Switching to insulin glargine 300 units/mL in real-world older patients with type 2 diabetes (DELIVER 3).

AIM: To compare the second-generation basal insulin glargine 300 units/mL (Gla-300) and first-generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). MATERIALS AND METHODS: DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow-up who switched from basal insulin to Gla-300 were propensity score-matched to 1176 older adults who switched to a first-generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla-100)]. Outcomes were follow-up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization. RESULTS: Following basal insulin switching, HbA1c reductions were greater/similar with Gla-300 versus IDet/Gla-100 (variable follow-up: -0.45% ± 1.40% vs. -0.29% ± 1.57%; P = .021; fixed follow-up: -0.48% ± 1.49% vs. -0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla-300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53-0.75; P < .001] and inpatient/emergency department-associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37-0.90; P = .016; aRR: 0.43, 95% CI: 0.31-0.60; P < .001) by variable follow-up. By fixed follow-up, hypoglycaemia results significantly or numerically favoured Gla-300. CONCLUSION: Among older adults with T2D, switching to Gla-300 versus Gla-100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. METHODS: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. CONCLUSION: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02451137.

Safety analysis of a hemostatic powder in a porcine model of acute severe gastric bleeding.

BACKGROUND: Non-variceal upper gastrointestinal (UGI) bleeding is a common condition that requires prompt lifesaving therapy and traditional endoscopic treatments require high technical proficiency to perform. AIMS: This study was conducted to identify any local or systemic histopathologic effects of a hemostatic powder in a porcine model of active, severe, non-variceal UGI hemorrhage. METHODS: This prospective, non-blinded animal study was performed in accordance with Good Laboratory Practice and Animal Care and Use Guidelines. Six animals underwent gastrotomy and creation of a looped vascular bundle, which was placed into the stomach lumen. The transplanted vascular bundle was punctured with an endoscopic needle-knife to create Forrest grade Ia or Ib bleeding. The hemostatic powder was then applied until hemostasis was achieved. RESULTS: Initial hemostasis was achieved in all animals. Results of pre- and post-treatment coagulation studies were similar. All animals survived at least 9 days post-procedure. The hemostatic powder was not found in any local, regional, or systemic tissues. Gross and histologic analysis of systemic organs showed no infarct, particulate, or embolic effects. No gross or microscopic necropsy findings were treatment-related. CONCLUSIONS: The hemostatic powder achieved initial hemostasis (even in animals with spurting arterial bleeding) with no bowel obstruction or unintended luminal effects, no local or regional particulate effects, no systemic embolic effects, and no systemic coagulopathic effects.

Time course of esophageal lesions after catheter ablation with cryothermal and radiofrequency ablation: implication for atrio-esophageal fistula formation after catheter ablation for atrial fibrillation.

BACKGROUND: Atrio-esophageal fistulas have been described as a consequence of radiofrequency (RF) ablation for the treatment of atrial fibrillation (AF). However, whether cryoablation can avoid this potential fatal complication remains unclear. METHODS AND RESULTS: We studied the effects of direct application of RF and cryoablation on the cervical esophagus in 16 calves. Cryoablation was performed with a 6.5-mm catheter probe using a single 5-minute freeze at <-80 degrees C, and RF ablation was delivered with an 8-mm catheter electrode at 50 W and 50 degrees C for 45-60 seconds. Histopathologic assessments were performed at 1, 4, 7, and 14 day(s) after completion of the ablation protocol: four animals were examined each day. A total of 85 direct esophageal ablations were performed: 41 with RF and 44 with cryoablation. There were no significant differences in lesion width, depth, or volume between cryoablation and RF ablation at Day 1, 4, and 14 after the procedure (P > 0.05). However, lesion width and volume were significantly larger with RF than with cryoablation at Day 7. Although acute (Day 1) and chronic (Day 14) RF and cryoablation lesions were of comparable size, histologic evidence of partial- to full-wall esophageal lesion ulceration was observed in 0 of 44 (0%) lesions with cryoablation, compared with 9 of 41 (22%) lesions with RF ablation (P = 0.0025). CONCLUSIONS: Direct application of cryoablation and RF ablation created similar acute and chronic lesion dimensions on the esophagus. However, cryoablation was associated with a significantly lower risk of esophageal ulceration, compared with RF ablation.

Comparison of pressure ulcer treatments in long-term care facilities: clinical outcomes and impact on cost.

This study compared clinical outcomes and nursing labor costs associated with (a) balsam Peru, hydrogenated castor oil, and trypsin (BCT) ointment; (b) BCT + Other; and (c) Other treatments in 2014 wound episodes occurring in 861 patients (mean 2.34 wounds/patient). Treatment with BCT ointment or BCT + Other was associated with a higher healing rate (P < .05). No Stage 1 or 2 ulcer treated with BCT ointment progressed, compared with 13.8% treated with BCT + Other and 13.4% treated with Other. The reported mean duration of treatment and time to heal were shorter for ulcers treated with BCT ointment, but differences did not reach significance, possibly because of the variability in reported treatment times. Mean daily nursing labor costs were lower for treatment with BCT than Other ($50.8 vs $61.7, P < .05). These data suggest that treatment of Stage 1 or 2 ulcers with BCT may be associated with shorter treatment time and time to heal and a potential reduction in treatment-related nursing labor costs.

Effects of temporal application parameters on lesion dimensions during transvenous catheter cryoablation.

UNLABELLED: Lesion dimension of cryoablation. BACKGROUND: Transvenous catheter cryoablation is a novel technique for treating cardiac arrhythmias. However, the relative importance of temporal application parameters on lesion dimension and clinical efficacy has not been studied. METHODS AND RESULTS: We investigated the effects of (1) application duration: single 2.5 (2.5x1) versus single 5 versus double 2.5 (2.5x2) versus double 5 (5x2) minutes, (2) number of freeze-thaw cycles: single versus double, and (3) electrode contact area: horizontal versus vertical orientation, on the lesion diameter and depth during catheter cryoablation (10F, 6.5-mm tip-electrode, CryoCor, San Diego) in a thigh muscle preparation. A total of 175 lesions (horizontal=90, vertical=85) were created in thigh muscle preparations on 10 swine. The lesion diameter and depth were significantly greater using 2.5x2 and 5x2 application modes as compared with 2.5x1 applications (P<0.05). Horizontal tip-electrode orientation produced larger lesion diameter (P<0.05), but not lesion depth as compared with vertical orientation. Multivariate analysis demonstrated that both tip-electrode orientation and duration of freeze >2.5 minutes were independent predictors for lesion diameter (P<0.001). However, only duration of freeze >2.5 minutes was an independent predictor for lesion depth (P<0.001). CONCLUSIONS: The dimensions of lesions created by catheter cryoablation are affected by mode of cryoablation application and electrode orientation. Increasing the duration of application, employing multiple freeze-thaw cycles at shorter cycle durations, and orienting the catheter to enhance/increase tissue contact can create a larger lesion.

Structural, functional, and molecular characterization of the SHHF model of heart failure.

Heart failure is a complex multifactorial disease resulting in a myriad of progressive changes at the molecular, cellular, and physiological level. To better understand the mechanisms associated with the development of congestive heart failure, a comprehensive examination of the aging lean male spontaneously hypertensive, heart failure-prone rat (SHHF) was conducted. Myocardial function and structural integrity progressively diminished as evidenced by decreased ejection fraction and increased left ventricular volume measured using echocardiography. Functional and structural changes were accompanied by elevations in circulating inflammatory markers, including tumor necrosis factor-alpha (TNF-alpha), IL-6, and TNF receptors type 1 and 2. Increased systemic inflammatory marker levels were consistent with age-dependent changes in the expression pattern of genes that contribute to stress, inflammation, and the extracellular matrix in SHHF animals analyzed from age 4 to 18 mo. In summary, the SHHF rat shares many hallmark features of the human disease state and represents a key experimental model for the dissection of complex human heart failure pathophysiology.