bluuebunny/crossref_metadata_2025 huggingface dataset:
A Functional Link between RNA Replication and Virion Assembly in the Potyvirus
Plum Pox Virus
Authors: Gallo Araiz , Valli Adrian , Calvo María , García Juan Antonio
Published: February 2018

Accurate assembly of viral particles in the potyvirus
Plum pox virus
(PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in
Nicotiana benthamiana
leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied
in trans
, was assembled into virus-like particles and remained stable after
in vitro
incubation. In contrast, deletions in multiple regions of the LONG coding sequence prevented the CP stabilization mediated by HCPro. In particular, we demonstrated that the first 178 amino acids of P3, but not a specific nucleotide sequence coding for them, are required for CP stability and proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we observed that the subviral LONG RNA replicates and locally spreads in
N. benthamiana
leaves expressing an RNA silencing suppressor. The analysis of the effect of both point and deletion mutations affecting RNA replication in LONG and full-length PPV demonstrated that this process is essential for the assembly of stable viral particles. Interestingly, in spite of this requirement, the CP produced by a nonreplicating viral RNA can be stably assembled into virions as long as it is coexpressed with a replication-proficient RNA. Altogether, these results highlight the importance of coupling encapsidation to other viral processes to secure a successful infection.

IMPORTANCE
Viruses of the family
Potyviridae
are among the most dangerous threats for basically every important crop, and such socioeconomical relevance has made them a subject of many research studies. In spite of this, very little is currently known about proteins and processes controlling viral genome encapsidation by the coat protein. In the case of
Plum pox virus
(genus
Potyvirus
), for instance, we have previously shown that the multitasking viral factor HCPro plays a role in the production of stable virions. Here, by using this potyvirus as a model, we move further to show that additional factors are also necessary for the efficient production of potyviral particles. More importantly, a comprehensive screening for such factors led us to the identification of a functional link between virus replication and packaging, unraveling a previously unknown connection of these two key events of the potyviral infection cycle.
SCC
mec
Finder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome
mec
in Staphylococcus aureus Using Whole-Genome Sequence Data
Authors: Kaya Hülya , Hasman Henrik , Larsen Jesper , Stegger Marc , Johannesen Thor Bech , Allesøe Rosa Lundbye , Lemvigh Camilla Koldbæk , Aarestrup Frank Møller , Lund Ole , Larsen Anders Rhod
Published: February 2018

SCC
mec
in MRSA is acknowledged to be of importance not only because it contains the
mecA
or
mecC
gene but also for staphylococcal adaptation to different environments, e.g., in hospitals, the community, and livestock. Typing of SCC
mec
by PCR techniques has, because of its heterogeneity, been challenging, and whole-genome sequencing has only partially solved this since no good bioinformatic tools have been available. In this article, we describe the development of a new bioinformatic tool, SCC
mec
Finder, that includes most of the needs for infection control professionals and researchers regarding the interpretation of SCC
mec
elements. The software detects all of the SCC
mec
elements accepted by the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements, and users will be prompted if diverging and potential new elements are uploaded. Furthermore, SCC
mec
Finder will be curated and updated as new elements are found and it is easy to use and freely accessible.
Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study
Authors: Ahmed Ausman , Mekonnen Desalew , Shiferaw Atsede M , Belayneh Fanuel , Yenit Melaku K
Published: February 2018

Objective

This study assessed the incidence of tuberculosis (TB) and its predictors among adults living with HIV/AIDS in government health facilities in north-east Ethiopia.

Setting

A 5-year retrospective cohort study was conducted from May to June 2015 on 451 adult HIV/AIDS-infected individuals who enrolled in the HIV care clinics of government health facilities in north-east Ethiopia.

Participants

A total of 451 HIV-infected adults who newly enrolled in the adult HIV care clinic from 1 July 2010 with complete information were followed until May 2015.

Primary outcome measure

The primary outcome was the proportion of patients diagnosed with TB or the TB incidence rate.

Secondary outcome measure

The incidence of TB was investigated in relation to years of follow-up.

Results

A total of 451 charts with complete information were followed for 1377.41 person-years (PY) of observation. The overall incidence density of TB was 8.6 per 100 PYof observation. Previous TB disease (adjusted HR (AHR) 3.65, 95% CI 1.97 to 6.73), being bedridden (AHR 5.45, 95% CI 1.16 to 25.49), being underweight (body mass index (BMI) <18.5 kg/m2) (AHR 2.53, 95 % CI 1.27 to 5.05), taking isoniazid preventive therapy (IPT) (AHR 0.14, 95% CI 0.05 to 0.39), haemoglobin below 11 g/dL (AHR 2.31, 95% CI 1.35 to 3.93), and being in WHO clinical stages III and IV (AHR 2.84, 95% CI 1.11 to 7.27; AHR 3.07, 95% CI 1.08 to 8.75, respectively) were significant for the incidence of TB.

Conclusion

The incidence of TB among adults living with HIV/AIDS in the first 3 years of follow-up was higher compared with that of subsequent years. Previous TB disease, no IPT, low BMI and haemoglobin level, advanced WHO clinical stage, and bedridden condition were the determinants of the incidence of TB. Therefore, addressing the significant predictors and improving TB/HIV collaborative activities should be strengthened in the study setting.
Correlates of intensity-specific physical activity in children aged 9–11 years: a multilevel analysis of UK data from the International Study of Childhood Obesity, Lifestyle and the Environment
Authors: Wilkie Hannah J , Standage Martyn , Gillison Fiona B , Cumming Sean P , Katzmarzyk Peter T
Published: February 2018

Objectives

Physical activity (PA) can provide numerous physical and psychological health gains, yet a low proportion of children in England are sufficiently active to accrue benefit. Analysing the correlates of PA from a socioecological perspective may help to identify factors that promote versus discourage PA. The purpose of the present study was to: (1) assess the relationships between a wide range of potential correlates and intensity-specific PA and (2) explore which correlates are associated with meeting government PA guidelines.

Design, setting and participants

Cross-sectional study on children aged 9–11 years from the South West of England (n=425; 183 males).

Outcome measures

A mixture of self-reported and objective measures (eg, body mass index (BMI), accelerometer-derived PA, self-reported sport participation, etc) were collected from child participants, parents and school teachers. After adjusting for covariates (ie, age, sex and accelerometer wear time), multilevel modelling techniques were employed to examine the relationships between potential correlates and light-intensity, moderate-intensity and vigorous-intensity PA, as measured with an ActiGraph GT3X+ accelerometer. Generalised linear mixed modelling was used to analyse the correlates associated with government-recommended levels of PA.

Results

Computer use shared a negative association whereas parent support for PA showed a positive relationship with light-intensity PA. In terms of moderate-intensity PA, computer use and BMI z-score shared a negative association whereas positive relationships were found for sport participation, active transport and for outdoor time after school. Children at schools with 25%–49% of pupils attending school sport/PA clubs did more moderate-intensity PA than those attending schools with lower participation rates. For vigorous-intensity PA, a negative relationship was observed for BMI z-score, and positive associations for self-efficacy, active transport, parent support and the presence of crossing guards on routes to school. Correlates associated with meeting the PA guidelines were BMI z-score (negative), sport participation, active transport and outdoor time after school (all positive).

Conclusion

Results demonstrate that factors pertaining to the individual, home and school environment may play an important role in understanding the correlates of differing PA intensities in children.

Trial registration number

NCT01722500.
Portuguese version of a stress and well-being evaluation tool (ASSET)at the workplace: validation of the psychometric properties
Authors: Heitor dos Santos Maria João , Moreira Sérgio , Carreiras Joana , Cooper Cary , Smeed Matthew , Reis Maria de Fátima , Pereira Miguel José
Published: February 2018

Objective

The main objective of this work was to translate the English version of ASSET (A Shortened Stress Evaluation Tool) into the Portuguese version and to validate its psychometric properties. Additionally, this work tested the convergent validity of the instrument.

Methods

The translation and retroversion were conducted by experts and submitted to the authors for approval. Within an observational, cross-sectional study, regarding mental health at the workplace, ASSET together with other scales was applied to a sample of 405 participants. The psychometric validity of the subscales was studied using confirmatory factorial analysis.

Results

The factorial structure of ASSET is globally supported by the results, with the Perceptions of Your Job and Attitudes Towards your Organisation subscales requiring slight adjustments in the item structure and the Your Health subscales replicating the original structure. The convergent validity also supports the ASSET, showing that all subscales are significantly correlated with variables used to test convergence.

Conclusions

Globally, the results constitute an important contribution to ASSET and open the possibility of its usage among Portuguese-speaking countries. The results provide an evidence on the validity of the instrument and, in particular, of the mental and physical health subscales.
Scoping review on the use of socially assistive robot technology in elderly care
Authors: Abdi Jordan , Al-Hindawi Ahmed , Ng Tiffany , Vizcaychipi Marcela P
Published: February 2018

Objective

With an elderly population that is set to more than double by 2050 worldwide, there will be an increased demand for elderly care. This poses several impediments in the delivery of high-quality health and social care. Socially assistive robot (SAR) technology could assume new roles in health and social care to meet this higher demand. This review qualitatively examines the literature on the use of SAR in elderly care and aims to establish the roles this technology may play in the future.

Design

Scoping review.

Data sources

Search of CINAHL, Cochrane Library, Embase, MEDLINE, PsychINFO and Scopus databases was conducted, complemented with a free search using Google Scholar and reference harvesting. All publications went through a selection process, which involved sequentially reviewing the title, abstract and full text of the publication. No limitations regarding date of publication were imposed, and only English publications were taken into account. The main search was conducted in March 2016, and the latest search was conducted in September 2017.

Eligibility criteria

The inclusion criteria consist of elderly participants, any elderly healthcare facility, humanoid and pet robots and all social interaction types with the robot. Exclusions were acceptability studies, technical reports of robots and publications surrounding physically or surgically assistive robots.

Results

In total, 61 final publications were included in the review, describing 33 studies and including 1574 participants and 11 robots. 28 of the 33 papers report positive findings. Five roles of SAR were identified: affective therapy, cognitive training, social facilitator, companionship and physiological therapy.

Conclusions

Although many positive outcomes were reported, a large proportion of the studies have methodological issues, which limit the utility of the results. Nonetheless, the reported value of SAR in elderly care does warrant further investigation. Future studies should endeavour to validate the roles demonstrated in this review.

Systematic review registration

NIHR 58672.
Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over­active bladder syndrome? An Australian cohort study
Authors: Mintzes Barbara , Swandari Swestika , Fabbri Alice , Grundy Quinn , Moynihan Ray , Bero Lisa
Published: February 2018

Objectives

To investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment.

Design and setting

This retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population.

Main outcome measures

Event and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates.

Results

Over the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events.

Conclusions

This 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often provided and that a few companies sponsored most events. In most cases, sponsors’ products are not cost-effective choices for the specified condition. This pattern highlights the need for professional education to be free of commercial sponsorship.
Does exposure to simulated patient cases improve accuracy of clinicians’ predictive value estimates of diagnostic test results? A within-subjects experiment at St Michael’s Hospital, Toronto, Canada
Authors: Armstrong Bonnie , Spaniol Julia , Persaud Nav
Published: February 2018

Objective

Clinicians often overestimate the probability of a disease given a positive test result (positive predictive value; PPV) and the probability of no disease given a negative test result (negative predictive value; NPV). The purpose of this study was to investigate whether experiencing simulated patient cases (ie, an ‘experience format’) would promote more accurate PPV and NPV estimates compared with a numerical format.

Design

Participants were presented with information about three diagnostic tests for the same fictitious disease and were asked to estimate the PPV and NPV of each test. Tests varied with respect to sensitivity and specificity. Information about each test was presented once in the numerical format and once in the experience format. The study used a 2 (format: numerical vs experience) × 3 (diagnostic test: gold standard vs low sensitivity vs low specificity) within-subjects design.

Setting

The study was completed online, via Qualtrics (Provo, Utah, USA).

Participants

50 physicians (12 clinicians and 38 residents) from the Department of Family and Community Medicine at St Michael’s Hospital in Toronto, Canada, completed the study. All participants had completed at least 1 year of residency.

Results

Estimation accuracy was quantified by the mean absolute error (MAE; absolute difference between estimate and true predictive value). PPV estimation errors were larger in the numerical format (MAE=32.6%, 95% CI 26.8% to 38.4%) compared with the experience format (MAE=15.9%, 95% CI 11.8% to 20.0%,d=0.697, P<0.001). Likewise, NPV estimation errors were larger in the numerical format (MAE=24.4%, 95% CI 14.5% to 34.3%) than in the experience format (MAE=11.0%, 95% CI 6.5% to 15.5%,d=0.303, P=0.015).

Conclusions

Exposure to simulated patient cases promotes accurate estimation of predictive values in clinicians. This finding carries implications for diagnostic training and practice.
Clinician, patient and general public beliefs about diagnostic imaging for low back pain: protocol for a qualitative evidence synthesis
Authors: Traeger Adrian C , Reed Benjamin J , O’Connor Denise A , Hoffmann Tammy C , Machado Gustavo C , Bonner Carissa , Maher Chris G , Buchbinder Rachelle
Published: February 2018

Introduction

Little is known about how to reduce unnecessary imaging for low back pain. Understanding clinician, patient and general public beliefs about imaging is critical to developing strategies to reduce overuse.

Objective

To synthesise qualitative research that has explored clinician, patient or general public beliefs about diagnostic imaging for low back pain.

Methods and analysis

We will perform a qualitative evidence synthesis of relevant qualitative research exploring clinician, patient and general public beliefs about diagnostic imaging for low back pain. Exclusions will be studies not using qualitative methods and studies not published in English. Studies will be identified using sensitive search strategies in MEDLINE, EMBASE, CINAHL, AMED and PsycINFO. Two reviewers will independently apply inclusion and exclusion criteria, extract data, and use the Critical Appraisal Skills Programme quality assessment tool to assess the quality of included studies. To synthesise the data we will use a narrative synthesis approach that involves developing a theoretical model, conducting a preliminary synthesis, exploring relations in the data, and providing a structured summary. We will code the data using NVivo. At least two reviewers will independently apply the thematic framework to extracted data. Confidence in synthesis findings will be evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool.

Ethics and dissemination

Ethical approval is not required to conduct this review. We will publish the results in a peer-reviewed journal.

PROSPERO registration number

CRD42017076047.
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

Objectives

The 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 mass

Setting

DECiMaL Study is a multicentre, retrospective, collaborative cohort study in seven UK surgical sites.

Participants

Between 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 measures

Sensitivity, specificity, positive and negative predicted values of [18F]-FDG PET in determining malignant aetiology for an anterior mediastinal mass.

Results

The 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%).

Conclusions

The 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

Objective

To 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.

Design

A cross-sectional retrospective household survey.

Setting

12 administrative villages from rural Anhui, China.

Participants

2160 rural adult residents aged ≥18 years registered as rural residents and actually living in the sampled villages when this study was conducted.

Method

The 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.

Results

A 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).

Conclusions

Reported 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

Introduction

Rheumatic 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 analysis

Electronic 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 dissemination

Ethics 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 number

CRD42016051261.
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

Background

Clinical 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.

Methods

This 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.

Results

A 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).

Conclusions

Approximately 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

Objectives

To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect.

Methods

Systematic 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.

Results

Four 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).

Conclusion

Prophylactic 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

Objective

Many 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.

Design

Our 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.

Results

A 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.

Conclusion

Our 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

Objectives

Yttrium-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.

Design

Time-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.

Results

TILs 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.

Conclusion

High-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

Objective

To 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 results

This 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.

Conclusions

The 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

Background

Defects 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.

Methods

We describe clinical, genetic and biochemical findings of 21 patients withGMPPB-associated dystroglycanopathy.

Results

We 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.

Conclusions

Our 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

Background

Frontotemporal 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.

Methods

This 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.

Results

Higher 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.

Conclusion

Plasma 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.
Vitamin D shows in vivo efficacy in a placebo‐controlled, double‐blinded, randomised clinical trial on canine atopic dermatitis
Authors: Klinger Christoph J , Hobi Stefan , Johansen Cornelia , Koch Hans‐Joachim , Weber Karin , Mueller Ralf S
Published: February 2018

Atopic dermatitis (AD) in dogs is among the most common skin diseases in small animal practice. It is an inflammatory disease based on a genetic predisposition to develop hypersensitivity against environmental and food allergens and typical clinical signs up exposure. Treatment sometimes can be difficult and associated with adverse effects. Previous studies evaluating cholecalciferol as treatment for human AD have shown promising results. With canine AD being a good animal model for its human counterpart, it was hypothesised that cholecalciferol might have beneficial clinical effects in dogs, too. In this randomised, placebo‐controlled, double‐blinded eight‐week cross‐over study, 23 client‐owned dogs received either systemic cholecalciferol (n=16), a vitamin D receptor analogue (n=8) or placebo (n=13). Blood samples for ionised calcium were obtained regularly during the study, and Canine Atopic Dermatitis Extent and Severity Index and pruritus scores, blood levels of vitamin D metabolites, measurements of skin pH and transepidermal water loss were determined before and after. Pruritus and lesion scores decreased significantly in the cholecalciferol group versus placebo. No differences in water loss or skin pH were observed. An increase in serum 25‐hydroxycholecalciferol strongly correlated with a reduction in pruritus. Systemic cholecalciferol may be a viable treatment option for canine AD.
Movement ecology of a mobile predatory fish reveals limited habitat linkages within a temperate estuarine seascape
Authors: Kenworthy Matthew D. , Grabowski Jonathan H. , Layman Craig A. , Sherwood Graham D. , Powers Sean P. , Peterson Charles H. , Gittman Rachel K. , Keller Danielle A. , Fodrie F. Joel
Published: February 2018

Large predatory fishes, capable of traveling great distances, can facilitate energy flow linkages among spatially separated habitat patches via extended foraging behaviors over expansive areas. Here, we tested this concept by tracking the movement of a large mobile estuarine fish, red drum (Sciaenops ocellatus). Specifically, we addressed the following two questions: (i) What are the spatial and temporal patterns of red drum movement (rates of dispersal) and activity space? (ii) Does red drum movement facilitate linkages among estuarine marsh complexes? Dispersal from the release location was greatest during the first 2 weeks at liberty before declining to less than 0.5 km·week–1 for the remainder of the study. Activity space initially increased rapidly before reaching an asymptote at 2.5 km2 2 weeks postrelease. Connectivity indices calculated among marsh complexes corroborated these observations, suggesting high residency and limited seascape-scale linkages via red drum movement behaviors. These data highlight potential within-estuary spatial structure for mobile fishes and could inform subsequent efforts to track energy flows in coastal food webs, predict the footprint of local habitat restoration benefits, and enhance the design of survey regimes to quantify overall population demography.
Pharmacological Effects of Scutellarin, An Active Component of GenusScutellariaandErigeron: A Systematic Review
Authors: Chledzik Sebastian , Strawa Jakub , Matuszek Katarzyna , Nazaruk Jolanta
Published: February 2018

Flavonoid compound scutellarin (Scu) is quite frequently met in the plant kingdom, particularly in the genus Scutellaria (Lamiaceae) and Erigeron (Asteraceae). The extract of the herb of Erigeron breviscapus, containing this component in high amount, has been used for many years in traditional Chinese medicine. In recent years, studies have made great progress on the usefulness of Scu for treating various diseases by testing its mechanism of action. They support the traditional use of Scu rich plant in heart and cerebral ischemia. Scu can potentially be applied in Alzheimer’s disease, Helicobacter pylori infection, vascular complications of diabetes and as an inhibitor of certain carcinomas. Various methods were designed to improve its isolation from plant material, solubility, absorption and bioavailability. On the basis of recent studies, it is suggested that Scu could be a promising candidate for new natural drug and deserves particular attention in further research and development.