Effectiveness of V-Go® for Patients with Type 2 Diabetes in a Real-World Setting: A Prospective Observational Study.

BACKGROUND: V-Go is a wearable, patch-like, 24-h insulin delivery device that delivers both a continuous preset basal rate and on-demand bolus dosing. The aim of this study was to observe glycemic control, insulin dosing, and hypoglycemia risk in patients switched to V-Go in a real-world setting. The primary objective was to compare change in mean hemoglobin A1c (HbA1c) from baseline to the end of V-Go use. METHODS: This prospective, open-label, multicenter study recruited patients with type 2 diabetes (T2D) and suboptimal glycemic control (HbA1c ≥ 7%) across 28 centers. Efficacy analyses were conducted for all patients with a post-baseline HbA1c and results stratified based on prior antihyperglycemic medication therapies. Insulin dosing was at the discretion of the health care provider and the protocol did not mandate glycemic targets. Treatment satisfaction surveys were utilized to gain patient feedback on the use of V-Go. RESULTS: One hundred eighty-eight patients were enrolled in the study, among whom 140 patients had a valid post-baseline HbA1c and were included in the primary efficacy analysis. Use of V-Go resulted in a change of - 0.64%; (P = 0.003) in HbA1c from baseline, and in those prescribed insulin, the total daily dose of insulin was decreased by 12 units/day (P < 0.0001). Twenty-two patients (12%) reported hypoglycemic events (≤ 70 mg/dL), with an event rate of 1.51 events/patient/year. CONCLUSION: In a T2D population with suboptimal HbA1c, initiating V-Go therapy in a real-world setting significantly improved glycemic control and led to significant insulin dose reductions. ClinicalTrial.gov registry identifier: NCT01326598.

A Pragmatic Clinical Trial to Compare the Real-World Effectiveness of V-Go versus Standard Delivery of Insulin in Patients with Advanced Type 2 Diabetes.

BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs. OBJECTIVE: This prospective pragmatic clinical trial evaluated V-Go, a wearable insulin delivery device, compared with standard treatment optimization (STO) among insulin-treated patients with T2DM in a real-world, community-based practice setting. METHODS: Study sites, rather than individual patients, were randomized to V-Go or STO via cluster randomization. Patients were treated according to routine clinical practice and followed up to 4 months. T2DM medications and supplies were purchased utilizing usual insurance and co-pay systems. The primary analysis was an unadjusted treatment group comparison of glycosylated hemoglobinA1c (HbA1c) change from baseline to end of study (EOS). A cost of therapy analysis was completed on patients who had received comparable baseline T2DM treatment with multiple daily basal-bolus insulin injections (MDI). RESULTS: Analysis included 415 patients (169 V-Go, 246 STO) enrolled from 52 US sites. Mean baseline HbA1c (9.6%) was higher in V-Go (9.9%, range 8.0% - 14.2%) than STO (9.3%, range 7.9% - 13.9%, p <.001). HbA1c decreased from baseline to EOS in both V-Go (-1.0%, p<.001) and STO (-0.5%, p<.001); V-Go had significantly larger decrease (p=.002). V-Go had a significant reduction (p<.001) in mean insulin total daily dose (TDD; 0.76 U/kg baseline, 0.57 U/kg EOS), not seen in STO (0.72 U/kg baseline and EOS). The MDI group included 95 (56.2%) V-Go and 113 STO (45.9%) patients. Mean baseline HbA1c was significantly higher in V-Go (9.9%) than STO (9.4%). V-Go also experienced larger decrease in HbA1c from baseline (-1.0%) than STO (-0.36%) (p=.006) with a decrease in TDD, while STO TDD remained unchanged. EOS mean per patient per day cost of diabetes treatment was lower for V-Go ($30.59) vs STO ($32.20) (p=.006). V-Go was more cost effective than STO ($24.02 per 1% drop in HbA1c vs $58.86, respectively). CONCLUSIONS: This pragmatic clinical trial demonstrated improved HbA1c levels, lower cost, and decreased insulin dose in patients with T2DM initiating V-Go vs STO in a real-world community-based practice setting. Observed baseline HbAlc indicated use of V-Go in more difficult to manage diabetes patients.

Efficacy and clinical safety of pegbovigrastim for preventing naturally occurring clinical mastitis in periparturient primiparous and multiparous cows on US commercial dairies.

Periparturient dairy cows experience impaired immune function, exhibited as a transient decrease in neutrophil function. This decrease in immune competence is associated with an increase in susceptibility to bacterial infections, including mastitis and metritis. Bovine granulocyte colony stimulating factor (bG-CSF) is an endogenous protein that enhances neutrophil bactericidal functions and increases the production of neutrophils from bone marrow precursors. Administration of pegbovigrastim (recombinant bG-CSF covalently bound to polyethylene glycol) around the time of calving has been shown to reduce the incidence of new clinical mastitis cases in a natural disease model system. To further explore the application of pegbovigrastim under herd management systems typical of those found in the US dairy industry, we conducted a multicenter field study to evaluate the efficacy and clinical safety of pegbovigrastim administered to multiparous cows and heifers approximately 7 d before calving and within 24 h of calving. Responses of treated cows were compared with those of animals treated with sterile saline. Animals treated with pegbovigrastim exhibited 4- to 5-fold increases in circulating neutrophil numbers within 24 h of treatment initiation, and this increase persisted at least a week beyond the second dose. Pegbovigrastim-treated animals exhibited a 35% decrease in the incidence of clinical mastitis relative to the controls during the first 30 d of lactation. Animals treated with pegbovigrastim also exhibited a 52% reduction in failure to return to visual estrus within 80 d of calving. We observed no differences in somatic cell count or milk composition between treated and control animals. We also found no differences in the duration of pregnancy or proportion of viable calves in treated cows relative to control animals. These results indicate that administration of pegbovigrastim provides a well-tolerated, novel approach to overcoming periparturient immune suppression, resulting in reduced susceptibility to clinical mastitis during early lactation.

A Retrospective Chart Review of Two Different Insulin Administration Systems on Glycemic Control in Older Adults in Long-Term Care.

The current retrospective chart review compared glycemic control and cost impact of two insulin administration systems, V-Go® versus usual care with standard of care (SOC) insulin injections, in eight patients residing in a nursing home (NH). A total of 1,937 blood glucose (BG) values were collected over 61 days. Significant improvements were observed for the V-Go versus SOC group in time in range 100 mg/dL to 200 mg/dL (V-Go 59.09% vs. SOC 34.02%; p < 0.001), reduced BG fluctuations as measured by standard deviation (V-Go 61.2 vs. SOC 92.1; p < 0.001), and improved mean daily BG (V-Go 159.38 mg/dL vs. SOC 223.86 mg/dL; p < 0.001). The estimated A1c change, calculated from BG values, decreased from 8.9% to 7.2% in the V-Go group and increased from 9.0% to 9.4% in the SOC group. Compared to SOC, use of V-Go decreased the mean time for insulin administration by nursing staff by 26.3 minutes per patient per day and associated labor costs by $328.75 per patient per month. Insulin administration with V-Go may improve glycemic control and reduce administration costs compared to existing care in the NH setting. [Journal of Gerontological Nursing, 43(1), 10-16.].

Darwin's Influence on Mendel: Evidence from a New Translation of Mendel's Paper.

Gregor Mendel's classic paper, Versuche über Pflanzen-Hybriden (Experiments on Plant Hybrids), was published in 1866, hence 2016 is its sesquicentennial. Mendel completed his experiments in 1863 and shortly thereafter began compiling the results and writing his paper, which he presented in meetings of the Natural Science Society in Brünn in February and March of 1865. Mendel owned a personal copy of Darwin's Origin of Species, a German translation published in 1863, and it contains his marginalia. Its publication date indicates that Mendel's study of Darwin's book could have had no influence while he was conducting his experiments but its publication date coincided with the period of time when he was preparing his paper, making it possible that Darwin's writings influenced Mendel's interpretations and theory. Based on this premise, we prepared a Darwinized English translation of Mendel's paper by comparing German terms Mendel employed with the same terms in the German translation of Origin of Species in his possession, then using Darwin's counterpart English words and phrases as much as possible in our translation. We found a substantially higher use of these terms in the final two (10th and 11th) sections of Mendel's paper, particularly in one key paragraph, where Mendel reflects on evolutionary issues, providing strong evidence of Darwin's influence on Mendel.

The Clinical and Economic Impact of the V-Go® Disposable Insulin Delivery Device for Insulin Delivery in Patients with Poorly Controlled Diabetes at High Risk.

BACKGROUND: Diabetes is a chronic condition and when poorly controlled can lead to complications and death. Patients with glycated hemoglobin (A1C) measures >9 % are at significant risk for diabetes-related complications impacting the patient's quality of life and imposing higher costs on the healthcare system. A1C reductions of 1 % or greater in this population have demonstrated substantial health and economic benefits. Reducing the percent of patients at risk is an essential component of quality-care measures established for patients with diabetes. OBJECTIVE: To evaluate if switching patients prescribed subcutaneous insulin injections to V-Go for insulin delivery would impact clinical and economic parameters in patients with poorly controlled diabetes (A1C > 9 %). METHODS: The study was a retrospective analysis using data extracted from the electronic medical records database of a multicenter diabetes system. Outcome measures included mean change in A1C from baseline, the percent of patients achieving a reduction in A1C ≥1 % while on V-Go therapy, and the impact to quality measures. In addition, economic analyses were conducted to assess the pharmacy budget impact and projected implication to total healthcare cost. RESULTS: Ninety-seven patients were evaluated after a mean duration of 13.6 ± 6.9 weeks of insulin delivery with V-Go. Switching to V-Go resulted in an overall mean change (95 % CI) in A1C of -2.0 % (-1.7 to -2.3; p < 0.001) from a baseline of 10.5 %. Seventy-three percent of patients achieved an A1C reduction ≥1 %. Cost analysis supported a direct pharmacy savings of $119.30 (18.80-219.60, p = 0.020) per patient per month compared with baseline. CONCLUSION: Switching to V-Go for insulin delivery resulted in significant glycemic improvement and proved cost effective. This real-world assessment could be applied more broadly at the health system and plan level.

Using observational data to inform the design of a prospective effectiveness study for a novel insulin delivery device.

OBJECTIVE: To inform the design and assess the feasibility of a prospective effectiveness study evaluating an insulin delivery device for patients with diabetes mellitus to be conducted within the membership of a large US commercial insurer. METHODS: Providers who issued ≥1 insulin prescription between January 1, 2011 and September 30, 2011 were selected from administrative claims contained in the HealthCore Integrated Research Database(SM). Adult diabetes patients with visits to these providers were identified. Providers were dichotomized into high- (HVPs) and low-volume providers (LVPs) based on median number of diabetes patients per provider. RESULTS: We identified 15,349 HVPs and 15,313 LVPs (median number of patients = 14). Most HVPs were located in the Midwest (6,291 [41.0%]) and South (5,092 [33.2%]), while LVPs were evenly distributed across regions. Over 80% (12,769) of HVPs practiced family or internal medicine; 6.4% (989) were endocrinologists. HVPs prescribed insulin to an average of 25% of patients. Patients of HVPs (522,527) had similar characteristics as patients of LVPs (80,669), except for geographical dispersion, which followed that of providers. Approximately 65% of patients were aged 21-64 years and 97% had type 2 diabetes. Among patients with ≥1 available HbA1C result during 2011 (103,992), 48.3% (50,193) had an average HbA1C ≥7.0%. Among patients initiating insulin, 79.6% (22,205) had an average HbA1C ≥7.0%. CONCLUSION: The observed provider and patient populations support the feasibility of the prospective study. Sampling of patients from HVPs is efficient while minimizing bias as patient characteristics are similar to those from LVPs. The study also highlights unmet needs for improved glycemic control since approximately half of patients with diabetes are not on goal.

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.