A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Advancing the Science of Healthcare Service Delivery: The NHLBI Corporate Healthcare Leaders' Panel.

There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation. In this context, the National Heart, Lung, and Blood Institute convened a panel made up of leaders of corporate health care entities, including academic health centers, and government agency representatives to inform contemporary strategic partnerships with health care companies. This article provides insights from the meeting on how to execute a transformative innovation research agenda that will foster improvements in health care service delivery by leveraging the translation of biomedical research evidence in real-world settings.

Healthcare costs and nonadherence among chronic opioid users.

OBJECTIVES: To assess the health economic burden of chronic opioid users and to determine whether opioid regimen nonadherence contributes to increased healthcare costs. STUDY DESIGN: Retrospective claims-based analysis of patients with long-term prescription opioid use (>120 days of supply over 6 months). METHODS: Twelve-month healthcare utilization and costs were compared for chronic opioid users (n = 49,425) and, among chronic opioid users with urine drug-monitoring results (n = 2100), between adherent patients versus patients with evidence of nonadherence to their opioid regimen. Likely nonadherence was based on urine test results indicating absence of the prescribed drug, higher or lower than expected drug levels based on a proprietary algorithm, or presence of unprescribed or illegal drugs. The influence of nonadherence on total healthcare costs was assessed using multivariate models. RESULTS: Prevalence of chronic opioid use was 1.3%. Chronic opioid users had significantly greater healthcare utilization and costs than matched nonusers ($23,049 vs $4975; P <.001). Adherent patients (n = 442) had lower total healthcare costs than likely nonadherent patients (n = 1658; $23,160 vs $26,433; P = .036). After adjustment for demographics, likely nonadherence was significantly associated with elevated total healthcare costs (cost ratio [CR] 1.136; 95% confidence interval [CI] 1.00, 1.29; P = .048). When adjusting for other types of nonadherence, the presence of higher than expected levels of the prescribed opioid was associated with significantly elevated costs (CR 1.121; 95% CI 1.01, 1.25; P = .039). CONCLUSION: Chronic opioid users represent a substantial cost burden relative to similar patients without evidence of chronic pain. Among likely nonadherent chronic opioid users, those with evidence of opioid overuse had significantly elevated healthcare costs.

High rates of inappropriate drug use in the chronic pain population.

Chronic opioid treatment is a highly effective method to treat chronic pain; however, the prevalence of abuse of opioids can make treating patients with these agents difficult for clinicians. The objective of this study was to describe rates of inappropriate utilization, abuse, and diversion in a population of patients who were prescribed chronic opioids, as measured by urine drug testing in the clinical setting. A retrospective analysis was conducted of results from all urine drug tests conducted by Ameritox, Ltd. between January 2006 and January 2009, for patients whose physicians ordered the test in order to screen for noncompliance. Data from 938,586 patient test samples showed that 75% of patients were unlikely to be taking their medications in a manner consistent with their prescribed pain regimen. Thirty-eight percent of patients were found to have no detectable level of their prescribed medication, 29% had a nonprescribed medication present, 27% had a drug level higher than expected, 15% had a drug level lower than expected, and 11% had illicit drugs detected in their urine. Note that all categories add to a total greater than 100% as each category is not mutually exclusive, and a single patient could fall into multiple categories. The high observed rate of noncompliance demonstrates a significant clinical concern and confirms the importance of periodic urine drug screening for the population prescribed long-term opioid therapy.

Use of an algorithm applied to urine drug screening to assess adherence to an oxycontin regimen.

OBJECTIVE: This study examined the ability of an algorithm applied to urine drug levels of oxycodone in healthy adult volunteers to differentiate among low, medium, and high doses of OxyContin. PARTICIPANTS AND INTERVENTIONS: Thirty-six healthy volunteers were randomized to receive 80, 160, or 240 mg of daily OxyContin to steady state while under a naltrexone blockade. During days 3 and 4 of the study, urine samples of all participants were collected, and oxycodone levels detected in the urine were obtained using a liquid chromatography-mass spectrometry (LC-MS-MS) assay. OUTCOME MEASURES: The concordance was calculated for raw and adjusted LC-MS-MS urine oxycodone values within each study participant between their third and fourth day values. Also, an analysis of medians was calculated for each of the dosage groupings using Bonett-Price confidence intervals for both raw and adjusted LC-MS-MS values. RESULTS: The concordance correlation coefficient for the raw LC-MS-MS values between days 3 and 4 was 0.689 (95% confidence intervals = 0.515, 0.864), whereas the concordance correlation coefficient for the LC-MS-MS values using the algorithm (ie, normalized values) was 0.882 (95% confidence intervals = 0.808, 0.956). Because of greater variability in the raw values, some overlap was observed in the confidence intervals of the various OxyContin doses, whereas no overlap was observed in the normalized confidence intervals regardless of the application of a Bonferroni adjustment. CONCLUSIONS: In contrast to raw LC-MS-MS values, an algorithm that normalizes oxycodone urine drug levels for pH, specific gravity, and lean body mass discriminates well among all three of the daily doses of OxyContin tested (80, 160, and 240 mg), even with correcting for multiple analyses.