Multicenter Research Study Research Articles

Is it time to confine Snellen charts to the annals of history?

A paper published by the author in 1988 in this journal provided some important findings about the lack of precision of visual acuity (VA) measures made with commonly used Snellen charts and the advantages of using letter charts designed using the principles proposed by Bailey and Lovie in 1976. That 1988 paper has been cited a number of times since, mostly supporting the findings. The purpose of this review is to examine the changes that have occurred in VA measurement in research and clinical practice since that earlier study. While precise measures of VA using Bailey-Lovie or ETDRS charts are now commonly used in major, multi-centre research studies, it is disappointing to see that many research papers still report VA measured with Snellen charts and even use Snellen fractions, invalidly converted to logMAR notation, in parametric analyses of VA. Many studies have examined the test-retest variability (TRV) of VA measures in groups and individuals, but it is difficult to determine if clinicians or researchers determine patients' individual TRVs to more accurately detect real changes in VA for each individual. This paper summarises the findings of the 1988 study: (1) Snellen charts and VA notations are not appropriate for accurate clinical and research measures of VA; (2) Charts employing the Bailey-Lovie design principles should be used to provide precise measures of VA. (3) Test-retest variability should be used to determine the limit for detecting significant change in VA. This author suggests that it is time for Snellen charts, Snellen fractions and decimal notation to be confined to the teaching of the history of VA measurement. A request is also made to stop the use of the redundant term 'best corrected' VA (BCVA). Recommended procedures are given for precise measures of VA and accurately monitoring changes in VA in clinical practice and research.

A survey on the resources and practices in pediatric critical care of resource-rich and resource-limited countries.

BackgroundContemporary critical care research necessitates involvement of multiple centers, preferably from many countries. Adult and pediatric research networks have produced outstanding data; however, their involvement is restricted to a small percentage of the industrialized nations. Implementation of their findings in low- and middle-income countries (LMICs) is fraught with challenges.MethodsWe conducted an online international survey to assess and compare disease burden and resources to participate in multicenter research studies through a listserv of the World Federation of Pediatric Intensive and Critical Care Societies. Respondents were grouped into high-income countries and LMICs on the basis of World Bank classification.ResultsSurvey was completed by 73 centers in 34 countries (34 from high-income countries and 39 from LMICs). Compared with high-income countries, the pediatric intensive care units in LMICs were characterized by a lower number of critical care specialists, more difficult access to hemodialysis, and a lower number of elective postoperative patients, but a similar overall disease burden. Training and resources for research were comparable in the two cohorts.ConclusionsAlthough differences exist in access to both trained providers and equipment, the survey results were more striking in their similarity. It is essential that centers from LMICs be included in multinational studies, to generate results applicable to all children worldwide.

History of the Congenital Heart Surgeons' Society.

The Congenital Heart Surgeons' Society is a group of over 100 pediatric heart surgeons representing 72 institutions that specialize in the treatment of patients with congenital heart defects. The Society began in 1972 and incorporated as a not-for-profit charitable organization in 2004. It has become the face and voice of congenital heart surgery in North America. In 1985, the Society established a data center for multicenter clinical research studies to encourage congenital heart professionals to participate in improving outcomes for our patients. The goals of the Congenital Heart Surgeons' Society are to stimulate the study of congenital cardiac physiology, pathology, and management options which are instantiated in data collection, multi-institutional studies, and scientific meetings. Honest and open discussion of problems with possible solutions to the challenges facing congenital heart professionals have been the strength of the Congenital Heart Surgeons' Society. It is imperative for the growth of an organization to know from where it came in order to know to where it is going. The purpose of this article is to review the history of the Congenital Heart Surgeons' Society.

TCT-182 One-year Outcomes With Prasugrel (Pre-)Treatment in Routine Practice: Early Results from the Dutch, Multicenter and Observational Rijnmond Collective Cardiology Research (CCR) Study

Increased platelet inhibition by prasugrel has been shown to result in reduced ischemic events along with greater bleeding hazards in patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI). Yet, there is limited experience with the use of prasugrel in

Wheezing, a significant clinical phenotype of COPD: experience from the Taiwan Obstructive Lung Disease Study.

BackgroundCOPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.MethodsThe Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.ResultsOf the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P<0.001), higher modified Medical Research Council grade (2.0±1.0 versus 1.7±0.9, P<0.001), and more acute exacerbations within the past year (0.9±1.3 versus 0.4±0.9, P<0.001) than the nonwheezing group. The postbronchodilator forced expiratory volume in 1 second was lower in wheezing patients (1.2±0.5 L versus 1.5±0.6 L, P<0.001). Even in patients with maintenance treatment fitting the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines, the wheezing group still had worse symptom scores and more exacerbations.ConclusionWheezing is an important phenotype in patients with COPD. Patients with COPD having the wheezing phenotype are associated with worse symptoms, more exacerbations, and worse lung function.

Novel composite MRI scale correlates highly with disability in multiple sclerosis patients

Understanding genotype–phenotype relationships or development/validation of biomarkers requires large multicenter cohorts integrated by universal quantification of crucial phenotypical traits, such as central nervous system (CNS) tissue destruction. We hypothesized that mathematical modeling-guided combination of biologically meaningful, semi-quantitative MRI elements characterized by high signal-to-noise ratio will provide such reliable, universal tool for measuring CNS tissue destruction. We retrospectively graded 15 elements in MRI scans performed in 419 untreated subjects with or without neurological diseases, while being blinded to their prospectively acquired clinical scores. We then used 305 subjects for disability-guided mathematical modeling to select and combine MRI elements that had non-redundant contributions to clinical disability, resulting in Combinatorial MRI Scale (COMRIS). We validated our model on the remaining 114 independent subjects. COMRIS requires 5–10min per scan on average to compute and demonstrates highly significant (p<0.0001) and validation-consistent Spearman correlation coefficients (0.75, 0.76, and 0.65) for the expanded disability status scale (EDSS), Scripps neurological rating scale (SNRS), and symbol digit modality test (SDMT) measures of neurological disability, respectively. Because COMRIS is not greatly influenced by MRI scanners or protocols and can be computed even in the presence of some motion artifacts, it does not require censoring out patients and it provides comparable results across different cohorts. As such, it represents a broadly available clinical and research tool that can facilitate multicenter research studies and comparative analyses across patient cohorts and research projects.

Second Arab Society for Pediatric Endocrinology and Diabetes Conference, 6th-8th November 2014, Abu Dhabi, United Arab Emirates

The scientific program of the conference featured 62 oral and 84 poster presentations. Diabetes was the topic most heavily presented due to its widespread prevalence and unique features in our region. Milestones in diabetes care, diabetes education, epidemiology, updates in neonatal diabetes and hyperinsulinemic hypoglycemia as well as insulin resistance and type 2 diabetes mellitus were among the topics discussed by leading world-renown authorities as well as by regional experts. Diabetes technology was a particularly hot topic in the meeting featuring 2 symposia on the recent advances in artificial pancreas and regional experience with insulin pumps and continuous glucose monitoring systems. Experience pertinent to diabetes and fasting was elegantly presented by regional experts. The meeting also featured workshops dedicated to diabetes educators and stimulating discussions with behavioral psychologists. Growth disorders were presented in different formats of plenary, “Meet the Expert”, multicenter research study presentation, case presentations. Surveillance of growth hormone use was presented from Tunisia and Kuwait. In addition, pubertal disorders were widely covered. Speakers highlighted regional trends in precocious puberty, updates on PCOS management, adrenal disorders and novel mutations in a variety of puberty-related disorders. Exciting data regarding survivors of childhood cancer as well as updates in Turner syndrome management were brilliantly presented. A session of particular interest tackled disorders of sexual differentiation (DSDs), starting with an overview of medical approach to DSDs, followed by an animated presentation and discussion of religion point of view regarding DSDs as well as a valuable psychological approach to youth with DSDs and their families. Last but not least, a highly informative session was held on bone disorders and vitamin D status in the region.

Assessment of third ventriculostomy patency with the 3D-SPACE technique: a preliminary multicenter research study.

The goal of this study was to determine the value of the 3D sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) technique in the evaluation of endoscopic third ventriculostomy (ETV) patency. Twenty-six patients with ETV were examined using 3-T MRI units. Sagittal-plane 3D-SPACE with variant flip-angle mode, 3D T1-weighted (T1W), and 3D heavily T2-weighted (T2W) images were obtained with isotropic voxel sizes. Also, sagittal-axial plane phase-contrast cine (PC)-MR images were obtained. The following findings were evaluated: diameters of stoma and third ventricle, flow-void sign on 3D-SPACE and PC-MR images, integrity of the third ventricle on heavily T2W images, and quantitative PC-MRI parameters of the stoma. Obtained sequences were evaluated singly, in combination with one another, and all together. The mean area, flow, and velocity values measured at the level of stoma in patients with patent stoma were significantly higher than those measured in patients with closed stoma (p < 0.05). There was significant correlation among PC-MRI, 3D-SPACE, and 3D heavily T2W techniques regarding assessment of ETV patency (p < 0.001). The 3D-SPACE technique provided the lowest rate of ambiguous results. The 3D-SPACE technique seems to be the most efficient one for determination of ETV patency. The authors suggest the use of 3D-SPACE as a stand-alone first-line sequence in addition to routine brain MRI protocols in assessing patients with ETV, thereby decreasing scan time and reserving the use of a combination of additional sequences such as PC-MRI and 3D heavily T2W images in suspicious or complex cases.

Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: an international survey of clinician practice

ObjectiveNational clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, significant variation in practice occurs in other settings....

A recursively partitioned mixture model for clustering time-course gene expression data.

Longitudinally collected gene expression data provides an opportunity to investigate the dynamic behavior of gene expression and is crucial for establishing causal links between changes on a molecular level and disease development and progression. In terms of the analysis of such data, clustering of subjects based on time-course expression data may improve our understanding of temporal expression patterns that result in disease phenotypes. Although there are numerous existing methods for clustering subjects using gene expression data, most are not suitable when expression measurements are repeatedly collected over a time-course. We present a modified version of the recursively partitioned mixture model (RPMM) for clustering subjects based on longitudinally collected gene expression data. In the proposed time-course RPMM (TC-RPMM), subjects are clustered on the basis of their temporal profiles of gene expression using a mixture of mixed effects models framework. This framework captures changes in gene expression over time and models the autocorrelation between repeated gene expression measurements for the same subject. We assessed the performance of TC-RPMM using extensive simulation studies and a dataset from a multi-center research study of inflammation and response to injury (www.gluegrant.org), which consisted of time-course gene expression data for 140 subjects. Our simulation studies encompassed several different scenarios and were aimed at assessing the ability of TC-RPMM to correctly recover true class memberships when the expression trajectories that characterized those classes differed. Overall, our simulation studies revealed favorable performance of TC-RPMM compared to competing approaches, however clustering performance was observed to be highly dependent on the proportion of class discriminating genes used in clustering analysis. When applied to real epidemiologic data with repeated-measures, longitudinal gene expression measurements, TC-RPMM identified clusters that had strong biological and clinical significance. Methods for clustering subjects based on temporal gene expression profiles is a high priority for molecular biology and bioinformatics research. Along these lines, the proposed TC-RPMM represents a promising new approach for analyzing time-course gene expression data.

Organizational update: American Heart Association Stroke Council.

This report represents the Spring 2014 update of the Stroke Council. Much has happened in the past 6 months, and we want to particularly focus on the new strategic plan for the American Heart Association (AHA)/American Stroke Association (ASA) and new research opportunities within the AHA/ASA. Each Stroke Council Update starts with restating our 2020 Goals: By 2020 to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. To reach this goal, the AHA/ASA has worked hard, with input from throughout the organization, to craft the next detailed strategic plan for the entire AHA/ASA, including the strategic plan for the ASA that will be distributed throughout the organization in the upcoming months. One issue became apparent while reviewing the strategic plan for AHA/ASA: stroke rehabilitation and recovery are not emphasized currently in the Strategic Plan for the AHA as they deserve. In part, this reflects more limited research data and metrics available for assessing the effect of various approaches to stroke recovery compared with extensive research and public data about cardiac rehabilitation. Our stroke strategic plan must prioritize increasing engagement and advocacy for stroke recovery and rehabilitation. For example, in March, Congress passed another temporary fix to the Medicare therapy caps. They extended the exceptions process for 1 additional year (through March 31, 2015). This process allows stroke survivors on Medicare to get more outpatient therapy than the $1920 caps allow but only if their healthcare provider jumps through additional hoops to get those services covered. Although this short-term fix is good and is a direct result of advocacy from many stroke-related organizations, a long-term fix to Medicare therapy caps is paramount, and advocacy by all of us will be needed to ensure a long-term solution. …

P03 Clinician variation in treating childhood wheeze in Emergency Departments of the United Kingdom AND Ireland – an international survey

AimsNational clinical guidelines for childhood wheeze have existed for several years. Despite being one of the commonest reasons for childhood Emergency Department (ED) attendance, significant variation in practice has been...

A DICOM based radiotherapy plan database for research collaboration and reporting

Purpose: To create a central radiotherapy (RT) plan database for dose analysis and reporting, capable of calculating and presenting statistics on user defined patient groups. The goal is to facilitate multi-center research studies with easy and secure access to RT plans and statistics on protocol compliance. Methods: RT institutions are able to send data to the central database using DICOM communications on a secure computer network. The central system is composed of a number of DICOM servers, an SQL database and in-house developed software services to process the incoming data. A web site within the secure network allows the user to manage their submitted data. Results: The RT plan database has been developed in Microsoft .NET and users are able to send DICOM data between RT centers in Denmark. Dose-volume histogram (DVH) calculations performed by the system are comparable to those of conventional RT software. A permission system was implemented to ensure access control and easy, yet secure, data sharing across centers. The reports contain DVH statistics for structures in user defined patient groups. The system currently contains over 2200 patients in 14 collaborations. Conclusions: A central RT plan repository for use in multi-center trials and quality assurance was created. The system provides an attractive alternative to dummy runs by enabling continuous monitoring of protocol conformity and plan metrics in a trial.

Abstract NS19: Exploring Clinician Perspectives of Treating Acute Stroke with Thrombolytic Therapy: Results of a Multi-Center Qualitative Research Study

Study Objectives: Multiple guidelines endorse recombinant tissue plasminogen activator (rt-PA) in eligible patients with acute ischemic stroke (AIS), but only 4-6% of patients are treated. Clinician doubts about treatment benefits or operational barriers may be among the reasons for not treating potentially eligible patients. Through qualitative interviews, we sought to better understand the issues and perspectives for AIS treatment from Emergency Medicine Physicians (EMP) and Neurology and Emergency based Advanced Practice Nurses (APN) looking for similarities and differences. Methods: A multidisciplinary research team conducted in-depth interviews of 23 EMPs from 11 sites, and 20 APNs from 18 sites across the US. An interview guide was designed to elicit their current experience using rt-PA in AIS, approach to discussing rt-PA with patients and families, and cultural attitudes. Results: EMPs (male = 74%; 12 average years of experience) and APNs (male = 5%; 9.4 average years of experience) described two themes as shared perspectives: Timely Presentation and Neurology Presence were both thought to be important facilitators to receive rt-PA. However, differing perspectives emerged in four themes: Knowledge of Long-term Outcomes; Impression of Data; Communication of Risk and Benefit; and Use of Written/Educational Material (Table). The themes and representative quotes are presented by subject number and years in practice. Conclusions: While common perspectives were described, mainly contrasting beliefs emerged, most of which provide an opportunity to develop future strategies to improve guideline adherence for rt-PA use in AIS for each discipline.

Barriers to conducting multicenter nursing research

Introduction: The move towards evidence-based nursing practice requires active participation by nurses at all levels along the continuum of care. Despite this fact, nursing involvement in multicenter research is limited. This not only limits the generalizability of findings, but hinders collaborative and interdisciplinary research networking between hospitals. Reasons for single site nursing research barriers have been explored. Yet, knowledge of the barriers nurses face when they seek to engage in multicenter research activities is limited. Methods: A core group of experienced nurse researchers sought to initiate a multicenter observational research study of intracranial pressure monitoring. This article uses a case series approach to highlight the challenges encountered throughout the process. Results: Barriers to multicenter nursing research were identified and categorized by theme. Conclusions: Institutional changes are suggested to support the participation of clinical nurses in research and recommendations are made for future study.

九州山口地区における基質拡張型&beta;ラクタマーゼ産生菌の検出状況と抗菌薬使用状況に関する合同調査

九州山口地区における基質拡張型&beta;ラクタマーゼ産生菌の検出状況と抗菌薬使用状況に関する合同調査

Board 152 - Program Innovations Abstract Transcontinental Telesimulation

Introduction/Background The Managing Emergencies in Paediatric Anaesthesia (MEPA) course was conceived in the UK in 2006.1 Initially, a collaboration comprising a few simulation centres with a core faculty of paediatric anesthesiology educators, the spirit of collaboration has been maintained as the group has grown to include MEPA centres delivering a standardized curriculum in multiple centres on four continents. We describe the evolution of the program from a local simulation course to an international network. Methods Post-graduate training in paediatric anesthesiology is of insufficient duration to encounter those operating room emergencies, which would be considered key competencies for any anesthesiologist. In 2005 our group liaised with the Royal College of Anaesthetists (UK) to define which crises would be considered core for inclusion in a one day simulation course designed for year four anaesthesia trainees. Our initial group was a collaboration between several UK paediatric hospital simulation centres. Each case scenario was constructed based on a thorough literature review and then subjected to the scrutiny and refinement of a national committee of paediatric anesthesiologists thus creating a robust course content. The MEPA movement grew to include more centres in the UK. Start-up centres would send their faculty to observe a course at an existing centre before running their first course with the assistance of visiting faculty from the established centre. This "ambassador faculty" model allowed standardization of content, uniformity of delivery and quality assurance. The MEPA collaboration grew such that by 2010 it was available in every post-graduate medical training program in the UK (over twenty deaneries). In 2010 we began dissemination of the course across paediatric hospitals in Canada and also exploring some research questions. Within Ontario we used the ambassador faculty model but the large distances involved in interprovincial collaboration prohibited this and so we used "telesimulation". The existing telemedicine secure videoconferencing infrastructure is used for multiple new centres to observe remotely the course conducted in Toronto. Between scenarios, collaborators can contribute to the debriefing of learners ("tele-debriefing") or observe debriefs, thus there is a faculty development component to the activity. Similarly, new centres’ first courses are observed remotely by established faculty to provide support, feedback and guidance. In this way, the scenarios are conducted identically in all the centres worldwide - important as they are the foundation of some multicentre education research studies. Via presentation and publication2 of early Results, networking at international simulation meetings and word-of-mouth, uptake of the MEPA course has continued. Telesimulation has facilitated expansion into centres in the USA, Australia and Africa. The committee meets at least annually at international paediatric anaesthesia or simulation conferences and maintains connectivity via website www.mepa.org.uk. The research focus of the group has been the validation of simulation-based assessment tools in paediatric anaesthesia to inform the evolution of summative evaluations of trainee competence. The course is also the focus of some multicentre research in debriefing.3 The course content has expanded, with an allied course aimed at practicing anesthesiologists with occasional commitment to paediatric anaesthesia. This MEPA - For Consultants (MEPA-FC) course has been incorporated into the revalidation (maintenance of certification) process in the UK. In the last year, MEPA-FC has been run at a number of MEPA centres in the UK and starts in Australia in September 2013. Results: Conclusion Our group has expanded internationally with sustained momentum, taking advantage of a range of technological solutions to recruit new centres. We have created a paediatric anesthesia simulation network that is, to our knowledge, the largest worldwide. We continue to seek new centres to join the collaboration in the delivery and expansion of the existing curriculum and/or participation in the research projects.

Ultrasound methodology used to construct the fetal growth standards in the INTERGROWTH‐21st Project

A unified protocol is essential to ensure that fetal ultrasound measurements taken in multicentre research studies are accurate and reproducible. This paper describes the methodology used to take two-dimensional, ultrasound measurements in the longitudinal, fetal growth component of the INTERGROWTH-21(st) Project. These standardised methods should minimise the systematic errors associated with pooling data from different study sites. They represent a model for carrying out similar research studies in the future.

Standardization and Cross Validation of Alloreactive IFNγ ELISPOT Assays Within the Clinical Trials in Organ Transplantation Consortium

Emerging evidence indicates memory donor-reactive T cells are detrimental to transplant outcome and that quantifying the frequency of IFNγ-producing, donor-reactive PBMCs by ELISPOT has potential utility as an immune monitoring tool. Nonetheless, differences in assay performance among laboratories limit the ability to compare results. In an effort to standardize assays, we prepared a panel of common cellular reagent standards, developed and cross validated a standard operating procedure (SOP) for alloreactive IFNγ ELISPOT assays in several research laboratories supported by the NIH-funded Clinical Trials in Organ Transplantation (CTOT) Consortium. We demonstrate that strict adherence to the SOP and centralized data analysis results in high reproducibility with a coefficient of variance (CV) of ∼30%. This standardization of IFNγ ELISPOTassay will facilitate interpretation of data from multicenter transplantation research studies and provide the foundation for developing clinical laboratory testing strategies to guide therapeutic decision-making in transplant patients.

PAM50 HER2-enriched (HER2E) phenotype as a predictor of early-response to neoadjuvant lapatinib plus trastuzumab in stage I to IIIA HER2-positive breast cancer.

TPS665 Background: Combinations of two different anti-HER2 therapies without chemotherapy have generated great expectations. However, it is unclear which group of patients benefits the most from this strategy. Within HER2-positive breast cancer, the PAM50 assay identifies a HER2-Enriched HER2-E intrinsic subtype characterized by high activation of the EGFR/HER2 pathway. Trial Design: This non-randomized, open label multi-centre translational research study will evaluate the ability of the HER2-E subtype to predict pathological complete response (pCR) to dual HER2 blockade with lapatinib and trastuzumab for a total of 18 weeks. Patients with hormone receptor (HR)-positive disease will also receive endocrine therapy. Eligibility Criteria: Operable primary Stage I-IIIa HER2+ breast cancer. Specific Aims: The primary objective is to evaluate the ability of the PAM50 assay to predict pCR in the breast at the time of surgery.Secondary objectives are to (1) assess the correlation of HER2-E with pCR in the breast and axilla, (2) assess the correlation of HER2-E with Residual Cancer Burden (RCB) (3) evaluate the gene expression changes from Day 0 to Day 14 and the correlations with Ki67-IHC at Day 14, (4), identify additional gene expression signatures predictive of pCR, and (5) evaluate safety and tolerability. Methods: The statistical plan is based on the assumption that breast pCR rate will be 35.0% for HER2-E tumors and 8.0% for non-HER2E. The study will have a 95% power with a significance level of 5% (two-sided) and an assumed drop-out rate of 15%. Biomarker Analyses: Baseline, 14-day treated and post-treatment (surgical) formalin–fixed, paraffin–embedded tissues will be obtained. The expression of 547 genes will be explored with the nCounter platform. Subtype will be identified using the PAM50 predictor (Parker et al. J Clin Oncol 2009). Ki-67-IHC will also be evaluated on pre-treatment and Day-14 samples. Target Accrual: 150 patients with a maximum of 75 HR-positive patients across Spain and Portugal. Patient enrollment will begin in May 2013.