bluuebunny/crossref_metadata_2025 huggingface dataset:
A short‐term educational program improved physicians’ adherence to guidelines for COPD and asthma in Shanghai
Authors: Fang Xiaocong , Li Shanqun , Gao Lei , Zhao Naiqing , Wang Xiangdong , Bai Chunxue
Published: July 2012

Background

Chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and asthma exert increasing burden on society while the management of them is far from adequate. The objective of this study is to evaluate adherence to guidelines through a patient study, and then investigate the effects of a short‐term quality improvement educational program among clinicians in Shanghai, China.

Methods

A prescription survey was performed in a random sample of 100 COPD and asthma outpatients to assess their pharmacological therapy. Then, an educational program was conducted in young pulmonary physicians from 83 hospitals in Shanghai. The training course was divided into 7 sessions of 2 hours delivered over 4 days from July 2010 to August 2011. Three months later, all of the participants were asked to take a written examination to assess the efficiency of training.

Results

Prescription survey among the patients indicated the prescriptions are not consistent with the recommendations of current GOLD and GINA guidelines. The mainly existing issue is the overuse of inhaled glucocorticosteroid. For the educational program, 161 pulmonary physicians have attended the training course, and 110 clinicians finished the tests with an attendance rate of 68.3%. Although most of the clinicians recognized the increasing burden of COPD and asthma, they do not know well about the core elements of guidelines and their clinical practice is not fully in agreement with current recommendations. Through crossover comparison, our results suggested clinicians’ knowledge of the guidelines was improved after training.

Conclusions

We concluded that application of continuous educational programs among physicians might promote their adherence to guidelines, and by that improve the quality of healthcare.
Defining cut-off values for disease activity states and improvement scores for patient-reported outcomes: the example of the Rheumatoid Arthritis Impact of Disease (RAID)
Authors: Dougados Maxime , Brault Yves , Logeart Isabelle , van der Heijde Désirée , Gossec Laure , Kvien Tore
Published: July 2012

Introduction

The Rheumatoid Arthritis Impact of Disease (RAID) is a patient-reported outcome measure evaluating the impact of rheumatoid arthritis (RA) on patient quality of life. It comprises 7 domains that are evaluated as continuous variables from 0 (best) to 10 (worst). The objective was to define and identify cut-off values for disease activity states as well as improvement scores in order to present results at the individual level (for example, patient in acceptable state, improved patient).

Methods

Patients with definite active RA requiring anti-tumour necrosis factor (anti-TNF) therapy were seen at screening, baseline and after 4 and 12 weeks of etanercept therapy. Answers to "Gold standard" questions on improvement (MCII: Minimum Clinically Important Improvement) and an acceptable status (PASS: Patient Acceptable Symptom State) were collected as well as the RAID score and Disease Activity Score 28- erythrocyte sedimentation rate (DAS28-ESR). Cut-offs were defined by different techniques including empirical, measurement error and gold standard anchors. The external validity of these cut-offs was evaluated using the positive likelihood ratio (LR) based on the patient's perspective (for example, patient's global) and on low disease activity status (such as DAS28-ESR).

Results

Ninety-seven (97) of the 108 recruited patients (age: 54 ± 13 years old, female gender: 75%, rheumatoid factor positive: 81%, disease duration: 8 ± 7 years, CRP: 18 ± 30 mg/l, DAS28-ESR: 5.4 ± 0.8) completed the 12 weeks of the study. The different techniques suggested thresholds ranging from 0.2 to 3 (absolute change) and from 6 to 50% (relative change) for defining MCII and thresholds from less than 1 to less than 4.2 for defining PASS. The evaluation of external validity (LR+) showed the highest LR+ was obtained with thresholds of 3 for absolute change; 50% for relative change and less than 2 for an acceptable status.

Conclusions

This study showed that thresholds defined for continuous variables are closely related to the methodological technique, justifying a systematic evaluation of their validity. Our results suggested that a change of at least 3 points (absolute) or 50% (relative) in the RAID score should be used to define a MCII and that a maximal value of 2 defines an acceptable status.

Trial Registration

Clinicaltrial.gov: NCT004768053
Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO)
Authors: Lecarpentier Julie , Noguès Catherine , Mouret-Fourme Emmanuelle , Gauthier-Villars Marion , Lasset Christine , Fricker Jean-Pierre , Caron Olivier , Stoppa-Lyonnet Dominique , Berthet Pascaline , Faivre Laurence , Bonadona Valérie , Buecher Bruno , Coupier Isabelle , Gladieff Laurence , Gesta Paul , Eisinger François , Frénay Marc , Luporsi Elisabeth , Lortholary Alain , Colas Chrystelle , Dugast Catherine , Longy Michel , Pujol Pascal , Tinat Julie ,   GENEPSO, Lidereau Rosette , Andrieu Nadine
Published: July 2012

Introduction

Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity.

Methods

We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model.

Results

Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3).

Conclusions

Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.
Benefit of a single recruitment maneuver after an apnea test for the diagnosis of brain death
Authors: Paries Marie , Boccheciampe Nicolas , Raux Mathieu , Riou Bruno , Langeron Olivier , Nicolas-Robin Armelle
Published: July 2012

Introduction

Many potential lung transplants are lost because of hypoxemia during donor management. We hypothesized that the apnea test, necessary to confirm the diagnosis of brain death in potential lung donors, was involved in the decrease in the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FiO2) and that a single recruitment maneuver performed just after the apnea test can reverse this alteration.

Methods

In this case-control study, we examined the effectiveness of the recruitment maneuver with a comparison cohort of brain dead patients who did not receive the maneuver. Patients were matched one-to-one on the basis of initial PaO2/FiO2 and on the duration of mechanical ventilation before the apnea test. PaO2/FiO2 was measured before (T1), at the end (T2) and two hours after apnea test (T3).

Results

Twenty-seven patients were included in each group. The apnea test was associated with a significant decrease in PaO2/FiO2 from 284 ± 98 to 224 ± 104 mmHg (P < 0.001). The decrease in PaO2/FiO2 between T1 and T3 was significantly lower in the recruitment maneuver group than in the control group (-4 (-68-57) vs -61 (-110--18) mmHg, P = 0.02). The number of potential donors with PaO2/FiO2 > 300 mmHg decreased by 58% (95% CI: 28-85%) in the control group vs 0% (95% CI: 0-34%) in the recruitment maneuver group (P < 0.001).

Conclusions

The apnea test induced a decrease in PaO2/FiO2 in potential lung donors. A single recruitment maneuver performed immediately after the apnea test can reverse this alteration and may prevent the loss of potential lung donors.
A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples
Authors: Dollive Serena , Peterfreund Gregory L , Sherrill-Mix Scott , Bittinger Kyle , Sinha Rohini , Hoffmann Christian , Nabel Christopher S , Hill David A , Artis David , Bachman Michael A , Custers-Allen Rebecca , Grunberg Stephanie , Wu Gary D , Lewis James D , Bushman Frederic D
Published: July 2012

Eukaryotic microorganisms are important but understudied components of the human microbiome. Here we present a pipeline for analysis of deep sequencing data on single cell eukaryotes. We designed a new 18S rRNA gene-specific PCR primer set and compared a published rRNA gene internal transcribed spacer (ITS) gene primer set. Amplicons were tested against 24 specimens from defined eukaryotes and eight well-characterized human stool samples. A software pipeline https://sourceforge.net/projects/brocc/ was developed for taxonomic attribution, validated against simulated data, and tested on pyrosequence data. This study provides a well-characterized tool kit for sequence-based enumeration of eukaryotic organisms in human microbiome samples.
Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization
Authors: Barclay G Robin , Tura Olga , Samuel Kay , Hadoke Patrick WF , Mills Nicholas L , Newby David E , Turner Marc L
Published: July 2012

Introduction

Endothelial progenitor cells (EPC) capable of initiating or augmenting vascular growth were recently identified within the small population of CD34-expressing cells that circulate in human peripheral blood and which are considered hematopoietic progenitor cells (HPC). Soon thereafter human HPC began to be used in clinical trials as putative sources of EPC for therapeutic vascular regeneration, especially in myocardial and critical limb ischemias. However, unlike HPC where hematopoietic efficacy is related quantitatively to CD34+ cell numbers implanted, there has been no consensus on how to measure EPC or how to assess cellular graft potency for vascular regeneration. We employed an animal model of spontaneous neovascularization to simultaneously determine whether human cells incorporate into new vessels and to quantify the effect of different putative angiogenic cells on vascularization in terms of number of vessels generated. We systematically compared competence for therapeutic angiogenesis in different sources of human cells with putative angiogenic potential, to begin to provide some rationale for optimising cell procurement for this therapy.

Methods

Human cells employed were mononuclear cells from normal peripheral blood and HPC-rich cell sources (umbilical cord blood, mobilized peripheral blood, bone marrow), CD34+ enriched or depleted subsets of these, and outgrowth cell populations from these. An established sponge implant angiogenesis model was adapted to determine the effects of different human cells on vascularization of implants in immunodeficient mice. Angiogenesis was quantified by vessel density and species of origin by immunohistochemistry.

Results

CD34+ cells from mobilized peripheral blood or umbilical cord blood HPC were the only cells to promote new vessel growth, but did not incorporate into vessels. Only endothelial outgrowth cells (EOC) incorporated into vessels, but these did not promote vessel growth.

Conclusions

These studies indicate that, since EPC are very rare, any benefit seen in clinical trials of HPC in therapeutic vascular regeneration is predominantly mediated by indirect proangiogenic effects rather than through direct incorporation of any rare EPC contained within these sources. It should be possible to produce autologous EOC for therapeutic use, and evaluate the effect of EPC distinct from, or in synergy with, the proangiogenic effects of HPC therapies.
Phase I Multidose-Escalation Study of the Anti-CD19 Maytansinoid Immunoconjugate SAR3419 Administered by Intravenous Infusion Every 3 Weeks to Patients With Relapsed/Refractory B-Cell Lymphoma
Authors: Younes Anas , Kim Stella , Romaguera Jorge , Copeland Amanda , Farial Silvana de Castro , Kwak Larry W. , Fayad Luis , Hagemeister Frederick , Fanale Michelle , Neelapu Sattva , Lambert John M. , Morariu-Zamfir Rodica , Payrard Sandrine , Gordon Leo I.
Published: July 2012

Purpose

We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma.

Patients and Methods

Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days.

Results

Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m2, and an elimination half-life in the range of 3 to 7 days.

Conclusion

Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.
Tumor Response and Toxicity of Neoadjuvant Erlotinib in Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Schaake Eva E. , Kappers Ingrid , Codrington Henk E. , Valdés Olmos Renato A. , Teertstra Hendrik J. , van Pel Renée , Burgers Jacobus A. , van Tinteren Harm , Klomp Houke M.
Published: July 2012

Purpose

The development of targeted therapy has introduced new options to improve treatment outcome in selected patients. The objective of this prospective study was to investigate the safety of preoperative erlotinib treatment and the (in vivo) response in patients with early-stage resectable non–small-cell lung cancer (NSCLC).

Patients and Methods

This study was designed as an open-label phase II trial, performed in four hospitals in the Netherlands, according to a Simon's minimax two-stage procedure. Initially, operable patients with early-stage NSCLC (n = 15) were entered from an enriched population (never-smoker, female sex, nonsquamous histology, or Asian ethnicity); thereafter, unselected patients were included to a total of N = 60. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Response to treatment was evaluated using [18F] fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) scans during treatment and histologic examination of the resection specimen. Primary end points were toxicity and pathologic response.

Results

Sixty patients were included. Seven patients stopped treatment prematurely (12%). Skin toxicity was present in 37 patients (62%), and diarrhea was present in 21 patients (35%). PET evaluation revealed metabolic response (> 25% standardized uptake value decrease) in 16 patients (27%); CT evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) showed response in three patients (5%). At surgery, no unexpected complications occurred. Pathologic examination showed more than 50% necrosis in 14 patients (23%), of whom three (5%) had more than 95% tumor necrosis. The response rate in the enriched population was 34% (10 of 29 patients).

Conclusion

According to predefined criteria, neoadjuvant erlotinib has low toxicity and sufficient activity to deserve further testing in future studies in an enriched population.
Stage Migration, Selection Bias, and Survival Associated With the Adoption of Positron Emission Tomography Among Medicare Beneficiaries With Non–Small-Cell Lung Cancer, 1998-2003
Authors: Dinan Michaela A. , Curtis Lesley H. , Carpenter William R. , Biddle Andrea K. , Abernethy Amy P. , Patz Edward F. , Schulman Kevin A. , Weinberger Morris
Published: July 2012

Purpose

Previous studies have linked the use of positron emission tomography (PET) with improved outcomes among patients with non–small-cell lung cancer (NSCLC). However, this association may be confounded by PET-induced stage migration and selection bias. We examined the association between PET use and overall survival among Medicare beneficiaries with NSCLC.

Patients and Methods

Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) –Medicare data was used to characterize changes in overall survival, stage-specific survival, and stage distribution among Medicare beneficiaries with NSCLC between 1998 and 2003.

Results

A total of 97,007 patients with NSCLC diagnosed between 1998 and 2003 met the study criteria. Two-year and 4-year survival remained unchanged, despite widespread adoption of PET. The proportion of patients staged with advanced disease increased from 44% to 50%. Upstaging of disease was accompanied by stage-specific improved survival, with 2-year survival of stage IV disease increasing from 8% to 11% between 1998 and 2003. PET was more likely to be administered to patients with less advanced disease (stages I through IIIA) and greater overall survival.

Conclusion

Overall survival among Medicare beneficiaries with NSCLC was unchanged between 1998 and 2003, despite widespread adoption of PET. The association between PET use and increased survival likely reflects an artifact of selection bias and consequent stage migration.
Intrapatient Cetuximab Dose Escalation in Metastatic Colorectal Cancer According to the Grade of Early Skin Reactions: The Randomized EVEREST Study
Authors: Van Cutsem Eric , Tejpar Sabine , Vanbeckevoort Dirk , Peeters Marc , Humblet Yves , Gelderblom Hans , Vermorken Jan B. , Viret Frederic , Glimelius Bengt , Gallerani Elisa , Hendlisz Alain , Cats Annemieke , Moehler Markus , Sagaert Xavier , Vlassak Soetkin , Schlichting Michael , Ciardiello Fortunato
Published: July 2012

Purpose

Skin toxicity in patients receiving cetuximab has been associated positively with clinical outcome in several tumor types. This study investigated the effect of cetuximab dose escalation in patients with irinotecan-refractory metastatic colorectal cancer who had developed no or mild skin reactions after 21 days of treatment at the standard dose. This article reports clinical and pharmacokinetic (PK) data.

Patients and Methods

After 21 days of standard-dose cetuximab (400 mg/m2 initial dose, then 250 mg/m2 per week) plus irinotecan, patients with ≤ grade 1 skin reactions were randomly assigned to standard-dose (group A) or dose-escalated (to 500 mg/m2 per week; group B) cetuximab. Patients with ≥ grade 2 skin reactions continued on standard-dose cetuximab plus irinotecan (group C).

Results

The intent-to-treat population comprised 157 patients. PK profiles reflected the dose increase and were predictable across the dose range investigated. Weekly cetuximab doses of up to 500 mg/m2 were well tolerated, and grade 3 and 4 adverse events were generally comparable between treatment groups. Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively). Dose escalation, compared with standard dosing, showed some evidence for improved response rate (30% v 16%, respectively) and disease control rate (70% v 58%, respectively) but no indication of benefit in relation to overall survival. In an exploratory analysis, dose escalation seemed to increase response rate compared with standard dosing in patients with KRAS wild-type but not KRAS mutant tumors.

Conclusion

Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated. The possible indication for improved efficacy in the dose-escalation group warrants further investigation.
International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer: MONET1
Authors: Scagliotti Giorgio V. , Vynnychenko Ihor , Park Keunchil , Ichinose Yukito , Kubota Kaoru , Blackhall Fiona , Pirker Robert , Galiulin Rinat , Ciuleanu Tudor-Eliade , Sydorenko Oleksandr , Dediu Mircea , Papai-Szekely Zsolt , Banaclocha Natividad Martinez , McCoy Sheryl , Yao Bin , Hei Yong-jiang , Galimi Francesco , Spigel David R.
Published: July 2012

Purpose

We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non–small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma.

Patients and Methods

Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m2) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS.

Results

A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment.

Conclusion

Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis
Authors: Mauguen Audrey , Le Péchoux Cécile , Saunders Michele I. , Schild Steven E. , Turrisi Andrew T. , Baumann Michael , Sause William T. , Ball David , Belani Chandra P. , Bonner James A. , Zajusz Aleksander , Dahlberg Suzanne E. , Nankivell Matthew , Mandrekar Sumithra J. , Paulus Rebecca , Behrendt Katarzyna , Koch Rainer , Bishop James F. , Dische Stanley , Arriagada Rodrigo , De Ruysscher Dirk , Pignon Jean-Pierre
Published: July 2012

Purpose

In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation.

Material and Methods

We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy.

Results

In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities.

Conclusion

Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.
Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats
Authors: Abreu Mariana , Aguado Delia , Benito Javier , Gómez de Segura Ignacio A
Published: July 2012

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane ( n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.
Liability for the Suicide of a Patient
Authors: Samuels Alec
Published: July 2012

The doctor suspects or knows that the patient will or might commit suicide. If the patient does in fact commit suicide, is the doctor or the health authority liable?
Structural insights into the function of 23S rRNA methyltransferase RlmG (m2G1835) from Escherichia coli
Authors: Zhang Heng , Gao Zeng-Qiang , Wei Yong , Wang Wen-Jia , Liu Guang-Feng , Shtykova Eleonora V. , Xu Jian-Hua , Dong Yu-Hui
Published: July 2012

RlmG is a specific AdoMet-dependent methyltransferase (MTase) responsible for N2-methylation of G1835 in 23S rRNA of Escherichia coli. Methylation of m2G1835 specifically enhances association of ribosomal subunits and provides a significant advantage for bacteria in osmotic and oxidative stress. Here, the crystal structure of RlmG in complex with AdoMet and its structure in solution were determined. The structure of RlmG is similar to that of the MTase RsmC, consisting of two homologous domains: the N-terminal domain (NTD) in the recognition and binding of the substrate, and the C-terminal domain (CTD) in AdoMet-binding and the catalytic process. However, there are distinct positively charged protuberances and a distribution of conserved residues contributing to the charged surface patch, especially in the NTD of RlmG for direct binding of protein-free rRNA. The RNA-binding properties of the NTD and CTD characterized by both gel electrophoresis mobility shift assays and isothermal titration calorimetry showed that NTD could bind RNA independently and RNA binding was achieved by the NTD, accomplished by a coordinating role of the CTD. The model of the RlmG-AdoMet-RNA complex suggested that RlmG may unfold its substrate RNA in the positively charged cleft between the NTD and CTD, and then G1835 disengages from its Watson-Crick pairing with C1905 and flips out to insert into the active site. Our structure and biochemical studies provide novel insights into the catalytic mechanism of G1835 methylation.
Sequential RNA degradation pathways provide a fail-safe mechanism to limit the accumulation of unspliced transcripts in Saccharomyces cerevisiae
Authors: Sayani Shakir , Chanfreau Guillaume F.
Published: July 2012

The nuclear exosome and the nonsense-mediated mRNA decay (NMD) pathways have been implicated in the degradation of distinct unspliced transcripts in Saccharomyces cerevisiae. In this study we show that these two systems can act sequentially on specific unspliced pre-mRNAs to limit their accumulation. Using steady-state and decay analyses, we show that while specific unspliced transcripts rely mostly on NMD or on the nuclear exosome for their degradation, some unspliced RNAs are stabilized only when both the nuclear exosome and NMD are inactivated. We found that the mechanism of degradation of these unspliced pre-mRNAs is not influenced by promoter identity. However, the specificity in the pre-mRNAs degradation pathways can be manipulated by changing the rate of export or retention of these mRNAs. For instance, reducing the nuclear export of pre-mRNAs mostly degraded by NMD results in a higher fraction of unspliced transcripts degraded by the nuclear exosome. Reciprocally, inactivating the Mlp retention factors results in a higher fraction of unspliced transcripts degraded by NMD for precursors normally targeted by the nuclear exosome. Overall, these results demonstrate that a functional redundancy exists between nuclear and cytoplasmic degradation pathways for unspliced pre-mRNAs, and suggest that the degradation routes of these species are mainly determined by the efficiency of their nuclear export rates. The presence of these two sequential degradation pathways for unspliced pre-mRNAs underscores the importance of limiting their accumulation and might serve as a fail-safe mechanism to prevent the expression of these nonfunctional RNAs.
Electronic interactions of silicon nanocrystals and nanocarbon materials: Hybrid solar cells
Authors: Švrček Vladimir , Mariotti Davide
Published: July 2012

Hybrid inorganic/nanocarbon solar cells represent low-cost solutions for the large-scale manufacturing of energy conversion devices. Here we discuss results that relate to the electronic interactions of nanocarbon materials with freestanding and surfactant-free silicon nanocrystals (Si-ncs) with quantum confinement effects, integrated in bulk-heterojunction solar cells. In particular, we demonstrate the feasibility of bulk-heterojunction photovoltaic solar cells that consist of Si-ncs combined with fullerenes or with semiconducting single-walled carbon nanotubes (SWCNTs). We show that the energy levels between Si-ncs with energy gap exceeding 1.75 eV and fullerenes are adequate for exciton dissociation and carriers (electrons/holes) generation and that hybrid solar cells formed by Si-ncs and semi-conducting SWCNTs favor exciton dissociation only when a distinct chiral index [i.e., (7,5)] is used. While fullerenes show energy conversion capabilities in the visible spectral region (1.7–3.1 eV), the cells containing the SWCNTs, in comparison, have a considerably expanded optical response covering a broad range of the spectrum (0.9–3.1 eV).
Government Effectiveness, the Global Financial Crisis, and Multinational Enterprise Internationalization
Authors: Williams Christopher , Martinez Candace A.
Published: July 2012

This study examines the influence of national institutions on multinational enterprise entry mode behavior during economic downturns. Drawing on institutional and transaction cost theories, the authors propose (1) alternative hypotheses for the effect of host-country government effectiveness (a spatial institution) and (2) hypotheses for a direct and an indirect effect of a global financial crisis (a temporal event affecting all countries) on firms’ internationalization strategy. With a sample comprising 624 foreign expansion investments conducted by Dutch multinational enterprises between 2004 and 2009 into 66 countries, this investigation confirms that majority control more likely occurs when host-country government effectiveness is high or when the investment is made during a global financial crisis. The authors also find support for a hypothesized moderating effect of a global financial crisis. Concluding remarks discuss the implications of these findings for scholars and practitioners.
Comedy of Abandon: Lars von Trier's Melancholia
Authors: Figlerowicz Marta
Published: July 2012

The piece reviews Lars von Trier's Melancholia (2011). This film marks a break with von Trier's prior work. Rather than push its plot to the limits of emotional intensity and gravity, Melancholia studies and comically questions our sense of feelings’ proportion and scale.
Film Acting and the Arts of Imitation
Authors: Naremore James
Published: July 2012

Modern theories of acting follow Stanislavsky and emphasize emotional truthfulness achieved through self-expression, but an older tradition emphasizes technique and imitation and this emphasis is argued to be equally relevant to movie acting.
The Nation before Taste: The Challenges of American Culinary History
Authors: Haley Andrew P.
Published: July 2012

Food is material and familiar, and because it is, we are often overconfident about our ability to understand the culinary past. It is easy to believe that if we can discover the recipe for some forgotten dish, the history of the dish becomes intelligible. When it does not, it tempts those who consume culinary history to impose modern sensibilities on our predecessors. “The Nation before Taste” argues that historians and museum curators must be especially vigilant when presenting the history of food. Reviewing a series of historical challenges that stemmed from studying the United States in the late nineteenth and early twentieth centuries, the author suggests three strategies for grounding food history in the past: recognizing that taste is constructed and temporal; engaging with material and social contexts, especially physiology, class, and gender; and admitting to our audiences that not all culinary mysteries have immediate or simple answers.
Delayed-Onset Seizure and Cardiac Arrest After Amitriptyline Overdose, Treated With Intravenous Lipid Emulsion Therapy
Authors: Levine Michael , Brooks Daniel E. , Franken Aimee , Graham Robert
Published: July 2012

In recent years, intravenous lipid emulsion (ILE) therapy has emerged as a new rescue antidote for treatment of certain toxicities, including cyclic antidepressants, and as the primary treatment of toxic manifestations after local anesthetic exposure. We present a case of a 13-year-old girl who developed delayed seizures and cardiac arrest after amitriptyline ingestion. As part of the treatment, she was treated with ILE therapy. The patient's laboratories were not interpretable for several hours after the lipid emulsion. The patient developed pancreatitis after the ILE therapy. This case is unique; not only is it one of the first reported cases of lipid emulsion being used in a pediatric patient, but in that the patient developed delayed toxicity and iatrogenic harm from the ILE.
Primary Sex Headache in Adolescents
Authors: Gelfand Amy A. , Goadsby Peter J.
Published: July 2012

Primary headache associated with sexual activity is a rare headache disorder that has only been reported twice previously in adolescents. Although it can mimic life-threatening causes of thunderclap-onset headache, primary sex headache is benign, self-limited, and highly responsive to indomethacin. Given the sensitive nature of sexual development in adolescents, it is important that pediatric providers know when to ask about this symptom and how to proceed with diagnostics and therapy when it arises. We report 2 new adolescent cases and review the semiology, epidemiology, and treatment of primary sex headache.
Economic Evaluation of Strategies to Reduce Sudden Cardiac Death in Young Athletes
Authors: Schoenbaum Michael , Denchev Peter , Vitiello Benedetto , Kaltman Jonathan R.
Published: July 2012

OBJECTIVE:

There is controversy about appropriate methods to reduce sudden cardiac death (SCD) in young athletes, but there is limited evidence on costs or consequences of alternative strategies. The objective of this study was to evaluate the cost-effectiveness of adding electrocardiogram (ECG) screening to the currently standard practice of preparticipation history and physical examination (H&P) to reduce SCD.

METHODS:

Decision analysis modeling by using a societal perspective, with annual Markov cycles from age 14 until death. Three screening strategies were evaluated: (1) H&P, with cardiology referral if abnormal (current standard practice); (2) H&P, plus ECG after negative H&P, and cardiology referral if either is abnormal; and (3) ECG only, with cardiology referral if abnormal. Children identified with SCD-associated cardiac abnormalities were restricted from sports and received cardiac treatment. Main outcome measures were costs of screening and treatment, quality-adjusted life years (QALYs), and premature deaths averted.

RESULTS:

Relative to strategy 1, incremental cost-effectiveness is $68 800/QALY for strategy 2 and $37 700/QALY for strategy 3. Monte Carlo simulation revealed the chance of incremental cost-effectiveness compared with strategy 1 was 30% for strategy 2 and 66% for strategy 3 (assumed willingness to pay ≤$50 000/QALY). Compared with strategy 1, strategy 2 averted 131 additional SCDs at $900 000 per case, and strategy 3 averted 127 SCDs at $600 000 per case.

CONCLUSIONS:

Under a societal willingness to pay threshold of $50 000/QALY, adding ECGs to current preparticipation evaluations for athletes is not cost-effective, with costs driven largely by false-positive findings.
Two-Year Follow-up of an Adolescent Behavioral Weight Control Intervention
Authors: Lloyd-Richardson Elizabeth E. , Jelalian Elissa , Sato Amy F. , Hart Chantelle N. , Mehlenbeck Robyn , Wing Rena R.
Published: July 2012

OBJECTIVE:

This study examined the 24-month outcomes of a randomized controlled trial of a group-based behavioral weight control (BWC) program combined with either activity-based peer intervention or aerobic exercise.

METHODS:

At baseline, 118 obese adolescents (68% female; BMI = 31.41 ± 3.33) ages 13 to 16 years (mean = 14.33; SD = 1.02) were randomized to receive 1 of 2 weight loss interventions. Both interventions received the same 16-week group-based cognitive-behavioral treatment, combined with either aerobic exercise or peer-based adventure therapy. Eighty-nine adolescents (75% of original sample) completed the 24-month follow-up. Anthropometric and psychosocial measures were obtained at baseline, at the end of the 16-week intervention, and at 12 and 24 months following randomization.

RESULTS:

An intent-to-treat mixed factor analysis of variance indicated a significant effect for time on both percent over 50th percentile BMI for age and gender and standardized BMI score, with no differences by intervention group. Post hoc comparisons showed a significant decrease in percent overweight at 4 months (end of treatment), which was maintained at both 12- and 24-month follow-up visits. Significant improvements on several dimensions of self-concept were noted, with significant effects on physical appearance self-concept that were maintained through 24 months.

CONCLUSIONS:

Both BWC conditions were effective at maintaining reductions in adolescent obesity and improvements in physical appearance self-concept through 24-month follow-up. This study is one of the first to document long-term outcomes of BWC intervention among adolescents.
Recooling for Rebound Seizures After Rewarming in Neonatal Encephalopathy
Authors: Kendall Giles S. , Mathieson Sean , Meek Judith , Rennie Janet M.
Published: July 2012

Infants undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy are at risk for rebound seizures during and after the rewarming phase. We report a term male infant who was cooled for hypoxic ischemic encephalopathy. He developed electrographic seizures for the first time during the warming phase, which continued in the hours after rewarming. The seizures stopped within 30 minutes of recooling to 33.5°C without anticonvulsant medication. He was uneventfully cooled for an additional 24 hours and then rewarmed with no recurrence of seizures. Hypothermia appeared to have an antiepileptic effect in this case and may be worthy of additional investigation as an adjunct to antiepileptic drug therapy in newborns.
Health related quality of life and productivity of women with overactive bladder
Authors: Péntek Márta , Gulácsi László , Majoros Attila , Piróth Csaba , Rubliczky Levente , Böszörményi Nagy Géza , Törzsök Ferenc , Timár Petra , Baji Petra , Brodszky Valentin
Published: July 2012

The objektive of the research was to assess the health related quality of life and productivity of women with overactive bladder. Methods: A cross-sectional survey was performed in 5 outpatient centers. General health status (EQ-5D), disease-specific quality of life (King’s Health Questionnaire) and productivity (Work Productivity and Activity Impairment) were assessed. Results: Sixty-one women with mean age of 57.7 (SD = 11.6) years have had symptoms for 6.6 (SD = 6.2) years and 57 (93%) had incontinence. The EQ-5D (mean 0.668, SD = 0.314) was not significantly lower than that of the average population (p>0.05). The impact of incontinence and physical limitation (mean 70.5 and 68.9, respectively) were significant, the King’s Health Questionnaire-utility was 0.932 (SD = 0.029). Productivity scores of involved patients were: absenteeism 0.04% (SD = 0.11), presenteeism 43.64% (SD = 28.54), overall work impairment 40.97% (SD = 26.91), and other activities 47.72% (SD = 27.24). Conclusions: Applicability of the EQ-5D and King’s Health Questionnaire as utility measures in overactive bladder deserve further research. Presenteeism should be considered in the evaluation of the therapy. Orv. Hetil., 2012, 153, 1068–1076.
Paciente laringectomizado total: perspectivas para a ação clínica do psicólogo
Authors: Barbosa Leopoldo Nelson Fernandes , Francisco Ana Lúcia
Published: July 2012

A cirurgia de laringectomia total implica a necessidade de procedimentos agressivos e provoca lesões estéticas e funcionais irrecuperáveis, acarretando repercussões biopsicossociais. Por meio de pesquisa de natureza qualitativa foram investigadas as repercussões psicossociais na construção subjetiva de pacientes laringectomizados e de seus cuidadores. O percurso do adoecimento é vivido como um momento de crise em que predomina o sentimento de desamparo e desalojamento. A perda da fala pode levar o paciente a isolar-se socialmente, afastar-se de suas funções profissionais, com sentimentos de vergonha e culpa, provocando intensa angústia e sofrimento. Os cuidadores sofrem diante da possibilidade da perda de um ente querido e, também, por tentativas, nem sempre bem sucedidas, de dar suporte e oferecer ambiência para as novas necessidades que se apresentam. Os resultados evidenciam que conhecer as repercussões psicossociais dessa experiência pode fornecer importantes subsídios para a psicologia clínica.
Grupo de orientação de mães no contexto de uma clínica-escola
Authors: Pardo Maria Benedita Lima , Carvalho Margarida Maria Silveira Britto de
Published: July 2012

O ambiente familiar vem merecendo atenção de estudiosos que analisam a influência de diferentes ambientes sociais no desenvolvimento infantil. Elaborou-se uma proposta de grupo de orientação para mães de crianças em fila de espera para atendimento psicoterápico. Os objetivos do presente estudo são descrever as características de funcionamento desse grupo e analisar seus resultados sob a perspectiva dos orientadores do grupo e das próprias mães. Os dados foram coletados em entrevistas iniciais e finais e no decorrer dos encontros. Procedeu-se à análise de conteúdo das informações relacionadas às falas das mães e aos procedimentos de intervenção. Os resultados indicaram estar ocorrendo aumento nos diálogos com os filhos, preocupação em dedicar-lhes mais tempo e a entender seus pontos de vista, busca em estabelecer limites, envolvendo também outras pessoas da família. Tais mudanças revelaram, portanto, alterações no funcionamento do microssistema familiar.
Liver damages and nuclear abnormalities in erythrocytes of Atherinella brasiliensis (Actynopterigii, Atherinopsidade) from two beaches in Southeast of Brazil
Authors: Fernandez Welingtom S. , Dias June Ferraz , Ribeiro Ciro Alberto Oliveira , Azevedo Juliana de Souza
Published: July 2012

There are few environmental studies using biomarkers for the species Atherinella brasiliensis in Brazil. In the present work, the presence of hepatic histopathological lesions and nuclear abnormalities in erythrocytes were investigated in A. brasiliensis from Lamberto, a beach under influence of domestic wastes and marine activities. For comparison, fish were also sampled in Puruba, a non-polluted beach, located in the northeastern of São Paulo State. The frequency of lesions found in liver was in higher numbers in individuals from Lamberto than Puruba beach. The most critical injuries observed in A. brasiliensis were the presence of necrotic areas, leucocytes infiltration and piknotic nucleus. A high occurrence of cells with vacuolization was also observed. The hepatic lesion index of the fish from Lamberto beach showed significant high values (Iorg=13) when compared with fish from Puruba beach (Iorg=7) suggesting the influence of the several human activities in the studied site. Notched and blebed nucleous were observed in this study, and significant differences were found between the studied sites. However, these differences did not reflect the total nuclear alterations.