Citations

Abstract Objective The opioid epidemic is a national public health emergency that requires a comprehensive approach to reduce opioid-related deaths. Proper and timely disposal of unused prescription opioids is one method to deter improper use of these medications and prevent overdose. The objective of this study was to understand how recommendations for disposing of unused prescription opioids, including both take-back programs and toilet disposal, are communicated to the public. Methods Two hundred sixty-three US newspaper articles published between January 1, 2014, and June 30, 2017, containing information on opioids and take-back programs were found using LexisNexis. Using content analysis, articles were coded for the presentation of and recommendation for opioid disposal practices, beliefs about environmental harm from toilet disposal, and additional strategies to reduce opioid supply. The entity responsible for the statement was also captured. Results Take-back programs were presented as a recommended disposal strategy for unused prescription opioids in 88.6% of coded articles. Toilet disposal was presented as a recommended disposal strategy for unused prescription opioids in 3.4% of articles and as harmful to the environment in 16.0% of articles. Individuals from health care, government, and law enforcement were primarily involved in discussing opioid disposal practices. Conclusions Although toilet disposal is recommended by the US Food and Drug Administration (FDA) for disposal of unused prescription opioids when a take-back program is not readily available, it was infrequently presented or recommended in news media articles. These results highlight the importance of improving communication of FDA guidelines for opioid disposal in the media, particularly by health care providers, government employees, and law enforcement officials.

AbstractDisruptions in the medication supply chain and consequent drug product shortages, including shortages of parenteral products used for parenteral nutrition (PN) compounding, have become an increasingly common occurrence. The amino acid solution shortage that resulted from the devastating impact of Hurricanes Maria and Irma on manufacturing facilities in Puerto Rico in 2017 necessitated a rapid, coordinated shift from use of compounded PN to commercial multichamber‐bag PN (MCB‐PN) at our hospitals. We describe our experience operationalizing this intervention via a framework that may be adapted for addressing other drug product shortages to promote rapid yet safe use of therapeutic alternatives.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

Background: The AMPLIFY randomized clinical trial showed that apixaban was associated with significantly lower major bleeding (MB) compared to warfarin for patients with venous thromboembolism (VTE). The main objective of this study was to compare the risk of major bleeding (MB), clinically relevant non-major bleeding (CRNM), and recurrent VTE among VTE patients treated with apixaban vs warfarin in the US Medicare population. Methods: Patients (aged ≥65 years) prescribed apixaban or warfarin within 30 days following a VTE event diagnosed in hospital or ambulatory setting were identified from 01SEPT2014-31DEC2016 using 100% CMS Medicare data. The first apixaban or warfarin prescription claim outside of the hospital was defined as the index date. Patients were required to have had continuous health plan enrollment for 6 months and no parenteral or oral anticoagulant use before the index VTE event. Outcomes were assessed from index date to the earliest of discontinuation, switch, health plan disenrollment, death, 6 months post-index date, or 31DEC2016. One-to-one propensity score matching (PSM) was used to balance patient characteristics. Cox proportional hazard models were used to estimate the risk of MB, CRNM bleeding, and recurrent VTE. Results: Among 37,799 patients meeting inclusion criteria, 25,284 patients initiated warfarin (66.9%) and 12,515 patients initiated apixaban (33.1%). Post-PSM, 11,363 matched pairs of apixaban-warfarin patients were identified, with a mean follow-up period of 4.0 and 4.4 months. Mean age was 78 years; nearly 37% of patients were male with a mean Charlson Comorbidity Index score of 2.9 in both groups. Apixaban was associated with a lower risk of MB (HR: 0.76; 95% CI: 0.64-0.91) and CRNM bleeding (HR: 0.77; 95% CI: 0.70-0.84) compared to warfarin. The risk of recurrent VTE was similar among apixaban and warfarin patients (HR: 1.04; 95% CI: 0.75-1.43; Figure). Conclusions: Among US Medicare patients with VTE, apixaban was associated with a lower risk of MB and CRNM bleeding and similar risk of recurrent VTE compared to warfarin. These results may be supportive in evaluating the risk-benefit ratio of apixaban for treatment of elderly VTE patients.

Summary Opioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years.

Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

PURPOSE Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM. METHODS INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs. CONCLUSION INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure.

Background: The patient/caregiver experience during CAR-T therapy is stressful, overwhelming, terrifying, and often a patient’s last treatment option. The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Innovation and Design team has worked with the CAR-T therapy clinical team to develop a patient experience that provides patients with a sense of caring, supportive environment, timely knowledge, and realistic expectations. Using a human-centered design approach, the Innovation and Design team worked with patients and caregivers to understand latent and unspoken needs in order to develop an ideal CAR-T therapy patient journey. Methods: With qualitative interviewing techniques, patient observation, and low fidelity experimentation, 21 patients/caregiver pairs were interviewed throughout their CAR-T therapy experience in 2018. Patients were interviewed at several touch points as well as encouraged to reach out to the Innovation and Design team at any point with reflections on their experiences. Patients were recruited as they began their evaluation phase for CAR-T therapy. The interviews were unscripted to allow for a breadth of discovery by not constraining the conversations to previously developed themes. As themes emerged from patient/caregiver interviews, artifacts and interventions were designed to alleviate pain points and improve the patient/caregiver experience. These artifacts and interventions were integrated into the clinical processes in real time and patient/caregivers were interviewed to understand the impact of these activities. Results: Several themes emerged from qualitative interviews with patients and caregivers. From the themes, interventions were developed. We were able to demonstrate a qualitative improvement in patient/caregiver experience through these interventions (Figure 1). Conclusions: Patients/caregivers undergoing CAR-T therapy have unique issues surrounding the logistics of care, emotional burden, and physical effects of treatment. We implemented processes to address these issues and observed a qualitative improvement via patient interviews/feedback. Ongoing work includes optimizing remote monitoring, digital platforms for patient education, and a quantitative study looking at patient reported outcomes (PROs) in such patients. To our knowledge, this is the first report for care delivery optimization in real-world practice for this new therapy.