Design and rationale of DISCOVER global registry in type 2 diabetes:Real-world insights of treatment patterns and its relationship with cardiovascular, renal, and metabolic multimorbidities

10.1016/j.jdiacomp.2021.108077Journal of Diabetes and its Complications351210807

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

Global patterns of comprehensive cardiovascular risk factor control in patients with type 2 diabetes mellitus: Insights from the DISCOVER study.

AIM: To investigate global patterns of cardiovascular risk factor control in patients with type 2 diabetes mellitus (T2D). METHODS: DISCOVER is an international, observational cohort study of patients with T2D beginning second-line glucose-lowering therapy. Risk factor management was examined among eligible patients (ie, those with the risk factor) at study baseline. Inter-country variability was estimated using median odds ratios (MORs). RESULTS: Among 14 343 patients with T2D from 34 countries, the mean age was 57.4 ± 12.0 years and the median (interquartile range) duration of T2D was 4.2 (2.0-8.0) years; 11.8% had documented atherosclerotic cardiovascular disease (ASCVD). Among eligible patients, blood pressure was controlled in 67.5% (9284/13756), statins were prescribed in 43.7% (5775/13208), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were prescribed in 55.6% (5292/9512), aspirin was prescribed in 53.3% of those with established ASCVD (876/1645), and 84.4% (12 102/14343) were non-smoking. Only 21.5% of patients (3088/14343) had optimal risk factor management (defined as control of all eligible measures), with wide inter-country variability (10%-44%), even after adjusting for patient and site differences (MOR 1.47, 95% confidence interval 1.24-1.66). CONCLUSION: Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes

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

New synthesis of 3-Fluoropyrroles

5-Alkoxymethyl-2-aryl-3-fluoro-1H-pyrroles and 2-aryl-3-fluoro-1H-pyrrole-5-carbaldehydes were efficiently prepared from the corresponding 2-aryl-5-(bromomethyl)-1-pyrrolines via electrophilic α,α-difluorination of the imino bond, using Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bistetrafluoroborate) and subsequent aromatization by dehydrofluorination. This methodology provides a new and easy entry toward various new 3-fluorinated pyrroles

Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009–2011

This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes. Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation. Outcome was also assessed one month after discharge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities. One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20% were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pneumococcal etiology in hospitalised children with community-acquired penumonia in Belgium :evaluation by culture, RT-PCR and serotype-specific IgG and IgA serology.

info:eu-repo/semantics/nonPublishe

Pneumococcal aetiology and serotype distribution in paediatric community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a major cause of morbidity in children. This study estimated the proportion of children with pneumococcal CAP among children hospitalised with CAP in Belgium and describes the causative serotype distribution after implementation of the 7-valent pneumococcal conjugate vaccine. Children 0-14 years hospitalised with X-ray-confirmed CAP were prospectively enrolled in a multicentre observational study. Acute and convalescent blood samples were collected. Pneumococcal aetiology was assessed by conventional methods (blood or pleural fluid cultures with Quellung reaction capsular typing or polymerase chain reaction [PCR] in pleural fluid), and recently developed methods (real-time PCR in blood and World Health Organization-validated serotype-specific serology). A total of 561 children were enrolled. Pneumococcal aetiology was assessed by conventional methods in 539, serology in 171, and real-time PCR in blood in 154. Pneumococcal aetiology was identified in 12.2% (66/539) of the children by conventional methods alone but in 73.9% by the combination of conventional and recently developed methods. The pneumococcal detection rate adjusted for the whole study population was 61.7%. Serotypes 1 (42.3%), 5 (16.0%), and 7F(7A) (12.8%) were predominant. In conclusion, Streptococcus pneumoniae remains the predominant bacteria in children hospitalised for CAP in Belgium after implementation of 7-valent pneumococcal conjugate vaccine, with non-vaccine-serotypes accounting for the majority of cases. The use of recently developed methods improves diagnosis of pneumococcal aetiology