tbuckley/cabot-search huggingface dataset:
The Presence of Diabetes and Higher HbA1c Are Independently Associated With Adverse Outcomes After Surgery
Authors: Priscilla H. Yong, Laurence Weinberg, Niloufar Torkamani, Leonid Churilov, Raymond J. Robbins, Ronald Ma, Rinaldo Bellomo, Que T. Lam, James D. Burns, Graeme K. Hart, Jeremy F. Lew, Johan Mårtensson, David Story, Andrew N. Motley, Douglas Johnson, Jeffrey D. Zajac, Elif I. Ekinci
Journal: Diabetes Care (2018)

OBJECTIVE Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA1c as a continuous measure, with postoperative outcomes. RESEARCH DESIGN AND METHODS In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA1c &amp;lt;5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model. RESULTS Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05–1.58]; P = 0.014), major complications (1.32 [1.14–1.52]; P &amp;lt; 0.001), intensive care unit (ICU) admission (1.50 [1.28–1.75]; P &amp;lt; 0.001), mechanical ventilation (1.67 [1.32–2.10]; P &amp;lt; 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04–1.12]; P &amp;lt; 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01–1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07–1.21]; P &amp;lt; 0.001), and hospital LOS (aIRR 1.05 [1.03–1.06]; P &amp;lt; 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors. CONCLUSIONS Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery.
Incidence and degree of hypoxaemia in Malawian infants under 2 months of age presenting to district hospitals and its correlation with mortality: a retrospective analysis
Authors: Shubhada Hooli, Carina King, Charles Makwenda, Beatiwel Zatudsa, Norman Lufesi, Anthony Costello, Bejoy Nambiar, Charles Mwansambo, Tim Colbourn, Eric D McCollum
Journal: The Lancet Global Health (2018)

BackgroundPneumonia is a leading cause of death in Malawian infants under 2 months of age. Consensus defines hypoxaemia in infants as a peripheral capillary oxygen saturation (SpO2) of less than 90%. We aimed to estimate the incidence and degree of hypoxaemia and its correlation with mortality in infants younger than 2 months presenting to district hospitals in Malawi.MethodsWe retrospectively analysed a child pneumonia surveillance dataset prospectively collected during routine care at seven hospitals in Malawi between 2011 and 2014. Infants aged 0–2 months with pneumonia according to 2012 WHO case management guidelines were included. We used logistic regression to determine correlation between degree of hypoxaemia and in-hospital death.Findings1810 infant pneumonia admissions were analysed. The case fatality rate was 3·6% (n=65). SpO2 could not be measured in 8·5% (n=154) of patients. Median SpO2 was 96% (IQR 91–98). Infants for whom SpO2 measurement was successful versus unsuccessful had a similar prevalence of chest indrawing (85·6% vs 79·2%) and WHO danger signs (68·4% vs 61·0%; p=0·064), and the distribution of girls (40·9% vs 39·6%) was also comparable. Compared with infants with an SpO2 of 93–100% (n=1160), infants with an SpO2 of 90–92% (n=187) or <90% (n=309) had an increased adjusted odds of death (aOR 5·7, 95% CI 2·4–13·9 and 4·9, 2·2–11·0, respectively). Infants for whom SpO2 was not measurable (n=154) had a greatly increased adjusted odds of death compared with infants with a SpO2 of 93–100% (aOR 17·5, 95% CI 7·5–40·8).InterpretationThe case definition of hypoxaemia in infants less than 2 months of age warrants re-evaluation. Infants with an SpO2 of 90–92% have a higher odds of death than those with a SpO2 of 93–100%. Infants for whom SpO2 could not be measured, despite having similar demographic and physical examination findings, had a higher odds ratio for death than any other observed group. Interestingly, these infants had a lower rate of WHO danger signs, but probably had severe disease such as shock with diminished peripheral perfusion resulting in inability to measure SpO2. WHO danger signs may not adequately capture such physiological derangements. The inability to measure pulse oximetry is clinically meaningful in our setting. Implementation of compulsory SpO2 measurement could result in improved referral rates and recognition of severe disease in infants younger than 2 months of age with pneumonia.FundingNone.
It's time to evolve from Scadding: phenotyping sarcoidosis
Authors: Daniel A. Culver, Robert P. Baughman
Journal: European Respiratory Journal (2018)

Sarcoidosis is complex and highly variable, with protean clinical manifestations and a wide array of consequences for patients. The course is likewise unpredictable, leading to the moniker "sarcoidoses" to connote that sarcoidosis may be a syndrome rather than a single disease [1]. Delineating distinct subgroups, "phenotypes", has been an attempt to simplify prediction about individual patients and to homogenise groups for research purposes. Sarcoidosis phenotypes have been used most often to predict prognosis or to cluster patients with similar outcomes [2–5]. But phenotyping could also be used primarily to stratify patients by clinical features such as extent of organ involvement, or by perceived severity [6, 7]. Novel approaches to cluster sarcoidosis by organ clusters may yield new clinical and pathophysiologic insights <http://ow.ly/uCVG30hMsro>
News review 2008
Authors: Lynn Eaton
Journal: BMJ (2008)

After the problems with the 2007 appointment round for junior doctors, 2008 was a much quieter year after the centralised computer application process was abandoned.

The Tooke inquiry report, Aspiring to Excellence , published in January, proposed ringfencing the budget for medical education and training and creating a new body called NHS: Medical Education England (NHS: MEE) to oversee training in England. This proposal was agreed by the Department of Health, and the new body should start work in January 2009. MEE will be an independent advisory body that should give a coherent, professional voice on medical education and training and advise the Department of Health.

Professor Tooke also proposed the merger of the General Medical Council and Postgraduate Medical Education Training Board, which should happen in 2010.

In February, the Home Office made changes to the immigration system that meant far fewer medical graduates who gained their degrees outside the European Economic Area were eligible for posts in the NHS.

And although the number of posts available for those training to work in a hospital setting is still under review, the Department of Health announced in September that the intake to year 1 of GP specialty training programmes would increase by 400 in the 2009-10 allocations.

As Newshound reported in August, there were none of the problems encountered the previous year with junior doctors scrabbling around to find a post. The BMA said that although there were still some uncertainties around the start of the placements, most juniors did get jobs.

Remedy UK, which built itself a reputation as a single issue campaign group in 2007, had to rethink its tactics in 2008. Remedy launched its own magazine, R-UK , and as its editor Jamie Wilson admits in his December editorial, the organisation is “certainly at a crossroads, …
Master of science in clinical education
Authors: Andrew Fung
Journal: BMJ (2012)

The aim of the master of science in clinical education at the University of Edinburgh is to promote high quality clinical education by helping those attending the course to develop an understanding of best practice in clinical education.

This course is for any clinician who is interested in the theory and practice of clinical education. The course is not limited to doctors; nurses and dentists also participate.

At my annual review of competence progression the panel suggested that I gain a clinical education qualification and develop the theoretical knowledge underpinning medical education.

I am in the second year of …
Immunotherapy: a new standard of care in thoracic malignancies?
Authors: Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S. Tsao, Frances A. Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G.J.V. Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
Journal: European Respiratory Journal (2018)

In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled “Immunotherapy, a new standard of care in thoracic malignancies?” was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events. The need for biological selection, currently based on immunohistochemistry testing to identify the tumour expression of programmed death ligand (PD-L)1, was stressed, as well as the need to harmonise PD-L1 testing and techniques. Finally, sessions were dedicated to the combination of ICIs and radiotherapy and the place of ICIs in nonsmall cell lung cancer with oncogenic addictions. Finally, an important presentation was dedicated to the future of antitumour vaccination and of all ongoing trials in thoracic oncology.
Where can I train in neurolinguistic programming? I am confused by all the different providers and would welcome advice that points me to a relevant course for doctors.
Authors: Susan Kersley
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>
Three quarters of young anaesthetists might leave NHS if subconsultant grade were introduced
Authors: Helen Jaques
Journal: BMJ (2013)

More than three quarters of trainees and new consultants in anaesthetics would consider leaving the NHS if a subconsultant grade were introduced to manage the expected oversupply of consultants in the UK, a survey shows.12

Nearly 2000 anaesthetists were surveyed by the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland. A total of 79% of respondents said that they would emigrate or move to the private sector if a graded career structure was introduced for consultants.

Richard Paul, chairman of …
Editor’s Choice: Strange times
Authors: Tom Moberly
Journal: BMJ (2015)

Some will have thought it was probable, and others will have seen it as inevitable. But many doctors will be surprised by the news that the UK may not be able to offer training posts to all of its future medical graduates (http://careers.bmj.com/careers/advice/view-article.html?id=20022443).

The reason for this is relatively straightforward: the limited number of places on the foundation programme will soon be dwarfed …
HIV dilemmas day
Authors: Paul Collini
Journal: BMJ (2012)

The HIV dilemmas day, run by the British Infection Association and Hartley Taylor Medical Communications, is designed for any trainees or specialists working in HIV medicine, including those from infectious diseases, genitourinary medicine, microbiology, virology, and pharmacology.

I took the course in January 2010 while I was a third year specialist registrar in infectious diseases, and I attended again for the fifth version of the course in January 2012 in Manchester.

Although I regularly see complex HIV cases, the sheer breadth of these means I only see some of the conditions once or twice a year. This course allowed me to reacquaint myself with some important HIV related scenarios and update on the latest evidence and current best practice in their management.

The workshop covers clinical scenarios that occur frequently enough to be important, but not so regularly that they don’t still present considerable …
ASSESSMENT OF RIGHT ATRIAL PRESSURE IN CHILDREN WITH CONGENITAL HEART DISEASE: SIMULTANEOUS THREE-DIMENSIONAL ECHOCARDIOGRAPHY AND CATHETERIZATION STUDY
Authors: Kanako Kishiki, Haruka Fujimaki, Mai Terada, Takumi Kobayashi, Tomomi Ueda, Yuji Hamamichi, Akio Inage, Taku Ishii, Tadahiro Yoshikawa, Satoshi Yazaki, Keitaro Mahara
Journal: Journal of the American College of Cardiology (2018)
PECULIAR: An open label, multicenter, single-arm, phase 2 study of neoadjuvant pembrolizumab (PEM) and epacadostat (EPA), preceding radical cystectomy (Cy), for patients (pts) with muscle-invasive urothelial bladder cancer (MIUBC).
Authors: Andrea Necchi, Luigi Mariani, Andrea Anichini, Antonella Messina, Patrizia Giannatempo, Daniele Raggi, Alberto Briganti, Francesco Montorsi
Journal: Journal of Clinical Oncology (2018)

TPS534 Background: MIUBC is a systemic disease and &gt; 40% of pts develop recurrence after Cy. Despite neoadjuvant chemotherapy yields Level 1 evidence, it is underutilized worldwide and a small survival improvement is deemed over Cy alone. PEM (MK-3475) is the standard-of-care for second-line metastatic UC and is being evaluated as single-agent neoadjuvant therapy for MIUBC (NCT02736266). EPA, an anti-IDO1 agent, combined with PEM, safely improved the response-rate in metastatic UC. Our hypothesis is that PEM+EPA, given neoadjuvantly, could further improve downstaging MIUBC. Methods: Pts with T2-T4a N0 UC with residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence), regardless of cisplatin eligibility, will receive 3 cycles of PEM 200mg intravenously, q3 weekly. EPA will be orally taken at the dose of 100 mg BID, from d1 until 10 days before Cy. Cy should be performed within 3 weeks of the last PEM dose. Computed tomography (CT) scan, 18 FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI) will be done during screening and before Cy to stage and evaluate response. After Cy, pts will be managed according to EAU guidelines. Adjuvant anti PD-1 therapy is not allowed. PD-L1 status will be assessed on TURB specimen (Dako, clone 22C3), relying on the combined positivity score (CPS, 10% cutoff). Pathologic complete response (pT0) is the primary endpoint. All pts enrolled who receive at least 1 cycle of study drug will be includes in the ITT analysis. The H 1 is pT0≥20% and H 0 pT0≤10%. A 2-stage design will be used to estimate the number of pts required. Out of 90 pts overall, with the first stage of 49 pts, ≥6 pT0 will be required in the first stage, and ≥13 pT0 in the whole study population (80% power and a 2-sided test of significance at the 10% level). Correlative research on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). Radiologic findings from mpMRI will be associated with pathologic response (EudraCT number 2017-002379-24). Clinical trial information: 2017-002379-24.
SINUS RHYTHM PRIOR TO CATHETER ABLATION POSITIVELY IMPACTS ABLATION OUTCOME IN NON-PAROXYSMAL ATRIAL FIBRILLATION PATIENTS
Authors: Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Carola Gianni, Domenico Giovanni Della Rocca, John Burkhardt, Javier Sanchez, Patrick Hranitzky, Gerald Gallinghouse, Amin Al-Ahmad, Rodney Horton, Luigi Di Biase, Andrea Natale
Journal: Journal of the American College of Cardiology (2018)
Risk of preterm delivery and small-for-gestational-age births in women with autoimmune disease using biologics before or during pregnancy: a population-based cohort study
Authors: Nicole W Tsao, Eric C Sayre, Gillian Hanley, Mohsen Sadatsafavi, Larry D Lynd, Carlo A Marra, Mary A De Vera
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To assess the risk of preterm delivery and small-for-gestational-age (SGA) births in women with autoimmune diseases using biologics before or during pregnancy. <h3>Methods</h3> Using population-based administrative data in British Columbia, Canada, women with one or more autoimmune diseases who had pregnancies between 1 January 2002 and 31 December 2012 were included. Exposure to biologics was defined as having at least one biologic prescription 3 months before or during pregnancy. Each exposed pregnancy was matched with five unexposed pregnancies using high-dimensional propensity scores (HDPS). Logistic regression modelling was used to evaluate the association between biologics use and preterm delivery and SGA. <h3>Results</h3> There were 6218 women with 8607 pregnancies who had an autoimmune disease diagnosis; of which 109 women with 120 pregnancies were exposed to biologics 3 months before or during pregnancy. In unadjusted analyses, the ORs for the association of biologics exposure with preterm deliveries were 1.64 (95% CI 1.02 to 2.63) and 1.34 (95% CI 0.72 to 2.51) for SGA. After HDPS matching with 600 unexposed pregnancies, the ORs for the association of biologics exposure and preterm deliveries were 1.13 (95% CI 0.67 to 1.90) and 0.91 (95% CI 0.46 to 1.78) for SGA. Sensitivity analyses using HDPS deciles, continuous HDPS covariate or longer exposure window did not result in marked changes in point estimates and CIs. <h3>Conclusions</h3> These population-based data suggest that the use of biologics before and during pregnancy is not associated with an increased risk of preterm delivery or SGA births.
I am considering applying to join the armed forces as a medical officer. I was wondering what the career prospects are like postservice? Would I be on a par with other doctors if I chose to leave the forces?
Authors: Ian Palmer
Journal: BMJ (2006)

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>
MA in the History of Medicine at the Wellcome Trust Centre for the History of Medicine, University College London
Authors: Claire Hilton
Journal: BMJ (2008)

For anyone interested in the history of medicine, including an international studentship with a wide range of ages and backgrounds, including clinicians, career historians, and others. Part time participants have commuted from as far away as Dublin.

After seven years as a consultant old age psychiatrist, while continuing to do clinical work.

With a longstanding interest in history, I wanted an academic challenge and the opportunity to learn more of the history of medicine.

The course, reading, and assignments have occupied at least 16 hours a week every week for the past two years. It has been extremely rewarding but hard work.

Yes, but it is only a small …
Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer
Authors: Toni M. Brand, Stefan Hartmann, Neil E. Bhola, Hua Li, Yan Zeng, Rachel A. O'Keefe, Max V. Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Nevan J. Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Theresa LaVallee, Daniel E. Johnson, Michelle A. Ozbun, Julie E. Bauman, Jennifer R. Grandis
Journal: Cancer Research (2018)

Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.
Insights into maleimide-thiol conjugation chemistry: Conditions for efficient surface functionalization of nanoparticles for receptor targeting
Authors: Lucía Martínez-Jothar, Sofia Doulkeridou, Raymond M. Schiffelers, Javier Sastre Torano, Sabrina Oliveira, Cornelus F. van Nostrum, Wim E. Hennink
Journal: Journal of Controlled Release (2018)
Balanced Crystalloids versus Saline in Noncritically Ill Adults
Authors: Wesley H. Self, Matthew W. Semler, Jonathan P. Wanderer, Li Wang, Daniel W. Byrne, Sean P. Collins, Corey M. Slovis, Christopher J. Lindsell, Jesse M. Ehrenfeld, Edward D. Siew, Andrew D. Shaw, Gordon R. Bernard, Todd W. Rice
Journal: New England Journal of Medicine (2018)

Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU).