tbuckley/cabot-search huggingface dataset:
Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy
Authors: L. Schwartzberg, E. Roeland, Z. Andric, D. Kowalski, J. Radic, D. Voisin, G. Rizzi, R. Navari, R.J. Gralla, M. Karthaus
Journal: Annals of Oncology (2018)

BackgroundNEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline–cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed.Patients and methodsThis randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1–4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms.ResultsA total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed.ConclusionsIntravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.
Socioeconomic disparity is not a given
Authors: Babak Khoshnood
Journal: BMJ (2018)

I thank The BMJ and Fiona Godlee for the thought provoking debate on the tension between patient and population health.1

Socioeconomic characteristics are too often taken as non-modifiable risk factors for health outcomes. Setting aside the role of health professionals as actors for social change (the tradition going back at least to Villerme and Virchow), considering socioeconomic …
Sulfur Ointment Treatment of Cutaneous Myiasis Caused by the Tumbu Fly
Authors: Chuncui Shi, Rui Xu, Xuhua Tang, Hui Zhou
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles
Authors: Daniel S. Knight, Giulia Zumbo, William Barcella, Jennifer A. Steeden, Vivek Muthurangu, Ana Martinez-Naharro, Thomas A. Treibel, Amna Abdel-Gadir, Heerajnarain Bulluck, Tushar Kotecha, Rohin Francis, Tamer Rezk, Candida C. Quarta, Carol J. Whelan, Helen J. Lachmann, Ashutosh D. Wechalekar, Julian D. Gillmore, James C. Moon, Philip N. Hawkins, Marianna Fontana
Journal: JACC. Cardiovascular imaging (2018)
Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years
Authors: Cecilie Utke Rank, Nina Toft, Ruta Tuckuviene, Kathrine Grell, Ove Juul Nielsen, Thomas Leth Frandsen, Hanne Vibeke Hansen Marquart, Birgitte Klug Albertsen, Ulf Tedgård, Helene Hallböök, Ellen Ruud, Kirsten Brunsvig Jarvis, Petter Quist-Paulsen, Pasi Huttunen, Ulla Wartiovaara-Kautto, Ólafur Gísli Jónsson, Sonata Saulyte Trakymiene, Laimonas Griškevičius, Kadri Saks, Mari Punab, Kjeld Schmiegelow
Journal: Blood (2018)
Loss of MED12 Induces Tumor Dormancy in Human Epithelial Ovarian Cancer via Downregulation of EGFR
Authors: Xiao-Lin Luo, Cheng-Cheng Deng, Xiao-Dong Su, Fang Wang, Zhen Chen, Xing-Ping Wu, Shao-Bo Liang, Ji-Hong Liu, Li-Wu Fu
Journal: Cancer Research (2018)

Abstract A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation. Additionally, MED12 bound to the promoter of EGFR, and correlation studies showed that MED12 expression positively correlated with EGFR expression in EOC patient samples. Clinical data demonstrated that chemotherapy-resistant patients expressed lower levels of MED12 compared with responsive patients. Overall, our data show that MED12 plays an important role in regulating dormancy of EOC through regulation of EGFR. Significance: MED12 is identified as a novel, important regulator of tumor dormancy in human ovarian cancer. Cancer Res; 78(13); 3532–43. ©2018 AACR.
Trends in Post–Acute Care Use Among Medicare Beneficiaries: 2000 to 2015
Authors: Rachel M. Werner, R. Tamara Konetzka
Journal: JAMA (2018)

This study uses MedPAR data to characterize trends in use of skilled nursing facilities (SNFs) and inpatient rehabilitation facilities (IRFs) after acute care hospitalizations and trends in hospital and SNF/IRF lengths of stay among Medicare beneficiaries.
Novel technique of insulin loading into porous carriers for oral delivery
Authors: Sarah Y. Eilleia, Mahmoud E. Soliman, Samar Mansour, Ahmed. S. Geneidi
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The increasing demand for oral macromolecule delivery encouraged the development of microencapsulation technologies to protect such drugs against gastric and enzymatic degradation. However, microencapsulation often requires harsh conditions that may jeopardize their biological activity. Accordingly, many trials attempted to load macromolecules into porous drug carriers to bypass any formulation induced instability. In this study, we prepared chitosan coated porous poly (d, l-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with insulin using a novel loading technique; double freeze-drying. The results showed a significant increase in drug loading using only 5 mg/ml initial insulin concentration and conveyed a sustained drug release over uncoated MPs. Furthermore, SEM and confocal microscopy confirmed pore blocking and insulin accumulation within the MPs respectively. The oral pharmacodynamic data on rats also proved the preservation of insulin bioactivity after formulation. Finally, the new coating technique proved to be efficient in producing robust layer of chitosan with higher insulin loading while maintaining insulin activity.
Abstract #5326: Kinesin family member 7 (KIF7) in endometrial and ovarian cancers
Authors: Xiaoyun Liao, Kelvin Chan, Lai-Sze Chan, Kai-Yau Wong, Esther Wong, Hoi-Yan Chan, Michelle Siu, Ui-Soon Khoo, Hextan Ngan, Annie Cheung
Journal: Cancer Research (2009)

KIF7 is a kinesin superfamily member important in the intracellular transport system and is involved in the Hedgehog signaling pathway. The Hedgehog signaling pathway and some kinesin members have been demonstrated to be associated with human carcinogenesis. In this study, the expression status as well as genetic and epigenetic alterations of KIF7 in endometrial and ovarian cancers was examined. Five endometrial and nine ovarian cancer cell lines as well as 40 endometrial and ovarian cancer cases with available paired tumor and non-tumor tissues were studied. All endometrial and 5 out of 9 ovarian cancer cell lines demonstrated absent to weak KIF7 mRNA expression. KIF7 was also found to be significantly reduced in the endometrial and ovarian cancers comparing to the non-tumors (P   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5326.
Direct acting anti-viral therapy rescues neutrophil dysfunction in hepatitis C infection by reduction of heamolysis
Authors: B. Leber, A. Horvath, B. Schmerboeck, A. Posch, A. Streit, W. Spindelböck, P. Stiegler, R.E. Stauber, V. Stadlbauer
Journal: Journal of Hepatology (2018)
Factors Associated With Emergency Department Visits and Hospital Admissions After Invasive Outpatient Procedures in the Veterans Health Administration
Authors: Hillary J. Mull, Ziad F. Gellad, Rajan T. Gupta, Javier A. Valle, Danil V. Makarov, Tyler Silverman, Westyn Branch-Elliman
Journal: JAMA Surgery (2018)

Outpatient surgical care and invasive medical procedures are increasing.Prior research from the Veterans Health Administration (VHA) found that wrong-side or wrong-site adverse events were more common in the outpatient setting than the inpatient setting when the procedure was performed outside the operating room. 1 Both inpatient and outpatient operating room-based surgical procedures are evaluated by the National Surgical Quality Improvement Program 2 ; however, non-operating room outpatient invasive procedures are not assessed.To address this gap and inform future research, we measured the prevalence of postprocedure emergency department (ED) visits and admissions and explored the association of these outcomes with relevant patient, procedure, and facility factors. 3thods | The VHA Corporate Data Warehouse fiscal years 2012 to 2015 outpatient and procedure files were used to identify cases by Current Procedural Terminology code and outpatient setting for 5 high-volume subspecialties: urology, podiatry, cardiology (invasive and electrophysiologic procedures), interventional radiology, and gastroenterology.Only elective invasive procedures, defined as requiring general, monitored, or regional anesthesia, incision, device implantation, injection, or endoscopic entry of a sterile site, performed in facilities that treat more than 50 cases per year were retained. 4Patient demographics, including self-reported race/ethnicity and sex, comorbidities, 30-day prior visits and hospitalizations, number of procedures, procedural relative value unit, and facility's geographic region, were extracted from the Corporate Data Warehouse.
Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma
Authors: Ann S. LaCasce, R. Gregory Bociek, Ahmed Sawas, Paolo Caimi, Edward Agura, Jeffrey Matous, Stephen M. Ansell, Howland E. Crosswell, Miguel Islas-Ohlmayer, Caroline Behler, Eric Cheung, Andres Forero-Torres, Julie Vose, Owen A. O’Connor, Neil Josephson, Yinghui Wang, Ranjana Advani
Journal: Blood (2018)
Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery
Authors: Paul S. Myles, Rinaldo Bellomo, Tomas Corcoran, Andrew Forbes, Philip Peyton, David Story, Chris Christophi, Kate Leslie, Shay McGuinness, Rachael Parke, Jonathan Serpell, Matthew T.V. Chan, Thomas Painter, Stuart McCluskey, Gary Minto, Sophie Wallace
Journal: New England Journal of Medicine (2018)

Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion.
Role of Invasive Functional Assessment in Surgical Revascularization of Coronary Artery Disease
Authors: Bipul Baibhav, Maheedhar Gedela, Michael Moulton, Gregory Pavlides, Vincent Pompili, Tanveer Rab, George Dangas, Deepak L. Bhatt, Aleem Siddique, Yiannis S. Chatzizisis
Journal: Circulation (2018)

In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization.
Ibalizumab: First Global Approval
Authors: Anthony Markham
Journal: Drugs (2018)

TaiMed Biologics is developing ibalizumab (Trogarzo™, ibalizumab-uiyk)—a humanised IgG4 monoclonal antibody—as a treatment for HIV-1 infection. Ibalizumab blocks HIV entry into CD4 cells while preserving normal immunological function and is the first CD4-directed post-attachment HIV-1 inhibitor and the first humanised monoclonal antibody for the treatment of HIV/AIDS. This article summarizes the milestones in the development of ibalizumab leading to this first approval in HIV-1 treatment.
Tobacco Cessation Interventions and Smoke-Free Policies in Mental Health and Substance Abuse Treatment Facilities — United States, 2016
Authors: Kristy Marynak, Brenna VanFrank, Sonia Tetlow, Margaret Mahoney, Elyse Phillips, Ahmed Jamal, MBBS, Anna Schecter, Doug Tipperman, Stephen Babb
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Persons with mental or substance use disorders or both are more than twice as likely to smoke cigarettes as persons without such disorders and are more likely to die from smoking-related illness than from their behavioral health conditions (1,2). However, many persons with behavioral health conditions want to and are able to quit smoking, although they might require more intensive treatment (2,3). Smoking cessation reduces smoking-related disease risk and could improve mental health and drug and alcohol recovery outcomes (1,3,4). To assess tobacco-related policies and practices in mental health and substance abuse treatment facilities (i.e., behavioral health treatment facilities) in the United States (including Puerto Rico), CDC and the Substance Abuse and Mental Health Services Administration (SAMHSA) analyzed data from the 2016 National Mental Health Services Survey (N-MHSS) and the 2016 National Survey of Substance Abuse Treatment Services (N-SSATS). In 2016, among mental health treatment facilities, 48.9% reported screening patients for tobacco use, 37.6% offered tobacco cessation counseling, 25.2% offered nicotine replacement therapy (NRT), 21.5% offered non-nicotine tobacco cessation medications, and 48.6% prohibited smoking in all indoor and outdoor locations (i.e., smoke-free campus). In 2016, among substance abuse treatment facilities, 64.0% reported screening patients for tobacco use, 47.4% offered tobacco cessation counseling, 26.2% offered NRT, 20.3% offered non-nicotine tobacco cessation medications, and 34.5% had smoke-free campuses. Full integration of tobacco cessation interventions into behavioral health treatment, coupled with implementation of tobacco-free campus policies in behavioral health treatment settings, could decrease tobacco use and tobacco-related disease and could improve behavioral health outcomes among persons with mental and substance use disorders (1-4).
The long-term risk and outcome of non-neoplastic portal vein thrombosis developing in compesated caucasian HBV cirrhotics treated with Tenofovir or Entecavir
Authors: A. Loglio, G. Tosetti, G. Grossi, M. Iavarone, M. Viganò, F. Facchetti, M.G. Rumi, A. Sangiovanni, M. Primignani, P. Lampertico
Journal: Journal of Hepatology (2018)
Histologic stage is a stronger predictor of transplant free survival than APRI and FIB-4 in patients with primary biliary cholangitis
Authors: A. Gulamhusein, C.F.M. Perez, H. Van Buuren, C. Corpechot, P. Trivedi, M. Carbone, A. Pares, W.J. Lammers, M. Harms, A. Floreani, K. Lindor, C. Ponsioen, P. Invernizzi, M.J. Mayo, P.M. Battezzati, F. Nevens, T. Bruns, G. Dalekos, D. Thorburn, N. Larusso, K. Zachou, R. Poupon, V. Xavier, A.L. Mason, K.V. Kowdley, H. Janssen, G. Hirschfield, B. Hansen
Journal: Journal of Hepatology (2018)
Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial
Authors: Alan Mackay, Anna Burford, Valeria Molinari, David T.W. Jones, Elisa Izquierdo, Jurriaan Brouwer-Visser, Felice Giangaspero, Christine Haberler, Torsten Pietsch, Thomas S. Jacques, Dominique Figarella-Branger, Daniel Rodriguez, Paul S. Morgan, Pichai Raman, Angela J. Waanders, Adam C. Resnick, Maura Massimino, Maria Luisa Garrè, Helen Smith, David Capper, Stefan M. Pfister, Thomas Würdinger, Rachel Tam, Josep Garcia, Meghna Das Thakur, Gilles Vassal, Jacques Grill, Tim Jaspan, Pascale Varlet, Chris Jones
Journal: Cancer Cell (2018)

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8
Expressions of loss predict aggressive comments on Twitter among gang-involved youth in Chicago
Authors: Desmond Upton Patton, Owen Rambow, Jonathan Auerbach, Kevin Li, William Frey
Journal: npj Digital Medicine (2018)

Recent studies suggest social media shapes the transmission of firearm violence in high-poverty, urban neighborhoods. However, the exact pathways by which content on social media becomes threatening has not been studied. We consider a dataset of tweets by gang-involved Chicago youth that are coded for expressions of aggression and/or loss. Using a permutation test and mixed-effects log linear regression, we find that aggression and loss tweets do not occur randomly, and furthermore that in a 2-day window after loss expressions we find an increase in aggressive tweets. We discuss implications for intervention.
Optimising rotas, not doctors’ behaviour, will improve safety
Authors: Francesco P Cappuccio
Journal: BMJ (2018)

Frequent shifts in junior doctors’ rotas cause harm to patients and doctors due to tiredness, fatigue, attentional failures, and cognitive impairment.1234 A recent article in The BMJ may give the false impression that changing individual behaviour will solve the problem.5 The authors underestimate the barriers to implementing the measures suggested; individual choices are frustrated by unfavourable environmental and organisational structures. Unsafe working patterns …
Lower compliance to prior HCC surveillance and liver function impairment explain the apparent higher HCC incidence under direct antivirals in HCV compensated cirrhotic patients: the French multicenter prospective ANRS CO12 CirVir cohort experience
Authors: P. Nahon, L. Richard, B. Valerie, C. Carole, M. Patrick, D. Guyader, P. Stanislas, D. Larrey, R. Francoise, E. Audureau
Journal: Journal of Hepatology (2018)
Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors
Authors: Jeremy Lewin, Jean-Charles Soria, Anastasios Stathis, Jean-Pierre Delord, Solange Peters, Ahmad Awada, Philippe G. Aftimos, Mohamed Bekradda, Keyvan Rezai, Zhen Zeng, Azher Hussain, Susan Perez, Lillian L. Siu, Christophe Massard
Journal: Journal of Clinical Oncology (2018)

Birabresib (MK-8628/OTX015) is a first-in-class bromodomain inhibitor with activity in select hematologic tumors. Safety, efficacy, and pharmacokinetics of birabresib were evaluated in patients with castrate-resistant prostate cancer, nuclear protein in testis midline carcinoma (NMC), and non-small-cell lung cancer in this phase Ib study.Forty-seven patients were enrolled to receive birabresib once daily at starting doses of 80 mg continuously (cohort A) or 100 mg for 7 consecutive days (cohort B) in 21-day cycles using a parallel dose escalation 3 + 3 design. The primary objective was occurrence of dose-limiting toxicities (DLTs) and determination of the recommended phase II dose.Of 46 treated patients, 26 had castrate-resistant prostate cancer, 10 NMC, and 10 non-small-cell lung cancer. For cohort A, four of 19 (21%) evaluable patients had DLTs at 80 mg once daily (grade 3 thrombocytopenia [n = 3], ALT/hyperbilirubinemia [n = 1]) and two of three had DLTs at 100 mg once daily (grade 2 anorexia and nausea with treatment delay > 7 days [n = 1], grade 4 thrombocytopenia [n = 1]). No DLTs occurred in cohort B. Of 46 patients, 38 (83%) had treatment-related adverse events (diarrhea, 17 [37%]; nausea, 17 [37%]; anorexia, 14 [30%]; vomiting, 12 [26%]; thrombocytopenia 10 [22%]). Three patients with NMC (80 mg once daily) had a partial response (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) with duration of 1.4 to 8.4 months. Pharmacokinetic analysis indicated a dose-proportional increase in birabresib exposure and rapid absorption.The recommended phase II dose of birabresib in patients with select solid tumors is 80 mg once daily with continuous dosing. Birabresib has dose-proportional exposure and a favorable safety profile, with clinical activity observed in NMC. Future studies of birabresib must consider intermittent scheduling to possibly mitigate the toxicities of chronic dosing.