bluuebunny/crossref_metadata_2025_split huggingface dataset:
P42 The impact of a change to hospital guidelines on prescribing practices of nebulised 3% w/v ‘hypertonic’ saline
Authors: Diarmaid Semple , Paul McNally , Anne Fitzpatrick , Kenny Adeyemi , Niamh McGrory , Michael Fitzpatrick 
Published: January 2018

AimsRecent conclusive evidence has suggested that, contrary to previous limited evidence, there is no benefit to the use of 3% hypertonic saline (3% HS) in the treatment of bronchiolitis in infants.1,2 This led to a change in the clinical guideline during the 2015/2016 bronchiolitis season. We hypothesised that the use of hypertonic saline was preventing the use of other un-necessary treatments and that inappropriate prescribing would increase following the advice not to give hypertonic saline.The primary aim of the study was to determine if the removal of 3% hypertonic saline from the institutional clinical guideline would result in reduced prescribing patterns. A secondary aim was to evaluate the overall prescribing compliance with the guideline including in the prescribing of antibiotics and bronchodilators, and identify if the change in the clinical guideline impacted the prescribing of other agents in children admitted with a diagnosis of bronchiolitis.MethodsData on medical treatments and hospital outcomes were prospectively collected on all infants in the 2015/2016 season both before and after the change in guideline. Details of all medicines prescribed on the patients Medication Record particularly bronchodilators, antimicrobials and inhaled agents were collected. Patient demographics were collected from medical notes. Results were analysed using chi square and Mann Whitney in Excel and Stata.Results128 children (86 before, 42 after the change in guideline) were recruited to the study. Baseline demographics were similar except for a higher proportion of children with RSV in the pre-group. Overall guideline compliance was achieved by 2 infants pre, and 3 infants post guideline change (4%). The use of hypertonic saline decreased significantly after the change in guideline but did not cease (90% pre, 71% post p<0.01). Bronchodilators were used in one in 4 infants and antibiotics in one in 3 infants, and there was no significant difference in these rates before or after the change in guidelines.ConclusionThe change to the guideline reduced the use of 3%HS, however overall guideline compliance in children with bronchiolitis is poor. Hypertonic saline use decreased when the guideline changed but a significant portion of children before and after the guideline change received medications not indicated in the treatment of bronchiolitis, including bronchodilators and antibiotics. It appears that it remains difficult to ‘do nothing’ for bronchiolitis. Poor clinical practice remains and education of clinical staff is necessary in this regard.ReferencesGuidance: Bronchiolitis in children: diagnosis and management, NICE (NG9) Published date: June 2015.Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% hypertonic saline versus normal saline in inpatient bronchiolitis: A randomised controlled trial. Paediatrics2015;136:1036–1043.
P8 Chemotherapy standardisation in paediatric oncology: the our lady’s children’s hospital (olch) dublin experience
Authors: Owens Cormac , Funston Lesley-Ann , Keane Sinead , Clinton Frieda , Lee Mairead 
Published: January 2018

Background/objectivesSeveral centres (Children’s Hospital Philadelphia, Sick Kids Toronto) and organisations (COG) have developed chemotherapy standardisation programmes to reduce risk, increase efficiency and decrease cost associated with the presciption, preparation and administration of chemotherapy in paediatric patients.Most European paediatric chemotherapy protocols use different doses, infusion times, hydration protocols and supportive medicine doses for the same drugs. There is huge variety in how individual patients receive the same drugs. This introduces significant, unnecessary, potential risks and complexity.By 2016 our aim is that all children at our institution should have chemotherapy prescribed, prepared and administered according to a standard institutional protocol.Design/methodsWe set up a multi-disciplinary chemotherapy standardisation group within our department. The project was developed in association with a hospital quality initiative. We reviewed all treatment protocols in use at the current time at OLCH and assessed the variety in chemotherapy administration. We performed staff and parental questionnaires regarding their perceptions of the variety in administration, supportive medicines and discharge times.We held a meeting of all senior departmental management to review and critique the project and multiple staff education sessions to implement the recommended changes.ResultsThere is huge variation in how European protocols mandate that chemotherapy be administered, particularly in protocols using doxorubicin, cisplatin, ifosfamide and cyclophosphamide.We have developed a standard, institutional document which determines how chemotherapy and supportive medicines are administered, limiting variation and risk, increasing staff efficiency and decreasing lengths of hospital admissions.ConclusionThere is unnecessary variation in the way chemotherapy is administered to paediatric patients in Europe. Doses should not be changed, but length of chemotherapy infusion and associated hydration/supportive medicines are extremely varied and there is little evidence to say this is beneficial in terms of patient outcomes. Chemotherapy protocols can be standardised, limiting variation, reducing potential risk and increasing staff and ward efficiencies.
3 Pharmaco-stability of plasma-lyte 148 and plasma-lyte 148+5% glucose with commonly used therapeutic agents
Authors: Wignell Andrew 
Published: January 2018

AimsPlasma-Lyte 148 is a balanced, crystalloid intravenous fluid which is both calcium-free and isotonic. It has been demonstrated to reduce the risk of hyperchloraemic metabolic acidosis and iatrogenic hyponatraemia seen with use of normal saline and hypotonic solutions respectively. Investigating the compatibility of Plasma-Lyte 148 and Plasma-Lyte 148+5% gucose with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol and furosemide will provide vital data to facilitate the introduction of these fluids into routine paediatric practice.MethodChemical stability was assessed by high performance liquid chromatography (HPLC) using the ‘Hewlett Packard (Agilent) 1100’ HPLC system. A gradient method with 20 mM ammonium carbonate (A) and acetonitrile (B) mobile phases and an ‘ACE Excel 3 SuperC18’ column was used. The flow rate was set to 0.03 ml/min, temperature to 40°C and injection volume for all drug admixtures to 5 µL apart from ketamine (4 µL) and furosemide (1 µL). Physical stability was assessed by observation of precipitate formation or colour change. Six repeats of each IV fluid and drug mix were assayed at three time points: 0, 2 and 24 hours. pH changes were measured using Fisherbrand Hydrus 300. Normal saline and 5% glucose were used as controls for all experiments.ResultsNo precipitate formed in any of the samples. Chemical stability was defined as <5% concentration change. All examined therapeutic agents were stable at 2 and 24 hours relative to control solutions. Relative to starting concentration, all drugs except midazolam were stable to ±3%. Midazolam showed similar variation in concentration with all four fluids. All combinations remained in a safe peripheral administration pH range of 5–9. Plasma-Lyte 148 admixtures were found have a pH closest to that of the blood.ConclusionCompared to standard diluents, the tested therapeutic agents are chemically and physically stable for 24 hours at the concentrations measured, and are all stable at commonly encountered Y site concentrations, when diluted with Plasma-Lyte 148 or Plasma-Lyte 148+5% glucose. All are pH stable and all are suitable for peripheral administration.
Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease
Authors: Vinereanu Dragos , Wang Alice , Mulder Hillary , Lopes Renato D , Jansky Petr , Lewis Basil S , Gersh Bernard J , Avezum Alvaro , Hanna Michael , Held Claes , Wallentin Lars , Granger Christopher B , Alexander John H 
Published: January 2018

ObjectiveTo assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.MethodsThere were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.ResultsPatients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.ConclusionsIn anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.Clinical trial registrationARISTOTLE clinical trial numberNCT00412984.
Incidence, predictors and clinical outcomes of residual stenosis after aortic valve-in-valve
Authors: Bleiziffer Sabine , Erlebach Magdalena , Simonato Matheus , Pibarot Philippe , Webb John , Capek Lukas , Windecker Stephan , George Isaac , Sinning Jan-Malte , Horlick Eric , Napodano Massimo , Holzhey David M , Petursson Petur , Cerillo Alfredo , Bonaros Nikolaos , Ferrari Enrico , Cohen Mauricio G , Baquero Giselle , Jones Tara L , Kalra Ankur , Reardon Michael J , Chhatriwalla Adnan , Gama Ribeiro Vasco , Alnasser Sami , Van Mieghem Nicolas M , Rustenbach Christian Jörg , Schofer Joachim , Garcia Santiago , Zeus Tobias , Champagnac Didier , Bekeredjian Raffi , Kornowski Ran , Lange Rüdiger , Dvir Danny 
Published: January 2018

ObjectiveWe aimed to analyse the incidence of prosthesis–patient mismatch (PPM) and elevated gradients after aortic valve in valve (ViV), and to evaluate predictors and associations with clinical outcomes of this adverse event.MethodsA total of 910 aortic ViV patients were investigated. Elevated residual gradients were defined as ≥20 mm Hg. PPM was identified based on the indexed effective orifice area (EOA), measured by echocardiography, and patient body mass index (BMI). Moderate and severe PPM (cases) were defined by European Association of Cardiovascular Imaging (EACVI) criteria and compared with patients without PPM (controls).ResultsModerate or greater PPM was found in 61% of the patients, and severe in 24.6%. Elevated residual gradients were found in 27.9%. Independent risk factors for the occurrence of lower indexed EOA and therefore severe PPM were higher gradients of the failed bioprosthesis at baseline (unstandardised beta −0.023; 95% CI −0.032 to –0.014; P<0.001), a stented (vs a stentless) surgical bioprosthesis (unstandardised beta −0.11; 95% CI −0.161 to –0.071; P<0.001), higher BMI (unstandardised beta −0.01; 95% CI −0.013 to –0.007; P<0.001) and implantation of a SAPIEN/SAPIEN XT/SAPIEN 3 transcatheter device (unstandardised beta −0.064; 95% CI −0.095 to –0.032; P<0.001). Neither severe PPM nor elevated gradients had an association with VARC II-defined outcomes or 1-year survival (90.9% severe vs 91.5% moderate vs 89.3% none, P=0.44).ConclusionsSevere PPM and elevated gradients after aortic ViV are very common but were not associated with short-term survival and clinical outcomes. The long-term effect of poor post-ViV haemodynamics on clinical outcomes requires further evaluation.
Effectiveness of comprehensive social support interventions among elderly patients with tuberculosis in communities in China: a community-based trial
Authors: Li Xuhui , Wang Bin , Tan Dixin , Li Mengyu , Zhang Dandan , Tang Cong , Cai Xiaonan , Yan Yaqiong , Zhang Sheng , Jin Bo , Yu Songlin , Liang Xunchang , Chu Qian , Xu Yihua 
Published: January 2018

BackgroundWith the increasing of ageing population, tuberculosis in the elderly brings a challenge for the tuberculosis (TB) control in China. Enough social support can promote the treatment adherence and outcome of the elderly patients with TB. Exploring effective interventions to improve the social support of patients is of great significance for TB management and control.MethodsA community-based, repeated measurement trial was conducted. Patients with TB >65 years of age were allocated into the intervention or control group. Patients in the intervention group received comprehensive social support interventions, while those in the control group received health education alone. The social support level of patients was measured at baseline and at the first, third and sixth months during the intervention to assess the effectiveness of comprehensive social support interventions.ResultsA total of 201 patients were recruited into the study. Compared with the control group, social support for patients in the intervention group increased significantly over time (βgroup*time=0.61, P<0.01) in the following three dimensions: objective support (βgroup*time=0.15, P<0.05), subjective support (βgroup*time=0.32, P<0.05) and support utilisation (βgroup*time=0.16, P<0.05). The change in the scores in the control group was not statistically significant.ConclusionsThe intervention programme in communities, including health education, psychotherapy and family and community support interventions, can improve the social support for elderly patients with TB compared with single health education.Trial registration numberChiCTR-IOR-16009232
Prevalence of invehicle smoking and secondhand smoke exposure in Uruguay
Authors: Llambi Laura , Barros Mary , Parodi Carolina , Pippo Antonella , Nunez Virginia , Colomar Mercedes , Ciganda Alvaro , Cavalleri Fiorella , Goyeneche Juan J , Aleman Alicia 
Published: January 2018

IntroductionProtection from secondhand smoke (SHS) is one of the fundamental principles of the WHO Framework Convention for Tobacco Control. Objective data on SHS exposure in vehicles in South America is scarce. This study aimed to estimate prevalence of smoking inside vehicles.MethodsThe point prevalence of smoking in vehicles was observed, and a method for estimating smoking prevalence was piloted.ResultsWe observed 10 011 vehicles. In 219 (2.2%; 95% CI 1.91 to 2.49) of them, smoking was observed, and in 29.2% of these, another person was exposed to SHS. According to the ‘expansion factor’ we constructed, direct observation detected one of six to one to nine vehicles in which smoking occurred. The observed prevalence of smoking in vehicles (2.2%) could reflect a real prevalence between 12% and 19%. In 29.2% (95% CI 23.6 to 35.5) and 4.6% (95% CI 2.2 to 8.3) of vehicles in which smoking was observed, another adult or a child, respectively, was exposed to SHS.ConclusionsSmoking was estimated to occur in 12%–19% of vehicles, with involuntary exposure in one of three of vehicles observed. These data underscore a need for new public policies to eliminate SHS in vehicles to protect public health.
ERα-Mediated Nuclear Sequestration of RSK2 Is Required for ER+ Breast Cancer Tumorigenesis
Authors: Ludwik Katarzyna A. , McDonald Oliver G. , Brenin David R. , Lannigan Deborah A. 
Published: January 2018

Abstract
Although ribosomal protein S6 kinase A3 (RSK2) activation status positively correlates with patient responses to antiestrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of estrogen receptor–positive (ER+) breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N terminus to activate a proneoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status. ER+ tumor growth was strongly dependent on nuclear RSK2, and transgenic mice engineered to stably express nuclear RSK2 in the mammary gland developed high-grade ductal carcinoma in situ. Mammary cells isolated from the transgenic model and introduced systemically successfully disseminated and established metastatic lesions. Antiestrogens disrupted the interaction between RSK2 and ERα, driving RSK2 into the cytoplasm and impairing tumor formation. These findings establish RSK2 as an obligate participant of ERα-mediated transcriptional programs, tumorigenesis, and divergent patient responses to antiestrogen therapies.
Significance: Nuclear accumulation of active RSK drives a protumorigenic transcriptional program and renders ER+ breast cancer susceptible to endocrine-based therapies. Cancer Res; 78(8); 2014–25. ©2018 AACR.
Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors
Authors: Asiedu Michael K. , Thomas Charles F. , Dong Jie , Schulte Sandra C. , Khadka Prasidda , Sun Zhifu , Kosari Farhad , Jen Jin , Molina Julian , Vasmatzis George , Kuang Ray , Aubry Marie Christine , Yang Ping , Wigle Dennis A. 
Published: January 2018

Abstract
Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors.
Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum.
Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1. The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1. Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C&gt;T and T&gt;C transitions with a minor contribution of T&gt;G transversions.
Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res; 24(7); 1691–704. ©2018 AACR.
High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Authors: Diets Illja J. , Waanders Esmé , Ligtenberg Marjolijn J. , van Bladel Diede A.G. , Kamping Eveline J. , Hoogerbrugge Peter M. , Hopman Saskia , Olderode-Berends Maran J. , Gerkes Erica H. , Koolen David A. , Marcelis Carlo , Santen Gijs W. , van Belzen Martine J. , Mordaunt Dylan , McGregor Lesley , Thompson Elizabeth , Kattamis Antonis , Pastorczak Agata , Mlynarski Wojciech , Ilencikova Denisa , van Silfhout Anneke Vulto- , Gardeitchik Thatjana , de Bont Eveline S. , Loeffen Jan , Wagner Anja , Mensenkamp Arjen R. , Kuiper Roland P. , Hoogerbrugge Nicoline , Jongmans Marjolijn C. 
Published: January 2018

Abstract
Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer.
Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome.
Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein–Taybi syndrome, ARID1A-based Coffin–Siris syndrome, ACTB-based Baraitser–Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition.
Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. Clin Cancer Res; 24(7); 1594–603. ©2018 AACR.