bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustainability of knowledge translation interventions in healthcare decision-making: protocol for a scoping review
Authors: Tricco Andrea C , Cogo Elise , Ashoor Huda , Perrier Laure , McKibbon K Ann , Grimshaw Jeremy M , Straus Sharon E 
Published: May 2013

IntroductionKnowledge translation (KT also known as research utilisation, translational medicine and implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange and ethically sound application of knowledge to improve health. After the implementation of KT interventions, their impact on relevant outcomes should be monitored. The objectives of this scoping review are to: (1) conduct a systematic search of the literature to identify the impact on healthcare outcomes beyond 1 year, or beyond the termination of funding of the initiative of KT interventions targeting chronic disease management for end-users including patients, clinicians, public health officials, health services managers and policy-makers; (2) identify factors that influence sustainability of effective KT interventions; (3) identify how sustained change from KT interventions should be measured; and (4) develop a framework for assessing sustainability of KT interventions.Methods and analysisComprehensive searches of relevant electronic databases (eg, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of funding agencies and websites of healthcare provider organisations will be conducted to identify relevant material. We will include experimental, quasi-experimental and observational studies providing information on the sustainability of KT interventions targeting chronic disease management in adults and focusing on end-users including patients, clinicians, public health officials, health services managers and policy-makers. Two reviewers will pilot-test the screening criteria and data abstraction form. They will then screen all citations, full articles and abstract data in duplicate independently. The results of the scoping review will be synthesised descriptively and used to develop a framework to assess the sustainability of KT interventions.Discussion and disseminationOur results will help inform end-users (ie, patients, clinicians, public health officials, health services managers and policy-makers) regarding the sustainability of KT interventions. Our dissemination plan includes publications, presentations, website posting and a stakeholder meeting.
The Patient-Reported Incident in Hospital Instrument (PRIH-I): assessments of data quality, test–retest reliability and hospital-level reliability
Authors: Bjertnaes Oyvind , Skudal Kjersti Eeg , Iversen Hilde Hestad , Lindahl Anne Karin 
Published: May 2013

BackgroundThe objective of this study was to test the data quality, test–retest reliability and hospital-level reliability of the Patient-Reported Incident in Hospital Instrument (PRIH-I).Methods13 incident questions were included in a national patient-experience survey in Norway during the spring of 2011. All questions and a composite incident index were assessed by calculating missing-item rates, test–retest reliability and hospital-level reliability. A multivariate linear regression on a global item regarding incorrect treatment was used to assess the main sources of variation in patient-perceived incorrect treatment at hospitals.ResultsFive of the 13 patient-incident questions had a missing-item rate of >20%. Only one item met the criterion of 0.7 for test–retest reliability (wrong or delayed diagnosis), seven items had a score of >0.5, while the remainder had a reliability score of <0.5. However, the reliability was >0.7 for six of 10 items tested at the hospital level, and >0.6 for the remaining four items. A patient-incident index based on 12 of the incident items had no missing data, the test–retest reliability was 0.6 and the hospital-level reliability was 0.85.ConclusionsThe PRIH-I comprises 13 questions about patient-perceived incidents in hospitals, and can be easily and cost-effectively included in national patient-experience surveys with an acceptable increase in respondent burden. Although the missing-item rate and test–retest reliability were poor for several items, the hospital-level reliability was satisfactory for most of the items. The incident items contribute to a patient-reported incident index, with excellent data quality and hospital-level reliability.
Stable isotopes of organics and inorganics, clay mineralogy and chemical environment of an Aptian lacustrine succession in northeastern Brazil
Authors: Gratzer Reinhard , Neumann Virgínio Henrique , Vortisch Walter , Rocha Dunaldson E. A. , Bechtel Achim 
Published: May 2013

Abstract

The studied Aptian lacustrine succession of the continental Jatobá Rift Basin varies mainly between pure carbonates (predominantly laminated limestones), marls and shales, with some intercalations of presumably deltaic sandstone complexes. In accordance with geochemical data, the occurrence of dolomite indicates intensive microbial activity in a stratified water column with slightly enhanced salinity. Petrographic data prove mild weathering conditions. Aggregates of authigenic smectite observed in sandstones, probably representing transformed volcanogenic glass particles, strongly indicate explosive volcanic activity. Occasionally occurring dolomite seems to have been formed due to intensive microbial activity under moderately increased salinity conditions. Potential hydrocarbon source rocks containing Type I organic matter (OM) were deposited during various phases of the Aptian. Enhanced biological productivity is indicated by bulk organic geochemical data (C
org
, hydrogen index, extraction yield) and δ
13
C values of carbonates within peletoidal and laminated limestone layers. Carbon-isotope ratios of carbonates argue for OM cycling and remineralization. High δ
18
O values of carbonates are attributed to periods of lower lake levels. A major contribution of aquatic organisms (green algae, microalgae, zooplankton) and minor input from macrophytes and land plants to OM accumulation is indicated by
n
-alkane distributions, steroid composition and δ
13
C values of individual biomarkers. Microbial communities included heterotrophic bacteria and cyanobacteria, as well as purple and green sulphur bacteria. The sediments were deposited in an alkaline palaeolake. Highly reducing (saline) bottom water conditions and a stratified water column existed during OM accumulation of the Crato Formation. This is indicated by low pristane/phytane, gammacerane index, and the presence of β-carotane and aryl isoprenoids. Differences in OM composition and stable isotope data reflect the evolution of the basin from a stratified saline lake to a freshwater environment with limited potential for OM preservation.
Therapeutic Enhancement of ER Stress by Insulin-Like Growth Factor I Sensitizes Myeloma Cells to Proteasomal Inhibitors
Authors: Tagoug Inès , Jordheim Lars Petter , Herveau Stéphanie , Matera Eva-Laure , Huber Anne-Laure , Chettab Kamel , Manié Serge , Dumontet Charles 
Published: May 2013

Abstract
Purpose: Multiple myeloma is a clonal plasma cell disorder in which growth and proliferation are linked to a variety of growth factors, including insulin-like growth factor type I (IGF-I). Bortezomib, the first-in-class proteasome inhibitor, has displayed significant antitumor activity in multiple myeloma.
Experimental Design: We analyzed the impact of IGF-I combined with proteasome inhibitors on multiple myeloma cell lines in vivo and in vitro as well as on fresh human myeloma cells.
Results: Our study shows that IGF-I enhances the cytotoxic effect of proteasome inhibitors against myeloma cells. The effect of bortezomib on the content of proapoptotic proteins such as Bax, Bad, Bak, and BimS and antiapoptotic proteins such as Bcl-2, Bcl-XL, XIAP, Bfl-1, and survivin was enhanced by IGF-I. The addition of IGF-I to bortezomib had a minor effect on NF-κB signaling in MM.1S cells while strongly enhancing reticulum stress. This resulted in an unfolded protein response (UPR), which was required for the potentiating effect of IGF-I on bortezomib cytotoxicity as shown by siRNA-mediated inhibition of GADD153 expression.
Conclusions: These results suggest that the high baseline level of protein synthesis in myeloma can be exploited therapeutically by combining proteasome inhibitors with IGF-I, which possesses a “priming” effect on myeloma cells for this family of compounds. Clin Cancer Res; 19(13); 3556–66. ©2013 AACR.
PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies
Authors: Chen Benjamin J. , Chapuy Bjoern , Ouyang Jing , Sun Heather H. , Roemer Margaretha G.M. , Xu Mina L. , Yu Hongbo , Fletcher Christopher D.M. , Freeman Gordon J. , Shipp Margaret A. , Rodig Scott J. 
Published: May 2013

Abstract
Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed–Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors.
Experimental Design: Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1.
Results: Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1.
Conclusion: Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies. Clin Cancer Res; 19(13); 3462–73. ©2013 AACR.
Targeting 6-Phosphofructo-2-Kinase (PFKFB3) as a Therapeutic Strategy against Cancer
Authors: Clem Brian F. , O'Neal Julie , Tapolsky Gilles , Clem Amy L. , Imbert-Fernandez Yoannis , Kerr Daniel A. , Klarer Alden C. , Redman Rebecca , Miller Donald M. , Trent John O. , Telang Sucheta , Chesney Jason 
Published: May 2013

Abstract
In human cancers, loss of PTEN, stabilization of hypoxia inducible factor-1α, and activation of Ras and AKT converge to increase the activity of a key regulator of glycolysis, 6-phosphofructo-2-kinase (PFKFB3). This enzyme synthesizes fructose 2,6-bisphosphate (F26BP), which is an activator of 6-phosphofructo-1-kinase, a key step of glycolysis. Previously, a weak competitive inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), was found to reduce the glucose metabolism and proliferation of cancer cells. We have synthesized 73 derivatives of 3PO and screened each compound for activity against recombinant PFKFB3. One small molecule, 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15), was selected for further preclinical evaluation of its pharmacokinetic, antimetabolic, and antineoplastic properties in vitro and in vivo. We found that PFK15 causes a rapid induction of apoptosis in transformed cells, has adequate pharmacokinetic properties, suppresses the glucose uptake and growth of Lewis lung carcinomas in syngeneic mice, and yields antitumor effects in three human xenograft models of cancer in athymic mice that are comparable to U.S. Food and Drug Administration–approved chemotherapeutic agents. As a result of this study, a synthetic derivative and formulation of PFK15 has undergone investigational new drug (IND)-enabling toxicology and safety studies. A phase I clinical trial of its efficacy in advanced cancer patients will initiate in 2013 and we anticipate that this new class of antimetabolic agents will yield acceptable therapeutic indices and prove to be synergistic with agents that disrupt neoplastic signaling. Mol Cancer Ther; 12(8); 1461–70. ©2013 AACR.
Individual and Community Determinants of Calling 911 for Stroke Among African Americans in an Urban Community
Authors: Skolarus Lesli E. , Murphy Jillian B. , Zimmerman Marc A. , Bailey Sarah , Fowlkes Sophronia , Brown Devin L. , Lisabeth Lynda D. , Greenberg Emily , Morgenstern Lewis B. 
Published: May 2013

Background—
African Americans receive acute stroke treatment less often than non-Hispanic whites. Interventions to increase stroke preparedness (recognizing stroke warning signs and calling 911) may decrease the devastating effects of stroke by allowing more patients to be candidates for acute stroke therapy. In preparation for such an intervention, we used a community-based participatory research approach to conduct a qualitative study exploring perceptions of emergency medical care and stroke among urban African American youth and adults.

Methods and Results—
Community partners, church health teams, and church leaders identified and recruited focus group participants from 3 black churches in Flint, MI. We conducted 5 youth (11–16 years) and 4 adult focus groups from November 2011 to March 2012. A content analysis approach was taken for analysis. Thirty-nine youth and 38 adults participated. Women comprised 64% of youth and 90% of adult focus group participants. All participants were black. Three themes emerged from the adult and youth data: (1) recognition that stroke is a medical emergency; (2) perceptions of difficulties within the medical system in an under-resourced community, and; (3) need for greater stroke education in the community.

Conclusions—
Black adults and youth have a strong interest in stroke preparedness. Designs of behavioral interventions to increase stroke preparedness should be sensitive to both individual and community factors contributing to the likelihood of seeking emergency care for stroke.
Mortality in Medicare Patients Undergoing Elective Percutaneous Coronary Intervention With or Without Antecedent Stress Testing
Authors: Lin Grace A. , Lucas F. Lee , Malenka David J. , Skinner Jonathan , Redberg Rita F. 
Published: May 2013

Background—
Guidelines advise testing for ischemia, such as with stress testing, before elective percutaneous coronary intervention (PCI). However, pre-PCI stress testing is not always done; the implications of this practice are not known. Our objective was to evaluate whether receipt of stress testing before elective PCI predicts mortality.

Methods and Results—
Using claims data from a 20% random sample of Medicare beneficiaries, we identified patients who had elective PCI in 2004 and followed them for a median of 3.4 years (n=23 887). Cox proportional hazards models were used to test the relationship of pre-PCI stress testing to survival. Population-based rates of elective PCI and stress testing were calculated for 306 hospital referral regions and categorized into 4 groups: high stress test/high PCI, low stress test/low PCI, low stress test/high PCI, and high stress/low PCI regions. Cox modeling was used to test whether category of hospital referral regions is related to survival. Patients who underwent pre-PCI stress testing had a 13% lower risk of mortality than those who did not (adjusted hazard ratio, 0.87; 95% confidence interval, 0.81–0.92) after median follow-up of 3.4 years. Patients in low stress test/high PCI regions had a 14% higher risk of mortality than those in high stress test/high PCI regions (adjusted hazard ratio, 1.14; 95% confidence interval, 1.03–1.26).

Conclusions—
Pre-PCI stress testing is associated with lower mortality in patients undergoing elective PCI. Greater adherence to guidelines with respect to documenting ischemia before elective PCI may result in improved outcomes for patients.
High-Dose Statin Therapy in Patients With Stable Coronary Artery Disease
Authors: Dorresteijn Johannes A.N. , Boekholdt S. Matthijs , van der Graaf Yolanda , Kastelein John J.P. , LaRosa John C. , Pedersen Terje R. , DeMicco David A. , Ridker Paul M , Cook Nancy R. , Visseren Frank L.J. 
Published: May 2013

Background—
Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients in terms of reduction of 5-year absolute risk for myocardial infarction, stroke, coronary death, or cardiac resuscitation.

Methods and Results—
Based on data from the Treating to New Targets trial (TNT; n=10 001), a Cox proportional hazards model was developed comprising 13 easy-to-measure clinical predictors: age, sex, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, history of myocardial infarction, coronary artery bypass grafting, congestive heart failure or abdominal aortic aneurysm, glomerular filtration rate, and treatment status (ie, atorvastatin 80 mg or 10 mg). External validation in the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial (IDEAL; n=8888) confirmed adequate goodness-of-fit and calibration, but moderate discrimination (C-statistic, 0.63; 95% confidence interval, 0.62–0.65). Still, among participants of both trials combined, the model identified a group of 11.7% whose predicted 5-year number needed to treat was ≤25 and a group of 41.9% whose predicted needed to treat was ≥50. A decision curve shows that making treatment decisions on the basis of predictions using our model may improve net benefit.

Conclusions—
Estimation of the incremental treatment effect of high-dose versus usual-dose statin therapy in individual coronary artery disease patients enables selection of high-risk patients that benefit most from more aggressive therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00327691 and NCT00159835.
Low Serum Calcium Levels Contribute to Larger Hematoma Volume in Acute Intracerebral Hemorrhage
Authors: Inoue Yasuteru , Miyashita Fumio , Toyoda Kazunori , Minematsu Kazuo 
Published: May 2013

Background and Purpose—
We investigate whether admission serum calcium levels are associated with hematoma volume, stroke severity, and outcomes in patients with acute intracerebral hemorrhage.

Methods—
A total of 273 patients admitted within 24 hours after intracerebral hemorrhage onset was divided into quartiles based on admission serum calcium levels (Q1 [≤9.0], Q2 [9.1–9.3], Q3 [9.4–9.7], Q4 [≥9.8] mg/dL).

Results—

Median hematoma volumes for each quartile (Q1 to Q4) were 18, 9, 10, and 9 mL (
P
=0.005), and median National Institutes of Health Stroke Scale scores were 16, 11, 11, and 9 (
P
=0.010), respectively. On multivariate analysis, Q1 had larger hematoma volume (
P
=0.025) and higher National Institutes of Health Stroke Scale score (
P
=0.020) than Q4. There were fewer patients with modified Rankin Scale scores 0 to 2 in Q1 than Q4 after adjustment for risk factors and comorbidities (odds ratio, 0.31; 95% confidence interval, 0.11–0.84) but not after additional adjustment for hematoma volume and National Institutes of Health Stroke Scale score. There were more patients with modified Rankin Scale scores 5 to 6 (
P
=0.016) and with fatal outcomes (
P
=0.048) in Q1 than Q4 as crude values, but not after adjustment.

Conclusions—
Low admission serum calcium levels were associated with larger hematoma volume and higher National Institutes of Health Stroke Scale score among patients with acute intracerebral hemorrhage.
Insertable Cardiac Event Recorder in Detection of Atrial Fibrillation After Cryptogenic Stroke
Authors: Etgen Thorleif , Hochreiter Manfred , Mundel Markus , Freudenberger Thomas 
Published: May 2013

Background and Purpose—
Atrial fibrillation (AF) is the most frequent risk factor in ischemic stroke but often remains undetected. We analyzed the value of insertable cardiac event recorder in detection of AF in a 1-year cohort of patients with cryptogenic ischemic stroke.

Methods—
All patients with cryptogenic stroke and eligibility for oral anticoagulation were offered the insertion of a cardiac event recorder. Regular follow-up for 1 year recorded the incidence of AF.

Results—
Of the 393 patients with ischemic stroke, 65 (16.5%) had a cryptogenic stroke, and in 22 eligible patients, an event recorder was inserted. After 1 year, in 6 of 22 patients (27.3%), AF was detected.

Conclusions—
These preliminary data show that insertion of cardiac event recorder was eligible in approximately one third of patients with cryptogenic stroke and detected in approximately one quarter of these patients new AF.
Transient Receptor Potential Canonical 3 Inhibitor Pyr3 Improves Outcomes and Attenuates Astrogliosis After Intracerebral Hemorrhage in Mice
Authors: Munakata Masaya , Shirakawa Hisashi , Nagayasu Kazuki , Miyanohara Jun , Miyake Takahito , Nakagawa Takayuki , Katsuki Hiroshi , Kaneko Shuji 
Published: May 2013

Background and Purpose—
Intracerebral hemorrhage (ICH) stems from the rupture of blood vessels in the brain, with the subsequent accumulation of blood in the parenchyma. Increasing evidence suggests that blood-derived factors induce excessive inflammatory responses that are involved in the progression of ICH-induced brain injury. Thrombin, a major blood-derived factor, leaks into the brain parenchyma on blood–brain barrier disruption and induces brain injury and astrogliosis. Furthermore, thrombin dynamically upregulates transient receptor potential canonical 3 channel, which contributes to pathological astrogliosis through a feed-forward upregulation of its own expression. The present study investigated whether Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), a specific transient receptor potential canonical 3 inhibitor, can improve functional outcomes and attenuate astrogliosis after ICH in mice.

Methods—
Male C57BL6 mice received an intracerebral infusion of collagenase or autologous blood to induce ICH. Pyr3 was given both intracerebroventricularly and intraperitoneally after ICH induction. ICH-induced brain injury was evaluated by quantitative assessment of neurological deficits, brain swelling, and injury volume after ICH. Astrocyte activation was evaluated by immunohistochemical assessment of changes in S100 protein expression.

Results—
Neurological deficits, neuronal injury, brain edema, and astrocyte activation were all significantly improved by administration of Pyr3. Moreover, delayed administration of Pyr3 at 6 hours or 1 day after blood or collagenase infusion, respectively, also improved the symptoms.

Conclusions—
Pyr3, a specific inhibitor of transient receptor potential canonical 3, reduced the perihematomal accumulation of astrocytes and ameliorated ICH–induced brain injury. Therefore, transient receptor potential canonical 3 provides a new therapeutic target for the treatment of hemorrhagic brain injury.