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BackgroundAlthough practice guidelines stress individualization of glucose management in patients with type 2 diabetes (T2D), the extent to which providers take patient factors into account when selecting medications is not well known.MethodsDiabetes Collaborative Registry (DCR) is an outpatient diabetes registry including primary care, cardiology, and endocrinology practices. T2D medications were grouped as those which may be suboptimal for key patient subgroups, and we examined patient factors associated with use of these agents using hierarchical, multivariable Poisson models.ResultsIn DCR, 157,551 patients from 374 US practices were prescribed a glucose-lowering medication. Patients with morbid obesity were more likely treated with medications prone to cause weight gain (relative rate [RR] 1.09, 95% CI 1.07-1.11). Older patients were more likely to be treated with medications with increased risk of hypoglycemia (RR 1.04 per 5 years, 95% CI 1.04-1.05). Patients with CKD 4/5 were less likely to be treated with agents with known risk in patients with advanced CKD (RR 0.74, 95% CI 0.71-0.77). Patients with coronary artery disease were no more or less likely to be treated with medications with potential cardiovascular safety issues (RR 0.99, 95% CI 0.96-1.01).ConclusionsWe observed some targeted use of glucose-lowering therapies in certain subgroups but also identified potential opportunities for better personalization of treatment. Data sources such as the DCR can highlight potential areas for improving targeted approaches to pharmacologic therapy in order to optimize selection of patients most likely to benefit (and least likely to be harmed) from treatments.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF. In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking., Author(s): Michael E. Nassif [sup.1] [sup.2] , Sheryl L. Windsor [sup.1] , Barry A. Borlaug [sup.3] , Dalane W. Kitzman [sup.4] , Sanjiv J. Shah [sup.5] , Fengming Tang [sup.1] [...]

The purpose of the study is to evaluate the feasibility of blood oxygenation level-dependent MRI (BOLD-MRI) to early detect the femoral head osteonecrosis (FHON). One hundred twelve patients were recruited who had received steroid treatment. The normal control group included 10 volunteers with 20 hips. MRI examinations were performed in all patients following up at 1, 4 to 5, 7 to 8, and 12 to 13 months after steroid therapy. With the section cross as the biggest lesion in coronal images, we set 6 regions of interest (ROIs) per section to analyze the morphological performance of routine MRI sequences and the differences of R2* values and their dynamic changes of BOLD-MRI between the control and the FHON group. A total of 15 hip joints were diagnosed with FHON. Seven right hips and 8 left hips were affected. In the first and second MRI examinations, the area of the lesion for both conventional MRI and BOLD-MRI R2* mapping was difficult to distinguish the lesion border. However, at the third and the fourth MRI examinations, some of the affected regions for R2* mapping were larger than those in conventional sequences for the same patient. BOLD-MRI has some significant advantages in early detecting FHON over conventional MRI techniques and it can be feasible noninvasive tool for detecting and evaluating FHON after steroid therapy.

Although guidelines and performance measures exist for patients with diabetes mellitus, achievement of these metrics is not well known. The Diabetes Collaborative Registry® (DCR) was formed to understand the quality of diabetes mellitus care across the primary and specialty care continuum in the United States. We assessed the frequency of achievement of 7 diabetes mellitus-related quality metrics and variability across the Diabetes Collaborative Registry® sites. Among 574 972 patients with diabetes mellitus from 259 US practices, median (interquartile range) achievement of the quality metrics across the practices was the following: (1) glycemic control: 19% (5-47); (2) blood pressure control: 80% (67-88); (3) angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in patients with coronary artery disease: 62% (51-69); (4) nephropathy screening: 62% (53-71); (5) eye examination: 0.7% (0.0-79); (6) foot examination: 0.0% (0.0-2.3); and (7) tobacco screening/cessation counseling: 86% (80-94). In hierarchical, modified Poisson regression models, there was substantial variability in meeting these metrics across sites, particularly with documentation of glycemic control and eye and foot examinations. There was also notable variation across specialties, with endocrinology practices performing better on glycemic control and diabetes mellitus foot examinations and cardiology practices succeeding more in blood pressure control and use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. The Diabetes Collaborative Registry® was established to document and improve the quality of outpatient diabetes mellitus care. While target achievement of some metrics of cardiovascular risk modification was high, achievement of others was suboptimal and highly variable. This may be attributable to fragmentation of care, lack of ownership among various specialists concerning certain domains of care, incomplete documentation, true gaps in care, or a combination of these factors.

BackgroundPatients with paroxysmal and persistent atrial fibrillation experience a similar risk of thromboembolism. Therefore, consensus guidelines recommend anticoagulant therapy in those at risk for thromboembolism irrespective of atrial fibrillation classification. We sought to examine whether there are differences in rates of appropriate oral anticoagulant treatment among patients with paroxysmal vs persistent atrial fibrillation in real-world cardiology practices.MethodsWe studied 71,316 outpatients with atrial fibrillation and intermediate to high thromboembolic risk (CHADS2 score ≥2) enrolled in the American College of Cardiology PINNACLE Registry between 2008 and 2012. Using hierarchical modified Poisson regression models adjusted for patient characteristics, we examined whether anticoagulant treatment rates differed between patients with paroxysmal vs persistent atrial fibrillation.ResultsThe majority of outpatients (78.4%, n = 55,905) had paroxysmal atrial fibrillation. In both unadjusted and multivariable adjusted analyses, patients with paroxysmal atrial fibrillation were less frequently prescribed oral anticoagulant therapy than those with persistent atrial fibrillation (50.3% vs 64.2%; adjusted risk ratio [RR] 0.74; 95% confidence interval [CI], 0.72-0.76). Instead, patients with paroxysmal atrial fibrillation were prescribed more frequently only antiplatelet therapy (35.1% vs 25.0%; adjusted RR 1.77; 95% CI, 1.69-1.86) or neither antiplatelet nor anticoagulant therapy (14.6% vs 10.8%; adjusted RR 1.35; 95% CI, 1.26-1.44; P < .0001 for differences across all 3 comparisons).ConclusionsIn a large, real-world cardiac outpatient population, patients with paroxysmal atrial fibrillation with a moderate to high risk of stroke were less likely to be prescribed appropriate oral anticoagulant therapy and more likely to be prescribed less effective or no therapy for thromboembolism prevention.

OBJECTIVES: We sought to investigate the prevalence and predictors of oral anticoagulation prescription among patients with atrial fibrillation (AF) at the lowest risk for thromboembolism, despite contemporary consensus guidelines that do not recommend anticoagulation therapy in this population. BACKGROUND: In young and healthy AF patients without significant thromboembolic risk factors, anticoagulant treatment carries bleeding risks that outweigh stroke prevention benefit. METHODS: Within a large contemporary registry of cardiology outpatients, we identified low-risk patients with AF meeting criteria for a contemporary consensus guideline class III indication against use of anticoagulation (age < 60 years, CHADS2 Score=0, and no structural heart disease) between 2008–2012, and a second cohort with the same criteria and a CHA2DS2-VASc Score of 0. Using hierarchical modified Poisson regression models adjusted for patient characteristics, we examined predictors of oral anticoagulation treatment in these low thromboembolic risk AF patients. RESULTS: Oral anticoagulation was prescribed in a total of 2,561 of 10,995 (23.2%) AF patients with a CHADS2 score of 0 and 1,787 of 6,730 (26.6%) AF patients with a CHA2DS2-VASc score of 0. In multivariable analysis, older age (RR 1.48 per 10 years; 95% CI, 1.41–1.56; p

ObjectivesCHARISMA was a landmark randomized clinical trial that failed to demonstrate a benefit of dual antiplatelet therapy (DAPT) over aspirin alone for preventing cardiovascular events. However, subgroup analyses of the trial found fewer major adverse cardiovascular events (MACEs) for patients with established cardiovascular disease but more MACEs for patients with multiple risk factors without established cardiovascular disease. Our objective was to examine DAPT use in contemporary clinical practice after publication of CHARISMA results.Study designRetrospective analysis of a large clinical registry of outpatient cardiovascular visits to over 1000 physicians that collected data on patient clinical history, symptoms, vital signs, and medications.MethodsClinical characteristics and prescription rates of aspirin and clopidogrel were compared for patients with established cardiovascular disease and for patients with only multiple cardiovascular risk factors. Prescription of DAPT by calendar quarter was evaluated from 2008 to 2011 using multivariable Poisson regression models.ResultsOf 167,839 patients with established cardiovascular disease, 20.5% were prescribed both aspirin and clopidogrel. Of 20,478 patients with multiple risk factors but no known cardiovascular disease, 3.5% were prescribed both aspirin and clopidogrel. Across 14 calendar quarters, prescription rates of DAPT did not change significantly for patients with established CVD but decreased for patients with multiple risk factors with an incidence rate ratio of 0.77.ConclusionsUse of DAPT is modest in patients with established cardiovascular disease, for whom the CHARISMA trial suggested decreased MACEs, and prescription rates have remained stable over time. Use of DAPT in patients with multiple risk factors only, for whom CHARISMA suggested that DAPT may lead to increased MACE, was low and decreased over time.

Slow accrual rate is a major challenge in clinical trials for rare diseases and is identified as the most frequent reason for clinical trials to fail. This challenge is amplified in comparative effectiveness research where multiple treatments are compared to identify the best treatment. Novel efficient clinical trial designs are in urgent need in these areas. Our proposed response adaptive randomization (RAR) reusing participants trial design mimics the real-world clinical practice that allows patients to switch treatments when desired outcome is not achieved. The proposed design increases efficiency by two strategies: (i) Allowing participants to switch treatments so that each participant can have more than one observation and hence it is possible to control for participant specific variability to increase statistical power; and (ii) Using RAR to allocate more participants to the promising arms such that ethical and efficient studies will be achieved. Extensive simulations were conducted and showed that, compared with trials where each participant receives one treatment, the proposed participants reusing RAR design can achieve comparable power with a smaller sample size and a shorter trial duration, especially when the accrual rate is low. The efficiency gain decreases as the accrual rate increases. [ABSTRACT FROM AUTHOR]

Aims: To describe glucose‐lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow‐up from the start of second‐line therapy. Materials and Methods: This data analysis from the 3‐year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second‐line glucose‐lowering therapy. Treatment and HbA1c data were collected at baseline (start of second‐line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow‐up were analysed using the McNemar test, with carry‐forward imputation for intermediate missing values. Results: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow‐up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. Conclusions: Dual oral therapy was the most common treatment regimen at the start of second‐line treatment, and over half of the participants remained on the same treatment during follow‐up. [ABSTRACT FROM AUTHOR]