Association of Continuous Glucose Monitor Receipt and Diabetes Care Provider Type: A Cohort Study of West Virginia Medicaid Beneficiaries With Type 1 Diabetes.

OBJECTIVE: To compare the prevalence of West Virginia Medicaid (WVM) beneficiaries with type 1 diabetes (T1D) with a WVM administrative claim for continuous glucose monitoring (CGM) supplies by whether they received medical care from a board-certified endocrinologist. METHODS: A total of 1494 WVM beneficiaries aged 20-64 with T1D were retrospectively followed from May 2018 to April 2020. The sample consisted of 2 groups: those receiving medical care from board-certified endocrinologists and those receiving medical care from other providers. CGM prevalence is compared before and after WVM started providing insurance coverage for beneficiaries with T1D to use CGM systems in May 2019 using linear regression with and without adjustments for patient characteristics. RESULTS: Thirty-five percent of beneficiaries received care from a board-certified endocrinologist at any point during the sample period. Post-May 2019, the prevalence of WVM administrative claims for CGM supplies was significantly higher among beneficiaries receiving care from an endocrinologist compared with other providers. CONCLUSIONS: Receiving diabetes care from a board-certified endocrinologist is positively associated with having administrative claims for CGM supplies.

LONG-TERM BONE HEALTH AFTER ROUX-EN-Y GASTRIC BYPASS: A PILOT STUDY.

OBJECTIVE: This cross-sectional study was undertaken to assess metabolic bone disease by examining bone mineral density (BMD), fracture prevalence, and nutritional factors pertinent to bone in a cohort >9 years post-Rouxen-Y gastric bypass (RYGB). METHODS: Fifty-one subjects 9.4 to 36.0 years (mean 17.0 ± 8.1) post-RYGB provided a focused history. Dietary calcium and protein were assessed. Dual-energy X-ray absorptiometry (DXA) BMD at the spine, hip, and radius and routine serum chemistries, magnesium, phosphorus, parathyroid hormone, vitamin D, vitamin K, and micronutrients were analyzed. Sixteen subjects provided 24-hour urine for measurement of calcium. RESULTS: The mean maximum weight loss was 70.3 ± 20 kg (47.4 ± 8.9%), and mean net weight loss was 46.9 ± 23.1 kg (31.2 ± 12.5%). The prevalence rates of fracture, secondary hyperparathyroidism, and vitamin D deficiency were 15.7%, 37%, and 39%, respectively. BMD was in the osteoporotic range in 27.5%. The mean calcium:creatinine clearance ratio was 0.0124 ± 0.0131. Median intakes of dietary calcium, total calcium, protein, and vitamin D were 582.5 mg, 947.5 mg, 50.2 g, and 1,000 IU, respectively. Mean Z-scores at all sites were <0 (P<.01). A negative correlation (P<.05) was noted between distal radius Z-score and net change in BMI. Net change in BMI was greater for those with osteoporosis than those without. (P<.05) Conclusion: Many years after RYGB, BMD remains lower than expected compared to an age-, sex-, race-, and weight-matched reference population and is correlated with the amount of weight lost. Deficiencies of Vitamin D and calcium are prevalent. ABBREVIATIONS: BMD = bone mineral density BMI = body mass index Ca:Cr = calcium:creatinine DXA = dual-energy X-ray absorptiometry PTH = parathyroid hormone RYGB = Roux-en-Y gastric bypass UD = ultradistal WHO = World Health Organization.

Brief Report: Feasibility of Delivering the Secret Agent Society Group Social Skills Program via Telehealth During COVID-19: A Pilot Exploration.

During the Coronavirus Pandemic, many have worried about the adverse impact on the social functioning of children with autism spectrum disorder. Telehealth delivered group social skills programs offer one way to address this concern. This brief report describes modifications made to the telehealth delivery of the Secret Agent Society group social skills program to five children on the Autism Spectrum aged eight to nine years and their caregivers. It also presents parent-, child- and clinician- feedback on the pros and cons of the telehealth program format, and describes how the intervention helped children to transition to more in-person contact at a time when social distancing restrictions were lifted. Recommendations for telehealth delivery of future social skills group interventions are also discussed.

Implementation of Video Feedback Within a Community Based Naturalistic Developmental Behavioral Intervention Program for Toddlers With ASD: Pilot Study.

Video feedback (VF) is an intervention delivery technique that complements naturalistic developmental behavioral interventions (NDBI) and parent-mediated interventions (PMI) by using caregiver-child interaction videos reviewed with a clinician to facilitate behavioral change in caregivers. Although VF has been implemented in PMI with young children with ASD, examinations of feasibility and acceptability, as well as the potential effectiveness of VF in community settings, have been limited. In this pilot randomized control trial (NCT03397719; https://clinicaltrials.gov/ct2/show/NCT03397719), families were randomized into a state-funded Early Intervention (EI) NDBI program or the NDBI program augmented with VF. Results demonstrated high levels of implementation and acceptability of VF augmenting the community-based EI program in caregivers and clinicians. Both groups showed significant improvements after 6 months in social communication symptoms and some areas of developmental and adaptive skills. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03397719, identifier: NCT03397719.

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder.

We report on the first regulatory approved clinical trial of a prospective open-label physician-initiated study assessing the safety and efficacy of intradetrusor injected Autologous Muscle Derived Cells (AMDC) treatment for underactive bladder (UAB). 20 non-neurogenic UAB patients were treated. Approximately 50-250 mg of quadriceps femoris muscle was collected using a spirotome 8-gauge needle. The muscle biopsy samples were sent to Cook MyoSite (Pittsburgh, PA) for processing, isolation, and propagation of cells. Research patients received approximately 30 intradetrusor injections of 0.5 mL delivered to the bladder, for a total of 15 mL and 125 million AMDC, performed utilizing a flexible cystoscope under direct vision using topical local anesthesia. Follow-up assessments included adverse events and efficacy via voiding diary and urodynamic testing at 1, 3, 6 and 12 months post-injection. An optional second injection was offered at the end of the 6 months visit. 20 patients received the first injection and all 20 patients requested and received a second injection. Median patient age was 65 years old (range 41-82 years). There were 16 male (80%) and 4 female (20%) patients. Etiology included 7 men (35%) with persistent urinary retention after transurethral resection of the prostate for benign prostatic hyperplasia and 13 patients (65%) with idiopathic chronic urinary retention. At the primary outcome time point of 12 months, 11/19 patients (58%) reported a global response assessment (GRA) ≥ 5, showing slight to marked improvement in their UAB symptoms, compared to 6/20 (30%) patients at 3 months post-injection. No serious procedure or treatment-related adverse events occurred. Noted improvements included: decreased post void residual urine volume, increased voiding efficiency, and decreased catheter use. Intradetrusor-injected AMDC as a treatment for UAB was successfully completed in a 20-patient trial without serious adverse event and with signal of efficacy. Cellular therapy may be a promising novel treatment for catheter-dependent chronic urinary retention. A multicenter controlled trial is needed to further assess the promise of regenerative medicine in the treatment of lower urinary tract dysfunction.

Use of the Burden of Diabetes Mellitus Score for Cardiovascular Disease Risk Assessment.

Uncontrolled type II diabetes mellitus (DM) using single point hemoglobin A1c levels has been associated with poor cardiovascular outcomes. However, methods to quantify the effect of uncontrolled DM over time have been inconsistent. To quantify hyperglycemia over time and assess its cardiovascular effects we developed and tested a DM burden score which accounts for time in years prior to DM diagnosis, diagnostic HbA1c, and aggregate HbA1c levels thereafter. A retrospective cohort study was performed with patients (n = 188) from a single academic center with type II DM and no prior cardiac disease history. Patient scores were calculated from diagnosis until the year 2015 and were grouped into low (<5.3%; n = 55), moderate (5.3% to 5.5%; n = 80), and high (>5.5%; n = 53) DM burden score cohorts. At 48 months, the cohort with high DM burden scores correlated with significantly worse major adverse cardiovascular events (hazard ratio [HR] 3.07, p = 0.012), myocardial infarction (HR 12.78, p = 0.015), coronary revascularization (HR 4.53, p = 0.019), cardiovascular hospitalizations (HR 4.20, p = 0.005), and all-cause hospitalizations (HR 2.57, p = 0.01). Cardiovascular and all-cause mortality showed significant difference between groups in log-rank testing. Also, a multivariate regression model showed DM burden score (p = 0.045) to be an independent predictor of major adverse cardiovascular events (HR 9.38, p = 0.045). In conclusion, this study provides evidence that DM control over time impacts cardiovascular outcomes.

Incidence and Outcomes of Non-ST Elevation Myocardial Infarction in Patients Hospitalized with Decompensated Diabetes.

Single center studies suggested that non-ST elevation myocardial infarction (NSTEMI) in patients admitted with acute decompensated diabetes is associated with poor long-term prognosis. We hypothesize that acute decompensated diabetes is also associated with worse early morbidity and mortality in patients admitted with NSTEMI. Adult patients with a primary discharge diagnosis of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) were identified in the national inpatient sample. We then assessed contemporary trends in the incidence and management patents of NSTEMI in patients admitted with DKA/HHS and compared in-hospital morbidity and mortality, resource utilization, and cost between DKA/HHS patients with and without NSTEMI. In 431,037 patients admitted with decompensated diabetes from 2003 to 2014, 13,069 (3.03%) suffered a NSTEMI during their hospitalization. Patients with NSTEMI were older and had higher prevalence of atherosclerotic and nonatherosclerotic comorbidities. After propensity score matching, NSTEMI was associated with a 60% increase in in-hospitalmortality (9.1% vs 5.5%; p < 0.001), higher incidences of stroke, acute kidney injury, blood transfusion, longer hospitalizations, and higher costs. A minority (35%) ofNSTEMI patients underwent invasive coronary assessment, and those had lower in-hospitalmortality compared with NSTEMI patients who did not undergo invasive assessment(3.3% vs 12.2%, adjusted OR 0.30, 95%CI 0.24 to 0.36, p < 0.001). About 3% of patients admitted with decompensated diabetes suffer a NSTEMI and those experience higher in-hospital morbidity and mortality, longer hospitalization, and higher cost.

An iterative model for in vitro laboratory assessment of tamper deterrent formulations.

BACKGROUND: In an effort to address the continuing problem of prescription opioid abuse, manufacturers are incorporating new technologies into formulations that are designed to deter product tampering and misuse. Standards for laboratory assessment of tamper deterrent properties of new formulations have not previously been developed. METHODS: Experimental designs were developed for the in vitro laboratory assessment of the tamper deterrent properties of reformulated oxycodone. Given that an exhaustive study of all potential tampering methods was impractical; this model was developed to evaluate the product in an incremental fashion with iterative changes that were amenable to objective and replicable laboratory testing. RESULTS: A description of the model is provided along with pertinent examples involving assessment of reformulated oxycodone with comparisons to the original formulation. Physical and chemical procedures were developed that relate to "real-world" scenarios that may be applied to opioid formulations. Test results were interpreted in relation to the relative ease or difficulty of the manipulation as compared to control materials and the amount and purity of active drug that could be accessed. Results from some of the tests were designed to be useful in predicting whether specific tampering methods would facilitate or deter drug administration by different routes of administration. CONCLUSIONS: This model, developed to assess the tamper deterrent properties of reformulated oxycodone, should have application in the assessment of other drug formulations designed to exhibit tamper deterrence properties.

Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API.

PURPOSE: The bioavailability of a development candidate active pharmaceutical ingredient (API) was very low after oral dosing in dogs. In order to improve bioavailability, we sought to increase the dissolution rate of the solid form of the API. When traditional methods of forming salts and amorphous material failed to produce a viable solid form for continued development, we turned to the non-traditional approach of cocrystallization. METHODS: A crystal engineering approach was used to design and execute a cocrystal screen of the API. Hydrogen bonding between the API and pharmaceutically acceptable carboxylic acids was identified as a viable synthon for associating multiple components in the solid state. A number of carboxylic acid guest molecules were tested for cocrystal formation with the API. RESULTS: A cocrystal containing the API and glutaric acid in a 1:1 molecular ratio was identified and the single crystal structure is reported. Physical characterization of the cocrystal showed that it is unique regarding thermal, spectroscopic, X-ray, and dissolution properties. The cocrystal solid is nonhygroscopic, and chemically and physically stable to thermal stress. Use of the cocrystal increased the aqueous dissolution rate by 18 times as compared to the homomeric crystalline form of the drug. Single dose dog exposure studies confirmed that the cocrystal increased plasma AUC values by three times at two different dose levels. CONCLUSIONS: APIs that are non-ionizable or demonstrate poor salt forming ability traditionally present few opportunities for creating crystalline solid forms with desired physical properties. Cocrystals are an additional class of crystalline solid that can provide options for improved properties. In this case, a crystalline molecular complex of glutaric acid and an API was identified and used to demonstrate an improvement in the oral bioavailability of the API in dogs.