tbuckley/cabot-search huggingface dataset:
Endoscopic submucosal dissection or endoscopic mucosal resection for large colorectal laterally spreading lesions? Scientific and economic data are still lacking
Authors: Jérémie Jacques, Stanislas Chaussade, Thierry Ponchon, Emmanuel Coron, Vincent Lepilliez, Martin Dahan, Jeremie Albouys, Denis Sautereau, Sarah Leblanc, Gabriel Rahmi, Romain Legros, Mathieu Pioche
Journal: Gut (2018)

We read with great interest the paper of Bahin et al comparing piecemeal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for large colorectal laterally spreading lesions (LSLs) from a medico-economic point of view.1 Since the expanded use of ESDs in Japan that began in the early 2000s, a debate still persists in Western countries about the absolute need for en bloc resection of large colorectal lesions with a low risk of submucosal cancer.2 3 ESDs are associated with a high en bloc resection rate, low risk of recurrence and perfect pathological analysis.4 Defenders of piecemeal EMR point out the higher risk of ESD, the long duration of procedures, the discrepancies between Eastern and Western series, and the low proportion of lesions with superficial submucosal cancer.5 They also point out the good results of wide-field (WF)-EMR for complete eradication even when several sessions are needed.6 Economic reasons are not often mentioned, although they could be considered …
miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6
Authors: Quanbo Ji, Xiaojie Xu, Qi Song, Yameng Xu, Yanhong Tai, Stuart B. Goodman, Wenzhi Bi, Meng Xu, Shunchang Jiao, William J. Maloney, Yan Wang
Journal: Molecular Therapy (2018)

Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.
Errors found on 350 foundation scheme papers, but effect on allocations is still unknown
Authors: Tom Moberly
Journal: BMJ (2013)

Scanning errors have affected the test papers of over 350 medical students, but the number of students whose foundation school allocation will now change remains unknown, the UK Foundation Programme Office (UKFPO) has said.1

Over 7200 medical students have had their situational judgment test (SJT) scores rechecked by medical schools after an error in the marking of …
Master's degree in gerontology
Authors: Laura S Hill, Judith SL Partridge
Journal: BMJ (2007)

This course would suit anyone with an interest in studying older people and ageing from biological, psychosocial, and demographic perspectives. Students included geriatricians, psychiatrists, general practitioners, allied health professionals, sociologists, voluntary sector workers, and those involved with information technology and politics. Past graduates have gone on to work in strategic positions influencing lives of older people in medicine, social care and policy, or within local government, voluntary organisations, or non-governmental organisations.

We did the course part time over two years as specialist registrars in psychiatry and geriatric medicine.

Despite our different career choices, we …
Collateral effects encountered by families of children living with physical or mental disabilities, or both, in Kilimanjaro, Tanzania: a cross-sectional study
Authors: Caleb Joel, Sia Msuya, Beatrice John, Johnston George
Journal: The Lancet Global Health (2018)

BackgroundDisability in low-income and middle-income countries (LMICs) is a neglected global health topic. Apart from the challenges faced by children living with disabilities, families of children living with disabilities are at increased risk of stress, weakened family and social relationships, reduced level of income, sense of depressed worthiness, decisions about whether to have more children, and reduced care to siblings without disabilities. This study focused on assessing collateral impacts on families of children younger than 18 years living with physical or metal disabilities, or both, in Kilimanjaro, Tanzania.MethodsThis cross-sectional study was done between April and June, 2017. We used a household survey to assess families of children living with physical or mental disabilities, or both. Families were identified using convenience sampling, and data were analysed using SPSS version 23.Findings83 families from 33 villages in Kilimanjaro region were interviewed. 24 (29%) respondents reported weakened family relationships, the most profound effect being the father abandoning the mother and the child with disability (reported by nine [39%] respondents) and the least being misunderstanding between parents (reported by two [9%] respondents). 49 (59%) families reported having a decreased level of income, and 21 (25%) families mentioned reduced care to other siblings who have no disabilities. Furthermore, 20 (24%) families faced challenges in making decisions about whether to have more children, whereas 16 (19%) families felt a sense of worthlessness.InterpretationDecreased income level and reduced care to other siblings have been associated with high costs of care, time, and resources spent taking care of the child with a disability. Adequate rehabilitation centres, special schools, and financial support for health-care accessibility could help reduce time and resources spent and hence potentiate productivity. Efforts should be focused on increasing the number of rehabilitation centres and special schools in the region, as Kilimanjaro has only one rehabilitation centre.FundingNone.
Major incident medical management and support (MIMMS): the practical approach at the scene
Authors: Philip Spreadborough
Journal: BMJ (2010)

This course looks at the structure and management of the scene of a major incident and how the emergency services are commanded.

The course is aimed primarily at individuals from a medical, nursing, or paramedic background, but my course also included participants from hospital management. It would benefit anyone who is involved at the scene of a major incident or who comes into contact with the emergency services and wants to understand their roles.

I took this course in 2009. At the time I was working in west Cornwall with the Royal Navy and my role involved the potential planning and response to major incidents. 

The course is run by the Advanced Life Support Group at various locations throughout the country during …
Nonoperative management of locally advanced esophageal and junctional (GEJ) cancers: The University of Rochester experience.
Authors: Rachel Julie David, Andrea Baran, Alan W. Katz, Richard Francis Dunne, Marcus Smith Noel, Aram F. Hezel, Mohamedtaki Abdulaziz Tejani
Journal: Journal of Clinical Oncology (2018)

144 Background: Neoadjuvant (NA) chemoradiation (CRT) followed by surgery is a standard treatment for locally advanced esophageal/GEJ tumors. The optimal management strategy is less clear for unresectable tumors or in patients (pts) who are medically inoperable. Methods: We retrospectively identified all pts with stage II/III esophageal/GEJ cancers treated without surgery at our institution from 2011-2015. Objectives were to describe treatment regimens used and assess outcomes based on clinicopathologic features. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Results: 38 pts were identified. 66% were male; median age was 69 years (range 43-91). 19 pts had adenocarcinoma, 18 had squamous cell, and 1 had small cell. Primary sites were distal (n = 22), mid (n = 13), and cervical esophagus (n = 3). 31 pts were treated with curative intent, 7 with best supportive care. 30 pts underwent CRT: 16 in a NA setting, 14 in a definitive setting. Chemotherapy regimens used were Carboplatin/Paclitaxel (19 pts) and Cisplatin/5-FU (10 pts). Median NA radiation (RT) dose was 45 Gy vs 50.4 Gy in the definitive setting (p = 0.008). Best response included 6 pts with complete responses (CR), 12 with partial responses, and 12 with progressive disease/death (PD). In the NA group, resection was avoided due to PD (n = 10), comorbidities (n = 4), unresectability (n = 1), and CR (n = 1). Median PFS and OS for all 38 patients were 6.5 and 11.1 months (mos). Median PFS and OS for adenocarcinoma pts were 4.6 and 7.2 mos, compared to 9.1 and 12.5 mos for pts with squamous. Compared to NA CRT, pts treated with definitive CRT had significantly prolonged PFS (18.5 vs 2.5 mos, p = 0.001) and OS (27.1 vs 5.3 mos, p = 0.03). Conclusions: In the absence of resection, outcomes for locally advanced esophageal/GEJ tumors remain poor, especially for adenocarcinoma pts who progress during NA CRT. A PET-directed approach as suggested by CALGB 80803 may help to identify these pts earlier in their course, allowing for treatment change. Multidisciplinary assessment to identify non-surgical candidates at diagnosis is critical since RT doses used in the definitive setting are generally higher.
Comparative effectiveness of non-cisplatin (cis)-based first-line (1L) regimens in patients with metastatic urothelial carcinoma (mUC): Veterans Affairs control cohorts vs. IMvigor210.
Authors: Nancy S. Vander Velde, Annie Guerin, Raluca Ionescu-Ittu, Sherry Shi, Eric Wu, Shih-Wen Lin, Ling-I Hsu, Kai-Uwe Saum, Sabine De Ducla, Jingjing Wang, Shi Li, Christina Louise Derleth, Shuqian Liu, Lizheng Shi, John Leppert
Journal: Journal of Clinical Oncology (2018)

496 Background: For mUC patients (pts) ineligible for cis, 1L carboplatin (carbo)-based regimens and checkpoint inhibitors are recommended, but comparative data are lacking. We assessed OS in pts given 1L atezolizumab (atezo; anti–PD-L1) from Ph 2 study IMvigor210 and Veterans Affairs (VA) mUC pts treated with carbo standards. Methods: Carbo-based control cohorts were derived from the VA Health Care Network databases (diagnosed 2006-2017), with treatment (tx) defined per NCCN guidelines V2.2005. IMvigor210 eligibility criteria were used to refine non-cis VA cohorts. Prespecified OS predictors were balanced between VA and IMvigor210 pts using entropy (e)-balance weighting. OS was evaluated by Kaplan-Meier (KM) and Cox regression (weighted). Sensitivity analyses used stabilized inverse probability weighting (sIPW) and statistical adjustments. Results: Of 2056 VA pts included, 926 received carbo-based tx, of whom 380 received carbo+gemcitabine [CarboGem]; after IMvigor210 exclusion criteria, the carbo-based cohort included 282 pts, of whom 120 had CarboGem. Non-proportional hazards were seen with KM curves crossing at ≈ 5 (CarboGem) and 9 mo (carbo based). OS data are in the table. Weighted analyses showed OS benefit for atezo vs CarboGem and delayed benefit vs carbo-based tx. HRs from sensitivity analyses were consistent in direction and significance. Conclusions: We compared OS in mUC pts receiving 1L non-cis regimens in VA (carbo) and IMvigor210 (atezo) mUC cohorts. A lower risk of death was seen for atezo vs carbo, manifesting after a few months of tx. Randomized studies may validate these 1L mUC tx trends. Clinical trial information: NCT02951767. [Table: see text]
Feasibility study of preoperative chemotherapy for patients with advanced esophageal cancer with or without naso-gastric ED tube for enteral feeding.
Authors: Takashi Ogata, Hiroaki Osakabe, Shinsuke Nagasawa, Masato Nakazono, Kentaro Hara, Yuta Kumazu, Tsutomu Hayashi, Takanobu Yamada, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2018)

184 Background: Advanced esophageal cancer patients sometimes have a difficulty to swallow food. On the other hand, standard treatment for resectable advanced esophageal cancer patients is surgery after 2 course preoperative chemotherapy of CDDP-5-FU (JCOG 9907). So we usually use naso-gastric ED tube for patients with difficulty of oral intake during preoperative chemotherapy to administrate adequate nutrition. But there is no report of the safety of this trial. Methods: The aim of this study is to clarify the safety of using ED tube during preoperative chemotherapy and compare the nutritional status between using ED tube or not. From Jan 2012 to June 2017, 122 patients were undergone esophagectomy with 2 course of preoperative chemotherapy, and 14 patients were treated with ED tube for nutrition(Group A) and 108 patients without ED tube(Group B). We evaluated the changes of nutritional status and postoperative complication as an indicator of safety. Results: Changes before and after preoperative chemotherapy(GroupA/B): average of body weight: 53.1→50.8/58.1→57.0, BMI: 20.0→19.2/22.0→21.6, TP: 6.7→6.9/7.3→6.9, alb: 3.5→3.8/4.3→4.2, pre-alb: 20.1→21.7/24.8→23.4, RBP: 2.77→3.33/3.15→3.23. Adverse events during chemotherapy: 1 case of Grade 3 hematologic toxicity and 1 case of Grade 2 non-hematologic toxicity were found at Group A(14.2%), and 11 cases of Grade 3 hematologic toxicity and 8 cases of Grade 2 non-hematologic toxicity were found at Group B(17.61%)(p = 0.758). Postoperative complications (clavien-dindo classification, Grade3 or more): 2 cases were observed at Group A(14.2%), and 21 cases were observed at Group B(19.4%)(p = 0.62). Conclusions: Preoperative chemotherapy with ED tube for nutrition was safe and effective to maintain the preoperative nutritional status.
Quality of life and complications in lower limb amputees in Tanzania: results from a pilot study
Authors: Jeremy Shaw, Sravya Challa, Devin Conway, Max Liu, Billy Haonga, Edmund Eliezer, Saam Morshed, David Shearer
Journal: The Lancet Global Health (2018)

BackgroundThe most common reason for lower extremity amputation in developing countries is trauma, which is an increasingly recognised global epidemic. Despite the rising rates of traumatic injury and the level of disability experienced by amputees, there are few data focusing on this specific population in low-income and middle-income countries (LMICs). The purpose of this study is to investigate the causes and health-related outcomes of lower extremity amputations in Tanzania, and the socioeconomic barriers preventing access to prosthetics.MethodsThis was an observational pilot study conducted at the Muhimbili Orthopaedic Institute in Dar es Salaam, Tanzania, from 2015 to 2016. Adult patients who had undergone lower extremity amputation less than 1 year before enrolment were included. Baseline data on demographics, socioeconomic factors, and health-related information were collected at enrolment. Patients' health, health-related quality of life (using the EQ-5D questionnaire), and complication data were recorded 3 and 6 months later.FindingsWe enrolled 44 patients, 35 of whom were men, with a mean age of 39·5 years. 39 (89%) of the patients were employed (36 [82%] informally) and 36 (82%) had no health insurance. Below-knee amputations were the most common (23 [52%]) type of amputation. The most common cause of amputation was trauma (29 [66%]), followed by diabetes (7 [16%]), vascular pathology (3 [7%]), and tumours (2 [5%]). Complications including delayed healing, infection, and wound dehiscence were seen in 20 (51%) of the 39 patients who were followed up. Seven patients required reoperation. The average baseline EQ-5D index was 0·912. The population norm based on mean age is 0·889 for the USA and 0·793 for Zimbabwe (the only African country-specific norm available). The average EQ5D index at 3 months and 6 months decreased to 0·714 and 0·847, respectively. Only two amputees (5%) have received a prosthetic. Lack of materials, unsuitable wound, and cost were most commonly cited as barriers to prosthetics.InterpretationThis study demonstrates that amputees in Tanzania experience a high rate of post-operative complications, poor quality of life, and extremely limited access to prosthetics. Educational initiatives to reduce wound-related complications and improved access to lower extremity prosthetics and rehabilitation are needed to address the dearth of knowledge and resources for amputees.FundingGlobal Research Initiative.
Cost-effectiveness of sunitinib or pazopanib for metastatic renal cell carcinoma in Brazil: A public health system perspective.
Authors: Andre Deeke Sasse, Adriana Camargo Carvalho
Journal: Journal of Clinical Oncology (2018)

680 Background: The first-line treatment with tyrosine kinase inhibitors results in significant clinical benefits for patients with metastatic renal cell carcinoma (mRCC). However, in Brazilian public health system Interferon still remains as standard treatment. In an innovative way, the Brazilian Society of Clinical Oncology made a price negotiation directly with the pharmaceutical company, aiming to propose a formal request for the incorporation of these technologies to the National Committee for Health Technology Incorporation (CONITEC). Our objective was to estimate the cost-effectiveness of Sunitinib or Pazopanib versus Interferon in patients with mRCC, under the perspective of the Brazilian public health system. Methods: A cost-effectiveness analysis was conducted using a Markov model over a lifetime horizon. The model considers three health states: 1st-line treatment, disease progression and death. Transition probabilities were extracted from randomized studies. Costs of standard treatment, complications, and surveillance were obtained from Brazilian public hospitals. Sunitinib and Pazopanib prices were those negotiated with the manufacturing companies. Benefits are presented in life-years (LY) and costs in USD. The relation between costs and benefits were used to present the incremental cost-effectiveness ratio (ICER) per life-year saved. Results: Patients with mRCC treated with Interferon were projected to have 1.92 LY with a total cost of $2,000. Sunitinib or Pazopanib were projected to increase the life expectancy to 2.84 LY, with a total cost of $19,584 (Sunitinib) and $19,646 (Pazopanib). The ICERs for Sunitinib and Pazopanib were estimated at $18,565 and $18,634 per LY respectively. Conclusions: Using the discount prices, at a willingness-to-pay (WTP) threshold of $25,615 per LY (three times gross domestic product per capita), both Pazopanib and Sunitinib are cost-effective strategies compared to Interferon. Potential impacts of targeted therapies for mRCC on the overall health care expenditures need to be assessed in a budget impact analysis. A formal request for the incorporation of these technologies to the CONITEC is in progress.
Doctors’ behaviour is as important as their clinical skills, say medical leaders
Authors: Abi Rimmer
Journal: BMJ (2018)

The way doctors treat their peers is as important as their clinical skills, medical leaders have said.

Speaking at a conference on tackling undermining behaviour and bullying in the NHS held on 8 February, Henrietta Hughes, the national “freedom to speak up” guardian, said that doctors should be judged on both their competence and their conduct.

As national guardian, Hughes leads a network of guardians throughout the NHS. Staff can approach these guardians when they want to raise …
Novel small-molecule RORγ agonist immuno-oncology agent LYC-55716: Tumor selection and evaluation of renal cell and bladder cancer for inclusion in phase 2a expansion.
Authors: Xiao Hu, Xikui Liu, Hongxiu Li, Elizabeth Zawidzka, Garry Alan Weems, Yilin Gao, Brian Fox, H. Jeffrey Wilkins, Laura Carter
Journal: Journal of Clinical Oncology (2018)

424 Background: The master transcription factor retinoic acid receptor–related orphan receptor γt (RORγ) controls Type 17 effector T cell differentiation and function. Synthetic RORγ agonists modulate gene expression to enhance immune effector functions and decrease regulatory T cell (Treg) development and expression of checkpoint pathways. RORγ agonists have shown promise as mono- and combination therapy in syngeneic tumor models. Translational and bioinformatics analyses were performed to evaluate renal cell carcinoma (RCC) and bladder cancer (BC) for inclusion in a Phase 2a expansion trial of the investigational RORγ agonist LYC-55716 (NCT02929862). Methods: A gene signature was identified through transcriptional profiling of murine and human T cells treated ± RORγ agonists. Bioinformatics analyses were then conducted using data on RCC and BC patients from The Cancer Genome Atlas (TCGA) to determine (a) RORγ and RORγ-inducing cytokine expression; (b) signature genes associated with RORγ biology, biomarkers for endogenous RORγ ligands, and correlations with patient survival rates; and (c) tumor microenvironment (TME) immune profiles. Results: Expression: RNA sequencing analysis identified RORγ + cells in a significant fraction of RCC and BC samples. RORγ-inducing cytokines IL6, IL23a, and IL1b as well as other genes that support Type 17 differentiation were highly expressed in RCC and BC. Biology: Low expression of sterol efflux genes in RCC and BC tumors suggested low levels of endogenous RORγ ligands in the TME. Importantly, analysis revealed a positive correlation between patient survival and expression of RORγ (or the RORγ signature gene IL17A) for RCC. Immune profile: Analysis of RCC and BC tumors indicated high infiltration of CD3 + , CD4 + , and CD8 + T cells and high mutation burden, which are associated with immunotherapy efficacy. Conclusions: Translational and bioinformatics studies of RORγ expression, biology, and tumor immune profiles support the inclusion of RCC and BC patients in an ongoing Phase 2a expansion trial of LYC-55716.