tbuckley/cabot-search huggingface dataset:
Chronic obstructive pulmonary disease: missed diagnosis versus misdiagnosis:
Authors: Martin R Miller, Mark L Levy
Journal: BMJ (2015)

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By 2004 chronic obstructive pulmonary disease (COPD) was claimed to be the fourth most important cause of death worldwide,1 and its global prevalence and mortality are on the increase.2 Smoking accounts for about 75% of cases,3 but environmental exposures to tobacco smoke and other pollutants such as biomass fuels and occupational exposures may account for the remaining cases.4 5 6 COPD is a progressive disease, and in the later stages patients have frequent admissions to hospital, with over a third being readmitted in 30 days, contributing to an annual cost of £800m (€1bn; $1.24bn) in the UK.7 In the UK concern has …
Preliminary results: surveillance for Guillain-Barré Syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.
Authors: C. Prothro, K. Kudish, M. Fielline, J. Meek, N. Tellman, M. Milewski, B. Hogan, C. Holtzman, R. Danila, L. Dunning, R. Lynfield, K. Scherzinger, W. Connor, J. Baumbach, G. P. Giambrone, S. M. Zansky, P. F. Smith, A. Thomas, E. Mosites, D. Kirschke, M. Viray, P. Lewis, J. Sejvar, A. Baughman, C. Vollozzi, S. Fridkin
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
A Fifty Percent Reduction of Platelet Surface Glycoprotein Ib Does Not Affect Platelet Adhesion Under Flow Conditions
Authors: G. Henrita van Zanten, Harry F.G. Heijnen, Yaping Wu, Karin M. Schut-Hese, Pieter J. Slootweg, Philip G. de Groot, Jan J. Sixma, Rienk Nieuwland
Journal: Blood (1998)
Role of biologic therapy in the treatment of unresectable appendiceal epithelial neoplasms (AEN).
Authors: Cathy Eng, Michael J. Overman, Keith F. Fournier, Richard E. Royal, Aki Ohinata, Safia Rafeeq, Jonathan Phillips, Robert A. Wolff, Paul F. Mansfield
Journal: Journal of Clinical Oncology (2012)

628 Background: AEN ranges from benign appearing cells to poorly differentiated signet cell adenocarcinoma. Currently, cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is believed to be optimal treatment. Systemic chemotherapy (SC) +/- biologic therapy (BT) is considered when CRS is not feasible. VEGF expression reportedly is a poor prognostic indicator in AEN pts. The purpose of this analysis is to determine the benefit of BT in chemotherapy naïve suboptimal candidates for CRS. Methods: A retrospective chart review of AEN pts registered in our tumor registry between Jan. 2005 to Dec. 2009 was undertaken. Electronic medical records (EMR) were reviewed for CRS, HIPEC, histology, stage, SC + BT, CEA, CA-125, and/or CA 19-9, response (R), and progression-free survival (PFS). All patients were required to be radiographically restaged at MDACC. R was defined as clinical or radiographic benefit. K-M method, Log-Rank, and Cox proportional hazard regression models were used for statistical analysis. Results: Of 625 pts with a diagnosis of AEN, 132 (21%) fulfilled the inclusion criteria and were evaluable for PFS and R. Sixty-five (49%) pts received SC + BT; 67 (51%) pts received SC alone. SC included: 5-FU = 28 (21%), FOLFIRI = 20 (15%), FOLFOX = 71 (54%), and other = 13 (10%). BT included: bevacizumab = 58 (89%), EGFR inhibitor = 6 (9%); 1 pt (2%) received both. Median lines of BT = 1 (range: 1-3). Histologically, 51 (38%) were poorly differentiated and 33 (25%) were signet ring; 26 (20%) had both features. After a median follow-up of 33M, 40 (62%) had stable disease, 12 (19%) partial response, and 12 (19%) progressive disease. Biologic therapy improved median PFS and OS (17M vs. 7M, p-value = 0.007; 68M vs. 50M, p-value = 0.08, respectively). Multivariate analysis indicated improved PFS (HR: 0.49; 95% CI: 0.3-0.8; p-value: &lt;0.001) and OS (HR: 0.52; 95% CI: 0.3-0.8; p value = 0.007) in favor of biologic therapy. Conclusions: Biologic therapy in combination with chemotherapy appears to have a role in surgically unresectable AEN pts with improvement in PFS and OS. Tissue/blood correlatives and quality of life analysis are underway. Prospective analysis including cost-benefit should be considered.
Abstract P024: Temporal Trends in Hospitalizations for Acute Decompensated Heart Failure in the U.S.: Calibration using The Atherosclerosis Risk in Communities (ARIC) Surveillance Study
Authors: Sunil K Agarwal, Lisa Wruck, Miguel Quibrera, Kunihiro Matsushita, Laura R Loehr, Patricia P Chang, Lloyd E Chambless, Wayne R Rosamond, Jacqueline Wright, Gerardo Heiss, Josef Coresh
Journal: Circulation (2014)

Background: Trends for acute decompensated heart failure (ADHF) hospitalizations based on the primary discharge ICD codes have declined in the U.S. However, HF ICD codes are increasingly found in non-primary positions. Validation data are needed to estimate the frequency of ADHF hospitalizations. Methods: The ARIC Study conducts surveillance for hospitalized ADHF in four U.S. communities for age ≥ 55 years since 2005. Hospital records are sampled, abstracted, and classified as ADHF or not by an expert physician panel. Analyses were stratified on code groups (a) 428.xx in primary-position, (b) 428.xx in non-primary position, and (c) other sampled HF ICD code (398, 402, 404, 415, 416, 425, 518, 786) in any position. We calculated ADHF probability in each group overall (positive predictive value, PPV), and by using regression models. We estimated the nationwide trends of ADHF hospitalizations from the National Inpatient Sample (NIS), a 20% probability sample of U.S. community hospitals, by applying the calibration factors derived in the ARIC study. Results: In ARIC surveillance 42% of eligible hospitalizations (n=12,450 charts) validated as ADHF. NIS data included 9 million eligible hospitalizations during 1999-2010. The estimated numbers of US ADHF hospitalization in 2010 among Americans ≥ 55 years old was 1.8 (SE 0.02) million as compared to 0.8 (SE 0.002) million with 428.xx in the primary position ( Figure ). The estimated ADHF hospitalizations in the U.S. increased from 1.6 million in 1999 to 1.9 million in 2006, and then decreased to 1.8 million in 2010 (average annual increase of 1%, p-trend &lt;0.01). Estimated ADHF based on regression models for each of the three code groups gave similar results. The temporal increase was steeper among men and in age category 55-64 years than older ages. Conclusions: Estimated frequency of ADHF hospitalizations by ARIC validation criteria is about two times higher than ICD 428 in primary position; with an overall increasing vs. declining trend over the last decade.
Effectiveness of Breast Cancer Surveillance in <i> BRCA1/2</i> Gene Mutation Carriers and Women With High Familial Risk
Authors: C.T.M. Brekelmans, C. Seynaeve, C.C.M. Bartels, M.M.A. Tilanus-Linthorst, E.J. Meijers-Heijboer, C.M.G. Crepin, A.N. van Geel, M. Menke, L.C. Verhoog, A. van den Ouweland, I.M. Obdeijn, J.G.M. Klijn
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Women with a high breast cancer risk due to a familial predisposition may choose between preventive surgery and regular surveillance. The effectiveness of surveillance in high-risk women and especially BRCA1/2 mutation carriers is unknown. We present first results from a single large family cancer clinic. PATIENTS AND METHODS: Women with breast cancer risk over 15% were examined by physical examination every 6 months and mammography every year. Detection rates and screening parameters were calculated for the total group and separately for different age and genetic risk groups. RESULTS: At least one examination was performed in 1,198 women: 449 moderate and 621 high-risk women and 128 BRCA1/2 mutation carriers. Within a median follow-up of 3 years, 35 breast cancers were detected (four ductal carcinoma-in-situ; 31 invasive tumors); the average detection rate was 9.7 per 1,000. Detection rates (95% confidence interval) for moderate and high-risk women and BRCA1/2 carriers were 3.3 (1.1 to 8.6), 8.4 (5.4 to 13.2), and 33 (17 to 63) per 1,000 person-years, respectively. The ratio of observed cases versus breast cancers expected in an average-risk population of comparable age was 2.7, 7.0 and 23.7 respectively. Overall, node negativity was 65%; 34% of primary tumors were less than 10 mm; sensitivity was 74%. Results with respect to tumor stage and sensitivity were less favorable in BRCA1/2 carriers and in women under the age of 40. CONCLUSION: It is possible to identify young women at high risk for breast cancer. The number of cancers detected was significantly greater than expected in an age-matched average-risk population and related to the risk category. Overall, screening parameters were comparable to population screening data, with less favorable results in the youngest age group (&lt; 40) and BRCA1/2 carriers.
Intensified Mycophenolate Mofetil (MMF) Dosing Every 8 Hours Is Safe From The Standpoint Of Engraftment and May Ameliorate Severe Acute Graft-Versus-Host Disease (GVHD) After Double-Unit Cord Blood Transplantation (CBT)
Authors: Doris M Ponce, Stephen J. Harnicar, Sean Devlin, Patrick Hilden, Katherine L Evans, Marissa N Lubin, Sergio A Giralt, Jenna D Goldberg, Miguel-Angel Perales, Nancy A. Kernan, Susan E. Prockop, Andromachi Scaradavou, Juliet N Barker
Journal: Blood (2013)
Derived neutrophil lymphocyte ratio may predict benefit from cisplatin in the advanced biliary cancer: the ABC-02 and BT-22 studies
Authors: T. Grenader, S. Nash, Y. Plotkin, J. Furuse, N. Mizuno, T. Okusaka, H. Wasan, J. Valle, J. Bridgewater
Journal: Annals of Oncology (2015)
Antitoxin Treatment of Tetanus
Authors: A A Qazilbash, M Ajmal
Journal: BMJ (1894)

A random study of 300 cases suffering from tetanus was conducted at the Lady Reading Hospital Peshawar. Three groups each of hundred patients were formed depending on the dose of A.T.S. administered. No particular difference was noted in the mortality of groups receiving 100,000 units and 20,000 units. A dose of 20,000 units is thus sufficient for most of the tetanus cases. 1000,000 units A.T.S. may be given to postpartum and abortion cases where the infection is more generalised and severe.
Striking the balance between too little and too much physical activity
Authors: Hilde Moseby Berge, Ben Clarsen
Journal: British Journal of Sports Medicine (2015)

It should be pretty obvious; movement is good, sitting still is bad. However, physical activity rates continue to fall across the world.1 As sports and exercise medicine practitioners, we could be seen as frontline soldiers in the fight against inactivity. As such, we need to be well armed with knowledge about the consequences of inactivity, about what can be done to combat it and about who we should be targeting. These themes are all covered in this issue which shines the spotlight on an increasingly researched topic in Norway—the relationship between physical activity and health.

We start with a study documenting the declining activity levels of British school children as they age from 10 to 14 years ( see page 730 ). We hope their increased sedentary time is not spent in front of a computer or watching TV, because in their huge meta-analysis, Zhai et al show that these behaviours are …
Therapy for idiopathic pulmonary fibrosis: lessons from pooled data analyses
Authors: Lauren K. Troy, Tamera J. Corte
Journal: European Respiratory Journal (2015)

In 2014, two landmark clinical trials (ASCEND and INPULSIS) were published demonstrating, for the first time, a treatment benefit for patients with idiopathic pulmonary fibrosis (IPF). Both pirfenidone and nintedanib were shown to have a clear therapeutic benefit in slowing the relentless disease progression evident in IPF patients. The results of these studies have had a major impact upon management of IPF patients worldwide, with subsequent changes made to international guidelines, which now recommend in favour of antifibrotic therapy. However, this is not the whole story: there are many unanswered questions with regard to the real-world treatment benefit and use of antifibrotic therapy. In this issue of the European Respiratory Journal , Noble et al . [1] present the pooled data of the three multinational, phase 3, placebo-controlled trials of pirfenidone in IPF patients, the ASCEND, and CAPACITY 004 and 006 studies. Examining the combined patient population reveals important insights about specific subgroups along with broader inferences that are only possible through pooled analysis. The pooled analysis of three large phase 3 trials sheds further light on the role of antifibrotic therapy in IPF <http://ow.ly/UNTWQ>
Preserved effector functions of human ORAI1- and STIM1-deficient neutrophils
Authors: Roland Elling, Baerbel Keller, Carl Weidinger, Monika Häffner, Sachin D. Deshmukh, Isabelle Zee, Carsten Speckmann, Stephan Ehl, Klaus Schwarz, Stefan Feske, Philipp Henneke
Journal: Journal of Allergy and Clinical Immunology (2015)
Heritability of naevus pattern
Authors: C. Longo, S. Ribero
Journal: British Journal of Dermatology (2015)

Journal Article Heritability of naevus pattern Get access C. Longo, C. Longo Dermatology and Skin Cancer Unit Arcispedale S. Maria Nuova‐IRCCS Reggio Emilia Italy Search for other works by this author on: Oxford Academic Google Scholar S. Ribero S. Ribero Dermatologic Unit Department of Medical Sciences University of Turin Turin Italy Correspondence: Simone Ribero. E‐mail: simone.ribero@unito.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 265–266, https://doi.org/10.1111/bjd.14386 Published: 01 February 2016
Cold urticaria and an oral contraceptive [letter]
Authors: Burns Mr, Schoch Dr, Grayzel Ai
Journal: Annals of Internal Medicine (1983)

Cold urticaria is a well-recognized entity of unknown cause occurring in both familial and acquired forms.  We describe a case of cold urticaria in which the inciting agent appears to be an oral contraceptive (OC) containing 1 mg of norethindrone and 0.035 mg of mestranol.  A MEDLINE search failed to show any cases with such an association.  A 19-year-old Hispanic woman with a benign medical history began taking the medication in October 1981.  The next summer she noted the onset of swelling of the face and extremities after swimming.  No episodes or dizziness or fainting occurred.  During the next winter (in New York City) she noted swelling of any part of her body exposed to temperatures lower than 10 degrees Celsius.  This occurred upon rewarming.  The areas were white and nonpruritic.  Touching cold soda cans or drinking cold liquids would cause reactions localized to the fingertips or lips respectively.  The symptoms became progressively more severe.  There was no association with her menstrual periods.  Her family history was unremarkable.  Physical findings were normal.  An ice cube was placed on the volar aspect of the right forearm for 4 minutes.  Starting 3-4 minutes later a white nonpruritic wheal developed in the exact shape of the ice cube and the path of the cold melting water.  The reaction lasted 12 hours.  Results of a complete blood count urinalysis and liver function tests were normal and those of tests for antinuclear antibody cryoglobulins hepatitis B surface antigen heterophil VDRL and cold agglutinins were negative.  The erythrocyte sedimentation rate was 15 mm/h (Westergren).  Assays for total hemolytic complement C3 C4 and Clq-esterase inhibitor gave normal results.  Her OC was stopped and the symptoms disappeared within 2 weeks despite the cold weather.  No other treatment was given.  Rechallenge with the medication or its components was not attempted.  This patient seems to have had a case of cold urticaria induced by an OC.  We did not prove the relation and cannot determine which component was responsible.  The abrupt termination of symptoms after months of gradual worsening however is highly suggestive of an association.  (full text)
Failures in Phase III: Causes and Consequences
Authors: Bostjan Seruga, Alberto Ocana, Eitan Amir, Ian F. Tannock
Journal: Clinical Cancer Research (2015)

Abstract Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. Clin Cancer Res; 21(20); 4552–60. ©2015 AACR. See all articles in this CCR Focus section, “Innovations to Speed Drug Development.”
Phase I study of sunitinib (S) in combination with metronomic dosing of cyclophosphamide and methotrexate (CM) in patients with metastatic breast cancer (MBC)
Authors: J. Lyandres, M. M. Moasser, M. Melisko, A. Goga, J. W. Park, H. S. Rugo
Journal: Journal of Clinical Oncology (2008)

13540 Background: Antiangiogenic therapy targeting VEGF with bevacizumab in combination with paclitaxel is effective in the treatment of MBC. S is a potent multitargeted tyrosine kinase inhibitor and has activity against VEGFR, PDGFR, c-Kit, and Flt-3. S has demonstrated activity in a variety of tumors and is approved at a dose of 50mg 4 wks on/ 2 wks off. Single agent continuous dosing (CD) at 37.5 mg/d is safe in limited phase II trials, and may avoid a flare in angiogenesis with drug withdrawal. The effects of metronomic chemotherapy in preclinical studies are enhanced in combination with antiangiogenic agents, and CM has demonstrated efficacy in MBC. We combined S with CM in a phase I dose escalation study to evaluate an all oral regimen with CD. Methods: Eligible patients (pts) have measurable or evaluable progressing MBC. Pts receive a two week lead-in course of escalating dose S, followed by continuous dosing S combined with CM. The primary endpoint is to determine the MTD S + CM, secondary endpoints include toxicity, response. Quantitative analysis for circulating tumor cells (CTC) and endothelial cells (CEC) is performed at baseline, before starting CM then every 3 wks. 3 patients are enrolled in each cohort, starting at 12.5mg/d; 6 patients will be enrolled at MTD followed by a phase II trial at MTD. Efficacy is assessed at wk 8 then q6 wks. Results: 11 pts have been treated to date (median age 58 (range 36–86); PS 0–2; median number prior chemo regimens 5 (range 2–7) in two dose cohorts (12.5, 25 mg/d). 3 pts discontinued during the “run-in” due to symptomatic PD. 3 of 6 evaluable pts at 25 mg/d had asymptomatic grade 3 neutropenia requiring responding to dose reduction in CM. 3 pts had grade 2 neutropenia. Other AEs include grade 1/2 LFTs (3/8 pts), thrombocytopenia (2/8), and mucositis (4/8). One pt had grade 2 fingertip desquamation resolving in two weeks off all meds. At wk 8, 4/6 evaluable pts at 25 mg/d S with CM had stable disease (SD). One pt has SD at 35 weeks on study. The third cohort at 37.5 mg S and CM is currently accruing. Conclusion: The combination of S with CM is well tolerated in heavily pretreated pts with MBC and has shown preliminary evidence of efficacy. Final phase I data and data on CTC and CEC will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer
Abstract P016: Galectin-3 and Incident Heart Failure among Patients with Pre-existing Coronary Artery Disease: the ADVANCE Study
Authors: Carlos Iribarren, Malini Chandra, Mark A Hlatky, Stephen Fortmann, Thomas Quertermous, Alan S Go
Journal: Circulation (2014)

Galecin-3 (Gal-3) is a novel beta-galactoside-binding lectin implicated in pro-fibrotic pathways that are upregulated during cardiac remodeling. Gal-3 has been associated with poor prognosis among patients with heart failure and with development of heart failure after acute coronary syndrome. In this study we sought to ascertain: 1) the cross-sectional demographic, behavioral and clinical correlates of serum levels of Gal-3, and 2) its independent predictive value for incident heart failure among 1,312 participants in The Atherosclerotic Disease, VAscular FunctioN and GenetiC Epidemiology (ADVANCE) Study whose initial presentation of coronary artery disease (CAD) between 10/2001 and 12/2003 was acute myocardial infarction (n=871; mean ± SD age; 62 ± 8 years; 23% female) or stable angina (n=441; mean ± SD age; 61 ± 8 years ; 34% female). Gal-3 was measured in frozen serum collected at the baseline examination (2002 to 2004) with the ARCHITECT assay (Abbott Diagnostics, Abbott Park, IL). Follow-up for incident heart failure using ICD-9 hospital principal discharge diagnostic codes 428, 402, 404 and 398 through 12/31/2012 resulted in 74 events (63 among AMI patients, 11 among stable angina patients). The mean ± SD Gal-3 concentration was 16.9 ± 5.3 ng/mL among AMI patients and 16.1 ± 4.4 ng/mL among stable angina patients. The significant independent correlates of Gal-3 were CAD presentation, age, gender, physical activity and estimated glomerular filtration rate (eGFR). In Cox regression with adjustment for age, gender, race and CAD presentation, each 1 SD increment of Gal-3 was associated with 1.64-fold increased hazard of heart failure (95% CI, 1.40 to 1.93; p&lt;0.0001). After further adjustment for smoking status, activity level, alcohol intake, body mass index, LDL-C, HDL-C, triglycerides, diabetes, hypertension, hs-CRP and e-GFR, Gal-3 remained associated with incident heart failure (HR=1.44; 95% CI, 1.18 to 1.75; p=0.0003). Also in fully-adjusted analysis, and relative to quartile 1, the HRs were 1.10 (95% CI, 0.45 to 2.86) for quartile 2, 1.29 (95% CI, 0.53 to 3.11) for quartile 3 and 2.39 (95% CI, 1.06 to 5.37) for quartile 4 of Gal-3. Our results support the value of Gal-3 as a biomarker of heart failure development among patients with pre-existing CAD.