tbuckley/cabot-search huggingface dataset:
Abstract P2-13-03: Statin use and breast cancer survival – a Swedish nationwide study
Authors: S Borgquist, P Broberg, H Olsson
Journal: Cancer Research (2018)

Abstract Background: A sizeable body of evidence shows that statins can cease proliferation of breast cancer and prevent breast cancer recurrence. Given the epidemiological findings from other Scandinavian populations, we hypothesized that statins may have anticancer effects and therefore reduce cancer-related mortality in a Swedish population. This study investigates the association between both pre- and post diagnostic statin use and breast cancer outcome. Methods: A Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer-specific death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality. Results: During follow-up, a total of 4,678 patients died, whereof 2,669 were considered breast cancer-specific deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer-specific death (HR=0.77 (95%CI 0.63-0.95), P=0.014). When evaluating diabetes patients only (N=545), this association was strengthened (HR=0.63 (95%CI 0.40-0.98), P=0.044). Post diagnostic statin use was in similarity associated with lower risk of breast cancer–related death compared to non-use (HR=0.83 (95%CI 0.75-0.93), P=0.001). Conclusion: This study supports the notion that statin use is protective regarding breast cancer-specific mortality in agreement with previous Scandinavian studies, although less so with British studies. These disparities should be investigated further. Citation Format: Borgquist S, Broberg P, Olsson H. Statin use and breast cancer survival – a Swedish nationwide study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-03.
Abstract P370: Utility of Cardiovascular Risk Algorithms in Prediction of Subclinical Atherosclerosis in the Young
Authors: Alexi Geevarghese, Michael Garshick, Eugenia Gianos, Ricardo Benenstein
Journal: Circulation (2018)

Background: Prediction of cardiovascular risk in younger patients is particularly challenging. Most current risk estimators underestimate risk potentially leading to under-treatment in younger patients with significant risk factors for atherosclerosis. Methods: A retrospective analysis of patients age 20 to 50 (n = 274) referred to a cardiology clinic between 2013 and 2016 and undergoing carotid ultrasound for risk stratification and statin initiation was conducted. A medical history was obtained by chart review at the time of carotid ultrasound. The 2008 Framingham general risk score was used to calculate a 10-year cardiac risk. Carotid plaque was defined using standard definitions as carotid artery focal wall thickening 50% or greater than the surrounding vessel wall or a focal region &gt; 1.5 mm protruding into the lumen. Results: Average age was 41 ± 7.9 years, 60% male, 77% Caucasian, 4% diabetes. Ten percent (n = 27) had carotid plaque noted on ultrasound. Those with plaque compared to those without were older (46 ± 4.3 vs. 41 ± 7.5, p &lt; 0.01), more likely to have hypertension (HTN) (52% vs. 20%, p &lt; 0.01), more likely to be active smokers (19% vs. 6%, p = 0.02) and had higher total cholesterol (222 ± 53 mg/dl vs. 202 ± 45 mg/dl, p = 0.04) and LDL-C (140 ± 40 mg/dl vs. 121 ± 43 mg/dl, p = 0.04). No differences were noted in gender, race, body mass index, diabetes or family history of early heart disease. The average cardiac risk score was 5.9 ± 3.5% for those with plaque and 4.2 ± 3.2% for those without (p &lt; 0.01). When assessing the same population by number of risk factors, 93% (n = 25) of individuals with carotid plaque had ≥ 2 cardiac risk factors (one point each for age 40 to 50, smoking, family history of heart early disease, obesity, LDL &gt; 160 mg/dl, DMII or HTN). This compared to 37% (n=10) who had carotid plaque on imaging and a risk score ≥ 7.5%. Receiver operator curve characteristics to predict plaque were similar for the cardiac risk score (AUC 0.674) and number of cardiac risk factors (AUC 0.674, p = 0.96). Conclusion: In patients 50 years or younger, ≥ 2 cardiac risk factors revealed a higher percentage of carotid plaque than a Framingham cardiac risk score cut off value of ≥ 7.5%. In younger patients with cardiac risk factors, novel algorithms are needed to more accurately guide medication therapy.
HIV INFECTION IS ASSOCIATED WITH INCREASED LEFT VENTRICULAR MASS IN THE MULTICENTER AIDS COHORT STUDY (MACS)
Authors: Elizabeth Hutchins, Ruibin Wang, Sina Rahmani, Rine Nakanishi, Mallory Witt, Lawrence Kingsley, Sabina Haberlen, Lisa Jacobson, Frank Palella, Matthew Budoff, Wendy Post
Journal: Journal of the American College of Cardiology (2018)
Doctors and parents agree care plan for toddler with terminal condition
Authors: Clare Dyer
Journal: BMJ (2018)

Parents and doctors in a legal battle over the treatment of a toddler with a terminal condition have come to an agreement after the judge refused to make a blanket declaration that mechanical ventilation or cardiopulmonary resuscitation would be against her best interests.

Mr Justice Williams said last November that he would not rule out ventilation or cardiopulmonary resuscitation in all circumstances, pending a final hearing in a month’s time. An unnamed NHS trust had asked for a declaration that it would be in the best interests of the 2.5 year old girl to have only palliative care if her condition worsened.

The case was heard in November and December, but the judgment from both hearings has just been published.1 In this …
What psychology and cognitive neuroscience know about the communicative function of memory
Authors: David C Rubin
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra (M&amp;C) include interesting ideas about the nature of memory from outside of the field of cognitive psychology and cognitive neuroscience. However, the target article's inaccurate claims about those fields limit its usefulness. I briefly review the most serious omissions and distortions of the literature by the target article, including its misrepresentation of event memory, and offer suggestions for forwarding the goal of understanding the communicative function of memory.
Abstract 16999: Analysis of Risk Factors for Mortality and Morbidity of Surgical Aortic Valve Replacement for Aortic Stenosis: Risk Models From a Japanese Database
Authors: Hiroshi Takano, Hiroaki Miyata, Noboru Motomura, Takashi Yamauchi, Yukitoshi Shirakawa, Shinichi Takamoto
Journal: Circulation (2015)

Background: Surgical aortic valve replacement (sAVR) is the standard treatment for atherosclerotic aortic stenosis; however, trans-catheter aortic valve replacement (tAVR) is being increasingly used for high risk patients. The risks associated with sAVR have usually been assessed by operative mortality. However, it may be meaningful to assess the risk for operative morbidity. Purpose: This study aimed to create risk models associated with sAVR for mortality, as well as for combined mortality and morbidity (M-M), using the Japan Adult Cardiovascular Surgery Database. Methods: A total of 14,100 patients who underwent sAVR with/without CABG between 2009 and 2012 were retrospectively evaluated. We excluded patients with contraindications to tAVR, except for chronic dialysis. Multiple logistic regression analysis was used to create a risk model for mortality (30 days postoperative and in-hospital), and for M-M (patient was hospitalized longer than 90 days or patient’s daily activities were disturbed with a modified Rankin scale of 4 or more at discharge). Results: Mortality was 3.1%, and rate of M-M was 10.9%. Significant risk factors are listed in the table. Risk factors common to both mortality and M-M were older age, chronic dialysis, atrial fibrillation, higher NYHA class, chronic lung disease, cerebrovascular disease, and congestive heart failure. Risk factors specific to M-M were history of psychoneurotic disorder, diabetes mellitus, obesity, and left ventricular dysfunction. Conclusions: Analyzing the risk factors not only for mortality but also for M-M may be useful in identifying appropriate candidates for tAVR.
Aegeline inspired synthesis of novel β3-AR agonist improves insulin sensitivity in vitro and in vivo models of insulin resistance
Authors: Sujith Rajan, Sabbu Satish, Kripa Shankar, Sukanya Pandeti, Salil Varshney, Ankita Srivastava, Durgesh Kumar, Abhishek Gupta, Sanchita Gupta, Rakhi Choudhary, Vishal M Balaramnavar, Tadigoppula Narender, Anil N Gaikwad
Journal: Metabolism (2018)
HYPERNATREMIA IS ASSOCIATED WITH INCREASED INPATIENT MORTALITY IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: A NATIONWIDE ANALYSIS
Authors: Bing Yue, Mike Gorenchtein, Shuyang Fang, Xin Wei, Mariam Khandaker, Chayakrit Krittanawong, Ashish Correa, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Transport Barriers and Oncophysics in Cancer Treatment
Authors: Sara Nizzero, Arturas Ziemys, Mauro Ferrari
Journal: Trends in cancer (2018)

Transport processes in cancer are the focus of transport oncophysics (TOP). In the TOP approach, the sequential negotiation of transport barriers is critical to both drug delivery and metastasis development. New and creative therapeutic opportunities are currently emerging, stimulated by the study of cancer hallmarks with the TOP approach.
Assessing the ProMCol classifier as a prognostic marker for non-metastatic colorectal cancer within the Melbourne Collaborative Cohort Study
Authors: Jihoon E Joo, Harindra Jayasekara, Ee Ming Wong, Mark Clendenning, Christophe Rosty, Ingrid M Winship, Mark A Jenkins, John L Hopper, Dallas R English, Roger L Milne, Graham G Giles, Melissa C Southey, Daniel D Buchanan
Journal: Gut (2018)

We read with interest the work by Gundert and colleagues, which describes a new prognostic classifier for non-metastatic colorectal cancer (CRC), ProMCol, derived from DNA methylation levels at 20 CpG sites in colorectal tumour tissue.1 Here, we tested the ProMCol classifier on an independent cohort of 526 non-metastatic CRC tumours from the Melbourne Collaborative Cohort Study (MCCS). The MCCS is a prospective cohort study of 41 513 healthy adult volunteers recruited between 1990 and 1994.2 By 31 December 2009, 1046 participants had a first histopathological diagnosis of invasive adenocarcinoma of the colon or rectum identified through the Victorian Cancer Registry (VCR) following the baseline study visit (a total of 1101 CRCs). Characterisation of this CRC-affected cohort is described in Buchanan et al .3 Vital status was ascertained through the VCR and the National Death Index.

From all 1046 participants with a CRC diagnosis, we excluded 26 tumours with the tumour site listed as overlapping lesions of rectum, anus and anal canal (International Statistical  Classification of Diseases and Related Health Problems 10th Revision code C21.8) or had unknown site, we removed 228 tumours without available formalin-fixed paraffin embedded (FFPE) tissue specimens, a further 142 tumours were unavailable for DNA methylation testing, and finally we removed 124 metastatic cases (stage 4 American Joint Committee on Cancer (AJCC)) and tumours with unknown stages, leaving a total of 526 CRC tumours …
Cardioprotection by ischemic postconditioning and cyclic guanosine monophosphate-elevating agents involves cardiomyocyte nitric oxide-sensitive guanylyl cyclase
Authors: Sandra Frankenreiter, Dieter Groneberg, Anna Kuret, Thomas Krieg, Peter Ruth, Andreas Friebe, Robert Lukowski
Journal: Cardiovascular Research (2018)

It has been suggested that the nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine monophosphate (cGMP)-dependent signalling pathway affords protection against cardiac damage during acute myocardial infarction (AMI). It is, however, not clear whether the NO-GC/cGMP system confers its favourable effects through a mechanism located in cardiomyocytes (CMs). The aim of this study was to evaluate the infarct-limiting effects of the endogenous NO-GC in CMs in vivo.Ischemia/reperfusion (I/R) injury was evaluated in mice with a CM-specific deletion of NO-GC (CM NO-GC KO) and in control siblings (CM NO-GC CTR) subjected to an in vivo model of AMI. Lack of CM NO-GC resulted in a mild increase in blood pressure but did not affect basal infarct sizes after I/R. Ischemic postconditioning (iPost), administration of the phosphodiesterase-5 inhibitors sildenafil and tadalafil as well as the NO-GC activator cinaciguat significantly reduced the amount of infarction in control mice but not in CM NO-GC KO littermates. Interestingly, NS11021, an opener of the large-conductance and Ca2+-activated potassium channel (BK), an important downstream effector of cGMP/cGKI in the cardiovascular system, protects I/R-exposed hearts of CM NO-GC proficient and deficient mice.These findings demonstrate an important role of CM NO-GC for the cardioprotective signalling following AMI in vivo. CM NO-GC function is essential for the beneficial effects on infarct size elicited by iPost and pharmacological elevation of cGMP; however, lack of CM NO-GC does not seem to disrupt the cardioprotection mediated by the BK opener NS11021.
Nudge Units to Improve the Delivery of Health Care
Authors: Mitesh S Patel, Kevin G Volpp, David A Asch
Journal: New England Journal of Medicine (2018)

The final common pathway for the application of nearly every advance in medicine is human behavior.No matter how effective a drug, how protective a vaccine, or how targeted a therapy may be, a clinician usually has to prescribe it, and a patient accept and use it as directed, for it to improve health.Clinicians' and patients' environments influence their decisions about taking these actions, and the seemingly subtle design of information and choices can have outsize effects on our behavior.When the "choice architecture" is designed to influence behavior in a predictable way but without restricting choice, it is often called a "nudge."Key information and important choices are constantly being presented in health care. 1 Consider the way in which a physician offers influenza vaccination, or the default settings in electronic health records (EHRs) for the duration of a new opioid prescription.Yet often, these frames or default options are selected haphazardly, without attention to shared goals of overcoming common barriers to vaccination or balancing pain relief against addiction risk.
Public health doctors think they lack influencing skills for work in councils
Authors: Caroline White
Journal: BMJ (2014)

Public health doctors believe that they have the professional knowledge necessary to work in councils but that they lack the influencing skills to demonstrate their value, a report has found.

A report by the Royal Society for Public Health1 looked at the effects of a shift of public health responsibilities from the NHS to local authorities in April 2013. It drew on focus group discussions, in-depth interviews, and a survey of 261 public health professionals working in local government across England.

Contributors included directors of public health, consultants, public health specialists, and health improvement practitioners. Their comments showed that no two local authority environments were the same but that …
High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Authors: Illja J. Diets, Esmé Waanders, Marjolijn J. Ligtenberg, Diede A.G. van Bladel, Eveline J. Kamping, Peter M. Hoogerbrugge, Saskia Hopman, Maran J. Olderode-Berends, Erica H. Gerkes, David A. Koolen, Carlo Marcelis, Gijs W. Santen, Martine J. van Belzen, Dylan Mordaunt, Lesley McGregor, Elizabeth Thompson, Antonis Kattamis, Agata Pastorczak, Wojciech Mlynarski, Denisa Ilencikova, Anneke Vulto- van Silfhout, Thatjana Gardeitchik, Eveline S. de Bont, Jan Loeffen, Anja Wagner, Arjen R. Mensenkamp, Roland P. Kuiper, Nicoline Hoogerbrugge, Marjolijn C. Jongmans
Journal: Clinical Cancer Research (2018)

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer.Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome.Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition.Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. Clin Cancer Res; 24(7); 1594-603. ©2018 AACR.
Caring for Ms. L. — Overcoming My Fear of Treating Opioid Use Disorder
Authors: Audrey M. Provenzano
Journal: New England Journal of Medicine (2018)

Caring for Ms. L. Like a swimmer pulled into the undertow, Ms. L. had been dragged back into the cold, dark brine of addiction. But her primary care physician, having chosen not to obtain a waiver to prescribe buprenorphine, referred her to a colleague.
Incidence of Delayed Intracranial Hemorrhage in Older Patients After Blunt Head Trauma
Authors: James A. Chenoweth, Samuel D. Gaona, Mark Faul, James F. Holmes, Daniel K. Nishijima
Journal: JAMA Surgery (2018)

Current guidelines conflict on the management of older adults who have blunt head trauma taking anticoagulant and antiplatelet medications. This is partially due to the limited data comparing patients who are taking these medications with those who are not.To investigate the incidence of delayed traumatic intracranial hemorrhage in older adults with head trauma, including those taking anticoagulant and antiplatelet medications.This prospective observational cohort study included patients 55 years and older who had blunt head trauma and were transported via emergency medical services between August 1, 2015, and September 30, 2016. The setting was a multicenter study conducted at 11 hospitals in northern California. Patients were excluded if they had traumatic intracranial hemorrhage on the initial cranial computed tomographic scan, did not have a cranial computed tomographic scan performed at the initial emergency department visit, refused consent for a follow-up telephone call, or did not have reliable means of follow-up.The primary outcome of this study was the incidence of delayed traumatic intracranial hemorrhage within 14 days of injury.Among 859 patients enrolled in the study, the median age was 75 years (interquartile range, 64-85 years), and 389 (45.3%) were male. A total of 343 patients (39.9%) were taking an anticoagulant or antiplatelet medication. Three patients (0.3%; 95% CI, 0.1%-1.0%) had a delayed traumatic intracranial hemorrhage. Of the 3 patients, 1 of 75 patients (1.3%; 95% CI, 0.0%-7.2%) who were taking warfarin sodium alone and 2 of 516 patients (0.4%; 95% CI, 0.1%-1.4%) who were not taking any anticoagulant or antiplatelet medication had a delayed traumatic intracranial hemorrhage. Thirty-nine patients (4.5%; 95% CI, 3.2%-6.2%) were lost to follow-up.Overall, the incidence of delayed intracranial hemorrhage in older adults who have blunt head trauma is low, including patients taking an anticoagulant or antiplatelet medication. These findings suggest that routine observation and serial cranial computed tomography may not be necessary in these patients.
I've just got my first locum consultant job after completing my specialist registrar training. What salary scale should I be paid?
Authors: Alastair Hull
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>