bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temozolomide plus radiotherapy for glioblastoma in a Canadian province: Efficacy versus effectiveness and the impact of O6-methylguanine-DNA-methyltransferase promoter methylation
Authors: Lam Nadine , Chambers Carole R 
Published: November 2011

Background: Radiotherapy with concomitant and adjuvant temozolomide has been the standard of care for newly diagnosed glioblastoma in adults since the pivotal trial by Roger Stupp and colleagues. The effectiveness of this regimen has not been evaluated in Canada. Additionally, the impact of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation on patient survival has not been confirmed. Hence, survival outcomes and MGMT predictive value were compared for the patients in Alberta versus the Stupp trial population. Methods: Retrospective chart review of 215 adult glioblastoma patients who started radiotherapy and temozolomide between January 2007 and December 2010 at the Cross Cancer Institute (Edmonton, Alberta) or the Tom Baker Cancer Centre (Calgary, Alberta). Results: In the Alberta population, median overall survival was 14.3 months (vs. 14.6 months in trial, p = NS) and median progression-free survival was 5.8 months (vs. 6.9 months in trial, p = NS). However, unlike the trial, the Alberta MGMT subgroup analysis for overall survival was not statistically significant, despite a hazard ratio of 0.65 in favor of the methylated group. More Alberta patients received corticosteroids ( p < 0.0001) and fewer underwent complete resection ( p = 0.0001) or a postprogression second surgery ( p = 0.01) than the Stupp population, but characteristics were otherwise similar. Conclusion: Current practice in Alberta enables patients to achieve overall and progression-free survival similar to the clinical trial. Further follow-up is required to confirm the predictive value of the MGMT assay. Until that is clarified or better treatments are developed, it is reasonable to continue offering this treatment regimen to patients regardless of MGMT methylation status.
A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design
Authors: Fox Edward , Wynn Daniel , Cohan Stanley , Rill Donna , McGuire Dawn , Markowitz Clyde 
Published: November 2011

Background: Tovaxin is an autologous T-cell immunotherapy under investigation for the treatment of MS. The product consists of in vitro expanded myelin-reactive T-cells manufactured against up to six immunodominant peptides derived from three myelin antigens. Methods: A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing-remitting MS and clinically isolated syndrome subjects. Results: Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease-modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naïve subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR≥1, ARR>1). However, clinical benefit was not was accompanied by a treatment-dependent improvement in MRI measures. Conclusions: Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment-naïve individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration.
Vascular endothelial growth factor polymorphisms are involved in the late vascular complications in Type II diabetic patients
Authors: Bleda Silvia , De Haro Joaquin , Varela Cesar , Esparza Leticia , Ferruelo Antonio , Acin Francisco 
Published: November 2011

Aim: To determine the potential genotype differences in the vascular endothelial growth factor (VEGF) gene in diabetic patients, which might explain the difference in terms of the development of clinical vascular complications: great vessels atherosclerosis vs. retinopathy. Methods: Genotyping of the VEFG gene insertion/deletion −2549, the C−2578A and the G+405C polymorphisms was done in 40 diabetic patients (26 with peripheral artery disease (PAD) and 14 with diabetic retinopathy (DR)). Results: There was a significant increase in the frequency of the VEGF −2549 DD genotype in PAD patients compared with the DR group (34.6 vs. 0; p = 0.016), as well as in the distribution of the VEGF −2549 ID genotype in DR compared with PAD patients (85.7 vs. 38.4; p = 0.005). There was a significant increase in the frequency of the VEGF −2578 CC genotype in the PAD group compared with DR (34.6 vs. 0; p = 0.016), as well as in the VEGF −2578 CA genotype in DR patients compared with PAD (85.7 vs. 34.6; p = 0.002). The VEGF +405 genotype was not associated with diabetic vascular complications. Conclusion: This study provides preliminary evidence that VEGF polymorphisms are associated with a differential presentation of diabetic vascular complications.
The potential for central monitoring techniques to replace on-site monitoring: findings from an international multi-centre clinical trial
Authors: Bakobaki Julie M , Rauchenberger Mary , Joffe Nicola , McCormack Sheena , Stenning Sally , Meredith Sarah 
Published: November 2011

Background Compliance with Good Clinical Practice (GCP) guidelines should ensure the safety of trial participants and the reliability of trial results. Over the last decade, increasing emphasis has been placed on the role of costly on-site monitoring and source data verification as processes to demonstrate that GCP is being followed, despite a lack of empirical evidence that these are effective. Purpose To assess whether findings from on-site monitoring of a recent international multi-centre clinical trial could have been identified using central data review and other centralised monitoring techniques. Methods Findings documented in a sample of site monitoring reports, and Programme Management Board Executive (PMBe) reports, from the Microbicides Development Programme (MDP) 301 trial – a randomised placebo-controlled trial of a microbicide gel to prevent vaginally acquired HIV infection conducted in four countries in East and Southern Africa – were extracted and individually assessed to determine whether they could have been detected in the trial database or through other central means. Results Four site visit reports contained 268 monitoring findings from a review of 104 participant files covering 324 study visits. Of the 268 findings, 76 (28.4%) were also identified in the study database. Central checks, had these been in place (such as central receipt and review of back-translated documents, enrolment and testing logs, informed consent, and more complex database queries), could have identified a further 179 (66.8%); 13 (4.9%) other findings (all minor) could have been identified through a review of the participant folder at site. The four PMBe reports reviewed included six major and three critical findings from a review of over 1000 participant files: only two of these (both major) were assessed as unlikely to be identified using central monitoring techniques. Limitations The study data used were not collected with this retrospective review in mind. It suggests that prospective work is needed to compare monitoring practices in real time. Conclusions While there may be some categories of findings that it is not possible to identify centrally, the very large majority of findings reviewed in this analysis could be identified using central monitoring strategies. These data suggest that with better central and targeted on-site monitoring, it should be possible to identify and address most protocol and procedural compliance issues without performing intensive and costly routine on-site data monitoring.
Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome: the role of integrin β1 and β3 in platelet adhesion to collagen
Authors: van de Vijver Edith , De Cuyper Iris M. , Gerrits Anja J. , Verhoeven Arthur J. , Seeger Karl , Gutiérrez Laura , van den Berg Timo K. , Kuijpers Taco W. 
Published: November 2011

Abstract
Patients with Glanzmann thrombasthenia or Leukocyte Adhesion Deficiency-III syndrome (LAD-III or LAD-1/variant) present with increased bleeding tendency because of the lack or dysfunction of the fibrinogen receptor GPIIb/IIIa (integrin αIIbβ3), respectively. Although the bleeding disorder is more severe in LAD-III patients, classic aggregometry or perfusion of Glanzmann or LAD-III platelets over collagen-coated slides under physiologic shear rate does not discriminate between these 2 conditions. However, in a novel flow cytometry-based aggregation assay, Glanzmann platelets were still capable of forming small aggregates upon collagen stimulation, whereas LAD-III platelets were not. These aggregates required functional GPIa/IIa (integrin α2β1) instead of integrin αIIbβ3, thus explaining the clinically more severe bleeding manifestations in LAD-III patients, in which all platelet integrins are functionally defective. These findings provide genetic evidence for the differential requirements of platelet integrins in thrombus formation and demonstrate that correct integrin function assessment can be achieved with a combination of diagnostic methods.
Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis
Authors: Andersson Cecilia K , Andersson-Sjöland Annika , Mori Michiko , Hallgren Oskar , Pardo Annie , Eriksson Leif , Bjermer Leif , Löfdahl Claes-Göran , Selman Moises , Westergren-Thorsson Gunilla , Erjefält Jonas S 
Published: November 2011

AbstractBackgroundAlthough mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.MethodsSmall airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MCTand MCTCmast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.ResultsIn the alveolar parenchyma in lungs from patients with CF, MCTCnumbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTCand MCTcells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTCdensity was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTCcorrelated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTCexpression of TGF-β, correlated negatively with patient lung function.ConclusionsThe present study reveals that altered mast cell populations, with increased numbers of MCTCin diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.
Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice
Authors: Huang Szu-Wei , Lee Yi-Ping , Hung Yu-Ting , Lin Chun-Hung , Chuang Jih-Ing , Lei Huan-Yao , Su Ih-Jen , Yu Chun-Keung 
Published: November 2011

Abstract

Background
Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident.

Methods
To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection.

Results
After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1)-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS). While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only.

Conclusions
Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.
Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis
Authors: Chen Xiaowei S , Penny David , Collins Lesley J 
Published: November 2011

Abstract

Background
Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis.

Results
We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs.

Conclusions
Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes.
Mycobacterium genavense as a cause of subacute pneumonia in patients with severe cellular immunodeficiency
Authors: Rammaert Blandine , Couderc Louis-Jean , Rivaud Elisabeth , Honderlick Patrick , Zucman David , Mamzer Marie-France , Cahen Pierre , Bille Emmanuel , Lecuit Marc , Lortholary Olivier , Catherinot Emilie 
Published: November 2011

Abstract

Background

Mycobacterium genavense is a rare nontuberculous mycobacteria (NTM). Human infections are mostly disseminated in the setting of the AIDS epidemic or the use of aggressive immunosuppressive treatments. M. genavense culture is fastidious, requiring supplemented media. Pulmonary involvement rarely occurs as a primary localization.

Cases presentation
We report here two patients with pneumonia as the predominant manifestation of M. genavense infection: one kidney transplanted patient and one HIV-infected patient. Both patients were initially treated with anti-tuberculous drugs before the identification of M. genavense on sputum or broncho-alveolar lavage fluid culture. A four-drug regimen including clarithromycin and rifabutin was started. Gamma interferon has been helpful in addition to antimycobacterial treatment for one patient.

Conclusion
Clinicians should be aware that M. genavense could be the etiologic agent of sub-acute pneumonia mimicking tuberculosis in patients with cellular immunodeficiency status.
Chemotherapeutic errors in hospitalised cancer patients: attributable damage and extra costs
Authors: Ranchon Florence , Salles Gilles , Späth Hans-Martin , Schwiertz Vérane , Vantard Nicolas , Parat Stéphanie , Broussais Florence , You Benoît , Tartas Sophie , Souquet Pierre Jean , Dussart Claude , Falandry Claire , Henin Emilie , Freyer Gilles , Rioufol Catherine 
Published: November 2011

Abstract

Background
In spite of increasing efforts to enhance patient safety, medication errors in hospitalised patients are still relatively common, but with potentially severe consequences. This study aimed to assess antineoplastic medication errors in both affected patients and intercepted cases in terms of frequency, severity for patients, and costs.

Methods
A 1-year prospective study was conducted in order to identify the medication errors that occurred during chemotherapy treatment of cancer patients at a French university hospital. The severity and potential consequences of intercepted errors were independently assessed by two physicians. A cost analysis was performed using a simulation of potential hospital stays, with estimations based on the costs of diagnosis-related groups.

Results
Among the 6, 607 antineoplastic prescriptions, 341 (5.2%) contained at least one error, corresponding to a total of 449 medication errors. However, most errors (n = 436) were intercepted before medication was administered to the patients. Prescription errors represented 91% of errors, followed by pharmaceutical (8%) and administration errors (1%). According to an independent estimation, 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage, while 2.6% would have compromised the vital prognosis of the patient, with four to eight deaths thus being avoided. Overall, 13 medication errors reached the patient without causing damage, although two patients required enhanced monitoring. If the intercepted errors had not been discovered, they would have resulted in 216 additional days of hospitalisation and cost an estimated annual total of 92, 907€, comprising 69, 248€ (74%) in hospital stays and 23, 658€ (26%) in additional drugs.

Conclusion
Our findings point to the very small number of chemotherapy errors that actually reach patients, although problems in the chemotherapy ordering process are frequent, with the potential for being dangerous and costly.
Determinants of rapid weight gain during infancy: baseline results from the NOURISH randomised controlled trial
Authors: Mihrshahi Seema , Battistutta Diana , Magarey Anthea , Daniels Lynne A 
Published: November 2011

AbstractBackgroundRapid weight gain in infancy is an important predictor of obesity in later childhood. Our aim was to determine which modifiable variables are associated with rapid weight gain in early life.MethodsSubjects were healthy infants enrolled in NOURISH, a randomised, controlled trial evaluating an intervention to promote positive early feeding practices. This analysis used the birth and baseline data for NOURISH. Birthweight was collected from hospital records and infants were also weighed at baseline assessment when they were aged 4-7 months and before randomisation. Infant feeding practices and demographic variables were collected from the mother using a self administered questionnaire. Rapid weight gain was defined as an increase in weight-for-age Z-score (using WHO standards) above 0.67 SD from birth to baseline assessment, which is interpreted clinically as crossing centile lines on a growth chart. Variables associated with rapid weight gain were evaluated using a multivariable logistic regression model.ResultsComplete data were available for 612 infants (88% of the total sample recruited) with a mean (SD) age of 4.3 (1.0) months at baseline assessment. After adjusting for mother's age, smoking in pregnancy, BMI, and education and infant birthweight, age, gender and introduction of solid foods, the only two modifiable factors associated with rapid weight gain to attain statistical significance were formula feeding [OR = 1.72 (95%CI 1.01-2.94), P = 0.047] and feeding on schedule [OR = 2.29 (95%CI 1.14-4.61), P = 0.020]. Male gender and lower birthweight were non-modifiable factors associated with rapid weight gain.ConclusionsThis analysis supports the contention that there is an association between formula feeding, feeding to schedule and weight gain in the first months of life. Mechanisms may include the actual content of formula milk (e.g. higher protein intake) or differences in feeding styles, such as feeding to schedule, which increase the risk of overfeeding.Trial RegistrationAustralian Clinical Trials RegistryACTRN12608000056392
Statistical learning methods as a preprocessing step for survival analysis: evaluation of concept using lung cancer data
Authors: Behera Madhusmita , Fowler Erin E , Owonikoko Taofeek K , Land Walker H , Mayfield William , Chen Zhengjia , Khuri Fadlo R , Ramalingam Suresh S , Heine John J 
Published: November 2011

Abstract

Background
Statistical learning (SL) techniques can address non-linear relationships and small datasets but do not provide an output that has an epidemiologic interpretation.

Methods
A small set of clinical variables (CVs) for stage-1 non-small cell lung cancer patients was used to evaluate an approach for using SL methods as a preprocessing step for survival analysis. A stochastic method of training a probabilistic neural network (PNN) was used with differential evolution (DE) optimization. Survival scores were derived stochastically by combining CVs with the PNN. Patients (n = 151) were dichotomized into favorable (n = 92) and unfavorable (n = 59) survival outcome groups. These PNN derived scores were used with logistic regression (LR) modeling to predict favorable survival outcome and were integrated into the survival analysis (i.e. Kaplan-Meier analysis and Cox regression). The hybrid modeling was compared with the respective modeling using raw CVs. The area under the receiver operating characteristic curve (Az) was used to compare model predictive capability. Odds ratios (ORs) and hazard ratios (HRs) were used to compare disease associations with 95% confidence intervals (CIs).

Results
The LR model with the best predictive capability gave Az = 0.703. While controlling for gender and tumor grade, the OR = 0.63 (CI: 0.43, 0.91) per standard deviation (SD) increase in age indicates increasing age confers unfavorable outcome. The hybrid LR model gave Az = 0.778 by combining age and tumor grade with the PNN and controlling for gender. The PNN score and age translate inversely with respect to risk. The OR = 0.27 (CI: 0.14, 0.53) per SD increase in PNN score indicates those patients with decreased score confer unfavorable outcome. The tumor grade adjusted hazard for patients above the median age compared with those below the median was HR = 1.78 (CI: 1.06, 3.02), whereas the hazard for those patients below the median PNN score compared to those above the median was HR = 4.0 (CI: 2.13, 7.14).

Conclusion
We have provided preliminary evidence showing that the SL preprocessing may provide benefits in comparison with accepted approaches. The work will require further evaluation with varying datasets to confirm these findings.