Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors:an analysis from the CVD-REAL 2 multinational cohort study

Background Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12.2), 170 335 (44.1%) of 386 248 were women, and 111933 (30.1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0.69, 95% CI 0. 61-0. 77; p Interpretation In this large, international, observational study, initiation of SGLT2 inhibitors versus DPP-4 inhibitors was associated with lower risks of heart failure, death, myocardial infarction, and stroke, providing further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes. Copyright (C) 2020 Elsevier Ltd. All rights reserved

Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data

BACKGROUND: Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. METHODS: De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. RESULTS: Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. CONCLUSIONS: This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-021-01345-z

Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

Assessment of colonoscopy skill using machine learning to measure quality: Proof-of-concept and initial validation

Background and study aims: Low-quality colonoscopy increases cancer risk but measuring quality remains challenging. We developed an automated, interactive assessment of colonoscopy quality (AI-CQ) using machine learning (ML). Methods: Based on quality guidelines, metrics selected for AI development included insertion time (IT), withdrawal time (WT), polyp detection rate (PDR), and polyps per colonoscopy (PPC). Two novel metrics were also developed: HQ-WT (time during withdrawal with clear image) and WT-PT (withdrawal time subtracting polypectomy time). The model was pre-trained using a self-supervised vision transformer on unlabeled colonoscopy images and then finetuned for multi-label classification on another mutually exclusive colonoscopy image dataset. A timeline of video predictions and metric calculations were presented to clinicians in addition to the raw video using a web-based application. The model was externally validated using 50 colonoscopies at a second hospital. Results: The AI-CQ accuracy to identify cecal intubation was 88%. IT ( P = 0.99) and WT ( P = 0.99) were highly correlated between manual and AI-CQ measurements with a median difference of 1.5 seconds and 4.5 seconds, respectively. AI-CQ PDR did not significantly differ from manual PDR (47.6% versus 45.5%, P = 0.66). Retroflexion was correctly identified in 95.2% and number of right colon evaluations in 100% of colonoscopies. HQ-WT was 45.9% of, and significantly correlated with ( P = 0.85) WT time. Conclusions: An interactive AI assessment of colonoscopy skill can automatically assess quality. We propose that this tool can be utilized to rapidly identify and train providers in need of remediation

Hydration Strategies and Changes in Body Mass During Soccer Pre-Season Two-a-Days

Fluid loss and dehydration can negatively impact physical and skill performance, and potentially cause physical harm. PURPOSE: To monitor hydration strategies during, and changes in body mass as a result of pre-season soccer two-a-days. METHODS: 16 female DII soccer players volunteered, with four players monitored each day during linked morning and afternoon training sessions. Prior to each session, body mass (BM) and dry uniform weight were determined and core (intestinal) body temperature (Tint) and environmental conditions were measured. Participants were able to drink ad libitum water and/or Gatorade (6% carbohydrate sports drink). During each break between drills, Tint, heart rate (HR), and environmental conditions were recorded. At the end of each session, Tint, HR, BM, wet uniform weight and volumeof both fluids consumed were determined. Statistical analyses were performed on within- and between-session variables using paired t statistic. RESULTS: There were no substantial differences in either Tint or HR between sessions. More total fluid was consumed in morning compared to afternoon sessions (0.20 L, 90% CI 0.05 to 0.34 L), but there were no marked within or between session differences in volumeof specific fluid consumed. Net BM loss was greater in morning compared to afternoon sessions (mean difference = 0.37 kg, 90% CI 0.17 to 0.57 kg), which equated to 2.7±0.6% and 2.2±0.4% net BM loss, respectively. Overall, there was a net daily BM loss of 2.8±0.5 kg (4.4±0.7%). CONCLUSION: Hydration strategies used failed to offset the session-specific and daily body mass losses encountered during pre-season soccer two-a-days

Exercise-heat stress with and without water replacement alters brain structures and impairs visuomotor performance

Effects of exercise-heat stress with and without water replacement on brain structure and visuomotor performance were examined. Thirteen healthy adults (23.6 ± 4.2 years) completed counterbalanced 150 min trials of exercise-heat stress (45°C, 15% RH) with water replacement (EHS) or without (~3% body mass loss; EHS-DEH) compared to seated rest (CON). Anatomical scans and fMRI Blood-Oxygen-Level-Dependent responses during a visuomotor pacing task were evaluated. Accuracy decreased (P 0.50) between structural changes and visuomotor accuracy. EHS-DEH increased neural activation (P &lt; 0.05) within motor and visual areas versus EHS and CON. Brain structural changes are related to bidirectional plasma osmolality perturbations resulting from exercise-heat stress (with and without water replacement), but do not explain visuomotor impairments. Negative impacts of exercise-heat stress on visuomotor tasks are further exacerbated by dehydration

Assessment of the high risk and unmet need in patients with CAD and type 2 diabetes (ATHENA): US healthcare resource utilization, cost and burden of illness in the Diabetes Collaborative Registry

BackgroundTHEMIS (NCT01991795) showed that in patients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) but with no prior myocardial infarction (MI) or stroke, ticagrelor plus acetylsalicylic acid (ASA) decreased the incidence of ischaemic cardiovascular events compared with placebo plus ASA. To complement these findings, we assessed disease burden and healthcare resource utilization (HRU) in US patients with CAD and T2D, but without a prior MI or stroke.MethodsThis observational study used 2013-2014 data from the Diabetes Collaborative Registry linked to Medicare administrative claims. Two cohorts of patients with T2D were studied: patients at high cardiovascular risk (THEMIS-like cohort; N&nbsp;=&nbsp;56&nbsp;040) and patients at high cardiovascular risk or taking P2Y12 inhibitors (CAD-T2D cohort; N&nbsp;=&nbsp;69&nbsp;790). Outcomes included the composite of all-cause death, MI and stroke; the individual events from the composite endpoint; HRU; and costs.ResultsMedian age was 73.0&nbsp;years, and median follow-up was 1.3&nbsp;years in both cohorts. Event rates of the composite outcome were 16.34 (95% confidence interval: 16.31-16.37) and 17.64 (17.61-17.67) per 100 person-years for the THEMIS-like and CAD-T2D cohorts, respectively. The incidence rate of bleeding events was 0.13 events per 100 person-years in both cohorts. Healthcare costs per patient-year were USD 8741 and USD 9150 in the THEMIS-like and CAD-T2D cohorts, respectively.ConclusionsPatients in the THEMIS-like cohort and the broader CAD-T2D population had similarly substantial cardiovascular event rates and healthcare costs, indicating that patients with CAD and T2D similar to the THEMIS population are at an increased cardiovascular risk

Association of sodium‐glucose cotransporter‐2 inhibitors with outcomes in type 2 diabetes with reduced and preserved left ventricular ejection fraction: Analysis from the CVD‐REAL

This study of real-world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors versus other glucose-lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity-matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), similar to 43% had cardiovascular disease, similar to 7% had heart failure and similar to 20% had chronic kidney disease. A total of 2876 patients (similar to 9%) had reduced EF