bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital Resource Utilization and Costs of Inappropriate Treatment of Candidemia
Authors: Arnold Heather M. , Micek Scott T. , Shorr Andrew F. , Zilberberg Marya D. , Labelle Andrew J. , Kothari Smita , Kollef Marin H. 
Published: March 2010

Study Objectives. To evaluate the impact of inappropriate therapy—defined as delayed antifungal therapy beyond 24 hours from culture collection, inadequate antifungal dosage, or administration of an antifungal to which an isolate was considered resistant—on postculture hospital length of stay and costs, and to evaluate the relationship between modifiable risk factors, including failure to remove a central venous catheter, antifungal delay, and inadequate dosage, for an additive effect on hospital length of stay and costs.Design. Single‐center retrospective cohort study.Setting. 1250‐bed academic medical center.Patients. One hundred sixty‐seven consecutive adult patients admitted between January 2004 and May 2006 with culture‐confirmed Candida bloodstream infections that occurred within 14 days of hospital admission and who received at least one dose of antifungal treatment.Measurements and Main Results. Patients were stratified according to appropriateness of antifungal therapy. Appropriate therapy was defined as initiation of an antifungal to which the isolated pathogen was sensitive in vitro within 24 hours of positive culture collection, in addition to receipt of an adequate dose as recommended by the Infectious Diseases Society of America and the antifungal package insert. Postculture length of stay was the primary outcome and hospital costs the secondary outcome. An evaluation of modifiable risk factors was performed separately. Data were analyzed for 167 patients (22 in the appropriate therapy group and 145 in the inappropriate therapy group). Postculture length of stay was shorter in the appropriate therapy group (mean 7 vs 10.4 days, p=0.037). This correlated with total hospital costs that were lower in the appropriate therapy group (mean $15,832 vs $33,021, p<0.001.) A graded increase in costs was noted with increasing number of modifiable risk factors (p=0.001).Conclusion. Inappropriate therapy for Candida bloodstream infection occurring within 14 days of hospitalization was associated with prolonged postculture length of stay and increased costs. A rise in costs, but not length of stay, was noted with increasing modifiable risk factors.
Unfractionated Heparin Dose Requirements Targeting Intermediate Intensity Antifactor Xa Concentration During Pregnancy
Authors: Clark Nathan P. , Delate Thomas , Cleary Steven J. , Witt Daniel M. 
Published: March 2010

Study Objective. To describe unfractionated heparin (UFH) dosing requirements and monitoring parameters to achieve target antifactor Xa concentrations in pregnant women receiving intermediate‐dose UFH therapy.Design. Retrospective cohort analysis.Setting. Centralized anticoagulation service in an integrated health care delivery system.Patients. Twenty‐five pregnant women (who had 27 pregnancies) who received intermediate‐dose UFH between January 1, 1998, and March 31, 2005.Measurements and Main Results. Demographic and clinical data were retrieved by using an integrated electronic medical, pharmacy, and laboratory records system. The primary outcome was the required UFH dose at the time of first target antifactor Xa level achieved. Antifactor Xa levels were measured at the mid‐dosing interval for UFH. An antifactor Xa assay concentration of 0.1–0.3 unit/ml was used as the target range for intermediate‐dose UFH for antithrombotic management of pregnant women as described in the American College of Chest Physicians clinical practice guidelines. The mean UFH dose required to achieve this target antifactor Xa range was 236.9 units/kg/day. The UFH doses required to achieve target antifactor Xa levels correlated significantly with patient weight (r = 0.682, p<0.001). The final UFH dose/kg required at the end of pregnancy was similar to that at the first target level (p>0.05) when adjusted for weight. However, the total daily amount of UFH did increase by the end of pregnancy (21,889 vs 19,320 units, p=0.02). There was an average of 7.9 antifactor Xa determinations and 3.1 dosage modifications during the mean of 19 weeks of antenatal UFH therapy. Most (62%) antifactor Xa levels were within the target range. No thromboembolic events, heparin‐induced thrombocytopenia, or osteopenic fracture occurred. There was one hemorrhagic complication that resolved with temporary withdrawal of UFH.Conclusions. Pregnant women required a mean UFH dose of 236.9 units/kg/day to achieve the targeted antifactor Xa level of 0.1–0.3 unit/ml. The required UFH doses correlated with patient weight, and most antifactor Xa levels were within the desired target range. These findings may assist clinicians in more precisely initiating and monitoring intermediate‐dose UFH in pregnant patients.
FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma
Authors: Kwitkowski Virginia E. , Prowell Tatiana M. , Ibrahim Amna , Farrell Ann T. , Justice Robert , Mitchell Shan Sun , Sridhara Rajeshwari , Pazdur Richard 
Published: March 2010

Abstract

Learning Objectives
After completing this course, the reader will be able to: Compare temsirolimus with IFN-α for the treatment of adults with treatment-naïve, advanced, poor-prognosis RCC and discuss the differences in OS time and PFS time for each.Enumerate the laboratory parameters that should be monitored at baseline and while patients are receiving temsirolimus and implement appropriate laboratory monitoring procedures.
This article is available for continuing medical education credit at CME.TheOncologist.com
This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel®), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review.
A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-α versus those receiving temsirolimus alone or in combination with IFN-α.
In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-α arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-α did not lead to a significant difference in OS compared with IFN-α alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-α arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001).
Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed.
Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-α and provides an additional treatment option for patients with advanced RCC.
Caspase Inhibitor Therapy Synergizes With Costimulation Blockade to Promote Indefinite Islet Allograft Survival
Authors: Emamaullee Juliet A. , Davis Joy , Pawlick Rena , Toso Christian , Merani Shaheed , Cai Sui-Xiong , Tseng Ben , Shapiro A.M. James 
Published: March 2010

OBJECTIVE
Costimulation blockade has emerged as a selective nontoxic maintenance therapy in transplantation. However, these drugs must be combined with other immunomodulatory agents to ensure long-term graft survival.

RESEARCH DESIGN AND METHODS
Recent work has demonstrated that caspase inhibitor therapy (EP1013) prevents engraftment phase islet loss and markedly reduces the islet mass required to reverse diabetes. The “danger” hypothesis suggests that reduction in graft apoptosis should reduce the threshold for immunosuppression and increase the possibility for tolerance induction. Thus, the impact of combination of EP1013 treatment with costimulation blockade (CTLA4-Ig) was investigated in this study.

RESULTS
Islet allografts were completed in fully major histocompatibility complex (MHC)-mismatched mice (Balb/C to B6). When animals received vehicle or EP1013, there was no difference in graft survival. CTLA4-Ig resulted in prolonged graft survival in 40% of the animals, whereas EP1013+CLTA4-Ig resulted in a significant increase in graft survival (91% &gt;180 days; P = 0.01). Ex vivo analysis revealed that animals receiving EP1013 or EP1013+CTLA4-Ig had a reduced frequency of alloreactive interferon (IFN)-γ–secreting T-cells and an increased frequency of intragraft Foxp3+ Treg cells. Alloantibody assays indicated that treatment with EP1013 or CTLA4-Ig prevented allosensitization.

CONCLUSIONS
This study suggests that addition of caspase inhibitor therapy to costimulation blockade will improve clinical transplantation by minimizing immune stimulation and thus reduce the requirement for long-term immunosuppressive therapy. The approach also prevents allosensitization, which may be an important component of chronic graft loss in clinical transplantation.
Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Subjects With and Without Pre-Diabetes
Authors: Rosenstock Julio , Klaff Leslie J. , Schwartz Sherwyn , Northrup Justin , Holcombe John H. , Wilhelm Kenneth , Trautmann Michael 
Published: March 2010

OBJECTIVE
To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance (IGT) or impaired fasting glucose (IFG).

RESEARCH DESIGN AND METHODS
Obese subjects (n = 152; age 46 ± 12 years, female 82%, weight 108.6 ± 23.0 kg, BMI 39.6 ± 7.0 kg/m2, IGT or IFG 25%) were randomized to receive exenatide (n = 73) or placebo (n = 79), along with lifestyle intervention, for 24 weeks.

RESULTS
Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo (exenatide − placebo, P &lt; 0.001). Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5% (P &lt; 0.001). Both groups reduced their daily calorie intake (exenatide, −449 cal; placebo, −387 cal). IGT or IFG normalized at end point in 77 and 56% of exenatide and placebo subjects, respectively.

CONCLUSIONS
Exenatide plus lifestyle modification decreased caloric intake and resulted in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG.
Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes
Authors: Gaziano J. Michael , Cincotta Anthony H. , O'Connor Christopher M. , Ezrokhi Michael , Rutty Dean , Ma Z.J. , Scranton Richard E. 
Published: March 2010

OBJECTIVE
Quick-release bromocriptine (bromocriptine-QR), a D2 dopamine receptor agonist, is indicated as a treatment for type 2 diabetes. The Cycloset Safety Trial, a 52-week, randomized, double-blind, multicenter trial, evaluated the overall safety and cardiovascular safety of this novel therapy for type 2 diabetes.

RESEARCH DESIGN AND METHODS
A total of 3,095 patients with type 2 diabetes were randomized 2:1 to bromocriptine-QR or placebo in conjunction with the patient's usual diabetes therapy (diet controlled only or up to two antidiabetes medications, including insulin). The all-cause–safety end point was the occurrence of any serious adverse event (SAE), with a hazard ratio (HR) noninferiority margin of 1.5. In a prespecified analysis, the frequency of cardiovascular disease (CVD) events defined as a composite of myocardial infarction, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure was evaluated using modified intent-to-treat analysis (clinicaltrials.gov, NCT00377676).

RESULTS
In the bromocriptine-QR group, 176 (8.6%) people reported SAEs compared with 98 (9.6%) in the placebo group (HR 1.02 [96% one-sided CI 1.27]). Fewer people reported a CVD end point in the bromocriptine-QR group versus the placebo group (37 [1.8%] vs. 32 [3.2%], respecively) (HR 0.60 [95% two-sided CI 0.35–0.96]). Nausea was the most commonly reported adverse event in the bromocriptine-QR group.

CONCLUSIONS
The frequency of SAEs was comparable between the treatment arms. Compared with patients in the placebo arm, fewer patients taking bromocriptine-QR experienced a cardiovascular end point.
The Cost-Effectiveness of Continuous Glucose Monitoring in Type 1 Diabetes
Authors: Huang Elbert S. , O'Grady Michael , Basu Anirban , Winn Aaron , John Priya , Lee Joyce , Meltzer David , Kollman Craig , Laffel Lori , Tamborlane William , Weinzimer Stuart , Wysocki Tim ,   the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group
Published: March 2010

OBJECTIVE
Continuous glucose monitoring (CGM) has been found to improve glucose control in type 1 diabetic patients. We estimated the cost-effectiveness of CGM versus standard glucose monitoring in type 1 diabetes.

RESEARCH DESIGN AND METHODS
This societal cost-effectiveness analysis (CEA) was conducted in trial populations in which CGM has produced a significant glycemic benefit (A1C ≥7.0% in a cohort of adults aged ≥25 years and A1C &lt;7.0% in a cohort of all ages). Trial data were integrated into a simulation model of type 1 diabetes complications. The main outcome was the cost per quality-adjusted life-year (QALY) gained.

RESULTS
During the trials, CGM patients experienced an immediate quality-of-life benefit (A1C ≥7.0% cohort: 0.70 quality-adjusted life-weeks [QALWs], P = 0.49; A1C &lt;7.0% cohort: 1.39 QALWs, P = 0.04) and improved glucose control. In the long-term, CEA for the A1C ≥7.0% cohort, CGM was projected to reduce the lifetime probability of microvascular complications; the average gain in QALYs was 0.60. The incremental cost-effectiveness ratio (ICER) was $98,679/QALY (95% CI −60,000 [fourth quadrant] to −87,000 [second quadrant]). For the A1C &lt;7.0% cohort, the average gain in QALYs was 1.11. The ICER was $78,943/QALY (15,000 [first quadrant] to −291,000 [second quadrant]). If the benefit of CGM had been limited to the long-term effects of improved glucose control, the ICER would exceed $700,000/QALY. If test strip use had been two per day with CGM long term the ICER for CGM would improve significantly.

CONCLUSIONS
Long-term projections indicate that CGM is cost-effective among type 1 diabetic patients at the $100,000/QALY threshold, although considerable uncertainty surrounds these estimates.
Renal Hyperfiltration Is a Determinant of Endothelial Function Responses to Cyclooxygenase 2 Inhibition in Type 1 Diabetes
Authors: Cherney David Z.I. , Miller Judith A. , Scholey James W. , Nasrallah Rania , Hébert Richard L. , Dekker Maria G. , Slorach Cameron , Sochett Etienne B. , Bradley Timothy J. 
Published: March 2010

OBJECTIVE
Our aim was to examine the effect of cyclooxygenase 2 (COX2) inhibition on endothelial function in subjects with type 1 diabetes analyzed on the basis of renal filtration status.

RESEARCH DESIGN AND METHODS
Flow-mediated dilation (FMD) was determined in type 1 diabetic subjects and hyperfiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 13) or normofiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 11). Studies were performed before and after celecoxib (200 mg daily for 14 days) during euglycemia and hyperglycemia.

RESULTS
Baseline parameters were similar in the two groups. Pretreatment, FMD was augmented in normofiltering versus hyperfiltering subjects during clamped euglycemia (10.2 ± 5.3% vs. 5.9 ± 2.3%, P = 0.003). COX2 inhibition suppressed FMD in normofiltering (10.2 ± 5.3% to 5.8 ± 3.4%, P = 0.006) versus hyperfiltering subjects (ANOVA interaction, P = 0.003).

CONCLUSIONS
Systemic hemodynamic function, including the response to COX2 inhibition, is related to filtration status in diabetic subjects and may reflect general endothelial dysfunction.
High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes
Authors: Ficociello Linda H. , Rosolowsky Elizabeth T. , Niewczas Monika A. , Maselli Nicholas J. , Weinberg Janice M. , Aschengrau Ann , Eckfeldt John H. , Stanton Robert C. , Galecki Andrzej T. , Doria Alessandro , Warram James H. , Krolewski Andrzej S. 
Published: March 2010

OBJECTIVE
We previously described a cross-sectional association between serum uric acid and reduced glomerular filtration rate (GFR) in nonproteinuric patients with type 1 diabetes. Here, we prospectively investigated whether baseline uric acid impacts the risk of early progressive renal function loss (early GFR loss) in these patients.

RESEARCH DESIGN AND METHODS
Patients with elevated urinary albumin excretion (n = 355) were followed for 4–6 years for changes in urinary albumin excretion and GFR. The changes were estimated by multiple determinations of albumin-to-creatinine ratios (ACRs) and serum cystatin C (GFRcystatin).

RESULTS
At baseline, the medians (25th–75th percentiles) for uric acid, ACR, and GFRcystatin values were 4.6 mg/dl (3.8–5.4), 26.2 mg/g (15.1–56.0), and 129 ml/min per 1.73 m2 (111–145), respectively. During the 6-year follow-up, significant association (P &lt; 0.0002) was observed between serum uric acid and development of early GFR loss, defined as GFRcystatin decline exceeding 3.3% per year. In baseline uric acid concentration categories (in mg/dl: &lt;3.0, 3.0–3.9, 4.0–4.9, 5.0–5.9, and ≥6), the risk of early GFR loss increased linearly (9, 13, 20, 29, and 36%, respectively). This linear increase corresponds to odds ratio 1.4 (95% CI 1.1–1.8) per 1 mg/dl increase of uric acid. The progression and regression of urinary albumin excretion were not associated with uric acid.

CONCLUSIONS
We found a clear dose-response relation between serum uric acid and risk of early GFR loss in patients with type 1 diabetes. Clinical trials are warranted to determine whether uric acid–lowering drugs can halt renal function decline before it becomes clinically significant.
Global mapping of ZBTB7A transcription factor binding sites in HepG2 cells
Authors: Zu Xuyu , Yu Lingling , Sun Yiming , Tian Jing , Liu Feng , Sun Qinsheng , He Shengnan , Sun Guang , Luo Weishi , Jiang Yuyang 
Published: March 2010

AbstractZBTB7A is a known proto-oncogene that is implicated in carcinogenesis and cell differentiation and development. Fully understanding the function of ZBTB7A in cellular processes could provide useful strategies for cancer treatment and development-associated disease therapy. Here, global mapping of ZBTB7A transcription factor binding sites was developed by utilizing microarray technology in HepG2 cells. The data obtained from the microarrays was further validated via chromatin immunoprecipitation-PCR (ChIP-PCR) and real time-PCR, and it was revealed that ZBTB7A may be one of the regulators of neural development. ZBTB7A target signal pathways were identified in signal pathway and GO (Gene Ontology) analyses. This is the first report on the global mapping of ZBTB7A downstream direct targets, and these findings will be useful in understanding the roles of ZBTB7A in cellular processes.
The anti-apoptotic protein lifeguard is expressed in breast cancer cells and tissues
Authors: Bucan Vesna , Reimers Kerstin , Choi Claudia , Eddy Mau-Thek , Vogt Peter 
Published: March 2010

AbstractLifeguard (LFG) is an anti-apoptotic protein that inhibits Fas-mediated death in tumour cells. However, the molecular function of human LFG in the carcinogenesis of human breast cells is uncertain. We studied the expression and function of endogenous LFG in four breast cancer cell lines (MCF-7, MDA-MB-231, T-47D and HS 578T), a human breast epithelial cell line (HS 578Bst), and in healthy and cancerous breast tissues. Molecular (Western blot and RT-PCR) and immunohistochemical techniques were used to investigate the LFG expression. To investigate the breast cancer cell proliferation in the presence of Fas, we performed fluorescent cell viability assays. The possible association of Fas with LFG was analyzed by immunofluorescence microscopy. In this paper, we provide convincing evidence that LFG is overexpressed in several human breast cancer cell lines. More importantly, we found that the LFG expression correlates with high tumour grades in primary breast tumours. Finally, we demonstrated that Fas sensitivity is reduced in breast cancer cell lines expressing LFG. Our results indicated that LFG is strongly expressed in breast cancer epithelial cells. Moreover, the overexpression of LFG correlated with tumour grade and reduced Fas sensitivity. Our findings support the idea that LFG may have a role in the downregulation of apoptosis in breast cancer cells.
The INQUA Loess Commission as a Central European Enterprise
Authors: Smalley Ian , Markovic Slobodan , O’Hara-Dhand Ken 
Published: March 2010

Abstract
The International Union of Quaternary Research (INQUA) organized the study and consideration of the Quaternary Period (the last 2.6 million years in Earth’s history) via a set of commissions, sub-commissions, working groups, projects and programmes. One of the most successful and best records was the Loess Commission (LC) which functioned assub-commission and then commission from 1961 to 2003, resulting in 40 years of useful activity. The history of the LC can be divided into three phases: 1, from 1961–1977 when the President was Julius Fink; 2, from 1977–1991, with President Marton Pecsi; 3, from 1991–2003 with Presidents An Zhi-Sheng and Ian Smalley.
Fink, from Vienna, and Pecsi, from Budapest, gave the LC a distinctly Central European aspect. The nature of loess in Central Europe influenced the nature of the LC but the settings for phases 1 and 2 were quite distinct. Phase 1 was a small scale academic operation, carried out in German. As phase 2 began in 1977 the scope expanded and Central Europe became a base for worldwide loess studies. where the LC language changed to English. Phase 2 was run from a National Geographical Institute and demonstrated a different approach to loess research, although the basic programmes of continent-wide mapping and stratigraphy remained the same. The Commission benefited from this change of style and emphasis. In phase 3 the administration moved away from Central Europe but the Finkian ethos remained solid.
New approaches to European loess: a stratigraphic and methodical review of the past decade
Authors: Zoeller Ludwig 
Published: March 2010

Abstract
This review paper intends to summarize the state of the art in loess research at the first international “Loess-fest’99” conference and to outline progress in loess research during the past decade. The focus is on loess as a terrestrial archive of climatic and environmental change during the Quaternary. The review highlights remarkable new results from regional investigations into European loess, as well as the emergence of new methods and refinements of established techniques, focussing on stratigraphy, dating and palaeoenvironment. It is concluded that loess research during the past decade not only has developed rapidly to take an outstanding place in Quaternary sciences, but also promises exciting perspectives for the next decade, in particular when combined approaches are applied to benefit from the now comprehensive pool of established and new methods.