tbuckley/cabot-search huggingface dataset:
Medical millennials: a mismatch between training preferences and employment opportunities
Authors: Paul Jung, Colin Smith
Journal: The Lancet Global Health (2019)

BackgroundMillennials, defined as those born between 1981 and 1996, have begun to enter the physician workforce, and now represent 15% of all working physicians. A better understanding of their aspirations and consideration of the unique education and skillset of millennials may lead to more effective recruitment and retention. In this study, we aimed to measure the availability of cross-training opportunities—that is, completion of more than one degree or complete combined medical residency training—for millennial physicians at the undergraduate and graduate levels in the USA. Further, we compared the availability of medical jobs that advertised for cross-trained physicians.MethodsData were obtained from published statistics fom the Association of American Medical Colleges and National Resident Matching Program. Additional data were obtained from a literature search and April 2018 internet searches of medical school websites.FindingsUS undergraduates had a 70% increase in college double majors between 2001 and 2011 and double majors are increasing among matriculated medical students. The number of medical schools offering an MBA in 2018 (n=63), has nearly doubled since 2006 (n=37). Before 2001, no residency programmes, apart from those in preventive medicine, provided trainees with formal opportunities to obtain an MBA or MPH. However, in 2018, 45 residency programmes have a pathway for residents to pursue an MBA, MPH, or PhD during residency. In the past 20 years, the rate of increase in total number of combined residency programmes (49% [from 128 in 1996 to 191 in 2017]) is triple that of corresponding categorical programmes (16% [from 1350 to 1562 in the same time period]). Between 1996 and 2016, 17 new specialty combinations became available for residency training. Data from USAJobs, the federal employment website, and the New England Journal of Medicine online CareerCenter show few advertised jobs that specifically require skills demonstrated by combined degrees or combined residency training.InterpretationMillennial physicians are choosing to cross-train throughout undergraduate, medical, and graduate medical education; however, the current physician marketplace does not match the skills of this population. A mismatch between provider skills and available jobs is costly for both employers and workers, and such a mismatch can adversely affect health systems. Health-care organisations should capitalise on the availability of multiskilled graduates in order to effectively recruit and retain the next generation of physicians.FundingNone.
Practice Variation in Anticoagulation Prescription and Outcomes After Device-Detected Atrial Fibrillation
Authors: Alexander C. Perino, Jun Fan, Mariam Askari, Paul A. Heidenreich, Edmund Keung, Merritt H. Raitt, Jonathan P. Piccini, Paul D. Ziegler, Mintu P. Turakhia
Journal: Circulation (2019)

Device-detected atrial fibrillation (AF) is associated with increased risk of stroke; however, there are no clearly defined thresholds of AF burden at which to initiate oral anticoagulation (OAC). We sought to describe OAC prescription practice variation in response to new device-detected AF and the association with outcomes.
Comparative effectiveness of enzalutamide before and after chemotherapy in patients with metastatic castration-resistant prostate cancer: A meta-analysis.
Authors: Kevin Y Xu, Raji Shameem, Shenhong Wu
Journal: Journal of Clinical Oncology (2015)

e16001 Background: Enzalutamide (MDV3100), an androgen signaling inhibitor, has been found to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients with and without prior chemotherapy. We performed a meta-analysis to compare the efficacy and safety of enzalutamide between mCRPC patients who received chemotherapy and those who were chemotherapy-naïve. Methods: Both PubMed and ASCO conference abstracts up to June 2014 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which enzalutamide was compared to placebo in mCRPC patients with or without prior chemotherapy. Heterogeneity tests were performed to examine between-study differences in efficacy and toxicity. Summary incidences, relative risks (RR), hazard ratios (HR), and 95% confidence intervals (CI) were calculated using random- or fixed-effects models. Results: Two phase III RCTs were included in our analysis, with one trial for patients without prior chemotherapy (N = 1,717) and another for patients after chemotherapy with docetaxel (N = 1,199). Prior chemotherapy did not alter the effect of enzalutamide on overall survival (P = 0.33) but reduced its effect on radiographic-progression free survival (P < 0.001), PSA-progression free survival (P = 0.01), objective response rate (P < 0.001), and PSA response rate (P < 0.001). While prior chemotherapy was associated with a decreased risk of all-grade cardiac disorder (P = 0.02), fatigue (P < 0.001), and hypertension (P < 0.001), it was associated with an increased risk of headache (P < 0.001) attributable to enzalutamide. Conclusions: The effectiveness of enzalutamide may be favored in metastatic CRPC patients without prior chemotherapy. Our study’s results support enzalutamide’s suitability as a first-line treatment for mCRPC patients.
Abstract P050: Competing Health Priorities Lead Young Women to Worry Little About Heart Disease
Authors: Holly C Gooding, Courtney A Brown, Anna C Revette, Jingyi Liu, Catherine Stamoulis, Sarah D de Ferranti
Journal: Circulation (2019)

Introduction: The American Heart Association (AHA) Go Red for Women campaign has substantially improved heart disease awareness among adult women. Little is known about how younger women in adolescence and young adulthood (AYA) perceive their risk of heart disease during this key time in the life course for primordial prevention. Methods: We used an explanatory sequential mixed method design consisting of the AHA National Women’s Health Study survey and follow-up focus groups. We surveyed a random convenience sample of 331 AYA women ages 15-24 years presenting for care at an urban academic medical center and a community health center. Survey results guided development of a qualitative guide used during eight online, semi-structured focus groups with 32 young women. We report descriptive statistics performed using Matlab (Mathworks, Inc.) and thematic analyses conducted to synthesize data from the online focus groups using NVivo 11. Results: Only 10% [n=33] of AYA identified heart disease as the leading cause of death in women. Very few identified it as the top health concern for women of all ages [16 (4.8%)] or women in their age group [3 (0.9%)]. Most young women surveyed worried little [131 (39.6%)] or not at all [123 (37.2%)] about getting heart disease. In contrast, mood disorders were the most commonly noted top health concern for women of all ages [66 (19.9%)] and women in their age group [59 (17.8%)] and many AYA [142 (42.9%)] worried a lot about getting depression or anxiety. AYA discussed age (“I feel like those are things I associate with older people like 40”), competing health priorities (“because we’re so pressured just to grow up and more focused on pregnancies or depression or our weight”), and lack of perceived risk (“I like to think that I’m conscious of what I eat and drink”) as personal reasons for not worrying about heart disease. At the end of the focus group discussions, AYA women expressed being more motivated to both learn about heart health and to perform heart healthy behaviors (“I am definitely more motivated because I wasn’t aware that it was the number one kill[er] so I will definitely make sure to start working out”). Many group participants also noted the importance of receiving heart health information as well as personalized risk information from doctors. Conclusions: Younger women are unaware that heart disease is the leading cause of death in women and express little worry about their future risk. As the antecedents of heart disease begin in childhood and adolescence, these findings demonstrate a major unmet need. Campaigns to promote heart healthy behaviors in young women should directly address low perceived risk, the importance of lifetime risk, and competing health priorities with both young women and their health care providers.
SARM1 deficiency up-regulates XAF1, promotes neuronal apoptosis, and accelerates prion disease
Authors: Caihong Zhu, Bei Li, Karl Frontzek, Yingjun Liu, Adriano Aguzzi
Journal: The Journal of Experimental Medicine (2019)

SARM1 (sterile α and HEAT/armadillo motif–containing protein) is a member of the MyD88 (myeloid differentiation primary response gene 88) family, which mediates innate immune responses. Because inactivation of SARM1 prevents various forms of axonal degeneration, we tested whether it might protect against prion-induced neurotoxicity. Instead, we found that SARM1 deficiency exacerbates the progression of prion pathogenesis. This deleterious effect was not due to SARM1-dependent modulation of prion-induced neuroinflammation, since microglial activation, astrogliosis, and brain cytokine profiles were not altered by SARM1 deficiency. Whole-transcriptome analyses indicated that SARM1 deficiency led to strong, selective overexpression of the pro-apoptotic gene XAF1 (X-linked inhibitor of apoptosis-associated factor 1). Consequently, the activity of pro-apoptotic caspases and neuronal death were enhanced in prion-infected SARM1−/− mice. These results point to an unexpected function of SARM1 as a regulator of prion-induced neurodegeneration and suggest that XAF1 might constitute a therapeutic target in prion disease.
Axitinib versus sunitinib as first-line therapies for metastatic renal cell carcinoma: A multicenter retrospective analysis.
Authors: Shingo Hatakeyama, Toshiaki Tanaka, Yoshinori Ikehata, Naoki Fujita, Naoya Masumori, Hiroshi Kitamura, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2019)

555 Background: No previous study has compared the efficacy and safety of first-line axitinib and sunitinib. We aimed to compare oncological outcomes and safety of axitinib and sunitinib in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). Methods: We retrospectively evaluated 169 patients with mRCC who were treated with axitinib or sunitinib as the first-line therapy in five hospitals between October 2008 and August 2018.Oncological outcomes and safety were compared between axitinib (n = 68) and sunitinib (n = 101) groups. Inverse probability of treatment weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate effects of first-line therapies on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Patients in the axitinib group were significantly older (66 vs 72 years) than those in the sunitinib group. Median relative dose intensity was significantly higher in the axitinib group (94 ± 62%) than in the sunitinib group (65 ± 20%; P = 0.001). Objective response rate was significantly higher in the axitinib group (21%) than in the sunitinib group (10%; P = 0.042). IPTW-adjusted Cox regression analysis revealed significant differences in CSS and OS but not in PFS between the two groups. Safety in terms of grade ≥3 adverse events was significantly different between the axitinib (34%) and sunitinib (55%) groups ( P = 0.006). Conclusions: Compared with sunitinib, axitinib significantly prolonged CSS and OS and showed a safer profile as the first-line therapy for treatment-naïve mRCC.
Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation
Authors: Hélène Fontaine, Laurent Alric, Julien Labreuche, Benjamin Legendre, Alexandre Louvet, Corinne Antoine, Christophe M. Legendre, Marc Hazzan, Nassim Kamar, Sebastien Dharancy, Stanislas Pol, Alain Duhamel, Philippe Mathurin
Journal: Journal of Hepatology (2019)
Results of a 50 patient single-center phase II prospective trial of Lutetium-177 PSMA-617 theranostics in metastatic castrate-resistant prostate cancer.
Authors: Michael Hofman, John A Violet, Rodney J Hicks, Justin Ferdinandus, Sue Ping Thang, Amir Iravani, Grace Kong, Aravind Ravi Kumar, Timothy J. Akhurst, Jennifer Mooi, Christina Guo, Ben Tran, Price Jackson, Mark Scalzo, Peter Eu, Scott Williams, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2019)

228 Background: Lutetium-177 ( 177 Lu)-PSMA-617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling targeted delivery of beta-radiation. We have previously reported favourable activity with low toxicity in a 30 patient study in men with metastatic castrate-resistant prostate cancer (mCRPC) and now report updated results including a twenty patient extension cohort. Methods: In this phase II trial, 50 pts with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. The primary endpoints were PSA response (PCWG2) and toxicity (CTCAE v4). Other endpoints included imaging response, PSA PFS and OS. Cut-off for analysis 5 Oct 2018. Results: 76 men were screened to identify 50 patients eligible for treatment. Median PSA doubling time was 2.6 months. The majority of patients had received prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with a PSA decline ≥ 80%. 27 patients had measurable soft tissue at baseline and 56% of these patients had a partial or complete response by RECIST 1.1. The most common toxicities attributed to LuPSMA were transient G1-2 dry mouth in 68%, G1-2 nausea in 48%, and G1-2 fatigue in 36%. G3-4 toxicities attributed to LuPSMA were infrequent with thrombocytopenia in 10% and anaemia in 10%. Median PSA PFS was 6.9 months (95% CI 6.0-8.7) and median OS was 13.3 months (95% CI 10.5-18.0). Upon subsequent progression, further LuPSMA was administered to 14 patients (median 2 cycles commencing 359 days from enrolment); PSA ≥ 50% response occurred in 9 patients (64%). Conclusions: This expanded 50 patient cohort confirms high response rates and low toxicity with LuPSMA in men who had progressed after standard therapies. In patients who subsequently progressed and were administered further LuPSMA, high response rates were also observed. These results have provided the basis for randomised controlled trials currently underway. Clinical trial information: ACTRN12615000912583.
Fierce-21: Phase II study of vofatmab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).
Authors: Andrea Necchi, Daniel E. Castellano, B Mellado, S Pang, Yuksul Urun, Se Hoon Park, Ulka N. Vaishampayan, Graeme Currie, Esteban Abella-Dominicis, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

409 Background: Patients (pts) with mUC who have failed platinum-based chemotherapy have a poor prognosis. About 20% of them usually respond to immune checkpoint inhibitors (ICI). Also, 20% of pts with mUC harbor FGFR3 mutations or fusions (M/F), and this feature may be associated with lower sensitivity to ICI. Vofatamab (B-701) is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. FIERCE-21 is a Phase 1b/2 study designed to evaluate vofatamab monotherapy (VM) or in combination with docetaxel (VD). Methods: The study consists of a P 1b lead-in (P1b with VD), previously reported followed by P2 expansion cohort in FGFR3 M/F+ pts (identified with the FoundationONE CDx™ assay on archival samples). The study enrolled mUC pts with failure to ≥ 1 line prior chemotherapy (including prior taxane treatment) or ≤12 months of (neo)adjuvant chemotherapy, measurable disease and ECOG ≤ 1. Treatment consisted of vofatamab at 25 mg/kg alone (VM) and in combination with D (VD) at 75 mg/m 2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and activity (objective response-rate [ORR]). Results: 55 pts have received treatment. In the Ph 2 study, 21 pts received VM, 15 pts received VD. 35% of pts were included as 2 nd line therapy, 65% in 3 rd or later line of treatment. For pts receiving VD, safety was consistent with Ph 1B data. For pts receiving VM, median age was 67 yrs, ECOG 1 = 71.4%, Hgb &lt; 10 gm/dL 13%, liver metastases 19%, ≥ 2 prior regimens 57%, (best response to prior therapy PD 31%). TEAEs occurring in ≥5% patients were asthenia (19%), diarrhea (9.5%), flushing 14%, chills (9.5%), hypotension (9.5%), decreased appetite (19%) and creatinine increased (9.5%). The majority of TEAS were grade 1 and 2. Only 1 patient on MF had a grade 3 TEAE and only 1 patient discontinued treatment due to an AE. The ORR have been seen in 7 pts to date including those receiving both VM and VD. Conclusions: Vofatamab both alone and combined with D in an every 3-week schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VM and VD have demonstrated efficacy in terms of ORR, and mature results with PFS data will be presented. Clinical trial information: NCT02401542.
Polypharmacy is Associated with High-Risk Medication-Related Problems in People with Decompensated Cirrhosis
Authors: Kelly Hayward, Preya J. Patel, Patricia C. Valery, Leigh U. Horsfall, Catherine Y. Li, Penny L. Wright, Caroline Tallis, Katherine A. Stuart, Katharine M. Irvine, Neil Cottrell, Elizabeth E. Powell, Jennifer H. Martin
Journal: Hepatology (2017)
The prognostic value of lymph node ratio in patients with curatively resected pancreatic adenocarcinoma.
Authors: Nedim Turan, Murat Araz, Efnan Algin, Olcun Umit Unal, Mustafa Benekli, Didem Tastekin, Faysal Dane, Tugba Unek, Tulay Eren, Esma Turkmen, Turgut Kacan, Mehmet Naci Aldemir, Ahmet Siyar Ekinci, Sukran Ulger, Zuhat Urakci, Asude Aksoy, Gulnihal Tufan, Ugur Coskun, Ahmet Ozet, Suleyman Buyukberber
Journal: Journal of Clinical Oncology (2015)

e15238 Background: We evaluated the prognostic influence of the lymph node ratio (LNR) on overal survival (OS) in resected pancreatic adenocarcinoma (PAC). Methods: A total of 472 consecutive patients who were curatively resected for PAC in 18 oncology centers in Turkey were retrospectively analyzed between January 2003 and June 2013. We excluded those patient with peripancreatic cancer (n = 108), no treatment due to poor performance or comorbidities (n = 27) and unknown lymph node status (n = 53). To further explore the prognostic value of LNR, those patients with less than five nodes removed (n = 22) and those with no nodal metastasis (n = 76) were also excluded. A cut off value of 0.2 was assigned to the LNR in accordance with published studies. Results: After exclusions, 186 patients remained for analysis. The median OS was 19 months, and survival rates at 1st, 3rd, and 5th years were 60%, 12% and 1%, respectively. The median lymph node removed was 14 (5-60), and 92 patients had a LNR > 0.2. The median metastatic lymph node was 2.5 (1-17). In patients with a LNR of > 0.2, the median OS was 12 versus 18 months in patients with an LNR ≤ 0.2 (p = 0.003). The low and high LNR groups were well balanced in terms of prognostics and baseline characteristics including; age, gender, intermediate-high grade tumor, tumor size less than 3 cm, margin status, perineural invasion, lenfovascular invasion, adjuvant chemotherapy and radiotherapy. Conclusions: LNR may be a useful prognostic in curatively resected PAC, especially for patients with incomplete lymphadenectomy or inadequate histopathologic examination.
Transient Elastography Anticipates the Diagnosis of VOD/SOS after Adult Allogeneic Stem Cell Transplant: Results from a Prospective Study
Authors: Francesca Bonifazi, Federico Ravaioli, Mariarosaria Sessa, Amanda Vestito, Luigina Vanessa Alemanni, Mario Arpinati, Giovanni Marasco, Pier Luigi Zinzani, Michele Cavo, Davide Festi, Antonio Colecchia
Journal: Blood (2018)
Abstract P260: NEFAs, Incident Disability, Mobility Limitation and Frailty
Authors: Peter Ahiawodzi, Luc Djousse, Joachim Ix, Jorge Kizer, Russell Tracy, Alice Arnold, Anne Newman, Mary Lou Biggs, Kenneth Mukamal
Journal: Circulation (2019)

Background: Non-esterified fatty acids (NEFAs) play central roles in the relationship between adiposity and glucose metabolism and have been implicated in the pathogenesis of cardiovascular disease, but few studies have assessed their effects on complex geriatric syndromes like frailty that cross multiple organ systems. We sought to determine the relationships between NEFAs and incident frailty, disability, and mobility limitation in a population-based cohort of elders. Methods: We measured circulating total NEFAs in 2742 non-frail Cardiovascular Health Study (CHS) participants (mean age 74 years) from stored samples collected in 1992-3. Participants underwent assessment of frailty again in 1996-7 and continue to report their activities of daily living and mobility restrictions. We used ordinal logistic regression to model frailty and Cox regression was used to model disability and mobility limitation in relation to baseline NEFAs. To minimize departure from proportional hazards, we truncated follow-up at 9 years for disability and 6.5 years for mobility limitation. Results: A total of 251 participants became frail and 1411 became pre-frail over a four-year period, and we documented 1448 cases of disability and 1609 cases of mobility limitation during follow-up. NEFAs were positively associated in a dose-dependent manner with higher risks of incident frailty, disability, and mobility limitation. The adjusted odds ratios for frailty were 1.31 (95%CI=1.07-1.61, p=0.01) across extreme tertiles and 1.13 (95%CI=1.04-1.23, P=0.004) per standard deviation increment. The corresponding hazard ratios for incident disability were 1.40 (95%CI=1.05-1.87, p=0.02) and 1.22 (95%CI=1.09-1.37, P=0.001), while those for incident mobility limitation were 1.28 (95%CI=0.90-1.84, p=0.17) and 1.18 (95%CI=1.02-1.36, P=0.03). Results were largely consistent among both men and women. Conclusion: Circulating NEFAs are significantly associated with frailty, disability, and mobility limitation among older adults. These results highlight the broad spectrum of adverse health issues associated with NEFA in elders.