tbuckley/cabot-search huggingface dataset:
Longitudinal Assessment of Resident Performance Using Entrustable Professional Activities
Authors: Daniel J. Schumacher, Daniel C. West, Alan Schwartz, Su-Ting Li, Leah Millstein, Elena C. Griego, Teri Turner, Bruce E. Herman, Robert Englander, Joni Hemond, Valera Hudson, Lauren Newhall, Kenya McNeal Trice, Julie Baughn, Erin Giudice, Hannah Famiglietti, Jonathan Tolentino, Kimberly Gifford, Carol Carraccio
Journal: JAMA Network Open (2020)

Entrustable professional activities (EPAs) are an emerging workplace-based, patient-oriented assessment approach with limited empirical evidence.To measure the development of pediatric trainees' clinical skills over time using EPA-based assessment data.Prospective cohort study of categorical pediatric residents over 3 academic years (2015-2016, 2016-2017, and 2017-2018) assessed on 17 American Board of Pediatrics EPAs. Residents in training at 23 pediatric residency programs in the Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network were included. Assessment was conducted by clinical competency committee members, who made summative assessment decisions regarding levels of supervision required for each resident and each EPA. Data were collected from May 2016 to November 2018 and analyzed from November to December 2018.Longitudinal, prospective assessment using EPAs.Trajectories of supervision levels by EPA during residency training and how often graduating residents were deemed ready for unsupervised practice in each EPA.Across the 5 data collection cycles, 1987 residents from all 3 postgraduate years in 23 residency programs were assigned 25 503 supervision level reports for the 17 general pediatrics EPAs. The 4 EPAs that required the most supervision across training were EPA 14 (quality improvement) on the 5-level scale (estimated mean level at graduation, 3.7; 95% CI, 3.6-3.7) and EPAs 8 (transition to adult care; mean, 7.0; 95% CI, 7.0-7.1), 9 (behavioral and mental health; mean, 6.6; 95% CI, 6.5-6.6), and 10 (resuscitate and stabilize; mean, 6.9; 95% CI, 6.8-7.0) on the expanded 5-level scale. At the time of graduation (36 months), the percentage of trainees who were rated at a supervision level corresponding to "unsupervised practice" varied by EPA from 53% to 98%. If performance standards were set to align with 90% of trainees achieving the level of unsupervised practice, this standard would be met for only 8 of the 17 EPAs (although 89% met this standard for EPA 17, performing the common procedures of the general pediatrician).This study presents initial evidence for empirically derived practice readiness and sets the stage for identifying curricular gaps that contribute to discrepancy between observed practice readiness and standards needed to produce physicians able to meet the health needs of the patient populations they serve. Future work should compare these findings with postgraduation outcomes data as a means of seeking validity evidence.
P-0266 Worse Prognosis of Kras C.35 G&gt;A Mutant Mcrc Patients Treated with Intensive Triplet Chemotherapy Plus Bevacizumab (FIR-B/FOX)
Authors: Gemma Bruera, Katia Cannita, Daniela Di Giacomo, Aude Lamy, Giancarlo Troncone, Antonella Dal Mas, Gino Coletti, Thierry Frébourg, Jean Christophe Sabourin, Mario Tosi, Corrado Ficorella, Enrico Ricevuto
Journal: Annals of Oncology (2012)
Randomized Phase IIIB Trial of Temsirolimus and Bevacizumab Versus Interferon and Bevacizumab in Metastatic Renal Cell Carcinoma: Results from Intoract
Authors: B.I. Rini, J. Bellmunt, J. Clancy, K. Wang, A. Niethammer, B. Escudier
Journal: Annals of Oncology (2012)
Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration
Authors: Quan Dong Nguyen, Arup Das, Diana V. Do, Pravin U. Dugel, Andre Gomes, Frank G. Holz, Adrian Koh, Carolyn K. Pan, Yasir J. Sepah, Nikhil Patel, Heather MacLeod, Patrik Maurer
Journal: Ophthalmology (2020)

Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.
Preseason shoulder range of motion screening and in-season risk of shoulder and elbow injuries in overhead athletes: systematic review and meta-analysis
Authors: Federico Pozzi, Hillary A Plummer, Ellen Shanley, Charles A Thigpen, Chase Bauer, Melissa L Wilson, Lori A Michener
Journal: British Journal of Sports Medicine (2020)

Objective To characterise whether preseason screening of shoulder range of motion (ROM) is associated with the risk of shoulder and elbow injuries in overhead athletes. Design Systematic review and meta-analysis. Data sources Six electronic databases up to 22 September 2018. Eligibility criteria Inclusion criteria were (1) overhead athletes from Olympic or college sports, (2) preseason measures of shoulder ROM, (3) tracked in-season injuries at the shoulder and elbow, and (4) prospective cohort design. Exclusion criteria were (1) included contact injuries, (2) lower extremity, spine and hand injuries, and (3) full report not published in English. Results Fifteen studies were identified, and they included 3314 overhead athletes (baseball (74.6%), softball (3.1%), handball (16.1%), tennis (2.0%), volleyball (2.0%) and swimming (2.2%)). Female athletes are unrepresented (12% of the overall sample). Study quality ranged from 11 to 18 points on a modified Downs and Black checklist (maximum score 21, better quality). In one study, swimmers with low (&lt;93°) or high (&gt;100°) shoulder external rotation were at higher risk of injuries. Using data pooled from three studies of professional baseball pitchers, we showed in the meta-analysis that shoulder external rotation insufficiency (throwing arm &lt;5° greater than the non-throwing arm) was associated with injury (odds ratio=1.90, 95% confidence interval 1.24 to 2.92, p&lt;0.01). Conclusion Preseason screening of shoulder external rotation ROM may identify professional baseball pitchers and swimmers at risk of injury. Shoulder ROM screening may not be effective to identify handball, softball, volleyball and tennis players at risk of injuries. The results of this systematic review and meta-analysis should be interpreted with caution due to the limited number of studies and their high degree of heterogeneity. PROSPERO registration number CRD42017072895.
EMT and Back Again: Visualizing the Dynamic Phenotypes of Metastasis
Authors: Fred Bunz
Journal: Cancer Research (2020)

Abstract To what extent does the acquisition of mesenchymal phenotypes by tumor epithelial cells contribute to metastasis? A definitive answer to this question has remained elusive despite much experimentation and debate. Recently, an influential study based on fluorescence-based lineage tracing technology provided evidence that very few of the cells that populate experimental metastases in fact undergo the epithelial-to-mesenchymal transition. Persistent questions regarding the concordance between marker conversion and cell phenotypes prompted Lourenco and colleagues to complement their lineage tracking system with single-cell analysis. This granular approach provides an unprecedented view of the phenotypic transitions that take place during metastasis and their striking heterogeneity. See related article by Lourenco et al., p. 163
Effect of a Behavioral Intervention to Increase Vegetable Consumption on Cancer Progression Among Men With Early-Stage Prostate Cancer
Authors: J. Kellogg Parsons, David Zahrieh, James L. Mohler, Electra Paskett, Donna E. Hansel, Adam S. Kibel, Heshan Liu, Drew K. Seisler, Loki Natarajan, Martha White, Olwen Hahn, John Taylor, Sheri J. Hartman, Sean P. Stroup, Peter Van Veldhuizen, Lannis Hall, Eric J. Small, Michael J. Morris, John P. Pierce, James Marshall
Journal: JAMA (2020)

<h3>Importance</h3> Guidelines endorsing vegetable-enriched diets to improve outcomes for prostate cancer survivors are based on expert opinion, preclinical studies, and observational data. <h3>Objective</h3> To determine the effect of a behavioral intervention that increased vegetable intake on cancer progression in men with early-stage prostate cancer. <h3>Design, Setting, and Participants</h3> The Men’s Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) was a randomized clinical trial conducted at 91 US urology and medical oncology clinics that enrolled 478 men aged 50 to 80 years with biopsy-proven prostate adenocarcinoma (International Society of Urological Pathology grade group = 1 in those &lt;70 years and ≤2 in those ≥70 years), stage cT2a or less, and serum prostate-specific antigen (PSA) level less than 10 ng/mL. Enrollment occurred from January 2011 to August 2015; 24-month follow-up occurred from January 2013 to August 2017. <h3>Interventions</h3> Patients were randomized to a counseling behavioral intervention by telephone promoting consumption of 7 or more daily vegetable servings (MEAL intervention; n = 237) or a control group, which received written information about diet and prostate cancer (n = 241). <h3>Main Outcomes and Measures</h3> The primary outcome was time to progression; progression was defined as PSA level of 10 ng/mL or greater, PSA doubling time of less than 3 years, or upgrading (defined as increase in tumor volume or grade) on follow-up prostate biopsy. <h3>Results</h3> Among 478 patients randomized (mean [SD] age, 64 [7] years; mean [SD] PSA level, 4.9 [2.1] ng/mL), 443 eligible patients (93%) were included in the primary analysis. There were 245 progression events (intervention: 124; control: 121). There were no significant differences in time to progression (unadjusted hazards ratio, 0.96 [95% CI, 0.75 to 1.24]; adjusted hazard ratio, 0.97 [95% CI, 0.76 to 1.25]). The 24-month Kaplan-Meier progression-free percentages were 43.5% [95% CI, 36.5% to 50.6%] and 41.4% [95% CI, 34.3% to 48.7%] for the intervention and control groups, respectively (difference, 2.1% [95% CI, −8.1% to 12.2%]). <h3>Conclusions and Relevance</h3> Among men with early-stage prostate cancer managed with active surveillance, a behavioral intervention that increased vegetable consumption did not significantly reduce the risk of prostate cancer progression. The findings do not support use of this intervention to decrease prostate cancer progression in this population, although the study may have been underpowered to identify a clinically important difference. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01238172
A Dual Phase I/II Study of th-302 and Bevacizumab in Resectable Recurrent Glioblastoma Following Bevacizumab Failure
Authors: R.M. Zuniga, J. Sun, J.R. Floyd, S.R. Yerragudi, C. Hart, C. Eng, A.J. Brenner
Journal: Annals of Oncology (2012)
Assessment of Anatomic Restoration of Distal Radius Fractures Among Older Adults
Authors: Kevin C. Chung, Hoyune E. Cho, Yeonil Kim, H. Myra Kim, Melissa J. Shauver
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The value of precise anatomic restoration for distal radius fractures (DRFs) in older adults has been debated for many decades, with conflicting results in the literature. In light of the growing population of adults aged 60 years and older, both fracture incidence and associated treatment costs are expected to increase. <h3>Objective</h3> To determine the association between radiographic measures of reduction and patient outcomes after DRF in older patients. <h3>Design, Setting, and Participants</h3> Data were collected from the Wrist and Radius Injury Surgical Trial (WRIST), a multicenter randomized clinical trial of DRF treatments for adults aged 60 years and older (enrollment from April 10, 2012, to December 31, 2016, with a 2-year follow-up). Data analysis was performed from January 3, 2019, to August 19, 2019. WRIST participants who completed 12-month assessments were included in the study. According to the biomechanical principle of alignment, 2-phase multivariable regression models were adopted to assess the association between radiographic measures of reduction and functional and patient-reported outcomes 12 months following treatment. <h3>Interventions</h3> Participants were randomized to receive volar locking plate, percutaneous pinning, or external fixation. Those who opted for nonoperative treatment received casts. <h3>Main Outcomes and Measures</h3> Hand grip strength, wrist arc of motion, radial deviation, ulnar deviation, the Michigan Hand Outcomes Questionnaire (MHQ) total score, MHQ function score, and MHQ activities of daily living score were measured at 12 months following treatment. <h3>Results</h3> Data from 166 WRIST participants (144 [86.7%] women; mean [SD] age, 70.9 [8.9] years) found that only 2 of the 84 correlation coefficients calculated were statistically significant. For patients aged 70 years or older, every degree increase in radial inclination away from normal (22°) grip strength in the injured hand was 1.1 kg weaker than the uninjured hand (95% CI, 0.38-1.76;<i>P</i> = .004) and each millimeter increase toward normal (0 mm) in ulnar variance was associated with a 10.4-point improvement in MHQ ADL score (95% CI, −16.84 to −3.86;<i>P</i> = .003). However, neither of these radiographic parameters appeared to be associated with MHQ total or function scores. <h3>Conclusions and Relevance</h3> The study results suggest that precise restoration of wrist anatomy is not associated with better patient outcomes for older adults with DRF 12 months following treatment. Surgeons can consider this evidence to improve quality of care by prioritizing patient preferences and efficient use of resources over achieving exact realignment. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01589692
Abstract 21036: Differences in Arrhythmia Induction Between Isoproterenol versus Combination of Drugs and Impact on Outcomes in Patients Undergoing Catheter Ablation for Ventricular and Supraventricular Arrhythmias
Authors: Mohit K Turagam, Vijay Swarup, Jie Cheng, Chandra Bomma, Donita Atkins, Akash Makkar, Luigi Di Biase, Andrea Natale, Dhanunjaya Lakkireddy
Journal: Circulation (2017)

Background: Catheter ablation (CA) has an estimated success rate of 50-90% after first procedure for atrial tachycardia/fibrillation (AT/AF), supraventricular tachycardia (SVT), premature ventricular complexes (PVC) and ventricular tachycardia (VT). We studied if combination of induction agents including isoproterenol (ISO), Caffeine, Calcium Chloride (CC), Atropine and Phenylephrine (PE) is better than ISO alone to uncover additional arrhythmic triggers or substrates, where supplemental CA may potentially improve long term procedural success. Methods: This is an observational study including 132 consecutive patients [AT/AF (N=27), SVT (N=25), PVC (N=42), VT (N=38)] undergoing CA for symptomatic atrial and ventricular arrhythmias. We compared combination chemical induction protocol (COMBO) which included ISO (range 5-20mcg/min) + Caffeine (50-250 mg) +CC (1gm) ± PE (range 5 -10 mcg/kg) ±intravenous atropine (0.25 mg, one time) with ISO-only (5-20 mcg/min) infusion to assess for arrhythmia re-inducibility after performing standard CA. Results: There was no significant difference in baseline or procedural characteristics between both groups. COMBO group had significantly higher induction of stable clinical arrhythmia triggers and substrates in patients undergoing CA for AT/AF (53.3% vs. 8.3%, p=0.01), SVT (33% vs 0%, p=0.04), PVC (28.5% vs 0%, p=0.02) and VT (33.3% vs. 4.3%, p=0.02) when compared with ISO group which were additionally ablated. At 1-year follow up, COMBO group had significantly higher freedom from arrhythmias in AT/AF (20% vs. 41.6%, p=0.05), SVT (0% vs. 23%, p=0.04), PVC (4.7% vs. 43%, p=0.009) and VT ablation (26% vs. 61%, p=0.05) groups. Conclusion: COMBO induction protocol during CA may uncover additional triggers and arrhythmia substrates in patients with supraventricular and ventricular arrhythmias. COMBO directed supplemental CA may improve freedom from clinical arrhythmias on long term follow up.
A Phase II Study of Erlotinib Monotherpay in Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) Without EGFR Gene Mutation who have Never/Light Smoking History: NEJ006/TCOG0903
Authors: Y. Demura, M. Maemondo, Y. Ishii, K. Okudera, K. Takamura, K. Kobayashi, N. Morikawa, A. Gemma, O. Ishimoto, M. Harada, S. Miura, Y. Fujita, K. Usui, Y. Saijo
Journal: Annals of Oncology (2012)
Indole Alleviates Diet‐Induced Hepatic Steatosis and Inflammation in a Manner Involving Myeloid Cell 6‐Phosphofructo‐2‐Kinase/Fructose‐2,6‐Biphosphatase 3
Authors: Linqiang Ma, Honggui Li, Jinbo Hu, Juan Zheng, Jing Zhou, Rachel Botchlett, Destiny Matthews, Tianshu Zeng, Lulu Chen, Xiaoqiu Xiao, Giri Athrey, David W. Threadgill, Qingsheng Li, Shannon Glaser, Heather Francis, Fanyin Meng, Qifu Li, Gianfranco Alpini, Chaodong Wu
Journal: Hepatology (2020)

Background and Aims Indole is a microbiota metabolite that exerts anti‐inflammatory responses. However, the relevance of indole to human non‐alcoholic fatty liver disease (NAFLD) is not clear. It also remains largely unknown whether and how indole acts to protect against NAFLD. The present study sought to examine the association between the circulating levels of indole and liver fat content in human subjects and explore the mechanisms underlying indole actions in mice with diet‐induced NAFLD. Approach and Results In a cohort of 137 subjects, the circulating levels of indole were reversely correlated with body mass index. In addition, the circulating levels of indole in obese subjects were significantly lower than those in lean subjects and were accompanied with increased liver fat content. At the whole‐animal level, treatment of high‐fat diet (HFD)–fed C57BL/6J mice with indole caused significant decreases in the severity of hepatic steatosis and inflammation. In cultured cells, indole treatment stimulated the expression of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3), a master regulatory gene of glycolysis, and suppressed macrophage proinflammatory activation in a PFKFB3‐dependent manner. Moreover, myeloid cell–specific PFKFB3 disruption exacerbated the severity of HFD‐induced hepatic steatosis and inflammation and blunted the effect of indole on alleviating diet‐induced NAFLD phenotype. Conclusions Taken together, our results demonstrate that indole is relevant to human NAFLD and capable of alleviating diet‐induced NAFLD phenotypes in mice in a myeloid cell PFKFB3‐dependent manner. Therefore, indole mimetic and/or macrophage‐specific PFKFB3 activation may be the viable preventive and/or therapeutic approaches for inflammation‐associated diseases including NAFLD.
Phase I Dose-Escalation Study of Oral Selective C-Met Inhibitor Emd 1214063 in Patients with Advanced Solid Tumors
Authors: G.S. Falchook, D.S. Hong, H.M. Amin, S. Fu, S.A. Piha-Paul, M.B. Klevesath, V. Jego, A. Johne, S. Stinchi, R. Kurzrock
Journal: Annals of Oncology (2012)
Envisioning a Better U.S. Health Care System for All: Coverage and Cost of Care
Authors: Ryan Crowley, Hilary Daniel, Thomas G. Cooney, Lee S. Engel
Journal: Annals of Internal Medicine (2020)

This paper is part of the American College of Physicians' policy framework to achieve a vision for a better health care system, where everyone has coverage for and access to the care they need, at a cost they and the country can afford. Currently, the United States is the only wealthy industrialized country that has not achieved universal health coverage. The nation's existing health care system is inefficient, unaffordable, unsustainable, and inaccessible to many. Part 1 of this paper discusses why the United States needs to do better in addressing coverage and cost. Part 2 presents 2 potential approaches, a single-payer model and a public choice model, to achieve universal coverage. Part 3 describes how an emphasis on value-based care can reduce costs.
Reporting of the Medical Licensing Examination
Authors: George Douglas Everett, Luis Isea
Journal: JAMA (2020)

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