bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma
Authors: Advani Ranjana , Forero-Torres Andres , Furman Richard R. , Rosenblatt Joseph D. , Younes Anas , Ren Hong , Harrop Kate , Whiting Nancy , Drachman Jonathan G. 
Published: July 2009

Purpose To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL). Patients and Methods In this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle. Results In the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in ≥ 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade ≥ 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients. Conclusion Dacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.
Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma
Authors: Jonasch Eric , Wood Christopher G. , Matin Surena F. , Tu Shi-Ming , Pagliaro Lance C. , Corn Paul G. , Aparicio Ana , Tamboli Pheroze , Millikan Randall E. , Wang Xuemei , Araujo John C. , Arap Wadih , Tannir Nizar 
Published: July 2009

Purpose To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy. Patients and Methods Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred. Results Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others. Conclusion Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.
Comparison of Commission on Cancer–Approved and –Nonapproved Hospitals in the United States: Implications for Studies That Use the National Cancer Data Base
Authors: Bilimoria Karl Y. , Bentrem David J. , Stewart Andrew K. , Winchester David P. , Ko Clifford Y. 
Published: July 2009

Background The Commission on Cancer (CoC) designates cancer programs on the basis of the ability to provide a wide range of oncologic services and specialists. All CoC-approved hospitals are required to report their cancer diagnoses to the National Cancer Data Base (NCDB), and the cancer diagnoses at these hospitals account for approximately 70% of all new cancers diagnosed in the United States annually. However, it is unknown how CoC-approved programs compare with non–CoC-approved hospitals. Methods By using the American Hospital Association Annual Survey Database (2006), CoC-approved and non–CoC-approved hospitals were compared with respect to structural characteristics (ie, accreditations, geography, and oncologic services provided). Results Of the 4,850 hospitals identified, 1,412 (29%) were CoC-approved hospitals, and 3,438 (71%) were not CoC-approved hospitals. The proportion of CoC-approved hospitals varied at the state level from 0% in Wyoming to 100% in Delaware. Compared with non–CoC-approved hospitals, CoC-approved programs were more frequently accredited by the Joint Commission, designated as a Comprehensive Cancer Center by the National Cancer Institute, and affiliated with a medical school or residency program (P < .001). CoC-approved hospitals were less likely to be critical access hospitals or located in rural areas (P < .001). CoC-approved hospitals had more total beds and performed more operations per year (P < .001). CoC-approved programs more frequently offered oncology-related services, including screening programs, chemotherapy and radiation therapy services, and hospice/palliative care (P < .001). Conclusion Compared with non–CoC-approved hospitals, CoC-approved hospitals were larger, were more frequently located in urban locations, and had more cancer-related services available to patients. Studies that use the NCDB should acknowledge this limitation when relevant.
D-Dimer and Prothrombin Fragment 1 + 2 Predict Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study
Authors: Ay Cihan , Vormittag Rainer , Dunkler Daniela , Simanek Ralph , Chiriac Alexandru-Laurentiu , Drach Johannes , Quehenberger Peter , Wagner Oswald , Zielinski Christoph , Pabinger Ingrid 
Published: July 2009

Purpose Venous thromboembolism (VTE) is a well-recognized complication of cancer. Laboratory parameters might be useful to assess the VTE risk in patients with cancer. The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 (F 1 + 2), which reflect activation of blood coagulation and fibrinolysis, for prediction of cancer-associated VTE. Patients and Methods In a prospective, observational, cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy, radiotherapy, or surgery were enrolled and followed for a median of 501 days (interquartile range, 255 to 731 days). The malignancies in these patients were as follows: breast (n = 132), lung (n = 119), stomach (n = 35), lower gastrointestinal tract (n = 106), pancreas (n = 46), kidney (n = 22), and prostate (n = 101) cancers; high-grade glioma (n = 102); malignant lymphoma (n = 94); multiple myeloma (n = 17); and other tumor types (n = 47). The study end point was occurrence of objectively confirmed symptomatic or fatal VTE. Results VTE occurred in 62 patients (7.6%). The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population. In multivariable analysis that included elevated D-dimer, elevated F 1 + 2, age, sex, surgery, chemotherapy, and radiotherapy, the hazard ratios (HRs) of VTE in patients with elevated D-dimer (HR, 1.8; 95% CI, 1.0 to 3.2; P = .048) and elevated F 1 + 2 (HR, 2.0; 95% CI, 1.2 to 3.6; P = .015) were statistically significantly increased. The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 (15.2%) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 (5.0%; P < .001). Conclusion High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer.
Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411
Authors: Crane Christopher H. , Winter Kathryn , Regine William F. , Safran Howard , Rich Tyvin A. , Curran Walter , Wolff Robert A. , Willett Christopher G. 
Published: July 2009

Purpose The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR). Patients and Methods Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA). Results Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05). Conclusion The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.
Innovative moments and change pathways: A good outcome case of narrative therapy
Authors: Santos Anita , Gonçalves Miguel , Matos Marlene , Salvatore Sergio 
Published: July 2009

Objectives. Our aim was to explore the development of innovative moments (i‐moments) in therapeutic conversation and to study how they match our heuristic model that accounts for the development of change, drawn from previous empirical research.Design. In this therapeutic process research, we analysed a good outcome case of narrative therapy with a woman victim of intimate violence.Methods. This case, composed of 12 sessions, was analysed with the Innovative Moments Coding System: Version 1. This coding system allowed the identification of five different types of innovations (i‐moments) that appeared during the therapeutic process: action, reflection, protest, re‐conceptualization, and performing change. For each session, an index of temporal salience was computed, as the percentage of the time in the session that client and therapist spent talking about each i‐moment. Our analysis procedures provided a quantitative and also a complementary qualitative approach.Results. Data showed that the types of i‐moments emerged differently throughout the process. Early sessions were characterized mainly by action and reflection (low temporal salience), middle sessions were found to have mainly protest i‐moments (low or middle temporal salience), and final sessions were characterized by the combination of high salient re‐conceptualization and performing change i‐moments.Conclusions. Findings suggested that narrative change seems to develop in a cyclical way, in which different types of i‐moments contribute to the development of a new self‐narrative in different phases.
The Role of MITF Phosphorylation Sites During Coat Color and Eye Development in Mice Analyzed by Bacterial Artificial Chromosome Transgene Rescue
Authors: Bauer Georg L , Praetorius Christian , Bergsteinsdóttir Kristín , Hallsson Jón H , Gísladóttir Bryndís K , Schepsky Alexander , Swing Deborah A , O'Sullivan T Norene , Arnheiter Heinz , Bismuth Keren , Debbache Julien , Fletcher Colin , Warming Søren , Copeland Neal G , Jenkins Nancy A , Steingrímsson Eiríkur 
Published: July 2009

Abstract
The microphthalmia-associated transcription factor (Mitf) has emerged as an important model for gene regulation in eukaryotic organisms. In vertebrates, it regulates the development of several cell types including melanocytes and has also been shown to play an important role in melanoma. In vitro, the activity of MITF is regulated by multiple signaling pathways, including the KITL/KIT/B-Raf pathway, which results in phosphorylation of MITF on serine residues 73 and 409. However, the precise role of signaling to MITF in vivo remains largely unknown. Here, we use a BAC transgene rescue approach to introduce specific mutations in MITF to study the importance of specific phospho-acceptor sites and protein domains. We show that mice that carry a BAC transgene where single-amino-acid substitutions have been made in the Mitf gene rescue the phenotype of the loss-of-function mutations in Mitf. This may indicate that signaling from KIT to MITF affects other phospho-acceptor sites in MITF or that alternative sites can be phosphorylated when Ser73 and Ser409 have been mutated. Our results have implications for understanding signaling to transcription factors. Furthermore, as MITF and signaling mechanisms have been shown to play an important role in melanomas, our findings may lead to novel insights into this resilient disease.
Signature of Diversifying Selection on Members of the Pentatricopeptide Repeat Protein Family in Arabidopsis lyrata
Authors: Foxe John Paul , Wright Stephen I 
Published: July 2009

Abstract
Pentatricopeptide repeat (PPR) proteins compose a family of nuclear-encoded transcriptional regulators of cytoplasmic genes. They have shown dramatic expansion in copy number in plants, and although the functional importance of many remains unclear, a subset has been repeatedly implicated as nuclear restorers for cytoplasmic male sterility. Here we investigate the molecular population genetics and molecular evolution of seven single-copy PPR genes in the outcrossing model plant Arabidopsis lyrata. In comparison with neutral reference loci, we find, on average, elevated levels of polymorphism and an excess of high-frequency variants at these PPR genes, suggesting that natural selection is maintaining polymorphism at some of these loci. This elevation in diversity persists when we control for divergence and generally decreases in the flanking regions, suggesting that these genes are themselves the targets of selection. Some of the PPR genes also demonstrate elevated population differentiation, which is consistent with spatially varying selection. In contrast, no comparable patterns are observed at these loci in A. thaliana, providing no evidence for the action of balancing selection in this selfing species. Taken together, these results suggest that a subset of PPR genes may be subject to balancing selection associated with ongoing cytonuclear coevolution in the outcrossing A. lyrata, which is possibly mediated either by intergenomic conflict or by compensatory evolution.
Assessment of an Alternative Meropenem Dosing Strategy Compared with Imipenem‐Cilastatin or Traditional Meropenem Dosing After Cefepime Failure or Intolerance in Adults with Neutropenic Fever
Authors: Arnold Heather M. , McKinnon Peggy S. , Augustin Kristan M. , Hladnik Lindsay M. , Casabar Ed , Reichley Richard M. , Dubberke Erik R. , Westervelt Peter , Ritchie David J. 
Published: July 2009

Study Objective. To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem‐cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia.Design. Retrospective, single‐center cohort study.Setting. 1250‐bed urban academic medical center.Patients. One hundred twenty‐seven adults with neutropenic fever who received either imipenem‐cilastatin or meropenem; imipenem‐cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem.Measurements and Main Results. Of the 127 patients, 40 received imipenem‐cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem‐cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in‐hospital mortality (5% vs 7% vs 7%), and 30‐day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively.Conclusion. The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem‐cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.
Intramuscular Haloperidol versus Intramuscular Olanzapine for Treatment of Acute Agitation: A Cost‐Minimization Study
Authors: Freeman Darren J. , DiPaula Bethany A. , Love Raymond C. 
Published: July 2009

Study Objectives. To investigate prescribing patterns for antipsychotic regimens based on intramuscular haloperidol or intramuscular olanzapine for treating acute agitation; to compare the costs of each drug regimen, which included adjunctive anxiolytics and/or anticholinergics; and to compare the effectiveness and safety of each drug regimen.Design. Retrospective medical record review.Setting. State psychiatric facility.Patients. Twenty‐seven patients who received intramuscular haloperidol to treat 47 episodes of acute agitation and 26 patients who received intramuscular olanzapine to treat 38 episodes.Measurements and Main Results. Data from patients receiving the antipsychotic regimens between August 2004 and March 2007 were reviewed. Mean ± SD doses were 6.4 ± 2.4 mg (range 2.5–10 mg) for haloperidol and 8.1 ± 2.3 mg (range 5–10 mg) for olanzapine. The mean ± SD cost of treating an episode of agitation with haloperidol was significantly lower at $4.06 ± 3.98 (range $1.74‐18.35) versus $27.84 ± 10.40 (range $21.58‐52.46) for olanzapine (p<0.0001). Significantly fewer patients who received haloperidol than patients who received olanzapine required additional pharmacotherapy to manage agitation (41% vs 69%, χ2=4.34, p=0.04). No significant differences were found between groups in the mean number of repeat doses of psychotropic drugs needed/episode (0.6 [range 0–5] for haloperidol vs 0.8 [range 0–3] for olanzapine, p=0.47), in the percentages of patients who required seclusion and/or restraints (59% for haloperidol vs 58% for olanzapine, χ2=0.01, p=0.91), or in time spent in seclusion and/or restraints (3.7 ± 7.1 for haloperidol vs 3.6 ± 6.5 hrs for olanzapine, p=0.92). No adverse events were documented with either drug.Conclusion. For the treatment of acute episodes of agitation, regimens based on intramuscular haloperidol were significantly less expensive than and at least as effective as those based on intramuscular olanzapine.
Assessment of a Point‐of‐Care Metabolic Risk Screening Program in Outpatients Receiving Antipsychotic Agents
Authors: Schneiderhan Mark E. , Batscha Catherine L. , Rosen Cherise 
Published: July 2009

Study Objective. To assess the usefulness of a metabolic risk screening program, including point‐of‐care glucose testing, to quantify baseline metabolic risk in outpatients receiving antipsychotics.Design. Retrospective, cross‐sectional, cohort study.Setting. University‐affiliated department of psychiatry clinic.Patients. A total of 92 adult outpatients (49 women, 43 men; mean ± SD age 38.96 ± 12 yrs) who were receiving antipsychotics and had undergone screening for metabolic syndrome at the clinic during 2004–2007.Measurements and Main Results. Patient data were recorded on a metabolic screening checklist by a pharmacist or nurse. The checklist captured demographics, vital signs (height, weight, body mass index [BMI], blood pressure, waist and hip circumference, point‐of‐care random glucose level), personal and family knowledge of current illnesses (diabetes mellitus, hypertension, hyperlipidemia), modifiable risk factors (smoking, alcohol, level of activity), current drug therapy, and recommendations to the psychiatrist. The patient population who underwent screening included 49 African‐Americans (53%), 21 Caucasians (23%), 16 Hispanics (17%), and 6 Asians (7%). Diagnoses were documented for 88 patients: schizophrenia or schizoaffective disorder in 53 patients (60%), and bipolar disorder and major depressive disorder was equally divided in the remaining 35 patients (40%). Of 89 patients (three patients had missing data on waist circumference), 63 (71%) met criteria for level 1 metabolic risk (abdominal obesity); of these 63 patients, 38 (60%) met criteria for level 2 risk (abdominal obesity plus hypertension). Patients with a random glucose level greater than 140 mg/dl had a higher likelihood for being at level 2 risk than level 1 risk (χ2=5.99, df=1, p=0.014). Women had a significantly higher likelihood for level 1 metabolic risk compared with men (χ2=5.99, df=1, p=0.019). African‐Americans had a significantly higher likelihood of level 1 risk (p=0.026) and BMI greater than 30 kg/m2 (p=0.003) compared with Caucasians. Patients with a BMI greater than 30 kg/m2 had a significantly higher likelihood of diabetes (p=0.006), hypertension (p=0.03), and hyperlipidemia (p=0.05). Overall, 5 (5%) of the 92 patients met criteria for prediabetes risk.Conclusion. Point‐of‐care metabolic risk screening, done with a systematic interprofessional team approach, can provide clinicians with a practical method for identifying metabolic risk in patients prescribed antipsychotics.