Recent Publications by CFE Educators

Pharmacogenomics aims to use molecular genetic markers to predict treatment outcome. Indeed, within the past decade there has been a rapid emergence of pharmacogenetic tests to aid clinicians in predicting efficacy or toxicity for some drugs. Despite this major advance in therapeutic drug management, there remain challenges to the appropriate use of pharmacogenetic tests. We discuss UGT1A1 pharmacogenetic testing to illustrate the knowledge gaps impeding widespread use of pharmacogenetic tests in the clinical setting.

Starting clerkships is anxiety provoking for medical students. To ease the transition from preclerkship to clerkship curricula, schools offer classroom-based courses which may not be the best model for preparing learners. Drawing from workplace learning theory, the authors developed a seven-day transitional clerkship (TC) in 2007 at the University of California, San Francisco School of Medicine in which students spent half of the course in the hospital, learning routines and logistics of the wards along with their roles and responsibilities as members of ward teams. Twice, they admitted and followed a patient into the next day as part of a shadow team that had no patient-care responsibilities. Dedicated preceptors gave feedback on oral presentations and patient write-ups. Satisfaction with the TC was higher than with the previous year's classroom-based course. TC students felt clearer about their roles and more confident in their abilities as third-year students compared with previous students. TC students continued to rate the transitional course highly after their first clinical rotation. Preceptors were enthusiastic about the course and expressed willingness to commit to future TC preceptorships. The transitional course models an approach to translating workplace learning theory into practice and demonstrates improved satisfaction, better understanding of roles, and increased confidence among new third-year students.

OBJECTIVE

Higher surgeon volume is associated with improved patient outcomes. This finding has prompted recommendations for increasing specialization and referrals to high-volume surgeons, yet their implementation in clinical practice has not been measured.

METHODS

We performed cross-sectional analyses using 1999 and 2005 discharge information from the Health Care Utilization Project National Inpatient Sample to measure whether the number of procedures performed by high-volume surgeons increased over time. Procedures included those demonstrated to have strong surgeon volume-outcome associations in the literature. International Classification of Diseases, Ninth Revision codes were employed for colorectal procedures, esophagectomy, gastrectomy, pancreatectomy, thyroidectomy, coronary artery bypass graft surgery, and carotid endarterectomy. Bivariate analyses and hierarchical generalized linear models were employed to measure association between surgeon volume and length of stay (LOS) and mortality or complications.

RESULTS

There was a significant increase in the proportion of procedures performed by high-volume surgeons over time, with the most dramatic increases seen for gastrectomy (54%), pancreatectomy (31%), and thyroidectomy (23%). Having a procedure performed by a high-volume surgeon was associated with patient race and insurance status. Overall, unadjusted mortality and LOS were significantly lower for high-volume surgeons compared with low-volume surgeons in 1999 and 2005. In multivariable hierarchical generalized linear models, only differences in LOS by surgeon volume remained significant in both years.

CONCLUSIONS

The proportion of procedures performed by high-volume surgeons increased over a 6-year period, as evidence mounted in support of a surgeon volume-outcome association. Efforts are still needed to improve access among underserved subsets of the population and eliminate apparent disparities based on patient race and insurance status.

OBJECTIVE

Evidence-based surgery is predicated on the quality of published literature. We measured the quality of surgery manuscripts selected by peer review and identified predictors of excellence.

METHODS

One hundred twenty clinical surgery manuscripts were randomly selected from 1998 in 5 eminent peer-reviewed surgery and medical journals. Manuscripts were blinded for author, institution, and journal of origin. Four surgeons and 4 methodologists evaluated the quality using novel instruments based on subject selection, study protocol, statistical analysis/inference, intervention description, outcome assessments, and results presentation. Predictors of quality and impact factor were identified using bivariate and multivariate regression.

RESULTS

Oncology was the most common subject (26%), followed by general surgery/gastrointestinal (24%). The average number of study subjects was 417; the majority of manuscripts were American (53%), from a single institution (59%). Eighteen percent had a statistician author. Mean number of citations was 128. Surgery manuscripts from medical, compared with surgery journals, had better total quality scores (3.8 vs. 5.2, P 0.001). They had more subjects and were more likely to have a statistician as coauthor (43% vs. 10%, P 0.001), multi-institutional, international collaboration (30% vs. 8%, P 0.001), and higher citation index (mean: 350 vs. 54, P 0.001). They were more often foreign (70% vs. 40%, P 0.001). Independent predictors of quality were having a statistician coauthor, study funding, European origin, and more study subjects. Quality assessment using our instruments predicted the number of citations after 10 years (P 0.01), along with having a statistician coauthor, international multi-institutional collaboration, and more subjects.

CONCLUSION

The quality of surgery manuscripts can be improved by including a statistician as coauthor, with efforts directed toward implementing multi-institutional/interdisciplinary trials. Peer-review across journals can be standardized through the use of instruments measuring methodologic and clinical quality.

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCbeta3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCbeta3 and the TRPV1 channel; 2) serotonin, or a selective agonist, alpha-methyl-serotonin (alpha-Me-5-HT), requires the presence of PLCbeta3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCbeta3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD(+) neurons that represent approximately 90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1(+) nociceptors led to a significant behavioral deficit for pruritogens, including alpha-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.

Many policymakers believe that comparative effectiveness research will reduce "waste" in the U.S. health care system by providing guidance on what health care options work best for different patients. How such research will produce findings that identify waste has not been clearly elucidated. This paper presents a conceptual framework for different evidentiary categories of what we call "marginal medicine." This framework could help clinicians, researchers, and policymakers align the results of comparative effectiveness research with efforts to identify opportunities to improve the value of health care services.

Seizures are relatively common in Alzheimer disease (AD) and other neurodegenerative disorders. To our knowledge, however, there have been no reports of seizures associated with corticobasal degeneration (CBD). We describe a patient with brain biopsy features suggestive of CBD whose course was complicated by complex partial seizures with secondary generalization. Thus, the occurrence of seizures in a patient with dementia should not exclude the diagnosis of CBD.

Delta and mu opioid receptors (DORs and MORs) are inhibitory G protein-coupled receptors that reportedly cooperatively regulate the transmission of pain messages by substance P and TRPV1-expressing pain fibers. Using a DOReGFP reporter mouse we now show that the DOR and MOR are, in fact, expressed by different subsets of primary afferents. The MOR is expressed in peptidergic pain fibers, the DOR in myelinated and nonpeptidergic afferents. Contrary to the prevailing view, we demonstrate that the DOR is trafficked to the cell surface under resting conditions, independently of substance P, and internalized following activation by DOR agonists. Finally, we show that the segregated DOR and MOR distribution is paralleled by a remarkably selective functional contribution of the two receptors to the control of mechanical and heat pain, respectively. These results demonstrate that behaviorally relevant pain modalities can be selectively regulated through the targeting of distinct subsets of primary afferent pain fibers.