bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial
Authors: Ntalas Ioannis V. , Kalantzi Kallirroi I. , Tsoumani Maria E. , Bourdakis Adamantios , Charmpas Christos , Christogiannis Zaharias , Dimoulis Nikolaos , Draganigos Antonios , Efthimiadis Ioannis , Giannakoulas Giorgos , Giatrakos Ioannis , Giogiakas Vassilios , Goumas Giorgos , Hatziathanasiou Giorgos , Kazakos Evangelos , Kipouridis Nikolaos , Konstantinou Spiros , Milionis Haralampos , Nikolopoulos Dimitrios , Peltekis Leonidas , Prokopakis Nikolaos , Sinteles Ioannis , Stroumbis Christos , Terzoudi Kyriafina , Thoma Maria , Tsilias Karmelos , Vakalis Ioannis , Vardakis Konstantinos , Vasilakopoulos Vasileios , Vemmos Konstantinos , Voukelatou Maria , Xaraktsis Ioannis , Panagiotakos Demosthenes B. , Goudevenos John A. , Tselepis Alexandros D. 
Published: April 2016

Background: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. Methods: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. Results: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. Conclusion: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).
Incidence of Antiphospholipid Antibodies in Patients With Immune Thrombocytopenia and Correlation With Treatment With Steroids in North Indian Population
Authors: Dayama Aniruddha , Dass Jasmita , Mahapatra Manoranjan , Saxena Renu 
Published: April 2016

Introduction: Antiphospholipid antibodies (APLAs) have been variably reported in 14% to 75% of patients with immune thrombocytopenia (ITP). There is lack of Indian data on incidence of APLA in ITP. Objective: We studied the incidence of APLA in patients with pediatric and adult Indian ITP. Materials and Methods: We prospectively studied 100 patients including acute (n = 37), persistent (n = 13), and chronic (n = 50) ITP. Male to female ratio was 1.22:1. Median age was 18 years (1.5-56). All patients underwent investigations for lupus anticoagulant (LA), anticardiolipin (aCL) immunoglobulin G (IgG) and IgM antibodies, and anti-β2 glycoprotein 1 (β2GP1) IgG and IgM antibodies. Patients with secondary ITP were excluded. Bleeding manifestations were recorded. Patients with acute and persistent ITP were assessed for steroid response. Response rates were compared between APLA-positive and APLA-negative patients. Results: Antiphospholipid antibodies were detected in ∼12% of patients with ITP: 8.1% (3 of 37) in acute, 0% (0 of 13) in persistent, and 18% (9 of 50) in chronic ITP. Anti-β2GP1 antibodies were most frequent (9%). Only 2 patients each were positive for anti-aCL antibodies and LA. Although platelet counts were significantly higher in APLA-positive patients, there was no significant difference in bleeding between the APLA-positive versus APLA-negative patients with ITP. There was also no significant difference in steroid response between APLA-positive and APLA-negative patients with acute/persistent ITP. In the short follow-up (median 8 months), none of the APLA-positive patients developed thrombosis. Conclusions: Incidence of APLA in Indian population was lower than reported in the West, which indicates that not all patients of ITP need to be subjected to these manifestations upfront at diagnosis.
Growth Deficiency in Cystic Fibrosis Is Observable at Birth and Predictive of Early Pulmonary Function
Authors: Darrah Rebecca , Nelson Rebecca , Damato Elizabeth G. , Decker Michael , Matthews Anne , Hodges Craig A. 
Published: April 2016

Introduction: Cystic fibrosis (CF) is a complex disease that includes both pulmonary and gastrointestinal challenges, resulting in decreased weight. Pulmonary symptoms of CF are extremely variable. Greater body mass at an early age is associated with improved pulmonary function, but it is unknown at what age weight becomes predictive of pulmonary disease severity. The purpose of this study was to investigate the relationship between birth weight and pulmonary function in CF. Methods: Birth weight and pulmonary data were obtained. Linear regressions were used to examine the relationship between these two variables. A one-tailed t-test was used to compare birth weights between CF patients and the national average. Results: Birth weight was significantly lower in babies with CF and correlated with pulmonary disease at ages 6 and 10 years but not with age at which Pseudomonas aeruginosa colonization was observed. Discussion: These data suggest that CF growth deficiency has prenatal origins. Early nutritional intervention for babies with CF and a low birth weight is warranted to maximize pulmonary potential.
Thrombus remnant despite intra-arterial thrombolysis for thrombus formation during endovascular treatment of ruptured cerebral aneurysms: Does it harm?
Authors: Jun Hyo Sub , Ahn Jun Hyong , Kim Ji Hee , Oh Jae Keun , Song Joon Ho , Chang In Bok 
Published: April 2016

Background The fate and safety of thrombus remnant despite intra-arterial thrombolysis for unexpected thrombus formation has rarely been reported. Methods From January 2010 to May 2015, 131 consecutive patients with ruptured intracranial aneurysms were treated by endovascular methods at our institution. Among the 21 patients (16%) treated by intra-arterial thrombolysis for the thrombus formation during the procedure, nine patients (nine aneurysms) suffered from thrombus remnant. We reviewed the clinical and radiologic outcomes of patients with thrombus remnant as well as intraoperative and postoperative management of thrombus formation. Results Thrombus formation occurred near the coiled aneurysm in eight patients, and distal embolic occlusion was observed in one patient. All nine patients were initially managed by intra-arterial thrombolysis with tirofiban. One patient with persistent distal embolic occlusion and two patients with distal migration of the thrombus after intra-arterial thrombolysis were additionally treated with stent retriever. One patient with occlusion of the parent artery near the coiled aneurysm despite intra-arterial thrombolysis was partially recanalized by permanent deployment of a stent retriever. Delayed cerebral angiography showed no increase in size of thrombus remnant in any patients. After the procedure, thrombus remnant was managed by intravenous tirofiban. Follow-up CT angiography on the first postoperative day showed patent arterial flow, and ischemic complication related with thromboembolism did not occur in any patients. One patient suffered from hemorrhagic complication. Conclusion If the patency of parent artery is maintained and the size of the thrombus remnant does not increase on delayed angiography after intra-arterial thrombolysis, postoperative thromboembolic events rarely occur.
Less can be more: Targeted embolization of aneurysms associated with arteriovenous malformations unsuitable for surgical resection
Authors: Alexander Matthew D , Cooke Daniel L , Hallam Danial K , Kim Helen , Hetts Steven W , Ghodke Basavaraj V 
Published: April 2016

Introduction To mitigate risks of hemorrhage, high-risk features of brain arteriovenous malformations (BAVMs) can be targeted to reduce the risk of rupture. Previous investigation has examined embolization of a pedicle supplying a high-risk feature; this study examines embolization targeted specifically at aneurysms associated with BAVMs. Materials and methods Patients with BAVMs treated at two high-volume neurointerventional services were retrospectively reviewed. Patients treated with intention to occlude only the associated aneurysm itself were analyzed. Demographic and lesion characteristics were identified, as were technical and clinical outcomes. Adverse events were defined as hemorrhage, new seizure, and death. Results Thirty-two patients met inclusion criteria out of 1103 patients treated during the study period. Twenty-seven (84.4%) BAVMs were acutely ruptured, all with the aneurysm identified as the hemorrhage source. Twenty-four (75.0%) lesions involved eloquent territory. There were equal numbers of feeding artery and nidus aneurysms. Follow-up data were available for a total of 101.3 patient-years for a mean follow-up time of 2.9 years. One patient died; the remaining 31 patients had improved functional status at last contact. Annualized rate of hemorrhage after treatment was 1.0%; rate of adverse events after treatment was 3.0%. Excluding time after confirmed occlusion following radiosurgery, annualized rates were 1.4% and 4.8%, respectively. Conclusion In inoperable BAVMs, targeted embolization of associated aneurysms can be performed safely and effectively. This should be considered in high-risk lesions prior to radiosurgery or in cases when no other treatment options are available. Such intervention warrants further investigation.
Improving the legibility of prescription medication labels for older adults and adults with visual impairment
Authors: Leat Susan J. , Krishnamoorthy Abinaya , Carbonara Antonio , Gold Deborah , Rojas-Fernandez Carlos 
Published: April 2016

Objectives: Most current prescription labels fail to meet print guidelines, especially in print size. We therefore compared the legibility of current prescription medication labels against the legibility of prototype labels, based on current guidelines for legibility. Method: Sample medication labels were obtained from pharmacies, and prototype medication labels were developed according to legibility guidelines from nongovernmental organizations and pharmacy organizations. Three groups of participants, consisting of older adults with normal vision, older adults with visual impairment and younger adults with visual impairment (total N = 71) took part. Participants were asked to read and rank the labels. Reading speed and accuracy were determined. Results: Accuracies were high (75%–100%), and there were no significant differences between samples or prototypes or between groups. Prototypes, however, were read faster than samples ( p < 0.001). Subjectively, participants preferred the largest print option ( p < 0.001) and instructions with the numbers written in highlighted uppercase words ( p < 0.001). Discussion: The results indicate that improvements to the label would include larger print size, a consistent layout with left justification and using upper case with highlighting for emphasis of the numbers in the instructions.
Multimorbidity, mortality, and physical activity
Authors: Loprinzi Paul D , Addoh Ovuokerie , Joyner Chelsea 
Published: April 2016

Objectives Multimorbidity and physical inactivity are individually associated with increased mortality risk, but the possibility for physical activity to moderate the multimorbidity–mortality relationship has yet to be investigated. Methods Data from the 1999–2006 NHANES were employed, with 16,091 participants constituting the analytic sample. Participants were followed through 2011, including a median follow-up of 99 months. Physical activity was assessed via self-report with multimorbidity assessed from physician diagnosis. Results After adjustment, for every 1 morbidity increase, participants had a 23% increased risk of all-cause mortality (HR = 1.23; 95% CI: 1.19–1.28; p < 0.001). Multimorbidity mostly remained associated with all-cause mortality across all levels of physical activity, with the exception of those achieving four times the dose of the government guidelines. Discussion With the exception of those who engaged in high levels of self-reported physical activity, physical activity had a minimal effect on the multimorbidity–mortality relationship.
Contrast-enhanced ultrasonography for detecting histological carotid plaque rupture: Quantitative analysis of ulcer
Authors: Hamada Omi , Sakata Noriyuki , Ogata Toshiyasu , Shimada Hirofumi , Inoue Tooru 
Published: April 2016

Background Few studies have evaluated the distinct ability of contrast-enhanced ultrasonography for detecting carotid plaque rupture versus histological observations. Aims The aim of this study was to quantitatively assess the ability of contrast-enhanced ultrasonography to detect plaque rupture compared to ultrasonographic and histological images in terms of geometric accordance. Methods Carotid plaque morphology was classified as “smooth,” “irregular,” or “ulcerated” on 45 conventional ultrasonography and contrast-enhanced ultrasonography images from consecutive patients undergoing endarterectomy, and 55 regions of interests were captured on contrast-enhanced ultrasonography. A comparative study with a receiver operating characteristic analysis was performed using histological findings for reference. Results Contrast-enhanced ultrasonography exhibited a higher percentage of “ulcerated” findings in patients with plaque rupture compared to conventional ultrasonography (P = 0.002) as well as an association with thrombus formation (P = 0.048) and fibrous cap disruption (P < 0.0001). On contrast-enhanced ultrasonography, “ulcerated” were significantly more likely than “smooth” findings when the fibrous cap was disrupted (odds ratio (OR), 41.5). The receiver operating characteristic areas under the curve for the orifice, depth, and width of the concavities on contrast-enhanced ultrasonography were significantly greater than 0.5, while their optimal cut-off values were 1.40 mm, 1.30 mm, and 1.88 mm, respectively. When one of these variables was greater than the optimal cut-off value, the sensitivity, negative hit rate, and odds ratio for detecting fibrous cap disruption were 91.3%, 91.6%, and 23.1, respectively. Conclusions In our study, contrast-enhanced ultrasonography has high sensitivity for identifying histological plaque rupture, and the measurement of concavity on contrast-enhanced ultrasonography may enable the accurate detection of fibrous cap disruption.
The effects of distress and the dimensions of coping strategies on physicians’ satisfaction with competence
Authors: Lepnurm Rein , Nesdole Robert , Dobson Roy Thomas , Peña-Sánchez Juan-Nicolás 
Published: April 2016

Objectives: The purposes of this study were to (1) articulate the dimensions of Coping strategies used by physicians, and (2) determine whether Coping strategies alleviated Distress and enhanced Satisfaction with Competence. Methods: Comprehensive questionnaires on factors associated with Satisfaction with Competence were sent to a stratified sample of 5300 physicians across Canada. The response rate was 57% with negligible bias. Factor analysis was used to articulate the dimensions of Coping strategies. The classic Baron and Kenny regression series was used to establish whether Coping mediates the effects of Distress on Satisfaction with Competence. Years in Practice, Self-Reported Health, and Duties of Physicians were control factors. Results: A reliable 15-item measure of Coping was confirmed (α = .76) with four reasonably reliable dimensions: Collegiality (α = .80), Attitude (α = .63), Managing Work (α = .60), and Self-Care (α = .62). Physicians reported a mean Satisfaction with Competence of ( M = 4.26 out of 6.0, standard deviation ( SD) = 0.64) with General practitioners reporting slightly lower levels of Satisfaction with Competence than average. Conversely, chronic disease, clinical, and procedural specialists reported higher levels of Satisfaction with Competence. The mean Distress level for all physicians was ( M = 3.66 out of 7.0, SD = 0.93). The highest levels of distress were reported by emergency physicians, general practitioners, and surgeons. Clinical specialists, anesthesiologists, and psychiatrists reported the lowest levels of distress. Physicians reported ( M = 4.48 out of 7.0, SD = 0.78) as the mean level of Coping ability with clinical specialists and general practitioners reporting lower than average abilities to cope. Laboratory and chronic care specialists reported greater than average coping abilities. Regression analyses established Coping as a mediator of Distress which predicted physicians’ Satisfaction with Competence. Conclusion: Four groups of coping strategies were significant in relieving the pressures of work: (1) Collegiality, (2) Self-Care, (3) Managing Work, and (4) Positive Attitude.
The expansion of endoscopic submucosal dissection in France: A prospective nationwide survey
Authors: Barret Maximilien , Lepilliez Vincent , Coumaros Dimitri , Chaussade Stanislas , Leblanc Sarah , Ponchon Thierry , Fumex Fabien , Chabrun Edouard , Bauret Paul , Cellier Christophe , Coron Emmanuel , Bichard Philippe , Bulois Philippe , Charachon Antoine , Rahmi Gabriel , Bellon Serge , Lerhun Marc , Arpurt Jean‐Pierre , Koch Stéphane , Napoleon Bertrand , Vaillant Eric , Esch Anouk , Farhat Said , Robin Francoise , Kaddour Nadira , Prat Frédéric ,   for the Société Française d’Endoscopie Digestive (SFED)
Published: April 2016

IntroductionEarly reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time.Material and methodsAll consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow‐up data were recorded. The results obtained over three years were compared to previously published data covering the 2008–2010 period.ResultsBetween November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010–2013 vs 32.1 ± 21 for 2008–2010 (p  = 0.004). En bloc resection improved from 77.1% to 91.7% (p  < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p  = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p  < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p  = 0.01) and perforations from 18.1% to 8.1% (p  = 0.002) over time. No procedure‐related mortality was recorded.ConclusionsIn this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.
The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism
Authors: Anderson Mary Ann , Deng Jing , Seymour John F. , Tam Constantine , Kim Su Young , Fein Joshua , Yu Lijian , Brown Jennifer R. , Westerman David , Si Eric G. , Majewski Ian J. , Segal David , Heitner Enschede Sari L. , Huang David C. S. , Davids Matthew S. , Letai Anthony , Roberts Andrew W. 
Published: April 2016

Key Points
Venetoclax potently induces rapid onset apoptosis of CLL cells in vitro and in vivo, independently of TP53 function. Objective responses in patients with del(17p) and/or TP53-mutated CLL are as deep as patients with no perturbation of TP53.
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
Authors: Arber Daniel A. , Orazi Attilio , Hasserjian Robert , Thiele Jürgen , Borowitz Michael J. , Le Beau Michelle M. , Bloomfield Clara D. , Cazzola Mario , Vardiman James W. 
Published: April 2016

Abstract
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.
Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)
Authors: Gnanasakthy Ari , DeMuro Carla , Clark Marci , Haydysch Emily , Ma Esprit , Bonthapally Vijayveer 
Published: April 2016

Purpose To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. Methods FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Results Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Conclusion Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.