tbuckley/cabot-search huggingface dataset:
Cardiologist is cleared of sexual assault charges
Authors: Clare Dyer
Journal: BMJ (2017)

A consultant cardiologist has been cleared of sexually assaulting three women during medical examinations at Lewisham Hospital in southeast London.

Sumit Basu, 59, was acquitted at Woolwich Crown Court in London of seven charges of sexual assault and three charges of assault by penetration against the three women between 2006 and 2014.

Allegations were first made to …
Interpretability of Cancer Clinical Trial Results Using Restricted Mean Survival Time as an Alternative to the Hazard Ratio
Authors: Kyongsun Pak, Hajime Uno, Dae Hyun Kim, Lu Tian, Robert C. Kane, Masahiro Takeuchi, Haoda Fu, Brian Claggett, Lee-Jen Wei
Journal: JAMA Oncology (2017)

<h3>Importance</h3> In a comparative clinical study with progression-free survival (PFS) or overall survival (OS) as the end point, the hazard ratio (HR) is routinely used to design the study and to estimate the treatment effect at the end of the study. The clinical interpretation of the HR may not be straightforward, especially when the underlying model assumption is not valid. A robust procedure for study design and analysis that enables clinically meaningful interpretation of trial results is warranted. <h3>Objective</h3> To discuss issues of conventional trial design and analysis and to present alternatives to the HR using a recent immunotherapy study as an illustrative example. <h3>Design, Setting, and Participants</h3> By comparing 2 groups in a survival analysis, we discuss issues of using the HR and present the restricted mean survival time (RMST) as a summary measure of patients' survival profile over time. We show how to use the difference or ratio in RMST between 2 groups as an alternative for designing and analyzing a clinical study with an immunotherapy study as an illustrative example. <h3>Main Outcomes and Measures</h3> Overall survival or PFS. Group contrast measures included HR, RMST difference or ratio, and the event rate difference. <h3>Results</h3> For the illustrative example, the HR procedure indicates that nivolumab significantly prolonged patient OS and was numerically better than docetaxel for PFS. However, the median PFS time of docetaxel was significantly better than that of nivolumab. Therefore, it may be difficult to use median OS and/or PFS to interpret of the HR value clinically. On the other hand, using RMST difference, nivolumab was significantly better than docetaxel for both OS and PFS. We also provide details regarding design of a future study with RMST-based measures. <h3>Conclusions and Relevance</h3> The design and analysis of a conventional cancer clinical trial can be improved by adopting a robust statistical procedure that enables clinically meaningful interpretations of the treatment effect. The RMST-based quantitative method may be used as a primary tool for future cancer trials or to help us to better understand the clinical interpretation of the HR even when its model assumption is plausible.
Phase 1 study of the safety and efficacy of INCB050465 combined with obinutuzumab and bendamustine for relapsed or refractory (R/R) follicular lymphoma (FL) (CITADEL-102).
Authors: Morton Coleman, Antonio Salar, Javier Munoz, Natalie Galanina, Thea Faivre, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2017)

TPS7578 Background: Aberrant PI3Kδ activation is implicated in B-cell non-Hodgkin lymphomas (NHL) including FL, the most common indolent subtype. INCB050465, a selective PI3Kδ inhibitor, is being evaluated in an ongoing phase 1/2 study as monotherapy for r/r B-cell NHL, including FL (ASH 2016; Abstract 4195). Obinutuzumab plus bendamustine is approved for patients (pts) with rituximab-refractory FL. This phase 1 cohort expansion study will assess the safety, efficacy, and pharmacokinetics of INCB050465 combined with obinutuzumab and bendamustine in pts with r/r FL (NCT03039114). Methods: Eligible adults will have documented CD20+ FL r/r to 1–4 prior treatments (must include rituximab), ≥1 measurable lesion ( &gt; 1.5 cm in ≥1 dimension), ECOG PS ≤2, and adequate hematologic, hepatic and renal function. Exclusion criteria will include: transformation of FL to aggressive lymphoma or receipt of allogeneic stem cell transplant (SCT) ≤6 months (or having graft-versus-host-disease after allogeneic or autologous SCT ≤3 months) before study start; receipt of any PI3K inhibitor, obinutuzumab, or bendamustine ≤12 months, or rituximab ≤1 month prior to study. Part 1 (safety run-in) will use a 3+3 design. Pts will receive INCB050465 PO at a dose of 20 mg QD continuously for 2 cycles (1 cycle = 4 wks) followed by 20 mg QW. Up to 2 dose reductions will be allowed. Pts will receive obinutuzumab 1000 mg IV (cycle 1: days 1, 8, and 15; cycles 2–6: day 1) and bendamustine 90 mg/m 2 IV (cycles 1–6: days 1 and 2). In part 2 (expansion), the safety and efficacy of INCB050465 (maximum tolerated dose) plus obinutuzumab and bendamustine will be evaluated in 30 pts, including pts treated in part 1 at the dose level deemed safe and tolerated. In both parts 1 and 2, pts not progressing after 6 cycles will be maintained on INCB050465 at the dose deemed safe and tolerated, and will continue on obinutuzumab 1000 mg IV administered on Day 1 of every second cycle for an additional 24 cycles or until disease progression. Response will be assessed using Lugano criteria (FDG-PET; CT/MRI) every 12 wks until cycle 12 and every 16 wks thereafter. The trial is open for enrollment. Clinical trial information: NCT03039114.
Liraglutide for the Treatment of Antipsychotic Drug-Induced Weight Gain—Reply
Authors: Anders Fink-Jensen, Christoph U. Correll, Tina Vilsbøll
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
Total neoadjuvant treatment (CAPOX plus radiotherapy) for patients with locally advanced rectal cancer with high risk factors: a phase 2 trial
Authors: Xin Wang, Yongyang Yu, Xiangbing Deng, Wenjian Meng, Hong Zhu, Dan Jiang, Hua Zhuang, Bing Wu, Zhiping Li, Meng Qiu, Hongfeng Gou, Feng Bi, Feng Xu, Ziqiang Wang, Zongguang Zhou
Journal: The Lancet Oncology (2017)
TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort
Authors: Christoph Molnar, Almut Scherer, Xenofon Baraliakos, Manouk de Hooge, Raphael Micheroli, Pascale Exer, Rudolf O Kissling, Giorgio Tamborrini, Lukas M Wildi, Michael J Nissen, Pascal Zufferey, Jürg Bernhard, Ulrich Weber, Robert B M Landewé, Désirée van der Heijde, Adrian Ciurea
Journal: Annals of the Rheumatic Diseases (2017)

To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis.A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97).TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.
Protecting whistleblowers
Authors: G. Yamey
Journal: BMJ (2000)

Whistleblowers have been likened to bees1: a whistleblowing employee has only one sting to use, and using it may well lead to career suicide. In a survey of 87 American whistleblowers from both public service and private industry all but one experienced retaliation, with those employed longer experiencing more.2 Whistleblowers face economic and emotional deprivation, victimisation, and personal abuse and they receive little help from statutory authorities.3 Last month the BMJ held a conference to consider how medicine and its institutions should change to protect and empower whistleblowers.

Dr David Edwards, a general practitioner from Merseyside, gave a personal testimony of the dire consequences he suffered when he blew the whistle on his senior partner, Dr Geoffrey Fairhurst. Dr Fairhurst was funded by the pharmaceutical industry to conduct research on antihypertensive medication, but he was submitting forged consent forms and falsified electrocardiograms. When Dr Edwards challenged him about this misconduct, Dr Fairhurst launched a campaign to discredit Dr Edwards' concerns. In March 1996 the General …
Association of programmed cell death 1 ligand (PD-L1) expression with molecular alterations in non-small cell lung cancer (NSCLC) patients (pts): Results from the European Thoracic Oncology Platform (ETOP) Lungscape cohort
Authors: K.M. Kerr, E. Thunnissen, U. Dafni, A. Soltermann, S. Finn, L. Bubendorf, E. Verbeken, W. Biernat, A. Warth, A. Marchetti, E.-J. Speel, S. Pokharel, A.M. Quinn, K. Monkhorst, A. Navarro, V. Polydoropoulou, R. Kammler, S. Peters, R.A. Stahel, O.B. Lungscape Consortium
Journal: Annals of Oncology (2017)
A blocking of Janus kinase signaling might provoke growth inhibition through multiple signal pathways in head and neck cancer cells
Authors: Susan D. Mertins, Erik Harris, Melinda G. Hollingshead, Anne Monks
Journal: Cancer Research (2005)

2307  An aromatic sulfonamide, E7820 (Eisai Co., Ltd., Tsukuba-shi, Japan), shown to have antiangiogenic activity, demonstrated a differential cytotoxicity profile in the 60 cell line panel of the NCI Anti-cancer Drug Screen. The biological response profile of E7820 was similar to CQS (chloroquinoxaline sulfonamide; PCC=0.70) by COMPARE analysis. CQS is a topoisomerase-IIα and -β poison which underwent phase I testing. In our in vivo studies, E7820 has significantly inhibited growth of HCT116 human colon tumor xenografts at a variety of doses. Thus, in order to explore mechanisms underlying the activity of E7820, transcriptional profiles were generated for HCT-116 cells treated with E7820, CQS, and etoposide, another known topoisomerase II inhibitor. DKK-1, a gene whose protein inhibits Wnt signaling, was induced by E7820 and CQS but not etoposide, indicating the possibility that β-catenin translocation to the nucleus would be inhibited. However, immunofluorescent microscopy revealed that E7820 and CQS treatment augmented β-catenin translocation in HCT-116 cells. Moreover, the lack of inhibition of translocation was also confirmed in the APC mutant colon cell line SW480. It is notable that no change in the protein expression of β-catenin target genes, cyclin D and c-myc was found, but both p53 protein levels and nuclear translocation were increased by treatment with E7820 and CQS. As a positive control, the lithium chloride response was found to be intact. Lastly, we determined there was no difference in E7820 induced cytotoxicity in HCT-116 cell lines expressing exclusively wild type or mutant β-catenin. Taken together, these findings suggested that DKK-1 involvement in E7820 cytotoxicity might be through a non-canonical Wnt pathway linked to cytoskeletal regulation, corroborated further by the observation that E7820 and CQS induced actin and actin binding genes. Staining with TRITC-phalloidin for actin and DAPI for DNA revealed increased actin fibers (as early as 2 hrs), and double nuclei. In comparison, HCT-116 cells treated with the actin inhibitors, dolastatin 11 and jaskaplinolide, displayed characteristic aggregation post treatment. Because actin regulates cytokinetic events, the mitotic spindle and nuclei were examined in drug treated cells. Immunofluorescent staining for α-tubulin revealed structures consistent with monopolar spindles in cells treated with both agents. Cell cycle analysis will be presented. In summary, E7820, a unique sulfonamide entering clinical trials, may disrupt signaling associated with microfilaments and microtubules in the non-canonical Wnt pathway that regulates migration and differentiation.
Use of a nomogram to predict the closure rate of diverting ileostomy after low anterior resection: A retrospective cohort study
Authors: Shinya Abe, Kazushige Kawai, Hiroaki Nozawa, Keisuke Hata, Tomomichi Kiyomatsu, Toshiaki Tanaka, Takeshi Nishikawa, Kensuke Otani, Kazuhito Sasaki, Manabu Kaneko, Koji Murono, Shigenobu Emoto, Toshiaki Watanabe
Journal: International Journal of Surgery (2017)
Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC).
Authors: Dean F. Bajorin, Ronald De Wit, David J. Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J. Vogelzang, Miguel Ángel Climent, Daniel Peter Petrylak, Toni K. Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stephane Culine, Cora N. Sternberg, Yabing Mai, Markus Puhlmann, Rodolfo F. Perini, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2017)

4501 Background: Second-line chemotherapies (chemo) for advanced UC have limited clinical benefit (OS, 7-9 mo). Data from the open-label, phase 3 KEYNOTE-045 study (NCT02256436) showed significantly longer OS with pembro v chemo (median, 10.3 v 7.4 mo; hazard ratio [HR], 0.73; P = 0.002) in recurrent, advanced UC. Data from a planned survival analysis are presented. Methods: Pts had histologically or cytologically confirmed UC, progression after platinum, ECOG PS 0-2, measurable disease (RECIST v1.1), and ≤2 lines of systemic therapy. Pts were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m 2 Q3W, docetaxel 75 mg/m 2 Q3W, or vinflunine 320 mg/m 2 Q3W. Primary efficacy end points were OS and PFS (RECIST v1.1, blinded central review). ORR (RECIST v1.1, blinded central review) was a secondary end point. Results: 542 pts were enrolled (pembro, 270; chemo, 272). Baseline characteristics were generally similar between arms. As of Jan 18, 2017, median follow-up was 18.5 mo (range, 14.2-26.5). Median OS was significantly longer with pembro v chemo (10.3 v 7.4 mo; HR, 0.70; P &lt; 0.001), and significance was maintained regardless of PD-L1 expression as measured by combined positive score (HR: CPS &lt; 1%, 0.84; CPS ≥1%, 0.59; CPS &lt; 10%, 0.76; CPS ≥10%, 0.57). OS benefit with pembro v chemo was seen regardless of age, ECOG PS, prior therapy, liver metastases, histology, and choice of chemo. The 18-mo OS rate (95% CI) was 36.1% (30.1%-42.0%) with pembro v 20.5% (15.2%-25.8%) with chemo (KM estimate). PFS was not different between arms. ORR was higher with pembro v chemo (21.1% v 11.0%), and median (range) duration of response was longer (not reached [1.6+-20.7+ mo] v 4.4 mo [1.4+-20.3]). 69% (pembro) v 36% (chemo) of responses lasted ≥12 mo. Fewer pts experienced a treatment-related AE with pembro v chemo (any grade, 61.3% v 90.2%; grade ≥3, 16.5% v 49.8%). Conclusions: The OS benefit and superior safety profile of pembro over chemo are maintained with longer follow-up. Combined, these results support the potential of pembro as a new standard of care for patients with UC who previously received platinum. Clinical trial information: NCT02256436.
Prognostic significance of the chemokine CXCL13 in node-negative breast cancer.
Authors: Marcus Schmidt, Leonie van de Sandt, Daniel Boehm, Isabel Sicking, Marco Johannes Battista, Antje Lebrecht, Christine Solbach, Gert Naumann, Joerg Rahnenfuehrer, Ralph M Wirtz, Jan G Hengstler
Journal: Journal of Clinical Oncology (2013)

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CXCL13 was related to better MFS in a meta-analysis of the whole cohort (HR 0.88, 95% CI 0.83-0.94, P&lt;0.0001). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.72, 95% CI 0.59-0.87, P=0.0009) as compared to ER+/HER2- (HR 0.86, 95% CI 0.76-0.98, P=0.0024) and ER-/HER2- (HR 0.85, 95% CI 0.75-0.98), P=0.02) carcinomas of the breast. CXCL13 showed independent prognostic significance (HR 0.81, 95% CI 0.7336 0.8982, P=0.0001) in multivariate analysis. In addition to CXCL13, only histological grade of differentiation (HR 2.20, 95% CI 1.41-3.42, P=0.0005) and tumor size (HR 1.72, 95% CI 1.13-2.61, P=0.012), but neither age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The chemokine CXCL13 has independent prognostic significance in node-negative breast cancer. Higher expression of CXCL13 is associated with improved outcome.
An in-depth interview study of oncology nurses and infusion pharmacists of bendamustine product attributes that drive relative product preferences.
Authors: Susan Gabriel, Jennifer Welstead, Shannon Shockley, Peri Barr
Journal: Journal of Clinical Oncology (2017)

e19007 Background: Two bendamustine products, Treanda and Bendeka, are currently in the market. This study sought to better understand which attributes are meaningful in driving product preferences between these products as determined by a sample of front-line oncology nurses and infusion pharmacists. Methods: Two target panels of 10-15 oncology nurses and infusion pharmacists/pharmacy technicians who practice at different settings across the US were identified. Each study-eligible respondent was required to complete a pre-interview survey designed to collect background information on their practice site and their relative preferences for the two bendamustine products. All interviews were conducted between October and December 2016 by a trained nurse facilitator, and were taped and later transcribed. The survey results were analyzed using descriptive statistics, while content analysis was used to analyze the interview transcripts. Results: A total of 11 nurses and 10 pharmacists completed the pre-interview survey and participated in the in-depth interviews. The majority of nurse respondents were female (90.1%), resided in the South (72.7%), and practiced primarily in ambulatory care clinics (60%). The pharmacist respondents were also mostly female (60%), resided in the Mid-West (40%), and practiced primarily in comprehensive cancer care centers (40%). Both nurse and pharmacist responders reported that product attributes that address better safety, cost savings, productivity improvements, and improved workflow efficiency were most meaningful to them and drove their preferences for either Treanda or Bendeka. The majority of respondents reported a stronger preference for Bendeka over Treanda based on their respective product attributes that addressed these domains. Conclusions: Nurses and pharmacists involved in compounding, dispensing, and administering Bendeka or Treanda revealed that specific product attributes that impact safety, cost, productivity, and workflow efficiency drive usage of Bendeka.
Westminster Medical Society: Saturday, Feb. 26, 1842
Authors: G. Bird
Journal: BMJ (1842)

The PRESIDENT wished to kniow the experience of memlbers relative to the effects of the acetate of lead.He had been in the habit of giving it in cases of breinoptysis, in doses of two grains every four hiours, and had never witnessed anly ill effeets from its exhibi- tion.He spoke from the experience of many years, and he had been much surprised, therefore, at the simultaneous occurrence of three recent cases, in which symptoms of colic had beeni manifested.He was very desirous of ascertaining from members whether he was to consider tilese three cases as the rule or the exception.In one of tilcse, hbemoptysis was complicated with tuberculous consumptioin, the hirmorrhage was stopped in four hours, aild o0i the next day symptoms of colic manifested themselves;