Evaluation of Extended Infusion Set Performance in Adults with Type 1 Diabetes: Infusion Set Survival Rate and Glycemic Outcomes from a Pivotal Trial.

Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).

An analysis of Medtronic MiniMed 670G insulin pump use in clinical practice and the impact on glycemic control, quality of life, and compliance.

AIMS: This study evaluated the use of the Medtronic MiniMed 670G system in adults with type 1 diabetes mellitus from a large endocrinology practice and its impact on glycemic control, quality of life (QoL), compliance and safety. METHODS: 84 participants completed one site visit for data collection. Percentage of time in range (TIR: 70-180 mg/dL), hyperglycemia or time above range (TAB) (>180 mg/dL), hypoglycemia or time below range (TBR) (<70 mg/dL), HbA1c, average blood glucose (ABG), and other metrics were evaluated at the last visit using the system (LVMM) and compared between the last visit on previous insulin therapy (LVPT). RESULTS: The mean percentage of TIR at the LVMM was 74.0 ± 12.1%, with an increase of 27.1% (p < 0.001) in TIR from the LVPT. The mean percentage of TAR was 22.9 ± 11.8% and the mean percentage of TBR was 3.2 ± 5.1%. CONCLUSIONS: The use of the Medtronic MiniMed 670G system in our practice resulted in a TIR above the recommended target with a high degree of treatment satisfaction and compliance in adults with type 1 diabetes. Furthermore, the system may be a reasonable choice for patients struggling with significant amounts of hypoglycemia.

Improved postprandial glucose control with ultra rapid lispro versus lispro with continuous subcutaneous insulin infusion in type 1 diabetes: PRONTO-Pump-2.

AIM: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro (Humalog® ) in people with type 1 diabetes on continuous subcutaneous insulin infusion (CSII). MATERIALS AND METHODS: This was a phase 3, 16-week, treat-to-target study in patients randomized to double-blind URLi (N = 215) or lispro (N = 217). The primary endpoint was change from baseline HbA1c (non-inferiority margin 4.4 mmol/mol [0.4%]), with multiplicity-adjusted objectives for postprandial glucose (PPG) levels during a meal test, and time spent in the target range 70-180 mg/dL (TIR). RESULTS: URLi was non-inferior to lispro for change in HbA1c, with a least-squares mean (LSM) difference of 0.3 mmol/mol (95% confidence interval [CI] -0.6, 1.2) or 0.02% (95% CI -0.06, 0.11). URLi was superior to lispro in controlling 1- and 2-h PPG levels after the meal test: LSM difference -1.34 mmol/L (95% CI -2.00, -0.68) or -24.1 mg/dL (95% CI -36.0, -12.2) at 1 h and -1.54 mmol/L (95% CI -2.37, -0.72) or -27.8 mg/dL (95% CI -42.6, -13.0) at 2 h; both p < .001. TIR and time in hyperglycaemia were similar between groups but URLi resulted in significantly less time in hypoglycaemia (<3.0 mmol/L [54 mg/dL]) over the daytime, night-time and 24-h period: LSM difference -0.41%, -0.97% and -0.52%, respectively, all p < .05. The incidence of treatment-emergent adverse events was higher with URLi (60.5% vs. 44.7%), driven by infusion-site reaction and infusion-site pain, which was mostly mild or moderate. Rates of severe hypoglycaemia and diabetic ketoacidosis were similar between groups. CONCLUSIONS: URLi was efficacious, providing superior PPG control and less time in hypoglycaemia but with more frequent infusion-site reactions compared with lispro when administered by CSII.

Accuracy and Precision of a Point-of-Care HbA1c Test.

BACKGROUND: Point-of-care (POC) hemoglobin A1c (HbA1c) testing has advantages over laboratory testing, but some questions have remained regarding the accuracy and precision of these methods. The accuracy and the precision of the POC Afinion™ HbA1c Dx test were investigated. METHODS: Samples spanning the assay range were collected from prospectively enrolled subjects at three clinical sites. The accuracy of the POC test using fingerstick and venous whole blood samples was estimated via correlation and bias with respect to values obtained by an NGSP secondary reference laboratory (SRL). The precision of the POC test using fingerstick samples was estimated from duplicate results by calculating the coefficient of variation (CV) and standard deviation (SD), and separated into its components using analysis of variance (ANOVA). The precision of the POC test using venous blood was evaluated from samples run in four replicates on each of three test cartridge lots, twice per day for 10 consecutive days. The SD and CV by study site and overall were calculated. RESULTS: Across the assay range, POC test results from fingerstick and venous whole blood samples were highly correlated with results from the NGSP SRL (r = .99). The mean bias was -0.021% HbA1c (-0.346% relative) using fingerstick samples and -0.005% HbA1c (-0.093% relative) using venous samples. Imprecision ranged from 0.62% to 1.93% CV for fingerstick samples and 1.11% to 1.69% CV for venous samples. CONCLUSIONS: The results indicate that the POC test evaluated here is accurate and precise using both fingerstick and venous whole blood.

Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial.

CONTEXT: Hashimoto's thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid found in Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto's thyroiditis. OBJECTIVE: The effects of anatabine in patients with Hashimoto's thyroiditis were studied. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a double-blind, randomized, placebo-controlled multisite study. A total of 146 patients (70 treated with anatabine and 76 with placebo) completed the study. Approximately 50% of patients in each group were taking levothyroxine. Anatabine lozenges (9-24 mg/d) or placebo, each containing vitamins A and D3, were administered orally 3 times a day for 3 months. MAIN OUTCOME MEASURES: Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were assessed. Safety was assessed through adverse events, clinical laboratory evaluations, and vital sign measurements. RESULTS: Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those receiving placebo (P=.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels. Mean±SD TgAb values decreased by 46.2±101.1 and 3.9±83.9 World Health Organization units for the anatabine and placebo groups, respectively. Significantly more patients had a >20% drop in TgAb levels in the anatabine than placebo group (P=.023). Overall, the anatabine supplement was safe and well tolerated, although significantly (P<.05) more patients in the anatabine group reported adverse events. CONCLUSIONS: These results demonstrate an immunological effect of anatabine on TgAb levels. Further studies are warranted to determine the longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis.

An 18-month open-label trial of teriparatide in patients with previous parathyroidectomy at continued risk for osteoporotic fractures: an exploratory study.

OBJECTIVE: To determine whether teriparatide increases lumbar spine bone mineral density (BMD) in patients who have undergone parathyroidectomy for primary hyperparathyroidism (PHPT) and are at continued risk for fracture. METHODS: This open-label, nonrandomized, uncontrolled exploratory design study included patients who had undergone parathyroidectomy for PHPT and were judged to be at continued risk for fracture according to National Osteoporosis Foundation criteria. Patients were administered teriparatide subcutaneously, 20 mcg daily, for 18 months after they satisfactorily completed the screening period to ensure their eligibility for study participation. BMD was assessed by dual-energy x-ray absorptiometry at baseline, 6 months, 12 months, and 18 months. Secondary objectives included efficacy of teriparatide on increasing hip BMD, incidence of fractures, and safety measurements. RESULTS: Seven women and 3 men were included. Change in mean lumbar spine BMD was 0.059 gm/cm2, which is a 7.1% increase (P = .005). Change in mean femoral neck BMD was 0.019 gm/cm2, which is a nonsignificant increase of 3.3% (P = .49). There was no incidence of fractures. There were no significant changes in the safety measurements. CONCLUSIONS: The use of teriparatide in patients with PHPT who have undergone parathyroidectomy and are still at risk for fracture is effective in improving lumbar spine BMD without deleterious effects on safety. Teriparatide should therefore be considered as a viable alternative for the treatment of these patients, as it may help in the prevention of fractures and their complications.

A macro-economic framework for evaluation of cyber security risks related to protection of intellectual property.

The article is based on the premise that, from a macro-economic viewpoint, cyber attacks with long-lasting effects are the most economically significant, and as a result require more attention than attacks with short-lasting effects that have historically been more represented in literature. In particular, the article deals with evaluation of cyber security risks related to one type of attack with long-lasting effects, namely, theft of intellectual property (IP) by foreign perpetrators. An International Consequence Analysis Framework is presented to determine (1) the potential macro-economic consequences of cyber attacks that result in stolen IP from companies in the United States, and (2) the likely sources of such attacks. The framework presented focuses on IP theft that enables foreign companies to make economic gains that would have otherwise benefited the U.S. economy. Initial results are presented.