bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE MEDICAL BOOMERANG—WILL IT COME BACK?
Authors: McDermott Cian , Sheridan Michael , Moore Katie 
Published: August 2014

Objectives & BackgroundTo explore the increasing numbers of Emergency Medicine registrars that obtained their primary medical degree from United Kingdom (UK) or Irish universities, who work in Emergency Departments (ED) throughout Australia and New Zealand.Table 1Trends in Australasian Emergency Medicine registrar numbers 2008–2013 (courtesy of ACEM Policy & Research Department)YearTotal registrarsTotal IMGsUK/Ire IMGs% UK/Ire of total IMGs% UK/Ire of total registrars2008142078728536.220.12009165495832934.319.920101952113741336.321.220111973114443738.222.120122078118548140.623.120132258125256645.225.1MethodsThe VERS-2013 (Victoria Emergency Registrar Study) was published at the Australasian College for Emergency Medicine (ACEM) annual scientific meeting in Adelaide in November 2013.1As a follow on, ACEM provided the authors with data regarding country of primary degree for international medical graduates (IMG) working in Australasian EDs.ResultsUK and Irish Emergency Medicine registrars make up the largest proportion of IMGs in working in Australasian EDs. These figures have increased from 36.2% in 2008 to 45.2% in 2013 (table 1). In 2013 alone, the largest year-on-year increase occurred, of UK and Irish ED IMG registrars, migrating to work in Australia and New Zealand. Current data shows that over 25% of all ED registrars working in Australasian EDs, studied for their primary medical degree in a university either in Ireland or the UK (table 1).ConclusionMany IMGs (in particular from UK and Ireland) leave their country of origin to work overseas in Australia and New Zealand. Highly trained, skilled independent practitioners have, in the past, returned to the UK to work at consultant level. However, evidence from ACEM (table 1) and the VERS-20131 study show clearly that these doctors are now migrating to Australia for the long-term, leaving EDs the length and breath of the British Isles bereft of talented senior EM decision-making personnel. Meanwhile in Australia, continued IMG influx is at odds with a stated Health Workforce Australia taskforce aim to achieve self-sufficiency by 2025.2 The challenge is set for the College of Emergency Medicine, in conjunction with the UK and Irish governments, to enhance the attractiveness of Emergency Medicine as a credible and sustainable career option.
HIP 7: USING A BUNDLE OF CARE TO STREAMLINE THE MANAGEMENT OF PATIENTS WITH A FRACTURED NECK OF FEMUR
Authors: Kerr Jacques , Bishop Mary , Meikle Alastair , Lakie Kirk , Davidson Jane 
Published: August 2014

Objectives & BackgroundSIGN guideline 111 makes recommendations on the optimal management of patients with a hip fracture.1It is clear from the use of care bundles in other conditions, eg sepsis, that these perform very well in time-critical settings and ensure that all necessary actions for person-centred care are achieved timeously. Given the success of our Emergency Department (ED) compliance with the Sepsis 6 bundle (100%–unpublished data) the principal author (JK) rationalised that a bundle applied to the SIGN hip fracture recommendations would ensure that all actions were achieved in a timely manner.MethodsWe used an improvement methodology strategy to devise a bundle of care for patients with a fractured neck of femur. This work culminated in a list of 7 actions that could be captured in an acronym devised by the principal author as an aide-memoir (see table 1). The principal author ran training sessions on the bundle with all ED medical and nursing staff and data were captured over a four-month period (October 2013–February 2014) to examine compliance and to compare with data from the same period in the previous year. All actions in the bundle had to be achieved within the hour.Table 1FEMORAL-Hip 7 Bundle of CareF - Fasttrack to ED Procedure RoomE - Establish IV access & take bloodsM - Medical assessment, including SIRS chart & ECGO - Opiates & fascia iliaca blockR - Radiology – fasttrack for pelvis and hip X raysA - Abbreviated Mental Test ScoreL - Liaise with Orthopaedic Ward for admissionResultsAnalysis of data from the study period showed a significant improvement in compliance witha) intravenous fluid therapy administration: 37% pre- and 91.4% post-bundle;b) opiates and regional nerve block administration: 35% pre- and 75% post-bundle;c) documentation of SIRS score: 40% pre- and 91% post-bundle, andd) inspection of pressure areas: 5% pre- and 100% post-bundle.ConclusionAlthough fractures of the neck of femur do not necessarily result in the physiological derangement associated with sepsis, it is evident that the use of a bundle of care will ensure that hip fracture patients are managed in a timely, person-centred and safe fashion as recommended in SIGN 111. Future work will concentrate on improving compliance with all seven actions within one hour of patient attendance.
RESTRICTIVE VERSUS LIBERAL BLOOD TRANSFUSION FOR ACUTE UPPER GASTROINTESTINAL BLEEDING (TRIGGER): PRAGMATIC, CLUSTER RANDOMISED, FEASIBILITY TRIAL
Authors: Gray A , Jairath V , Kahan B , Dore C , Palmer K , Travis S , Logan R , Walsh T , Murphy M 
Published: August 2014

Objectives & BackgroundTransfusion thresholds for upper gastrointestinal bleeding (UGIB) are controversial. Observational studies suggest associations between liberal red blood cell (RBC) transfusion and adverse outcome. A recent trial reported increased mortality following liberal transfusion. We delivered a cluster randomised trial to evaluate the feasibility and safety of implementing a restrictive (transfusion when haemoglobin (Hb) <8 g dL) vs liberal (transfusion when Hb <10 g/dL) RBC transfusion policy for UGIB.MethodsHospitals were randomised to a policy which was implemented through a multi-faceted educational intervention. Patients were recruited in Emergency Departments and acute admission units. All adult patients were eligible to participate, regardless of co-morbidity; the only exclusion criterion was exsanguinating haemorrhage. Feasibility and exploratory clinical outcomes were recorded up to day 28.Results936 patients were enrolled in six hospitals. Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% in the restrictive policyvs83% in the liberal policy (difference 14%, 95% CI 7 to 21%). In patients with Hb <120 g/L, Hb at discharge was lower for the restrictive policy (difference −0.7; 95% CI −1.4 to 0.0; p=0.05). For the restrictive policy fewer patients received RBCs (difference −13%, 95% CI −35 to 11%) with on average 0.8 (−1.9 to 0.3) fewer RBC units transfused. Clinical outcomes were better in the restrictive policy: 28-day further bleeding, 5% restrictivevs9% liberal (difference −3.7%, 95% CI -12.2 to 4.8%); 28-day mortality, 5% restrictivevs7% liberal (difference −1.3%, 95% CI −8.0 to 5.5%).; serious adverse events, 18% restrictivevs22% liberal (difference −4.9%, 95% CI −22.6 to 12.8%). In the subgroup with IHD, there was a large observed difference for mortality (12% restrictive arm (n=6) vs. 3% liberal arm (n=2); interaction P=0.11).ConclusionAdherence to both policies was high, resulting in a reduction in RBC transfusion and separation in the degree of anaemia and RBC exposure. There was a trend towards improved safety in the restrictive policy. We have demonstrated that a large-scale cluster randomised trial is feasible and is now warranted to determine the effectiveness of implementing restrictive RBC transfusion for all patients with AUGIB.
PRE-HOSPITAL CONTINUOUS POSITIVE AIREWAY PRESSURE (CPAP) FOR ACUTE RESPIRATORY FAILURE: AN ECONOMIC ANALYSIS
Authors: Goodacre Steve , Thokala Praveen 
Published: August 2014

Objectives & BackgroundWe aimed to determine the cost-effectiveness of pre-hospital CPAP compared with standard care for adults presenting to the emergency services with acute respiratory failure.MethodsAn economic model was developed to explore the costs and health outcomes when pre-hospital CPAP provided by paramedics and standard care (in-hospital non-invasive ventilation (NIV)) were applied to a hypothetical cohort with acute respiratory failure. The model assigned each patient a probability of intubation or death depending upon their characteristics and whether they had pre-hospital CPAP or standard care. The patients that survived accrued lifetime quality-adjusted life year (QALYs) and health care costs according to their age and sex. Costs were accrued through costs of intervention and hospital treatment costs, which depended on patient outcomes.ResultsPre-hospital CPAP was more effective than standard care but was also more expensive, with an incremental cost-effectiveness ratio (ICER) of £20,514/QALY and a 49.5% probability of being cost-effective at the £20,000/QALY threshold. The probability of pre-hospital CPAP being cost-effective at the £20,000/QALY threshold depended on the incidence of eligible patients, and varied from 35.4% when a low estimate of incidence was used to 91.3% with a high estimate. If a typical ambulance service treated 175 appropriate patients per year it could save around 11 lives while incurring £241,250 additional costs, whereas if a typical ambulance service treated 2000 appropriate patients per year it could save 124 lives while incurring £876,480 additional costs. Variation in the incidence of eligible patients also had a marked impact on the expected value of sample information for a future randomised trial.ConclusionThe cost-effectiveness of pre-hospital CPAP is uncertain and current evidence is insufficient to support widespread implementation. The immediate research priority is to estimate the incidence of patients eligible for pre-hospital CPAP. This appears to be the key determinant of the cost-effectiveness of a future trial and of pre-hospital CPAP itself.Model structure
MODIFIED BRUNELLI PULL-OUT SUTURE TECHNIQUE IN ZONE II FLEXOR TENDON RUPTURE: A FRESH HUMAN CADAVER STUDY
Authors: Başar Hakan , Tetik Cihangir 
Published: August 2014

Purpose: The aim of our study is to develop a suture technique that has sufficient strength of active mobilization. Methods: Thirty two fingers of six fresh human cadavers were divided into two groups. Flexor digitorum profundus (FDP) tendons in the study group were repaired by modified Brunelli suture technique and modified Kessler suture technique, while those in the control group were repaired by Modified Kessler suture technique. Flexion and extension movements were performed with 10 N of load, increasing 1 N at a time to the tendons in both groups. Rupture and significant gap formation was evaluated up to 20 N of load. In the study, to evaluate the resistance to active motion, 1000 times flexion and extension motion cycle was performed with a load of 20 N. The succeeding repaired tendons was also tested with flexion and extension movements increasing the load 1 N at a time. Results: In the study group, failure and significant gap formation on the repair zone were not observed after 20 N of load and 1000 times cyclic flexion and extension movements for resisting to active motion. The rupture and significant gap formation was observed on a average load of 98.43 ± 0.47 N. In the Modified Kessler suture technique, on the eight tendons before reaching the 20 N of load for resisting to active motion, and the remaining eight tendons, during the 20 N loaded motion cycle essential for active motion, rupture and significant gap formation was observed. The failure and significant gap formation was observed on a average load of 18.37 ± 1.89 N. It is measured that by accompanying Modified Brunelli suture to the Modified Kessler suture technique, the resistance was increased up to 5–6 times. Discussion: By the Modified Brunelli suture technique, active motion can be started to the finger without a dorsal block sling immediately after the surgery. Clinical Relavans: By the modified technique, the rehabilitation difficulty and joint stiffness will be minimized.
A Miracle That Accelerates Operating Room Functionality: Sugammadex
Authors: Dogan Erdal , Akdemir Mehmet Salim , Guzel Abdulmenap , Yildirim Mehmet Besir , Baysal Yildirim Zeynep , Kuyumcu Mahir , Gümüş Abdurrahman , Akelma Hakan 
Published: August 2014

Background.Sugammadex offers a good alternative to the conventional decurarisation process currently performed with cholinesterase inhibitors. Sugammadex, which was developed specifically for the aminosteroid-structured rocuronium and vecuronium neuromuscular blockers, is a modified cyclodextrin made up of 8 glucose monomers arranged in a cylindrical shape.Methods.In this study, the goal was to investigate the efficacy of sugammadex. Sugammadex was used when there was insufficient decurarisation following neostigmine. This study was performed on 14 patients who experienced insufficient decurarisation (TOF<0.9) with neostigmine after general anaesthesia in the operating rooms of a university and a state hospital between June, 2012, and January, 2014. A dose of 2 mg/kg of sugammadex was administered.Results.Time elapsed until sugammadex administration following neostigmine37 ± 6min, following sugammadex it took2.1 ± 0.9min to reach TOF≥ 0.9, and the extubation time was3.2 ± 1.4min. No statistically significant differences were detected in the hemodynamic parameters before and after sugammadex application. From the time of administration of sugammadex to the second postoperative hour, no side effects or complications occurred. None of the patients experienced acute respiratory failure or residual block during this time period.Conclusion.Sugammadex was successfully used to reverse rocuronium-induced neuromuscular block in patients where neostigmine was insufficient.
Abstract P1-05-07: Prognostic relevance of Claudin-2 expression in metastatic breast cancer
Authors: Hedenfalk I , Kimbung S , Kovacs A , Skoog L , Einbeigi Z , Walz T , Malmberg M , Loman N , Fernö M , Hatschek T ,   TEX Study Group
Published: August 2014

Abstract
The site of relapse is known to be a strong prognostic factor of survival from metastatic breast cancer. The liver is the third most frequent site affected and patients with hepatic metastases have an inferior prognosis relative to patients with bone and lung metastases. Predicting the likelihood of liver metastasis after adjuvant therapy of primary breast cancer is challenging. The aim of this study was to identify and characterize genes associated with breast cancer liver metastases. We thus performed global transcriptional profiling of 120 metastatic lesions from different anatomical sites from breast cancer patients enrolled in a randomized clinical trial1 and found that while the expression of other matrix remodelling and tight-junction molecules was down-regulated in liver metastases, Claudin-2 (CLDN2) was significantly up-regulated (p = 0.001). Furthermore, high expression of CLDN2 was also observed amongst patients diagnosed with a liver metastasis, irrespective of the specific site of the metastasis that was profiled, compared to patients without hepatic metastases (p = 0.001). We further investigated the prognostic significance of CLDN2 protein expression by immunohistochemical staining of primary tumours and matched lymph node metastases from a larger cohort of patients (n∼200) with metastatic breast cancer. We found CLDN2 to be significantly more frequently expressed in lymph node metastases compared to primary tumours (p = 0.013). Also, consistent with mRNA expression levels, more frequent expression of CLDN2 protein was observed in the primary tumours of patients who eventually developed a liver metastasis (p = 0.027). Interestingly, high expression of CLDN2 in the primary tumour was associated with a shorter time to recurrence (p = 0.032). Specifically, high expression of CLDN2 in the primary tumour was associated with a shorter progression to liver metastasis (p = 0.002). These data highlight a potential role of CLDN2 in the development and prognosis of breast cancer liver metastases.
1. Hatschek, T., et al. Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat. 2012, 131(3):939–47.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-07.
Abstract P1-07-03: Quantification of HER2 expression at the single cell level and HER2 intratumoral heterogeneity of breast cancer tissue samples using automated image analysis
Authors: Geretti E , Paragas V , Onsum M , Kudla A , Moulis S , Luus L , Wickham T , McDonagh C , MacBeath G , Hendriks B 
Published: August 2014

Abstract
HER2 is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or FISH testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to accurate HER2 assessment and patient stratification may include intratumoral heterogeneity, lack of assays that are quantitative and/or objective, and differences between measuring HER2 at the protein vs. DNA level. We have developed a novel immunofluorescence method for absolute quantitation of HER2 protein expression at the single cell level on formalin-fixed, paraffin-embedded (FFPE) patient samples. Our assay utilizes automated image analysis software to identify cells, classify them as tumor or non-tumor cells, and quantitate the level of HER2 staining for each tumor cell. The HER2 staining level is then converted to absolute HER2 receptor numbers per cell using an array composed of cell lines that span a range of HER2 levels. This cell pellet array standard is stained in parallel with each tissue sample. With this approach we quantitate HER2 expression at the single cell level and describe the heterogeneity of HER2 expression within breast cancer tissue samples. Our assay provides additional insight into the absolute level of HER2 expression and heterogeneity of HER2 expression within tumors, and allows for direct comparison with the currently existing HER2 assessments by standard IHC and/or FISH. This new assay could be used to increase understanding of the relationship between HER2 expression and patient response to HER2-targeted therapies.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-03.
Abstract P1-15-12: Single Nucleotide Polymorphism (SNP) Bayesian networks (BNs) Predict Risk of Chemotherapy-Induced Side Effects in Patients with Breast Cancer Receiving Dose Dense (DD) Doxorubicin/Cyclophosphamide Plus Paclitaxel (AC+T)
Authors: Schwartzberg LS , Sonis ST , Walker MS , Weidner SM , Alterovitz G 
Published: August 2014

Abstract
Background: Despite advances in supportive care, patients undergoing standard chemotherapy for breast cancer are at significant, but unequal, risk for the development of treatment-induced side effects. Current methods for predicting risk are inconsistent and unreliable. Because the pathobiology of many side effects are regulated by the synergistic interaction of simultaneously expressed genes, we reasoned that a novel approach to risk prediction could be achieved by the development of clusters of SNPs defined by BNs. The present study was designed to assess the feasibility of identifying BNs that were associated with regimen-related diarrhea, oral mucositis, nausea and vomiting, fatigue, cognitive dysfunction and neuropathy in patients with breast cancer treated with dose-dense AC+T. The primary endpoint was an area under the receiver operating characteristic curve (aROC) &gt;0.80.
Methods: After informed consent, 78 patients with breast cancer who had received at least 3 cycles of (DD) AC+T were enrolled and saliva samples were collected. Salivary DNA was isolated and analyzed on Illumina Omni microarrays (2.5 × 106 SNPs). Standard supportive therapy for prevention and management of side effects was provided. The frequency and severity of diarrhea, oral mucositis, fatigue, cognitive dysfunction, neuropathy&lt;INS dateTime=2012-09-25T18:35 cite=“mailto:CJordan”&gt;,&lt;/INS&gt; and nausea and vomiting were determined using Patient Care Monitor©, a validated patient-reported symptom assessment instrument. BNs were developed for each of the six side effects using Bayesian methods including ten-fold internal cross-validation.
Results: The incidence of clinically significant side effects was higher than anticipated by the literature and are reported in Table 1 along with the accuracy and aROC.

Conclusions: We identified SNP-BNs associated with moderate to severe common side effects of AC+T regimens used to treated breast cancer. These BNs, sourced from salivary SNPs, should provide &lt;/DEL&gt; clinicians with accurate actionable information which predicts side effect risk for patients who are scheduled to receive dose-dense doxorubicin/cyclophosphamide and paclitaxel for the treatment of breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-12.
Abstract P2-01-05: Parallel DNA and RNA profiling of EpCAM-positive cells in blood of metastatic breast cancer (MBC) patients confirm their malignant nature
Authors: Magbanua MJM , Hauranieh L , Sosa EV , Pendyala P , Scott JH , Rugo HS , Park JW 
Published: August 2014

Abstract
Background: Molecular studies of EpCAM-positive cells found in the blood of cancer patients have been limited to immuno-enriched samples containing a high background of leukocytes. We developed a process to isolate rare EpCAM-positive cells and subjected them to DNA and RNA profiling.
Methods: Blood was subjected to immunomagnetic enrichment using EpCAM beads followed by fluorescence activated cell sorting (IE/FACS) to isolate EpCAM-positive cells away from leukocytes (CD45+). Duplicate samples of 20 cells were isolated from the same enriched blood from 53 MBC patients and then subjected to DNA and RNA profiling in parallel. For DNA profiling, sorted cells were subjected to BAC array comparative genomic hybridization analysis following whole genome amplification. For RNA profiling, QPCR analysis was performed on sixty four (64) cancer-related genes using Taqman® low density arrays. For non-tumor controls, RNA profiling was performed on matched leukocytes (CD45+) isolated from the same enriched blood samples from 44 of the 53 patients.
Results: Differential gene expression analysis between EpCAM-positive cells and matched leukocytes confirmed the up-regulation of EPCAM and other genes including MUC1 and KRT19 (adjusted p &lt;0.05). In addition, EpCAM-positive cells showed a significant down-regulation of the leukocyte-specific marker PTPRC (encodes CD45) as well as CD44 and VIM, markers associated with stem cellness and epithelial to mesenchymal transition, respectively. Unsupervised hierarchical clustering analysis of RNA profiles showed that EpCAM-positive cells clustered away from the leukocytes. Genome-wide copy number analysis of EpCAM-expressing cells revealed gains (e.g. 1q and 8q), losses (e.g. 8p and 16q), and focal amplifications (e.g. on 8q and 11q including CCND1) frequently seen in primary breast cancers.
Discussion: We demonstrate the feasibility of isolation and molecular analysis of highly pure EpCAM-positive cells in the blood. Our results strongly suggest that epithelial cells captured from blood of MBC patients are malignant in nature and are therefore circulating tumor cells. This approach can serve as a non-invasive source of highly pure metastatic tumor tissue for further molecular characterization. This study was supported by CALGB and BCRF.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-05.