A Multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage (AMPAS): observational registry study

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with very high mortality and morbidity. Our limited knowledge on predictors of long-term outcome in poor-grade patients with aSAH definitively managed comes from retrospective and prospective studies of small case series of patients in single center. The purpose of the AMPAS is to determine the long-term outcomes in poor-grade patients with different managements within different time after aSAH, and identify the independent predictors of the outcome that help guide the decision on definitive management. METHODS/DESIGN: The AMPAS study is a prospective, multicenter, observational registry of consecutive hospitalized patients with poor grade aSAH (WFNS grade IV and V). The aim is to enroll at least 226 poor-grade patients in 11 high-volume medical centers (eg, >150 aSAH cases per year) affiliated to different universities in China. This study will describe poor grade patients and aneurysm characteristics, treatment strategies (modality and time of definitive management), hospitalization complications and outcomes evolve over time. The definitive management is ruptured aneurysm treatment. Outcomes at 3, 6, 12 months after the management were measured using the Glasgow Outcome Scale and the Modified Rankin Scale. DISCUSSION: The AMPAS is the first prospective, multicenter, observational registry of poor grade aSAH with any management. This study will contribute to a better understanding of significant predictors of outcome in poor grade patients and help guide future treatment of the worst patients after aSAH. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TNRC-10001041

A Randomized, Controlled Treatment Trial of Eyelid-Warming Therapies in Meibomian Gland Dysfunction

AIM: The main treatment for meibomian gland dysfunction (MGD), a major cause of dry eye, is eyelid warming. Lack of compliance is the main reason for treatment failure. This has led to the development of eyelid-warming devices that are safe, effective and convenient. To obtain robust evidence demonstrating their efficacy, the authors conducted a 3-arm randomized clinical study. METHODS: The authors conducted a 3-month assessor-blinded, randomized, controlled trial of patients from the Singapore National Eye Centre experiencing at least one of eight dry eye symptoms ‘often’ or ‘all the time’. Patients who wore contact lenses, had an active infection or known diagnosis of thyroid dysfunction and rheumatoid arthritis were excluded from the study. MGD participants were randomly assigned to warm towel (n = 25), EyeGiene(®) (Eyedetec Medical Inc., Danville, CA, USA) (n = 25) and Blephasteam(®) (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) (n = 25) treatments. The primary efficacy and safety outcomes included the proportions of participants with improved symptoms and changes in best corrected visual acuity (BCVA), respectively. Other outcomes included tear break up time (TBUT), Schirmer test, corneal fluorescein dye staining and number of visibly occluded meibomian gland (MG) orifices. RESULTS: The study population was 53.5 ± 11.1 years old and predominantly Chinese. For severity of symptom after 3 months of treatment, 78.3% Blephasteam(®) participants reported improvement compared to 45.5% warm towel participants (p = 0.023). The corresponding proportions for improvement in the frequency of symptoms were 82.6% and 50.0%, respectively (p = 0.020). The proportions of improvement of symptoms in EyeGiene(®) patients were not significantly different from warm towel intervention. At 1 month of treatment, the crude odds ratio of improvement of severity of irritation for Blephasteam(®) compared to control was 3.0 (95% CI 0.88–10.18). However, the odds ratio adjusted by age was 5.67 (1.30–24.66). The lid-warming treatments did not significantly change the TBUT, Schirmer test results or number of visibly occluded MGs in the study period. All treatment modalities did not worsen BCVA after 3 months. CONCLUSION: Blephasteam(®) is more effective than warm towel for MGD treatment, with warm towel and EyeGiene(®) being comparable effective. Older age might predict for treatment efficacy. All studied therapies were safe for visual acuity (VA) for 3 months of treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40123-014-0025-8) contains supplementary material, which is available to authorized users

Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV(1)); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV(1i)); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV(1p)). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVC(i)); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVC(p)). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV(1)/FVC <0.7 and FEV(1)% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV(1)-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.ALTANA Aventis AstraZeneca Boehringer-Ingelheim Chiesi GlaxoSmithKline Merck Novartis Pfizer Schering-Plough Sepracor University of Kentucky Boehringer Ingelheim Schering Ploug

Search for dark matter in events with heavy quarks and missing transverse momentum in pp collisions with the ATLAS detector

This article reports on a search for dark matterpair production in association with bottom or top quarks in20.3fb−1ofppcollisions collected at√s=8TeVbytheATLAS detector at the LHC. Events with large missing trans-verse momentum are selected when produced in associationwith high-momentum jets of which one or more are identifiedas jets containingb-quarks. Final states with top quarks areselected by requiring a high jet multiplicity and in some casesa single lepton. The data are found to be consistent with theStandard Model expectations and limits are set on the massscale of effective field theories that describe scalar and tensorinteractions between dark matter and Standard Model par-ticles. Limits on the dark-matter–nucleon cross-section forspin-independent and spin-dependent interactions are alsoprovided. These limits are particularly strong for low-massdark matter. Using a simplified model, constraints are set onthe mass of dark matter and of a coloured mediator suitableto explain a possible signal of annihilating dark matter

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 8 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three leptons and missing transverse momentum is presented. The analysis is based on 20.3 fb−1 of s√ = 8 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations and limits are set in R-parity-conserving phenomenological Minimal Supersymmetric Standard Models and in simplified supersymmetric models, significantly extending previous results. For simplified supersymmetric models of direct chargino (χ˜±1) and next-to-lightest neutralino (χ˜02) production with decays to lightest neutralino (χ˜01) via either all three generations of sleptons, staus only, gauge bosons, or Higgs bosons, (χ˜±1) and (χ˜02) masses are excluded up to 700 GeV, 380 GeV, 345 GeV, or 148 GeV respectively, for a massless (χ˜01

Parkinson’s Disease-related Circulating microRNA Biomarkers - a Validation Study

Parkinson’s disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

The role of radiologist in the changing world of healthcare: a White Paper of the European Society of Radiology (ESR)

Radiology as a specialty has been enormously successful since its beginnings, moving over time from an adjunct to clinical decision-making to a crucial component of multidisciplinary patient care. However, this increased centrality of radiology and reliance on our services carries within it dangers, prominent among them being the danger of our being viewed as deliverers of a commodity, and the risk of our becoming overwhelmed by increasing workload, unable to interact sufficiently with patients and referrers due to pressure of work. With this White Paper, the Board of Directors of the European Society of Radiology (ESR) seeks to briefly explain the position of the radiologist in the modern healthcare environment, considering our duties and contributions as doctors, protectors, communicators, innovators, scientists and teachers. This statement is intended to serve as a summary of the breadth of our responsibilities and roles, and to assist radiologists in countering misunderstanding of who we are and what we do