Recent Publications by CFE Educators

The process by which excitatory neurons are generated and mature during the development of the cerebral cortex occurs in a stereotyped manner; coordinated neuronal birth, migration, and differentiation during embryonic and early postnatal life are prerequisites for selective synaptic connections that mediate meaningful neurotransmission in maturity. Normal cortical function depends upon the proper elaboration of neurons, including the initial extension of cellular processes that lead to the formation of axons and dendrites and the subsequent maturation of synapses. Here, we examine the role of cell-based signaling via the receptor tyrosine kinase EphA7 in guiding the extension and maturation of cortical dendrites. EphA7, localized to dendritic shafts and spines of pyramidal cells, is uniquely expressed during cortical neuronal development. On patterned substrates, EphA7 signaling restricts dendritic extent, with Src and Tsc1 serving as downstream mediators. Perturbation of EphA7 signaling in vitro and in vivo alters dendritic elaboration: Dendrites are longer and more complex when EphA7 is absent and are shorter and simpler when EphA7 is ectopically expressed. Later in neuronal maturation, EphA7 influences protrusions from dendritic shafts and the assembling of synaptic components. Indeed, synaptic function relies on EphA7; the electrophysiological maturation of pyramidal neurons is delayed in cultures lacking EphA7, indicating that EphA7 enhances synaptic function. These results provide evidence of roles for Eph signaling, first in limiting the elaboration of cortical neuronal dendrites and then in coordinating the maturation and function of synapses.

Skilled clinical decision making in the diagnosis and treatment of chronic pain can create unique clinical and ethical challenges, particularly when opioid medications are involved. This report presents the case of a pregnant woman who sought treatment for an illicit opioid dependence, initiated by opioid analgesic treatment of chronic pain. While recognizing opioids' high level of effectiveness for pain relief, the case demonstrates the potential harms of opioid medications for particular patients. Using a framework informed by medical ethics, the report discusses how clinicians might assess the benefits and risks of opioid treatment by careful data gathering, knowledge of the evidence base and patient-centered, shared decision making.

BACKGROUND

Adrenalectomy is a complex procedure performed in many settings, with and without residents and fellows. Patients often ask, "Will trainees be participating in my operation?" and seek reassurance that their care will not be adversely affected. The purpose of this study was to determine the association between trainee participation and adrenalectomy perioperative outcomes.

STUDY DESIGN

We performed a cohort study of patients who underwent adrenalectomy from the 2005 to 2011 American College of Surgeons NSQIP database. Trainee participation was classified as none, resident, or fellow, based on postgraduate year of the assisting surgeon. Associations between trainee participation and outcomes were determined via multivariate linear and logistic regression.

RESULTS

Of 3,694 adrenalectomies, 732 (19.8%) were performed by an attending surgeon with no trainee, 2,315 (62.7%) involved a resident, and 647 (17.5%) involved a fellow. The participation of fellows was associated with fewer serious complications (7.9% with no trainee, 6.0% with residents, and 2.8% with fellows; p 0.001). In a multivariate model, the odds of serious 30-day morbidity were lower when attending surgeons operated with residents (odds ratio = 0.63; 95% CI, 0.45-0.89). Fellow participation was associated with significantly lower odds of overall (odds ratio = 0.51; 95% CI, 0.32-0.82) and serious (odds ratio = 0.31; 95% CI, 0.17-0.57) morbidity. There was no significant association between trainee participation and 30-day mortality.

CONCLUSIONS

In this analysis of multi-institutional data, the participation of residents and fellows was associated with decreased odds of perioperative adrenalectomy complications. Attending surgeons performing adrenalectomies with trainee assistance should reassure patients of the equivalent or superior care they are receiving.

Smoking is a major contributor to premature mortality among people with mental illness and substance abuse. Historically, the Substance Abuse and Mental Health Services Administration (SAMHSA) did not include smoking cessation in its mission. We describe the development of a unique partnership between SAMHSA and the University of California, San Francisco's Smoking Cessation Leadership Center. Starting with an educational summit in Virginia in 2007, it progressed to a jointly sponsored "100 Pioneers for Smoking Cessation" campaign that provided grants and technical assistance to organizations promoting cessation. By 2013, the partnership established 7 "Leadership Academies," state-level multidisciplinary collaboratives of organizations focused on cessation. This academic-public partnership increased tobacco quit attempts, improved collaboration across multiple agencies, and raised awareness about tobacco use in vulnerable populations.

OBJECTIVE

Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.

APPROACH AND RESULTS

Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P2×10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P2×10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.

CONCLUSIONS

Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.

The incidence and prevalence of cardiovascular (CV)-related morbidity and mortality significantly increase with age. In the elderly, hypercholesterolemia with elevated total and low-density-lipoprotein cholesterol is a significant predictor of incident and recurrent CV disease. Multiple lines of evidence have established the benefit of statin therapy to lower cholesterol levels and reduce the risk of CV events as well as prevent progression of subclinical atherosclerotic disease. Elderly patients, particularly those older than 75 years, have not been well represented in randomized clinical trials evaluating lipid lowering therapy. The limited available data from clinical trials do support the benefit of statin therapy in the elderly population. Based upon these data, cholesterol treatment guidelines endorse statin therapy as the primary treatment of hypercholesterolemia in elderly patients, though caution is recommended given the greater number of co-morbid conditions and concern for poly-pharmacy common in the elderly. Additional research is needed to better establish the benefit of statin therapy in the elderly within the context of reducing CV risk, minimizing side effects, and improving overall quality of life.

INTRODUCTION

The need to train physicians committed to learning throughout their careers has prompted medical schools to encourage the development and practice of self-regulated learning by students. Longitudinal integrated clerkships (LICs) require students to exercise self-regulated learning skills. As mobile tools, tablets can potentially support self-regulation among LIC students.

METHODS

We provided 15 LIC students with tablet computers with access to the electronic health record (EHR), to track their patient cohort, and a multiplatform online notebook, to support documentation and retrieval of self-identified clinical learning issues. Students received a 1-hour workshop on the relevant features of the tablet and online notebook. Two focus groups with the students were used to evaluate the program, one early and one late in the year and were coded by two raters.

RESULTS

Students used the tablet to support their self-regulated learning in ways that were unique to their learning styles and increased access to resources and utilization of down-time. Students who used the tablet to self-monitor and target learning demonstrated the utility of tablets as learning tools.

CONCLUSIONS

LICs are environments rich in opportunity for self-regulated learning. Tablets can enhance students' ability to develop and employ self-regulatory skills in a clinical context.

BACKGROUND

The coronary artery calcium (CAC) score predicts future coronary heart disease (CHD) events and could be used to guide primary prevention interventions, but CAC measurement has costs and exposes patients to low-dose radiation.

METHODS AND RESULTS

We estimated the cost-effectiveness of measuring CAC and prescribing statin therapy based on the resulting score under a range of assumptions using an established model enhanced with CAC distribution and risk estimates from the Multi-Ethnic Study of Atherosclerosis. Ten years of statin treatment for 10,000 55-year-old women with high cholesterol (10-year CHD risk, 7.5%) was projected to prevent 32 myocardial infarctions, cause 70 cases of statin-induced myopathy, and add 1108 years to total life expectancy. Measuring CAC and targeting statin treatment to the 2500 women with CAC>0 would provide 45% of the benefit (+501 life-years), but CAC measurement would cost $2.25 million and cause 9 radiation-induced cancers. Treat all was preferable to CAC screening in this scenario and across a broad range of other scenarios (CHD risk, 2.5%-15%) when statin assumptions were favorable ($0.13 per pill and no quality of life penalty). When statin assumptions were less favorable ($1.00 per pill and disutility=0.00384), CAC screening with statin treatment for persons with CAC>0 was cost-effective ($50 000 per quality-adjusted life-year) in this scenario, in 55-year-old men with CHD risk 7.5%, and in other intermediate risk scenarios (CHD risk, 5%-10%). Our results were critically sensitive to statin cost and disutility and relatively robust to other assumptions. Alternate CAC treatment thresholds (>100 or >300) were generally not cost-effective.

CONCLUSIONS

CAC testing in intermediate risk patients can be cost-effective but only if statins are costly or significantly affect quality of life.

Among children, the incidence of bicycle-related genitourinary (GU) injuries was 448 per 100 000 (95% CI 383 to 514) and, among adults, was 53 per 100 000 (95% CI 36 to 71). Although children sustained more injuries, adults were more likely to being admitted to the hospital for the GU injury (OR 1.95, 95% CI 1.13 to 3.37). Children sustain nearly 10 times more GU injuries due to bicycles than adults, but adults have higher odds of sustaining injuries requiring admission.

OBJECTIVE

(1) To determine baseline demographic, geographic, clinical, and pathologic characteristics of patients who had transoral robotic surgery (TORS) for oropharyngeal cancer. (2) To analyze margin status and unplanned readmission after TORS versus nonrobotic surgery.

STUDY DESIGN

Retrospective database review.

SETTING

National Cancer Database (2010-2011).

SUBJECTS AND METHODS

Searching the National Cancer Database for adults with oropharyngeal cancer, we identified 877 patients who had TORS and 4269 patients who had nonrobotic surgery. Outcomes of interest included likelihood of adjuvant therapy, margin status, and unplanned readmission. Statistical analysis included chi-square, t tests, and multivariate regression.

RESULTS

From 2010 to 2011, there was a 67% increase in the use of TORS for oropharyngeal cancer. Compared with patients who had nonrobotic surgery, TORS patients were more likely to be at academic centers (80.8% vs 49.1%, P .001), to have private insurance (62.2% vs 57.4%, P .001), and to have human papilloma virus (HPV)-positive tumors (48.3% vs 27.1%, P .001). TORS (odds ratio, 0.50; 95% CI, 0.39-0.63) and HPV positivity (odds ratio, 0.73; 95% CI, 0.53-0.99) were independently associated with decreased likelihood of adjuvant chemoradiation versus radiation therapy. TORS patients were less likely to have positive margins than were patients who had nonrobotic surgery (20.2% vs 31.0%, P .001). High-volume TORS centers had lower rates of positive margins (15.8% vs 26.1%, P .001) and unplanned readmissions (3.1% vs 6.1%, P .03) than did low-volume centers.

CONCLUSIONS

TORS is being rapidly adopted by academic and community cancer centers. TORS is associated with a lower rate of positive margins than nonrobotic surgery, and high-volume centers have the lowest rates of positive margins and unplanned readmissions.