bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems Strategies to Support Cancer Screening in U.S. Primary Care Practice
Authors: Yabroff K. Robin , Zapka Jane , Klabunde Carrie N. , Yuan Gigi , Buckman Dennis W. , Haggstrom David , Clauser Steven B. , Miller Jacqueline , Taplin Stephen H. 
Published: December 2011

Abstract
Background: Although systems strategies are effective in improving health care delivery, little is known about their use for cancer screening in U.S. primary care practice.
Methods: We assessed primary care physicians' (N = 2,475) use of systems strategies for breast, cervical, and colorectal cancer (CRC) screening in a national survey conducted in 2007. Systems strategies included patient and physician screening reminders, performance reports of screening rates, electronic medical records, implementation of in-practice guidelines, and use of nurse practitioners/physician assistants. We evaluated use of both patient and physician screening reminders with other strategies in separate models by screening type, adjusted for the effects of physician and practice characteristics with multivariate logistic regression.
Results: Fewer than 10% of physicians used a comprehensive set of systems strategies to support cancer screening; use was greater for mammography and Pap testing than for CRC screening. In adjusted analyses, performance reports of cancer screening rates, medical record type, and in-practice guidelines were associated with use of both patient and physician screening reminders for mammography, Pap testing, and CRC screening (P &lt; 0.05).
Conclusion: Despite evidence supporting use of systems strategies in primary care, few physicians report using a comprehensive set of strategies to support cancer screening.
Impact: Current health policy initiatives underscore the importance of increased implementation of systems strategies in primary care to improve the use and quality of cancer screening in the United States. Cancer Epidemiol Biomarkers Prev; 20(12); 2471–9. ©2011 AACR.
A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction
Authors: Le Dung T. , Brockstedt Dirk G. , Nir-Paz Ran , Hampl Johannes , Mathur Shruti , Nemunaitis John , Sterman Daniel H. , Hassan Raffit , Lutz Eric , Moyer Bentley , Giedlin Martin , Louis Jana-Lynn , Sugar Elizabeth A. , Pons Alice , Cox Andrea L. , Levine Jordana , Murphy Aimee Luck , Illei Peter , Dubensky Thomas W. , Eiden Joseph E. , Jaffee Elizabeth M. , Laheru Daniel A. 
Published: December 2011

AbstractPurpose: Listeria monocytogenes (Lm)-based vaccines stimulate both innate and adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm ΔactA/ΔinlB). Uptake by phagocytes in the liver results in local inflammatory responses and activation and recruitment of natural killer (NK) and T cells, in association with increased survival of mice bearing hepatic metastases. The Lm ΔactA/ΔinlB strain, engineered to express human mesothelin (CRS-207), a tumor-associated antigen expressed by a variety of tumors, induces mesothelin-specific T-cell responses against mesothelin-expressing murine tumors. These two phase I studies test ANZ-100 and CRS-207 in subjects with liver metastases and mesothelin-expressing cancers, respectively.Experimental Design: A single intravenous injection of ANZ-100 was evaluated in a dose escalation study in subjects with liver metastases. Nine subjects received 1 × 106, 3 × 107, or 3 × 108 colony-forming units (cfu). CRS-207 was evaluated in a dose-escalation study in subjects with mesothelioma, lung, pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 × 108, 3 × 108, 1 × 109, or 1 × 1010 cfu.Results: A single infusion of ANZ-100 was well tolerated to the maximum planned dose. Adverse events included transient laboratory abnormalities and symptoms associated with cytokine release. Multiple infusions of CRS-207 were well tolerated up to 1 × 109 cfu, the determined maximum tolerated dose. Immune activation was observed for both ANZ-100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell responses were detected and 37% of subjects lived ≥15 months.Conclusions: ANZ-100 and CRS-207 administration was safe and resulted in immune activation. Clin Cancer Res; 18(3); 858–68. ©2011 AACR.
Predictive and Prognostic Roles ofBRAFMutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803
Authors: Ogino Shuji , Shima Kaori , Meyerhardt Jeffrey A. , McCleary Nadine J. , Ng Kimmie , Hollis Donna , Saltz Leonard B. , Mayer Robert J. , Schaefer Paul , Whittom Renaud , Hantel Alexander , Benson Al B. , Spiegelman Donna , Goldberg Richard M. , Bertagnolli Monica M. , Fuchs Charles S. 
Published: December 2011

AbstractPurpose: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer.Methods: We assessed status of BRAF c.1799T&gt;A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI status.Results: Compared with 431 BRAF wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank P = 0.015; multivariate HR = 1.66; 95% CI: 1.05–2.63]. By assessing combined status of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR = 0.52; 95% CI: 0.25–1.10). Among patients with BRAF wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02; 95% CI: 0.72–1.46).Conclusions: BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy. Clin Cancer Res; 18(3); 890–900. ©2011 AACR.
Molecular and Cellular Pharmacology of the Hypoxia-Activated Prodrug TH-302
Authors: Meng Fanying , Evans James W. , Bhupathi Deepthi , Banica Monica , Lan Leslie , Lorente Gustavo , Duan Jian-Xin , Cai Xiaohong , Mowday Alexandra M. , Guise Christopher P. , Maroz Andrej , Anderson Robert F. , Patterson Adam V. , Stachelek Gregory C. , Glazer Peter M. , Matteucci Mark D. , Hart Charles P. 
Published: December 2011

Abstract
TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo-isophosphoramide mustard currently undergoing clinical evaluation. Here, we describe broad-spectrum activity, hypoxia-selective activation, and mechanism of action of TH-302. The concentration and time dependence of TH-302 activation was examined as a function of oxygen concentration, with reference to the prototypic HAP tirapazamine, and showed superior oxygen inhibition of cytotoxicity and much improved dose potency relative to tirapazamine. Enhanced TH-302 cytotoxicity under hypoxia was observed across 32 human cancer cell lines. One-electron reductive enzyme dependence was confirmed using cells overexpressing human NADPH:cytochrome P450 oxidoreductase and radiolytic reduction established the single-electron stoichiometry of TH-302 fragmentation (activation). Examining downstream effects of TH-302 activity, we observed hypoxia-dependent induction of γH2AX phosphorylation, DNA cross-linking, and cell-cycle arrest. We used Chinese hamster ovary cell–based DNA repair mutant cell lines and established that lines deficient in homology-dependent repair, but not lines deficient in base excision, nucleotide excision, or nonhomologous end-joining repair, exhibited marked sensitivity to TH-302 under hypoxia. Consistent with this finding, enhanced sensitivity to TH-302 was also observed in lines deficient in BRCA1, BRCA2, and FANCA. Finally, we characterized TH-302 activity in the three-dimensional tumor spheroid and multicellular layer models. TH-302 showed much enhanced potency in H460 spheroids compared with H460 monolayer cells under normoxia. Multicellular layers composed of mixtures of parental HCT116 cells and HCT116 cells engineered to express an oxygen-insensitive bacterial nitroreductase showed that TH-302 exhibits a significant bystander effect. Mol Cancer Ther; 11(3); 740–51. ©2011 AACR.
Variation in the Use of Lower Extremity Vascular Procedures for Critical Limb Ischemia
Authors: Goodney Philip P. , Travis Lori L. , Nallamothu Brahmajee K. , Holman Kerianne , Suckow Bjoern , Henke Peter K. , Lee Lucas F. , Goodman David C. , Birkmeyer John D. , Fisher Elliott S. 
Published: December 2011

Background—
Many believe that variation in vascular practice may affect limb salvage rates in patients with severe peripheral arterial disease. However, the extent of variation in procedural vascular care obtained by patients with critical limb ischemia (CLI) remains unknown.

Methods and Results—

By using Medicare 2003 to 2006 data, we identified all patients with CLI who underwent major lower extremity amputation in the 306 hospital referral regions described in the Dartmouth Atlas of Healthcare. For each patient, we studied the use of lower extremity vascular procedures (open surgery or endovascular intervention) in the year before amputation. Our main outcome measure was the
intensity of
vascular care
, defined as the proportion of patients in the hospital referral region undergoing a vascular procedure in the year before amputation. Overall, 20 464 patients with CLI underwent major lower extremity amputations during the study period, and collectively underwent 25 800 vascular procedures in the year before undergoing amputation. However, these procedures were not distributed evenly: 54% of patients had no vascular procedures performed in the year before amputation, 14% underwent 1 vascular procedure, and 32% underwent >1 vascular procedure. In the regions in the lowest quintile of vascular intensity, vascular procedures were performed in 32% of patients. Conversely, in the regions in the highest quintile of vascular intensity, revascularization was performed in 58% of patients in the year before amputation (
P
<0.0001). In analyses accounting for differences in age, sex, race, and comorbidities, patients in high-intensity regions were 2.4 times as likely to undergo revascularization in the year before amputation than patients in low-intensity regions (adjusted odds ratio, 2.4; 95% CI, 2.1–2.6;
P
<0.001).

Conclusions—
Significant variation exists in the intensity of vascular care provided to patients in the year before major amputation. In some regions, patients receive intensive care, whereas in other regions, far less vascular care is provided. Future work is needed to determine the association between intensity of vascular care and limb salvage.
Introduction of the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Costing Tool
Authors: Reed Shelby D. , Li Yanhong , Kamble Shital , Polsky Daniel , Graham Felicia L. , Bowers Margaret T. , Samsa Gregory P. , Paul Sara , Schulman Kevin A. , Whellan David J. , Riegel Barbara J. 
Published: December 2011

Background—
Patient-centered health care interventions, such as heart failure disease management programs, are under increasing pressure to demonstrate good value. Variability in costing methods and assumptions in economic evaluations of such interventions limit the comparability of cost estimates across studies. Valid cost estimation is critical to conducting economic evaluations and for program budgeting and reimbursement negotiations.

Methods and Results—
Using sound economic principles, we developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure (TEAM-HF) Costing Tool, a spreadsheet program that can be used by researchers and health care managers to systematically generate cost estimates for economic evaluations and to inform budgetary decisions. The tool guides users on data collection and cost assignment for associated personnel, facilities, equipment, supplies, patient incentives, miscellaneous items, and start-up activities. The tool generates estimates of total program costs, cost per patient, and cost per week and presents results using both standardized and customized unit costs for side-by-side comparisons. Results from pilot testing indicated that the tool was well-formatted, easy to use, and followed a logical order. Cost estimates of a 12-week exercise training program in patients with heart failure were generated with the costing tool and were found to be consistent with estimates published in a recent study.

Conclusions—
The TEAM-HF Costing Tool could prove to be a valuable resource for researchers and health care managers to generate comprehensive cost estimates of patient-centered interventions in heart failure or other conditions for conducting high-quality economic evaluations and making well-informed health care management decisions.
Notch Activation of Jagged1 Contributes to the Assembly of the Arterial Wall
Authors: Manderfield Lauren J. , High Frances A. , Engleka Kurt A. , Liu Feiyan , Li Li , Rentschler Stacey , Epstein Jonathan A. 
Published: December 2011

Background—
Notch signaling in vascular smooth muscle precursors is required for smooth muscle differentiation. Jagged1 expression on endothelium activates Notch in vascular smooth muscle precursors including those of neural crest origin to initiate the formation of a smooth muscle layer in a maturing blood vessel.

Methods and Results—

Here, we show that
Jagged1
is a direct Notch target in smooth muscle, resulting in a positive feedback loop and lateral induction that propagates a wave of smooth muscle differentiation during aortic arch artery development. In vivo, we show that Notch inhibition in cardiac neural crest impairs
Jagged1
messenger RNA expression and results in deficient smooth muscle differentiation and resultant aortic arch artery defects. Ex vivo, Jagged1 ligand activates Notch in neural crest explants and results in activation of
Jagged1
messenger RNA, a response that is blocked by Notch inhibition. We examine 15 evolutionary conserved regions within the
Jagged1
genomic locus and identify a single Notch response element within the second intron. This element contains a functional Rbp-J binding site demonstrated by luciferase reporter and chromatin immunoprecipitation assays and is sufficient to recapitulate aortic arch artery expression of
Jagged1
in transgenic mice. Loss of Jagged1 in neural crest impairs vascular smooth muscle differentiation and results in aortic arch artery defects.

Conclusions—

Taken together, these results provide a mechanism for lateral induction that allows for a multilayered smooth muscle wall to form around a nascent arterial endothelial tube and identify
Jagged1
as a direct Notch target.
Self-Monitoring of Blood Glucose
Authors: Hortensius Johanna , van der Bijl Jaap J. , Kleefstra Nanne , Houweling Sebatiaan T. , Bilo Henk J. G. 
Published: December 2011

Purpose This study investigated the advice given by diabetes educators in Europe, and the daily practice of Dutch patients with diabetes regarding the use of the first or second drop of blood and other aspects concerning self-monitoring of blood glucose (SMBG). Method During a diabetes conference in 2009, 96 European diabetes educators (including 46 Dutch educators) completed a single-item questionnaire about the use of the first or second drop of blood for glucose monitoring. A self-reported questionnaire with 20 questions about performing SMBG was filled out by 111 patients from an outpatient diabetes clinic of a Dutch hospital. Results Patients were advised to wash their hands with water and soap and use the first drop of blood by 89% of the Dutch and 72% of other European diabetes educators, while 58% of the patients reported to do this. When the patient cannot wash the hands, 85% of the Dutch and 52% of the other European educators advised to use the second drop of blood, while 26% of the patients reported always using the first drop without washing hands. Always using the side of the fingertip and using the lancet once, as advised in guidelines, was reported by only 41% and 55% of the patients, respectively. Conclusions There is no general agreement between professionals regarding the advice on aspects concerning SMBG. Patients also reported different acts in daily practice. Developing uniform international SMBG guidelines, education, and repeated evaluation of the process of collecting an accurate blood sample are needed.
Robot-assisted gait training in multiple sclerosis patients: a randomized trial
Authors: Schwartz Isabella , Sajin Anna , Moreh Elior , Fisher Iris , Neeb Martin , Forest Adina , Vaknin-Dembinsky Adi , Karusis Dimitrios , Meiner Zeev 
Published: December 2011

Background: Preservation of locomotor activity in multiple sclerosis (MS) patients is of utmost importance. Robotic-assisted body weight-supported treadmill training is a promising method to improve gait functions in neurologically impaired patients, although its effectiveness in MS patients is still unknown. Objective: To compare the effectiveness of robot-assisted gait training (RAGT) with that of conventional walking treatment (CWT) on gait and generalized functions in a group of stable MS patients. Methods: A prospective randomized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS score 5–7. Primary outcome measures were gait parameters and the secondary outcomes were functional and quality of life parameters. All tests were performed at baseline, 3 and 6 months post-treatment by a blinded rater. Results: Fifteen and 17 patients were randomly allocated to RAGT and CWT, respectively. Both groups were comparable at baseline in all parameters. As compared with baseline, although some gait parameters improved significantly following the treatment at each time point there was no difference between the groups. Both FIM and EDSS scores improved significantly post-treatment with no difference between the groups. At 6 months, most gait and functional parameters had returned to baseline. Conclusions: Robot-assisted gait training is feasible and safe and may be an effective additional therapeutic option in MS patients with severe walking disabilities.
Perceived social support and coping strategies in advanced cancer patients
Authors: Zabalegui Adelaida , Cabrera Esther , Navarro Montserrat , Cebria María Isabel 
Published: December 2011

Background: Cancer patients who perceived themselves as having adequate social support resources fare better and make adaptation easier than patients who perceive their support as inadequate. Besides, the levels of social support can have an important impact on patient's ways of coping when confronting the challenge of advanced cancer. Objective: To analyze the relationships among demographic and medical variables, perceived social support, and coping strategies in patients with advanced cancer. Methods: A descriptive correlational study was performed in 132 advanced cancer patients under chemotherapy treatment. The participants were asked to provide their demographic data and complete the questionnaires of Personal Resource Questionnaire-85 that measure perceived social support and Ways of Coping Inventory – Cancer version that measure coping strategies. Besides, medical data was obtained from participants’ hospital records. The data was analyzed using SPSS statistical package. Results: This study has contributed to a better understanding of the theoretical linkages among perceived social support and coping mechanisms in advanced cancer patients. The results showed that there was a significant moderate positive relationship between perceived social support and seeking and using social support, and focusing on the positive. Also, there was a significant positive relationship between perceived social support, income, and health perception. Discussion: The findings indicate that in advanced cancer there is a need to monitorize patients with low levels of perceived social support and enhance their social support resources, particularly in men.
Using the Biology of Chronic Lymphocytic Leukemia to Choose Treatment
Authors: Hillmen Peter 
Published: December 2011

AbstractIn recent years, our understanding of the pathophysiology of chronic lymphocytic leukemia (CLL) has advanced significantly. It is now clear that CLL is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the CLL cell occurs in most, if not all, patients through antigen stimulation via the BCR. In addition, there is now a clearer appreciation of the role of the p53 pathway leading to chemoresistance. These insights are allowing a more targeted approach with the use of p53-independent drugs such as mAbs and high-dose steroids to overcome genetically poor-risk CLL. The elucidation of the molecular and intracellular signaling mechanisms of disease is just beginning to facilitate the development of several targeted small molecules that promise to revolutionize the treatment of CLL. The measurement of the level of minimal residual disease (MRD) in CLL is becoming more available, facilitating approaches in which the aim of therapy is the eradication of detectable MRD. This also promises to improve personalization of therapy to the individual. Recently, the addition of rituximab to fludarabine plus cyclophosphamide (FCR) has improved overall survival in CLL for the first time, and it appears that this will only be the first small step on the path to much more effective therapies and, hopefully, less toxic targeted therapies.
Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: Approach to Patients with Treatment-Naive or Refractory Chronic-Phase Disease
Authors: Smith Catherine C. , Shah Neil P. 
Published: December 2011

Abstract
The 21st century ushered in the dawn of a new era of targeted therapeutics and a dramatic shift in the management of chronic-phase chronic myeloid leukemia (CP-CML) patients. Groundbreaking scientific and translational studies have led to the rapid development and approval of several effective BCR-ABL tyrosine kinase inhibitors (TKIs). In the United States, there are currently 3 approved BCR-ABL TKIs for newly diagnosed CP-CML patients. It is anticipated that clinical outcomes will continue to improve as more TKIs that address unmet medical needs are approved. However, to achieve this goal, it is critical to carefully monitor and optimally manage patients. To this end, the latest seminal clinical trial results of approved and investigational BCR-ABL TKIs and some of the salient unique features of each of these agents are summarized herein.