tbuckley/cabot-search huggingface dataset:
Government dismisses call to ringfence public health budgets
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The government has rejected a recommendation from a major parliamentary inquiry to ringfence public health budgets for at least the next 10 years.

Last April the House of Lords select committee’s inquiry12 into the long term sustainability of the NHS and adult social care condemned public health budget cuts as “counterproductive.” The inquiry urged the government to restore funding that had been cut in recent years and to maintain ringfenced national and local public health budgets for at least a decade.

But in its response published on 20 February,3 the Department of Health said that it was not accepting the recommendation.

“Public health is about far more than the services funded through the grant [given to local authorities],” it said. “The transfer to local government provided the opportunity to join up public health with decisions on other local services such as …
Suboptimality in perceptual decision making
Authors: Dobromir Rahnev, Rachel N Denison
Journal: Behavioral and Brain Sciences (2018)

Human perceptual decisions are often described as optimal. Critics of this view have argued that claims of optimality are overly flexible and lack explanatory power. Meanwhile, advocates for optimality have countered that such criticisms single out a few selected papers. To elucidate the issue of optimality in perceptual decision making, we review the extensive literature on suboptimal performance in perceptual tasks. We discuss eight different classes of suboptimal perceptual decisions, including improper placement, maintenance, and adjustment of perceptual criteria; inadequate tradeoff between speed and accuracy; inappropriate confidence ratings; misweightings in cue combination; and findings related to various perceptual illusions and biases. In addition, we discuss conceptual shortcomings of a focus on optimality, such as definitional difficulties and the limited value of optimality claims in and of themselves. We therefore advocate that the field drop its emphasis on whether observed behavior is optimal and instead concentrate on building and testing detailed observer models that explain behavior across a wide range of tasks. To facilitate this transition, we compile the proposed hypotheses regarding the origins of suboptimal perceptual decisions reviewed here. We argue that verifying, rejecting, and expanding these explanations for suboptimal behavior - rather than assessing optimality per se - should be among the major goals of the science of perceptual decision making.
Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1BRx Improves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes
Authors: Andres Digenio, Nguyen C. Pham, Lynnetta M. Watts, Erin S. Morgan, Shiangtung W. Jung, Brenda F. Baker, Richard S. Geary, Sanjay Bhanot
Journal: Diabetes Care (2018)

OBJECTIVE To evaluate safety and efficacy of IONIS-PTP-1BRx, a second-generation 2′-O-methoxyethyl antisense inhibitor of protein tyrosine phosphatase 1B, as add-on therapy in overweight patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea therapy. RESEARCH DESIGN AND METHODS In this phase II, double-blind, randomized, placebo-controlled, multicenter trial, overweight and obese patients (BMI ≥27 kg/m2) with type 2 diabetes (HbA1c ≥7.5% [58 mmol/mol] and ≤10.5% [91 mmol/mol]) on a stable dose of metformin alone or with sulfonylurea were randomized 2:1 to IONIS-PTP-1BRx 200 mg (n = 62) or placebo (n = 30) once weekly for 26 weeks. RESULTS Mean baseline HbA1c was 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol) in placebo and active treatment, respectively. At week 27, IONIS-PTP-1BRx reduced mean HbA1c levels by −0.44% (−4.8 mmol/mol; P = 0.074) from baseline and improved leptin (−4.4 ng/mL; P = 0.007) and adiponectin (0.99 μg/mL; P = 0.026) levels compared with placebo. By week 36, mean HbA1c was significantly reduced (−0.69% [−7.5 mmol/mol]; P = 0.034) and accompanied by reductions in fructosamine (−33.2 μmol/L; P = 0.005) and glycated albumin (−1.6%; P = 0.031) versus placebo. Despite both treatment groups receiving similar lifestyle counseling, mean body weight significantly decreased from baseline to week 27 with IONIS-PTP-1BRx versus placebo (−2.6 kg; P = 0.002) independent of HbA1c reduction (R2 = 0.0020). No safety concerns were identified in the study. CONCLUSIONS Compared with placebo, IONIS-PTP-1BRx treatment for 26 weeks produced prolonged reductions in HbA1c, improved medium-term glycemic parameters, reduced leptin and increased adiponectin levels, and resulted in a distinct body weight–reducing effect.
Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation
Authors: Difeng Fang, Kairong Cui, Gangqing Hu, Rama Krishna Gurram, Chao Zhong, Andrew J. Oler, Ryoji Yagi, Ming Zhao, Suveena Sharma, Pentao Liu, Bing Sun, Keji Zhao, Jinfang Zhu
Journal: The Journal of Experimental Medicine (2018)

GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein–protein interaction, and they colocalize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5, and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3 dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells.
New-onset congestive heart failure (CHF) and cardiovascular disease (CVD) in older colorectal cancer (CRC) survivors: A population-based study.
Authors: Kelly Kenzik, Courtney Balentine, Smita Bhatia, Grant Richard Williams
Journal: Journal of Clinical Oncology (2017)

10011 Background: CRC is primarily a disease of the elderly. The high burden of pre-existing comorbidities alone or in concert with cancer treatment place the older patients with CRC at increased risk of new-onset morbidities, specifically, CVD and CHF. However, the magnitude of risk of new-onset morbidity, and its association with pre-existing comorbidities or treatment remain unknown. Methods: Using SEER-Medicare data, we evaluated individuals diagnosed with incident stage I-III CRC at age ≥66y between 1/1/2000 and 12/31/2011 who had survived ≥2y after diagnosis (n = 57,256; 77% with colon cancer). We compared these to an age, sex-, and race-frequency matched comparison group of non-cancer Medicare patients (n = 104,731). We evaluated new-onset CHF and CVD using competing risk cumulative incidence functions and multivariable Cox regression models. Results: The median age at diagnosis was 77y (66-106y); 45% males; and 85% non-Hispanic white. Median follow-up was 8y (2-14y) from diagnosis of CRC. Treatment included surgery for 99%, chemotherapy for 31%, and radiation for 12%. New-onset morbidity: The 10y cumulative incidence of new-onset CHF and CVD were 43.6% and 58.9%, respectively. After controlling for pre-cancer comorbidities, CRC survivors were at increased risk of new-onset CHF (HR 1.29) and CVD (HR 1.74) (all p &lt; 0.001) compared to controls. Patients receiving radiation (HR 1.29) or 5-FU+oxaliplatin (HR 1.09) were at increased risk of CVD compared to those without those therapies (p &lt; 0.001). Pre-existing diabetes (HR 1.16) and CHF (HR 1.21) independently increased the risk of CVD (p &lt; 0.001). While 5FU+oxaliplatin did not increase the risk of CHF independently (HR 0.97), diabetic patients treated with 5-FU+oxaliplatin were at 1.71-fold increased risk of developing CHF (p &lt; 0.001) when compared with those without pre-existing diabetes. Conclusions: Older CRC survivors are at increased of developing CHF and CVD. Monitoring survivors with a history of exposure to 5FU+oxaliplatin or radiation, and improving management of pre-existing comorbidities may reduce the burden of long-term morbidity for older CRC survivors.
LONG TERM SURVIVAL BENEFIT OF CHRONIC TOTAL OCCLUSION REVASCULARIZATION VERSUS CONSERVATIVE TREATMENT IN ELDERLY PATIENTS
Authors: Eduardo Flores, Victoria Martin-Yuste, Ignacio Ferreira-Gonzalez, Guillem Caldentey, Sara Vazquez, Rodolfo San Antonio Dharandas, Gustavo Jimenez, Xavier Freixa, Ander Regueiro, Manel Sabate
Journal: Journal of the American College of Cardiology (2018)
Lateral Displacement of the Inner Canthi in a Child of Deaf Parents
Authors: Valentina Carrato, Sara Lega, Alessandro Ventura
Journal: JAMA Pediatrics (2018)

A young boy presented with lateral displacement of the inner canthi of the eyes with a broad nasal root, small nostrils, and medial eyebrow flare and a family history of deafness in both parents. What is your diagnosis?
Review: Atraumatic lumbar puncture needles reduce postdural puncture headache compared with conventional needles
Authors: Ken Uchino
Journal: Annals of Internal Medicine (2018)

ACP Journal Club20 March 2018Review: Atraumatic lumbar puncture needles reduce postdural puncture headache compared with conventional needlesKen Uchino, MDKen Uchino, MDCleveland Clinic, Cleveland, Ohio, USA (K.U.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-6-034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNath S, Koziarz A, Badhiwala JH, et al. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2017. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/29223694Clinical Impact RatingsNeurology: Author, Article, and Disclosure InformationAffiliations: Cleveland Clinic, Cleveland, Ohio, USA (K.U.)This article was published at Annals.org on 6 March 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 March 2018Volume 168, Issue 6Page: JC34KeywordsAnalgesiaAnesthesiaBloodHeadachesHearingLumbar punctureNervesPatientsRelative riskSystematic reviews ePublished: 20 March 2018 Issue Published: 20 March 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
EMERGENCY DEPARTMENT VISITS AMONG CHILDREN WITH CONGENITAL HEART DISEASE IN THE UNITED STATES FROM 2006 TO 2014
Authors: Jonathan Edelson, Joseph William Rossano, Heather Griffis, Dingwei Dai, Jennifer Faerber, Chitra Ravishankar, Christopher Mascio, Laura Mercer-Rosa, Andrew Glatz, Kimberly Lin
Journal: Journal of the American College of Cardiology (2018)
I am training in London but am interested in applying for house jobs outside of London. I know colleagues who have done this in the past but I have heard that it is not possible any more to work outside the trust that you trained with.
Authors: Simon Eccles
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Doctors must attend workplace and provide emergency care during industrial action
Authors: Helen Jaques
Journal: BMJ (2012)

Should industrial action be called, doctors must attend their workplace as scheduled but should provide emergency and urgent care only at their discretion, the BMA has said.

Next week the association will ballot its members on whether to take industrial action over changes to the NHS pension scheme. The BMA has ruled out complete withdrawal of labour should the ballot return a positive vote and will instead ask members to provide urgent and emergency care only for one or more 24 hour periods.

“Urgent and emergency care” will include any treatment that cannot be safely postponed to another day, the BMA has said in its new guidance on what industrial action would entail.

Hospital doctors would not be required to do non-urgent surgery and investigations, elective clinics and theatre lists, outpatient consultations, and some non-clinical work such as audit or multidisciplinary meetings. Consultants would still need to …
A qualitative analysis of the impact of Carboplatin AUC 10 on physical, work functioning, and bone marrow toxicity, in patients with metastatic seminoma: A single centre experience.
Authors: Marina Milic, Anand Sharma, Andrew Gogbashian, Annette Hawkins, Gordon J. S. Rustin, Marcia Hall
Journal: Journal of Clinical Oncology (2018)

558 Background: We studied the efficacy, safety and tolerability of dose dense Carboplatin AUC10 chemotherapy and explored the HRQoL (health-related quality of life) in metastatic seminoma patients receiving this regimen. Methods: 46 patients with metastatic seminoma treated with Carboplatin AUC10 were identified in our centre. Carboplatin dosing at AUC 10 was used and calculated based on Calvert formula and EDTA clearance. Treatment was administered as a single dose every 21 days for 3 or 4 cycles. Response to treatment was determined by radiological imaging and serum tumour markers. Toxicities were evaluated using the CTCAE Version 4.0. Quality of life (QOL) and long-term treatment related toxicities were assessed post treatment using a self-designed telephonic questionnaire consisting of 4 questions about toxicity, which included- hair loss, hearing impairment, days absence from work and neuropathy. Results: Clinical characteristics are as follows: median age 44 (range 26-77), 34 patients had stage II and 12 stage III seminoma; average dose of carboplatin administered was 1240mg per cycle. 4.3% patients received 2, 87% 3 and 8.7.% 4 cycles of chemotherapy. 93% of patients achieved a complete remission (CR), 4 (all stage IIC) patients required a fourth cycle of chemotherapy, 2 undergoing RPLND and 2 watchful waiting. There was no disease relapse at median follow-up of 27.5 (range 4-84) months. 13 patients (28%) had grade 3 and 2 (4%) grade 4 neutropenia, thirteen (28%) grade 3/4 thrombocytopenia, Nine (19.5%) patients required prophylactic filgrastim. Commonest non-heamatological toxicities were fatigue in 28 (50%) and nausea 14(28%) patients. QOL data was available for 35/46 (76%) of patients. 40/46 (87%) patients had no residual tinnitus, one had residual grade 1 peripheral neuropathy. Eight patients continued to work throughout treatment, 16(45%) took &lt; 5 days off work during chemotherapy, 4 took 5 to 21 days, 13 &gt; 21 days, two were retired. Conclusions: Carbo AUC10 is a safe and effective treatment. Our results suggest the lack of negative impact of Carbo AUC10 on short and intermediate QOL without compromising treatment outcomes.
Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis
Authors: Jahnavi Daru, Javier Zamora, Borja M Fernández-Félix, Joshua Vogel, Olufemi T Oladapo, Naho Morisaki, Özge Tunçalp, Maria Regina Torloni, Suneeta Mittal, Kapila Jayaratne, Pisake Lumbiganon, Ganchimeg Togoobaatar, Shakila Thangaratinam, Khalid S Khan
Journal: The Lancet Global Health (2018)

BackgroundAnaemia affects as many as half of all pregnant women in low-income and middle-income countries, but the burden of disease and associated maternal mortality are not robustly quantified. We aimed to assess the association between severe anaemia and maternal death with data from the WHO Multicountry Survey on maternal and newborn health.MethodsWe used multilevel and propensity score regression analyses to establish the relation between severe anaemia and maternal death in 359 health facilities in 29 countries across Latin America, Africa, the Western Pacific, eastern Mediterranean, and southeast Asia. Severe anaemia was defined as antenatal or postnatal haemoglobin concentrations of less than 70 g/L in a blood sample obtained before death. Maternal death was defined as death any time after admission until the seventh day post partum or discharge. In regression analyses, we adjusted for post-partum haemorrhage, general anaesthesia, admission to intensive care, sepsis, pre-eclampsia or eclampsia, thrombocytopenia, shock, massive transfusion, severe oliguria, failure to form clots, and severe acidosis as confounding variables. These variables were used to develop the propensity score.Findings312 281 women admitted in labour or with ectopic pregnancies were included in the adjusted multilevel logistic analysis, and 12 470 were included in the propensity score regression analysis. The adjusted odds ratio for maternal death in women with severe anaemia compared with those without severe anaemia was 2·36 (95% CI 1·60–3·48). In the propensity score analysis, severe anaemia was also associated with maternal death (adjusted odds ratio 1·86 [95% CI 1·39–2·49]).InterpretationPrevention and treatment of anaemia during pregnancy and post partum should remain a global public health and research priority.FundingBarts and the London Charity.
Primary prevention of cardiovascular disease: The past, present, and future of blood pressure- and cholesterol-lowering treatments
Authors: Maarten J. G. Leening, M. Arfan Ikram
Journal: PLoS Medicine (2018)

Shortly after World War II, coronary heart disease was recognized as an epidemic.Cardiovascular disease (CVD) had become the leading cause of death in Western societies.This led to the formation of the National Heart, Lung, and Blood Institute in the United States and initiation of the seminal Framingham Heart Study in 1948.This population-based cohort study on the etiology and consequences of CVD has shed light on many of the well-known causes of CVD.In one of their initial publications in 1961, the investigators from the Framingham Heart Study introduced the concept of "factors of risk in the development of coronary heart disease", nowadays known as traditional cardiovascular risk factors [1].The identification of high blood pressure and cholesterol levels as causes of CVD led to the idea of screening and treatment thereof in otherwise healthy persons, in order to halt atherosclerosis and forestall the occurrence of cardiovascular events.Initial treatment recommendations in the 1970s and 1980s were based on the levels of the specific risk factors, with antihypertensive treatment recommended for "virtually all persons with a diastolic blood pressure exceeding 105 mmHg" [2].However, a gradual diversification then took place in preventive cardiology: hypertension guidelines remained focused on blood pressure levels, whereas cholesterol treatment guidelines moved towards more sophisticated approaches by recommending pharmacological interventions informed by the individual's cardiovascular risk based on the presence and levels of multiple cardiovascular risk factors.
ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Angel L. Guerrero-Zotano, Thomas P. Stricker, Luigi Formisano, Katherine E. Hutchinson, Daniel G. Stover, Kyung-Min Lee, Luis J. Schwarz, Jennifer M. Giltnane, Monica V. Estrada, Valerie M. Jansen, Alberto Servetto, Joaquín Gavilá, J. Alejandro Perez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice André, Mónica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L. Arteaga
Journal: Clinical Cancer Research (2018)

This study aimed to identify biomarkers of resistance to endocrine therapy in estrogen receptor-positive (ER
Seven day NHS would not be cost effective use of resources, researchers say
Authors: Abi Rimmer
Journal: BMJ (2015)

Implementing seven day services across the NHS in England would not be a cost effective use of resources, researchers have said.

In a paper published in Health Economics the researchers, from the University of Manchester, said that the “crude 30-day mortality rate was 3.70% for patients admitted during the week and 4.05% for those admitted during the weekend.”1 They calculated that between …
DEVICES, DRUGS AND TEAMWORK: FIRST SUCCESSFUL COMBINATION OF THE IMPELLA LEFT VENTRICULAR ASSIST DEVICE AND STEROIDS AS A BRIDGE TO RECOVERY IN A PATIENT WITH CARDIOGENIC SHOCK SECONDARY TO EOSINOPHILIC MYOCARDITIS - THE IMPORTANCE OF THE CARDIOGENIC SHOCK TEAM
Authors: Carlos Davila, Navin Kapur
Journal: Journal of the American College of Cardiology (2018)
Putting the brake on accelerated lung function decline in asthma
Authors: Dominic Shaw
Journal: European Respiratory Journal (2018)

The focus of most asthma care is on symptom control and exacerbation (attack) prevention. This focus is needed; asthma is a very common disease, still leads to an unnecessarily high symptom burden and is a cause of preventable deaths [1, 2]. This negative impact occurs despite the recognition that asthma is a heterogeneous disease with various subtypes [3] requiring different treatment approaches [4], with the development of multiple new targeted therapies [5]. Although the identification of biomarkers to help predict exacerbations and understand the interactions between asthma, risk and comorbidities is a key research priority area [6], one of the major problems still affecting our ability to improve asthma outcomes is persuading patients to take potentially lifelong inhaled therapy when, at least for mild and moderate asthma, patients often feel well most of the time. Assessing for risk of lung function decline in asthma is important and needs more attention <http://ow.ly/L57h30hME3c>
High-Impact CVs: Make Your Résumé Sensational
Authors: Ruth Chambers
Journal: BMJ (2006)

John Middleton

Infinite Ideas, 2005, £8.57, 256 pages

ISBN: 1 90490 220 0

Rating: ★★★★★/5



This is one of the series of Brilliant Ideas books that contain 52 chapters, each packed with ideas to inspire you to action to achieve positive changes in your life. The book helps you to present yourself and your experience and skills, qualifications, and personal information in your best light on your CV. The chapters contain hundreds of tips and lots of detailed advice.

The book is useful for anyone who wants to progress in their career, and is as relevant to someone in a medical career as in …
What is the obstetrics list, do you need to be on it as a general practitioner, and do you need to do obstetrics and gynaecology in your GP training to get on it?
Authors: Judith Harvey London
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>