bluuebunny/crossref_metadata_2025 huggingface dataset:
Results from the International Silver Graft Registry for high-risk patients treated with a metallic-silver impregnated vascular graft
Authors: Zegelman Max , Guenther Gisela , Waliszewski Matthias , Pukacki Fryderyk , Stanisic Michal Goran , Piquet Philippe , Passon Marius , Halloul Zuhir , Tautenhahn Jörg , Claeys Luc , Agostinho Claudia , Simici Dragos , Doebrich Dinah , Mueller Carsten , Balzer Kai
Published: May 2013

The purpose of this postmarket surveillance registry was to document the efficacy of a vascular prosthesis coated with metallic silver in high-risk patients undergoing vascular reconstructions. Patency (primary endpoint) and freedom from graft infection (secondary endpoint) data were assessed at a minimum of 12 months in patients with significant co-morbidity and/or confirmed graft infections or infected native vessels. Between November 2006 and December 2009, 230 patients with high-risk factors underwent aortic, peripheral and/or extra-anatomic reconstructions with Silver Graft® (SG) in six German, one French and one Polish vascular center. All participating centers used the metallic silver-coated polyester graft (SG) in various diameters and lengths including tubular and bifurcate vascular grafts. Doppler ultrasound follow-ups to determine graft patency were planned at 12 months or done at an earlier time in case the patient became symptomatic. A total of 230 patients were studied. Ten of these 230 patients had graft infections at baseline whereas the remaining 220 subjects had significant risk factors such as coronary artery disease (62.7%, 138/220), vascular access in scar tissue (27.3%, 60/220), Fontaine III/IV (38.2%, 84/220), chronic renal insufficiency (26.8%, 59/220) and diabetes (21.0%, 46/220). The long-term follow-up at 15.5 ± 8.3 months revealed a secondary patency rate of 93.2% (205/220) and an ‘all cause’ mortality rate of 18.6% (41/220). There was a freedom from de novo graft infection rate of 95.9% (211/220) in the high-risk group without graft infections at baseline. One regraft infection occurred distal of the revisional reconstruction in the 10 patients with graft infection at baseline. The presence of perigraft fluid at follow-up and Fontaine III/IV at baseline were found to be predictors for graft patency whereas perigraft fluid presence was the only predictor for de novo graft infections. This registry revealed favorable patency and freedom from de novo infections rates in a ‘high-risk’ population with significant co-morbidities.
Extracorporeal photopheresis in the treatment of graft-versus-host disease: evidence and opinion
Authors: Hart James W. , Shiue Lisa H. , Shpall Elizabeth J. , Alousi Amin M.
Published: May 2013

Despite significant advances in prevention and treatment strategies, graft- versus-host disease remains the most significant cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cellular transplantation. Corticosteroids remain the standard frontline therapy for graft- versus-host disease; however, a considerable number of patients will not respond adequately and others will be significantly affected by adverse effects. Extracorporeal photopheresis is one of several secondary therapies which have shown promise in the clinical setting. While the procedure itself has been around for over 20 years, our understanding of the mechanisms from which therapeutic benefits are seen, and the population they are seen in, remains limited. In this article, we review the use of extracorporeal photopheresis for the treatment of graft- versus-host disease including details covering the procedure’s mechanism of action, safety profile and clinical efficacy data.
Comparison of endosonography‐guided vs. percutaneous biliary stenting when papilla is inaccessible for ERCP
Authors: Bapaye Amol , Dubale Nachiket , Aher Advay
Published: May 2013

Background

Endoscopic retrograde cholangiopancreatography (ERCP) and biliary stenting fails in 5–10% patients of malignant biliary obstruction because papilla is inaccessible. Percutaneous transhepatic biliary drainage (PTBD) is an accepted alternative. Endosonography‐guided biliary drainage (EUS‐BD) has been described recently.

Aim

To compare success rates and complications of EUS‐BD and PTBD internal stenting.

Methods

This retrospective study included failed ERCP in inoperable malignant biliary obstruction due to inaccessible papilla undergoing PTBD or EUS‐BD. Percutaneous transhepatic cholangiography guided/EUS‐guided rendezvous procedures were excluded. When PTBD internal stenting failed, external drainage was performed. EUS‐BD was performed using either intra‐ or extrahepatic approach, and stents were placed by transmural (choledocho‐duodenostomy or hepatico‐gastrostomy) or antegrade approach. Self‐expandable metallic stents or plastic stents were placed in both groups. Success of internal stenting and complications were compared using t‐test and chi‐squared test.

Results

Retrospective review of 6 years of records (2005–2011) revealed 50 patients meeting the required criteria. EUS‐BD was attempted in 25 and PTBD in 26 patients (one crossover from EUS‐BD to PTBD). Internal stenting was technically and clinically successful in 23/25 (92%) EUS‐BD vs. 12/26 (46%) PTBD (p  < 0.05). External catheter drainage was performed in remaining 14 PTBD patients. Complications occurred in 5/25 (20%) EUS‐BD (one major, four minor) and in 12/26 (46%) PTBD (four major, eight minor; p  < 0.05). Late stent occlusion occurred in one EUS‐BD and three PTBD.

Conclusions

In this retrospective study comparing success and complications of EUS‐BD and PTBD in patients with inoperable malignant biliary obstruction and inaccessible papilla, EUS‐BD was found superior to PTBD for both comparators.
Cervical Cancer Screening among HIV-Positive Women in Nigeria
Authors: Dim Cyril C. , Onyedum Cajetan C. , Dim Ngozi R. , Chukwuka Judith C.
Published: May 2013

Introduction:

The sustainability of donor-supported cervical cancer screening for HIV-positive women in underresourced setting is a concern. The authors aimed to determine the willingness of HIV-positive women for out-of-pocket payment for the cancer screening, if necessary.

Methods:

Questionnaires were administered to 400 HIV-positive women at the Adult HIV clinic, University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria.

Results:

In all 11 (2.8%) respondents were aware of Pap smear, but only 1 (9.1%) of them had used it. After cervical cancer screening counseling, 378 (94.5%) respondents were willing to pay for Pap smear, irrespective of the cost. This willingness showed no trend across marital or educational groups. Younger age of respondents was not associated with willingness to pay for Pap smear (odds ratio = 1.24; confidence interval 95%: 0.52, 2.94).

Conclusion:

Willingness to pay for Pap smear by HIV-positive women in Enugu, Nigeria, is high. This has implication for the program sustainability.
Effect of Lipodystrophy on the Quality of Life among People Living with HIV (PLHIV) on Highly Active Antiretroviral Therapy
Authors: Shenoy Archana , Ramapuram John T. , Unnikrishan Bhaskaran , Achappa Basavaprabhu , Madi Deepak , Rao Satish , Mahalingam Soundarya
Published: May 2013

Background:

Lipodystrophy is a known adverse effect of highly active antiretroviral therapy (HAART). Lipodystrophy resulting in body dysmorphism can lower the quality of life (QoL) among HAART recipients. The main aim of our study was to find the effect of lipodystrophy on QoL among people living with HIV (PLHIV) on HAART.

Methods:

This cross-sectional study was conducted in a tertiary care hospital in south India. The participants were assessed for the presence of lipodystrophy. Their QoL was assessed using HIV-AIDS-targeted QoL questionnaire (HAT-QoL). Statistical analysis was carried out using SPSS version 11.5.

Results:

Lipodystrophy was present in 21 participants (42%). The QoL among individuals with lipodystrophy was found to be significantly lower in terms of disclosure worries ( P = .023) and financial worries ( P = .049).

Conclusions:

Lipodystrophy adversely affects QoL among PLHIV. There is a need for studies analyzing factors that can potentially improve the QoL in such individuals.
The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation
Authors: Smith Brenden W. , Rozelle Sarah S. , Leung Amy , Ubellacker Jessalyn , Parks Ashley , Nah Shirley K. , French Deborah , Gadue Paul , Monti Stefano , Chui David H. K. , Steinberg Martin H. , Frelinger Andrew L. , Michelson Alan D. , Theberge Roger , McComb Mark E. , Costello Catherine E. , Kotton Darrell N. , Mostoslavsky Gustavo , Sherr David H. , Murphy George J.
Published: May 2013

Key Points

This breakthrough involves the role of the aryl hydrocarbon receptor in the expansion and specification of hematopoietic progenitor cells. This work sets a precedent for the use of an in vitro platform for the clinically relevant production of blood products.
Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation
Authors: Zhang Guoqi , Yang Li , Kim Gab Seok , Ryan Kieran , Lu Shulin , O’Donnell Rebekah K. , Spokes Katherine , Shapiro Nathan , Aird William C. , Kluk Michael J. , Yano Kiichiro , Sanchez Teresa
Published: May 2013

Key Points

Endothelial S1PR2 plays a critical role in the induction of vascular permeability and vascular inflammation during endotoxemia. S1PR2 could be a novel therapeutic target to promote vascular integrity in inflammatory vascular disorders.
Safety of formoterol in asthma clinical trials: an update
Authors: Sears Malcolm R. , Radner Finn
Published: May 2013

Use of long-acting β-agonists (LABAs) in asthma remains controversial, and large safety trials are in progress. We have previously reported safety outcomes with formoterol in 117 AstraZeneca asthma trials (78 339 patients, 92% using inhaled corticosteroids) completed by December 2006, and have now added 32 trials with formoterol (26 124 patients, 100% using inhaled corticosteroids) completed by December 2011.

The primary dataset of 79 randomised controlled trials includes 94 684 patients, 67 380 of whom were exposed to formoterol, while the complete dataset comprises 149 trials and 104 463 patients. There were no new asthma-related deaths in the expanded primary dataset, with eight asthma-related deaths among formoterol-randomised patients and two among non-LABA-randomised patients (relative risk 1.13, 95% CI 0.23–10.9), and 15versusnine cardiac-related deaths (relative risk 0.47, 95% CI 0.19–1.22). Nonfatal asthma-related serious adverse events were significantly reduced with formoterol (relative risk 0.63, 95% CI 0.53–0.75), as were discontinuations due to adverse events. Examining 40 trials with direct formoterolversusnon-LABA comparisons, Mantel–Haenszel relative risk for asthma-related death was 2.75 (95% CI 0.52–14.4) and for serious adverse events 0.83 (95% CI 0.68–1.02).

We conclude that this enlarged dataset indicates no increased risk of asthma-related deaths among patients exposed to formoterol compared with non-LABA treatments, although the wide confidence interval precludes certainty.
Dose-dependent association of smoking and bronchial hyperresponsiveness
Authors: Juusela Maria , Pallasaho Paula , Rönmark Eva , Sarna Seppo , Sovijärvi Anssi , Lundbäck Bo
Published: May 2013

Our aim was to study the association of smoking habits and environmental tobacco smoke (ETS) exposure with bronchial hyperresponsiveness (BHR).

A random sample of 292 adults was examined using a structured interview, spirometry, skin prick tests, exhaled nitric oxide fraction (FeNO) and bronchial histamine challenge.

A large majority of subjects with BHR were smokers or ex-smokers. Starting to smoke before 20 years of age was significantly associated with BHR, as was current smoking, quantity of smoking and ETS exposure. The severity of BHR increased significantly with increasing pack-years of exposure (p<0.001). Current smokers with decreased lung function were at a particularly high risk of BHR. Impaired forced expiratory volume in 1 s and mean maximal expiratory flow were independent determinants for more severe BHR, regardless of age. In multivariate analysis, smoking remained an independent determinant for BHR after adjustment for impaired lung function and other covariates: ≥15 pack-years yielded an odds ratio of 3.00 (95% CI 1.33–6.76) for BHR. The association between BHR andFeNOwas dependent on smoking habits.

The results indicate that smoking is a significant risk factor for BHR, with a dose-dependent pattern, and that the severity of BHR increases with pack-years. The findings strongly suggest assessment of smoking habits in subjects with BHR.
Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis
Authors: Rosenfeld Margaret , Farrell Philip M. , Kloster Margaret , Swanson Jonathan O. , Vu Thuy , Brumback Lyndia , Acton James D. , Castile Robert G. , Colin Andrew A. , Conrad Carol K. , Hart Meeghan A. , Kerby Gwendolyn S. , Hiatt Peter W. , Mogayzel Peter J. , Johnson Robin C. , Davis Stephanie D.
Published: May 2013

The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics.

Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. Chest radiographs ∼1 year apart were scored using the Wisconsin and Brasfield systems. Associations of infant pulmonary function tests with clinical characteristics were evaluated with mixed effects models.

The 100 participants contributed 246 acceptable flow/volume (forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of the forced vital capacity (FEF75%)), 303 functional residual capacity measurements and 171 chest radiographs. Both Brasfield and Wisconsin chest radiograph scores worsened significantly over the 1-year interval. Worse Wisconsin chest radiograph scores andStaphylococcus aureuswere both associated with hyperinflation (significantly increased functional residual capacity), but not with diminished FEV0.5or FEF75%. Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation.

In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score andS. aureusand hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.
Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation
Authors: Held Matthias , Walthelm Johanna , Baron Stefan , Roth Christine , Jany Berthold
Published: May 2013

We aimed to characterise the association of pulmonary hypertension due to hypoventilation and exercise capacity, and the haemodynamic and functional changes under noninvasive ventilation.

A retrospective analysis was carried out to assess haemodynamics and functional capacity in 18 patients with daytime pulmonary hypertension, due to hypoventilation, at baseline and after 3 months of noninvasive ventilation.

Patients presented with a mean±sdpulmonary artery pressure of 49±13 mmHg, preserved cardiac index (3.2±0.66 L·min−1·m−2), 6-min walking distance of 303±134 m and severely elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Mean pulmonary artery pressure correlated negatively with maximum work rate (R= -0.72; p=0.03) and 6-min walking distance (R= -0.62; p=0.01). Following noninvasive ventilation we found a significant reduction of mean pulmonary artery pressure (-18 mmHg; p<0.001) and NT-proBNP levels (-2110 pg·mL−1; p=0.001), and improvement in the 6-min walking distance (+66 m; p=0.008) and maximum work rate (+18 W; p=0.028). Changes in work rate correlated inversely with pulmonary artery pressure (R= -0.75; p=0.031).

In this specific cohort with hypoventilation and severe pulmonary hypertension, pulmonary hypertension was associated with reduced exercise capacity. Following noninvasive ventilation, haemodynamics and exercise capacity improved significantly.
Dual bronchodilation with QVA149versussingle bronchodilator therapy: the SHINE study
Authors: Bateman Eric D. , Ferguson Gary T. , Barnes Neil , Gallagher Nicola , Green Yulia , Henley Michelle , Banerji Donald
Published: May 2013

We investigated the efficacy and safety of dual bronchodilation with QVA149versusits monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, open-label tiotropium 18 μg or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149versusits monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety.

Trough FEV1at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health statusversusplacebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated.

Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomesversusplacebo and superiorityversustreatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist combinations for the treatment of COPD.
The constrained multiple-sets split feasibility problem and its projection algorithms
Authors: Zheng Yaqin , Shi Jinwei , Liou Yeong-Cheng
Published: May 2013

The projection algorithms for solving the constrained multiple-sets split feasibility problem are presented. The strong convergence results of the algorithms are given under some mild conditions. Especially, the minimum norm solution of the constrained multiple-sets split feasibility problem can be found.
Phylogenetic analysis of symbionts in feather-feeding lice of the genus Columbicola: evidence for repeated symbiont replacements
Authors: Smith Wendy A , Oakeson Kelly F , Johnson Kevin P , Reed David L , Carter Tamar , Smith Kari L , Koga Ryuichi , Fukatsu Takema , Clayton Dale H , Dale Colin
Published: May 2013

Background

Many groups of insects have obligate bacterial symbionts that are vertically transmitted. Such associations are typically characterized by the presence of a monophyletic group of bacteria living in a well-defined host clade. In addition the phylogeny of the symbiotic bacteria is typically congruent with that of the host, signifying co-speciation. Here we show that bacteria living in a single genus of feather lice, Columbicola (Insecta: Phthiraptera), present an exception to this typical pattern.

Results

The phylogeny of Columbicola spp. symbionts revealed the presence of three candidate clades, with the most species-rich clade having a comb-like topology with very short internodes and long terminal branches. Evolutionary simulations indicate that this topology is characteristic of a process of repeated symbiont replacement over a brief time period. The two remaining candidate clades in our study exhibit high levels of nucleotide substitution, suggesting accelerated molecular evolution due to relaxed purifying selection or smaller effective population size, which is typical of many vertically transmitted insect symbionts. Representatives of the fast-evolving and slow-evolving symbiont lineages exhibit the same localization, migration, and transmission patterns in their hosts, implying direct replacement.

Conclusions

Our findings suggest that repeated, independent symbiont replacements have taken place over the course of the relatively recent radiation of Columbicola spp. These results are compatible with the notion that lice and other insects have the capability to acquire novel symbionts through the domestication of progenitor strains residing in their local environment.
The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild
Authors: Prado-Martinez Javier , Hernando-Herraez Irene , Lorente-Galdos Belen , Dabad Marc , Ramirez Oscar , Baeza-Delgado Carlos , Morcillo-Suarez Carlos , Alkan Can , Hormozdiari Fereydoun , Raineri Emanuele , Estellé Jordi , Fernandez-Callejo Marcos , Valles Mònica , Ritscher Lars , Schöneberg Torsten , de la Calle-Mustienes Elisa , Casillas Sònia , Rubio-Acero Raquel , Melé Marta , Engelken Johannes , Caceres Mario , Gomez-Skarmeta Jose Luis , Gut Marta , Bertranpetit Jaume , Gut Ivo G , Abello Teresa , Eichler Evan E , Mingarro Ismael , Lalueza-Fox Carles , Navarro Arcadi , Marques-Bonet Tomas
Published: May 2013

Background

The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas.

Results

We successfully identified the causal genetic variant for Snowflake’s albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake’s parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla.

Conclusions

In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost.
Pan-genome analysis of the emerging foodborne pathogen Cronobacterspp. suggests a species-level bidirectional divergence driven by niche adaptation
Authors: Grim Christopher J , Kotewicz Michael L , Power Karen A , Gopinath Gopal , Franco Augusto A , Jarvis Karen G , Yan Qiong Q , Jackson Scott A , Sathyamoorthy Venugopal , Hu Lan , Pagotto Franco , Iversen Carol , Lehner Angelika , Stephan Roger , Fanning Séamus , Tall Ben D
Published: May 2013

Background

Members of the genus Cronobacter are causes of rare but severe illness in neonates and preterm infants following the ingestion of contaminated infant formula. Seven species have been described and two of the species genomes were subsequently published. In this study, we performed comparative genomics on eight strains of Cronobacter, including six that we sequenced (representing six of the seven species) and two previously published, closed genomes.

Results

We identified and characterized the features associated with the core and pan genome of the genus Cronobacter in an attempt to understand the evolution of these bacteria and the genetic content of each species. We identified 84 genomic regions that are present in two or more Cronobacter genomes, along with 45 unique genomic regions. Many potentially horizontally transferred genes, such as lysogenic prophages, were also identified. Most notable among these were several type six secretion system gene clusters, transposons that carried tellurium, copper and/or silver resistance genes, and a novel integrative conjugative element.

Conclusions

Cronobacter have diverged into two clusters, one consisting of C. dublinensis and C. muytjensii (Cdub-Cmuy) and the other comprised of C. sakazakii, C. malonaticus, C. universalis, and C. turicensis, (Csak-Cmal-Cuni-Ctur) from the most recent common ancestral species. While several genetic determinants for plant-association and human virulence could be found in the core genome of Cronobacter, the four Cdub-Cmuy clade genomes contained several accessory genomic regions important for survival in a plant-associated environmental niche, while the Csak-Cmal-Cuni-Ctur clade genomes harbored numerous virulence-related genetic traits.
Variability of antibiotic prescribing in patients with chronic obstructive pulmonary disease exacerbations: a cohort study
Authors: Boggon Rachael , Hubbard Richard , Smeeth Liam , Gulliford Martin , Cassell Jackie , Eaton Susan , Pirmohamed Munir , van Staa Tjeerd-Pieter
Published: May 2013

Background

The role of antibiotics in treating mild or moderate exacerbations in patients with acute chronic obstructive pulmonary disease (COPD) is unclear. The aims were to: (i) describe patient characteristics associated with acute exacerbations amongst a representative COPD population, (ii) explore the relationship between COPD severity and outcomes amongst patients with exacerbations, and (iii) quantify variability by general practice in prescribing of antibiotics for COPD exacerbations.

Method

A cohort of 62,747 patients with COPD was identified from primary care general practices (GP) in England, and linked to hospital admission and death certificate data. Exacerbation cases were matched to three controls and characteristics compared using conditional logistic regression. Outcomes were compared using incidence rates and Cox regression, stratified by disease severity. Variability of prescribing at the GP level was evaluated graphically and by using multilevel models.

Results

COPD severity was found to be associated with exacerbation and subsequent mortality (very severe vs. mild, odds ratio for exacerbation 2.12 [95%CI 19.5–2.32]), hazard ratio for mortality 2.14 [95%CI 1.59–2.88]). Whilst 61% of exacerbation cases were prescribed antibiotics, this proportion varied considerably between GP practices (interquartile range, 48–73%). This variation is greater than can be explained by patient characteristics alone.

Conclusions

There is significant variability between GP practices in the prescribing of antibiotics to COPD patients experiencing exacerbations. Combined with a lack of evidence on the effects of treatment, this supports the need and opportunity for a large scale pragmatic randomised trial of the prescribing of antibiotics for COPD patients with exacerbations, in order to clarify their effectiveness and long term outcomes whilst ensuring the representativeness of subjects.
Increased rate of cholecystectomies performed with doubtful or no indications after laparoscopy introduction: a single center experience
Authors: Pulvirenti Elia , Toro Adriana , Gagner Michel , Mannino Maurizio , Di Carlo Isidoro
Published: May 2013

Background

During recent years laparoscopic cholecystectomy has dramatically increased, sometimes resulting in overtreatment. Aim of this work was to retrospectively analyze all laparoscopic cholecystectomies performed in a single center in order to find the percentage of patients whose surgical treatment may be explained with this general trend, and to speculate about the possible causes.

Methods

831 patients who underwent a laparoscopic cholecystectomy from 1999 to 2008 were retrospectively analyzed.

Results

At discharge, 43.08% of patients were operated on because of at least one previous episode of biliary colic before the one at admission; 14.08% of patients presented with acute lithiasic cholecystitis; 14.68% were operated on because of an increase in bilirubin level; 1.56% were operated on because of a previous episode of jaundice with normal bilirubin at admission; 0.72% had gallbladder adenomas, 0.72% had cholangitis, 0.36% had biliodigestive fistula and one patient (0.12%) had acalculous cholecystitis. By excluding all these patients, 21.18% were operated on without indications.

Conclusions

The broadening of indications for laparoscopic cholecystectomy is undisputed and can be considered a consequence of new technologies that have been introduced, increased demand from patients, and the need for practice by inexperienced surgeons. If not prevented, this trend could continue indefinitely.
Primary adenocarcinoma of the thymus: an immunohistochemical and molecular study with review of the literature
Authors: Maghbool Maryam , Ramzi Mani , Nagel Inga , Bejarano Pablo , Siebert Reiner , Saeedzadeh Abolfazl , Daneshbod Yahya
Published: May 2013

Background

Primary adenocarcinoma of thymus is extremely rare.

Case presentation

This is a case of primary adenocarcinoma with intestinal differentiation and focal mucin production in the thymus. Thymic cyst was associated with this tumor. Intestinal differentiation was confirmed by immunohistochemical stain with positivity for CDX-2, CK20, villin, MOC31 and focal positivity of CK7. Array comperative genomic hybridization (CGH) analysis showed a complex pattern of chromosomal imbalances including homozygous deletion at the HLA locus in chromosomal region 6p21.32.

Conclusion

This rare tumor shows a similar genetic aberration with other studied thymic epithelial tumors.
Vivax malaria and bacteraemia: a prospective study in Kolkata, India
Authors: Bhattacharya Sujit Kumar , Sur Dipika , Dutta Shanta , Kanungo Suman , Ochiai R Leon , Kim Deok Ryun , Anstey Nicholas M , von Seidlein Lorenz , Deen Jacqueline
Published: May 2013

Background

Falciparum malaria increases the risk for bacteraemia, whereas the relationship between vivax malaria and bacteraemia is not clear. Data from a prospective fever surveillance study in Kolkata, India were reanalysed for the potential association between Plasmodium vivax malaria and bacteraemia.

Methods

Patients of all ages presenting with fever of three days or more to a project health outpost were invited to participate. A blood film and blood culture was performed on presentation. Treatment and referral were provided according to national guidelines. The case fraction and incidence of malaria, bacteraemia, and co-infection were calculated.

Results

3,371 participants were enrolled during a one-year study period, of whom 93/3,371 (2.8%) had malaria (89/93 [95.7%] Plasmodium vivax) and 256 (7.6%) bacteraemia. There were 154 malaria, 423 bacteraemia and 10 P. vivax-bacteremia coinfection episodes per 100,000/year. Among the malaria-bacteraemia co-infections, all were vivax malaria and 5/6 (83%) bacteria isolated were Gram-negative (one S. Typhi, one S. Paratyphi A, three other Gram-negative). Bacteraemia occurred in 6/89 (6.7% [95%CI: 3.1-13.9%]) of P. vivax cases versus 250/3,278 (7.6% [95% CI: 6.7-8.6%]) without Plasmodium infection (p=0.76).

Conclusions

While an increased risk was not demonstrated, concomitant bacteraemia occurs frequently in vivax malaria in an area with a high background incidence of bacteraemia, and should be considered in cases of vivax malaria with severe manifestations.
Effects of increase in fish oil intake on intestinal eicosanoids and inflammation in a mouse model of colitis
Authors: Bosco Nabil , Brahmbhatt Viral , Oliveira Manuel , Martin Francois-Pierre , Lichti Pia , Raymond Frederic , Mansourian Robert , Metairon Sylviane , Pace-Asciak Cecil , Bastic Schmid Viktoria , Rezzi Serge , Haller Dirk , Benyacoub Jalil
Published: May 2013

Background

Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affecting about 1% of western populations. New eating behaviors might contribute to the global emergence of IBD. Although the immunoregulatory effects of omega-3 fatty acids have been well characterized in vitro, their role in IBD is controversial.

Methods

The aim of this study was to assess the impact of increased fish oil intake on colonic gene expression, eicosanoid metabolism and development of colitis in a mouse model of IBD. Rag-2 deficient mice were fed fish oil (FO) enriched in omega-3 fatty acids i.e. EPA and DHA or control diet for 4 weeks before colitis induction by adoptive transfer of naïve T cells and maintained in the same diet for 4 additional weeks. Onset of colitis was monitored by colonoscopy and further confirmed by immunological examinations. Whole genome expression profiling was made and eicosanoids were measured by HPLC-MS/MS in colonic samples.

Results

A significant reduction of colonic proinflammatory eicosanoids in FO fed mice compared to control was observed. However, neither alteration of colonic gene expression signature nor reduction in IBD scores was observed under FO diet.

Conclusion

Thus, increased intake of dietary FO did not prevent experimental colitis.
Right atrial to left atrial area ratio on early echocardiography predicts long-term survival after acute pulmonary embolism
Authors: Chow Vincent , Ng Austin Chin Chwan , Chung Tommy , Thomas Liza , Kritharides Leonard
Published: May 2013

Background

Current guidelines recommend that transthoracic echocardiography (TTE) should be performed for acute risk stratification following acute pulmonary embolism (PE), but it is unclear whether the initial TTE can predict long-term outcome beyond six months. We sought to assess the potential of the initial right atrial (RA) to left atrial (LA) area ratio (RA/LA ratio) on TTE to predict long-term mortality in survivors of submassive PE.

Methods

A derivation cohort comprised a previously reported group of 35 consecutive patients with acute PE who were intensively studied by serial TTE at 1, 2, 5 days, 2, 6, 12 and 26 weeks and RA/LA ratio related to long-term outcome. The Day 1 RA/LA ratio findings were then further related to long-term outcome in 158 patients followed for 3.6 ± 2.3 years.

Results

In the derivation cohort, total mortality was 28.6% (n = 10) following a mean (±standard deviation) follow-up of 4.3 ± 1.9 years. The RA/LA ratio was highly dynamic, being increased at day 1, but normalised rapidly within 2–5 days of presentation and this was most marked amongst long-term non-survivors. A RA/LA ratio > 1.0 on day 1 was independently associated with a three-fold increase in long-term mortality on Kaplan-Meier analysis. Pooled analysis of 158 patient indicated that age, Charlson Comorbidity Index (CCI), simplified Pulmonary Embolism Severity Score (PESI), troponin T, day 1 RA/LA Ratio and pulmonary arterial systolic pressure (PASP) were univariate predictors of long-term mortality. Multivariate analysis identified Day 1 RA/LA Ratio (HR 1.7 per 10% increase,p = 0.002), CCI (HR 2.2 per 1 unit increase, p = 0.004) and age (HR 1.1, p = 0.03) as the only independent predictors of long-term mortality.

Conclusion

A RA/LA Ratio >1.0 at presentation with acute PE was associated with a three-fold increased risk of long-term mortality. The RA/LA ratio on presentation with an acute PE is a simple, novel predictor of long-term survival.
Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction (TATORT-NSTEMI): study protocol for a randomized controlled trial
Authors: de Waha Suzanne , Eitel Ingo , Desch Steffen , Scheller Bruno , Böhm Michael , Lauer Bernward , Gawaz Meinrad , Geisler Tobias , Gunkel Oliver , Bruch Leonhard , Klein Norbert , Pfeiffer Dietrich , Schuler Gerhard , Zeymer Uwe , Thiele Holger
Published: May 2013

Background

Current guidelines recommend thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI); however, there are insufficient data to unequivocally support thrombectomy in patients with non-STEMI (NSTEMI).

Methods/Design

The TATORT-NSTEMI (Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction) trial is a prospective, controlled, multicenter, randomized, open-label trial enrolling 460 patients. The hypothesis is that, against a background of early revascularization, adjunctive thrombectomy leads to less microvascular obstruction (MO) compared with conventional percutaneous coronary intervention (PCI) alone, as assessed by cardiac magnetic resonance imaging (CMR) in patients with NSTEMI. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary endpoint is the extent of late MO assessed by CMR. Secondary endpoints include early MO, infarct size, and myocardial salvage assessed by CMR as well as enzymatic infarct size and angiographic parameters, such as thrombolysis in myocardial infarction flow post-PCI and myocardial blush grade. Furthermore, clinical endpoints including death, myocardial re-infarction, target vessel revascularization, and new congestive heart failure will be recorded at 6 and 12 months. Safety will be assessed by the incidence of bleeding and stroke.

The TATORT-NSTEMI trial has been designed to test the hypothesis that thrombectomy will improve myocardial perfusion in patients with NSTEMI and relevant thrombus burden in the culprit vessel reperfused by early PCI.

Trial registration

The trial is registered under http://www.clinicaltrials.gov: NCT01612312.
The effect of covariate adjustment for baseline severity in acute stroke clinicaltrials with responder analysis outcomes
Authors: Garofolo Kyra M , Yeatts Sharon D , Ramakrishnan Viswanathan , Jauch Edward C , Johnston Karen C , Durkalski Valerie L
Published: May 2013

Background

Traditionally in acute stroke clinical trials, the primary clinical outcomeemployed is a dichotomized modified Rankin Scale (mRS). New statisticalmethods, such as responder analysis, are being used in stroke studies toaddress the concern that baseline prognostic variables, such as strokeseverity, impact the likelihood of a successful outcome. Responder analysisallows the definition of success to vary according to baseline prognosticvariables, producing a more clinically relevant insight into the actualeffect of investigational treatments. It is unclear whether or notstatistical analyses should adjust for prognostic variables when responderanalysis is used, as the outcome already takes these prognostic variablesinto account. This research aims to investigate the effect of covariateadjustment in the responder analysis framework in order to determine theappropriate analytic method.

Methods

Using a current stroke clinical trial and its pilot studies to guidesimulation parameters, 1,000 clinical trials were simulated at varyingsample sizes under several treatment effects to assess power and type Ierror. Covariate-adjusted and unadjusted logistic regressions were used toestimate the treatment effect under each scenario. In the case ofcovariate-adjusted logistic regression, the trichotomized National Instituteof Health Stroke Scale (NIHSS) was used in adjustment.

Results

Under various treatment effect settings, the operating characteristics of theunadjusted and adjusted analyses do not substantially differ. Power and typeI error are preserved for both the unadjusted and adjusted analyses.

Conclusions

Our results suggest that, under the given treatment effect scenarios, thedecision whether or not to adjust for baseline severity when using aresponder analysis outcome should be guided by the needs of the study, astype I error rates and power do not appear to vary largely between themethods. These findings are applicable to stroke trials which use the mRSfor the primary outcome, but also provide a broader insight into theanalysis of binary outcomes that are defined based on baseline prognosticvariables.

Trial registration

This research is part of the Stroke Hyperglycemia Insulin Network Effort(SHINE) trial, Identification Number NCT01369069.
Tissue-specific DNA methylation profiles in newborns
Authors: Herzog Emilie , Galvez Jubby , Roks Anton , Stolk Lisette , Verbiest Michael , Eilers Paul , Cornelissen Jan , Steegers Eric , Steegers-Theunissen Régine
Published: May 2013

Background

Epidemiological studies demonstrate that foetal growth restriction and low birth weight affect long-term health. Derangements in tissue-specific epigenetic programming of foetal and placental tissues are a suggested underlying mechanism of which DNA methylation is best understood. DNA methylation has been mostly investigated in DNA from white blood cells. To improve baseline understanding of tissue-specific DNA methylation, we examined variation in DNA methylation profiles of the imprinted foetal growth genes IGF2 and H19 in three different tissues from the same newborn obtained at the same time.

Findings

We obtained DNA from umbilical cord blood mononuclear cells (MNC; CD34+ and CD34–, n = 6), foetal side of the placenta (n = 5) and umbilical cord Wharton jelly (n = 5). DNA methylation of the IGF2 differentially methylated region (DMR) and H19 DMR was measured using quantitative mass spectrometry. Analysis of variance testing showed no statistical difference between total mean methylation of CD34+ and CD34– MNC. Further comparisons were made with the pooled total MNC fraction. Mean IGF2 DMR methylation of Wharton jelly was 1.3 times higher (P = 0.001) than mean methylation of the pooled MNC. Placental mean methylation was 0.8 times lower (P <0.001) and Wharton jelly 0.9 times lower (P <0.001) than the pooled MNC of H19 DMR.

Conclusion

The total MNC fraction is a rather homogeneous cell population for methylation studies of imprinted genes in umbilical cord blood white blood cells, but may not always reflect the methylation levels of IGF2 and H19 in other organs.
Are interventions to reduce the impact of arsenic contamination of groundwater on human health in developing countries effective? A systematic review
Authors: Jones-Hughes Tracey , Peters Jaime , Whear Rebecca , Cooper Chris , Evans Hywel , Depledge Michael , Pearson Mark
Published: May 2013

Background

Within developing countries, groundwater provides an alternative drinking source to polluted surface water. However, the presence of arsenic in some groundwater sources has resulted in chronic worldwide poisoning. The aim of this review was to determine the effectiveness of field-based technologies for the removal of arsenic from groundwater in developing countries.

Methods

A structured search strategy was conducted in a range of databases. Titles, abstracts and full texts were screened using pre-defined inclusion criteria. Included studies were quality appraised prior to data extraction. The primary outcome was the percentage of effluent water samples meeting WHO guidelines for arsenic concentrations (≤0.01 mg/L). Secondary outcomes included: (a) arsenic concentrations in effluent water samples meeting the national guideline limit (≤0.05 mg/L), (b) arsenic concentrations in human tissue, and (c) knowledge and attitudes related to the interventions.

Results

Fifty-one reports, evaluating 50 different technologies, were included. Sixty-seven percent (n = 34) of studies were conducted in Bangladesh. Fifty of the included reports were appraised as ‘weak’, with one ‘strong’ report of a randomised-controlled trial.

In summary, the effectiveness of the oxidation and filtration interventions is poor, while the evidence for coagulation, co-precipitation and filtration, subterranean and membrane and electrolytic methods is mixed. Evidence regarding adsorption and zero valent iron interventions is more persuasive with most results suggesting good evidence of effectiveness (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L). In particular, activated alumina and sono/three-kolshi/gagri/pitcher filters have ≥95% of samples meeting national guidelines. Disappointingly, only one study reports excellent evidence of effectiveness: BRAC (2000) for activated alumina (i.e. ≥95% of samples with arsenic concentrations ≤0.01 mg/L).

The success of each technology was highly dependent on context, especially their acceptability to users, a sense of ownership and expectations of women’s roles in society.

Conclusions

Most studies were poorly conducted and reported. Consequently, although some technologies met national guidelines, the evidence-base for decision-making regarding arsenic mitigation technologies at household- and community-level is weak. To improve this situation, primary research needs to be commissioned with adequate sample sizes, testing the impact of key contextual factors, using valid tools for analysis, and meeting standards for completeness of reporting.
Content of the mechanism of management of sustainable socioeconomic development of the region
Authors: Сорокина  , Sorokina Natalia
Published: May 2013

In the article justified content of the mechanism of management of sustainable socio-economic development of the region, under which invited to understand the totality of the management, trust and providing subsystems, as well as ties between them and controlled subsystem. This approach has allowed the determination of the functions of the management of sustainable development of the region, describe the methods of management and to formulate the

principles of management of development of the region in order to ensure a high standard of quality of life of the population.
Internationalization of the structure of human capital in the conditions of globalization of economy
Authors: Сухов  , Sukhov Andrey
Published: May 2013

The article examines the structure of human capital, internationalization of international human capital and its influence on the content of the last one in the conditions of globalization of economy.
Economic growth and the development of innovations in modern Russia
Authors: Шишкин  , Shishkin Andrey
Published: May 2013

Analysis of terms associated with economic growth. In particular conducted a more detailed analysis of the gross domestic product. Describing the relationship of the gross domestic product, and social indicators connected with the movement of the labour force. The analysis of statistical indicators characterizing the innovation potential of the state. Touched upon the issues related to the preparation of personnel in the field of development of innovative processes. According to the survey of statistical data formed findings on the interaction of indicators characterizing the economic growth and indicators characterizing the innovative development of the state. Touched upon the issues of interaction of state corporations and the growth of the innovation development of the state, as well as the historical aspects of formation of state corporations. Analyzed the dependence between the development of innovation processes and the formation of human capital as a major factor of development of innovations. The conclusions which allow to compare the trends in the development of economic growth with the trends in the development of innovative processes.
From the Editors—Group Decisions, Preference Elicitation, Experienced Utility, Survival Probabilities, and Portfolio Value of Information
Authors: Sarin Rakesh K. , Keller L. Robin
Published: May 2013

This “From the Editors” column is co-authored by Editor-in-Chief Rakesh K. Sarin and former Editor-in-Chief L. Robin Keller. Our first article, by Ralph L. Keeney, presents “Foundations for Group Decision Analysis.” The second article is “Toward an Improved Methodology to Construct and Reconcile Decision Analytic Preference Judgments” by Richard M. Anderson and Robert Clemen. Next, Manel Baucells and Rakesh K. Sarin discuss “Determinants of Experienced Utility: Laws and Implications.” The fourth paper, “Estimating Second Order Probability Beliefs from Subjective Survival Data,” is by Péter Hudomiet and Robert J. Willis. The final paper, by Kun Zan and J. Eric Bickel, is on “Components of Portfolio Value of Information.”