution, are less effective in preventing HIV among sex workers than structural changes such as allowing safer work settings and reducing the harassment and abuse of sex workers by clients and police. In the US, HIV incidence has not declined in the last decade. This may be due in part to its policy of wilful ignorance about sex work, but the data to resolve the question simply do not exist. Political actions such as PEPFAR's prostitution pledge and a congressional campaign against "waste, fraud and abuse" in research are products of an ideological environment that suppresses research on HIV prevention and treatment needs of sex workers. Even basic prevalence data are missing because there is no "sex worker" category in the US National HIV Behavior Surveillance System. However, international efforts are taking a public health approach and are calling for decriminalization of sex work, as the most effective public health strategy for reducing HIV incidence among sex workers. Although such an approach is not yet politically feasible in the US, some urgent practical policy changes can be implemented to improve data collection and generation of evidence to support HIV prevention and treatment programs targeting sex workers.

Heart failure care in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. METHODS AND FINDINGS: Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. CONCLUSIONS: The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.

Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study.

Background: The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. Methods: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). Findings: Of 6,670,829 adults, we identified 516,491 (7.7%) with CKD, including 32.8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26.8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of people with CKD and co-existing T2D were indicated for treatment, compared to those without T2D (62.8% [n = 106,468] vs. 9.1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17.0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22.0% (n = 23,464) in those with T2D, and <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67-0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77-0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68-0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor, compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45-60 mL/min/1.73 m2 OR 0.65, 95% CI 0.62-0.68, p <0.0001, eGFR 30-45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69-0.78, p <0.0001, eGFR 15-30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46-0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00-0.23, p = 0.0037, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3-30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0.78, 95% CI 0.75-0.82, p <0.0001). Interpretation: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D. Funding: None.

Phenotype execution and modeling architecture to support disease surveillance and real-world evidence studies: English sentinel network evaluation.

Objective: To evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Quality Language (CQL) and intensional Systematised Nomenclature of Medicine (SNOMED) Clinical Terms (CT) Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor, and surveillance phenotypes. Method: We curated 3 phenotypes: Type 2 diabetes mellitus (T2DM), excessive alcohol use, and incident influenza-like illness (ILI) using CQL to define clinical and administrative logic. We defined our phenotypes with valuesets, using SNOMED's hierarchy and expression constraint language, and CQL, combining valuesets and adding temporal elements where needed. We compared the count of cases found using PhEMA with our existing approach using convenience datasets. We assessed our new approach against published desiderata for phenotypes. Results: The T2DM phenotype could be defined as 2 intensionally defined SNOMED valuesets and a CQL script. It increased the prevalence from 7.2% to 7.3%. Excess alcohol phenotype was defined by valuesets that added qualitative clinical terms to the quantitative conceptual definitions we currently use; this change increased prevalence by 58%, from 1.2% to 1.9%. We created an ILI valueset with SNOMED concepts, adding a temporal element using CQL to differentiate new episodes. This increased the weekly incidence in our convenience sample (weeks 26-38) from 0.95 cases to 1.11 cases per 100 000 people. Conclusions: Phenotypes for surveillance and research can be described fully and comprehensibly using CQL and intensional FHIR valuesets. Our use case phenotypes identified a greater number of cases, whilst anticipated from excessive alcohol this was not for our other variable. This may have been due to our use of SNOMED CT hierarchy. Our new process fulfilled a greater number of phenotype desiderata than the one that we had used previously, mostly in the modeling domain. More work is needed to implement that sharing and warehousing domains.

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study.

OBJECTIVES: Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. METHODS: Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. RESULTS: Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). CONCLUSIONS: Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed.

Mobilizing women at the grassroots to shape health policy: a case study of the Global Campaign for Microbicides.

Competition to advance issues on public policy agendas is constant. Political scientists agree that professional "policy entrepreneurs" (researchers, academics, and bureaucrats) serve as conduits in this process. Grassroots advocacy has always been part of the political landscape as non-professional people also take on the role of policy advocates or activists, to get specific problems and preferred solutions onto public and policy agendas and motivate policymakers to take action. The contribution of grassroots advocacy to significant policy changes is often under-funded because its impacts are hard to isolate and quantify, and are often most evident in retrospect. This paper examines the contribution of the Global Campaign for Microbicides to the movement to expand the range of HIV prevention options for women and describes how it mobilized hundreds of grassroots policy activists around the world to take coordinated action on this issue. It reviews the Campaign's accomplishments and highlights some of its strengths and weaknesses. Finally, the paper considers the value of similar efforts on the part of grassroots advocates seeking to influence the post-ICPD and post-2015 development agendas as they are being negotiated. Decisions regarding what kind of advocacy work is carried out during this process, and by whom and how, will inevitably shape the content of these new frameworks.

AAV8(gfp) preferentially targets large diameter dorsal root ganglion neurones after both intra-dorsal root ganglion and intrathecal injection.

Adeno-associated viral vectors (AAV) are increasingly used to deliver therapeutic genes to the central nervous system (CNS) where they promote transgene expression in post mitotic neurones for long periods with little or no toxicity. In adult rat dorsal root ganglia (DRG), we investigated the cellular tropism of AAV8 containing the green fluorescent protein gene (gfp) after either intra-lumbar DRG or intrathecal injection and showed that transduced DRG neurones (DRGN) expressed GFP irrespective of the delivery route, while non-neuronal cells were GFP(-). After intra-DRG delivery of AAV8(gfp), the mean DRGN transduction rate was 11%, while intrathecal delivery transduced a mean of 1.5% DRGN. After intra-DRG injection, 2% of small DRGN (<30 µm in diameter) were GFP(+) compared with 32% of large DRGN (>60 µm in diameter). Axons of transduced DRGN were also GFP(+); no intra-spinal neurones were transduced. A small number of contralateral DRGN were transduced after intra-DRG injection, suggesting that AAV8 may diffuse from injected DRG into the spinal canal. Microglia and astrocytes were highly ramified with increased GFAP(+) immunoreactivity (i.e. activated) in the neuropil around GFP(+) DRG axon projections within the cord after intra-DRG injection. This study showed that after both intra-DRG and intrathecal delivery, strong preferential AAV8 tropism exists for large DRGN unassociated with cell death, but GFP(+) axons projecting in the spinal cord induced local glial activation. These results open up opportunities for targeted delivery of therapeutics such as neurotrophic factors to the injured spinal cord.

Step-Wise Management of Anemia in Patients With Chronic Kidney Disease in Primary Care: Qualitative Study.

INTRODUCTION: Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed. METHODS: We conducted a qualitative study to evaluate how an audit-based education (ABE) intervention might improve the management of anemia in CKD. We explored outcomes that would be relevant to practitioners and patients, that exposed variation of practice from National Institute for Health and Care Excellence (NICE) guidelines, and whether the intervention was feasible and acceptable. RESULTS: Practitioners (n = 5 groups) and patients (n = 7) from 4 London general practices participated in discussions. Practitioners welcomed the evidence-based step-wise intervention. However, prescribing erythropoiesis-stimulating agents (ESAs) was felt to be outside of their scope of practice. There was a gap between NICE guidance and clinical practice in primary care. Iron studies were not well understood and anemia management was often conservative or delayed. Patients were often unaware of having CKD, and were more concerned about their other comorbidities, but largely trusted their GPs to manage them appropriately. CONCLUSIONS: The first steps of the intervention were welcomed by practitioners, but they expressed concerns about independently prescribing ESAs. Renal physicians and GPs could develop shared care protocols for ESA use in primary care. There is scope to improve awareness of renal anemia, and enhance knowledge of guideline recommendations; and our intervention should be modified accordingly.

Hepatitis A Vaccination Coverage Among People With Chronic Liver Disease in England (HEALD): Protocol for a Retrospective Cohort Study.

BACKGROUND: Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally. OBJECTIVE: This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine. METHODS: We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated. RESULTS: The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group. CONCLUSIONS: This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51861.

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.

Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status: A cross-sectional study using the UK Biobank data.

Background: Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting. Methods: A cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status. Findings: A total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% (n=152,896) had their UAC level recorded. Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.21 (95% CI 1.05 - 1.39, p=0.009), and 1.26 (95% CI 1.10 - 1.44, p=0.001), respectively. The odds declined after quitting in both groups, but it was not statistically significant (p>0.05). Each unit increase in HbA1c was associated with equivalent increased odds of albuminuria in current and ex-smokers, OR 1.035 (95% CI 1.030 - 1.039, p<0.001), and 1.026 (95% CI 1.023 - 1.028, p <0.001), respectively. Compared to females, male ex-smokers were at 15% increased odds of albuminuria. In ex-smokers, each unit increase in waist circumference was associated with 1% increased risk of albuminuria. Compared with the least deprived quintiles, the odds of albuminuria in the most deprived quintiles, in current and ex-smokers were identical, OR 1.18 (95% CI 1.04-1.324, p=0.010), and 1.19 (95% CI 1.11 - 1.27, p<0.001), respectively. Interpretation: Male smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria. Funding: University of Sheffield.

Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.

BACKGROUND: The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom. OBJECTIVE: This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d). METHODS: Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days. RESULTS: We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies. CONCLUSIONS: This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.

Chronic kidney disease in adults: assessment and management.

Chronic kidney disease (CKD) is a common condition associated with significant amenable morbidity and mortality, primarily related to the substantially increased risk of cardiovascular disease (CVD) in this population. Early detection of people with CKD is important so that treatment can be initiated to prevent or delay kidney disease progression, reduce or prevent the development of complications, and reduce the risk of CVD. Classification of CKD by the estimated glomerular filtration rate and urine albumin to creatinine ratio identifies those at greatest risk of adverse outcomes. This concise guideline highlights the key recommendations of the National Institute for Health and Care Excellence guideline Chronic kidney disease in adults: assessment and management: Clinical guideline [CG182], published in July 2014. It focuses on recommendations most relevant to secondary care physicians.

Head injury patterns in helmeted and non-helmeted cyclists admitted to a London Major Trauma Centre with serious head injury.

BACKGROUND: Cycle use across London and the UK has increased considerably over the last 10 years. With this there has been an increased interest in cycle safety and injury prevention. Head injuries are an important cause of mortality and morbidity in cyclists. This study aimed to ascertain the frequency of different head injury types in cyclists and whether wearing a bicycle helmet affords protection against specific types of head injury. METHODS: A retrospective observational study of all cyclists older than 16 years admitted to a London Major Trauma Centre between 1st January 2011 and 31st December 2015 was completed. A cohort of patients who had serious head injury was identified (n = 129). Of these, data on helmet use was available for 97. Comparison was made between type of injury frequency in helmeted and non-helmeted cyclists within this group of patients who suffered serious head injury. RESULTS: Helmet use was shown to be protective against intracranial injury in general (OR 0.2, CI 0.07-0.55, p = 0.002). A protective effect against subdural haematoma was demonstrated (OR 0.14, CI 0.03-0.72, p = 0.02). Wearing a helmet was also protective against skull fractures (OR 0.12, CI 0.04-0.39, p<0.0001) but not any other specific extracranial injuries. This suggests that bicycle helmets are protective against those injuries caused by direct impact to the head. Further research is required to clarify their role against injuries caused by shearing forces. CONCLUSIONS: In a largely urban environment, the use of cycle helmets appears to be protective for certain types of serious intra and extracranial head injuries. This may help to inform future helmet design.