tbuckley/cabot-search huggingface dataset:
Abstract 18333: Left Ventricular Systolic and Diastolic Dysfunction is an Uncommon Finding in a Pre-modern Society With High Inflammation and Low Atherosclerotic Risk Factors
Authors: Chris J Rowan, Sandeep C Sangodkar, Abinash P Achrekar, Kirsten Tolstrup, Brett Beheim, Jonathan Stieglitz, Ben Trumble, Michael Gurven, Hillard Kaplan
Journal: Circulation (2015)

Introduction: Ischemic cardiomyopathy from coronary atherosclerosis is the leading cause of mortality in developed nations. However, the natural history of cardiovascular disease in contemporary pre-industrial man is not well described. The Tsimane of Bolivia are a forager-horticulturalist population in the western Amazonian basin with high levels of inflammation and a low prevalence of atherosclerosis risk factors. We sought to define the cardiovascular health of a contemporary pre-industrial population with high inflammation and low atherosclerotic risk factors. Methods: Two-Dimensional echocardiograms with Color and Doppler were obtained on 934 Tsimane over age 40. Echocardiograms were reviewed by 2 cardiologists following the American Society of Echocardiography guidelines for interpretation. Patients had baseline clinical evaluations including age, height, weight, blood pressure, and gender. Blood was obtained for serology for inflammatory markers. Results: The average age was 53 years (SD +/- 11; range 40-90 years). 455 (48.7%) were male. The prevalences of hypertension, diabetes, and smoking were 4.8%, 0.5%, and 1.3%, respectively. Mean LVEF was 66% (SD +/- 6.1). There were 4 males with LVEF less than 52% and 11 females with LVEF less than 54%. There was no measured LVEF less than 44%. Complete diastolic data was available in 910. Normal diastolic parameters were observed in 741 (81.4%). Mild diastolic dysfunction was found in 167 (18.3%) and moderate dysfunction in 2 (0.2%). No echocardiograms showed severe diastolic dysfunction. Serologic data showed elevated CRP, ESR, and IL-6 with low high density lipoprotein (HDL) and low density lipoprotein (LDL) Conclusions: In a pre-modern population with high inflammation and low atherosclerotic risk factors, cardiovascular systolic and diastolic dysfunction was a rare finding.
Association of androgen receptor (AR) copy number gain with ARV7 expression and response to chemotherapy.
Authors: Mahesh Y. Iddawela, Carmel Jo Pezaro, Pavel Sluka, Jenna Kraska, Michelle Pereira, Sachin Subhashrao Joshi, Shafaet Jamil, Muhammad Adnan Khattak, Siobhan Ng, Ian D. Davis, Mel Ziman, Gail Risbridger, Elin Gray
Journal: Journal of Clinical Oncology (2018)

180 Background: Emerging data suggests that ARV7 mRNA (ARV7+) expression and AR copy number gain/amplification (AR+) are associated with resistance to androgen deprivation therapy. Most studies thus far have evaluated either AR copy number or ARV7 mRNA, but not both markers. It is likely that both markers are indicators of genomic changes that are seen in the prostate cancer cells in response to tumour evolution or treatment. Here we developed a digital droplet PCR (ddPCR) based assay to evaluate plasma ARV7 mRNA expression in the same samples used for AR copy number analysis in castrate resistant prostate cancer (CRPC). This assay was use to evaluate the role of AR+ and ARV7+ in CRPC using samples collected from multiple centers and correlated with outcome. Methods: We collected plasma samples from patients with CRPC treated with chemotherapy (C) or next generation androgen targeted agents (NAR) to evaluate circulating tumour DNA (ctDNA) for AR and plasma mRNA for ARV7. Some patients had sequential samples and we correlated PSA response (reduction PSA≥50 confirmed 3wks later (RR)) with AR and ARV7 status and clinical features. Results: A total of 52 samples were included from 26 patients, with matched samples from some patients at different time points. Of the CRPC patients, AR+ was seen in 70% (18/26), AR- in 30% (8/26), ARV7+ in 67% (12/18) and ARV7- in 33% (6/18). 75% (9/12) patients with AR+ also had ARV7+. In matched samples: 3/7 had change in AR status, 2/7 had change in ARV7 status, including 1 patient where both changed; and interestingly there was a group with no AR or ARV7 detected. Number of patients expressing both markers AR+/ARV7+ in 50% (9/18), AR+/ARV7- in 17% (3/18), AR-/ARV7+ 17% (3/18) and AR-/ARV7- in 11% (2/18). RR to C or NAR was 63% (12/19) for AR+ and 75% (9/12) for ARV7+ patients. In AR+ patients, response to NAR was 58% (12/16) but response to chemotherapy was 100% (5/5). Conclusions: AR gain/amplification in CRPC was associated with ARV7+ expression and leads to lower response to NAR compared to C. This approach can be used to undertake integrated DNA and mRNA analysis, has wide-scale utility and may be used for analysis of a larger number of circulating biomarkers.
The Psychology of Clinical Decision Making — Implications for Medication Use
Authors: Jerry Avorn
Journal: New England Journal of Medicine (2018)

Interview with Dr. Jerry Avorn on lessons for health care from behavioral economics and other fields. (07:15)Download Richard Thaler recently won the Nobel Prize in Economics for demonstrating that our once-neat model of human decision making is far too simple to explain reality. His work has profound implications for clinical practice, which is all about making the right choices.
Surgical intervention for intracranial metastases: worse outcomes if the primary tumour is unknown?
Authors: Molly Nielsen
Journal: Neuro-Oncology (2018)

Intracranial metastases are common in patients with known cancer and in those with cancer of unknown primary (CUP). The few studies reporting survival times have not found significant differences between the two groups, but 2010 NICE guidance discourages treatment of CUP metastases. AIM To compare the survival of patients whose primary tumour was identified prior to surgical intervention for intracranial metastasis to that of patients with CUP. Inclusion criteria: histological diagnosis of intracranial metastasis in patients aged over 18 surgically managed between 2010 – 2015. A pathology database identified 274 patients meeting this criteria (median age 62, range 31–83). A pro forma was used to collect data from patient notes and Trust Information Services. 47 patients alive at 31 December 2016 were censored. Data was analysed with SPSS to generate Kaplan-Meier curves. The location of the primary was known in 81% of patients (n=223) and unknown in the remaining 19% (n=51). Known primary: median survival 10 months (range 2 days - 81 months) Unknown primary (CUP): median survival 7 months (2 days - 56 months) The Log Rank was not statistically significant, p=0.065. The difference in median survival times reported here is not statistically significant, so amongst this patient group CUP metastases did not confer a substantially worse prognosis. If repetition of the study with an even larger cohort generates similar results, it would be reasonable to conclude that: 1. An aggressive search for a primary tumour does not significantly improve outcomes. 2. Surgical management of CUP brain metastases is appropriate, as the common accepted post-operative survival period of 3 months is achieved. Further analysis of the collected data will compare survival times using additional parameters: primary tumour site, extracranial metastases, post-operative radiotherapy, recurrence rate, and re-do craniotomy.
Active surveillance in prostate cancer patients: Modeling upgrading and upsizing at 1 year rebiopsy.
Authors: Nicola Nicolai, MariaFrancesca Alvisi, Tiziana Rancati, Barbara Avuzzi, Fabio Badenchini, Mario Catanzaro, Maurizio Colecchia, Teresa Di Florio, Tiziana Magnani, Cristina Marenghi, Sara Morlino, Barbara Noris Chiorda, Biagio Paolini, Silvia Stagni, Antonio Tesone, Tullio Torelli, Sergio Villa, Nadia Zaffaroni, Roberto Salvioni, Riccardo Valdagni
Journal: Journal of Clinical Oncology (2018)

90 Background: Prostate biopsy findings at diagnosis and follow-up are essential criteria in Active Surveillance (AS). In a previous work (Nicolai Eur Urol Suppl 2013) upgrading (UPG) and upsizing (UPS) at 1-yr rebiopsy resulted to be independent outcomes with different predictors. Aim of the present work is to validate these models on an independent population and to evaluate the probability of not-developing UPG, thus the chance of continuing AS Methods: Pts enrolled in 2011-2017 were considered for validation, while 318 AS pts enrolled in 2005-2011 were considered for model development. UPG model included: age (risk), PSA density (risk), prostate volume (&gt;60 cc, protective); UPS model: age (protective), % core length containing cancer (&gt;5%, risk), number of positive cores (&gt;1, risk) Performance on the independent population was evaluated through AUC and calibration. Logistic model for not-developing UPG at 1 yr was fitted using all available AS pts Results: 433 pts were included in the validation set. UPG and UPS were registered in 43 and 29 pts, respectively; 38 pts had UPG+UPS. Predictors for UPG and UPS were mainly confirmed in the validation cohort (Table), with Odds Ratios (OR) very similar to the development model. Discrimination was confirmed (AUCs) and calibration was excellent (slope~1, R2&gt;0.90). Probability of not-developing UPG (evaluated on 751 pts) was associated to age, prostate volume and PSA density (Table). Conclusions: UPG and UPS in AS pts should be considered as independent events and their management implying different strategies. Specifically, age, volume and PSA density play a key role in the chance to continue AS, i.e. in not developing UPG. A nomogram estimating the likelihood of continuing AS has been developed and will be presented. [Table: see text]
Seven day services must focus on care, not convenience, says NHS Confederation
Authors: Abi Rimmer
Journal: BMJ (2016)

The focus when introducing seven day NHS services must be on improving patient care rather than offering convenience, the NHS Confederation has said.

In a report published on 17 November,1 the NHS membership body said that seven day services should concentrate on patient outcomes.

“Implicit in media coverage of recent political announcements regarding seven-day services has been the …
68Ga-DOTANOC PET/CT in Medulloblastoma
Authors: Sreedharan Thankarajan Arunraj, Girish Kumar Parida, Nishikant Avinash Damle, Saurabh Arora, Sreenivasa Reddy, Dhritiman Chakraborty, Meghna Prabhu, Madhavi Tripathi, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2018)

Abstract Medulloblastoma, also known as cerebellar primitive neuroectodermal tumor, is the most common brain tumor in children and arises in the posterior cranial fossa. We present the case of a patient with desmoplastic type of medulloblastoma, which showed recurrence more than once. When 68 Ga-DOTANOC PET-CT was done, the lesions showed somatostatin receptor expression, opening another potential therapeutic option for this patient.
杜匹鲁单抗治疗提升了患有中度至重度异位性皮炎的成人患者的生活质量:来自随机、安慰剂对照临床试验
Authors: A. Tsianakas, T.A. Luger, A. Radin
Journal: British Journal of Dermatology (2018)

异位性皮炎是一种皮肤病,也称为异位性湿疹。10位成人里就有1位患有异位性皮炎。异位性皮炎常常会引起严重瘙痒,使患者在夜里难以入睡、情绪低沉。这种浑身不舒服的状态称为生活质量降低。杜匹鲁单抗是一种已获美国批准的新型药物,可用于治疗患有中度至重度异位性皮炎的成人患者。该药物能够抑制这种皮炎的某些机制。在欧洲开展的一项临床试验中,研究人员观察了109位患有中度至重度异位性皮炎的患者。这些患者服用杜匹鲁单抗超过了12周。他们发现这种药物改善了湿疹及其症状,例如瘙痒。研究人员在此项研究中还探讨了这种药物是如何影响64位患者(在109位患者中)的生活质量的。这些患者回答了一组问题,用于衡量异位性皮炎是如何影响他们的生活质量的(异位性皮炎的生活质量指数[QoLIAD])。有32位患者每周通过皮下注射的方式接受300 mg杜匹鲁单抗,而另外32位接受的则是安慰剂。在接受杜匹鲁单抗的患者中,约有五分之三的患者反应12周后生活质量有所改善;而在接受安慰剂的患者中,仅有十分之一的患者认为生活质量得到了改善。研究人员还发现,借助杜匹鲁单抗提高QoLIAD分数和改善湿疹及其症状之间存在较强的关联。患者对杜匹鲁单抗的耐受良好。作者总结道,杜匹鲁单抗这种针对异位性皮炎的新型突破性药物改善了湿疹及其症状,从而提高患者的生活质量。
LARGE INCREASES IN BLOOD PRESSURE ARE ASSOCIATED WITH MILD INCREASES IN MID ASCENDING AORTA DIAMETER: AN ECHOCARDIOGRAPHIC STUDY
Authors: Sachin Shah, Mirza Mujadil Ahmad, Ahad Jahangir, A. Jamil Tajik, Bijoy K. Khandheria, Khawaja Afzal Ammar
Journal: Journal of the American College of Cardiology (2018)
Abstract P5-22-22: Breast tumor location in <i>BRCA</i> mutation carriers and implications for prevention
Authors: A Hosseini, LJ Esserman, AM Wallace, A Au, RA Mukhtar
Journal: Cancer Research (2018)

Abstract Introduction: Close to 65% of BRCA mutation carriers do not choose prophylactic mastectomy, despite their high breast cancer risk. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk and can be modified to target specific areas of the breast. We wondered if a majority of tumors in BRCA mutation carriers would be confined to one quadrant, allowing for the use of targeted cosmetic mammoplasty as a novel method of risk reduction. Methods: We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning &amp;gt;1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squaredtest. Results: Mean age at breast cancer diagnosis was 44 years with mean tumor size of 2.2 cm (0.1-7cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant whether or not multicentric tumors were included in the analysis (p&amp;lt;0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p=0.021). Conclusions: More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that removing this quadrant through breast reduction mammoplasty could significantly reduce breast cancer risk. For women who are not ready for prophylactic mastectomy, this data supports an intermediate risk reduction step instead of only offering surveillance. Citation Format: Hosseini A, Esserman LJ, Wallace AM, Au A, Mukhtar RA. Breast tumor location in BRCA mutation carriers and implications for prevention [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 P5-22-22.
Paracrine Interactions within the Pancreatic Islet Determine the Glycemic Set Point
Authors: Rayner Rodriguez-Diaz, R. Damaris Molano, Jonathan R. Weitz, Midhat H. Abdulreda, Dora M. Berman, Barbara Leibiger, Ingo B. Leibiger, Norma S. Kenyon, Camillo Ricordi, Antonello Pileggi, Alejandro Caicedo, Per-Olof Berggren
Journal: Cell Metabolism (2018)
I am interested in working in the Caribbean (especially the Bahamas). Are such jobs available, where are they advertised, and do I need American exams?
Authors: Shahrul Izham Ibrahim
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>
DO-NOT-RESUSCITATE STATUS AND RISK-STANDARDIZED MORTALITY FOR ACUTE MYOCARDIAL INFARCTION: IMPLICATIONS FOR PUBLIC REPORTING AND REIMBURSEMENT
Authors: Jeffrey Bruckel, Brahmajee Nallamothu, Frederick Ling, Erik Howell, Charles Lowenstein, Sabu Thomas, Steven Bradley, Anuj Mehta, Allan Walkey
Journal: Journal of the American College of Cardiology (2018)
CONTINUOUS WEARABLE MONITORING ANALYTICS PREDICT HEART FAILURE DECOMPENSATION: THE LINK-HF MULTI-CENTER STUDY
Authors: Josef Stehlik, Carsten Schmalfuss, Biykem Bozkurt, Jose Nativi-Nicolau, Stephan Wegerich, Kevin Rose, Ranjan Ray, Richard Schofield, Anita Deswal, Jadranka Sekaric, Sebastian Anand, Dylan Richards, Heather Hanson, Matthew Pipke, Michael Pham
Journal: Journal of the American College of Cardiology (2018)
Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry
Authors: Jasper Tromp, Wan Ting Tay, Wouter Ouwerkerk, Tiew-Hwa Katherine Teng, Jonathan Yap, Michael R. MacDonald, Kirsten Leineweber, John J. V. McMurray, Michael R. Zile, Inder S. Anand, Carolyn S. P. Lam
Journal: PLoS Medicine (2018)

Background Comorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with patients' quality of life (QoL) and health outcomes. Methods and findings We used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients prospectively enrolled from in- and outpatient clinics from 11 Asian regions (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore, Indonesia, and Philippines). Latent class analysis was used to identify patterns of multimorbidity. The primary outcome was defined as a composite of all-cause mortality or HF hospitalization within 1 year. To assess differences in QoL, we used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759; youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261; ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low prevalence of obesity, high prevalence of chronic kidney disease). Patients in the lean diabetic group had the worst QoL, more severe signs and symptoms of HF, and the highest rate of the primary combined outcome within 1 year (29% versus 11% in the young group) (p for all <0.001). Adjusting for confounders (demographics, New York Heart Association class, and medication) the lean diabetic (hazard ratio [HR] 1.79, 95% CI 1.46–2.22), elderly/AF (HR 1.57, 95% CI 1.26–1.96), ischemic (HR 1.51, 95% CI 1.22–1.88), and metabolic (HR 1.28, 95% CI 1.02–1.60) groups had higher rates of the primary combined outcome compared to the young group. Potential limitations include site selection and participation bias. Conclusions Among Asian patients with HF, comorbidities naturally clustered in 5 distinct patterns, each differentially impacting patients' QoL and health outcomes. These data underscore the importance of studying multimorbidity in HF and the need for more comprehensive approaches in phenotyping patients with HF and multimorbidity. Trial registration ClinicalTrials.gov NCT01633398
The role of air pollution and lung function in cognitive impairment
Authors: Anke Hüls, Andrea Vierkötter, Dorothea Sugiri, Michael J. Abramson, Ulrich Ranft, Ursula Krämer, Tamara Schikowski
Journal: European Respiratory Journal (2018)

Air pollution has been associated with impaired lung and cognitive function, especially impairment in visuo-construction performance (VCP). In this article, we evaluate whether the effect of air pollution on VCP is mediated by lung function. We used data from the SALIA cohort (baseline 1985–1994 and follow-up 2007–2010) including 587 women aged 55 years at baseline. Particulate matter (PM) and nitrogen dioxide (NO 2 ) exposures at baseline were estimated via land-use regression models. Lung function was characterised by averages between baseline and follow-up. We used age- and height-controlled Global Lung Initiative (GLI) z-scores of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC. VCP was assessed at follow-up with the CERAD-Plus neuropsychological test battery and causal mediation analysis was conducted. An increase of one interquartile range in FEV 1 and FVC was positively associated with VCP (β=0.18 (95% CI 0.02–0.34) and β=0.23 (95% CI 0.07–0.39), respectively). The proportion of the association between NO 2 on VCP mediated by FEV 1 was 6.2% and this was higher in never smokers (7.2%) and non-carriers of the APOE-ε4 allele (11.2%). However, none of the mediations were statistically significant. In conclusion, air pollution associated VCP was partially mediated by lung function. Further studies on the mechanisms underlying this pathway are required to develop new strategies to prevent air pollution induced cognitive impairment.
Give Scottish GPs their own general medical services contract, urges think tank
Authors: Caroline White
Journal: BMJ (2012)

A Scottish think tank has called for the UK-wide GP contract to be ditched, in favour of a separate contract for family doctors in Scotland.

In its latest report , published earlier this week, Reform Scotland says that the devolution of healthcare from Westminster and diverging health policies across the four UK countries mean that a specific Scottish general medical services (GMS) contract should be negotiated.1

Currently, the GMS contract, under which 87% of general practices in Scotland operate, is negotiated on a UK-wide basis, but Reform Scotland’s director, Geoff …
Adherence to the World Cancer Research Fund/American Institute for Cancer Research Guideline Is Associated With Better Health-Related Quality of Life Among Chinese Patients With Breast Cancer
Authors: Yuan-Yuan Lei, Suzanne C. Ho, Ashley Cheng, Carol Kwok, Chi-Kiu Iris Lee, Ka Li Cheung, Roselle Lee, Herbert H.F. Loong, Yi-Qian He, Winnie Yeo
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guideline provides recommendations for cancer prevention among cancer survivors. Limited data have examined whether guideline adherence is related to health-related quality of life (HRQoL) among Chinese patients with breast cancer. Methods: An ongoing prospective cohort study involving 1,462 Chinese women with early-stage breast cancer assessed exercise, diet, and body mass index (BMI) at baseline and at 18-months follow-up after diagnosis. Each assessment recorded patient habits within the previous 12 months. HRQoL was evaluated by the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We first compared the level of adherence to WCRF/AICR recommendations before and after cancer diagnosis. We then examined whether adherence to these recommendations after diagnosis was associated with HRQoL at 18 months. Results: The mean adherence score significantly increased from baseline (3.2; SD, 1.1) to 18-month follow-up (3.9; SD, 1.1; P<.001). Overall, increasing adherence to the WCRF/AICR guideline was associated with higher scores of global health status/quality of life (QoL; Ptrend=.011), physical (Ptrend<.001) and role functioning (Ptrend=.024), and lower scores for fatigue (Ptrend=.016), nausea and vomiting (Ptrend<.001), pain (Ptrend=.004), dyspnea (Ptrend=.030), loss of appetite (Ptrend=.007), and diarrhea (Ptrend=.020). Patients with cancer who met the BMI recommendation had higher scores for physical functioning (P=.001) and lower scores for fatigue (P=.024), pain (P<.001), and dyspnea (P=.045). Adherence to physical activity recommendation was associated with better scores of global health status/QoL (P<.001), physical functioning (P=.003), fatigue (P=.002), pain (P=.018), and dyspnea (P=.021). Higher adherence to diet recommendation was associated with lower scores of nausea and vomiting (Ptrend=.005), loss of appetite (Ptrend=.026), constipation (Ptrend=.040), and diarrhea (Ptrend=.031). Conclusions: Chinese patients with breast cancer made positive lifestyle changes early after cancer diagnosis. Increased adherence to WCRF/AICR recommendations after cancer diagnosis may improve HRQoL. Our data suggest that Chinese patients with breast cancer should follow the WCRF/AICR guideline to improve overall well-being.