tbuckley/cabot-search huggingface dataset:
Canada makes deal to reduce generic drug prices
Authors: Owen Dyer
Journal: BMJ (2018)

The prices of 70 of the most commonly prescribed generic drugs in Canada will fall by 25-40% on 1 April in a deal between Canada’s provinces and territories, working together, and the Canadian Generic Pharmaceutical Association.

The provinces extracted the concession by threatening to resort to tendering when ordering generics for their drug formularies, which would have forced makers to compete on price. Manufacturers have avoided this only by conceding widespread price reductions and by promising to publish all of their prices in the future so that each buyer can see what others are paying.

The reductions …
XANTHINE OXIDASE INHIBITOR ALLOPURINOL PREVENTS OXIDATIVE STRESS-MEDIATED ATRIAL REMODELING IN ALLOXAN-INDUCED DIABETES RABBITS
Authors: Yajuan Yang, Jianping Zhao, Jiuchun Qiu, Jian Li, Xue Liang, Zhiwei Zhang, Xiaowei Zhang, Huaying Fu, Panagiotis Korantzopoulos, Konstantinos Letsas, Gary Tse, Guangping Li, Tong Liu
Journal: Journal of the American College of Cardiology (2018)
Response by Aubdool et al to Letters Regarding Article, “A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure”
Authors: Aisah A. Aubdool, Fulye Argunhan, Pratish Thakore, Susan D. Brain
Journal: Circulation (2018)
Correlation of β-catenin expression in non-small cell lung cancer to prognosis and CD8 positive cells infiltration.
Authors: Satoshi Muto, Yuki Ozaki, Takuya Inoue, Takumi Yamaura, Mitsuro Fukuhara, Takeo Hasegawa, Yutaka Shio, Hiroyuki Suzuki
Journal: Journal of Clinical Oncology (2018)

142 Background: It was reported that β-catenin expression in tumor cells suppresses dendritic cell infiltration into tumor in mouse model of melanoma. It results in less of tumor infiltrating lymphocytes. In non-small cell lung cancer (NSCLC), it is not well understood that β-catenin is involved in cancer immunity in that context. Methods: We studied the association between β-catenin expression and CD8 positive cells infiltration in NSCLC. Ninety-one patients with NSCLC who had complete surgical resection during January 2013 to June 2015 were subjected. β-catenin expression of tumor cells and CD8 positive cells infiltration were analyzed by immunohistochemistry. Survival analysis including over-all survival (OS) and progression-free survival (PFS) were also statistically examined by log-rank test. Results: Fourteen cases (15%) were β-catenin positive. Among 14 β-catenin positive cases, only 2 cases (14%) had CD8 positive cells infiltration. Seventy-five cases (97%) had CD8 positive cells infiltration in β-catenin negative tumors (p &lt; 0.01). Squamous cell carcinoma was relatively higher level of expression than others (44% vs. 9%) and mean primary tumor size was larger in β-catenin positive tumors (3.6 cm) than those in negative tumors (2.7 cm). Median OS was 43.8 months and median PFS was 37.0 months in β-catenin positive group. They were not reached in β-catenin negative group. Both OS and PFS were shorter in β-catenin positive cases (p &lt; 0.01). Conclusions: In NSCLC, β-catenin expression was negatively associated with CD8 positive cells infiltration and poor prognosis. We furthermore will focus on the association between β-catenin expression in tumor and clinical efficacy or resistant mechanism of immune checkpoint blockades.
Paediatric units should move towards resident on-call shifts for consultants
Authors: Helen Jaques
Journal: BMJ (2012)

Paediatric units should always have a consultant present in the hospital outside normal working hours, to improve quality of patients’ care around the clock, the Royal College of Paediatrics and Child Health has recommended.

This model of consultant delivered care will also ensure good handovers and improve communication with patients and their families, the college adds, and will help hospitals deal with rota vacancies, reduce costs of locums, and ensure compliance with the European Working Time Directive.

“Patients deserve to be treated with the same high standard of care whatever time of day or night they are admitted to hospital, whether that be at 11 am on Tuesday morning or …
The role of metastatic burden in cytoreductive/consolidative radical cystectomy.
Authors: Roger Li, Janet Baack Kukreja, Firas G. Petros, Matthew T. Campbell, Justin Nguyen, Graciela M. Nogueras-Gonzalez, Ashish M. Kamat, Louis L. Pisters, Colin P.N. Dinney, Neema Navai
Journal: Journal of Clinical Oncology (2018)

524 Background: The strategy of surgical extirpation of the primary tumor in the setting of metastatic disease has gained acceptance for a variety of solid tumors. The role of cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial cancer (UC) is unknown. We aimed to describe our institutional experience with CCRC for metastatic UC and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. Methods: We performed IRB approved review of our bladder cancer database, and identified 32 patients with metastatic cancer originating from the lower urinary tract who underwent CCRC. Of these, two patients had non−UC histology. Baseline demographics, regimen of chemotherapy, clinicopathologic features, and perioperative complications were collected. Progression free survival (PFS) and cancer specific survival (CSS) were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. Results: Of the 32 patients, 19 (59%) had clinical evidence of distant metastases, while 13 were found to harbor occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 17 patients. Solitary metastases were found in 19 patients (59%). Twenty−eight (88%) patients received chemotherapy prior to CCRC. Disease progression was detected in 29 patients after CCRC (median PFS 4.5 mo), while 28 died of metastatic cancer (median CSS 11.7 mo). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.51, 95% CI 1.06−5.92, p = 0.04), with median CSS of 16.9 mo vs. 5.6 mo (p = 0.003). Median postoperative LOS was 10 days. Overall, 59% suffered postoperative complications, including one perioperative mortality. Conclusions: CCRC is feasible in the setting of metastatic UC, with comparable perioperative morbidity and mortality to RC with curative intent. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.
Medical schools urged to offer more support to students with mental health problems
Authors: Caroline White
Journal: BMJ (2013)

Medical schools need to work harder to support students with mental health issues by fostering a culture in which mental illness can be openly discussed and where those who need help can easily access it, says new guidance.

The guidance, produced jointly by the General Medical Council and the Medical Schools Council,1 advises medical schools on how best to support their students, who, it says, face considerable pressures on demanding courses.

But the advice also targets medical students themselves in a bid to destigmatise mental illness and allay fears that a diagnosis will mar …
Impact of metastatic local treatment in the strategy of metastatic renal cell carinoma including sterotactic radiotherapy, surgery, and radiofrequency in an expert center.
Authors: Laura Salabert, Marine Gross-Goupil, Thibaud Haaser, Jean-Christophe Bernhard, Jean Palussière, Alain Ravaud
Journal: Journal of Clinical Oncology (2018)

596 Background: Standard treatment of metastatic renal clear cell carcinoma is based upon nephrectomy, and systemic treatment with targeted agents. These drugs induce frequent side effects that may compromise observance and quality of life. Considering a focal treatment of one or more metastases can lead to a drug-holidays, or allow to postpone systemic treatment start in oligometastatic disease. Such focal treatment techniques are surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SRT). Methods: In this retrospective, monocentric and analytic study, we analyzed progression-free survival (PFS) and overall survival (OS) after a focal treatment in a cohort of patients from Bordeaux University Hospital, involving similar staff members along time. We have also reported local control, complications and potential predictive factors associated with a better outcome. Results: Seventy-one patients with 78 focal treatments (23 RFA, 47 metastasectomy and 8 SRT) have been included in our study. For 44 patients, the disease was oligometastatic, (1 to sites, less than 5 metastases) including 15 patients with a partial response to systemic treatment before the focal approach, and 12 patients with a dissociated response to systemic treatment. Progression post focal treatment occurred in 53 (74.6 %) of patients. Median PFS was 14 months (95 % confidence interval [CI], - 8-16 months); and median OS was 77 months (95 % CI, 41 months-not reach). Local control rate was 83.3 %, and complication rate was 36.3 % due to local treatments, without death related to iatrogenic events. A diagnosis of metachrone metastases and a disease-free interval between the first diagnosis and the occurrence of the metastases of at least one year seemed to be associated with better outcomes. Conclusions: Data observed in our study are consistent with those reported in literature. The prolonged OS and PFS post focal treatment should encourage clinical oncologists to discuss this multimodal approach (association of systemic and focal treatments). This approach should be also evaluated in the context of the immunocheckpoint inhibitor in the future.
Necessary Clarifications Concerning Results of the SUMMIT Trial—Reply
Authors: Katherine E. Watkins, Claude Setodji, Colleen M. McCullough
Journal: JAMA Internal Medicine (2018)

In Reply We appreciate the letter from Bradley and Williams, which highlights 2 issues. We wish to clarify that the primary outcome is abstinence from both alcohol and opioids. We recognize the way it was presented in our Original Investigation1 was confusing and wish to correct it.
Operative Skills in Urology: Modules 1 to 4
Authors: Saheel Mukhtar
Journal: BMJ (2010)

The Operative Skills in Urology course is designed to give trainees who are pursuing or who wish to pursue a career in urology a basic understanding and a basic level of skill in the diagnostic and operative procedures required for the practice of “core urology.” It is divided into two smaller courses with modules 1 and 2 covered together and modules 3 and 4 covered together.

The course is aimed at surgical trainees at core training year 1-2 level who want a career in urology. It would also be appropriate for trainees who have just embarked on higher surgical training (specialty training year 3). 

I completed modules 1 and 2 during my specialty training year 2 and modules 3 and 4 while I was at year 3 level. Other colleagues sat both courses while they were at the …
Comment on Ohkuma et al. Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial. Diabetes Care 2017;40:1203–1209
Authors: Tomoyuki Kawada
Journal: Diabetes Care (2018)

Ohkuma et al. (1) examined biomarkers for the prediction of heart failure in patients with type 2 diabetes. They conducted a nested case-cohort study and presented adjusted hazard ratios for heart failure with 95% CIs based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6, and high-sensitivity C-reactive protein. I have some concerns about their study.

First, the authors clarified that only the addition of NT-proBNP to the model of conventional risk factors presented improvement of 5-year prediction …
IMPORTANCE OF MULTIDISCIPLINARY MANAGEMENT OF SYNDROMIC ADULT CONGENITAL HEART DISEASE: LEOPARD SYNDROME
Authors: Aditya Goud, Sawan Jalnapurkar, Amish Patel, Prashant Patel, Issa Alesh, Ashis Mukherjee, Ramdas Pai
Journal: Journal of the American College of Cardiology (2018)
I have recently passed my PLAB exams and I am interested in becoming a general practitioner. How can I get on to a training scheme, and what are my job prospects?
Authors: Bill Irish
Journal: BMJ (2004)

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 (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.
Scientific Exploration With Continuous Monitoring Systems: An Early Assessment of Arrhythmias During Hypoglycemia
Authors: Matthew C. Riddle, Michael E. Miller
Journal: Diabetes Care (2018)

> In the final analysis, very little is known about anything, and much that seems true today proves to be only partly true tomorrow.
> 
> —Fuller Albright, MD

Hypoglycemia is a leading concern in treating type 1 diabetes (T1D). Nocturnal hypoglycemia is especially feared because of reports of death presumed to be due to cardiac arrhythmias. However, until recently, little objective information has been available on the kinds of abnormal rhythms that might be associated with hypoglycemia, their frequency, and the clinical settings in which they occur. Because both glucose levels and electrocardiographic patterns can now be continuously monitored during everyday life, these questions can be directly studied.

Results from exploratory analyses of such data were reported in the May 2017 issue of Diabetes Care by Novodvorsky et al. (1). This was a study of 37 young adults with T1D who used continuous glucose monitoring (CGM) concurrently with continuous electrocardiographic monitoring (CECM) for up to 96 h during daily activities. Besides confirming the feasibility of concurrent monitoring over extended periods of time, the study produced some novel findings. Among other observations, the authors reported that in comparison with periods when glucose was normal, periods of hypoglycemia were associated with increased risk of atrial ectopic beats during the day but not at night. In contrast, the investigators reported that the risk of slow heart rate (bradycardia) was greater during nocturnal hypoglycemia than when glucose levels were normal during the night but was less during daytime hypoglycemia than when glucose levels were normal during the day.

This difference in CECM patterns accompanying hypoglycemia at different times of day is a new and potentially important finding. However, questions raised about the statistical methods used in this study have led to further analyses. In an online Comment in this issue of Diabetes Care , Home and …
Mass Customization, Ubiquitous Information, and Improvements to Health Outcomes in the United States
Authors: Robert M. Califf
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Association of dividing pathologically upstaged T3a renal cell carcinoma with improved alignment of outcomes: A call for TMN revision.
Authors: Zachary Hamilton, Umberto Capitanio, Deepak K. Pruthi, Ahmet Bindayi, Alessandro Larcher, Stephen Ryan, Madhumitha Reddy, Kendrick Yim, Aaron Bloch, Charles Field, Sean Berquist, Eric Ballon-Landa, Michael Liss, Thomas B McGregor, Francesco Montorsi, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2018)

642 Background: Incidental pathological upstaging to pT3a disease can occur after surgical treatment of clinical T1 and T2 Renal Cell Carcinoma (RCC), and upstaged pT3a disease is associated with worsened outcomes. Oncologic and survival outcomes within the pT3a category are heterogeneous. We investigated recurrence and survival outcomes in pT3a disease, and aimed to better categorize this cohort for improvement on current TMN staging. Methods: Multi-center retrospective analysis of patients with renal cell carcinoma (cT1-3aN0M0) from 1987-2016. After initial comparison of outcomes between pT1, pT2 and pT3a, patients were substratified within the pT3a category based on presenting clinical stage. Comparison was drawn between pT1, pT2 and the subdivided pT3a group (cT1 → pT3a, cT2 → pT3a, and cT3a → pT3a). Primary outcome was recurrence free survival (RFS). Secondary outcome was overall survival (OS). Kaplan−Meier (KM) analysis was utilized. Results: 2640 patients were analyzed (2125 cT1, 448 cT2, 67 cT3a, mean follow up 67.8 months). Rate of incidental T3a upstaging from cT1-2 was 14.7%. Compared to pT1-2 disease, patients with incidental pT3a upstaging had higher rate of recurrence (7.5% vs. 29.6%, p &lt; 0.001) and all-cause mortality at last follow up (15.9% vs. 25.4%, p &lt; 0.001). With regards to RFS, when pT3a was subdivided based on presenting clinical stage, significant differences in RFS emerged which aligned differently. Compared to 5 year RFS of pT1 (94.4%), cT1 → pT3a aligned with pT2 (76.6% and 81.2%, p = 0.346) while cT2 → pT3a aligned with cT3a → pT3a 47.4% and 44.0%, p = 0.815). With regards to OS, a similar alignment was noted for 5 year OS after subdivision, where pT1 was 89.9%, while cT1 → pT3a correlated with pT2 (79.8% and 83.1%, p = 0.640) and cT2 → pT3a correlated with cT3a → pT3a 67.0% and 64.2%; p = 0.893). Conclusions: Patients with cT1 → pT3a have outcomes more similar to pT2, than patients with cT2 → pT3a which align more closely to cT3a → pT3a. Future refinements of the TNM staging system for RCC should consider re-grouping cT1 → pT3a into the pT2 group. Further confirmation is requisite.
Assessing the quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) in immuno-oncology (I/O): An application to nivolumab vs. everolimus in previously treated advanced renal cell carcinoma (aRCC).
Authors: Ruchit Shah, Marc Botteman, Caitlyn Solem, Linlin Luo, Justin Doan, David Cella, Robert J. Motzer
Journal: Journal of Clinical Oncology (2018)

669 Background: Traditional progression definitions based on the RECIST 1.1 criteria may lead to a premature declaration of progression due to tumor flare or pseudo-progression effects associated with I/O drugs, especially among patients with solid tumors (such as RCC). This analysis compared the Q-TWiST between nivolumab and everolimus, using both traditional and novel I/O-relevant definitions of progression. Methods: Using Checkmate 025 data at ≤45 months (m) of follow up, overall survival (OS) was partitioned into 3 health states: TWiST (time without symptoms of disease progression or toxicity), TOX (time with grade ≥3 toxicity after randomization but before progression), and REL (time after progression). The following REL definitions were considered to declare progression: 1) RECIST 1.1 criteria (i.e., traditional Q-TWiST); 2) increase in tumor burden of ≥25% from nadir; 3) treatment discontinuation; 4) ≥2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Cancer Index-Diseases related Symptoms (FKSI-DRS) score; and 5) any combination of ≥2 out of 3 criteria (traditional progression, treatment discontinuation, FKSI-DRS reduction of ≥2-points from baseline). Mean Q-TWiST was calculated by weighting the restricted mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Relative Q-TWiST gain (Q-TWIST difference divided by mean everolimus OS) was calculated. Results: Compared to everolimus, nivolumab patients had statistically significant improvements in Q-TWiST based on all definitions: 1) traditional Q-TWiST: 3.3 m (relative gain:14.4%); 2) 3.5 m (relative gain: 15.3%); 3) 4.3 m (relative gain: 18.7%), 4) 4.8 m (relative gain: 20.9%); and 5) 4.8 m (relative gain: 20.9%). Conclusions: Regardless of progression definition, nivolumab resulted in a statistically significant and clinically important gain in quality adjusted OS vs. everolimus. These gains were greater when using progression definitions that incorporate more I/O-relevant response definitions and/or treatment discontinuation information. Clinical trial information: NCT01668784.
Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women
Authors: Qi Sun, Geng Zong, Damaskini Valvi, Flemming Nielsen, Brent Coull, Philippe Grandjean
Journal: Environmental Health Perspectives (2018)

Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies.Our objective was to examine the associations between PFAS exposures and subsequent incidence of T2D in the Nurses' Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations.A prospective nested case-control study of T2D was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in 1995-2000 [(mean±SD): 45.3±4.4 y) of age]. We identified and ascertained 793 incident T2D cases through 2011 (mean±SD) years of follow-up: 6.7±3.7 y). Each case was individually matched to a control (on age, month and fasting status at sample collection, and menopausal status and hormone replacement therapy). Plasma concentrations of five major PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonate, perfluorononanoic acid, and perfluorodecanoic acid were measured. Odds ratios (ORs) of T2D by PFAS tertiles were estimated by conditional logistic regression.Shorter breastfeeding duration and higher intake of certain foods, such as seafood and popcorn, were significantly associated with higher plasma concentrations of PFASs among controls. After multivariate adjustment for T2D risk factors, including body mass index, family history, physical activity, and other covariates, higher plasma concentrations of PFOS and PFOA were associated with an elevated risk of T2D. Comparing extreme tertiles of PFOS or PFOA, ORs were 1.62 (95% CI: 1.09, 2.41; ptrend=0.02) and 1.54 (95% CI: 1.04, 2.28; ptrend=0.03), respectively. Other PFASs were not clearly associated with T2D risk.Background exposures to PFASs in the late 1990s were associated with higher T2D risk during the following years in a prospective case-control study of women from the NHSII. These findings support a potential diabetogenic effect of PFAS exposures. https://doi.org/10.1289/EHP2619.