bluuebunny/crossref_metadata_2025_split huggingface dataset:
A diagnostic cohort study on the accuracy of 18-fluorodeoxyglucose (18FDG) positron emission tomography (PET)-CT for evaluation of malignancy in anterior mediastinal lesions: the DECiMaL study
Authors: Proli Chiara , De Sousa Paulo , Jordan Simon , Anikin Vladimir , Devaraj Anand , Love Susannah M , Shackcloth Michael , Kostoulas Nikolaos , Papagiannopoulos Kostas , Haqzad Yama , Loubani Mahmoud , Sellitri Francesco , Granato Felice , Bush Alexander , Marchbank Adrian , Iyer Swetha , Scarci Marco , Lim Eric 
Published: February 2018

ObjectivesThe aim of this study is to collate multi-institutional data to determine the value by defining the diagnostic performance of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for malignancy in patients undergoing surgery with an anterior mediastinal mass in order to ascertain the clinical utility of PET/CT to differentiate malignant from benign aetiologies in patients presenting with an anterior mediastinal massSettingDECiMaL Study is a multicentre, retrospective, collaborative cohort study in seven UK surgical sites.ParticipantsBetween January 2002 and June 2015, a total of 134 patients were submitted with a mean age (SD) of 55 years (16) of which 69 (51%) were men. We included all patients undergoing surgery who presented with an anterior mediastinal mass and underwent PET/CT. PET/CT was considered positive for any reported avidity as stated in the official report and the reference was the resected specimen reported by histopathology using WHO criteria.Primary and secondary outcome measuresSensitivity, specificity, positive and negative predicted values of [18F]-FDG PET in determining malignant aetiology for an anterior mediastinal mass.ResultsThe sensitivity and specificity of PET/CT to correctly classify malignant disease were 83% (95% CI 74 to 89) and 58% (95% CI 37 to 78). The positive and negative predictive values were 90% (95% CI 83% to 95%) and 42% (95% CI 26% to 61%).ConclusionsThe results of our study suggest reasonable sensitivity but no specificity implying that a negative PET/CT is useful to rule out the diagnosis of malignant disease whereas a positive result has no value in the discrimination between malignant and benign diseases of the anterior mediastinum.
How patients’ experiences of respiratory tract infections affect healthcare-seeking and antibiotic use: insights from a cross-sectional survey in rural Anhui, China
Authors: Diao Mengjie , Shen Xingrong , Cheng Jing , Chai Jing , Feng Rui , Zhang Panpan , Zhou Rongyao , Lambert Helen , Wang Debin 
Published: February 2018

ObjectiveTo investigate the occurrence of reported respiratory tract infection (RTI) symptoms and their effects on use of self and professional care among patients in the community.DesignA cross-sectional retrospective household survey.Setting12 administrative villages from rural Anhui, China.Participants2160 rural adult residents aged ≥18 years registered as rural residents and actually living in the sampled villages when this study was conducted.MethodThe respondents were recruited using stratified-clustered randomised sampling. A structured questionnaire was deployed to solicit information about social demographics, symptoms of last RTI and healthcare-seeking following the RTI. Descriptive analyses were performed to investigate the reported symptoms, and multivariate logistic regression models were developed to identify relationships between number of concurrent symptoms and healthcare-seeking and antibiotics use.ResultsA total of 1968 residents completed the survey, resulting in a response rate of 91.1%. The number of concurrent symptoms showed a clear increasing trend with seeking help from clinics and being prescribed antibiotics. Multivariate regression revealed statistically significant associations between the following: (a) visiting clinics and education (OR=0.790), sore throat (OR=1.355), cough (OR=1.492), shortness of breath (OR=1.707) and fever (OR=2.142); (b) buying medicine from shops without prescription and education (OR=1.230) and cough (OR=1.452); (c) getting antibiotics at clinics and sore throat (OR=2.05) and earache and/or tinnitus (OR=4.884); and (d) obtaining antibiotics at medicine shops and productive cough (OR=1.971).ConclusionsReported RTI symptoms play an important role in shaping both patient- and doctor-led responses.
Standard echocardiography versus handheld echocardiography for the detection of subclinical rheumatic heart disease: protocol for a systematic review
Authors: Telford Lisa H , Abdullahi Leila H , Ochodo Eleanor A , Zühlke Liesl J , Engel Mark E 
Published: February 2018

IntroductionRheumatic heart disease (RHD) is a preventable and treatable chronic condition which persists in many developing countries largely affecting impoverished populations. Handheld echocardiography presents an opportunity to address the need for more cost-effective methods of diagnosing RHD in developing countries, where the disease continues to carry high rates of morbidity and mortality. Preliminary studies have demonstrated moderate sensitivity as well as high specificity and diagnostic odds for detecting RHD in asymptomatic patients. We describe a protocol for a systematic review on the diagnostic performance of handheld echocardiography compared to standard echocardiography using the 2012 World Heart Federation criteria for diagnosing subclinical RHD.Methods and analysisElectronic databases including PubMed, Scopus, Web of Science and EBSCOhost as well as reference lists and citations of relevant articles will be searched from 2012 to date using a predefined strategy incorporating a combination of Medical Subject Heading terms and keywords. The methodological validity and quality of studies deemed eligible for inclusion will be assessed against review specific Quality Assessment of Diagnostic Accuracy Studies 2 criteria and information on metrics of diagnostic accuracy and demographics extracted. Forest plots of sensitivity and specificity as well as scatter plots in receiver operating characteristic (ROC) space will be used to investigate heterogeneity. If possible, a meta-analysis will be conducted to produce summary results of sensitivity and specificity using the Hierarchical Summary ROC method. In addition, a sensitivity analysis will be conducted to investigate the effect of studies with a high risk of bias.Ethics and disseminationEthics approval is not required for this systematic review of previously published literature. The planned review will provide a summary of the diagnostic accuracy of handheld echocardiography. Results may feed into evidence-based guidelines and should the findings of this review warrant a change in clinical practice, a summary report will be disseminated among leading clinicians and healthcare professionals in the field.PROSPERO registration numberCRD42016051261.
Prospective evaluation of medication-related clinical decision support over-rides in the intensive care unit
Authors: Wong Adrian , Amato Mary G , Seger Diane L , Rehr Christine , Wright Adam , Slight Sarah P , Beeler Patrick E , Orav E. John , Bates David W 
Published: February 2018

BackgroundClinical decision support (CDS) displayed in electronic health records has been found to reduce the incidence of medication errors and adverse drug events (ADE). Recent data suggested that medication-related CDS alerts were frequently over-ridden, often inappropriately. Patients in the intensive care unit (ICU) are at an increased risk of ADEs; however, limited data exist on the benefits of CDS in the ICU. This study aims to evaluate potential harm associated with medication-related CDS over-rides in the ICU.MethodsThis was a prospective observational study of adults admitted to any of six ICUs between July 2016 and April 2017 at our institution. Patients with provider-overridden CDS for dose (orders for scheduled frequency and not pro re nata), drug allergy, drug–drug interaction, geriatric and renal alerts (contraindicated medications for renal function or renal dosing) were included. The primary outcome was the appropriateness of over-rides, which were evaluated by two independent reviewers. Secondary outcomes included incidence of ADEs following alert over-ride and risk of ADEs based on over-ride appropriateness.ResultsA total of 2448 over-ridden alerts from 712 unique patient encounters met inclusion criteria. The overall appropriateness rate for over-rides was 81.6% and varied by alert type. More ADEs (potential and definite) were identified following inappropriate over-rides compared with appropriate over-rides (16.5 vs 2.74 per 100 over-ridden alerts, Fisher’s exact test P<0.001). An adjusted logistic regression model showed that inappropriate over-rides were associated with an increased risk of ADEs (OR 6.14, 95% CI 4.63 to 7.71, P<0.001).ConclusionsApproximately four of five identified CDS over-rides were appropriately over-ridden, with the rate varying by alert type. However, inappropriate over-rides were six times as likely to be associated with potential and definite ADEs, compared with appropriate over-rides. Further efforts should be targeted at improving the positive predictive value of CDS such as by suppressing alerts that are appropriately over-ridden.
Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis
Authors: D’Souza Ryan S , Mercogliano Christopher , Ojukwu Elizabeth , D’Souza Shawn , Singles Andrew , Modi Jaymin , Short Alexandra , Donato Anthony 
Published: February 2018

ObjectivesTo determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect.MethodsSystematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation.ResultsFour placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007).ConclusionProphylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.
New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm
Authors: Renzulli Matteo , Biselli Maurizio , Brocchi Stefano , Granito Alessandro , Vasuri Francesco , Tovoli Francesco , Sessagesimi Elisa , Piscaglia Fabio , D’Errico Antonietta , Bolondi Luigi , Golfieri Rita 
Published: February 2018

ObjectiveMany improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging.DesignOur study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology.ResultsA classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN.ConclusionOur new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN.
Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma
Authors: Chew Valerie , Lee Yun Hua , Pan Lu , Nasir Nurul J M , Lim Chun Jye , Chua Camillus , Lai Liyun , Hazirah Sharifah Nur , Lim Tony Kiat Hon , Goh Brian K P , Chung Alexander , Lo Richard H G , Ng David , Filarca Rene L F , Albani Salvatore , Chow Pierce K H 
Published: February 2018

ObjectivesYttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response.DesignTime-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE.ResultsTILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8+T cells, CD56+NK cells and CD8+CD56+NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB+CD8+T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8+and CD4+T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1+/Tim-3+CD8+T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs.ConclusionHigh-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment.
Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement
Authors: Del Trigo María , Muñoz-García Antonio J , Latib Azeem , Auffret Vincent , Wijeysundera Harindra C , Nombela-Franco Luis , Gutierrez Enrique , Cheema Asim N , Serra Vicenç , Amat-Santos Ignacio J , Kefer Joelle , Benitez Luis Miguel , Leclercq Florence , Mangieri Antonio , Le Breton Hervé , Jiménez-Quevedo Pilar , Garcia del Blanco Bruno , Dager Antonio , Abdul-Jawad Altisent Omar , Puri Rishi , Pibarot Philippe , Rodés-Cabau Josep 
Published: February 2018

ObjectiveTo evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy.Methods and resultsThis multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up.ConclusionsThe lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD.
Mobility shift of beta-dystroglycan as a marker ofGMPPBgene-related muscular dystrophy
Authors: Sarkozy Anna , Torelli Silvia , Mein Rachael , Henderson Matt , Phadke Rahul , Feng Lucy , Sewry Caroline , Ala Pierpaolo , Yau Michael , Bertoli Marta , Willis Tracey , Hammans Simon , Manzur Adnan , Sframeli Maria , Norwood Fiona , Rakowicz Wojtek , Radunovic Aleksandar , Vaidya Sujit S , Parton Matt , Walker Mark , Marino Silvia , Offiah Curtis , Farrugia Maria Elena , Mamutse Godwin , Marini-Bettolo Chiara , Wraige Elizabeth , Beeson David , Lochmüller Hanns , Straub Volker , Bushby Kate , Barresi Rita , Muntoni Francesco 
Published: February 2018

BackgroundDefects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies. Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy. Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date. With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.MethodsWe describe clinical, genetic and biochemical findings of 21 patients withGMPPB-associated dystroglycanopathy.ResultsWe report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition. In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean. This was only observed in patients with GMPPB in our large dystroglycanopathy cohort. We further demonstrate that this mobility shift in patients with GMPPB was due to abnormalN-linked glycosylation of β-DG.ConclusionsOur data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect inGMPPB.
Plasma tau is increased in frontotemporal dementia
Authors: Foiani Martha S , Woollacott Ione OC , Heller Carolin , Bocchetta Martina , Heslegrave Amanda , Dick Katrina M , Russell Lucy L , Marshall Charles R , Mead Simon , Schott Jonathan M , Fox Nick C , Warren Jason D , Zetterberg Henrik , Rohrer Jonathan D 
Published: February 2018

BackgroundFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder presenting clinically with personality change (behavioural variant FTD (bvFTD)) or language deficits (primary progressive aphasia (PPA)). About a third of FTD is familial with mutations in GRN, MAPT and C9orf72 being the major genetic causes. Robust biomarkers of the underlying pathology are still lacking in FTD with no markers currently being able to distinguish those with tau and TDP-43 inclusions during life.MethodsThis study used an ultrasensitive single molecule methodology to measure plasma tau concentrations in 176 participants: 71 with bvFTD, 83 with PPA and 22 healthy controls. The patient group included 36 with pathogenic mutations in either MAPT (n=12), GRN (n=9) or C9orf72 (n=15). Group comparisons were performed between clinical and genetic groups and controls using a linear regression model with bias-corrected bootstrap CIs. Correlative analyses were performed to investigate associations with measures of disease severity and progression.ResultsHigher plasma tau concentrations were seen in bvFTD (mean 1.96 (SD 1.07) pg/mL) and PPA (2.65 (2.15) pg/mL) compared with controls (1.67 (0.50) pg/mL). Investigating the PPA group further showed significantly higher levels compared with controls in each of the PPA subtypes (non-fluent, semantic and logopenic variants, as well as a fourth group not meeting criteria for one of the three main variants). In the genetic groups, only the MAPT group had significantly increased concentrations (2.62 (1.39) pg/mL) compared with controls. No significant correlations were seen with cross-sectional or longitudinal brain volumes, serum neurofilament light chain concentrations or disease duration.ConclusionPlasma tau levels are increased in FTD in all clinical groups, but in the genetic subtypes only in MAPT mutations, the group of patients who definitively have tau pathology at postmortem. Future studies will be required in pathologically confirmed cohorts to investigate this association further, and whether plasma tau will be helpful in differentiating patients with FTD with tau from those with other pathologies.