tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of pazopanib and sunitinib as first-line therapy for patients with advanced/metastatic renal cell carcinoma in a U.S. community oncology setting.
Authors: Bradford Richard Hirsch, Xiaolong Jiao, Thomas Wilson, Michelle Denise Hackshaw, Eric Jonasch, Sameer Ghate, Jose Ricardo Perez, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2016)

567 Background: The COMPARZ trial demonstrated that pazopanib was non-inferior to sunitinib regarding their efficacy as first line of therapy (LOT) for advanced/metastatic RCC (aRCC). However, no studies have compared the effectiveness of pazopanib to sunitinib outside the clinical trial setting. The purpose of this study was to compare the clinical outcomes of the two therapies in a US community oncology setting. Methods: A retrospective study was conducted using US Oncology’s (USON) iKnowMed electronic health record (EHR) database, supplemented with chart review. Patient eligibility criteria included: ≥ 18 years of age at first diagnosis of aRCC, treated with pazopanib or sunitinib as the 1st LOT between 11/1/2009 – 8/31/2012 in the USON with ≥ 2 office visits. A propensity score (PS) matching was performed to match patients receiving pazopanib to sunitinib. Clinical outcomes including progression free survival (PFS), overall survival (OS) and adverse events (AEs) were compared. Results: A total of 177 patients on pazopanib and 739 patients on sunitinib were identified from the EHR database. After PS matching, 153 pts were included in pazopanib and sunitinib cohort respectively. The mean age, gender distribution, and the Heng disease risk groups were similar between the two cohorts (p&gt;0.05). No significant difference in PFS was observed with pazopanib (median: 9.3 [95%CI, 7.0 to 11.8] months) compared to sunitinib (median: 8.3 [95%CI, 6.4 to 10.9] months, p = 0.43). Similarly, no significant difference was observed in OS for pazopanib (median: 22.3 [95% CI, 16.2 to 31.7] months) compared to sunitinib (median: 26.3 [95% CI, 16.4 to 38.2, p = 0.76] months). AEs (any grade) including diarrhea, hypertension, nausea, vomiting, fatigue were significantly lower in sunitinib (p&lt;0.05) while anorexia was lower in pazopanib (p&lt;0.05). Conclusions: Consistent with the results of COMPARZ, no significant difference was observed in PFS and OS among aRCC patients treated with pazopanib or sunitinib as the 1st LOT in the real world. AEs seemed to be less common with sunitinib, and this may be partially attributed to the limitation of retrospective data.
Analysis authors reply to Response by Corrado and colleagues
Authors: Hans Van Brabandt, Anja Desomer, Sophie Gerkens, Mattias Neyt
Journal: BMJ (2016)

We read with interest the comments from Corrado and colleagues on our paper related to pre-participation screening in young athletes.1 2

The authors start their critique by suggesting that we are laypersons in the field of sports cardiology. The first author of our paper is a cardiologist with 30 years’ clinical experience. We are all active in critically appraising scientific literature and/or teaching evidence based medicine on a daily, professional basis. We may not be directly involved in sports cardiology, but the absence of conflicts of interest helps in being neutral when assessing scientific evidence.

Furthermore, our manuscript has been peer reviewed through our submission to The BMJ by three renowned sports cardiologists from the UK, the US, and Australia. And the report from which our paper was extracted had been reviewed previously by independent Belgian and Dutch experts.3

More recently, two updated recommendations on pre-participation screening have been published, both from trusted sources. The UK National Screening Committee’s recommendation on screening to prevent sudden cardiac death (SCD) in 12-39 year olds, published in July 2015, is clear: “Systematic population screening programme is not recommended.”4 In December 2015 the …
Decreasing the undernotification of anaphylaxis deaths in Brazil through the International Classification of Diseases (ICD)-11 revision
Authors: L. K. Tanno, A. L. Bierrenbach, M. A. Calderon, A. Sheikh, F. E. R. Simons, P. Demoly
Journal: Allergy (2016)

In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter.To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths.We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed.We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision.This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis.
Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure
Authors: Scott A. Sands, Yoseph Mebrate, Bradley A. Edwards, Shamim Nemati, Charlotte H. Manisty, Akshay S. Desai, Andrew Wellman, Keith Willson, Darrel P. Francis, James P. Butler, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited.Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects.Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation.Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined).Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.
Systematic Evaluation of DNA-Based Quantitative-Polymerase Chain Reaction (Q-PCR) Assays to Track Treatment Response in Patients with JAK2-V617F Associated Myeloproliferative Neoplasms: A Joint European LeukemiaNet/ MPN&amp;MPNr-EuroNet Study
Authors: J V Jovanovic, A M Vannucchi, E Lippert, E Oppliger Leibundgut, N Maroc, S Hermouet, G Nickless, B Cassinat, P Guglielmelli, B van der Reijden, A Bench, K Tobal, B Wilkins, K Cuthill, A Ivey, K Yeoman, M J Percy, S Schwemmers, A Gruender, T W Kelley, S Reading, A Pancrazzi, MF McMullin, H L Pahl, C N Harrison, J T Prchal, C Chomienne, JJ Kiladjian, T Barbui, D Grimwade
Journal: Blood (2011)
Gene-Environment Interactions and Depression
Authors: Francis E. Lotrich
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Use of CD8 and Foxp3 immune infiltrates after neoadjuvant chemotherapy to predict survival in HER2-overexpressing breast cancer patients.
Authors: F. Ghiringhelli, B. P. Coudert, L. Arnould, P. Fumoleau, S. Ladoire
Journal: Journal of Clinical Oncology (2010)

10555 Background: The role of tumor-immune infiltrate modifications by chemotherapies in the outcome of breast cancer is unknown. We previously demonstrated that high CD8 infiltrate and absence of Foxp3 cells after primary systemic chemotherapy (PSC) for breast cancer was associated with complete pathological response, the gold standard prognostic factor in this setting (ladoire et al Clin Cancer Res 2008). We investigated the prognostic relevance of Foxp3 and CD8 lymphocyte infiltrates in tumor bed after neoadjuvant chemotherapy in patients with breast cancer in another independent series. Methods: In a series of 111 HER2 overexpressing breast cancer treated with PSC, we studied by immunohistochemistery the infiltration in Foxp3 and CD8 cells after chemotherapy. Kaplan-Meier analysis and Cox regression modeling were used to assess the overall survival and relapse-free survival. Results: Sixty-three patients were treated with docetaxel and trastuzumab, 48 patients were treated with anthracycline-based regimen. A strong positive correlation was observed between immune response and complete pathological response (p=0,0015 Fisher exact Test). Using unvivariate analysis, the presence of a good immune response (defined as a strong infiltration in CD8 combined with a weak infiltrate in Foxp3 cells), was associated with a better relapse-free survival and overall survival in whole population (p=0.0001 and p=0.008 Log Rank Test) but also in both anthracycline and trastuzumab subgroup. Using multivariate Cox analysis, good immunological response (hazard ratio 0.24 [0.11-0.51] and 0.29 [0.12-0.7]) and trastuzumab treatment (hazard ratio 0.51 [0.26-0.98] and 0.09 [0.02-0.38]) were independently associated with better relapse-free survival and overall survival. Conclusions: Immunological CD8 and Foxp3 infiltrate after PSC is as a new independent prognostic factor of relapse and survival in breast cancer patients with HER2 overexpressing tumors. The immunological scoring systems compared favorably to the previous clinical gold standard (pathological complete response). Future works are required for a prospective validation of these scoring systems. No significant financial relationships to disclose.
Value of progression-free survival (PFS) and health-related quality of life (HRQoL) improvements in refractory non-small cell lung cancer (NSCLC): An exploratory modeling analysis.
Authors: C. Ferrufino, D. Foley, K. Trochlil, J. Munakata
Journal: Journal of Clinical Oncology (2011)

e16616 Background: PFS is an attractive endpoint since it permits earlier assessment of treatment benefit compared to overall survival (OS) and is not influenced by subsequent lines of treatment. PFS may directly translate into symptom and HRQoL improvements associated with delayed disease progression. This study aims to quantify the economic and humanistic value of the PFS benefit. Methods: We developed a literature based, lifetime Markov model with 3 health states (progression free, disease progression, death) to estimate direct medical costs, life-years (LYs) and quality-adjusted life years (QALYs) gained of treating refractory NSCLC patients in multiple treatment settings from a US healthcare payer perspective. Costs, utilities, efficacy and safety data were obtained from published sources (Redbook 2010; Shepherd 2005). Costs and effects were discounted at 3%. The analysis included an approved 2nd line EGFR TKI therapy to which hypothetical improvements were made to both the baseline PFS and HRQoL estimates. Both treatment scenarios were assumed to have equal mean OS benefit and tolerability profiles. Results: Under baseline PFS and HRQoL assumptions, the model projected total lifetime discounted costs of $28,069, undiscounted LYs of 0.94 and QALYs of 0.30 for EGFR TKI treated patients. Incremental PFS benefits (hazard reduction range: 10 to 40%) resulted in incremental costs of $1,929 to $11,585 attributable to longer duration of anticancer therapy and related healthcare costs. However, the incremental costs associated with PFS benefit may be offset by utility improvements of 0.06 (13.3%) to 0.25 (54%) and still remain cost-effective up to $50,000/QALY. Conclusions: This exploratory model quantifies the incremental costs associated with up to a 40% PFS improvement. The model further shows that for a new intervention with PFS benefits to be cost-effective (up to $50,000/QALY), improvements in treatment-related HRQoL may offset the increased cost of therapy. An intervention with OS gains and reduced side effects may yield further improvements in QoL and cost-effectiveness.
Ballot on industrial action by GPs averted as government accepts BMA’s demands
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

The BMA’s GP leaders have said that they will not be balloting members on whether to take industrial action, after NHS England agreed to discuss the union’s plans for tackling the crisis in general practice.

GPs at the BMA’s conference of local medical committees in May voted to ballot members on their willingness to take industrial action should the government reject the BMA’s “urgent prescription for general practice,”1 published in January.2 The document called for a package of support in view of the growing crisis facing GP services.

GPs at …
Intravenous (i.v.) Busulfan (Bu) Plus Melphalan (Mel) Is a Well-Tolerated Preparative Regimen for Stem Cell Transplantation (SCT) in Patients (pts) with Advanced Lymphoid Malignancies.
Authors: Partow Kebriaei, Timothy Madden, Neil Thapar, Elizabeth J. Shpall, Chitra Hosing, Muzaffar H. Qazilbash, Marcos de Lima, Peter F. Thall, Stacie Wright, Issa F. Khouri, Richard E. Champlin, Roy Jones, Borje S. Andersson
Journal: Blood (2005)
Long-Term Prognosis of Deferred Acute Coronary Syndrome Lesions Based on Nonischemic Fractional Flow Reserve
Authors: Abdul Hakeem, Mohan M. Edupuganti, Ahmed Almomani, Naga Venkata Pothineni, Jason Payne, Amjad M. Abualsuod, Sabha Bhatti, Zubair Ahmed, Barry F. Uretsky
Journal: Journal of the American College of Cardiology (2016)
A phase II study of gefitinib (G) versus carboplatin and gemcitabine (CG) in chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC) and ECOG performance status (PS) 2.
Authors: S. Agarwal, V. Hirsh, J. S. Agulnik, V. Cohen, C. L. Mihalcioiu, R. Whittom
Journal: Journal of Clinical Oncology (2010)

e18090 Background: Patients (pts) with PS 2 and advanced NSCLC have poor response and tolerance to chemotherapy. G-an epidermal growth factor receptor tyrosine kinase inhibitor-is a more convenient and potentially less toxic treatment, with proven activity in advanced NSCLC, particularly in tumors with EGFR mutations. Consequently, in pts with PS 2, G could have a particular advantage over platinum based doublets, the current frontline standard in advanced NSCLC. Methods: 35 chemonaïve pts with Stage IIIB/IV NSCLC and PS 2 were randomly assigned between Oct ‘04 and July ‘07 to receive either G (250 mg/day orally; n = 18) or intravenous carboplatin (AUC 5 day 1) plus gemcitabine (1,000 mg/m (2) day 1 and 8; n = 17) every 3 weeks. The study (1839IL/0051), which was stopped prematurely because of slow accrual, consisted of pts with a median age of 69, 14 females, 21 males, 28 ex-smokers, 4 current and 3 never-smokers, 17 adenocarcinomas, 6 squamous, and 12 with anaplastic NSCLC. EGFR mutation status of pts was unknown. Results: Partial response rate on G was 0 of 18 pts and on CG was 4 of 17 pts (24%). Median PFS on G was 42 days (95% CI 35-90) and on CG was 131 days (95% CI 66-190). Median overall survival on G was 138 days (95% CI 63-268) and on CG was 213 days (95% CI 101-399). Both G and CG were generally well tolerated with no major differences in quality of life. Median time on G treatment was 60 days. Six pts crossed over from G to CG and 9 from CG to G. Conclusions: A numerically longer median PFS with CG versus G in this small phase II trial suggests that in PS 2 pts, without any biomarker selection, G is not better than CG in frontline treatment of unselected advanced NSCLC. However, tumors with EGFR exon 19 or 21 mutations, might select subsets of PS 2 pts who could initially benefit more from G than chemotherapy. While the EGFR mutation status was not assessed in our study, the incidence of positive mutations was likely to have been low. The PFS time was similar to previous studies of chemonaïve pts with EGFR mutation negative disease treated with G or CG. A prospective trial of mutation positive tumors specifically in PS 2 pts would be of interest. Sponsored by AstraZeneca. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain
Authors: Yu Shin Kim, Michael Anderson, Kyoungsook Park, Qin Zheng, Amit Agarwal, Catherine Gong, None Saijilafu, LeAnne Young, Shaoqiu He, Pamela Colleen LaVinka, Fengquan Zhou, Dwight Bergles, Menachem Hanani, Yun Guan, David C. Spray, Xinzhong Dong
Journal: Neuron (2016)
Electrical Storms in Patients With Implantable Cardioverter-Defibrillators for Primary Prevention
Authors: William Escande, Eloi Marijon, Pascal Defaye, Olivier Piot, Christophe Leclercq, Nicolas Sadoul, Jean-Claude Deharo, Jean-Philippe Empana, Serge Boveda, Didier Klug
Journal: Journal of the American College of Cardiology (2016)
Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.
Authors: Menache D, O'Malley Jp, Schorr Jb, Wagner B, Williams C, Alving Bm, Ballard Jo, Goodnight Sh, Hathaway We, Hultin Mb
Journal: Blood (1990)
Survey of dermatologists demonstrates widely varying approaches to perioperative antibiotic use: time for a randomized trial?
Authors: A.G.H. Wernham, G.A. Fremlin, S. Verykiou, N. Harper, S.A. Chan, N. Stembridge, R.N. Matin, R.A. Abbott
Journal: British Journal of Dermatology (2016)

post-operative wound infection rate following dermatological surgery ranges between 0.5%-8%.(1-3) Factors reported to increase the risk of surgical site infection (SSI) include procedure type (e.g. wedge excision, full thickness skin grafts); anatomic location (e.g. lower limb, groin); tumour ulceration; and patient-associated factors, such as immunodeficiency, diabetes and smoking.(4-6) A survey of UK Dermatologists demonstrated significant variation in the use of peri-operative oral antibiotics dependent upon various factors; presence of ulceration; diabetes; lower limb surgery; immunosuppression and flap / graft repairs.(7-8) These findings likely reflect a paucity of data in the literature. This article is protected by copyright. All rights reserved.
Analysis of KRAS mutations in colorectal cancer (CRC) patients by gender in a Brazilian cohort of 3,346 patients.
Authors: C. G. Ferreira, I. Zalcberg-Renault, F. M. Vieira, M. H. Bonamino, M. Zalis
Journal: Journal of Clinical Oncology (2010)

3614 Background: We previously reported that the profile of KRAS mutation in the Brazilian population is similar to that reported for Caucasian and Asian patients. Further we observed that KRAS mutation was more frequent in female than male. Although major advances in the last decades, there are still important gaps in our understanding of CRC carcinogenesis, particularly whether sex-linked factors play any role. Methods: Between July 2008 and November 2009, we analyzed 3,346 consecutive patient samples sent to a reference laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, éxon 1 was amplified by PCR and submitted to direct sequencing. Códons 12 and 13 were analyzed. Results: The median age was 59 years and well balanced according to gender with 50.1% of male and 49.9% female patients. The percentage of wild-type and mutated KRAS was 65 and 35%, respectively. Corroborating previous findings from our group a significant difference in the percentage of mutated KRAS patients was observed between female and male (37.7% versus 32.9%, p = 0.005). However there were no differences in the distribution of any specific KRAS mutation according to gender. Among the 1,171 mutated cases, 85% were in codon 12 versus 15% in codon 13. Mutation Gly12Asp was the most common being detected in 37% of the mutated cases. Conclusions: To the best of our knowledge this is one of the largest cohorts of KRAS genotyping in colorectal cancer patients and the first to indicate a higher incidence of KRAS-mutation in female than male. Further research is required to better address the impact of gender differences in colorectal cancer more specifically. No significant financial relationships to disclose.