bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-Based Estimates of the Effects of Efavirenz on Bedaquiline Pharmacokinetics and Suggested Dose Adjustments for Patients Coinfected with HIV and Tuberculosis
Authors: Svensson Elin M. , Aweeka Francesca , Park Jeong-Gun , Marzan Florence , Dooley Kelly E. , Karlsson Mats O. 
Published: April 2013

ABSTRACTSafe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV's induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Impact of induction was described as an instantaneous change in clearance 1 week after initialization of EFV treatment and estimated for all compounds. The model predicts average steady-state concentrations of BDQ and M2 to be reduced by 52% (relative standard error [RSE], 3.7%) with chronic coadministration. A range of models with alternative structural assumptions regarding onset of induction effect and fraction metabolized resulted in similar estimates of the typical reduction and did not offer a markedly better fit to data. Simulations to investigate alternative regimens mitigating the estimated interaction effect were performed. The results suggest that simple adjustments of the standard regimen during EFV coadministration can prevent reduced exposure to BDQ without increasing exposures to M2. However, exposure to M3 would increase. Evaluation in clinical trials of adjusted regimens is necessary to ensure appropriate dosing for HIV-infected TB patients on an EFV-based regimen.
Activity of Tedizolid (TR-700) against Well-Characterized Methicillin-Resistant Staphylococcus aureus Strains of Diverse Epidemiological Origins
Authors: Thomson Kenneth S. , Goering Richard V. 
Published: April 2013

ABSTRACT

The
in vitro
activities of tedizolid and 10 antistaphylococcal agents were compared against 111 methicillin-resistant
Staphylococcus aureus
(MRSA) strains from 14 epidemiologically characterized groups. Tedizolid, tigecycline, and daptomycin were the most potent agents, with tedizolid 4-fold more potent than linezolid. Tedizolid, linezolid, and vancomycin were unaffected by epidemiological types. Tigecycline and daptomycin had reduced potency against ST80-MRSA-IV and ST239-MRSA-III, respectively. Overall, tedizolid was highly potent against all MRSA strain types, including those resistant to other classes of drugs.
Extended-Infusion Cefepime Reduces Mortality in Patients with Pseudomonas aeruginosa Infections
Authors: Bauer Karri A. , West Jessica E. , O'Brien James M. , Goff Debra A. 
Published: April 2013

ABSTRACT

In an era of escalating resistance and a lack of new antimicrobial discovery, stewardship programs must utilize knowledge of pharmacodynamics to achieve maximal exposure in the treatment of
Pseudomonas aeruginosa
infections. We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of
P. aeruginosa
infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%;
P
= 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion (
P
= 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days;
P
= 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group (
P
= 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive
P. aeruginosa
infections.
Predicting the Next Eye Pathogen: Analysis of a Novel Adenovirus
Authors: Robinson Christopher M. , Zhou Xiaohong , Rajaiya Jaya , Yousuf Mohammad A. , Singh Gurdeep , DeSerres Joshua J. , Walsh Michael P. , Wong Sallene , Seto Donald , Dyer David W. , Chodosh James , Jones Morris S. 
Published: April 2013

ABSTRACT

For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of
in silico
and laboratory approaches revealed a potential ocular tropism for the new virus.
In vivo
, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses.

IMPORTANCE
The ongoing dance between a virus and its host distinctly shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. Here, we report a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of viral evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses.
Did the ‘Be Clear on Bowel Cancer’ public awareness campaign pilot result in a higher rate of cancer detection?
Authors: Bethune Rob , Marshall Morwena J , Mitchell Stephen J , Oppong Chris , Cartmel Mark T , Arumugam Ponnandai J , Gee Andrew S , Daniels Ian R 
Published: April 2013

Abstract

Objectives
To assess the impact of a 7-week public bowel cancer awareness campaign pilot by reviewing the number of 2-week referrals from general practitioners (GPs) to hospital, endoscopic procedures and new cancers diagnosed throughout the five acute hospitals in The Peninsular Cancer Network, UK.

Design
A retrospective before and after study.

Setting
The Peninsula Cancer Network in the South West of England, UK.

Main outcome measures
For the period July 2010–July 2011, data were collected on the number of 2-week referrals, number of endoscopic procedures performed and number of new cancers diagnosed. The average for the 6 months before the campaign was compared with the immediate 3 months and then the fourth to sixth months following the campaign. Student's t test was used to compare the means of the three groups.

Results
There was a statistically significant increase in the number of 2-week referrals from GPs to hospital in the 3 months following the campaign but this effect disappeared after that. There was no statistical increase in the number of endoscopic procedures or new cancers diagnosed following the awareness campaign.

Conclusions
The pilot ‘Be Clear on Cancer’ awareness campaign had a significant effect on the number of patients being referred from GPs to hospital; however, the effect was short lived and had returned to baseline by 3 months. The campaign had no effect on the number of new cancers diagnosed, which was the stated underlying aim of the pilot.
Getting Personal with Neoantigen-Based Therapeutic Cancer Vaccines
Authors: Hacohen Nir , Fritsch Edward F. , Carter Todd A. , Lander Eric S. , Wu Catherine J. 
Published: April 2013

Abstract
Despite years of preclinical efforts and hundreds of clinical studies, therapeutic cancer vaccines with the routine ability to limit or eliminate tumor growth in humans have been elusive. With advances in genome sequencing, it is now possible to identify a new class of tumor-specific antigens derived from mutated proteins that are present only in the tumor. These “neoantigens” should provide highly specific targets for antitumor immunity. Although many challenges remain in producing and testing neoantigen-based vaccines customized for each patient, a neoantigen vaccine offers a promising new approach to induce highly focused antitumor T cells aimed at eradicating cancer cells. Cancer Immunol Res; 1(1); 11–15. ©2013 AACR.
Peroxisome Proliferator–Activated Receptor-γ Activation Prevents Sepsis-Related Cardiac Dysfunction and Mortality In Mice
Authors: Drosatos Konstantinos , Khan Raffay S. , Trent Chad M. , Jiang Hongfeng , Son Ni-Huiping , Blaner William S. , Homma Shunichi , Schulze P. Christian , Goldberg Ira J. 
Published: April 2013

Background—
Cardiac dysfunction with sepsis is associated with both inflammation and reduced fatty acid oxidation. We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction.

Methods and Results—

Escherichia coli
lipopolysaccharide (LPS) administered to C57BL/6 mice (wild type) induced cardiac dysfunction and reduced fatty acid oxidation and mRNA levels of peroxisome proliferator–activated receptor (PPAR)-α and its downstream targets within 6–8 hours. Transgenic mice in which cardiomyocyte-specific expression of PPARγ is driven by the α-myosin heavy chain promoter (αMHC-PPARγ) were protected from LPS-induced cardiac dysfunction. Despite a reduction in PPARα, fatty acid oxidation and associated genes were not decreased in hearts of LPS-treated αMHC-PPARγ mice. LPS treatment, however, continued to induce inflammation-related genes, such as interleukin-1α, interleukin-1β, interleukin-6, and tumor necrosis factor-α in hearts of αMHC-PPARγ mice. Treatment of wild-type mice with LPS and the PPARγ agonist, rosiglitazone, but not the PPARα agonist (WY-14643), increased fatty acid oxidation, prevented LPS-mediated reduction of mitochondria, and treated cardiac dysfunction, as well as it improved survival, despite continued increases in the expression of cardiac inflammatory markers.

Conclusions—
Activation of PPARγ in LPS-treated mice prevented cardiac dysfunction and mortality, despite development of cardiac inflammation and PPARα downregulation.
Acetylcysteine for the Prevention of Renal Outcomes in Patients With Diabetes Mellitus Undergoing Coronary and Peripheral Vascular Angiography
Authors: Berwanger Otavio , Cavalcanti Alexandre Biasi , Sousa Amanda M.G. , Buehler Anna , Castello-Júnior Helio José , Cantarelli Marcelo J.C. , Mangione José Armando , Bergo Ricardo R. , São Thiago Luiz Eduardo K. , Nunes Paulo M.S. , da Motta Paulo Antônio Marra , Kodama Alessandra , Victor Elivane , Carvalho Vitor Oliveira , Sousa Jose Eduardo 
Published: April 2013

Background—
Diabetes mellitus represents an independent risk factor for contrast-induced acute kidney injury. We report the results of a prespecified substudy of patients with diabetes mellitus included in the Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT), the largest randomized study evaluating the effects of acetylcysteine for the prevention of contrast-induced acute kidney injury conducted to date.

Methods and Results—

From the 2308 patients included in the ACT, 1395 had diabetes mellitus and were considered for the present analysis. The study drugs (acetylcysteine 1200 mg or matching placebo) were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). Participants, healthcare staff, data collectors, and outcome assessors were blinded. All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 13.8% in the acetylcysteine group and 14.7% in the control group (relative risk 0.93; 95% confidence interval, 0.69–1.26;
P
=0.64). A combined end point of death or need for dialysis at 30 days was also similar in both the groups (2.2% and 2.1%, respectively; hazard ratio, 1.07; 95% confidence interval, 0.52–2.19;
P
=0.86).

Conclusions—
In this subanalysis, acetylcysteine did not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in patients with diabetes mellitus undergoing coronary and peripheral vascular angiography.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00736866.
Negative Diffusion-Weighted Imaging After Intravenous Tissue-Type Plasminogen Activator is Rare and Unlikely to Indicate Averted Infarction
Authors: Freeman Jason W. , Luby Marie , Merino José G. , Latour Lawrence L. , Auh Sungyoung , Song Shlee S. , Magadán Alejandro , Lynch John K. , Warach Steven , Hsia Amie W. 
Published: April 2013

Background and Purpose—
Some patients treated with intravenous (IV) tissue-type plasminogen activator (tPA) have negative diffusion-weighted imaging (DWI) on follow-up imaging. Without a visible infarct, there may be uncertainty as to whether the patient was having a stroke that was averted by tPA or whether the symptoms had not been cerebrovascular in origin. We evaluated patients presenting with suspected acute stroke with a positive DWI lesion before IV tPA to determine the probability of finding a negative DWI up to 48 hours after treatment.

Methods—
We included patients from the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) project who had acute MRI screening with a positive DWI lesion before IV tPA treatment and had follow-up MRI up to 48 hours later. Experienced readers interpreted all acute and follow-up MRIs looking for ischemic lesions on DWI.

Results—
There were 231 patients who met study inclusion criteria, of which 225 patients (97.4%) had a persistent positive DWI corresponding to the acute stroke lesion on all follow-up imaging. Four patients (1.7%) had transient DWI lesion reversal with positive DWI on subsequent follow-up imaging. There were only 2 cases (0.9%) of complete DWI lesion reversal on all follow-up imaging.

Conclusions—
Averted infarction after IV tPA is rare, occurring in 0.9% of patients with pretreatment positive DWI evidence of acute ischemia. For IV tPA-treated patients who have a negative DWI on follow-up imaging, a cause other than acute stroke should be explored.
The effects of health education on patients with hypertension in China: A meta-analysis
Authors: Xu LJ , Meng Q , He SW , Yin XL , Tang ZL , Bo HY , Lan XY 
Published: April 2013

Objective: This study collected on from all research relating to health education and hypertension in China and, with the aid of meta-analysis tools, assessed the outcomes of such health education. The analysis provides a basis for the further development of health-education programmes for patients with hypertension. Methods: Literature searches were carried out to identify studies that had evaluated the impact of health education on hypertension in China. The time interval searched was from 1 January 1991 to 31 December 2010. We searched the databases of PubMed, CBM, CNKI and VIP. Strict inclusion and exclusion criteria were used to screen the literature. We generated meta-analyses, using Cochrane RevMan 5.0 software, of outcomes of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results: Fourteen studies met the inclusion criteria. Results show that, after health education for patients with hypertension, SBP and DBP is substantially lowered; the effect was statistically significant ( P < 0.001). We extended subgroup analyses of the separate effects on SBP and DBP with respect to follow-up time, intervention site, intervention method and age. Conclusion: This review confirms that health education plays an important role in blood pressure control in hypertensive patients (especially the elderly): short-term follow-up intervention was more effective, and the effects were similar whether intervention was at the hospital or at the community level.
Polymerization kinetics of polyurethanes containing trisilanol isooctyl polyhedral oligomeric silsesquioxane
Authors: Fiorio Rudinei , Pistor Vincius , Zattera Ademir Jose , Petzhold Cesar Liberato 
Published: April 2013

Two polyurethane model compounds obtained from 4,4′-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO) or MDI and trisilanol isooctyl polyhedral oligomeric silsesquioxane (POSS) were synthesized and characterized by Fourier transform infrared spectroscopy and thermogravimetric analysis. Moreover, polymerization kinetics of the samples obtained from an isocyanate-terminated prepolymer and BDO containing 0, 0.23, 0.57, 1.14 and 2.28 wt% of POSS were studied from oscillatory rheometry and differential scanning calorimetry. A higher thermal stability was observed for MDI + POSS when compared with MDI + BDO compound. The addition of 1.14 and 2.28 wt% of POSS increased the activation energy of polymerization. The polymerization mechanisms observed were nucleation and growth (A2) at the beginning of synthesis and diffusion controlled (D n) at the last stage of conversion.
Performance of endovenous foam sclerotherapy in the USA for the treatment of venous disorders: ACP/SVM/AVF/SIR quality improvement guidelines
Authors: Rathbun S , Norris A , Morrison N , Gibson K , Raymond-Martimbeau P , Worthington-Kirsch R , Hohenwalter E , Lohr J , McLafferty R , Stoner J 
Published: April 2013

Objective This report summarizes the findings of the consensus panel based on the results of the comprehensive questionnaire of US American College of Phlebology annual congress attendees and results of the systematic meta-analysis of the literature and provides quality improvement guidelines for the use of endovenous foam sclerotherapy (EFS) for the treatment of venous disorders, as well as identifies areas of needed research. Methods Based on the above data, quality improvement guidelines were developed and reviewed by the ten US consensus panel members and approved by their respective societies. Results EFS is effective for the treatment of truncal and tributary varicose veins, both as primary treatment and for treatment of recurrence. It may improve the signs and symptoms associated with varicose veins including pain and swelling. EFS is contraindicated in patients who have experienced an allergic reaction to previous treatment with foam or liquid sclerosant, and in patients with acute venous thrombosis events secondary to EFS. Conclusion These guidelines for the use of EFS in the treatment of venous disorders provide an initial framework for the safe and efficacious use of this therapy, and the impetus to promote the evaluation of the questions remaining regarding the use of EFS through well-designed randomized and cohort studies.
A therapeutic option in nutcracker syndrome and ovarian vein insufficiency
Authors: Bekou V , Zollikofer C , Nieuwkamp N , Von Weymarn A , Duewell S , Traber J 
Published: April 2013

Objectives: The nutcracker syndrome (NS) may lead to insufficient perirenal collaterals as well as incompetence of the left ovarian vein with consecutive ovarian vein insufficiency. Methods: A female patient with NS and severe genital varicosis was treated with dilation of the renal vein and coiling of a left perirenal collateral vein feeding an insufficient left ovarian vein (LOV) with pelvic vein varicosity. Results: In re-evaluation 18 month later with left renal vein (LRV) and LOV phlebography, a widely patent LRV was found. The embolized LRV to LOV collateral was occluded. However, left hypogastric phlebography showed incompetent branches of the left hypogastric vein feeding the genital varicose veins. These were successfully embolized with coils and the genital varicosity decreased on follow-up. Conclusions: In our patient a combined therapeutic approach with balloon dilation of the NS and embolization of the genital varicose veins by left hypogastric vein coil was performed.
The European burden of primary varicose veins
Authors: Moore H M , Lane T R A , Thapar A , Franklin I J , Davies A H 
Published: April 2013

Background: The treatment of varicose veins has been demonstrated to improve quality of life, alleviate symptoms of depression and treat the complications of venous disease. This study aims to show the studies which contain information regarding the prevalence and distribution of venous disease. Then using the population and prevalence data for venous disease, and considering the cost of treating varicose veins, this study aims to analyse the treatment of varicose veins and assess whether there is a disparity between European countries. Methods: Relevant papers regarding the prevalence or incidence of venous disease were identified through searches of PubMed (1966 to October 2010). The search terms ‘prevalence OR incidence’ AND ‘varicose veins or venous disease’ were used. Population data, prevalence data and the number of varicose vein procedures performed in each country was obtained for 2010. Results: Four studies were included. From calculated values comparing the predicted and actual number of patients requiring treatment for venous disease, the UK, Finland and Sweden are potentially not treating all patients with C2 disease. In contrast to this, all other European countries represented are treating more patients, suggesting that they may be treating additional patients. There was up to a four-fold difference in the numbers of procedures per million population that were performed for varicose veins in different European countries. Conclusion: There is a marked disparity across Europe between the predicted number of patients with varicose veins requiring treatment and the actual care given. The factors influencing this need more detailed investigation.
Cost-effectiveness analysis: role and implications
Authors: Marsden G , Wonderling D 
Published: April 2013

Background: Cost-effectiveness analysis (CEA) is often misperceived to be a cost-cutting exercise. The intention of CEA is not to identify and implement cheap technologies, but rather those which offer maximum health gain, subject to available funds. Such analysis is crucial for decision making in health care, as tight budget constraints mean spending in one area of healthcare displaces spending elsewhere. Therefore in order to achieve the greatest health gain for the overall population, treatments must be selected which provide the greatest health gain within the available funds. Summary: The relevance of CEA in health care systems is explained, using varicose vein treatment in the UK NHS as an example. Treatment for varicose veins is often not commissioned to at a local level, most likely because it is misperceived to be a cosmetic problem. However, this view does not take into account the impact of quality of life. CEA balances costs against a quantitative measure of health related quality of life, and could therefore be used to determine whether it is cost-effective to provide varicose vein treatment. The current literature on the cost-effectiveness of varicose vein treatment is reviewed, and an overview of cost-effectiveness principles is provided. Concepts such as economic modelling, incremental cost-effectiveness ratios (ICERs), net monetary benefit (NMB) and sensitivity analysis are explained, using examples relevant to varicose veins where appropriate. Conclusion: This article explains how, far from cutting costs and sacrificing patient health, CEA provides a useful tool to maximise the health of the population in the face of ever tightening budget constraints. CEA could be used to compare the cost-effectiveness of the various treatment options for varicose veins, and efficiencies realised.