tbuckley/cabot-search huggingface dataset:
Gosport: new criminal investigation is launched into hundreds of deaths at hospital
Authors: Clare Dyer
Journal: BMJ (2019)

Police have opened a new criminal investigation into the deaths of hundreds of patients at the War Memorial Hospital in Gosport, Hampshire, where an inquiry found that many people had had their lives shortened by unnecessary administration of opioids.1

The investigation could result in criminal charges against Jane Barton, a local GP who worked part time as a clinical assistant at the hospital for 12 years.

The Crown Prosecution Service decided not to charge her after three previous investigations by Hampshire Constabulary into 92 deaths. But Kent Police, after …
PTH-040 Endoscopic duodenal mucosal resurfacing in type 2 diabetes – a single centre experience
Authors: Cormac Magee, Martin Everson, Jessica Mok, Janine Makaronidis, Giulia Argentesi, Sally Thorpe, Pajany Vythelingum, Andrea Pucci, Rachel Batterham, Rehan Haidry
Journal: Endoscopy (2018)

<h3>Introduction</h3> Evidence from bariatric surgical procedures (e.g. Roux-en-Y gastric bypass) suggests that the duodenum plays a crucial role in glycaemic control in patients with Type 2 Diabetes (T2DM). Duodenal mucosal resurfacing (DMR), a novel endoscopic therapy that resurfaces the duodenal mucosa via hydrothermal ablation, exerts an insulin-sensitising effect likely through modification of nutrient-mucosa signalling. DMR involves placing a catheter in the proximal duodenum distal to the papilla under endoscopic and fluoroscopic guidance. The duodenal mucosa is injected with saline to 'lift' it and a balloon is inflated with water and heated to 90°C to circumferentially ablate the mucosa for 10 cm. We describe the first series of patient cases from the UK treated with DMR at at University College London Hospitals (UCLH). <h3>Methods</h3> Cases were derived from two clinical studies: REVITA 1 a single arm, open-label multi-centre in T2DM, and the open-label phase of REVITA-2 an internationl, multi-centre, randomised, double-blinded, sham controlled study in T2DM. Eligible paitents were adults with T2DM and HbA1c of 7.5%–10.0% on ≥1 oral glucose lowering medication. Baseline blood tests were collected and following a 4–6 week run-in period, patient's were treated with the DMR procedure. Patients received dietetic advice were given a specific 2 week post procedure diet. Blood tests were analysed at regular intervals following the procedure to assess changes in HbA1c over time. Hepatic transaminases were also measured and calulations were made for Homeostasis Model Assessment index (HOMA-IR) – a measure of insulin resistance. Information on adverse events was recorded at each visit. <h3>Results</h3> A total of 11 patients (n=5 female, 58±11 years) were treated with DMR at UCLH from May 2015 – Dec 2017. Mean (±SEM) change in HbA1c at 3 months post DMR was 0.5% (±0.2) for all patients and −0.7% (±0.2 when one patient was excluded for whom gliclazide had to be stopped due to symptomatic hypoglycaemia in the month following DMR. A total of 5/11 patients completed 6 and 12 months of follow-up with mean changes in HbA1c of −1.3% and −1.5% respectively. Favourable directional changes were also observed in HOMA-IR and hepatic transaminases. Patients tolerated the procedure well and no SAEs or UADEs were reported. Two of the eleven patients (18%) patients experiencing transient constipation. <h3>Conclusion</h3> Based on our centre's experience, DMR appears to provide a safe and effective method of improving glycaemic control in patients with T2DM. We contintue to enrol patients in the REVITA-2 trial and the results of this study will be crucial in determining the effectiveness and durability of DMR.
A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder
Authors: Federico Bolognani, Marta del Valle Rubido, Lisa Squassante, Christoph Wandel, Michael Derks, Lorraine Murtagh, Jeff Sevigny, Omar Khwaja, Daniel Umbricht, Paulo Fontoura
Journal: Science Translational Medicine (2019)

There are no approved pharmacological therapies to address the core symptoms of autism spectrum disorder (ASD), namely, persistent deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behaviors, interests, or activities. The neuropeptide vasopressin has been implicated in the regulation of social behaviors, and its modulation has emerged as a therapeutic target for ASD. The phase 2 VANILLA clinical trial reported here evaluated balovaptan, an orally administered selective vasopressin V1a receptor antagonist, in 223 men with ASD and intelligence quotient ≥70. The drug was administered daily for 12 weeks and was compared with placebo. Participants were randomized to placebo (n = 75) or one of three balovaptan dose arms (1.5 mg, n = 32; 4 mg, n = 77; 10 mg, n = 39). Balovaptan treatment was not associated with a change from baseline compared with placebo at 12 weeks in the primary efficacy endpoint (Social Responsiveness Scale, 2nd Edition). However, dose-dependent and clinically meaningful improvements on the Vineland-II Adaptive Behavior Scales composite score were observed for participants treated with balovaptan 4 or 10 mg compared with placebo. This was driven principally by improvements in the Vineland-II socialization and communication scores. Balovaptan was well tolerated across all doses, and no drug-related safety concerns were identified. These results support further study of balovaptan as a potential treatment for the socialization and communication deficits in ASD.
Discrimination against hepatitis B infected medical students could end
Authors: Richard Hurley
Journal: BMJ (2005)

Students infected with hepatitis B, a highly infectious liver disease, may soon be allowed to train as doctors after a review by UK government and universities. Under the new plans, medical students would also be screened for HIV and hepatitis C for the first time. A positive result would not, however, mean that they could not become doctor.

The hepatitis B virus is thought to be the leading cause of liver cancer and is about 100 times more infectious than HIV. Currently students who test positive for …
Female genital mutilation is awful
Authors: Ahmed Magdy Kassem
Journal: BMJ (2005)

The question “when should doctors perform female genital mutilation?” sounds as if female genital mutilation (FGM) is a normal procedure that doctors do every day in their practice. In fact, it is an awful traditional procedure that is nowadays considered a crime in many countries. In this world of multidisciplinary communities, however, it is more likely for doctors to come into contact with girls who are at risk.1

Most parents seeking this procedure for their daughters believe that they are making the right decision for the sake of their child. Based on traditional, social, or mistaken religious beliefs, the parent seeks the doctor's help to perform this procedure simply …
How the Dead Live
Authors: Debashis Singh
Journal: BMJ (2001)

What exactly happens to us when we die? Do we rot away into oblivion; swagger up to Heaven or skid in to the burning belly of Hell; get reincarnated; or roam aimlessly around shopping malls looking for a bargain? This is one of the questions posed by Will Self in his new novel. Death and dying hardly seem like the topics of a bestseller, but welcome to “Will's World.” …
Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential — United States, 2003–2017
Authors: Mbabazi Kariisa, Lawrence Scholl, Nana Wilson, Puja Seth, Brooke Hoots
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In 2016, a total of 63,632 persons died from drug overdoses in the United States (1). Drug overdose deaths involving cocaine, psychostimulants with abuse potential (psychostimulants), or both substances combined increased 42.4% from 12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, methylphenidate (Ritalin), and caffeine. From 2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased 52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug overdoses in the United States in 2017; approximately two thirds of these deaths involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death rates involving cocaine and psychostimulants by demographic characteristics, urbanization levels, U.S. Census region, 34 states, and the District of Columbia (DC). CDC also examined trends in age-adjusted cocaine-involved and psychostimulant-involved death rates from 2003 to 2017 overall, as well as with and without co-involvement of opioids. Among all 2017 drug overdose deaths, 13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 for both drug categories across demographic characteristics, urbanization levels, Census regions, and states. In 2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and psychostimulant-involved overdoses, respectively, and the data suggest that increases in cocaine-involved overdose deaths from 2012 to 2017 were driven primarily by synthetic opioids. Conversely, increases in psychostimulant-involved deaths from 2010 to 2017 occurred largely independent of opioids, with increased co-involvement of synthetic opioids in recent years. Provisional data from 2018 indicate that deaths involving cocaine and psychostimulants are continuing to increase.† Increases in stimulant-involved deaths are part of a growing polysubstance landscape. Increased surveillance and evidence-based multisectoral prevention and response strategies are needed to address deaths involving cocaine and psychostimulants and opioids. Enhancing linkage to care, building state and local capacity, and public health/public safety collaborations are critical components of prevention efforts.
The benefits of taking a year out
Authors: Joanna Cook
Journal: BMJ (2001)

Joanna Cook explains how her year out in Zimbabwe rekindled her enthusiasm for medicine

It was about this time two years ago, when I was an intercalated student, that I began to think that medicine was not for me. I have always been a bit of an idealist and the presence of these doubts perhaps bothered me more than their actual, rather vague, content. Perhaps it was a fear of commitment.

I found a leaflet on a university notice board calling for volunteers to work in “youth development” in rural Africa and I made an appointment to see my dean. The medical school was surprisingly sympathetic and I was given permission to defer my entry into the clinical school for one year. This gave me some time to think about my reasons for finishing the course and also the opportunity to broaden my horizons a bit--to go and live and work somewhere with a completely different culture. For one year at least I wouldn't be …
Counting CD4 cells cheaply: diagnostic accuracy study
Authors: Kirsten Patrick
Journal: BMJ (2007)

### This month's paper

Diagnostic accuracy and clinical utility of a simplified low cost method of counting CD4 cells with flow cytometry in Malawi: diagnostic accuracy study by Calman A MacLennan and colleagues ( BMJ 2007;335:190 doi: 10.1136/bmj.39268.719780.BE).

#### Abstract

Objectives -To assess the diagnostic accuracy and clinical utility of a simplified low cost method for measuring absolute and percentage CD4 counts with flow cytometry.

Design -A CD4 counting method (Blantyre count) using a CD4 and CD45 antibody combination with reduced blood and reagent volumes. Diagnostic accuracy was assessed by measuring agreement of the index test with two other assays (TruCount and FACSCount). Clinical utility was investigated by comparing CD4 counts with the new assay with WHO clinical staging in patients with HIV.

Setting -Research laboratories and antiretroviral therapy clinic at a medical school and large government hospital in southern Malawi.

Participants -Assay comparisons were performed on consecutive blood samples sent for CD4 counting from 129 patients with HIV. Comparison of CD4 count with staging was conducted on 253 consecutive new patients attending the antiretroviral therapy clinic.

Main outcome measures -Limits of agreement with 95% confidence intervals between index test and reference standards.

Results -The limits of agreement for Blantyre count and TruCount were excellent (cell count -48.9 to 27.0 cells/micro l for absolute counts in the CD4 range >400 cells/micro l and -2.42% to 2.37% for CD4 percentage). The assay was affordable with reagent costs per test of $0.44 (0.22 pound; 0.33 euro) for both absolute count and CD4 percentage, and $0.11 for CD4 percentage alone. Of 193 patients with clinical stage I or II disease, who were ineligible for antiretroviral therapy by clinical staging criteria, 73 (38%) had CD4 counts >200 cells/micro l. By contrast, 12 (20%) of 60 patients with stage III or IV disease had CD4 counts <350 cells/micro l.

Conclusions -This simplified …
Combined Antitumor Effects of Sorafenib and GPC3-CAR T Cells in Mouse Models of Hepatocellular Carcinoma
Authors: Xiuqi Wu, Hong Luo, Bizhi Shi, Shengmeng Di, Ruixin Sun, Jingwen Su, Ying Liu, Hua Li, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2019)

Our previous study indicated that GPC3-targeted chimeric antigen receptor (CAR) T cell therapy has a high safety profile in patients with hepatocellular carcinoma (HCC). However, the response rate requires further improvement. Here, we analyzed the combined effect of GPC3-CAR T cells and sorafenib in both immunocompetent and immunodeficient mouse models of hepatocellular carcinoma. In immunocompetent mouse model, mouse CAR (mCAR) T cells induced regression of small tumors (approximately 130 mm3 tumor volume) but had no effect on large, established tumors (approximately 400 mm3 tumor volume). Sorafenib, at a subpharmacologic but not a pharmacologic dose, augmented the antitumor effects of mCAR T cells, in part by promoting IL12 secretion in tumor-associated macrophages (TAMs) and cancer cell apoptosis. In an immunodeficient mouse model, both subpharmacologic and pharmacologic doses of sorafenib had limited impacts on the function of human CAR (huCAR) T cells in vitro and showed synergistic effects with huCAR T cells in vivo, which can at least partially be ascribed to the upregulated tumor cell apoptosis induced by the combined treatment. Thus, this study applied two of the most commonly used mouse models for CAR T cell research and demonstrated the clinical potential of combining sorafenib with GPC3-targeted CAR T cells against HCC.
Abstract 18949: Socioeconomic Patterning of Hypertension in Grenada
Authors: Eric T Roberts, Leigh Quarles, Valentin Fuster, Bernadette Boden-Albala
Journal: Circulation (2012)

Over 80% of cardiovascular disease deaths occur in low and middle income countries with approximately two-thirds of stoke and one-half of ischemic heart disease estimated to be due to non-optimal blood pressure. Much is known about the social epidemiology of hypertension in “Western” contexts but less is known about these associations in developing or “non-Western” contexts. The island nation of Grenada, located off the Northeast coast of Venezuela with a population of approximately 110,000 persons, presents an instructive case study. This study describes the socioeconomic patterning of hypertension in a population of Grenadians. The Grenada Heart Project surveyed 2827 persons regarding the clinical, biological and psychosocial determinants of cardiovascular health between 2008 and 2010. We explored the association between education, income, occupation, nativity, residing in either the United States or Europe at one point in time, and parish of residence with definitive hypertension (≥140/90 mmHg) in separate logistic regression models adjusting for age and sex. The sample was 57.5% female with a mean age of 44.8 (sd = 17.1)., Participants that did not complete primary school [OR=2.04, 95%CI 1.37, 3.02)], participants that only completed primary school [OR=1.82, 95%CI 1.29, 2.58)], and participants that attended or completed secondary school [OR=1.48, 95%CI 0.99, 2.21)] had increased odds of having hypertension compared to those with more than a secondary education. Compared to government employees, homemakers [OR=2.45, 95%CI 1.52, 3.95)], retired persons [OR=2.40, 95%CI 1.69, 3.42)], and unemployed persons that are unable to work [OR=2.85, 95%CI 1.59, 5.11)] had increased odds of having hypertension whereas non-government employees [OR=1.09, 95%CI 0.79, 1.50)], self-employed persons [OR=1.09, 95%CI 0.96, 1.85)], and unemployed persons that are able to work [OR=1.09, 95%CI 0.68, 1.69)] did have significantly different odds of hypertension. We found significant differences in the prevalence of hypertension by parish. Income, nativity, and history of residing in western countries was not associated with hypertension. This work documents the importance of social variables in low and middle income countries in predicting hypertension.
EZH2 Is Overexpressed in <i>BRCA1</i>-like Breast Tumors and Predictive for Sensitivity to High-Dose Platinum-Based Chemotherapy
Authors: Julian Puppe, Mark Opdam, Philip C. Schouten, Katarzyna Jóźwiak, Esther Lips, Tesa Severson, Marieke van de Ven, Chiara Brambillasca, Peter Bouwman, Olaf van Tellingen, René Bernards, Jelle Wesseling, Christian Eichler, Fabinshy Thangarajah, Wolfram Malter, Gaurav Kumar Pandey, Luka Ozretić, Carlos Caldas, Maarten van Lohuizen, Michael Hauptmann, Kerstin Rhiem, Eric Hahnen, H. Christian Reinhardt, Reinhard Büttner, Peter Mallmann, Birgid Schömig-Markiefka, Rita Schmutzler, Sabine Linn, Jos Jonkers
Journal: Clinical Cancer Research (2019)

Abstract Purpose: BRCA1-deficient breast cancers carry a specific DNA copy-number signature (“BRCA1-like”) and are hypersensitive to DNA double-strand break (DSB) inducing compounds. Here, we explored whether (i) EZH2 is overexpressed in human BRCA1-deficient breast tumors and might predict sensitivity to DSB-inducing drugs; (ii) EZH2 inhibition potentiates cisplatin efficacy in Brca1-deficient murine mammary tumors. Experimental Design: EZH2 expression was analyzed in 497 breast cancers using IHC or RNA sequencing. We classified 370 tumors by copy-number profiles as BRCA1-like or non-BRCA1–like and examined its association with EZH2 expression. Additionally, we assessed BRCA1 loss through mutation or promoter methylation status and investigated the predictive value of EZH2 expression in a study population of breast cancer patients treated with adjuvant high-dose platinum-based chemotherapy compared with standard anthracycline-based chemotherapy. To explore whether EZH2 inhibition by GSK126 enhances sensitivity to platinum drugs in EZH2-overexpressing breast cancers we used a Brca1-deficient mouse model. Results: The highest EZH2 expression was found in BRCA1-associated tumors harboring a BRCA1 mutation, BRCA1-promoter methylation or were classified as BRCA1 like. We observed a greater benefit from high-dose platinum-based chemotherapy in BRCA1-like and non-BRCA1–like patients with high EZH2 expression. Combined treatment with the EZH2 inhibitor GSK126 and cisplatin decreased cell proliferation and improved survival in Brca1-deficient mice in comparison with single agents. Conclusions: Our findings demonstrate that EZH2 is expressed at significantly higher levels in BRCA1-deficient breast cancers. EZH2 overexpression can identify patients with breast cancer who benefit significantly from intensified DSB-inducing platinum-based chemotherapy independent of BRCA1-like status. EZH2 inhibition improves the antitumor effect of platinum drugs in Brca1-deficient breast tumors in vivo.
Higher testosterone levels may make Oscar success more likely
Authors: Karen Herbert
Journal: BMJ (2003)

Oscar worthy actors may have higher testosterone levels than their less successful counterparts. Dr James Dabb and PhD student Kelly Leach Cate from Georgia State University investigated the testosterone levels of 50 male actors auditioning for lead acting roles.

Actors gave saliva samples both before and after a videotaped audition. They also completed questionnaires which asked them to rate how “in character,” confident, and eager they felt before the audition. They were also asked to rate how satisfied they felt …
Gynaecological teaching associates are not the answer
Authors: Syed M A Sohaib
Journal: BMJ (2004)

The standardised patient—you might have tested their cranial nerves in an objective structured clinical exam or consoled them in an emotionally charged communication skills session. Now the United Kingdom is welcoming a new generation of standardised patients known as gynaecology teaching associates (GTAs). These are women who have been trained to teach medical students how to do vaginal examinations, and then let their tutees practise on them. The GTAs give students immediate feedback. Sessions with GTAs are designed to help students overcome psychological barriers to carrying out these intimate examinations, and to ensure they do them competently before seeing patients in clinic. …
Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose
Authors: Rahi Abouk, Rosalie Liccardo Pacula, David Powell
Journal: JAMA Internal Medicine (2019)

Given high rates of opioid-related fatal overdoses, improving naloxone access has become a priority. States have implemented different types of naloxone access laws (NALs) and there is controversy over which of these policies, if any, can curb overdose deaths. We hypothesize that NALs granting direct authority to pharmacists to provide naloxone will have the greatest potential for reducing fatal overdoses.
Clinical outcomes in patients switched from adalimumab to baricitinib due to non-response and/or study design: phase III data in patients with rheumatoid arthritis
Authors: Yoshiya Tanaka, Bruno Fautrel, Edward C Keystone, Robert A Ortmann, Li Xie, Baojin Zhu, Maher Issa, Himanshu Patel, Carol L Gaich, Stephanie de Bono, Terence P Rooney, Peter C Taylor
Journal: Annals of the Rheumatic Diseases (2019)

To evaluate clinical outcomes in patients who changed treatment from adalimumab to baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, during a phase III programme.In phase III RA-BEAM, patients were randomised 3:3:2 to placebo, baricitinib 4 mg once daily, or adalimumab 40 mg biweekly. At week 16 or subsequent visits, non-responders were rescued to open-label baricitinib 4 mg. At week 52, patients could enter a long-term extension (LTE) and continue on baricitinib or switch from adalimumab to baricitinib 4 mg with no adalimumab washout period. Percentage of patients achieving low disease activity and remission were assessed, along with physical function, patient's assessment of pain, and safety.Thirty-five (7%) baricitinib-treated and 40 (12%) adalimumab-treated patients were rescued to baricitinib in RA-BEAM; 78% (381/487) of baricitinib-treated and 72% (238/330) of adalimumab-treated patients who were not rescued in RA-BEAM, entered the LTE and continued/were switched to baricitinib. In both baricitinib-rescued and adalimumab-rescued patients, there were significant improvements in all measures up to 12 weeks after rescue compared with the time of rescue. Patients who switched from adalimumab to baricitinib showed improvements in disease control through 12 weeks in the LTE. Exposure-adjusted incidence rates for treatment-emergent adverse events (TEAEs) and infections, including serious events, were similar for patients who switched from adalimumab to baricitinib and those who continued on baricitinib.Switching from adalimumab to baricitinib (without adalimumab washout) was associated with improvements in disease control, physical function and pain during the initial 12 weeks postswitch, without an increase in TEAEs, serious adverse events or infections.NCT01710358, NCT01885078.