Citations

Purpose To examine medical student attitudes toward cost-conscious care and whether regional health care intensity is associated with reported exposure to physician role-modeling behaviors related to cost-conscious care. Method Students at 10 U.S. medical schools were surveyed in 2015. Thirty-five items assessed attitudes toward, perceived barriers to and consequences of, and observed physician role-modeling behaviors related to cost-conscious care (using scales for cost-conscious and potentially wasteful behaviors; Cronbach alphas of 0.82 and 0.81, respectively). Regional health care intensity was measured using Dartmouth Atlas End-of-Life Chronic Illness Care data: ratio of physician visits per decedent compared with the U.S. average, ratio of specialty to primary care physician visits per decedent, and hospital care intensity index. Results Of 5,992 students invited, 3,395 (57%) responded. Ninety percent (2,640/2,932) agreed physicians have a responsibility to contain costs. However, 48% (1,1416/2,960) thought ordering a test is easier than explaining why it is unnecessary, and 58% (1,685/2,928) agreed ordering fewer tests will increase the risk of malpractice litigation. In adjusted linear regression analyses, students in higher-health-care-intensity regions reported observing significantly fewer cost-conscious role-modeling behaviors: For each one-unit increase in the three health care intensity measures, scores on the 21-point cost-conscious role-modeling scale decreased by 4.4 (SE 0.7), 3.2 (0.6), and 3.9 (0.6) points, respectively (all P < .001). Conclusions Medical students endorse barriers to cost-conscious care and encounter conflicting role-modeling behaviors, which are related to regional health care intensity. Enhancing role modeling in the learning environment may help prepare future physicians to address health care costs.

OBJECTIVE Improvement in treatment outcome for patients with glioblastoma multiforme (GBM) requires a multifaceted approach due to dysregulation of numerous signaling pathways. The murine double minute 2 (MDM2) protein may fulfill this requirement because it is involved in the regulation of growth, survival, and invasion. The objective of this study was to investigate the impact of modulating MDM2 function in combination with front-line temozolomide (TMZ) therapy in GBM. METHODS The combination of TMZ with the MDM2 protein–protein interaction inhibitor nutlin3a was evaluated for effects on cell growth, p53 pathway activation, expression of DNA repair proteins, and invasive properties. In vivo efficacy was assessed in xenograft models of human GBM. RESULTS In combination, TMZ/nutlin3a was additive to synergistic in decreasing growth of wild-type p53 GBM cells. Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. Pharmacokinetic studies indicated that nutlin3a was detected in human intracranial tumor xenografts. To assess therapeutic potential, efficacy studies were conducted in a xenograft model of intracranial GBM by using GBM cells derived from a recurrent wild-type p53 GBM that is highly TMZ resistant (GBM10). Three 5-day cycles of TMZ/nutlin3a resulted in a significant increase in the survival of mice with GBM10 intracranial tumors compared with single-agent therapy. CONCLUSIONS Modulation of MDM2/p53-associated signaling pathways is a novel approach for decreasing TMZ resistance in GBM. To the authors' knowledge, this is the first study in a humanized intracranial patient-derived xenograft model to demonstrate the efficacy of combining front-line TMZ therapy and an inhibitor of MDM2 protein–protein interactions.

AbstractObjectivesCoronary computerized tomography angiography (CCTA) is a rapidly emerging technology for the evaluation of chest pain in the emergency department (ED). We assessed trends in CCTA use and compared downstream healthcare utilization between CCTA and cardiac stress testing modalities.MethodsUsing administrative claims data (Optum Labs Data Warehouse) from over 100 million geographically diverse privately insured and Medicare Advantage enrollees across the United States, we identified 2,047,799 ED patients from January 2006 to December 2013 who presented with chest pain and had a CCTA or cardiac stress test within 72 hours. Cohorts were established based on CCTA or functional stress testing (myocardial perfusion scintigraphy [MPS], stress echocardiogram [SE], or treadmill exercise electrocardiogram [TMET]) performed within 72 hours of the ED visit. We tracked subsequent invasive cardiac procedures (invasive coronary angiography [ICA], percutaneous coronary intervention [PCI], and coronary artery bypass grafting [CABG]), repeat noninvasive testing, return ED visits, hospitalization, and the rate of acute myocardial infarction (AMI) within 30 days. We used propensity‐score matching to adjust for coronary artery disease (CAD) risk factors, Charlson‐Deyo comorbidity index, and baseline differences between patients selected for CCTA or cardiac stress testing. Logistic regression was used to measure adjusted associations between testing modality and outcomes.ResultsDuring the study period, CCTA use increased from 0.8% to 4.5% of all cardiac testing within 72 hours, a change of 434% (p‐value for trend < 0.001), while rates of other cardiac stress testing modalities decreased (–22% for TMET [p < 0.001]; –11% for SE [p = 0.11]; –6% for MPS [p = 0.04]. After matching, there was no difference in the 30‐day rate of AMI between testing modalities. Compared to MPS, CCTA was associated with higher rates of PCI (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.04 to 1.51), and CABG (OR = 1.47; 95% CI = 1.03 to 2.13). Compared to SE and treadmill stress testing, CCTA was associated with more invasive procedures, hospitalizations, return ED visits, and repeat noninvasive testing.ConclusionsCCTA use increased fourfold during the study period and was associated with higher rates of PCI, CABG, repeat noninvasive testing, hospitalization, and return ED visits.The authors have no relevant financial information or potential conflicts to disclose.

Background: Pediatric obesity is a significant public health problem with a prevalence of 16.9% among US children. School-based obesity interventions show promise for reducing adiposity in elementary age children. This pilot study evaluated the impact of the Let’s Go! 5-2-1-0 pediatric obesity intervention program in an elementary school setting. Methods: This was a cluster randomized controlled field trial comprising 8 classrooms of second- and third-grade children. The impact of implementation of a standardized 5-2-1-0 curriculum was evaluated in the classrooms by looking at health behavior (self-reported fruit and vegetable and sugar-containing beverage intake, and screen time), physical activity (steps measured by pedometer), and body mass index (BMI). Half of the classrooms were given 5-2-1-0 teaching over a 4-month period. Results: There was no statistical difference in improvement of healthy habits, BMI, or physical activity in the intervention group compared with the control group. Conclusions: The 5-2-1-0 intervention used in this study was feasible. There was no significant change in healthy habits, likely due to the small number of participants in the study. The intervention and control sites were in different classrooms and there could be factors such as teacher enthusiasm, socioeconomic factors, and individual traits affecting habits. Future studies could use pre- and post-intervention quizzes to assess healthy habits knowledge retention, involving the environments the child participates in outside of school, using research-grade pedometers or accelerometers for measuring activity data collection, and recruiting larger samples to ensure adequate statistical power.

This paper describes the goals of the American Society of Health‐System Pharmacists' Pharmacy Practice Model Initiative (PPMI) and its recommendations for health‐system pharmacy practice transformation to meet future patient care needs and elevate the role of pharmacists as patient care providers. PPMI envisions a future in which pharmacists have greater responsibility for medication‐related outcomes and technicians assume greater responsibility for product‐related activities. Although the PPMI recommendations have elevated the level of practice in many settings, they also potentially affect existing clinical pharmacists, in general, and clinical pharmacy specialists, in particular. Moreover, although more consistent patient care can be achieved with an expanded team of pharmacist providers, the role of clinical pharmacy specialists must not be diminished, especially in the care of complex patients and populations. Specialist practitioners with advanced training and credentials must be available to model and train pharmacists in generalist positions, residents, and students. Indeed, specialist practitioners are often the innovators and practice leaders. Negotiation between hospitals and pharmacy schools is needed to ensure a continuing role for academic clinical pharmacists and their contributions as educators and researchers. Lessons can be applied from disciplines such as nursing and medicine, which have developed new models of care involving effective collaboration between generalists and specialists. Several different pharmacy practice models have been described to meet the PPMI goals, based on available personnel and local goals. Studies measuring the impact of these new practice models are needed.

Objectives/HypothesisTo evaluate outcomes of salvage surgery for vestibular schwannoma (VS) that failed primary stereotactic radiosurgery (SRS).MethodsCase‐control study of 37 patients who underwent surgical resection of sporadic VS following prior SRS at two tertiary academic referral centers between 2003 and 2015. A cohort of nonirradiated control subjects, matched according to tumor size, age, and treatment center, were used as comparison.ResultsThirty‐seven patients were included. The median time from radiation to surgical salvage was 36 months (range 9.6–153 months). Following tumor progression after SRS, 18 (49%) patients underwent gross total resection, 10 (27%) underwent near‐total resection, and nine (24%) underwent subtotal resection. Postoperative complications following salvage surgery included one (3%) case of stroke, four (11%) cases of cerebrospinal fluid leak, and two (5%) cases of meningitis. Twenty‐seven (73%) patients had good postoperative facial nerve outcome (House‐Brackmann Score I–II) at long‐term follow‐up. There were no cases of tumor recurrence or regrowth after a median length of 26 months following microsurgical salvage (range 3–114 months). The rate of satisfactory postoperative facial nerve function was not different between study and control subjects (73% vs. 76%; P = 0.8); however, less‐than‐complete resection was utilized more frequently among previously radiated patients (P = 0.01).ConclusionMicrosurgical salvage of VS following primary radiation therapy is challenging. Less‐than‐complete resection is required in a greater percentage of patients to preserve facial nerve integrity and prevent neurological complications. Long‐term follow‐up is needed to determine the risk of delayed progression following incomplete tumor removal.Level of Evidence3b. Laryngoscope, 126:2580–2586, 2016

Objectives: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Materials and Methods: Eligible patients included stage II-IIIB non–small cell lung cancer, stage I central non–small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Results: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients’ refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Conclusions: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.