Faculty Bibliography

Pre-exposure prophylaxis (PrEP) is considered an effective biomedical approach for HIV prevention. However, there is limited understanding of PrEP uptake among racially/ethnically and socioeconomically diverse young men who have sex with men (YMSM). This study examined attitudes and perceptions toward PrEP uptake among YMSM by conducting semistructured interviews with a sample (N = 100) of YMSM in New York City. Thematic analysis was employed to explore key issues related to attitudes and perceptions toward PrEP utilization. Findings suggest that self-perceived risk for HIV transmission, enjoying unprotected sex, and being in a romantic relationship were associated with PrEP uptake. The most prominent barriers to PrEP uptake included costs, adherence regimen, and access. In summary, these findings underscore the importance of addressing behavioral and structural factors in maximizing the effectiveness of PrEP. In addition, PrEP implementation programs ought to consider the role of social and structural challenges to PrEP uptake and adherence among YMSM.

BACKGROUND: Due to high melanoma immunogenicity, germline genetic variants in immune pathways have been studied for association with melanoma prognosis. However, limited candidate selection, inadequate power, or lack of independent validation have hampered the reproducibility of these prior findings, preventing personalised clinical applicability in melanoma prognostication. Our objective was to assess the prognostic utility of genetic variants in immunomodulatory pathways for prediction of melanoma clinical outcomes. METHODS: We genotyped 72 tag single nucleotide polymorphisms (SNPs) in 44 immunomodulatory genes in a population sample of 1022 melanoma patients and performed Cox regression analysis to test the association between SNPs and melanoma recurrence-free (RFS) and overall survival (OS). We have further investigated the most significant associations using a fine mapping strategy and followed with functional analyses in CD4+ T cells in a subset of 75 melanoma patients. RESULTS: The most significant associations were found with melanoma OS for rs3024493 in IL10 at chromosome 1q32.1 (heterozygous HR 0.58, 95% CI 0.39 to 0.86; p=0.0006), a variant previously shown to be linked with autoimmune conditions. Multiple additional SNPs at 1q32.1 were also nominally associated with OS confirming at least two independent association signals in this locus. In addition, we found rs3024493 associated with the downregulation of interleukin 10 (IL10) secretion in CD4+ T cells. CONCLUSIONS: We discovered novel associations of IL10 with melanoma survival at 1q32.1, suggesting this locus should be considered as a novel melanoma prognostic biomarker with potential for aiding melanoma patient management. Our findings also provide further support for an alternative role of IL10 in stimulation of anti-tumour immune response.

CONTEXT: Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. OBJECTIVE: To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. EVIDENCE ACQUISITION: Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. EVIDENCE SYNTHESIS: Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. CONCLUSIONS: There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. PATIENT SUMMARY: Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.

INTRODUCTION & OBJECTIVES: Many elderly men do not receive curative treatment for high risk, non-metastatic prostate cancer (HRnMPCa) despite high mortality with conservative management. We aimed to assess how age and comorbidity affect treatment of men with HRnMPCa. MATERIAL & METHODS: The proportion of men with HRnMPCa treated curatively in Sweden in 2001 to 2012 was assessed in this nationwide, population-based study. 19,190 men with HRnMPCa below age 80 at date of diagnosis were identified in the National Prostate Cancer Register (NPCR) and 95,948 age-matched control men were without prostate cancer retrieved from the Register of the Total Population. 10-year survival in control men, stratified by age and Charlson Comorbidity Index (CCI) was used as a measure of the life expectancy of the men with prostate cancer. RESULTS: The proportion receiving curative treatment co-varied with life expectancy in men below age 70, but not in men in their seventies with CCI 0-1. For example, only 10% of men aged 75-80 years with CCI 0 received curative treatment despite a 52% 10-year survival probability, whereas half of men younger than 70 years with similar life expectancy received curative treatment. The use of curative treatment for HRnMPCa increased during the study period in all counties, but a threefold difference between counties for men aged 70-80 years with CCI 0-1 remained in 2009-2012. CONCLUSIONS: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive treatment than younger men with a similar life expectancy. The disparities in use of curative treatment highlight the need for improved assessment of life expectancy

PURPOSE/OBJECTIVE:The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. MATERIALS AND METHODS/METHODS:From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. RESULTS:The Prostate Health Index was significantly higher in men with Gleason 7 or greater and "Epstein significant" cancer. On receiver operating characteristic analysis phi had the highest AUC for overall prostate cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant prostate cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. CONCLUSIONS:The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis.

BACKGROUND: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use. METHODS: We analyzed National Hospital Ambulatory Medical Care Survey data from 2010, the most current dataset available. The National Hospital Ambulatory Medical Care Survey is a public dataset collected and distributed by the Centers for Disease Control and Prevention. It is a multi-stage probability sample from randomly selected emergency departments across the country, designed to be representative of all US emergency department visits. We included in our analysis all patients with the ICD9 emergency department discharge diagnosis of migraine. We tabulated frequency of use of specific medications in 2010 and compared these results with the 1998 data. Using a logistic regression model, into which all of the following variables were entered, we explored the independent association between any opioid use in 2010 and sex, age, race/ethnicity, geographic region, type of hospital, triage pain score and history of emergency department use within the previous 12 months. RESULTS: In 2010, there were 1.2 (95% confidence interval 0.9, 1.4) million migraine visits to US emergency departments. Including opioid-containing oral analgesic combinations, opioids were administered in 59% of visits (95% confidence interval 51, 67). The most commonly used parenteral agent, hydromorphone, was used in 25% (95% confidence interval 19, 33) of visits in 2010 versus less than 1% (95% confidence interval 0, 3) in 1998. Conversely, use of meperidine had decreased markedly over the same timeframe. In 2010, it was used in just 7% (95% confidence interval 4, 12) of visits compared to 37% (95% confidence interval 29, 45) in 1998. Metoclopramide, the most commonly used anti-dopaminergic, was administered in 17% (95% confidence interval 12, 23) of visits in 2010 and 3% (95% confidence interval 1, 6) of visits in 1998. Use of any triptan was relatively uncommon in 2010 (7% (95% confidence interval 4, 11) of visits) and in 1998 (10% (95% confidence interval 6, 15) of visits). Of the predictor variables listed above, only emergency department use within the previous 12 months was associated with opioid administration (adjusted odds ratio: 2.87 (95% confidence interval 1.03, 7.97)). CONCLUSIONS: In spite of recommendations to the contrary, opioids are still used in more than half of all emergency department visits for migraine. Though use of meperidine has decreased markedly between 1998 and 2010, it has largely been replaced by hydromorphone. Opioid use in migraine visits is independently associated with prior visits to the same emergency department in the previous 12 months.

Although inferior vena cava filter placement is a safe and effective method of reducing the risk of pulmonary embolism, devastating complications can result from thrombosis and migration. Here we present a case of acute renal failure as a result of suprarenal inferior vena cava filter migration and caval thrombosis. We discuss a novel endovascular approach for its management by mechanical aspirational thrombectomy.

OBJECTIVE: The objectives of this study were to identify cancer-related health care services and to explore the presence of inter-organizational interactions among clinical and support oncology services in southern Puerto Rico. METHODS: From January through July of 2010, a survey was completed by 54 health care organizations offering clinical, supportive, or both services to cancer patients/survivors (CPS) in southern PR. Survey data were compiled and descriptive analyses performed using the software Statistical Package for a Social Science (SPSS), version 18.0. RESULTS: The distribution of the primary services provided by the participating organizations was the following: 26 had clinical services, 16 had support services, and 12 offered a combination of clinical and support services. Only 24 % of the surveyed organizations offered their services exclusively to patients diagnosed with cancer. In terms of referral practices, 61 % of the responses were for medical specialists, 43 % were for mental health services, and 37 % were referrals for primary care services. The most common reason for interacting (n = 27) was to provide a given patient both a referral and information. CONCLUSION: Findings suggest gaps in both the availability of oncology services and the delivery of integrated health care. Lack of communication among clinical and support organizations (for cancer patients, specifically) could negatively impact the quality of the services that they offer. Further network analysis studies are needed to confirm these gaps. Until systemic, structural changes occur, more efforts are needed to facilitate communication and collaboration among these kinds of organization.

We conducted a review of articles published in 2013 to identify high-quality research in medical education that was relevant to general medicine education practice. Our review team consisted of six general internists with expertise in medical education of varying ranks, as well as a professional medical librarian. We manually searched 15 journals in pairs, and performed an online search using the PubMed search engine for all original research articles in medical education published in 2013. From the total 4,181 citations identified, we selected 65 articles considered most relevant to general medicine educational practice. Each team member then independently reviewed and rated the quality of each selected article using the modified Medical Education Research Study Quality Instrument. We then reviewed the quality and relevance of each selected study and grouped them into categories of propensity for inclusion. Nineteen studies were felt to be of adequate quality and were of moderate to high propensity for inclusion. Team members then independently voted for studies they felt to be of the highest relevance and quality within the 19 selected studies. The ten articles with the greatest number of votes were included in the review. We categorized the studies into five general themes: Improving Clinical Skills in UME, Inpatient Clinical Teaching Methods, Advancements in Continuity Clinic, Handoffs/Transitions in Care, and Trainee Assessment. Most studies in our review of the 2013 literature in general medical education were limited to single institutions and non-randomized study designs; we identified significant limitations of each study. Selected articles may inform future research and practice of medical educators.