bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stigmatisation and body image impairment in dermatological patients: protocol for an observational multicentre study in 16 European countries
Authors: Dalgard Florence J , Bewley Anthony , Evers Andrea W , Gieler Uwe , Lien Lars , Sampogna Francesca , Ständer Sonja , Tomas-Aragones Lucia , Vulink Ninke , Kupfer Jörg 
Published: December 2018

IntroductionPatients with common skin diseases may have substantial psychosocial comorbidity and reduced quality of life. This study aims at exploring further the psychosocial burden of skin diseases by assessing stigmatisation and body image problems in a large sample of patients with skin disease across Europe.Methods and analysisThe study is an observational cross-sectional multicentre study across 16 European countries comparing stigmatisation and body image in patients with skin disease compared with controls. Consecutive patients will be recruited in outpatient clinics and will complete validated questionnaires prior to clinical examination by a dermatologist at each recruitment site. In addition to sociodemographic background information, the outcomes will be: mood disorders assessed by short versions of the Patient Health Questionnaire and the General Anxiety Disorder Assessment; general health assessed by the EuroQol-Visual Analogue Scale; stigmatisation experience assessed by the Perceived Stigmatisation Questionnaire; stress assessed by the Perceived Stress Scale and body image assessed by the Dysmorphic Concern Questionnaire. The main criteria for eligibility are to be 18 years old or more. The analysis will include comparison between patients and controls for the main outcomes using t-tests, analyses of covariance and multivariate logistic regression models adjusting for potential confounding factors.Ethics and disseminationThe study protocol is approved by the University of Giessen and by the local Ethical Committee in each recruitment centre. Informed consent will be given by each participant. The results of the study will be disseminated by publications in international peer-reviewed journals and presented at international conferences and general public conferences. Results will influence support intervention and management of patients with skin disease across Europe.Trial registration numberDRKS00012745; Pre-results.
Are anxiety levels associated with the decision to participate in a Swedish colorectal cancer screening programme? A nationwide cross-sectional study
Authors: Wangmar Johanna , von Vogelsang Ann-Christin , Hultcrantz Rolf , Fritzell Kaisa , Wengström Yvonne , Jervaeus Anna 
Published: December 2018

ObjectivesColorectal cancer (CRC) screening programmes are commonly challenged by low uptake, limiting their potential to reduce CRC burden. We aimed to investigate anxiety levels related to the decision to participate or not in CRC screening among screening participants and non-participants. Further to explore associations between higher anxiety levels related to the decision and individuals’ characteristics.DesignA nationwide cross-sectional study conducted with individuals included in a national randomised controlled CRC screening trial, the Screening of Swedish Colons (SCREESCO).ParticipantsA total of 1409 individuals, 60–62 years, recruited from SCREESCO during 2015–2016 participated in the study; 1256 had participated in CRC screening (faecal immunochemical test: n=958; colonoscopy: n=298) and 153 had declined screening participation.MeasuresAnxiety levels were assessed with the State-Trait Anxiety Inventory (STAI) S-Anxiety Scale. Health literacy (HL) was assessed with the Swedish Functional and Communicative and Critical Health Literacy Scales.ResultsAltogether, 79% of survey participants reported lower anxiety levels regarding their CRC screening decision (STAI S-Anxiety <40). Anxiety levels did not differ between screening participants and non-participants (mean STAI S-Anxiety score=34.1 vs 33.9, p=0.859). The odds of reporting higher anxiety levels increased by female sex (OR=1.37; CI 1.04 to 1.80; p=0.025) and previous faecal sampling (OR=1.53; CI 1.14 to 2.05; p=0.004), and decreased if living with partner (OR=0.65; CI 0.48 to 0.88; p=0.005), working (OR=0.72; CI 0.53 to 0.96; p=0.027) or having sufficient HL (functional: OR=0.49; CI 0.33 to 0.73, p≤0.001; communicative and critical: OR=0.55; CI 0.38 to 0.82; p=0.003).ConclusionsAnxiety levels did not differ between screening participants and non-participants. Higher anxiety scores were associated with certain characteristics. Interventions accounting for these characteristics can be applied to reduce anxiety and facilitate programme acceptance.Trial registration numberNCT02078804; Results.
Directing research funds to the right research projects: a review of criteria used by research organisations in Australia in prioritising health research projects for funding
Authors: Tuffaha Haitham W , El Saifi Najwan , Chambers Suzanne K , Scuffham Paul A 
Published: December 2018

ObjectivesHealthcare budgets are limited, and therefore, research funds should be wisely allocated to ensure high-quality, useful and cost-effective research. We aimed to critically review the criteria considered by major Australian organisations in prioritising and selecting health research projects for funding.MethodsWe reviewed all grant schemes listed on the Australian Competitive Grants Register that were health-related, active in 2017 and with publicly available selection criteria on the funders’ websites. Data extracted included scheme name, funding organisation, selection criteria and the relative weight assigned to each criterion. Selection criteria were grouped into five representative domains: relevance, appropriateness, significance, feasibility (including team quality) and cost-effectiveness (ie, value for money).ResultsThirty-six schemes were included from 158 identified. One-half of the schemes were under the National Health and Medical Research Council. The most commonly used criteria were research team quality and capability (94%), research plan clarity (94%), scientific quality (92%) and research impact (92%). Criteria considered less commonly were existing knowledge (22%), fostering collaboration (22%), research environment (19%), value for money (14%), disease burden (8%) and ethical/moral considerations (3%). In terms of representative domains, relevance was considered in 72% of the schemes, appropriateness in 92%, significance in 94%, feasibility in 100% and cost-effectiveness in 17%. The relative weights for the selection criteria varied across schemes with 5%–30% for relevance, 20%–60% for each appropriateness and significance, 20%–75% for feasibility and 15%–33% for cost-effectiveness.ConclusionsIn selecting research projects for funding, Australian research organisations focus largely on research appropriateness, significance and feasibility; however, value for money is most often overlooked. Research funding decisions should include an assessment of value for money in order to maximise return on research investment.
Supraciliary microstent implantation for open-angle glaucoma: multicentre 3-year outcomes
Authors: Grisanti Swaantje , Grisanti Salvatore , Garcia-Feijoo Julian , Dick H Burkhard , Munoz-Negrete Francisco Jose , Arrondo Elena , Ianchulev Tsontcho 
Published: December 2018

ObjectiveTo describe the safety and effectiveness of CyPass supraciliary microstent implantation alone in eyes with open-angle glaucoma (OAG) followed up for up to 3 years.Methods and analysisThis registry study included subjects with primary or secondary OAG who underwent CyPass Micro-Stent implantation alone at 12 sites in four European countries to reduce intraocular pressure (IOP) and/or use of IOP-lowering medications. The primary safety outcome was the incidence of adverse events. Secondary efficacy outcomes included mean changes from baseline in IOP and IOP-lowering medications. Eyes were subgrouped into those with low (< 21 mm Hg) and high (>21 mm Hg) baseline IOP.ResultsThis study included 225 eyes of 178 patients, with mean baseline IOP of 22.6 ± 6.7 mm Hg and a mean 2.2 ± 1.2 medications per eye. Common ocular adverse events included device obstruction (10.2%), IOP elevation>10 mm Hg during follow-up (8.9%), retinal complications (4.4%) and loss of > 2 lines of best-corrected visual acuity (2.7%). Seventy-one eyes (31.6%) required secondary glaucoma surgery, with trabeculectomy (33 eyes) and second microstent implantation (13 eyes) being most common. At months 6–36, mean IOP reductions ranged from 4.4 to 5.1 mm Hg (15.8%–19.5%) and mean medication reductions from 0.2 to 1.2 (9.1%–54.5%). Mean IOP reduction was greater in eyes with higher than lower baseline IOP. Both subgroups showed reductions of 0.5–1.0 medication at 12–18 months.ConclusionCyPass microstent implantation demonstrated a safety profile consistent with other minimally invasive glaucoma surgeries and effectively lowered IOP for up to 3 years in eyes with OAG.
Incidence of mortality due to rebound toxicity after ‘treat and release’ practices in prehospital opioid overdose care: a systematic review
Authors: Greene Jennifer Anne , Deveau Brent J , Dol Justine S , Butler Michael B 
Published: December 2018

IntroductionDeath due to opioid overdose was declared a public health crisis in Canada in 2015. Traditionally, patients who have overdosed on opioids that are managed by emergency medical services (EMS) are treated with the opioid antagonist naloxone, provided ventilatory support and subsequently transported to hospital. However, certain EMS agencies have permitted patients who have been reversed from opioid overdose to refuse transport, if the patient exhibits capacity to do so. Evidence on the safety of this practice is limited. Therefore, our intent was to examine the available literature to determine mortality and serious adverse events within 48 hours of EMS treat and release due to suspected rebound opioid toxicity after naloxone administration.MethodsA systematic search was performed on 11 May 2017 in PubMed, Cochrane Central, Embase and CINHAL. Studies that reported on the outcome of patients treated with prehospital naloxone and released at the scene were included. Analyses for incidence of mortality and adverse events at the scene were conducted. Risk of bias and assessment of publication bias was also done.Results1401 records were screened after duplicate removal. Eighteen full-text studies were reviewed with seven selected for inclusion. None were found to be high risk of bias. In most studies, heroin was the source of the overdose. Mortality within 48 hours was infrequent with only four deaths among 4912 patients ﴾0.081%﴿ in the seven studies. Only one study reported on adverse events and found no incidence of adverse events from their sample of 71 released patients.ConclusionMortality or serious adverse events due to suspected rebound toxicity in patients released on scene post-EMS treatment with naloxone were rare. However, studies involving longer-acting opioids were rare and no study involved fentanyl.
Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection
Authors: Hoogeveen Ruben C , Robidoux Maxwell P , Schwarz Tatjana , Heydmann Laura , Cheney James A , Kvistad Daniel , Aneja Jasneet , Melgaço Juliana G , Fernandes Carlos A , Chung Raymond T , Boonstra Andre , Kim Arthur Y , Baumert Thomas F , Timm Jörg , Lewis-Ximenez Lia L , Tonnerre Pierre , Lauer Georg M 
Published: December 2018

ObjectiveChronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control.DesignThe phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection.ResultsWe detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities.ConclusionHBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure.
Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity
Authors: Korf Hannelie , du Plessis Johannie , van Pelt Jos , De Groote Sofie , Cassiman David , Verbeke Len , Ghesquière Bart , Fendt Sarah-Maria , Bird Matthew J , Talebi Ali , Van Haele Matthias , Feio-Azevedo Rita , Meelberghs Lore , Roskams Tania , Mookerjee Rajeshwar P , Mehta Gautam , Jalan Rajiv , Gustot Thierry , Laleman Wim , Nevens Frederik , van der Merwe Schalk Willem 
Published: December 2018

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16−monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, anin vitromodel mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16−monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity ofin vitrogenerated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.
Revalidation of the RACE scale after its regional implementation in Catalonia: a triage tool for large vessel occlusion
Authors: Carrera David , Gorchs Montse , Querol Marisol , Abilleira Sònia , Ribó Marc , Millán Mònica , Ramos Anna , Cardona Pedro , Urra Xabier , Rodríguez-Campello Ana , Prats-Sánchez Luis , Purroy Francisco , Serena Joaquín , Cánovas David , Zaragoza-Brunet Josep , Krupinski Jerzy A , Ustrell Xavier , Saura Júlia , García Sonia , Mora Maria Àngela , Jiménez Xavier , Dávalos Antoni , Pérez de la Ossa Natalia 
Published: December 2018

Background and purposeOur aim was to revalidate the RACE scale, a prehospital tool that aims to identify patients with large vessel occlusion (LVO), after its region-wide implementation in Catalonia, and to analyze geographical differences in access to endovascular treatment (EVT).MethodsWe used data from the prospective CICAT registry (Stroke Code Catalan registry) that includes all stroke code activations. The RACE score evaluated by emergency medical services, time metrics, final diagnosis, presence of LVO, and type of revascularization treatment were registered. Sensitivity, specificity, and area under the curve (AUC) for the RACE cut-off value ≥5 for identification of both LVO and eligibility for EVT were calculated. We compared the rate of EVT and time to EVT of patients transferred from referral centers compared with those directly presenting to comprehensive stroke centers (CSC).ResultsThe RACE scale was evaluated in the field in 1822 patients, showing a strong correlation with the subsequent in-hospital evaluation of the National Institute of Health Stroke Scale evaluated at hospital (r=0.74, P<0.001). A RACE score ≥5 detected LVO with a sensitivity 0.84 and specificity 0.60 (AUC 0.77). Patients with RACE ≥5 harbored a LVO and received EVT more frequently than RACE <5 patients (LVO 35% vs 6%; EVT 20% vs 6%; all P<0.001). Direct admission at a CSC was independently associated with higher odds of receiving EVT compared with admission at a referral center (OR 2.40; 95% CI 1.66 to 3.46), and symtoms onset to groin puncture was 133 min shorter.ConclusionsThis large validation study confirms RACE accuracy to identify stroke patients eligible for EVT, and provides evidence of geographical imbalances in the access to EVT to the detriment of patients located in remote areas.
Direct Targeting of MYCN Gene Amplification by Site-Specific DNA Alkylation in Neuroblastoma
Authors: Yoda Hiroyuki , Inoue Takahiro , Shinozaki Yoshinao , Lin Jason , Watanabe Takayoshi , Koshikawa Nobuko , Takatori Atsushi , Nagase Hiroki 
Published: December 2018

Abstract

Amplification of MYCN plays a pivotal role in multiple types of tumors and correlates with poor prognosis in high-risk neuroblastoma. Despite recent advances in the treatment of neuroblastoma, no approaches directly target the master oncogene MYCN. Difficulties in targeting the MYCN protein inspired us to develop a new gene-level–inhibitory strategy using a sequence-specific gene regulator. Here, we generated a MYCN-targeting pyrrole-imidazole (PI) polyamide, MYCN-A3, which directly binds to and alkylates DNA at homing motifs within the MYCN transcript. Pharmacologic suppression of MYCN inhibited the proliferation of cancer cells harboring MYCN amplification compared with MYCN nonamplified cancer cells. In neuroblastoma xenograft mouse models, MYCN-A3 specifically downregulated MYCN expression and suppressed tumor progression with no detectable adverse effects and resulted in prolonged overall survival. Moreover, treatment with MYCN-A3, but not MYCN nontargeting PI polyamide, precipitated a copy number reduction of MYCN in neuroblastoma cells with MYCN amplification. These findings suggest that directly targeting MYCN with MYCN-A3 is a novel therapeutic approach to reduce copy number of the MYCN gene for MYCN-amplified neuroblastoma.

Significance:
This study presents a novel approach to drugging an amplified oncogene by showing that targeting gene amplification of MYCN suppresses MYCN expression and neuroblastoma growth.
Time Trends in Atrial Fibrillation-Associated Stroke and Premorbid Anticoagulation
Authors: Yiin Gabriel S.C. , Li Linxin , Bejot Yannick , Rothwell Peter M. 
Published: December 2018

Background and Purpose—
Prevalence of atrial fibrillation (AF) is increasing, but the impact on overall burden of stroke is uncertain, as is the proportion that could be attributed to under anticoagulation. We did a population-based study of AF-associated stroke and a systematic review of time trends in other stroke incidence studies and of rates of premorbid anticoagulation.

Methods—
The proportion of incident strokes with associated AF was determined in the OXVASC (Oxford Vascular Study; 2002–2017) and in other prospective, population-based stroke incidence studies published before December 2017. Proportions were pooled by Mantel Haenszel methods, and the pooled percentage of cases with premorbid anticoagulation was determined. Analyses were stratified by the age of study population, mid-study year, country, and ethnicity.

Results—

Of 1928 patients with incident ischemic stroke in OXVASC, 629 (32.6%; 95% CI, 30.5–34.7) were AF associated, consistent with the pooled estimate from 4 smaller studies over the same study period (608/1948; 31.2%, 30.0–32.4;
P
het
=0.80). The pooled estimate from all studies reporting premorbid AF over 25 million person-years of observation (1960 onwards; 33 reports) was lower (18.6%, 16.8–20.3) and more heterogeneous (
P
het
<0.0001), but 62% of heterogeneity was explained by the age of study population, study period, country, and ethnicity. The proportion of incident strokes on premorbid anticoagulation increased over time, both for ischemic stroke in OXVASC (2002–2007: 15.1%, 2008–2012: 19.6%, and 2013–2017: 35.9%;
P
trend
<0.0001), and across all studies (
P
=0.002), but the pooled estimates suggested substantial undertreatment even in the most recent periods (2001–2015: 25.7%, 21.1–30.3 and ≥2010: 31.6%, 18.2–44.9).

Conclusions—
About 1 in 3 incident ischemic strokes are still AF associated, due partly to low rates of anticoagulation for known prior AF, which therefore represents a major public health opportunity to reduce the burden of stroke.
Nationwide Analysis of Cost Variation for Treatment of Aneurysmal Subarachnoid Hemorrhage
Authors: Yoon Seungwon , Yoon Jennifer C. , Winkler Ethan , Liu Caterina , Lawton Michael T. 
Published: December 2018

Background and Purpose—
Aneurysmal subarachnoid hemorrhage (aSAH) has a high healthcare cost burden.

Methods—
We performed a cross-sectional analysis of the costs of clipping and coiling of aSAH using the National Inpatient Sample and Vizient databases. We conducted multiple regression analyses to estimate national costs and study associations between patient demographic, clinical, and hospital factors and treatment costs.

Results—

We identified 23 324 ruptured aneurysm patients in the National Inpatient Sample (2002–2013) and found mean inflation-adjusted costs for clipping increased 41.0% ($66 358±1354–$93 597±2339), whereas costs for coiling increased 38.9% ($62 972±2657–$87 441±2382). Multivariate analysis showed that age, length of stay, insurance, comorbidities, risk of mortality, and urban teaching hospital status were associated with higher hospital costs for clipping and coiling (all
P
<0.05). In the Vizient database (2013–2015), costs for clipping and coiling increased 11% and 5%, respectively. Both databases demonstrated that the western United States had the highest health expenditures for aSAH (
P
<0.05).

Conclusions—
Findings show substantial cost increases and regional cost disparities for aSAH treatments. Patient and hospital factors copredict higher costs for aSAH procedures. Interhospital and regional cost variations open the door for cost-containment strategic development.