Publications

PROBLEM

The Association of Program Directors in Internal Medicine, the Accreditation Council for Graduate Medical Education, the Alliance for Academic Internal Medicine, and the Carnegie Foundation report on medical education recommend creating individualized learning pathways during medical training so that learners can experience broader professional roles beyond patient care. Little data exist to support the success of these specialized pathways in graduate medical education.

INTERVENTION

We present the 10-year experience of the Primary Care Medicine Education (PRIME) track, a clinical-outcomes research pathway for internal medicine residents at the University of California San Francisco (UCSF). We hypothesized that participation in an individualized learning track, PRIME, would lead to a greater likelihood of publishing research from residency and accessing adequate career mentorship and would be influential on subsequent alumni careers.

CONTEXT

We performed a cross-sectional survey of internal medicine residency alumni from UCSF who graduated in 2001 through 2010. We compared responses of PRIME and non-PRIME categorical alumni. We used Pearson's chi-square and Student's t test to compare PRIME and non-PRIME alumni on categorical and continuous variables.

OUTCOME

Sixty-six percent (211/319) of alumni responded to the survey. A higher percentage of PRIME alumni published residency research projects compared to non-PRIME alumni (64% vs. 40%; p = .002). The number of PRIME alumni identifying research as their primary career role was not significantly different from non-PRIME internal medicine residency graduates (35% of PRIME vs. 29% non-PRIME). Process measures that could explain these findings include adequate access to mentors (M 4.4 for PRIME vs. 3.6 for non-PRIME alumni, p < .001, on a 5-point Likert scale) and agreeing that mentoring relationships affected career choice (M 4.2 for PRIME vs. 3.7 for categorical alumni, p = .001). Finally, 63% of PRIME alumni agreed that their research experience during residency influenced their subsequent career choice versus 46% of non-PRIME alumni (p = .023).

LESSONS LEARNED

Our results support the concept that providing residents with an individualized learning pathway focusing on clinical outcomes research during residency enables them to successfully publish manuscripts and access mentorship, and may influence subsequent career choice. Implementation of individualized residency program tracks that nurture academic interests along with clinical skills can support career development within medicine residency programs.

As the world's aging population grows, the surgical population is increasingly made up of older adults. Due to changes in physiologic function and increasing comorbidity burden, older adults are at increased risk of morbidity, mortality, and functional decline after surgery. In addition, decision to undergo surgery for the older adult may be based on the postoperative functional outcome rather than survival. Although few studies have evaluated an older adult's function as a postoperative outcome, surgeons are becoming increasingly aware of the importance of maintaining or regaining function in an older patient. Interventions to improve postoperative functional outcomes are being developed and show promising results. This review discusses existing literature on postoperative functional outcomes in older adults and recently developed interventions.

PURPOSE

Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy.

EXPERIMENTAL DESIGN

A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy.

RESULTS

A total of 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1,000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. An SNP in VAC14 (rs875858) surpassed genome-wide significance (P = 2.12 × 10, adjusted P = 5.88 × 10). siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (P = 0.0015) and branches (P < 0.0001). Prior to docetaxel treatment, VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (P = 0.001).

CONCLUSIONS

VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization. Clin Cancer Res; 22(19); 4890-900. ©2016 AACR.