tbuckley/cabot-search huggingface dataset:
Effect of Increased Inpatient Attending Physician Supervision on Medical Errors, Patient Safety, and Resident Education
Authors: Kathleen M. Finn, Joshua P. Metlay, Yuchiao Chang, Amulya Nagarur, Shaun Yang, Christopher P. Landrigan, Christiana Iyasere
Journal: JAMA Internal Medicine (2018)

While the relationship between resident work hours and patient safety has been extensively studied, little research has evaluated the role of attending physician supervision on patient safety.To determine the effect of increased attending physician supervision on an inpatient resident general medical service on patient safety and educational outcomes.This 9-month randomized clinical trial performed on an inpatient general medical service of a large academic medical center used a crossover design. Participants were clinical teaching attending physicians and residents in an internal medicine residency program.Twenty-two faculty provided either (1) increased direct supervision in which attending physicians joined work rounds on previously admitted patients or (2) standard supervision in which attending physicians were available but did not join work rounds. Each faculty member participated in both arms in random order.The primary safety outcome was rate of medical errors. Resident education was evaluated via a time-motion study to assess resident participation on rounds and via surveys to measure resident and attending physician educational ratings.Of the 22 attending physicians, 8 (36%) were women, with 15 (68%) having more than 5 years of experience. A total of 1259 patients (5772 patient-days) were included in the analysis. The medical error rate was not significantly different between standard vs increased supervision (107.6; 95% CI, 85.8-133.7 vs 91.1; 95% CI, 76.9-104.0 per 1000 patient-days; P = .21). Time-motion analysis of 161 work rounds found no difference in mean length of time spent discussing established patients in the 2 models (202; 95% CI, 192-212 vs 202; 95% CI, 189-215 minutes; P = .99). Interns spoke less when an attending physician joined rounds (64; 95% CI, 60-68 vs 55; 95% CI, 49-60 minutes; P = .008). In surveys, interns reported feeling less efficient (41 [55%] vs 68 [73%]; P = .02) and less autonomous (53 [72%] vs 86 [91%]; P = .001) with an attending physician present and residents felt less autonomous (11 [58%] vs 30 [97%]; P < .001). Conversely, attending physicians rated the quality of care higher when they participated on work rounds (20 [100%] vs 16 [80%]; P = .04).Increased direct attending physician supervision did not significantly reduce the medical error rate. In designing morning work rounds, residency programs should reconsider their balance of patient safety, learning needs, and resident autonomy.ClinicalTrials.gov Identifier: NCT03318198.
Sanctioned Stigma in Health Care Settings and Harm to LGBT Youth
Authors: Julia Raifman
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Trust in neuroendocrine tumors: The importance of communication in rare and chronic malignancies.
Authors: Eric Mou, Theresa A. Wittenberg, Pamela L. Kunz, Lidia Schapira
Journal: Journal of Clinical Oncology (2018)

75 Background: Trust is an integral component of the physician-patient relationship, and its importance is magnified in oncology. In patients with uncommon cancers, aspects pertaining to the rarity of their diagnosis may further influence their inclination towards and perception of trust. We sought to delineate the existing literature landscape of trust in oncology and explore the meaning of trust for patients living with neuroendocrine tumors (NETs), a comparatively rare and chronic malignancy. Methods: We performed a MEDLINE search including combinations of the MeSH headings ‘trust’ and ‘neoplasms’, categorizing articles according to recurrent themes. These themes were then presented to a Northern California NET support group, followed by a discussion. Discussants’ narratives and lived experiences were evaluated with those captured by the current literature to assess areas of concordance as well as to identify areas in need of further study. Results: 355 articles were reviewed, of which 40 articles were included for analysis. Frequently cited factors contributing to measures of trust consisted of race discordance, empathic physician communication, and healthcare systems dynamics. Medical mistrust was associated with poorer cancer screening compliance, reduced adherence to therapy recommendations, and decreased quality of life. Support group participants’ perspectives affirmed these conclusions, adding the lack of medical community awareness of NETs as the major barrier to communicating with their physicians about symptom recognition and shared decision making. Conclusions: Trust in oncology is determined by factors related to patients, physicians, and the healthcare system in which they interact. Medical mistrust is associated with worse measures of cancer surveillance, treatment adherence, and quality of life. Patients with NETs uniquely implicated the insidious and rare nature of their disease, as well as lack of clinician expertise in community settings, in impairing communication with, and therefore, trust in their physicians. Efforts to improve physician-patient communication in those with rare malignancies are needed in order strengthen trust and optimize their care.
Effectiveness of biomarker surveillance after treatment in locoregional breast cancer.
Authors: Timothy J Brown, Bernard Tawfik
Journal: Journal of Clinical Oncology (2018)

e12608 Background: Utilization of the biomarkers CA 15-3 and CA 27.29 to monitor recurrence or metastases does not improve outcomes after treatment in locoregional breast cancer. We sought to determine the utility and costs of further testing following a positive biomarker test in asymptomatic patients. Methods: The University of Texas Southwestern breast cancer registry was queried for all CA 15-3 and CA 27.29 tests in stage I-III breast cancer patients from January 1, 2010 to December 31, 2016. A biomarker was determined to lead to further testing if the patient had no symptoms and routine care would not have driven further investigation. Costs were determined by querying the Center for Medicare Services fee schedule. Results: In total, 5755 biomarker tests were obtained in 1070 patients. Four-hundred nineteen tests (7.3%) were positive in 172 patients with stage I-III breast cancer. Of the patients with positive tests, 116 were asymptomatic and had no further workup while 46 were symptomatic and had further testing which revealed metastatic disease. Furthermore, 10 asymptomatic patients had positive biomarker tests that clearly led to further testing - CT Chest (5), CT abdomen and pelvis (9), PET-CT(1), bone scan (4), ultrasound-guided liver biopsy (3), MRI Pelvis (1), and MRI Brain (1). Recurrent or metastatic breast cancer was diagnosed in only 4 of these 10 asymptomatic patients. Overall, $155,911 was spent on obtaining biomarkers and follow-up testing after positive results, with $38,977 spent for each diagnosis of metastatic breast cancer arising from a positive biomarker test in asymptomatic patients. Conclusions: In our cohort, very few positive tests led to further testing in the absence of symptoms. Even fewer positive tests led to a diagnosis of recurrent breast cancer and these were obtained with significant cost. The utility of screening biomarkers after definitive treatment for locoregional breast cancer appears to have low utility and a high cost.
Providing Surgery for Medically Intractable Epilepsy in Low- and Middle-Income Countries
Authors: Alireza Mansouri, George M. Ibrahim
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Kidney surveillance in the spotlight: contrast-induced acute kidney injury illuminated
Authors: Simon J. Atkinson
Journal: Journal of Clinical Investigation (2018)

Acute kidney injury comprises a heterogeneous group of conditions characterized by a sudden decrease in renal function over hours to days. Contrast-induced acute kidney injury (CI-AKI) is caused by radiographic contrast agents used in diagnostic imaging. In the current issue of the JCI, Lau et al. use a mouse model of CI-AKI to study the role of resident and infiltrating phagocytes, recruited leukocytes, and tubular cells in the immune surveillance response to contrast agents. This study has the potential to provide innovative therapies for human CI-AKI.
Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells
Authors: Anna-Kaisa Rimpelä, Marja Hagström, Heidi Kidron, Arto Urtti
Journal: Journal of Controlled Release (2018)

Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, Fic, were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity.
Ado-trastuzumab emtansine (T-DM1) in patients (pts) with HER2 amplified (amp) tumors excluding breast and gastric/gastro-esophageal junction (GEJ) adenocarcinomas: Results from the National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) trial.
Authors: Komal L. Jhaveri, Vicky Makker, Xin Victoria Wang, Alice P. Chen, Keith Flaherty, Barbara A. Conley, Peter J. O'Dwyer, Paul M. Williams, Stanley R. Hamilton, Lyndsay Harris, Lisa McShane, Lawrence Rubinstein, Robert James Gray, Shuli Li, Edith P. Mitchell, David Patton, Jeffrey Moscow, James A. Zwiebel, Carlos L. Arteaga, Shiuh-Wen Luoh
Journal: Journal of Clinical Oncology (2018)

100 Background: The NCI-MATCH is the largest national signal-finding trial incorporating centralized genomic testing to direct pts to molecularly targeted phase 2 treatment arms. HER2 gene amp is observed in many different tumor types. Methods: HER2 amp was defined as copy number (CN) ≥7 based on tumor sequencing on an adapted Oncomine AmpliSeq™ panel under FDA investigational device exemption. Pts with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Pts received T-DM1 at 3.6 mg/kg IV Q3 weeks until toxicity or disease progression. Tumor assessments occurred Q3 cycles for 33 cycles and Q4 cycles thereafter. Primary endpoint was objective response. Correlative studies included correlating HER2 CN, HER2 protein levels by IHC, HER2:CEP17 ratio (by FISH), PTEN loss, MYC amplification and PIK3CA mutation status with response. Results: 37 eligible pts were treated between 11/15-3/17. Median age was 65 (range 39-80). 33% had received > 3 lines of prior therapy. Median HER2 CN was 17 (7-139). Various histologies were treated: colon carcinoma (ca) (n = 7), ovarian ca (n = 6), rare tumors such as cholangioca (n = 1), carcinosarcoma of the uterus (n = 1), salivary gland ca (n = 3), among others. 3/37 (8.1%, 90% CI 2.2%-19.6%) had a confirmed partial response including 1 patient each with salivary duct ca of parotid gland, squamous cell ca of parotid gland and extramammary Paget's disease of the scrotum. Additionally, 43% had stable disease (SD) including 3/3 evaluable ovarian and uterine ca respectively. Median duration of SD was 4.6 months. The 6-month PFS rate was 24.8% (90% CI 15.0%-41.1%). Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. Median treatment duration was 4 cycles (range 1- 23). Data from correlative analysis will be presented at the meeting. Conclusions: T-DM1 was well tolerated. Clinical activity was observed in HER2 amp non breast and gastric/GEJ adenoca pts warranting further study either alone or in combinations particularly in some histologies such as salivary gland tumors. Clinical trial information: NCT02465060.
Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells
Authors: Yankai Zhang, Alireza Paikari, Pavel Sumazin, Carly C. Ginter Summarell, Jacy R. Crosby, Eric Boerwinkle, Mitchell J. Weiss, Vivien A. Sheehan
Journal: Blood (2018)
PTH-017 long-term outcomes for RFA in early barrett’s-associated neoplasia – are we succeeding?
Authors: Yuthiesshan Krishnamoorthy, Paul Brennan, Elaine Henry
Journal: Endoscopy (2018)

<h3>Introduction</h3> Minimally invasive, endoscopic therapies (radiofrequency ablation (RFA) with/without endoscopic resection (ER)) are widely performed for early Barrett's-associated neoplasia (dysplasia or intramucosal carcinoma) and appear to be effective in the short term. There is however, a paucity of longer term outcomes including overall survival, in a cohort of patients who are often significantly co-morbid or increasingly elderly. We aim to study and overall survival (OS) in a cohort of patients with early neoplasia in Barrett's oesophagus (BO-EN) treated since 2008. <h3>Methods</h3> A retrospective audit of a cohort of patients receiving RFA for BO-EN, of any length, at the Ninewells Hospital and Medical School was analysed. Between December 2008 and January 2018; 39 patients were undergoing/completed treatment and engaged in active surveillance. These patients were assessed for baseline demographics, duration of follow up and mortality, with a future directive being the assessment of complete resolution of both BO-EN and Barret's Oesophagus – Intestinal Metaplasia (BE-IM). <h3>Results</h3> In total, we have a completed cohort of 39 patients with absolute dataset who have undergone treatment. Of our population; 27 (69%) are male with the remaining 12 (31%) being female with a median age of 67 (Range 44–82 years). Patients were followed up for a median of 42 months (Range 1–172). A total of 39, 27 and 17 patients were included in the baseline (&lt;1 year post therapy), 3 year and 5 year analyses, respectively. The presenting histology was Low-Grade Dysplasia (LGD) – 8 (21%), High-Grade Dysplasia (HGD)- 22 (56%) and Carcinoma <i>In-Situ</i> – 9 (23%). Overall survival at 1, 3 and 5 years was 100%, with no progression to overt invasive malignancy demonstrated within this populace. <h3>Conclusions</h3> RFA (with/without ER) appears to be effective at controlling BO-EN and preventing progression to invasive adenocarcinoma, with a sustained effect appreciable to at least 5 years and possibly beyond. Not unsurprisingly men appear to develop higher grades of dysplasia; at younger ages, this is consistent with known risk bias within the published literature (Average age at diagnosis; M=65 years vs F=81). Our data suggests that despite the considerable comorbidity of these individuals, the intervention is well tolerated, with minimal deleterious sequelae and good survival prospects, albeit in a small sample size. We aim to continue to expand the dataset prospectively and actively record the capability for RFA treatment to completely reverse underlying intestinal metaplasia in this group.
Tumor stroma–targeted antibody-drug conjugate triggers localized anticancer drug release
Authors: Christopher Szot, Saurabh Saha, Xiaoyan M. Zhang, Zhongyu Zhu, Mary Beth Hilton, Karen Morris, Steven Seaman, James M. Dunleavey, Kuo-Sheng Hsu, Guo-Jun Yu, Holly Morris, Deborah A. Swing, Diana C. Haines, Yanping Wang, Jennifer Hwang, Yang Feng, Dean Welsch, Gary DeCrescenzo, Amit Chaudhary, Enrique Zudaire, Dimiter S. Dimitrov, Brad St. Croix
Journal: Journal of Clinical Investigation (2018)

Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid tumor mass, better strategies to exploit these cells for improved cancer therapy are needed. Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. Anti-TEM8 ADC elicited potent anticancer activity through an unexpected killing mechanism we term DAaRTS (drug activation and release through stroma), whereby the tumor microenvironment localizes active drug at the tumor site. Following capture of ADC prodrug from the circulation, tumor-associated stromal cells release active MMAE free drug, killing nearby proliferating tumor cells in a target-independent manner. In preclinical studies, ADC treatment was well tolerated and induced regression and often eradication of multiple solid tumor types, blocked metastatic growth, and prolonged overall survival. By exploiting TEM8+ tumor stroma for targeted drug activation, these studies reveal a drug delivery strategy with potential to augment therapies against multiple cancer types.
Exploratory biomarker analysis of a phase I study of AZD4547, an inhibitor of fibroblast growth factor receptor (FGFR), in patients with advanced solid tumors.
Authors: Elaine Kilgour, David Ferry, Matilde Saggese, Hendrik-Tobias Arkenau, Claire Rooney, Neil R. Smith, Dawn Baker, Brian Dougherty, Chris Womack, Paul D. Smith, Dana C. Ghiorghiu, Elizabeth A. Harrington, J. Carl Barrett, Nigel Brooks, Paul Stockman, Fabrice Andre
Journal: Journal of Clinical Oncology (2014)

11010 Background: AZD4547 is a selective inhibitor of FGFR 1, 2, and 3, with activity in patient-derived explant models with FGFR gene amplification. Study 1C1 assessed safety and clinical activity of AZD4547 (80 mg bid continuous dosing), in patients with advanced solid tumors, prospectively selected for amplification of FGFR 1 or 2. FGFR gene amplification status was determined using fluorescent in situ hybridization (FISH) analysis of archival tumor tissue. Methods: Analysis of FFPE diagnostic tumor samples included FGFR expression by IHC, expression analysis of ~200 pathway related genes by Nanostring and targeted Next Generation Sequencing (NGS) of a 287 gene panel at Foundation Medicine. Results: Of 21 patients dosed with AZD4547, seven had high FGFR amplification (ratio FGFR:Centromeric probe ≥ 3.0) and three of these, a squamous NSCLC, breast and bladder cancer patients, had target lesion shrinkage or prolonged (≥24 weeks) disease stabilization. NGS analysis of tumor from a partial response squamous NSCLC patient, confirmed high FGFR1 amplification together with amplification of 11q13 genes FGF3/4/19 and CCND1. A breast cancer patient, with 25% reduction in target lesions, was highly FGFR1 amplified by NGS and expressed FGFR1 protein. Four patients with high FGFR gene amplification by FISH had little sign of efficacy. Of these, one patient was not confirmed FGFR amplified by NGS analysis, likely due to tumor heterogeneity. The other three patient tumors had an additional Receptor Tyrosine Kinase (RTK) amplification (IGF1R, HER2 or EGFR), with accompanying high expression. Two out of three bladder cancer patients experienced prolonged disease stabilization, both with marked FGFR1 and FGFR3 expression, one with high FGFR1amplification while an FGFR3 ligand binding domain mutation was found in tumor from the other. Conclusions: In this AZD4547 Phase I study, evidence of FGFR pathway expression was observed in tumor samples from advanced cancer patients with signs of efficacy. Co-amplification of RTKs may confer resistance to AZD4547. FGFR1/3 expression, amplification and mutation are potential selection markers for bladder cancer patients. Clinical trial information: NCT00979134.
Sixty seconds on . . . Nipah virus
Authors: Owen Dyer
Journal: BMJ (2018)

Move over Ebola and Zika, it’s another scary zoonotic virus with a catchy name. Its reservoir is fruit bats and its home is in Asia. It recently broke out in northern Kerala in India, causing 18 confirmed infections and, so far, 17 deaths. And a good deal of panic.

No, it was first identified in Malaysia in 1998, when bats infected pigs which then infected farmers. It killed 105 people, and more than a million pigs had to be slaughtered. Sporadic cases have since cropped up in …
Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy
Authors: Xianjun Gao, Ning Ran, Xue Dong, Bingfeng Zuo, Rong Yang, Qibing Zhou, Hong M. Moulton, Yiqi Seow, HaiFang Yin
Journal: Science Translational Medicine (2018)

An exosomal anchor peptide enables targeting, drug loading, and capture of exosomes from diverse origins and targets oligonucleotides to muscle in mdx mice.