bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression-Free Survival as a Surrogate Endpoint for Median Overall Survival in Metastatic Colorectal Cancer: Literature-Based Analysis from 50 Randomized First-Line Trials
Authors: Giessen Clemens , Laubender Ruediger Paul , Ankerst Donna Pauler , Stintzing Sebastian , Modest Dominik Paul , Mansmann Ulrich , Heinemann Volker 
Published: November 2012

Abstract
Purpose: To evaluate progression-free survival (PFS) as a potential surrogate endpoint (SEP) for overall survival (OS) in metastatic colorectal cancer (mCRC) with a focus on applicability to trials containing targeted therapy with anti-VEGF- or anti-EGF receptor (EGFR)–directed monoclonal antibodies.
Experimental Design: A systematic literature search of randomized trials of first-line chemotherapy for mCRC reported from January 2000 to January 2012 was conducted. Adjusted weighted linear regression was used to calculate correlations within PFS and OS (endpoints; REP) and between treatment effects on PFS and on OS (treatment effects; RTE).
Results: Fifty trials reflecting 22,736 patients met the inclusion criteria. Correlation between treatment effects on PFS and OS and between the endpoints PFS and OS was high across all studies (RTE = 0.87, REP = 0.86). This was also observed in chemotherapy-only trials (RTE = 0.93, REP = 0.81) but less so for trials containing monoclonal antibodies (RTE = 0.47; REP = 0.52). Limiting the analysis to bevacizumab-based studies (11 trials, 3,310 patients) again yielded high correlations between treatment effects on PFS and on OS (RTE = 0.84), whereas correlation within PFS and OS was low (REP = 0.45). In 7 trials (1,335 patients) investigating cetuximab- or panitumumab-based studies, contrasting correlations with very wide confidence intervals were observed (RTE = 0.28; REP = 0.96).
Conclusions: PFS showed consistently high correlation with OS of an order that would justify its use as an SEP in chemotherapy regimens. For validation of surrogacy in anti-VEGF and anti-EGFR–directed therapies, further research and a larger set of trials is needed. Clin Cancer Res; 19(1); 225–35. ©2012 AACR.
Bivalirudin for Primary Percutaneous Coronary Interventions
Authors: Hibbert Benjamin , MacDougall Andrea , Labinaz Marino , O’Brien Edward R. , So Derek Y.F. , Dick Alexander , Glover Christopher , Froeschl Michael , Marquis Jean-Francois , Wells George A. , Blondeau Melissa , Le May Michel R. 
Published: November 2012

Background—
Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy.

Methods and Results—

From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment–elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61–5.45,
P
<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12–2.45,
P
=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60–2.44,
P
=0.59) or the composite end point (1.05, 95% CI: 0.68–1.63,
P
=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%).

Conclusions—
Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.
Timing, Predictive Factors, and Prognostic Value of Cerebrovascular Events in a Large Cohort of Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Nombela-Franco Luis , Webb John G. , de Jaegere Peter P. , Toggweiler Stefan , Nuis Rutger-Jan , Dager Antonio E. , Amat-Santos Ignacio J. , Cheung Anson , Ye Jian , Binder Ronald K. , van der Boon Robert M. , Van Mieghem Nicolas , Benitez Luis M. , Pérez Sergio , Lopez Javier , San Roman José A. , Doyle Daniel , DeLarochellière Robert , Urena Marina , Leipsic Jonathon , Dumont Eric , Rodés-Cabau Josep 
Published: November 2012

Background—
The objective of this study was to evaluate the timing, predictive factors, and prognostic value of cerebrovascular events (CVEs) after transcatheter aortic valve implantation.

Methods and Results—
The study included 1061 consecutive patients who underwent transcatheter aortic valve implantation with a balloon-expandable (64%) or self-expandable (36%) valve. CVEs were classified as acute (≤24 hours), subacute (1–30 days), or late (>30 days). CVEs occurred in 54 patients (5.1%; stroke, 4.2%) within 30 days after transcatheter aortic valve implantation (acute in 54% of cases). The predictors of acute CVEs were balloon postdilation of the valve prosthesis (odds ratio, 2.46; 95% confidence interval,1.07–5.67) and valve dislodgment/embolization (odds ratio, 4.36; 95% CI, 1.21–15.69); new-onset atrial fibrillation (odds ratio, 2.76; 95% CI, 1.11–6.83) was a predictor of subacute CVEs. Late CVEs occurred in 35 patients (3.3%; stroke, 2.1%) at a median follow-up of 12 months (3–23 months). The predictors of late CVEs were chronic atrial fibrillation (2.84; 95% CI, 1.46–5.53), peripheral vascular disease (hazard ratio, 2.02; 95% CI, 1.02–3.97), and prior cerebrovascular disease (hazard ratio, 2.04; 95% CI, 1.01–4.15). Major stroke was associated with 30-day (odds ratio, 7.43; 95% CI, 2.45–22.53) and late (hazard ratio, 1.75; 95% CI, 1.01–3.04) mortality.

Conclusions—
In a large cohort of patients undergoing transcatheter aortic valve implantation, the rates of acute and subacute CVEs were 2.7% and 2.4%, respectively. While balloon postdilation and valve dislodgment/embolization were the predictors of acute CVEs, new-onset atrial fibrillation determined a higher risk for subacute events. Late events were determined mainly by a history of chronic atrial fibrillation and peripheral and cerebrovascular disease. The occurrence of major stroke was associated with increased early and late mortality. These results provide important insights for the implementation of preventive measures for CVEs after transcatheter aortic valve implantation.
Antithrombotic Therapy and Bleeding Risk in a Prospective Cohort Study of Patients With Cerebral Cavernous Malformations
Authors: Schneble Hans-Martin , Soumare Aicha , Hervé Dominique , Bresson Damien , Guichard Jean-Pierre , Riant Florence , Tournier-Lasserve Elisabeth , Tzourio Christophe , Chabriat Hugues , Stapf Christian 
Published: November 2012

Background and Purpose—
Cerebral cavernous malformations (CCMs) are one of the most frequently diagnosed vascular malformations of the brain and constitute a potential source of intracranial hemorrhage. In CCM patients suffering ischemic stroke or heart disease, the use of anticoagulants or antiplatelet therapy is generally avoided by fear of hemorrhagic complications, but no systematic studies exist to support this hypothesis.

Methods—
We prospectively followed-up consecutive patients with a diagnosis of one or more CCMs in a prospective database since 2008. Retrospective data collection was used for patients with a diagnostic event or imaging studies done before first assessment. Symptomatic hemorrhage and other focal neurological events during prospective follow-up were defined according to the current guidelines of the Angioma Alliance Scientific Advisory board.

Results—
A total of 87 patients were prospectively enrolled in our cohort [50 women (57%), mean age 44.8 years (SD ± 17.6), mean follow-up 3.9 years], harboring a total of 738 CCMs. Fifty-five patients (63%) had a single CCM, and 32 patients (37%) had multiple CCMs. Longitudinal follow-up included 16 (18%) patients receiving long-term antithrombotic therapy by antiplatelet treatment (n=11) or oral anticoagulants (n=5). During 5536 lesion-years of observation, none of the patients under antithrombotic therapy experienced CCM hemorrhage on follow-up.

Conclusions—
Our observational data suggest that long-term antithrombotic treatment by antiplatelet drugs or warfarin does not increase the frequency of CCM-related hemorrhage. Patients harboring single or multiple CCMs suffering ischemic stroke or heart disease should not be withheld antithrombotic therapy.
Nonvitamin-K-Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack
Authors: Ntaios George , Papavasileiou Vasileios , Diener Hans-Christoph , Makaritsis Konstantinos , Michel Patrik 
Published: November 2012

Background and Purpose—
To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin.

Methods—
We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies.

Results—
Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074–0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8–2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075–0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032–0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139).

Conclusions—
In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.
Estimating the Permafrost-Carbon Climate Response in the CMIP5 Climate Models Using a Simplified Approach
Authors: Burke Eleanor J. , Jones Chris D. , Koven Charles D. 
Published: November 2012

Abstract
Under climate change, thawing permafrost may cause a release of carbon, which has a positive feedback on the climate. The permafrost-carbon climate response (γPF) is the additional permafrost-carbon made vulnerable to decomposition per degree of global temperature increase. A simple framework was adopted to estimate γPF using the database for phase 5 of the Coupled Model Intercomparison Project (CMIP5). The projected changes in the annual maximum active layer thicknesses (ALTmax) over the twenty-first century were quantified using CMIP5 soil temperatures. These changes were combined with the observed distribution of soil organic carbon and its potential decomposability to give γPF. This estimate of γPF is dependent on the biases in the simulated present-day permafrost. This dependency was reduced by combining a reference estimate of the present-day ALTmax with an estimate of the sensitivity of ALTmax to temperature from the CMIP5 models. In this case, γPF was from −6 to −66 PgC K−1(5th–95th percentile) with a radiative forcing of 0.03–0.29 W m−2 K−1. This range is mainly caused by uncertainties in the amount of soil carbon deeper in the soil profile and whether it thaws over the time scales under consideration. These results suggest that including permafrost-carbon within climate models will lead to an increase in the positive global carbon climate feedback. Under future climate change the northern high-latitude permafrost region is expected to be a small sink of carbon. Adding the permafrost-carbon response is likely to change this region to a source of carbon.
Precipitation and Convective Characteristics of Summer Deep Convection over East Asia Observed by TRMM
Authors: Xu Weixin 
Published: November 2012

AbstractThis study examines precipitation and convective characteristics of summer deep convection for five distinct regions (plateau, foothill, lowland, south China, and ocean) in East Asia using 13 yr of Tropical Rainfall Measuring Mission (TRMM)-based precipitation features. Every region has its own unique features in terms of elevation, rainfall amount, and dynamic/thermodynamic environments. Results show that large, deep convective systems contribute the majority of precipitation totals over all regions except the plateau. Mixed-phase precipitation processes are more important in the south China and the lowland regions than in the foothill and ocean regions. The plateau region also shows substantial dependence upon mixed-phase processes, though the mixed-phase region has a smaller depth than the other regions. Most metrics indicate that the south China region has the most intense storms, followed by the lowland, plateau, foothill, and ocean regions. However, ice scattering signatures do show that the ocean region is more “intense” than the foothill and plateau regions. Deep convective systems over the plateau are the smallest and ocean systems the largest, while storms over the foothill, lowland, and south China regions are in between. Alternatively, convective intensity (storm size) in all regions strengthens (decreases) from early summer to midsummer. Both regional and intraseasonal variations in convective intensity and morphology are mainly modulated by changes in the meteorological environment, such as the convective available potential energy, height of neutral buoyancy, total water vapor, and vertical wind shear.
Magris, symbolic spaces and European identity
Authors: Epstein Mark W. 
Published: November 2012

This essay examines selected aspects of Claudio Magris’s life and work, his analysis of Mitteleuropean culture, his use of symbolic spaces and his reflection on borders, frontiers, territorialism and identity, as part of a broader set of relations between literature, values, identity, ethics, and the politics and policies of human interaction in more inclusive communities and networks. Starting from his more local and regional northern Italian identity and Bildung, the essay traces some essential paths through his research into Mitteleuropean culture, centred especially around an examination of the ‘inner’ and individual dynamics of acculturation. It then proceeds to a comparison with the sense of intellectual, Italian and European identity of another famous Germanist, finally to arrive at some of his later works, both fictional and essayistic, placing them in the context of the current institutional dynamics shaping ‘European identity’, examining some the global/‘peripheral’ forces that are most responsible for this ‘shaping’.
Readiness for Living Independently Among Emerging Adults With Type 1 Diabetes
Authors: Hanna Kathleen M. , Weaver Michael T. , Stump Timothy E. , Slaven James E. , Fortenberry J. Dennis , DiMeglio Linda A. 
Published: November 2012

Purpose The purpose of the study was to examine the association of time (high school to post-high school), living situation (independent of parents or not), diabetes-specific self-efficacy, and worry about hypoglycemia and how diabetes-specific self-efficacy and worry about hypoglycemia are associated with diabetes management among emerging adults with type 1 diabetes. Methods Participants (N = 114) completed measures on diabetes management, diabetes-specific self-efficacy, and worry about hypoglycemia during the last 6 months in high school (T1) and diabetes management, diabetes-specific self-efficacy, and living situation post-high school (T2). General linear mixed model for the diabetes management outcome was used to test associations with diabetes-specific self-efficacy, worry about hypoglycemia, time, and living situation independent variables. Moderation by diabetes-specific self-efficacy and worry about hypoglycemia was also tested. Results Diabetes management increased from high school to post-high school but was not significantly associated with living situation (independent of parents or not). Diabetes management was better for youth with greater diabetes-specific self-efficacy. However, neither diabetes-specific self-efficacy nor worry about hypoglycemia moderated the relationship between diabetes management and time or between diabetes management and living situation. Conclusions Diabetes management improved over time for these emerging adults with type 1 diabetes. Diabetes-specific self-efficacy is important for diabetes management regardless of whether youth are in high school or post-high school and whether living with parents or not.
Transforming Community Members Into Diabetes Cultural Health Brokers
Authors: Cadzow Renee B. , Craig Mary , Rowe Jimmy , Kahn Linda S. 
Published: November 2012

Purpose The purpose of this study was to evaluate a community-based diabetes education pilot project. The Neighborhood Health Talker project aimed to train and implement cultural health brokers primarily targeting communities of color to improve community members’ diabetes knowledge and diabetes self-management skills. A secondary aim was to establish diabetes resource libraries accessible to communities that normally experience barriers to these resources. Methods Recruited community members completed 1 week of formal training developed by a multidisciplinary team in Buffalo, NY. The effect of training was evaluated through the use of baseline surveys, a pretest/posttest covering all training content, and daily quizzes evaluating knowledge relevant to each of the five training modules. Trained NHTs then held at least five community conversations in various locations and administered anonymous postconversation surveys to participants. Descriptive statistics and qualitative analysis techniques were used to summarize test, quiz, and survey results. Results Twelve women and 1 man completed the training program. Working alone as well as in pairs, each held at least five community conversations reaching over 700 community members of all ages over 3 months and established 8 diabetes resource libraries in the community. All trainees increased their diabetes knowledge and confidence as well as their abilities to perform the tasks of a cultural health broker. Trainees also indicated that the goals they set at training initiation were met. Conclusions The training was successful in increasing trainee knowledge and confidence about diabetes prevention and self-management. Participants not only developed proficiency in discussing diabetes, they also made important lifestyle changes that demonstrated their commitment to the cause and the project. Low-cost initiatives like this are easily reproducible in other communities of color and could be modified to meet the needs of other communities as well.
Developing and Piloting the Journey to Native Youth Health Program in Northern Plains Indian Communities
Authors: Brown Blakely , Noonan Curtis , Harris Kari Jo , Parker Martin , Gaskill Steven , Ricci Christiana , Cobbs Georgia , Gress Shannon 
Published: November 2012

Purpose The purpose of this study was to develop a lifestyle change program for Native American youth by modifying the Diabetes Prevention Program (DPP) and assess implementation indicators and short term behavioral and physiological outcomes of the intervention among a small pilot sample. Methods Community members and project staff modified the original DPP to be developmentally and culturally appropriate for youth targeting healthy weight maintenance, lowering fat intake, and increasing physical activity. Modifications included incorporating cultural aspects and delivering the program in small groups led by community members. Sixty-four Native American youth, aged 10-14 years old were recruited from 2 Montana Indian reservations to participate in the project, titled “Journey to Native Youth Health.” Participants were randomized to the Journey DPP or a health-oriented comparison condition. Pretest and posttest measures included body mass index (BMI), dietary intake, physical activity (PA), and nutrition knowledge, attitudes and beliefs (KAB). Results The target number of participants was recruited and 84% completed the program and final measures. Changes favoring the Journey DPP group were observed on measures of PA, KAB, and kilocalories from fat consumed. As expected given the short (3-month) duration of treatment, there was no overall effect on BMI at end of treatment. Among youth who were overweight or obese at baseline, however, the Journey DPP had lower BMI growth. Conclusions Results suggest the Journey DPP is feasible to implement and has the potential to impact behaviors and weight gain associated with risk for type-2 diabetes in Native American youth.
Screening for severe physical inactivity in chronic obstructive pulmonary disease
Authors: DePew Zachary S. , Garofoli Adrian C. , Novotny Paul J. , Benzo Roberto P. 
Published: November 2012

Objectively measured severe physical inactivity (SPI) has been reported as the strongest independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Activity monitoring is not feasible in routine clinical practice; therefore, we set out to determine the utility of simple clinical measures for predicting SPI in patients with COPD. A total of 165 patients with COPD wore an activity monitor for 5 days to define the presence or absence of SPI. Logistic models were generated including the modified Medical Research Council (MMRC) dyspnea grade, spirometry and the age–dyspnea–airflow obstruction (ADO) index. Physical Activity Scale for the Elderly (PASE) and Stanford Brief Activity Scale (SBAS) were also tested for validity and reliability in a subgroup of 67 patients. The MMRC dyspnea grade, PASE score, ADO index and SBAS score were associated with SPI, but general self-efficacy and spirometry were not. An MMRC dyspnea grade ≥3 was the best independent predictor of SPI (AUC: 0.74; PPV: 0.83; NPV: 0.68) followed closely by a PASE score of <111. The combination of MMRC dyspnea grade and PASE score provided the most robust model (AUC: 0.83; Positive Predictive Value (PPV): 0.95; Negative Predictive Value (NPV): 0.63). The results were confirmed using 5000 bootstrapped models from the cohort of 165 patients. MMRC dyspnea grade ≥3 may be the best triage tool for SPI in patients with COPD. The combination of the MMRC and PASE score provided the most robust prediction. Our results may have significant practical applicability for clinicians caring for patients with COPD.