Shared decision-making in end-stage renal disease: a protocol for a multi-center study of a communication intervention to improve end-of-life care for dialysis patients.

PubMed

Eneanya, Nwamaka D; Goff, Sarah L; Martinez, Talaya; Gutierrez, Natalie; Klingensmith, Jamie; Griffith, John L; Garvey, Casey; Kitsen, Jenny; Germain, Michael J; Marr, Lisa; Berzoff, Joan; Unruh, Mark; Cohen, Lewis M

2015-06-12

End-stage renal disease carries a prognosis similar to cancer yet only 20 % of end-stage renal disease patients are referred to hospice. Furthermore, conversations between dialysis team members and patients about end-of-life planning are uncommon. Lack of provider training about how to communicate prognostic data may contribute to the limited number of end-of-life care discussions that take place with this chronically ill population. In this study, we will test the Shared Decision-Making Renal Supportive Care communication intervention to systematically elicit patient and caretaker preferences for end-of-life care so that care concordant with patients' goals can be provided. This multi-center study will deploy an intervention to improve end-of-life communication for hemodialysis patients who are at high risk of death in the ensuing six months. The intervention will be carried out as a prospective cohort with a retrospective cohort serving as the comparison group. Patients will be recruited from 16 dialysis units associated with two large academic centers in Springfield, Massachusetts and Albuquerque, New Mexico. Critical input from patient advisory boards, a stakeholder panel, and initial qualitative analysis of patient and caretaker experiences with advance care planning have informed the communication intervention. Rigorous communication training for hemodialysis social workers and providers will ensure that standardized study procedures are performed at each dialysis unit. Nephrologists and social workers will communicate prognosis and provide advance care planning in face-to-face encounters with patients and families using a social work-centered algorithm. Study outcomes including frequency and timing of hospice referrals, patient and caretaker satisfaction, quality of end-of-life discussions, and quality of death will be assessed over an 18 month period. The Shared Decision-Making Renal Supportive Care Communication intervention intends to improve discussions about prognosis and end-of-life care with end-stage renal disease patients. We anticipate that the intervention will help guide hemodialysis staff and providers to effectively participate in advance care planning for patients and caretakers to establish preferences and goals at the end of life. NCT02405312.

A machine learning tool for re-planning and adaptive RT: A multicenter cohort investigation.

PubMed

Guidi, G; Maffei, N; Meduri, B; D'Angelo, E; Mistretta, G M; Ceroni, P; Ciarmatori, A; Bernabei, A; Maggi, S; Cardinali, M; Morabito, V E; Rosica, F; Malara, S; Savini, A; Orlandi, G; D'Ugo, C; Bunkheila, F; Bono, M; Lappi, S; Blasi, C; Lohr, F; Costi, T

2016-12-01

To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier. The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases. SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A prospective development study of software-guided radio-frequency ablation of primary and secondary liver tumors: Clinical intervention modelling, planning and proof for ablation cancer treatment (ClinicIMPPACT).

PubMed

Reinhardt, Martin; Brandmaier, Philipp; Seider, Daniel; Kolesnik, Marina; Jenniskens, Sjoerd; Sequeiros, Roberto Blanco; Eibisberger, Martin; Voglreiter, Philip; Flanagan, Ronan; Mariappan, Panchatcharam; Busse, Harald; Moche, Michael

2017-12-01

Radio-frequency ablation (RFA) is a promising minimal-invasive treatment option for early liver cancer, however monitoring or predicting the size of the resulting tissue necrosis during the RFA-procedure is a challenging task, potentially resulting in a significant rate of under- or over treatments. Currently there is no reliable lesion size prediction method commercially available. ClinicIMPPACT is designed as multicenter-, prospective-, non-randomized clinical trial to evaluate the accuracy and efficiency of innovative planning and simulation software. 60 patients with early liver cancer will be included at four European clinical institutions and treated with the same RFA system. The preinterventional imaging datasets will be used for computational planning of the RFA treatment. All ablations will be simulated simultaneously to the actual RFA procedure, using the software environment developed in this project. The primary outcome measure is the comparison of the simulated ablation zones with the true lesions shown in follow-up imaging after one month, to assess accuracy of the lesion prediction. This unique multicenter clinical trial aims at the clinical integration of a dedicated software solution to accurately predict lesion size and shape after radiofrequency ablation of liver tumors. Accelerated and optimized workflow integration, and real-time intraoperative image processing, as well as inclusion of patient specific information, e.g. organ perfusion and registration of the real RFA needle position might make the introduced software a powerful tool for interventional radiologists to optimize patient outcomes.

An Exploration of Radiation Physics in Electromagnetics

NASA Technical Reports Server (NTRS)

Lee, Katherine K.

2005-01-01

Contents include the following: NASA's Missions and Aeronautics Research. Today's Air Traffic Control System. Development of Decision-Support Tools. The Center-TRACON Automation System (CTAS). The Traffic Management Advisor (TMA). The Multi-Center Traffic Management Advisor (McTMA). The Surface Management System (SMS). Future Directions: The Joint Planning and Development Office.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal... project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (Asia...

Organizing for ontological change: The kernel of an AIDS research infrastructure

PubMed Central

Polk, Jessica Beth

2015-01-01

Is it possible to prepare and plan for emergent and changing objects of research? Members of the Multicenter AIDS Cohort Study have been investigating AIDS for over 30 years, and in that time, the disease has been repeatedly transformed. Over the years and across many changes, members have continued to study HIV disease while in the process regenerating an adaptable research organization. The key to sustaining this technoscientific flexibility has been what we call the kernel of a research infrastructure: ongoing efforts to maintain the availability of resources and services that may be brought to bear in the investigation of new objects. In the case of the Multicenter AIDS Cohort Study, these resources are as follows: specimens and data, calibrated instruments, heterogeneous experts, and participating cohorts of gay and bisexual men. We track three ontological transformations, examining how members prepared for and responded to changes: the discovery of a novel retroviral agent (HIV), the ability to test for that agent, and the transition of the disease from fatal to chronic through pharmaceutical intervention. Respectively, we call the work, ‘technologies’, and techniques of adapting to these changes, ‘repurposing’, ‘elaborating’, and ‘extending the kernel’. PMID:26477206

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

1. Contingency Preparedness: Collect information from transplant centers, build awareness of the Transplant Center Contingency Planning Committee and...Matched Donors: Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency ...Transplantation: Create a platform that facilitates multicenter collaboration and data management.

Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

PubMed

Nakanishi, Rine; Post, Wendy S; Osawa, Kazuhiro; Jayawardena, Eranthi; Kim, Michael; Sheidaee, Nasim; Nezarat, Negin; Rahmani, Sina; Kim, Nicholas; Hathiramani, Nicolai; Susarla, Shriraj; Palella, Frank; Witt, Mallory; Blaha, Michael J; Brown, Todd T; Kingsley, Lawrence; Haberlen, Sabina A; Dailing, Christopher; Budoff, Matthew J

2018-01-01

The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

[Design of a multicenter study for assessing the effectiveness of extracorporeal shockwave therapy in epicondylitis humeri radialis].

PubMed

Haake, M; Jensen, K; Prinz, H; Willenberg, T

2000-01-01

Previously published studies concerning, extracorporeal shock-wave therapy (ESWT) in the treatment of lateral epicondylitis do not fulfil the biometric standards of modern clinical research. The objective of the trial is to show that ESWT is effective in the treatment of chronic LE. A prospective, randomized, placebo-controlled, single-blinded, multicenter trial with an independent blinded observer was designed. The effectiveness of ESWT is evaluated by comparison with a control group in which sham-ESWT is performed, both under local anaesthesia. Outcome is determined on the basis of the Roles/Maudsley-Score. Inclusion criteria are a history of at least 6 months of LE and failure of conventional treatment. The therapy includes 3 sessions of low energy ESWT with 2000 impulses (energy flux density 0.07-0.09 mJ/mm2). Sample size is 272 patients. Randomisation started in October 1998 and is planned over a period of two and a half years. Only a randomised clinical trial with adequate control of placebo effects and observer bias can provide the required evidence for the efficiency of ESWT in the treatment of lateral epicondylitis of the elbow.

Dosimetry audit simulation of treatment planning system in multicenters radiotherapy

NASA Astrophysics Data System (ADS)

Kasmuri, S.; Pawiro, S. A.

2017-07-01

Treatment Planning System (TPS) is an important modality that determines radiotherapy outcome. TPS requires input data obtained through commissioning and the potentially error occurred. Error in this stage may result in the systematic error. The aim of this study to verify the TPS dosimetry to know deviation range between calculated and measurement dose. This study used CIRS phantom 002LFC representing the human thorax and simulated all external beam radiotherapy stages. The phantom was scanned using CT Scanner and planned 8 test cases that were similar to those in clinical practice situation were made, tested in four radiotherapy centers. Dose measurement using 0.6 cc ionization chamber. The results of this study showed that generally, deviation of all test cases in four centers was within agreement criteria with average deviation about -0.17±1.59 %, -1.64±1.92 %, 0.34±1.34 % and 0.13±1.81 %. The conclusion of this study was all TPS involved in this study showed good performance. The superposition algorithm showed rather poor performance than either analytic anisotropic algorithm (AAA) and convolution algorithm with average deviation about -1.64±1.92 %, -0.17±1.59 % and -0.27±1.51 % respectively.

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project

PubMed Central

Freyer Karn, Catharine; Fox, Kristen

2015-01-01

Abstract Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. PMID:26176343

The effect of urodynamic testing on clinical diagnosis, treatment plan and outcomes in women undergoing stress urinary incontinence surgery.

PubMed

Sirls, Larry T; Richter, Holly E; Litman, Heather J; Kenton, Kimberly; Lemack, Gary E; Lukacz, Emily S; Kraus, Stephen R; Goldman, Howard B; Weidner, Alison; Rickey, Leslie; Norton, Peggy; Zyczynski, Halina M; Kusek, John W

2013-01-01

We evaluated the influence of preoperative urodynamic studies on diagnoses, global treatment plans and outcomes in women treated with surgery for uncomplicated stress predominant urinary incontinence. We performed a secondary analysis from a multicenter, randomized trial of the value of preoperative urodynamic studies. Physicians provided diagnoses before and after urodynamic studies and global treatment plans, defined as proceeding with surgery, surgery type, surgical modification and nonoperative therapy. Treatment plan changes and surgical outcomes between office evaluation and office evaluation plus urodynamic studies were compared by the McNemar test. Of 315 subjects randomized to urodynamic studies after office evaluation 294 had evaluable data. Urodynamic studies changed the office evaluation diagnoses in 167 women (56.8%), decreasing the diagnoses of overactive bladder-wet (41.6% to 25.2%, p <0.001), overactive bladder-dry (31.4% to 20.8%, p = 0.002) and intrinsic sphincter deficiency (19.4% to 12.6%, p = 0.003) but increasing the diagnosis of voiding dysfunction (2.2% to 11.9%, p <0.001). After urodynamic studies physicians canceled surgery in 4 of 294 women (1.4%), changed the incontinence procedure in 13 (4.4%) and planned to modify mid urethral sling tension (more or less obstructive) in 20 women (6.8%). Nonoperative treatment plans changed in 40 of 294 women (14%). Urodynamic study driven treatment plan changes were not associated with treatment success (OR 0.96, 95% CI 0.41, 2.25, p = 0.92) but they were associated with increased postoperative treatment for urge urinary incontinence (OR 3.23, 95% CI 1.46, 7.14, p = 0.004). Urodynamic studies significantly changed clinical diagnoses but infrequently changed the global treatment plan or influenced surgeon decision to cancel, change or modify surgical plans. Global treatment plan changes were associated with increased treatment for postoperative urgency urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

PubMed

Piringer, Gudrun; Fridrik, Michael; Fridrik, Alfred; Leiherer, Andreas; Zabernigg, August; Greil, Richard; Eisterer, Wolfgang; Tschmelitsch, Jörg; Lang, Alois; Frantal, Sophie; Burgstaller, Sonja; Gnant, Michael; Thaler, Josef

2018-04-01

Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Measurement and Evaluation of Quantitative Performance of PET/CT Images before a Multicenter Clinical Trial.

PubMed

Zhu, Yanjia; Geng, Caizheng; Huang, Jia; Liu, Juzhen; Wu, Ning; Xin, Jun; Xu, Hao; Yu, Lijuan; Geng, Jianhua

2018-06-13

To ensure the reliability of the planned multi-center clinical trial, we assessed the consistence and comparability of the quantitative parameters of the eight PET/CT units that will be used in this trial. PET/CT images were scanned using a PET NEMA image quality phantom (Biodex) on the eight units of Discovery PET/CT 690 from GE Healthcare. The scanning parameters were the same with the ones to be used in the planned trial. The 18 F-NaF concentration in the background was 5.3 kBq/ml, while the ones in the spheres of diameter 37 mm, 22 mm, 17 mm and 10 mm were 8:1 as to that of the background and the ones in the spheres of diameter 28 mm and 13 mm were 0 kBq/ml. The consistency of hot sphere recovery coefficient (HRC), cold sphere recovery coefficient (CRC), hot sphere contrast (Q H ) and cold sphere contrast (Q c ) among these 8 PET/CTs was analyzed. The variation of the main quantitative parameters of the eight PET/CT systems was within 10%, which is acceptable for the clinical trial.

The Development of the Multi-Center Traffic Management Advisor (MCTMA): Traffic Flow Management Research in a Multi-Facility Environment

NASA Technical Reports Server (NTRS)

Lee, Katharine K.; Davis, Thomas J.; Levin, Kerry M.; Rowe, Dennis W.

2001-01-01

The Traffic Management Advisor (TMA) is a decision-support tool for traffic managers and air traffic controllers that provides traffic flow visualization and other flow management tools. TMA creates an efficiently sequenced and safely spaced schedule for arrival traffic that meets but does not exceed specified airspace system constraints. TMA is being deployed at selected facilities throughout the National Airspace System in the US as part of the FAA's Free Flight Phase 1 program. TMA development and testing, and its current deployment, focuses on managing the arrival capacity for single major airports within single terminal areas and single en route centers. The next phase of development for this technology is the expansion of the TMA capability to complex facilities in which a terminal area or airport is fed by multiple en route centers, thus creating a multicenter TMA functionality. The focus of the multi-center TMA (McTMA) development is on the busy facilities in the Northeast comdor of the US. This paper describes the planning and development of McTMA and the challenges associated with adapting a successful traffic flow management tool for a very complex airspace.

It Offers the Appropriate Big-Picture

NASA Astrophysics Data System (ADS)

Schläpfer, Markus

Every week, more than 1 million people are currently being added to cities across the globe. This unprecedented trend of urbanization, together with growing concerns over energy supply and climate change, rapidly outpaces existing approaches for the planning and design of cities. A prominent warning example is Beijing's recent failure to implement a multi-centered urban form that has led to counter-intuitive people flows, immense traffic congestion, and air pollution. Thus, a new quantitative understanding of cities is urgently needed to reduce the risks of such detrimental planning outcomes and to eventually build more sustainable and more livable urban spaces...

Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot).

PubMed

Olavarría, Verónica V; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro; Muñoz-Venturelli, Paula; Billot, Laurent; Lavados, Pablo M

2017-02-01

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.

Stakeholders' views on data sharing in multicenter studies.

PubMed

Mazor, Kathleen M; Richards, Allison; Gallagher, Mia; Arterburn, David E; Raebel, Marsha A; Nowell, W Benjamin; Curtis, Jeffrey R; Paolino, Andrea R; Toh, Sengwee

2017-09-01

To understand stakeholders' views on data sharing in multicenter comparative effectiveness research studies and the value of privacy-protecting methods. Semistructured interviews with five US stakeholder groups. We completed 11 interviews, involving patients (n = 15), researchers (n = 10), Institutional Review Board and regulatory staff (n = 3), multicenter research governance experts (n = 2) and healthcare system leaders (n = 4). Perceptions of the benefits and value of research were the strongest influences toward data sharing; cost and security risks were primary influences against sharing. Privacy-protecting methods that share summary-level data were acknowledged as being appealing, but there were concerns about increased cost and potential loss of research validity. Stakeholders were open to data sharing in multicenter studies that offer value and minimize security risks.

Interlaboratory quality control of total HIV-1 DNA load measurement for multicenter reservoir studies.

PubMed

Gantner, Pierre; Mélard, Adeline; Damond, Florence; Delaugerre, Constance; Dina, Julia; Gueudin, Marie; Maillard, Anne; Sauné, Karine; Rodallec, Audrey; Tuaillon, Edouard; Plantier, Jean-Christophe; Rouzioux, Christine; Avettand-Fenoel, Véronique

2017-11-01

Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in four samples (QCMD). Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log 10 copies/10 6 PBMC) for the three positive QC that were correctly classified by each laboratory (QC1

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project.

PubMed

McGovern, Kathleen; Karn, Catharine Freyer; Fox, Kristen

2015-10-01

Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. © 2015 Wiley Periodicals, Inc.

Multicenter Trial of Rivaroxaban for Early Discharge of Pulmonary Embolism From the Emergency Department (MERCURY PE): Rationale and Design.

PubMed

Singer, Adam J; Xiang, Jim; Kabrhel, Christopher; Merli, Gino J; Pollack, Charles; Tapson, Victor F; Wildgoose, Peter; Peacock, W Frank

2016-11-01

Traditionally, patients with pulmonary embolism (PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment. We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome. Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board. The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study. © 2016 by the Society for Academic Emergency Medicine.

Photodynamic therapy in neurosurgery: a proof of concept of treatment planning system

NASA Astrophysics Data System (ADS)

Dupont, C.; Reyns, N.; Mordon, S.; Vermandel, M.

2017-02-01

Glioblastoma (GBM) is the most common primary brain tumor. PhotoDynamic Therapy (PDT) appears as an interesting research field to improve GBM treatment. Nevertheless, PDT cannot fit into the current therapeutic modalities according to several reasons: the lack of reliable and reproducible therapy schemes (devices, light delivery system), the lack of consensus on a photosensitizer and the absence of randomized and controlled multicenter clinical trial. The main objective of this study is to bring a common support for PDT planning. Here, we describe a proof of concept of Treatment Planning System (TPS) dedicated to interstitial PDT for GBM treatment. The TPS was developed with the integrated development environment C++ Builder XE8 and the environment ArtiMED, developed in our laboratory. This software enables stereotactic registration of DICOM images, light sources insertion and an accelerated CUDA GPU dosimetry modeling. Although, Monte-Carlo is more robust to describe light diffusion in biological tissue, analytical model accelerated by GPU remains relevant for dose preview or fast reverse planning processes. Finally, this preliminary work proposes a new tool to plan interstitial or intraoperative PDT treatment and might be included in the design of future clinical trials in order to deliver PDT straightforwardly and homogenously in investigator centers.

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

A Multicenter Radiographic Evaluation of the Rates of Preoperative and Postoperative Malalignment in Degenerative Spinal Fusions.

PubMed

Leveque, Jean-Christophe A; Segebarth, Bradley; Schroerlucke, Samuel R; Khanna, Nitin; Pollina, John; Youssef, Jim A; Tohmeh, Antoine G; Uribe, Juan S

2018-07-01

Multicenter, retrospective, institutional-review-board -approved study at 18 institutions in the United States with 24 treating investigators. This study was designed to retrospectively assess the prevalence of spinopelvic malalignment in patients who underwent one- or two-level lumbar fusions for degenerative (nondeformity) indications and to assess the incidence of malalignment after fusion surgery as well as the rate of alignment preservation and/or correction in this population. Spinopelvic malalignment after lumbar fusion has been associated with lower postoperative health-related quality of life and elevated risk of adjacent segment failure. The prevalence of spinopelvic malalignment in short-segment degenerative lumbar fusion procedures from a large sample of patients is heretofore unreported and may lead to an under-appreciation of these factors in surgical planning and ultimate preservation or correction of alignment. Lateral preoperative and postoperative lumbar radiographs were retrospectively acquired from 578 one- or two-level lumbar fusion patients and newly measured for lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt. Patients were categorized at preop and postop time points as aligned if PI-LL < 10° or malaligned if PI-LL≥10°. Patients were grouped into categories based on their alignment progression from pre- to postoperative, with preserved (aligned to aligned), restored (malaligned to aligned), not corrected (malaligned to malaligned), and worsened (aligned to malaligned) designations. Preoperatively, 173 (30%) patients exhibited malalignment. Postoperatively, 161 (28%) of patients were malaligned. Alignment was preserved in 63%, restored in 9%, not corrected in 21%, and worsened in 7% of patients. This is the first multicenter study to evaluate the preoperative prevalence and postoperative incidence of spinopelvic malalignment in a large series of short-segment degenerative lumbar fusions, finding over 25% of patients out of alignment at both time points, suggesting that alignment preservation/restoration considerations should be incorporated into the decision-making of even degenerative lumbar spinal fusions. 3.

Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

PubMed Central

Kasper, Siegfried; Dienel, Angelika

2017-01-01

Purpose This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. Methods The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. Discussion The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with R. rosea. During administration of the study drug over the course of 12 weeks, a wide range of outcome measures associated with the syndrome clearly improved. Conclusion The results presented provide an encouraging basis for clinical trials further investigating the clinical outcomes of R. rosea extract in patients with the burnout syndrome. PMID:28367055

Accuracy of a Computer-Aided Surgical Simulation (CASS) Protocol for Orthognathic Surgery: A Prospective Multicenter Study

PubMed Central

Hsu, Sam Sheng-Pin; Gateno, Jaime; Bell, R. Bryan; Hirsch, David L.; Markiewicz, Michael R.; Teichgraeber, John F.; Zhou, Xiaobo; Xia, James J.

2012-01-01

Purpose The purpose of this prospective multicenter study was to assess the accuracy of a computer-aided surgical simulation (CASS) protocol for orthognathic surgery. Materials and Methods The accuracy of the CASS protocol was assessed by comparing planned and postoperative outcomes of 65 consecutive patients enrolled from 3 centers. Computer-generated surgical splints were used for all patients. For the genioplasty, one center utilized computer-generated chin templates to reposition the chin segment only for patients with asymmetry. Standard intraoperative measurements were utilized without the chin templates for the remaining patients. The primary outcome measurements were linear and angular differences for the maxilla, mandible and chin when the planned and postoperative models were registered at the cranium. The secondary outcome measurements were: maxillary dental midline difference between the planned and postoperative positions; and linear and angular differences of the chin segment between the groups with and without the use of the template. The latter was measured when the planned and postoperative models were registered at mandibular body. Statistical analyses were performed, and the accuracy was reported using root mean square deviation (RMSD) and Bland and Altman's method for assessing measurement agreement. Results In the primary outcome measurements, there was no statistically significant difference among the 3 centers for the maxilla and mandible. The largest RMSD was 1.0mm and 1.5° for the maxilla, and 1.1mm and 1.8° for the mandible. For the chin, there was a statistically significant difference between the groups with and without the use of the chin template. The chin template group showed excellent accuracy with largest positional RMSD of 1.0mm and the largest orientational RSMD of 2.2°. However, larger variances were observed in the group not using the chin template. This was significant in anteroposterior and superoinferior directions, as in pitch and yaw orientations. In the secondary outcome measurements, the RMSD of maxillary dental midline positions was 0.9mm. When registered at the body of the mandible, the linear and angular differences of the chin segment between the groups with and without the use of the chin template were consistent with the results found in the primary outcome measurements. Conclusion Using the CASS protocol, the computerized plan can be accurately and consistently transferred to the patient to position the maxilla and mandible at the time of surgery. The computer-generated chin template provides more accuracy in repositioning the chin segment than the intraoperative measurements. PMID:22695016

Preserving cognition, quality of life, physical health and functional ability in Alzheimer's disease: the effect of physical exercise (ADEX trial): rationale and design.

PubMed

Hoffmann, Kristine; Frederiksen, Kristian S; Sobol, Nanna Aue; Beyer, Nina; Vogel, Asmus; Simonsen, Anja Hviid; Johannsen, Peter; Lolk, Annette; Terkelsen, Ole; Cotman, Carl W; Hasselbalch, Steen G; Waldemar, Gunhild

2013-01-01

Exercise is hypothesized to improve cognition, physical performance, functional ability and quality of life, but evidence is scarce. Previous studies were of short duration, often underpowered and involving home-based light exercise programs in patients with undefined dementia. The aim of the ADEX ('Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish whether aerobic exercise is effective in improving cognition as well as in reducing the prevalence of psychiatric symptoms among patients with Alzheimer's disease (AD). The ADEX study is a multicenter, single-blind, randomized trial with two arms: an intervention group attending 16 weeks of continuously supervised moderate-to-high intensity aerobic exercise and a control group receiving usual care. We plan to recruit 192 patients with mild AD. The primary outcome measure is change from baseline in cognitive performance at 16 weeks (as measured by the Symbol Digit Modalities test). To our knowledge this is the first large-scale controlled study to investigate the effects of supervised moderate aerobic exercise on cognition in patients with AD. Recruitment began in January 2012 and results are expected to be available in 2014. We summarize the methodological challenges we and other studies have faced in this type of complex multicenter intervention with unique challenges to study design. © 2013 S. Karger AG, Basel.

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leong, Trevor, E-mail: trevor.leong@petermac.or; Joon, Daryl Lim; Willis, David

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined,more » multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less

What determines medical students' career preference for general practice residency training?: a multicenter survey in Japan.

PubMed

Ie, Kenya; Murata, Akiko; Tahara, Masao; Komiyama, Manabu; Ichikawa, Shuhei; Takemura, Yousuke C; Onishi, Hirotaka

2018-01-01

Few studies have systematically explored factors affecting medical students' general practice career choice. We conducted a nationwide multicenter survey (Japan MEdical Career of Students: JMECS) to examine factors associated with students' general practice career aspirations in Japan, where it has been decided that general practice will be officially acknowledged as a new discipline. From April to December 2015, we distributed a 21-item questionnaire to final year medical students in 17 medical schools. The survey asked students about their top three career preferences from 19 specialty fields, their demographics and their career priorities. Multivariable logistic regression was used to determine the effect of each item. A total of 1264 responses were included in the analyses. The top three specialty choice were internal medicine: 833 (65.9%), general practice: 408 (32.3%), and pediatrics: 372 (29.4%). Among demographic factors, "plan to inherit other's practice" positively associated with choosing general practice, whereas "having physician parent" had negative correlation. After controlling for potential confounders, students who ranked the following items as highly important were more likely to choose general practice: "clinical diagnostic reasoning (adjusted odds ratio (aOR): 1.65, 95% CI 1.40-1.94)", "community-oriented practice (aOR: 1.33, 95% CI 1.13-1.57)", and" involvement in preventive medicine (aOR: 1.18, 95% CI 1.01-1.38)". On the contrary, "acute care rather than chronic care", "mastering advanced procedures", and "depth rather than breadth of practice" were less likely to be associated with general practice aspiration. Our nationwide multicenter survey found several features associated with general practice career aspirations: clinical diagnostic reasoning; community-oriented practice; and preventive medicine. These results can be fundamental to future research and the development of recruitment strategies.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L; Clark, Amy E; Holubkov, Richard; Browning, Brittan; Slomine, Beth S; Christensen, James R; Dean, J Michael

2013-09-01

To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Multicenter randomized controlled trials. Pediatric intensive care and cardiac ICUs in the United States and Canada. Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Therapeutic hypothermia or therapeutic normothermia. From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

HDU Deep Space Habitat (DSH) Overview

NASA Technical Reports Server (NTRS)

Kennedy, Kriss J.

2011-01-01

This paper gives an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) project Deep Space Habitat (DSH) analog that will be field-tested during the 2011 Desert Research and Technologies Studies (D-RATS) field tests. The HDU project is a technology pull project that integrates technologies and innovations from multiple NASA centers. This project will repurpose the HDU Pressurized Excursion Module (PEM) that was field tested in the 2010 D-RATS, adding habitation functionality to the prototype unit. The 2010 configuration of the HDU-PEM consisted of a lunar surface laboratory module that was used to bring over 20 habitation-related technologies together in a single platform that could be tested as an advanced habitation analog in the context of mission architectures and surface operations. The 2011 HDU-DSH configuration will build upon the PEM work, and emphasize validity of crew operations (habitation and living, etc), EVA operations, mission operations, logistics operations, and science operations that might be required in a deep space context for Near Earth Object (NEO) exploration mission architectures. The HDU project consists of a multi-center team brought together in a skunkworks approach to quickly build and validate hardware in analog environments. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Exploration Mission Systems Office (EMSO) to test destination elements in analog environments. The 2011 analog field test will include Multi Mission Space Exploration Vehicles (MMSEV) and the DSH among other demonstration elements to be brought together in a mission architecture context. This paper will describe overall objectives, various habitat configurations, strategic plan, and technology integration as it pertains to the 2011 field tests.

A self-management approach using self-initiated action plans for symptoms with ongoing nurse support in patients with Chronic Obstructive Pulmonary Disease (COPD) and comorbidities: the COPE-III study protocol.

PubMed

Lenferink, Anke; Frith, Peter; van der Valk, Paul; Buckman, Julie; Sladek, Ruth; Cafarella, Paul; van der Palen, Job; Effing, Tanja

2013-09-01

Chronic Obstructive Pulmonary Disease (COPD) frequently coexists with other diseases. Whereas COPD action plans are currently part of usual care, they are less suitable and potentially unsafe for use in the presence of comorbidities. This study evaluates whether an innovative treatment approach directed towards COPD and frequently existing comorbidities can reduce COPD exacerbation days. We hypothesise that this approach, which combines self-initiated action plans and nurse support, will accelerate proper treatment actions and lead to better control of deteriorating symptoms. In this multicenter randomised controlled trial we aim to include 300 patients with COPD (GOLD II-IV), and with at least one comorbidity (cardiovascular disease, diabetes, anxiety and/or depression). Patients will be recruited from hospitals in the Netherlands (n = 150) and Australia (n = 150) and will be assigned to an intervention or control group. All patients will learn to complete daily symptom diaries for 12-months. Intervention group patients will participate in self-management training sessions to learn the use of individualised action plans for COPD and comorbidities, linked to the diary. The primary outcome is the number of COPD exacerbation days. Secondary outcomes include hospitalisations, quality of life, self-efficacy, adherence, patient's satisfaction and confidence, health care use and cost data. Intention-to-treat analyses (random effect negative binomial regression and random effect mixed models) and cost-effectiveness analyses will be performed. Prudence should be employed before extrapolating the use of COPD specific action plans in patients with comorbidities. This study evaluates the efficacy of tailored action plans for both COPD and common comorbidities. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluations of treatment efficacy of depression from perspective of both patients' symptoms and general sense of mental health and wellbeing: A large scale, multi-centered, longitudinal study in China.

PubMed

Zeng, Qingzhi; Wang, Wei Chun; Fang, Yiru; Mellor, David; Mccabe, Marita; Byrne, Linda; Zuo, Sai; Xu, Yifeng

2016-07-30

Relying on the absence, presence of level of symptomatology may not provide an adequate indication of the effects of treatment for depression, nor sufficient information for the development of treatment plans that meet patients' needs. Using a prospective, multi-centered, and observational design, the present study surveyed a large sample of outpatients with depression in China (n=9855). The 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Remission Evaluation and Mood Inventory Tool (REMIT) were administered at baseline, two weeks later and 4 weeks, to assess patients' self-reported symptoms and general sense of mental health and wellbeing. Of 9855 outpatients, 91.3% were diagnosed as experiencing moderate to severe depression. The patients reported significant improvement over time on both depressive symptoms and general sense after 4-week treatment. The effect sizes of change in general sense were lower than those in symptoms at both two week and four week follow-up. Treatment effects on both general sense and depressive symptomatology were associated with demographic and clinical factors. The findings indicate that a focus on both general sense of mental health and wellbeing in addition to depressive symptomatology will provide clinicians, researchers and patients themselves with a broader perspective of the status of patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

TU-FG-201-06: Remote Dosimetric Auditing for Clinical Trials Using EPID Dosimetry: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miri, N; Legge, K; Greer, P

2016-06-15

Purpose: To perform a pilot study for remote dosimetric credentialing of intensity modulated radiation therapy (IMRT) based clinical trials. The study introduces a novel, time efficient and inexpensive dosimetry audit method for multi-center credentialing. The method employs electronic portal imaging device (EPID) to reconstruct delivered dose inside a virtual flat/cylindrical water phantom. Methods: Five centers, including different accelerator types and treatment planning systems (TPS), were asked to download two CT data sets of a Head and Neck (H&N) and Postprostatectomy (P-P) patients to produce benchmark plans. These were then transferred to virtual flat and cylindrical phantom data sets that weremore » also provided. In-air EPID images of the plans were then acquired, and the data sent to the central site for analysis. At the central site, these were converted to DICOM format, all images were used to reconstruct 2D and 3D dose distributions inside respectively the flat and cylindrical phantoms using inhouse EPID to dose conversion software. 2D dose was calculated for individual fields and 3D dose for the combined fields. The results were compared to corresponding TPS doses. Three gamma criteria were used, 3%3mm-3%/2mm–2%/2mm with a 10% dose threshold, to compare the calculated and prescribed dose. Results: All centers had a high pass rate for the criteria of 3%/3 mm. For 2D dose, the average of centers mean pass rate was 99.6% (SD: 0.3%) and 99.8% (SD: 0.3%) for respectively H&N and PP patients. For 3D dose, 3D gamma was used to compare the model dose with TPS combined dose. The mean pass rate was 97.7% (SD: 2.8%) and 98.3% (SD: 1.6%). Conclusion: Successful performance of the method for the pilot centers establishes the method for dosimetric multi-center credentialing. The results are promising and show a high level of gamma agreement and, the procedure is efficient, consistent and inexpensive. Funding has been provided from Department of Radiation Oncology, TROG Cancer Research and the University of Newcastle. Narges Miri is a recipient of a University of Newcastle postgraduate scholarship.« less

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

PubMed

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

PubMed Central

Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2013-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

PubMed

Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

2009-01-01

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

Unmasking glucose metabolism alterations in stable renal transplant recipients: a multicenter study.

PubMed

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-05-01

Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and beta blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention.

Multicenter Guidelines | Division of Cancer Prevention

Cancer.gov

A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

Multicenter User Evaluation of ACCU-CHEK® Combo, an Integrated System for Continuous Subcutaneous Insulin Infusion

PubMed Central

Kerr, David; Hoogma, Roel P.L.M; Buhr, Andreas; Petersen, Bettina; Storms, Fred E.M.G

2010-01-01

Background The aim of this study was to evaluate a newly developed system for insulin delivery incorporating a multifunctional blood glucose meter and a remotely controlled insulin pump (ACCU-CHEK® Combo system) in established pump users with type 1 diabetes. The technology was assessed both from device performance and subject usability perspectives. Method A multicenter, prospective, single group study was carried out in five centers in the Netherlands and four centers in the United Kingdom for more than 6 months. The study was divided into two phases: Phase 1 (4 weeks) for device validation purposes and phase 2 (22 weeks) to observe the impact of the system on metabolic control, patient satisfaction [using the Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and device safety. Results Eighty subjects completed the planned study period. There were no unexpected device errors. Treatment satisfaction was high at baseline and further increased to study end (DTSQ change version: sum score, 10.6 ± 7.2; scale score range, -18 to +18, p < 0.0001). Hemoglobin A1c improved continuously over time, from 7.9% (±0.9%) to 7.7% (±0.8%) at month 3 (p < 0.001) and 7.6% (±0.8%) at month 6 (p < 0.0001). The frequency of severe hypoglycemia was 0.08 per patient years. There was no case of ketoacidosis. Conclusions The new system was evaluated by experienced continuous subcutaneous insulin infusion users as safe in daily practice and associated with favorable treatment satisfaction and a modest improvement in glycemic control. PMID:21129336

Accuracy of a computer-aided surgical simulation protocol for orthognathic surgery: a prospective multicenter study.

PubMed

Hsu, Sam Sheng-Pin; Gateno, Jaime; Bell, R Bryan; Hirsch, David L; Markiewicz, Michael R; Teichgraeber, John F; Zhou, Xiaobo; Xia, James J

2013-01-01

The purpose of this prospective multicenter study was to assess the accuracy of a computer-aided surgical simulation (CASS) protocol for orthognathic surgery. The accuracy of the CASS protocol was assessed by comparing planned outcomes with postoperative outcomes of 65 consecutive patients enrolled from 3 centers. Computer-generated surgical splints were used for all patients. For the genioplasty, 1 center used computer-generated chin templates to reposition the chin segment only for patients with asymmetry. Standard intraoperative measurements were used without the chin templates for the remaining patients. The primary outcome measurements were the linear and angular differences for the maxilla, mandible, and chin when the planned and postoperative models were registered at the cranium. The secondary outcome measurements were the maxillary dental midline difference between the planned and postoperative positions and the linear and angular differences of the chin segment between the groups with and without the use of the template. The latter were measured when the planned and postoperative models were registered at the mandibular body. Statistical analyses were performed, and the accuracy was reported using root mean square deviation (RMSD) and the Bland-Altman method for assessing measurement agreement. In the primary outcome measurements, there was no statistically significant difference among the 3 centers for the maxilla and mandible. The largest RMSDs were 1.0 mm and 1.5° for the maxilla and 1.1 mm and 1.8° for the mandible. For the chin, there was a statistically significant difference between the groups with and without the use of the chin template. The chin template group showed excellent accuracy, with the largest positional RMSD of 1.0 mm and the largest orientation RMSD of 2.2°. However, larger variances were observed in the group not using the chin template. This was significant in the anteroposterior and superoinferior directions and the in pitch and yaw orientations. In the secondary outcome measurements, the RMSD of the maxillary dental midline positions was 0.9 mm. When registered at the body of the mandible, the linear and angular differences of the chin segment between the groups with and without the use of the chin template were consistent with the results found in the primary outcome measurements. Using this computer-aided surgical simulation protocol, the computerized plan can be transferred accurately and consistently to the patient to position the maxilla and mandible at the time of surgery. The computer-generated chin template provides greater accuracy in repositioning the chin segment than the intraoperative measurements. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

PubMed Central

Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

2014-01-01

Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

Patient-Related Determinants of the Administration of Continuous Palliative Sedation in Hospices and Palliative Care Units: A Prospective, Multicenter, Observational Study.

PubMed

van Deijck, Rogier H P D; Hasselaar, Jeroen G J; Verhagen, Stans C A H H V M; Vissers, Kris C P; Koopmans, Raymond T C M

2016-05-01

Knowledge of determinants that are associated with the administration of continuous palliative sedation (CPS) helps physicians identify patients who are at risk of developing refractory symptoms, thereby enabling proactive care planning. This study aims to explore which patient-related factors at admission are associated with receiving CPS later in the terminal phase of life. A prospective multicenter observational study was performed in six Dutch hospices and three nursing home-based palliative care units. The association between patient-related variables at admission (age, gender, diagnosis, use of opioids or psycholeptics, number of medications, Karnofsky Performance Status scale score, Edmonton Symptom Assessment System distress score, and Glasgow Coma Scale score) and the administration of CPS at the end of life was analyzed. A total of 467 patients died during the study period, of whom 130 received CPS. In univariate analysis, statistically significant differences were noted between the sedated and nonsedated patients with respect to younger age (P = 0.009), malignancy as a diagnosis (P = 0.05), higher Karnofsky Performance Status score (P = 0.03), the use of opioids (P < 0.001), the use of psycholeptics (P = 0.003), and higher Edmonton Symptom Assessment System distress score (P = 0.05). Multivariate logistic regression analysis showed that only the use of opioids at admission (odds ratio 1.90; 95% confidence interval 1.18-3.05) was significantly associated with the administration of CPS. Physicians should be aware that patients who use opioids at admission have an increased risk for the administration of CPS at the end of life. In this group of patients, a comprehensive personalized care plan starting at admission is mandatory to try to prevent the development of refractory symptoms. Further research is recommended, to identify other determinants of the administration of CPS and to investigate which early interventions will be effective to prevent the need for CPS in patients at high risk. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A randomized controlled multimodal behavioral intervention trial for improving antiepileptic drug adherence.

PubMed

Pakpour, Amir H; Gholami, Maryam; Esmaeili, Ravanbakhsh; Naghibi, Seyed Abolhasan; Updegraff, John A; Molloy, Gerard J; Dombrowski, Stephan U

2015-11-01

Medication nonadherence is one of the most important reasons for treatment failure in patients with epilepsy. The present study investigated the effectiveness of a multicomponent intervention to improve adherence to antiepileptic drug (AED) medication in patients with epilepsy. In a prospective, randomized multicenter trial, three sessions of face-to-face motivational interviewing (MI) in combination with complementary behavior change techniques were compared with standard care. Motivational interviewing prompted change talk and self-motivated statements from the patients, planning their own medication intake regimen and also identifying and overcoming barriers that may prevent adherence. Participants were provided with calendars to self-monitor their medication taking behavior. A family member and the health-care team were invited to attend the last session of MI in order to improve the collaboration and communication between patients, their caregiver or family member, and their health-care provider. At baseline and 6-month follow-up, psychosocial variables and medical adherence were assessed. In total, 275 participants were included in the study. Compared with the active control group, patients in the intervention group reported significantly higher medication adherence, as well as stronger intention and perceptions of control for taking medication regularly. The intervention group also reported higher levels of action planning, coping planning, self-monitoring, and lower medication concerns. This study shows that MI can be effective in clinical practice to improve medication adherence in patients with epilepsy. It also provides evidence that combining volitional interventions, including action planning, coping planning, and self-monitoring with motivational interviewing can promote the effectiveness of the medical treatments for epilepsy by improving adherence. Copyright © 2015 Elsevier Inc. All rights reserved.

Change in Care Dependency of Stroke Patients: A Longitudinal and Multicenter Study.

PubMed

Nursiswati, Nursiswati; Halfens, Ruud J G; Lohrmann, Christa

2017-06-01

The study was conducted to investigate the change of care dependency in stroke patients from inpatient wards and outpatient units in Indonesia. This study is longitudinal and multicentered. One hundred and nine patients were included from four hospitals on the island of Java. Care dependency was assessed using the Indonesian version of the 15-item Care Dependency Scale (CDS) at five points in time: at inpatient wards for admission and discharge and at outpatient units after discharge in the 1st week, the 5th week, and the 13th week. Most of the patients were male (65.1%), and diagnosed with ischemic stroke (71.5%). The results showed that care dependency in stroke patients decreased significantly from admission to discharge, as well as from the 5th to the 13th week as measured by the CDS. At admission, 23.0% of the patients were completely dependent on care, and at the 13th week about 1.0% were. Patients' care dependency decreased significantly in all care dependency items of the CDS in the inpatient ward, but five care dependency items of the CDS did not significantly decrease in the outpatient unit. Based on the findings of this study, we recommend that hospital-based and community-based services should include continual care dependence monitoring using this comprehensive instrument. Care dependency is subject to change over time, therefore nurses have to plan and tailor adequate nursing care measures to patient needs in the different stages, especially with respect to the aspect of mobility. Copyright © 2017. Published by Elsevier B.V.

CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures

PubMed Central

2014-01-01

Background Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). Methods/Design CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. Discussion CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. Trial registration number ClinicalTrials.gov: NCT01828905 PMID:24606670

Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study.

PubMed

Mantke, Rene; Diener, Markus; Kropf, Siegfried; Otto, Ronny; Manger, Thomas; Vestweber, Boris; Mirow, Lutz; Winde, Günther; Lippert, Hans

2016-09-07

Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients' perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http://www.webcitation.org/6jK6ZVyUs).

Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

PubMed

Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

2013-10-01

Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martens, Milou H., E-mail: mh.martens@hotmail.com; Department of Surgery, Maastricht University Medical Center, Maastricht; GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3more » different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypT« less

Fesoterodine prescription fill patterns and evaluation of the YourWay patient support plan for patients with overactive bladder symptoms and physicians.

PubMed

Trocio, Jeffrey N; Brubaker, Linda; Schabert, Vernon F; Bavendam, Tamara; Chen, Chieh-I; Zou, Kelly H; Petrilla, Allison A; Burgio, Kathryn L

2014-05-01

Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication. To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan. In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay. Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences. Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

Variability of the institutional review board process within a national research network.

PubMed

Khan, Muhammad A; Barratt, Michelle S; Krugman, Scott D; Serwint, Janet R; Dumont-Driscoll, Marilyn

2014-06-01

To determine the variability of the institutional review board (IRB) process for a minimal risk multicenter study. Participants included 24 Continuity Research Network (CORNET) sites of the Academic Pediatric Association that participated in a cross-sectional study. Each site obtained individual institutional IRB approval. An anonymous questionnaire went to site investigators about the IRB process at their institution. Twenty-two of 24 sites (92%) responded. Preparation time ranged from 1 to 20 hours, mean of 7.1 hours. Individuals submitting ≤3 IRB applications/year required more time for completion than those submitting >3/year (P < .05). Thirteen of 22 (59%) study sites received approval with "exempt" status, and 6 (27%) approved as "expedited" studies. IRB experiences were highly variable across study sites. These findings indicate that multicenter research projects should anticipate barriers to timely study implementation. Improved IRB standardization or centralization for multicenter clinical studies would facilitate this type of practice-based clinical research.

IMpact of Platelet Rich plasma OVer alternative therapies in patients with lateral Epicondylitis (IMPROVE): protocol for a multicenter randomized controlled study: a multicenter, randomized trial comparing autologous platelet-rich plasma, autologous whole blood, dry needle tendon fenestration, and physical therapy exercises alone on pain and quality of life in patients with lateral epicondylitis.

PubMed

Chiavaras, Mary M; Jacobson, Jon A; Carlos, Ruth; Maida, Eugene; Bentley, Todd; Simunovic, Nicole; Swinton, Marilyn; Bhandari, Mohit

2014-09-01

Lateral epicondylitis, commonly known as tennis elbow, is the most common cause of lateral elbow pain and the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting. Many therapeutic options, including conservative, surgical, and minimally invasive procedures, have been advocated for the treatment of lateral epicondylitis. Although numerous small studies have been performed to assess the efficacy of various treatments, there are conflicting results with no clear consensus on the optimal treatment. In an economic environment with limited health care resources, it is paramount that optimal cost-effective therapies with favorable patient-important outcomes be identified. This is a protocol paper which outlines a multicenter, multidisciplinary, single-blinded, four-arm randomized controlled trial, comparing platelet-rich plasma (PRP), whole blood injection, dry needle tendon fenestration, and sham injection with physical therapy alone for the treatment of lateral epicondylitis. Patients are screened based on pre-established eligibility criteria and randomized to one of the four study groups using an Internet-based system. The patients are followed at 6-week, 12-week, 24-week, and 52-week time points to assess the primary and secondary outcomes of the study. The primary outcome is pain. Secondary outcomes include health-related quality of life and ultrasound appearance of the common extensor tendon. Two university centers (McMaster University and the University of Michigan) are currently recruiting patients. We have planned a sample size of 100 patients (25 patients per arm) to ensure over 80% power to detect a three-point difference in pain scores at 52 weeks of follow-up. This study has ethics approval from the McMaster University Research Ethics Board (REB# 12-146) and the University of Michigan Institutional Review Board (IRB# HUM00067750). Successful completion of this proposed study will significantly impact clinical practice and enhance patients' lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in ultrasound-guided interventions will follow. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Habitat Demonstration Unit Project Leadership and Management Strategies

NASA Technical Reports Server (NTRS)

Kennedy, Kriss J.

2011-01-01

This paper gives an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) project leadership and management strategies. The HDU project team constructed and tested an analog prototype lunar surface habitat/laboratory called the Pressurized Excursion Module (PEM) during 2010. The prototype unit subsystems were integrated in a short amount of time, utilizing a tiger team approach that brought together over 20 habitation-related technologies and innovations from a variety of NASA centers. This paper describes the leadership and management strategies as well as lessons learned pertaining to leading and managing a multi-center diverse team in a rapid prototype environment. The PEM configuration went from a paper design to an operational surface habitat demonstration unit in less than 12 months. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Exploration Mission Systems Office (EMSO) to test destination elements in analog environments. The 2011 HDU-Deep Space Habitat (DSH) configuration will build upon the PEM work, and emphasize validity of crew operations (remote working and living), EVA operations, mission operations, logistics operations, and science operations that might be required in a deep space context for Near Earth Object (NEO) exploration mission architectures. The 2011 HDU-DSH will be field-tested during the 2011 Desert Research and Technologies Studies (DRaTS) field tests. The HDU project is a "technology-pull" project that integrates technologies and innovations from multiple NASA centers. This project will repurpose the HDU 2010 demo unit that was field tested in the 2010 DRaTS, adding habitation functionality to the prototype unit. This paper will describe the strategy of establishing a multi-center project management team that put in place the key multi-center leadership skills and disciplines to enable a successful tiger team approach. Advocacy was established with key stakeholders and NASA Headquarters (HQ) by defining a strategic vision, mission, goals and objectives for the project and team. As a technology-pull testbed capability the HDU project was able to collaborate and leverage the Exploration Technology Development Program (ETDP) and individual NASA center investments which capitalized on their respective center core competencies and skills. This approach enable the leveraging of over $7.5m of value to create an operational habitat demonstration unit 2010 PEM configuration.

Spine device clinical trials: design and sponsorship.

PubMed

Cher, Daniel J; Capobianco, Robyn A

2015-05-01

Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

Contraceptive use and family planning after labor in the European part of the Russian Federation: 2-year monitoring.

PubMed

Vikhlyaeva, E; Nikolaeva, E; Brandrup-Lukanow, A

2001-12-01

To explore the main determinants of the reproductive behavior of nursing mothers, all inhabitants of the central part of the European region of the Russian Federation, their use of modern contraceptive methods and their attitude to future family planning. Open cohort multicenter study of 1200 nursing mothers aged 16-42 years interviewed at 3-5 days' postpartum, with subsequent longitudinal monitoring ofthe majority in the local family planning centers during the 2 years after labor. The main determinants of the reproductive behavior of this cohort of women are an early debut of sexual activity, several partners in their reproductive history, relatively early marriage with a motivation to have one child in their family and the tendency to use induced abortion as one of the methods of birth regulation. Our experience of postpartum counselling demonstrated positive changes in the women's attitudes to modern contraceptive methods. The data reveal that the induced abortion rate among 639 mothers regularly followed-up during the first year postpartum was 4.4%, and among 606 during the second year was 5.1%. The corresponding rates among 129 women who did not visit the family planning centers and who were only interviewed 2 years after labor were 9.3% and 8.5%, respectively. Our data show that the unmet needs are remarkably concentrated among women who have given birth within the last year or two, and who need augmented attention from the family planning and reproductive health services.

Factors Influencing Medical Student Attrition and Their Implications in a Large Multi-Center Randomized Education Trial

ERIC Educational Resources Information Center

Kalet, A.; Ellaway, R. H.; Song, H. S.; Nick, M.; Sarpel, U.; Hopkins, M. A.; Hill, J.; Plass, J. L.; Pusic, M. V.

2013-01-01

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the…

Alcohol Consumption among University Students in North Rhine-Westphalia, Germany--Results from a Multicenter Cross-Sectional Study

ERIC Educational Resources Information Center

Akmatov, Manas K.; Mikolajczyk, Rafael T.; Meier, Sabine; Kramer, Alexander

2011-01-01

Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information…

Identification and Validation of Established and Novel Biomarkers for Infections in Burns

DTIC Science & Technology

2017-10-01

in burn patients have been proposed, but not validated. In our four site study , we are enrolling severely burned adults and children , and...identify the early stages of infection prior to clinical detection. This multicenter study will enable us to identify novel biomarkers, validate whether...a multicenter study 3. Develop a model of prediction of infection using clinical data and proteomic information. Relevance: 5% of combat-sustained

Theoretical study of electron impact triple differential cross sections of N2O by a multicenter distorted-wave method

NASA Astrophysics Data System (ADS)

Gong, Maomao; Li, Xingyu; Zhang, Song Bin; Chen, Xiangjun

2018-05-01

A coplanar asymmetric (e, 2e) measurement on N2O has been reported in 1999 by Cavanagh and Lohmann (1999 J. Phys. B: At. Mol. Opt. Phys. 32 L261), however, the relevant ab initio theoretical study is not available even up to now. In this work, we report theoretical studies of (e, 2e) triple differential cross sections of N2O at the same kinematics using a multicenter distorted-wave method. The influence of the multicenter nature of N2O molecule on the continuum wave function of the ejected electron has been largely considered. The computed results show good agreement with the experimental data for both outer valence 2π and inner valence 4σ orbitals.

Who Donates Their Body to Science? An International, Multicenter, Prospective Study

ERIC Educational Resources Information Center

Cornwall, Jon; Perry, Gary F.; Louw, Graham; Stringer, Mark D.

2012-01-01

The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of…

Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

PubMed Central

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-01-01

Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

Economic analysis of centralized vs. decentralized electronic data capture in multi-center clinical studies.

PubMed

Walden, Anita; Nahm, Meredith; Barnett, M Edwina; Conde, Jose G; Dent, Andrew; Fadiel, Ahmed; Perry, Theresa; Tolk, Chris; Tcheng, James E; Eisenstein, Eric L

2011-01-01

New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models. We developed clinical research network economic models to evaluate three data management models: centralized, decentralized with local software, and decentralized with shared database. Descriptive information from three clinical research studies served as inputs for these models. The primary outcome was total data management costs. Secondary outcomes included: data management costs for sites, local data centers, and central coordinating centers. Both decentralized models were more costly than the centralized model for each clinical research study: the decentralized with local software model was the most expensive. Decreasing the number of local data centers and case book pages reduced cost differentials between models. Decentralized vs. centralized data management in multi-center clinical research studies is associated with increases in data management costs.

Economic Analysis of Centralized vs. Decentralized Electronic Data Capture in Multi-Center Clinical Studies

PubMed Central

Walden, Anita; Nahm, Meredith; Barnett, M. Edwina; Conde, Jose G.; Dent, Andrew; Fadiel, Ahmed; Perry, Theresa; Tolk, Chris; Tcheng, James E.; Eisenstein, Eric L.

2012-01-01

Background New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models. Methods We developed clinical research network economic models to evaluate three data management models: centralized, decentralized with local software, and decentralized with shared database. Descriptive information from three clinical research studies served as inputs for these models. Main Outcome Measures The primary outcome was total data management costs. Secondary outcomes included: data management costs for sites, local data centers, and central coordinating centers. Results Both decentralized models were more costly than the centralized model for each clinical research study: the decentralized with local software model was the most expensive. Decreasing the number of local data centers and case book pages reduced cost differentials between models. Conclusion Decentralized vs. centralized data management in multi-center clinical research studies is associated with increases in data management costs. PMID:21335692

Positive and negative psychosocial impact of being diagnosed with cancer as an adolescent or young adult.

PubMed

Bellizzi, Keith M; Smith, Ashley; Schmidt, Steven; Keegan, Theresa H M; Zebrack, Brad; Lynch, Charles F; Deapen, Dennis; Shnorhavorian, Margarett; Tompkins, Bradley J; Simon, Michael

2012-10-15

The objective of this study was to explore the psychosocial impact of cancer on newly diagnosed adolescent and young adult (AYA) cancer patients. This was a population-based, multicenter study of 523 newly diagnosed AYA survivors (ages 15-39 years) of germ cell cancer (n = 204), non-Hodgkin lymphoma (n = 131), Hodgkin lymphoma (n = 142), acute lymphocytic leukemia (n = 21), or sarcoma (n = 25) from 7 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registries. Age at diagnosis was categorized into 3 groups (ages 15-20 years, 21-29 years, and 30-39 years). Respondents (43% response rate), on average (±standard deviation), were aged 29 = 6.7 years, and most patients (80.1%) were not receiving treatment at the time the completed the survey. With modest differences between the age groups, the most prevalent areas of life impacted in a negative way were financial, body image, control over life, work plans, relationship with spouse/significant other, and plans for having children. Endorsement of positive life impact items also was evident across the 3 age groups, particularly with regard to relationships, future plans/goals, and health competence. The current results indicated that there will be future need for interventions targeting financial assistance, body image issues, relationships, and helping AYAs to attain their education objectives. Copyright © 2012 American Cancer Society.

Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis.

PubMed

Murata, Yoko; Song, Michael; Kikuchi, Hisayuki; Hisamichi, Katsuya; Xu, Xie L; Greenspan, Andrew; Kato, Mai; Chiou, Chiun-Fang; Kato, Takeshi; Guzzo, Cynthia; Thurmond, Robin L; Ohtsuki, Mamitaro; Furue, Masutaka

2015-02-01

This trial was conducted to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4 R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect. © 2014 Japanese Dermatological Association.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

PubMed

Nakai, Yousuke; Yamamoto, Ryuichi; Matsuyama, Masato; Sakai, Yuji; Takayama, Yukiko; Ushio, Jun; Ito, Yukiko; Kitamura, Katsuya; Ryozawa, Shomei; Imamura, Tsunao; Tsuchida, Kouhei; Hayama, Jo; Itoi, Takao; Kawaguchi, Yoshiaki; Yoshida, Yu; Sugimori, Kazuya; Shimura, Kenji; Mizuide, Masafumi; Iwai, Tomohisa; Nishikawa, Ko; Yagioka, Hiroshi; Nagahama, Masatsugu; Toda, Nobuo; Saito, Tomotaka; Yasuda, Ichiro; Hirano, Kenji; Togawa, Osamu; Nakamura, Kenji; Maetani, Iruru; Sasahira, Naoki; Isayama, Hiroyuki

2018-05-01

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial.

PubMed

Günter, Christina Irene; Bader, Augustinus; Dornseifer, Ulf; Egert, Silvia; Dunda, Sebastian; Grieb, Gerrit; Wolter, Thomas; Pallua, Norbert; von Wild, Tobias; Siemers, Frank; Mailänder, Peter; Thamm, Oliver; Ernert, Carsten; Steen, Michael; Sievers, Reiner; Reichert, Bert; Rahmanian-Schwarz, Afshin; Schaller, Hans; Hartmann, Bernd; Otte, Max; Kehl, Victoria; Ohmann, Christian; Jelkmann, Wolfgang; Machens, Hans-Günther

2013-05-03

Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824.

Prospective Multicenter Study of Pneumocystis jirovecii Colonization among Cystic Fibrosis Patients in France

PubMed Central

Hernández-Hernández, Francisca; Fréalle, Emilie; Caneiro, Patrick; Salleron, Julia; Durand-Joly, Isabelle; Accoceberry, Isabelle; Bouchara, Jean-Philippe; Wallaert, Benoit; Dei-Cas, Eduardo

2012-01-01

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of Pseudomonas aeruginosa colonization and a greater forced expiratory volume in 1 s. Results are discussed considering the natural history of CF. PMID:23015669

Prospective multicenter study of Pneumocystis jirovecii colonization among cystic fibrosis patients in France.

PubMed

Hernández-Hernández, Francisca; Fréalle, Emilie; Caneiro, Patrick; Salleron, Julia; Durand-Joly, Isabelle; Accoceberry, Isabelle; Bouchara, Jean-Philippe; Wallaert, Benoit; Dei-Cas, Eduardo; Delhaes, Laurence

2012-12-01

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of Pseudomonas aeruginosa colonization and a greater forced expiratory volume in 1 s. Results are discussed considering the natural history of CF.

Multimodal neuroimaging in presurgical evaluation of drug-resistant epilepsy☆

PubMed Central

Zhang, Jing; Liu, Weifang; Chen, Hui; Xia, Hong; Zhou, Zhen; Mei, Shanshan; Liu, Qingzhu; Li, Yunlin

2013-01-01

Intracranial EEG (icEEG) monitoring is critical in epilepsy surgical planning, but it has limitations. The advances of neuroimaging have made it possible to reveal epileptic abnormalities that could not be identified previously and improve the localization of the seizure focus and the vital cortex. A frequently asked question in the field is whether non-invasive neuroimaging could replace invasive icEEG or reduce the need for icEEG in presurgical evaluation. This review considers promising neuroimaging techniques in epilepsy presurgical assessment in order to address this question. In addition, due to large variations in the accuracies of neuroimaging across epilepsy centers, multicenter neuroimaging studies are reviewed, and there is much need for randomized controlled trials (RCTs) to better reveal the utility of presurgical neuroimaging. The results of multiple studies indicate that non-invasive neuroimaging could not replace invasive icEEG in surgical planning especially in non-lesional or extratemporal lobe epilepsies, but it could reduce the need for icEEG in certain cases. With technical advances, multimodal neuroimaging may play a greater role in presurgical evaluation to reduce the costs and risks of epilepsy surgery, and provide surgical options for more patients with drug-resistant epilepsy. PMID:24282678

The interaction between equipoise and logistics in clinical trials: A case study.

PubMed

Warshaw, Meredith G; Carey, Vincent J; McFarland, Elizabeth J; Dawson, Liza; Abrams, Elaine; Melvin, Ann; Fairlie, Lee; Spiegel, Hans; Jay, Jonathan; Agwu, Allison L

2017-06-01

Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician's sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers' willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

Multicenter Collaborative Quality Assurance Program for the Province of Ontario, Canada: First-Year Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Létourneau, Daniel, E-mail: daniel.letourneau@rmp.uh.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; McNiven, Andrea

2013-05-01

Purpose: The objective of this work was to develop a collaborative quality assurance (CQA) program to assess the performance of intensity modulated radiation therapy (IMRT) planning and delivery across the province of Ontario, Canada. Methods and Materials: The CQA program was designed to be a comprehensive end-to-end test that can be completed on multiple planning and delivery platforms. The first year of the program included a head-and-neck (H and N) planning exercise and on-site visit to acquire dosimetric measurements to assess planning and delivery performance. A single dosimeter was used at each institution, and the planned to measured dose agreementmore » was evaluated for both the H and N plan and a standard plan (linear-accelerator specific) that was created to enable a direct comparison between centers with similar infrastructure. Results: CQA program feasibility was demonstrated through participation of all 13 radiation therapy centers in the province. Planning and delivery was completed on a variety of infrastructure (treatment planning systems and linear accelerators). The planning exercise was completed using both static gantry and rotational IMRT, and planned-to-delivered dose agreement (pass rates) for 3%/3-mm gamma evaluation were greater than 90% (92.6%-99.6%). Conclusions: All centers had acceptable results, but variation in planned to delivered dose agreement for the same planning and delivery platform was noted. The upper end of the range will provide an achievable target for other centers through continued quality improvement, aided by feedback provided by the program through the use of standard plans and simple test fields.« less

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Medical abortion options may advance in 1998.

PubMed

1997-12-01

The US debut of mifepristone (RU-486) was delayed in 1997 by legal and manufacturer problems. However, the Population Council is searching worldwide for companies to produce mifepristone for the US market. In the meantime, women in a number of US cities can obtain mifepristone through clinical trials coordinated by the New York City-based Abortion Rights Mobilization. The trials are evaluating the effectiveness of a 200 mg dosage of the drug and will continue until there is a commercial product. New developments in medical abortion will be announced in 1998. Currently, 29 Planned Parenthood Federation of America (PPFA) affiliates are recruiting women for its study of methotrexate and misoprostol. By midsummer 1998, the organization expects to have data from what is the largest multicenter trial to date of a methotrexate and misoprostol medical abortion regimen.

In vivo measurements of proton relaxation times in human brain, liver, and skeletal muscle: a multicenter MRI study.

PubMed

de Certaines, J D; Henriksen, O; Spisni, A; Cortsen, M; Ring, P B

1993-01-01

Quantitative magnetic resonance imaging may offer unique potential for tissue characterization in vivo. In this connection texture analysis of quantitative MR images may be of special importance. Because evaluation of texture analysis needs large data material, multicenter approaches become mandatory. Within the frame of BME Concerted Action on Tissue Characterization by MRI and MRS, a pilot multicenter study was launched in order to evaluate the technical problems including comparability of relaxation time measurements carried out in the individual sites. Human brain, skeletal muscle, and liver were used as models. A total of 218 healthy volunteers were studied. Fifteen MRI scanners with field strength ranging from 0.08 T to 1.5 T were induced. Measurement accuracy was tested on the Eurospin relaxation time test object (TO5) and the obtained calibration curve was used for correction of the in vivo data. The results established that, by following a standardized procedure, comparable quantitative measurements can be obtained in vivo from a number of MR sites. The overall variation coefficient in vivo was in the same order of magnitude as ex vivo relaxometry. Thus, it is possible to carry out international multicenter studies on quantitative imaging, provided that quality control with respect to measurement accuracy and calibration of the MR equipments are performed.

Center effect on ankle-brachial index measurement when using the reference method (Doppler and manometer): results from a large cohort study.

PubMed

Vierron, Emilie; Halimi, Jean-Michel; Tichet, Jean; Balkau, Beverley; Cogneau, Joel; Giraudeau, Bruno

2009-07-01

The ankle-brachial index (ABI) is a simple and noninvasive tool used to detect peripheral arterial disease (PAD). We aimed to assess, in a French multicenter cohort, the center effect associated with arterial pressure (AP) and ABI measurements using the reference method and using a semiautomatic device. This study included baseline and 9-year follow-up data from 3,664 volunteers of 10 health examination centers of the DESIR (Data from an Epidemiological Study on the Insulin Resistance) syndrome French cohort. Ankle and brachial AP were measured at inclusion by the reference method (a mercury sphygmomanometer coupled with a Doppler probe for ankle measurements) and at 9 years by a semiautomatic device (Omron HEM-705CP). The center effect was assessed by the intraclass correlation coefficient (ICC), ratio of the between-center variance to the total variance of the measurement. At inclusion, the sample mean age was 47.5 (s.d. 9.9) years; 49.3% were men. Although ICCs were smaller than 0.05 for brachial AP measurements, they were close to 0.18 and 0.20 for ankle systolic AP (SAP) and ABI measurements, respectively, when the reference method was used. No center effect for measures other than ankle SAP was detected. With the semiautomatic device method, all ICCs, including those for ankle SAP and ABI measurements, were between 0.005 and 0.04. We found an important center effect on ABI measured with a sphygmomanometer and a Doppler probe but not a semiautomatic device. A center effect should be taken into account when planning any multicenter study on ABI measurement.

Validation of STA-Liatest D-Di assay for exclusion of pulmonary embolism according to the latest Clinical and Laboratory Standard Institute/Food and Drug Administration guideline. Results of a multicenter management study.

PubMed

Pernod, Gilles; Wu, Haifeng; de Maistre, Emmanuel; Lazarchick, John; Kassis, Jeannine; Aguilar, Carlos; Vera, Pascual M; Palareti, Gualtiero; D'Angelo, Armando

2017-04-01

: Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population. This study was conducted following the CLSI guideline to upgrade the assay-intended use and obtain FDA clearance of STA-Liatest D-Di assay for pulmonary embolism exclusion in patient with low/moderate PTP. This was an international, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard of care setting. D-dimer assay was performed in consecutive, ambulatory outpatients suspected of pulmonary embolism, with low/moderate PTP, and without medical conditions or in clinical settings known to alter default D-dimer values regardless of the presence of thrombosis using a threshold of 0.5 μg/ml (fibrinogen equivalent units) for venous thromboembolism exclusion. Results were used to determine test performance. Of 1141 patients who underwent D-dimer testing, 1060 had valid results and completed study as planned. STA-Liatest D-Di assay performance has exceeded the CLSI/FDA guidance requirements, with a sensitivity of 97.6% (95% confidence interval: 91.7-99.7%) and a negative predictive value of 99.7% (95% confidence interval: 99.0-100%). STA-Liatest D-Di assay has an excellent performance when used in combination with a PTP score in relevant patients and has the potential to minimize the economic healthcare burden avoiding unnecessary and expensive imaging tests.

A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals.

PubMed

Ichihara, Kiyoshi; Ozarda, Yesim; Barth, Julian H; Klee, George; Qiu, Ling; Erasmus, Rajiv; Borai, Anwar; Evgina, Svetlana; Ashavaid, Tester; Khan, Dilshad; Schreier, Laura; Rolle, Reynan; Shimizu, Yoshihisa; Kimura, Shogo; Kawano, Reo; Armbruster, David; Mori, Kazuo; Yadav, Binod K

2017-04-01

The IFCC Committee on Reference Intervals and Decision Limits coordinated a global multicenter study on reference values (RVs) to explore rational and harmonizable procedures for derivation of reference intervals (RIs) and investigate the feasibility of sharing RIs through evaluation of sources of variation of RVs on a global scale. For the common protocol, rather lenient criteria for reference individuals were adopted to facilitate harmonized recruitment with planned use of the latent abnormal values exclusion (LAVE) method. As of July 2015, 12 countries had completed their study with total recruitment of 13,386 healthy adults. 25 analytes were measured chemically and 25 immunologically. A serum panel with assigned values was measured by all laboratories. RIs were derived by parametric and nonparametric methods. The effect of LAVE methods is prominent in analytes which reflect nutritional status, inflammation and muscular exertion, indicating that inappropriate results are frequent in any country. The validity of the parametric method was confirmed by the presence of analyte-specific distribution patterns and successful Gaussian transformation using the modified Box-Cox formula in all countries. After successful alignment of RVs based on the panel test results, nearly half the analytes showed variable degrees of between-country differences. This finding, however, requires confirmation after adjusting for BMI and other sources of variation. The results are reported in the second part of this paper. The collaborative study enabled us to evaluate rational methods for deriving RIs and comparing the RVs based on real-world datasets obtained in a harmonized manner. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.

PubMed

Hequet, Delphine; Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians' opinion on the test results and the patients' degree of anxiety, difficulties with therapy and quality of life. Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher's exact test). Prosigna test results also decreased patients' anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers

PubMed Central

Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

Purpose The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna’s assay information on physicians’ adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Methods Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians’ opinion on the test results and the patients’ degree of anxiety, difficulties with therapy and quality of life. Results Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher’s exact test). Prosigna test results also decreased patients’ anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. Conclusions The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer. PMID:29045452

Computer-assisted versus non-computer-assisted preoperative planning of corrective osteotomy for extra-articular distal radius malunions: a randomized controlled trial.

PubMed

Leong, Natalie L; Buijze, Geert A; Fu, Eric C; Stockmans, Filip; Jupiter, Jesse B

2010-12-14

Malunion is the most common complication of distal radius fracture. It has previously been demonstrated that there is a correlation between the quality of anatomical correction and overall wrist function. However, surgical correction can be difficult because of the often complex anatomy associated with this condition. Computer assisted surgical planning, combined with patient-specific surgical guides, has the potential to improve pre-operative understanding of patient anatomy as well as intra-operative accuracy. For patients with malunion of the distal radius fracture, this technology could significantly improve clinical outcomes that largely depend on the quality of restoration of normal anatomy. Therefore, the objective of this study is to compare patient outcomes after corrective osteotomy for distal radius malunion with and without preoperative computer-assisted planning and peri-operative patient-specific surgical guides. This study is a multi-center randomized controlled trial of conventional planning versus computer-assisted planning for surgical correction of distal radius malunion. Adult patients with extra-articular malunion of the distal radius will be invited to enroll in our study. After providing informed consent, subjects will be randomized to two groups: one group will receive corrective surgery with conventional preoperative planning, while the other will receive corrective surgery with computer-assisted pre-operative planning and peri-operative patient specific surgical guides. In the computer-assisted planning group, a CT scan of the affected forearm as well as the normal, contralateral forearm will be obtained. The images will be used to construct a 3D anatomical model of the defect and patient-specific surgical guides will be manufactured. Outcome will be measured by DASH and PRWE scores, grip strength, radiographic measurements, and patient satisfaction at 3, 6, and 12 months postoperatively. Computer-assisted surgical planning, combined with patient-specific surgical guides, is a powerful new technology that has the potential to improve the accuracy and consistency of orthopaedic surgery. To date, the role of this technology in upper extremity surgery has not been adequately investigated, and it is unclear whether its use provides any significant clinical benefit over traditional preoperative imaging protocols. Our study will represent the first randomized controlled trial investigating the use of computer assisted surgery in corrective osteotomy for distal radius malunions. NCT01193010.

The Habitat Demonstration Unit Project Overview

NASA Technical Reports Server (NTRS)

Kennedy, Kriss J.; Grill, Tracy R.; Tri, Terry O.; Howe, Alan S.

2010-01-01

This paper will describe an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) Project. The HDU project is a "technology-pull" project that integrates technologies and innovations from numerous NASA centers. This project will be used to investigate and validate surface architectures, operations concepts, and requirements definition of various habitation concepts. The first habitation configuration this project will build and test is the Pressurized Excursion Module (PEM). This habitat configuration - the PEM - is based on the Constellation Architecture Scenario 12.1 concept of a vertically oriented habitat module. The HDU project will be tested as part of the 2010 Desert Research and Technologies Simulations (D-RATS) test objectives. The purpose of this project is to develop, integrate, test, and evaluate a habitat configuration in the context of the mission architectures and surface operation concepts. A multi-center approach will be leveraged to build, integrate, and test the PEM through a shared collaborative effort of multiple NASA centers. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Lunar Surface Systems Project Office (LSSPO) to test surface elements in a surface analog environment. The 2010 analog field test will include two Lunar Electric Rovers (LER) and the PEM among other surface demonstration elements. This paper will describe the overall objectives, its various habitat configurations, strategic plan, and technology integration as it pertains to the 2010 and 2011 field analog tests. To accomplish the development of the PEM from conception in June 2009 to rollout for operations in July 2010, the HDU project team is using a set of design standards to define the interfaces between the various systems of PEM and to the payloads, such as the Geology Lab, that those systems will support. Scheduled activities such as early fit-checks and the utilization of a habitat avionics test bed prior to equipment installation into PEM are planned to facilitate the integration process.

Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

NASA Technical Reports Server (NTRS)

Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; Mccaul, E. W., Jr.

1993-01-01

This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall program of instrument development and scientific measurement. The focus of current research and plans for next year are presented.

Web-based international studies in limited populations of pediatric leukemia.

PubMed

Valsecchi, Maria Grazia; Silvestri, Daniela; Covezzoli, Anna; De Lorenzo, Paola

2008-02-01

Recent progress in cancer research leads to the characterization of small subgroups of patients by genetic/biological features. Clinical studies in this setting are frequently promoted by international networks of independent researchers and are limited by practical and methodological constraints, not least the regulations recently issued by national and international institutions (EU Directive 2001/20/EC). We reviewed various methods in the design of international multicenter studies, with focus on randomized clinical trials. This paper reports our experience in planning and conducting international studies in childhood leukemia. We applied a decentralized study conduct based on a two-level structure, comprising a national and an international coordinating level. For the more recent trials this structure was implemented as a web-based system. This approach accommodates major legal requirements (e.g., safety reporting) and ensures Good Clinical Practice principles by implementing risk-oriented monitoring procedures. Setting up international non-commercial trials is increasingly complicated. Still, they are strongly needed for answering relevant questions in limited populations. (c) 2007 Wiley-Liss, Inc.

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

Success of Intubation Rescue Techniques after Failed Direct Laryngoscopy in Adults: A Retrospective Comparative Analysis from the Multicenter Perioperative Outcomes Group.

PubMed

Aziz, Michael F; Brambrink, Ansgar M; Healy, David W; Willett, Amy Wen; Shanks, Amy; Tremper, Tyler; Jameson, Leslie; Ragheb, Jacqueline; Biggs, Daniel A; Paganelli, William C; Rao, Janavi; Epps, Jerry L; Colquhoun, Douglas A; Bakke, Patrick; Kheterpal, Sachin

2016-10-01

Multiple attempts at tracheal intubation are associated with mortality, and successful rescue requires a structured plan. However, there remains a paucity of data to guide the choice of intubation rescue technique after failed initial direct laryngoscopy. The authors studied a large perioperative database to determine success rates for commonly used intubation rescue techniques. Using a retrospective, observational, comparative design, the authors analyzed records from seven academic centers within the Multicenter Perioperative Outcomes Group between 2004 and 2013. The primary outcome was the comparative success rate for five commonly used techniques to achieve successful tracheal intubation after failed direct laryngoscopy: (1) video laryngoscopy, (2) flexible fiberoptic intubation, (3) supraglottic airway as part of an exchange technique, (4) optical stylet, and (5) lighted stylet. A total of 346,861 cases were identified that involved attempted tracheal intubation. A total of 1,009 anesthesia providers managed 1,427 cases of failed direct laryngoscopy followed by subsequent intubation attempts (n = 1,619) that employed one of the five studied intubation rescue techniques. The use of video laryngoscopy resulted in a significantly higher success rate (92%; 95% CI, 90 to 93) than other techniques: supraglottic airway conduit (78%; 95% CI, 68 to 86), flexible bronchoscopic intubation (78%; 95% CI, 71 to 83), lighted stylet (77%; 95% CI, 69 to 83), and optical stylet (67%; 95% CI, 35 to 88). Providers most frequently choose video laryngoscopy (predominantly GlideScope [Verathon, USA]) to rescue failed direct laryngoscopy (1,122/1,619; 69%), and its use has increased during the study period. Video laryngoscopy is associated with a high rescue intubation success rate and is more commonly used than other rescue techniques.

Why Public Comments Matter: The Case of the National Institutes of Health Policy on Single Institutional Review Board Review of Multicenter Studies.

PubMed

Ervin, Ann-Margret; Taylor, Holly A; Ehrhardt, Stephan; Meinert, Curtis L

2018-03-06

In 2014, the National Institutes of Health (NIH) requested public comments on a draft policy requiring NIH-funded, U.S.-based investigators to use a single institutional review board (sIRB) for ethical review of multicenter studies. The authors conducted a directed content analysis and qualitative summary of the comments and discuss how they shaped the final policy. Two reviewers independently assessed support for the policy from a review of comments responding to the draft policy in 2016. A reviewer conducted an open text review to identify prespecified and additional comment themes. A second researcher reviewed 20% of the comments; discrepancies were resolved through discussion. The NIH received 167 comments: 65% (108/167) supportive of the policy, 23% (38/167) not supportive, and 12% (21/167) not indicating support. Clarifications or changes to the policy were suggested in 102/167 comments (61%). Criteria for selecting sIRBs were addressed in 32/102 comments (31%). Also addressed were IRB responsibilities (39/102; 38%), cost (27/102; 26%), the role of local IRBs (14/102; 14%), and allowable policy exceptions (19/102; 19%). The NIH further clarified or provided additional guidance for selection criteria, IRB responsibilities, and cost in the final policy (June 2016). Local IRB reviews and exemptions guidance were unchanged. In this case study, public comments were effective in shaping policy as the NIH modified provisions or planned supplemental guidance in response to comments. Yet critical knowledge gaps remain and empirical data are necessary. The NIH is considering mechanisms to support the establishment of best practices for sIRB implementation.

Technical Note: Relationships between gamma criteria and action levels: Results of a multicenter audit of gamma agreement index results.

PubMed

Crowe, Scott B; Sutherland, Bess; Wilks, Rachael; Seshadri, Venkatakrishnan; Sylvander, Steven; Trapp, Jamie V; Kairn, Tanya

2016-03-01

The aim of this work was to use a multicenter audit of modulated radiotherapy quality assurance (QA) data to provide a practical examination of gamma evaluation criteria and action level selection. The use of the gamma evaluation method for patient-specific pretreatment QA is widespread, with most commercial solutions implementing the method. Gamma agreement indices were calculated using the criteria 1%/1 mm, 2%/2 mm, 2%/3 mm, 3%/2 mm, 3%/3 mm, and 5%/3 mm for 1265 pretreatment QA measurements, planned at seven treatment centers, using four different treatment planning systems, delivered using three different delivery systems (intensity-modulated radiation therapy, volumetric-modulated arc therapy, and helical tomotherapy) and measured using three different dose measurement systems. The sensitivity of each pair of gamma criteria was evaluated relative to the gamma agreement indices calculated using 3%/3 mm. A linear relationship was observed for 2%/2 mm, 2%/3 mm, and 3%/2 mm. This result implies that most beams failing at 3%/3 mm would also fail for those criteria, if the action level was adjusted appropriately. Some borderline plans might be passed or failed depending on the relative priority (tighter tolerance) used for dose difference or distance to agreement evaluation. Dosimeter resolution and treatment modality were found to have a smaller effect on the results of QA measurements than the number of dimensions (2D or 3D) over which the gamma evaluation was calculated. This work provides a method (and a large sample of results) for calculating equivalent action levels for different gamma evaluation criteria. This work constitutes a valuable guide for clinical decision making and a means to compare published gamma evaluation results from studies using different evaluation criteria. More generally, the data provided by this work support the recommendation that gamma criteria that specifically prioritize the property of greatest clinical importance for each treatment modality of anatomical site should be selected when using gamma evaluations for modulated radiotherapy QA. It is therefore suggested that departments using the gamma evaluation as a QA analysis tool should consider the relative importance of dose difference and distance to agreement, when selecting gamma evaluation criteria.

The Medical Humanities Effect: a Pilot Study of Pre-Health Professions Students at the University of Rochester.

PubMed

Baker, Clayton J; Shaw, Margie Hodges; Mooney, Christopher J; Daiss, Susan Dodge-Peters; Clark, Stephanie Brown

2017-12-01

Qualitative and quantitative research on the impact of medical and health humanities teaching in baccalaureate education is sparse. This paper reviews recent studies of the impact of medical and health humanities coursework in pre-health professions education and describes a pilot study of baccalaureate students who completed semester-long medical humanities courses in the Division of Medical Humanities & Bioethics at the University of Rochester. The study format was an email survey. All participants were current or former baccalaureate students who had taken one or more courses in literature and narrative in medicine, bioethics, history of medicine, and/or visual arts and healthcare during the past four years. The survey gathered numerical data in several areas: demographic information, career plans, self-reported influence of coursework on educational and career plans, and self-reported influence of coursework on intellectual skills and abilities. It also gathered narrative commentary that elaborated on students' responses to the numerically-based questions. Notable findings from preliminary analysis of the data include higher scores of self-reported impact of the coursework on specific habits of mind and on preparedness for intended career rather than on gaining admission to future educational programs. Discussion of the results focuses on several potential future directions this type of study might take, including multi-center, longitudinal, and sequential approaches.

Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy

DTIC Science & Technology

2008-08-01

S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13 . SUPPLEMENTARY NOTES 14. ABSTRACT Background...GRG-defined population groups to the overall epidemic varied significantly (0 to 13 %). Consistent with findings shown in Figure 2c, the highest AFs...Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279: 389–393. 13 . Gonzalez E

The Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Studies: Design and Baseline Characteristics: ProgStar Report No. 1.

PubMed

Strauss, Rupert W; Ho, Alex; Muñoz, Beatriz; Cideciyan, Artur V; Sahel, José-Alain; Sunness, Janet S; Birch, David G; Bernstein, Paul S; Michaelides, Michel; Traboulsi, Elias I; Zrenner, Eberhart; Sadda, SriniVas; Ervin, Ann-Margret; West, Sheila; Scholl, Hendrik P N

2016-04-01

To describe the design and baseline characteristics of patients enrolled into 2 natural history studies of Stargardt disease (STGD1). Multicenter retrospective and prospective cohort studies. Three hundred sixty-five unique patients aged 6 years and older at baseline harboring disease-causing variants in the ABCA4 gene and with specified ocular lesions were enrolled from 9 centers in the United States and Europe. In the retrospective study, patients contributed medical record data from at least 2 and up to 4 visits for at least 1 examination modality: fundus autofluorescence (FAF), spectral-domain (SD) optical coherence tomography (SD OCT), and/or microperimetry (MP). The total observational period was at least 2 years and up to 5 years between single visits. Demographic and visual acuity (VA) data also were obtained. In the prospective study, eligible patients were examined at baseline using a standard protocol, with 6-month follow-up visits planned for a 2-year period for serial Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected VA, SD OCT, FAF, and MP. Design and rationale of a multicenter study to determine the progression of STGD1 in 2 large retrospective and prospective international cohorts. Detailed baseline characteristics of both cohorts are presented, including demographics, and structural and functional retinal metrics. Into the retrospective study, 251 patients (458 eyes) were enrolled; mean follow-up ± standard deviation was 3.9±1.6 years. At baseline, 36% had no or mild VA loss, and 47% of the study eyes had areas of definitely decreased autofluorescence (DDAF) with an average lesion area of 2.5±2.9 mm(2) (range, 0.02-16.03 mm(2)). Two hundred fifty-nine patients (489 eyes) were enrolled in the prospective study. At baseline, 20% had no or mild VA loss, and 64% had areas of DDAF with an average lesion area of 4.0±4.4 mm(2) (range, 0.03-24.24 mm(2)). The mean retinal sensitivity with MP was 10.8±5.0 dB. The ProgStar cohorts have baseline characteristics that encompass a wide range of disease severity and are expected to provide valuable data on progression based on serial quantitative measurements derived from multiple methods, which will be critical to the design of planned clinical trials. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Habitat Demonstration Unit Project: Leadership and Management Strategies for a Rapid Prototyping Project

NASA Technical Reports Server (NTRS)

Kennedy, Kriss J.; Toup, Larry; Gill, Tracy; Tri, Terry; Howe, Scott; Smitherman, David

2011-01-01

This paper gives an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) project leadership and management strategies being used by the NASA HDU team for a rapid prototyping project. The HDU project team constructed and tested an analog prototype lunar surface habitat/laboratory called the Pressurized Excursion Module (PEM) during 2010. The prototype unit subsystems were integrated in a short amount of time, utilizing a tiger team rapid prototyping approach that brought together over 20 habitation-related technologies and innovations from a variety of NASA centers. This paper describes the leadership and management strategies as well as lessons learned pertaining to leading and managing a multi-center diverse team in a rapid prototype environment. The PEM configuration went from a paper design to an operational surface habitat demonstration unit in less than 12 months. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Exploration Mission Systems Office (EMSO) to test destination elements in analog environments. The 2011 HDU-Deep Space Habitat (DSH) configuration will build upon the PEM work, and emphasize validity of crew operations (remote working and living), EVA operations, mission operations, logistics operations, and science operations that might be required in a deep space context for Near Earth Object (NEO) exploration mission architectures. The 2011 HDU-DSH will be field-tested during the 2011 Desert Research and Technologies Studies (DRaTS) field tests. The HDU project is a "technology-pull" project that integrates technologies and innovations from multiple NASA centers. This project will repurpose the HDU 2010 demo unit that was field tested in the 2010 DRaTS, adding habitation functionality to the prototype unit. This paper will describe the strategy of establishing a multi-center project management team that put in place the key multi-center leadership skills and disciplines to enable a successful tiger team approach. Advocacy was established with key stakeholders and NASA Headquarters (HQ) by defining a strategic vision, mission, goals and objectives for the project and team. As a technology-pull testbed capability the HDU project was able to collaborate and leverage the Exploration Technology Development Program (ETDP) and individual NASA center investments which capitalized on their respective center core competencies and skills. This approach enable the leveraging of over $7.5m of value to create an operational habitat demonstration unit 2010 PEM configuration.

The Facial Growth Pattern and the Amount of Palatal Bone Deficiency Relative to Cleft Size Should Be Considered in Treatment Planning

PubMed Central

2016-01-01

Background: The aim of this study is to determine the best surgical/orthodontic treatment plan for the complete bilateral and unilateral cleft lip and palate patient to achieve all treatment goals of facial aesthetics, speech, dental function, and psychosocial development. Methods: Review of 40 years of serial complete bilateral cleft lip and palate and complete unilateral cleft lip and palate dental casts and photographs from birth to adolescence, with serial cephs starting at 4 years. This was part of a multicenter international 3-dimensional palatal growth study of serial dental casts of patients who developed good speech, occlusion, and facial growth. Results: Nasoalveolar molding and gingivoperiosteoplasty were introduced without proven longitudinal benefits. The procedure bodily retruded the premaxilla, which “telescoped” backward causing synostosis at the premaxillary vomerine suture. The resulting midfacial recessiveness with an anterior dental crossbite can only be corrected by midfacial protraction or a Le Fort I surgery. Conclusions: Staged orthodontic/surgical treatment limiting premaxillary retraction forces to lip adhesion or forces that cause only premaxillary ventroflexion produce the best results. The palatal cleft should be closed between 18 and 24 months when the ratio of the cleft to the palatal size medial to the alveolar ridge is at least 10%. The protruding premaxilla should only be ventroflexed but never bodily retruded. The facial growth pattern and degree of palatal bone deficiency are the main items to be considered in treatment planning. PMID:27579230

Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702).

PubMed

Nishio, Teiji; Shirato, Hiroki; Ishikawa, Masayori; Miyabe, Yuki; Kito, Satoshi; Narita, Yuichirou; Onimaru, Rikiya; Ishikura, Satoshi; Ito, Yoshinori; Hiraoka, Masahiro

2014-05-01

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤ 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

Multicenter neonatal databases: Trends in research uses.

PubMed

Creel, Liza M; Gregory, Sean; McNeal, Catherine J; Beeram, Madhava R; Krauss, David R

2017-01-13

In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.

Reliability of 3-Dimensional Measures of Single-Leg Cross Drop Landing Across 3 Different Institutions: Implications for Multicenter Biomechanical and Epidemiological Research on ACL Injury Prevention.

PubMed

DiCesare, Christopher A; Bates, Nathaniel A; Barber Foss, Kim D; Thomas, Staci M; Wordeman, Samuel C; Sugimoto, Dai; Roewer, Benjamin D; Medina McKeon, Jennifer M; Di Stasi, Stephanie; Noehren, Brian W; Ford, Kevin R; Kiefer, Adam W; Hewett, Timothy E; Myer, Gregory D

2015-12-01

Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Controlled laboratory study. Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated.

Participation of a coordinating center pharmacy in a multicenter international study.

PubMed

Jeon, Jihyun Esther; Mighty, Janet; Lane, Karen; McBee, Nichol; Majkowski, Ryan; Mayo, Steven; Hanley, Daniel

2016-11-15

The activities of a coordinating center pharmacy (CCP) supporting a multicenter, international clinical trial are described. Serving in a research support role comparable to that of a commercial clinical trial supply company, a CCP within the Johns Hopkins Hospital Investigational Drug Service (JHH IDS) uses its management expertise and infrastructure to support multicenter trials, such as the recently completed Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage, Phase III (CLEAR III) trial. The role of the CCP staff in supporting the CLEAR III trial was overall investigational product (IP) management through coordination of IP-related operations to ensure high-quality care for study participants at study sites in the United States and abroad. For the CLEAR III trial, the CCP coordinated IP supply activities; provided education to site pharmacists; developed study-specific documents, including pharmacy manuals; communicated with trial stakeholders, including third-party IP distributors; monitored treatment assignments; and performed quality assurance monitoring to ensure compliance with institutional, state, federal, and international regulations regarding IP procurement and storage. Acting as a CCP for a multicenter international study poses a number of operational challenges while providing opportunities for the CCP to contribute to research of global importance and enrich the skill sets of its personnel. The development and implementation of the CCP at JHH IDS for the CLEAR III trial included several responsibilities, such as IP supply management, communication, and database, regulatory, and finance management. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Design of a pragmatic trial in minority children presenting to the emergency department with uncontrolled asthma: The CHICAGO Plan.

PubMed

Krishnan, Jerry A; Martin, Molly A; Lohff, Cortland; Mosnaim, Giselle S; Margellos-Anast, Helen; DeLisa, Julie A; McMahon, Kate; Erwin, Kim; Zun, Leslie S; Berbaum, Michael L; McDermott, Michael; Bracken, Nina E; Kumar, Rajesh; Margaret Paik, S; Nyenhuis, Sharmilee M; Ignoffo, Stacy; Press, Valerie G; Pittsenbarger, Zachary E; Thompson, Trevonne M

2017-06-01

Among children with asthma, black children are two to four times as likely to have an emergency department (ED) visit and die from asthma, respectively, compared to white children in the United States. Despite the availability of evidence-based asthma management guidelines, minority children are less likely than white children to receive or use effective options for asthma care. The CHICAGO Plan is a three-arm multi-center randomized pragmatic trial of children 5 to 11years old presenting to the ED with uncontrolled asthma that compares: [1] an ED-focused intervention to improve the quality of care on discharge to home, [2] the same ED-focused intervention together with a home-based community health worker (CHW)-led intervention, and [3] enhanced usual care. All children receive spacers for the metered dose inhaler and teaching about its use. The Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Scale and Satisfaction with Participation in Social Roles at 6months are the primary outcomes in children and in caregivers, respectively. Other patient-reported outcomes and indicators of healthcare utilization are assessed as secondary outcomes. Innovative features of the CHICAGO Plan include early and continuous engagement of children, caregivers, the Chicago Department of Public Health, and other stakeholders to inform the design and implementation of the study and a shared research infrastructure to coordinate study activities. The objective of this report is to describe the development of the CHICAGO Plan, including the methods and rationale for engaging stakeholders, the shared research infrastructure, and other features of the pragmatic clinical trial design. Published by Elsevier Inc.

Design of a pragmatic trial in minority children presenting to the emergency department with uncontrolled asthma: The CHICAGO Plan

PubMed Central

Krishnan, Jerry A.; Martin, Molly A.; Lohff, Cortland; Mosnaim, Giselle S.; Margellos-Anast, Helen; DeLisa, Julie A.; McMahon, Kate; Erwin, Kim; Zun, Leslie S.; Berbaum, Michael L.; McDermott, Michael; Bracken, Nina E.; Kumar, Rajesh; Paik, S. Margaret; Nyenhuis, Sharmilee M.; Ignoffo, Stacy; Press, Valerie G.; Pittsenbarger, Zachary E.; Thompson, Trevonne M.

2017-01-01

Among children with asthma, black children are two to four times as likely to have an emergency department (ED) visit and die from asthma, respectively, compared to white children in the United States. Despite the availability of evidence-based asthma management guidelines, minority children are less likely than white children to receive or use effective options for asthma care. The CHICAGO Plan is a three-arm multi-center randomized pragmatic trial of children 5 to 11 years old presenting to the ED with uncontrolled asthma that compares: (1) an ED-focused intervention to improve the quality of care on discharge to home, (2) the same ED-focused intervention together with a home-based community health worker (CHW)-led intervention, and (3) enhanced usual care. All children receive spacers for the metered dose inhaler and teaching about its use. The Patient-Reported Outcomes Measurement Information System (PROMIS) Asthma Impact Scale and Satisfaction with Participation in Social Roles at 6 months are the primary outcomes in children and in caregivers, respectively. Other patient-reported outcomes and indicators of healthcare utilization are assessed as secondary outcomes. Innovative features of the CHICAGO Plan include early and continuous engagement of children, caregivers, the Chicago Department of Public Health, and other stakeholders to inform the design and implementation of the study and a shared research infrastructure to coordinate study activities. The objective of this report is to describe the development of the CHICAGO Plan, including the methods and rationale for engaging stakeholders, the shared research infrastructure, and other features of the pragmatic clinical trial design. PMID:28366780

Suicidality in obsessive-compulsive disorder: prevalence and relation to symptom dimensions and comorbid conditions.

PubMed

Torres, Albina R; Ramos-Cerqueira, Ana Teresa A; Ferrão, Ygor A; Fontenelle, Leonardo F; do Rosário, Maria Conceição; Miguel, Euripedes C

2011-01-01

Suicidal thoughts and behaviors, also known as suicidality, are a fairly neglected area of study in patients with obsessive-compulsive disorder (OCD). To evaluate several aspects of suicidality in a large multicenter sample of OCD patients and to compare those with and without suicidal ideation, plans, and attempts according to demographic and clinical variables, including symptom dimensions and comorbid disorders. This cross-sectional study included 582 outpatients with primary OCD (DSM-IV) recruited between August 2003 and March 2008 from 7 centers of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. The following assessment instruments were used: the Yale-Brown Obsessive Compulsive Scale, the Dimensional Yale-Brown Obsessive Compulsive Scale, the Beck Depression and Anxiety Inventories, the Structured Clinical Interview for DSM-IV Axis I Disorders, and 6 specific questions to investigate suicidality. After univariate analyses, logistic regression analyses were performed to adjust the associations between the dependent and explanatory variables for possible confounders. Thirty-six percent of the patients reported lifetime suicidal thoughts, 20% had made suicidal plans, 11% had already attempted suicide, and 10% presented current suicidal thoughts. In the logistic regression, only lifetime major depressive disorder and posttraumatic stress disorder (PTSD) remained independently associated with all aspects of suicidal behaviors. The sexual/religious dimension and comorbid substance use disorders remained associated with suicidal thoughts and plans, while impulse-control disorders were associated with current suicidal thoughts and with suicide plans and attempts. The risk of suicidal behaviors must be carefully investigated in OCD patients, particularly those with symptoms of the sexual/religious dimension and comorbid major depressive disorder, PTSD, substance use disorders, and impulse-control disorders. © Copyright 2011 Physicians Postgraduate Press, Inc.

Multi-investigator collaboration in orthopaedic surgery research compared to other medical fields.

PubMed

Brophy, Robert H; Smith, Matthew V; Latterman, Christian; Jones, Morgan H; Reinke, Emily K; Flanigan, David C; Wright, Rick W; Wolf, Brian R

2012-10-01

An increasing emphasis has been placed across health care on evidence-based medicine with higher level studies, such as randomized trials and prospective cohort studies. Historically, clinical research in orthopaedic surgery has been dominated by studies with low patient numbers from a limited number of surgeons. The purpose of this study was to test our hypothesis that orthopaedics has fewer multi-center collaborative studies as compared to other medical disciplines. We chose three leading journals from general medicine, a leading journal from the surgical subspecialties of obstetrics and gynecology, ophthalmology and otolaryngology, and three leading journals from orthopaedic surgery based on highest impact factor. We compared the percentage of collaborative studies and the number of contributing institutions and authors in original research manuscripts published in 2009 between general medical, surgical subspecialty and orthopaedic surgery journals. A significantly higher percentage of manuscripts resulted from multicenter collaborative efforts in the general medical literature (p < 0.000001) and the other surgical subspecialty literature (p < 0.000001) compared to the orthopaedic surgery literature. Manuscripts published in the general medical journals came from more institutions (p < 0.0001) and had significantly more authors (p < 0.000001) than those published in the orthopaedic surgery journals. There is an opportunity to stimulate greater multicenter collaborative research, which correlates with increased patient numbers, a higher level of evidence and more generalizable findings, in the orthopaedic surgery community. These efforts can be supported through increased funding, surgeon participation, and appropriate expansion of authorship for multicenter studies in orthopaedic journals. Copyright © 2012 Orthopaedic Research Society.

Prevalence and Correlates of Direct Self-Injurious Behavior among Chinese Adolescents: Findings from a Multicenter and Multistage Survey.

PubMed

Xin, Xiuhong; Wang, Yuping; Fang, Jianqun; Ming, Qingsen; Yao, Shuqiao

2017-05-01

Direct self-injurious behavior (DSIB) has become an important focus due to its perniciousness and perplexity. Little is known about its prevalence and correlative factors in Chinese adolescents, including how data may differ according to gender. A multicenter, multistage stratified cluster random sampling was used to examine the previous 12-month prevalence of DSIB, as well as the possible correlates of demographics, risky behaviors, suicidality, and psychosocial factors associated with DSIB in a school-based sample of 11,880 students (49.5 % boys and 50.5 % girls). Approximately 30 % of the adolescents in the sample reported at least one incident of DSIB in the past 12-month period. After controlling for demographic variables, analyses of the independent relationships of DSIB with risky behaviors, suicidality, and psychosocial factors were conducted for each gender. Smoking, binge drinking, running away from home, suicide ideation, suicide plans, positive affect, and physical symptoms were identified as common factors associated with DSIB for both genders in the final model. In addition, truancy, fighting, physical inactivity, motor impulsiveness, and depressed affect were found to be related to DSIB in boys, whereas suicide attempts and somatic complaints were found to be related to DSIB in girls. Separation anxiety and social anxiety associated negatively with DSIB in boys and girls, respectively. DSIB was not found to independently relate to attention impulsiveness, non-planned impulsiveness, self-esteem, or harm avoidance in either genders. DSIB was prevalent in Chinese adolescents. Programs intended to promote physical and mental health in adolescents should take into account gender differences in DSIB-associated factors, including risky behaviors, suicidality, and psychosocial factors.

Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial.

PubMed

Moreso, Francesc; Crespo, Marta; Ruiz, Juan C; Torres, Armando; Gutierrez-Dalmau, Alex; Osuna, Antonio; Perelló, Manel; Pascual, Julio; Torres, Irina B; Redondo-Pachón, Dolores; Rodrigo, Emilio; Lopez-Hoyos, Marcos; Seron, Daniel

2018-04-01

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m 2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m 2 ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012-2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2 ± 14.4 vs. -6.6 ± 12.0 mL/min per 1.73 m 2 , P-value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P-value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Consistency of clinical biomechanical measures between three different institutions: implications for multi-center biomechanical and epidemiological research.

PubMed

Myer, Gregory D; Wordeman, Samuel C; Sugimoto, Dai; Bates, Nathaniel A; Roewer, Benjamin D; Medina McKeon, Jennifer M; DiCesare, Christopher A; Di Stasi, Stephanie L; Barber Foss, Kim D; Thomas, Staci M; Hewett, Timothy E

2014-05-01

Multi-center collaborations provide a powerful alternative to overcome the inherent limitations to single-center investigations. Specifically, multi-center projects can support large-scale prospective, longitudinal studies that investigate relatively uncommon outcomes, such as anterior cruciate ligament injury. This project was conceived to assess within- and between-center reliability of an affordable, clinical nomogram utilizing two-dimensional video methods to screen for risk of knee injury. The authors hypothesized that the two-dimensional screening methods would provide good-to-excellent reliability within and between institutions for assessment of frontal and sagittal plane biomechanics. Nineteen female, high school athletes participated. Two-dimensional video kinematics of the lower extremity during a drop vertical jump task were collected on all 19 study participants at each of the three facilities. Within-center and between-center reliability were assessed with intra- and inter-class correlation coefficients. Within-center reliability of the clinical nomogram variables was consistently excellent, but between-center reliability was fair-to-good. Within-center intra-class correlation coefficient for all nomogram variables combined was 0.98, while combined between-center inter-class correlation coefficient was 0.63. Injury risk screening protocols were reliable within and repeatable between centers. These results demonstrate the feasibility of multi-site biomechanical studies and establish a framework for further dissemination of injury risk screening algorithms. Specifically, multi-center studies may allow for further validation and optimization of two-dimensional video screening tools. 2b.

Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?

PubMed

Markar, Sheraz; Gronnier, Caroline; Duhamel, Alain; Pasquer, Arnaud; Théreaux, Jérémie; du Rieu, Mael Chalret; Lefevre, Jérémie H; Turner, Kathleen; Luc, Guillaume; Mariette, Christophe

2015-11-20

The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome. Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from SALV for persistent (n = 234) versus recurrent disease (n = 74) were compared. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. SALV versus NCRS groups: In-hospital mortality was similar in both groups (8.4% v 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and surgical site infection, which were both more frequent in the SALV group. At 3 years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free survival (39.2% v 32.8%; P = .232) after matching, along with a similar recurrence pattern. Persistent versus recurrent disease groups: There were no significant differences between groups in incidence of in-hospital mortality or major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease-free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease group. The results of this large multicenter study from the modern era suggest that SALV can offer acceptable short- and long-term outcomes in selected patients at experienced centers. Persistent cancer after definitive chemoradiotherapy seems to be more biologically aggressive, with poorer survival compared with recurrent cancer. © 2015 by American Society of Clinical Oncology.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

Multicenter validation of the VITEK MS v2.0 MALDI-TOF mass spectrometry system for the identification of fastidious gram-negative bacteria.

PubMed

Branda, John A; Rychert, Jenna; Burnham, Carey-Ann D; Bythrow, Maureen; Garner, Omai B; Ginocchio, Christine C; Jennemann, Rebecca; Lewinski, Michael A; Manji, Ryhana; Mochon, A Brian; Procop, Gary W; Richter, Sandra S; Sercia, Linda F; Westblade, Lars F; Ferraro, Mary Jane

2014-02-01

The VITEK MS v2.0 MALDI-TOF mass spectrometry system's performance in identifying fastidious gram-negative bacteria was evaluated in a multicenter study. Compared with the reference method (DNA sequencing), the VITEK MS system provided an accurate, species-level identification for 96% of 226 isolates; an additional 1% were accurately identified to the genus level. © 2013.

[Emergency contraception in Brazil: facilitators and barriers].

PubMed

Hardy, E; Duarte, G A; Osis, M J; Arce, X E; Possan, M

2001-01-01

A multi-centered qualitative study was conducted in Brazil, Chile, and Mexico to assess the acceptability of emergency contraception both among potential users and possible providers, authorities, and opinion-makers, and to identify (according to participants' perceptions) factors facilitating or hindering the method's use and the most appropriate strategies to disseminate information and provide the method. Data were collected through semi-structured interviews, group interviews, and discussion groups, which were tape-recorded and transcribed. A thematic analysis of this material was conducted. Acceptability of emergency contraception was high among participants, who also felt that there were no barriers towards its acceptance by the population. Participants felt that the method's acceptability would be greater if it were included in reproductive health programs, emphasizing its prescription for emergency situations. Participants highlighted that strategic components in Brazil would be training of providers and inclusion of the method in family planning services.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

PubMed

Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2015-09-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

PubMed Central

Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2014-01-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

PubMed

Schmitt, Manfred; Mengele, Karin; Napieralski, Rudolf; Magdolen, Viktor; Reuning, Ute; Gkazepis, Apostolos; Sweep, Fred; Brünner, Nils; Foekens, John; Harbeck, Nadia

2010-11-01

The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.

Clinical trials: bringing research to the bedside.

PubMed

Arvay, C A

1991-02-01

Over the years, clinical trials with their structured treatment plans and multicenter involvement have been instrumental in developing new treatments and establishing standard of care therapy. While clinical trials strive to advance medical knowledge, they provide scientifically sound, state of the art care and their use should be increased. The Brain Tumor Cooperative Group, one such NCI-sponsored cooperative group, has been the primary group for the treatment of malignant gliomas. As the field of neuro-oncology expands, the neuroscience nurse needs to develop an understanding of clinical trials and their operation. The nurse is in an optimal position to support medical research and the research participant.

Stories and Music for Adolescent/Young Adult Resilience During Transplant Partnerships: Strategies to Support Academic-Clinical Nurse Collaborations in Behavioral Intervention Studies.

PubMed

Hendricks-Ferguson, Verna L; Barnes, Yvonne J; Cherven, Brooke; Stegenga, Kristin; Roll, Lona; Docherty, Sharon L; Haase, Joan E

Evidence-based nursing is in the forefront of healthcare delivery systems. Federal and state agencies, academic institutions, and healthcare delivery systems recognize the importance of nursing research. This article describes the mechanisms that facilitate nursing partnerships yielding high-level research outcomes in a clinical setting. A phase-II multicenter behavioral intervention study with pediatric stem cell transplant patients was the context of this academic/clinical research partnership. Strategies to develop and maintain this partnership involved a thorough understanding of each nurse's focus and barriers. A variety of communication plans and training events maximized preexisting professional networks. Academic/clinical nurses' discussions identified barriers to the research process, the most significant being role conflict. Communication and validation of benefits to each individual and institution facilitated the research process during challenging times. Establishing strong academic/clinical partnerships should lead to evidence-based research outcomes for the nursing profession, healthcare delivery systems, and patients and families.

Reliability of 3-Dimensional Measures of Single-Leg Drop Landing Across 3 Institutions: Implications for Multicenter Research for Secondary ACL-Injury Prevention.

PubMed

Myer, Gregory D; Bates, Nathaniel A; DiCesare, Christopher A; Barber Foss, Kim D; Thomas, Staci M; Wordeman, Samuel C; Sugimoto, Dai; Roewer, Benjamin D; Medina McKeon, Jennifer M; Di Stasi, Stephanie L; Noehren, Brian W; McNally, Michael; Ford, Kevin R; Kiefer, Adam W; Hewett, Timothy E

2015-05-01

Due to the limitations of single-center studies in achieving appropriate sampling with relatively rare disorders, multicenter collaborations have been proposed to achieve desired sampling levels. However, documented reliability of biomechanical data is necessary for multicenter injury-prevention studies and is currently unavailable. To measure the reliability of 3-dimensional (3D) biomechanical waveforms from kinetic and kinematic variables during a single-leg landing (SLL) performed at 3 separate testing facilities. Multicenter reliability study. 3 laboratories. 25 female junior varsity and varsity high school volleyball players who visited each facility over a 1-mo period. Subjects were instrumented with 43 reflective markers to record 3D motion as they performed SLLs. During the SLL the athlete balanced on 1 leg, dropped down off of a 31-cm-high box, and landed on the same leg. Kinematic and kinetic data from both legs were processed from 2 trials across the 3 laboratories. Coefficients of multiple correlations (CMC) were used to statistically compare each joint angle and moment waveform for the first 500 ms of landing. Average CMC for lower-extremity sagittal-plane motion was excellent between laboratories (hip .98, knee .95, ankle .99). Average CMC for lower-extremity frontal-plane motion was also excellent between laboratories (hip .98, knee .80, ankle .93). Kinetic waveforms were repeatable in each plane of rotation (3-center mean CMC ≥.71), while knee sagittal-plane moments were the most consistent measure across sites (3-center mean CMC ≥.94). CMC waveform comparisons were similar relative to the joint measured to previously published reports of between-sessions reliability of sagittal- and frontal-plane biomechanics performed at a single institution. Continued research is needed to further standardize technology and methods to help ensure that highly reliable results can be achieved with multicenter biomechanical screening models.

Comprehensive Multicenter Graduate Surgical Education Initiative Incorporating Entrustable Professional Activities, Continuous Quality Improvement Cycles, and a Web-Based Platform to Enhance Teaching and Learning.

PubMed

Anderson, Cheryl I; Basson, Marc D; Ali, Muhammad; Davis, Alan T; Osmer, Robert L; McLeod, Michael K; Haan, Pam S; Molnar, Robert G; Peshkepija, Andi N; Hardaway, John C; Chojnacki, Karen A; Pfeifer, Christopher C; Gauvin, Jeffrey M; Jones, Mark W; Mansour, M Ashraf

2018-07-01

It is increasingly important for faculty to teach deliberately and provide timely, detailed, and formative feedback on surgical trainee performance. We initiated a multicenter study to improve resident evaluative processes and enhance teaching and learning behaviors while engaging residents in their education. Faculty from 7 US postgraduate training programs rated resident operative performances using the perioperative briefing, intraoperative teaching, debriefing model, and rated patient visits/academic performances using the entrustable professional activities model via a web-based platform. Data were centrally analyzed and iterative changes made based on participant feedback, individual preferences, and database refinements, with trends addressed using the Plan, Do, Check, Act improvement methodology. Participants (92 surgeons, 150 residents) submitted 3,880 assessments during July 2014 through September 2017. Evidence of preoperative briefings improved from 33.9% ± 2.5% to 95.5% ± 1.5% between April and September 2014 compared with April and September 2017 (p < 0.001). Postoperative debriefings improved from 10.6% ± 2.7% to 90.2% ± 2.5% (p < 0.001) for the same period. Meaningful self-reflection by residents improved from 28.6% to 67.4% (p < 0.001). The number of assessments received per resident during a 6-month period increased from 6.4 ± 6.2 to 13.4 ± 10.1 (p < 0.003). Surgeon-entered assessments increased from 364 initially to 685 in the final period, and the number of resident assessments increased from 308 to 445. We showed a 4-fold increase in resident observed activities being rated. By adopting recognized educational models with repeated Plan, Do, Check, Act cycles, we increased the quality of preoperative learning objectives, showed more frequent, detailed, and timely assessments of resident performance, and demonstrated more effective self-reflection by residents. We monitored trends, identified opportunities for improvement and successfully sustained those improvements over time, applying a team-based approach. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Implementation of a "No Fly" safety culture in a multicenter radiation medicine department.

PubMed

Potters, Louis; Kapur, Ajay

2012-01-01

The safe delivery of radiation therapy requires multiple disciplines and interactions to perform flawlessly for each patient. Because treatment is individualized and every aspect of the patient's care is unique, it is difficult to regiment a delivery process that works flawlessly. The purpose of this study is to describe one safety-directed component of our quality program called the "No Fly Policy" (NFP). Our quality assurance program for radiation therapy reviewed the entire process of care prior, during, and after a patient's treatment course. Each component of care was broken down and rebuilt within a matrix of multidisciplinary safety quality checklists (QCL). The QCL process map was subsequently streamlined with revised task due dates and stopping rules. The NFP was introduced to place a holding pattern on treatment initiation pending reconciliation of associated stopping events. The NFP was introduced in a pilot phase using a Six-Sigma process improvement approach. Quantitative analysis on the performance of the new QCLs was performed using crystal reports in the Oncology Information Systems. Root cause analysis was conducted. Notable improvements in QCL performance were observed. The variances among staff in completing tasks reduced by a factor of at least 3, suggesting better process control. Steady improvements over time indicated an increasingly compliant and controlled adoption of the new safety-oriented process map. Stopping events led to rescheduling treatments with average and maximum delays of 2 and 4 days, respectively, with no reported adverse effects. The majority of stopping events were due to incomplete plan approvals stemming from treatment planning delays. Whereas these may have previously solicited last-minute interventions, including intensity modulated radiation therapy quality assurance, the NFP enabled nonpunitive, reasonable schedule adjustments to mitigate compromises in safe delivery. Implementation of the NFP has helped to mitigate risk from expedited care, convert reactive to proactive delays, and created a checklist, process driven, and variance-reducing culture in a large, multicenter department. Copyright © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

SPIRIT trial: A phase III pragmatic trial of an advance care planning intervention in ESRD.

PubMed

Song, Mi-Kyung; Unruh, Mark L; Manatunga, Amita; Plantinga, Laura C; Lea, Janice; Jhamb, Manisha; Kshirsagar, Abhijit V; Ward, Sandra E

2018-01-01

Advance care planning (ACP) is a central tenet of dialysis care, but the vast majority of dialysis patients report never engaging in ACP discussions with their care providers. Over the last decade, we have developed and iteratively tested SPIRIT (Sharing Patient's Illness Representation to Increase Trust), a theory-based, patient- and family-centered advance care planning intervention. SPIRIT is a six-step, two-session, face-to-face intervention to promote cognitive and emotional preparation for end-of-life decision making for patients with ESRD and their surrogates. In these explanatory trials, SPIRIT was delivered by trained research nurses. Findings consistently revealed that patients and surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, and surrogates in SPIRIT reported significantly improved post-bereavement psychological outcomes after the patient's death compared to a no treatment comparison condition. As a critical next step, we are conducting an effectiveness-implementation study. This study is a multicenter, clinic-level cluster randomized pragmatic trial to evaluate the effectiveness of SPIRIT delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics, compared to usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, including sustainability. We will recruit 400 dyads of patients at high risk of death in the next year and their surrogates from 30 dialysis clinics in four states. This trial of SPIRIT will generate novel, meaningful insights about improving ACP in dialysis care. ClinicalTrials.govNCT03138564, registered 05/01/2017. Copyright © 2017 Elsevier Inc. All rights reserved.

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run.

PubMed

Kirisits, Christian; Federico, Mario; Nkiwane, Karen; Fidarova, Elena; Jürgenliemk-Schulz, Ina; de Leeuw, Astrid; Lindegaard, Jacob; Pötter, Richard; Tanderup, Kari

2015-12-01

Upfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). EMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1-10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. Overall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. The comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical Dural Tears.

PubMed

O'Neill, Kevin R; Fehlings, Michael G; Mroz, Thomas E; Smith, Zachary A; Hsu, Wellington K; Kanter, Adam S; Steinmetz, Michael P; Arnold, Paul M; Mummaneni, Praveen V; Chou, Dean; Nassr, Ahmad; Qureshi, Sheeraz A; Cho, Samuel K; Baird, Evan O; Smith, Justin S; Shaffrey, Christopher; Tannoury, Chadi A; Tannoury, Tony; Gokaslan, Ziya L; Gum, Jeffrey L; Hart, Robert A; Isaacs, Robert E; Sasso, Rick C; Bumpass, David B; Bydon, Mohamad; Corriveau, Mark; De Giacomo, Anthony F; Derakhshan, Adeeb; Jobse, Bruce C; Lubelski, Daniel; Lee, Sungho; Massicotte, Eric M; Pace, Jonathan R; Smith, Gabriel A; Than, Khoi D; Riew, K Daniel

2017-04-01

Retrospective multicenter case series study. Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements ( P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

Transdiagnostic group CBT vs. standard group CBT for depression, social anxiety disorder and agoraphobia/panic disorder: Study protocol for a pragmatic, multicenter non-inferiority randomized controlled trial.

PubMed

Arnfred, Sidse M; Aharoni, Ruth; Hvenegaard, Morten; Poulsen, Stig; Bach, Bo; Arendt, Mikkel; Rosenberg, Nicole K; Reinholt, Nina

2017-01-23

Transdiagnostic Cognitive Behavior Therapy (TCBT) manuals delivered in individual format have been reported to be just as effective as traditional diagnosis specific CBT manuals. We have translated and modified the "The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders" (UP-CBT) for group delivery in Mental Health Service (MHS), and shown effects comparable to traditional CBT in a naturalistic study. As the use of one manual instead of several diagnosis-specific manuals could simplify logistics, reduce waiting time, and increase therapist expertise compared to diagnosis specific CBT, we aim to test the relative efficacy of group UP-CBT and diagnosis specific group CBT. The study is a partially blinded, pragmatic, non-inferiority, parallel, multi-center randomized controlled trial (RCT) of UP-CBT vs diagnosis specific CBT for Unipolar Depression, Social Anxiety Disorder and Agoraphobia/Panic Disorder. In total, 248 patients are recruited from three regional MHS centers across Denmark and included in two intervention arms. The primary outcome is patient-ratings of well-being (WHO Well-being Index, WHO-5), secondary outcomes include level of depressive and anxious symptoms, personality variables, emotion regulation, reflective functioning, and social adjustment. Assessments are conducted before and after therapy and at 6 months follow-up. Weekly patient-rated outcomes and group evaluations are collected for every session. Outcome assessors, blind to treatment allocation, will perform the observer-based symptom ratings, and fidelity assessors will monitor manual adherence. The current study will be the first RCT investigating the dissemination of the UP in a MHS setting, the UP delivered in groups, and with depressive patients included. Hence the results are expected to add substantially to the evidence base for rational group psychotherapy in MHS. The planned moderator and mediator analyses could spur new hypotheses about mechanisms of change in psychotherapy and the association between patient characteristics and treatment effect. Clinicaltrials.gov NCT02954731 . Registered 25 October 2016.

Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies.

PubMed

Höllig, Anke; Stoffel-Wagner, Birgit; Clusmann, Hans; Veldeman, Michael; Schubert, Gerrit A; Coburn, Mark

2017-01-01

Aneurysmal subarachnoid hemorrhage triggers an intense inflammatory response, which is suspected to increase the risk for secondary complications such as delayed cerebral ischemia (DCI). However, to date, the monitoring of the inflammatory response to detect secondary complications such as DCI has not become part of the clinical routine diagnostic. Here, we aim to illustrate the time courses of inflammatory parameters after aneurysmal subarachnoid hemorrhage (aSAH) and discuss the problems of inflammatory parameters as biomarkers but also their possible relevance for deeper understanding of the pathophysiology after aSAH and sophisticated planning of future studies. In this prospective cohort study, 109 patients with aSAH were initially included, n  = 28 patients had to be excluded. Serum and-if possible-cerebral spinal fluid samples ( n  = 48) were retrieved at days 1, 4, 7, 10, and 14 after aSAH. Samples were analyzed for leukocyte count and C-reactive protein (CRP) (serum samples only) as well as matrix metallopeptidase 9 (MMP9), intercellular adhesion molecule 1 (ICAM1), and leukemia inhibitory factor (LIF) [both serum and cerebrospinal fluid (CSF) samples]. Time courses of the inflammatory parameters were displayed and related to the occurrence of DCI. We illustrate the time courses of leukocyte count, CRP, MMP9, ICAM1, and LIF in patients' serum samples from the first until the 14th day after aSAH. Time courses of MMP9, ICAM1, and LIF in CSF samples are demonstrated. Furthermore, no significant difference was shown relating the time courses to the occurrence of DCI. We estimate that the wide range of the measured values hampers their interpretation and usage as a biomarker. However, understanding the inflammatory response after aSAH and generating a multicenter database may facilitate further studies: realistic sample size calculations on the basis of a multicenter database will increase the quality and clinical relevance of the acquired results.

Strategic Planning for Research in Pediatric Critical Care

PubMed Central

Tamburro, Robert F.; Jenkins, Tammara L.; Kochanek, Patrick M.

2016-01-01

Objective To summarize the scientific priorities and potential future research directions for pediatric critical care research discussed by a panel of experts at the inaugural Strategic Planning Conference of the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Data Sources Expert opinion expressed during the Strategic Planning Conference. Study Selection Not applicable Data Extraction Chaired by an experienced expert from the field, issues relevant to the conduct of pediatric critical care research were discussed and debated by the invited participants. Data Synthesis Common themes and suggested priorities were identified and coalesced. Conclusions Of the many pathophysiological conditions discussed, the multiple organ dysfunction syndrome emerged as a topic in need of more study that is most relevant to the field. Additionally, the experts offered that the inter-relationship and impact of critical illness on child development and family functioning are important research priorities. Consequently, long-term outcomes research was encouraged. The expert group also suggested that multidisciplinary conferences are needed to help identify key knowledge gaps to advance and direct research in the field. The Pediatric Critical Care and Trauma Scientist Development National K12 Program and the Collaborative Pediatric Critical Care Research Network were recognized as successful and important programs supported by the branch. The development of core data resources including biorepositories with robust phenotypic data using common data elements was also suggested to foster data sharing among investigators and to enhance disease diagnosis and discovery. Multicenter clinical trials and innovative study designs to address understudied and poorly understood conditions were considered important for field advancement. Finally, the growth of the pediatric critical care research workforce was offered as a priority that could be spawned in many ways including by expanded transdisciplinary and multiprofessional collaboration and diversity representation. PMID:27679964

Development and refinement of computer-assisted planning and execution system for use in face-jaw-teeth transplantation to improve skeletal and dento-occlusal outcomes.

PubMed

Hashemi, Sepehr; Armand, Mehran; Gordon, Chad R

2016-10-01

To describe the development and refinement of the computer-assisted planning and execution (CAPE) system for use in face-jaw-teeth transplants (FJTTs). Although successful, some maxillofacial transplants result in suboptimal hybrid occlusion and may require subsequent surgical orthognathic revisions. Unfortunately, the use of traditional dental casts and splints pose several compromising shortcomings in the context of FJTT and hybrid occlusion. Computer-assisted surgery may overcome these challenges. Therefore, the use of computer-assisted orthognathic techniques and functional planning may prevent the need for such revisions and improve facial-skeletal outcomes. A comprehensive CAPE system for use in FJTT was developed through a multicenter collaboration and refined using plastic models, live miniature swine surgery, and human cadaver models. The system marries preoperative surgical planning and intraoperative execution by allowing on-table navigation of the donor fragment relative to recipient cranium, and real-time reporting of patient's cephalometric measurements relative to a desired dental-skeletal outcome. FJTTs using live-animal and cadaveric models demonstrate the CAPE system to be accurate in navigation and beneficial in improving hybrid occlusion and other craniofacial outcomes. Future refinement of the CAPE system includes integration of more commonly performed orthognathic/maxillofacial procedures.

Prognostic study of cardiac events in Japanese high risk hemodialysis patients using I-BMIPP-SPECT: B-SAFE study design.

PubMed

Hasebe, Naoyuki; Moroi, Masao; Nishimura, Masato; Hara, Kazuhiro; Hase, Hiroki; Hashimoto, Akiyoshi; Kumita, Shinichiro; Haze, Kazuo; Momose, Mitsuru; Nagai, Yoji; Sugimoto, Tokuichiro; Kusano, Eiji; Akiba, Takashi; Nakata, Tomoaki; Nishimura, Tsunehiko; Tamaki, Nagara; Kikuchi, Kenjiro

2008-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis. Such patients frequently develop complications such as asymptomatic coronary artery disease (CAD). Accordingly, CAD must ideally be diagnosed at an early stage to improve prognosis. Although myocardial perfusion single photon emission computed tomography (SPECT) is valuable for diagnosing CAD, the stress test is not always applicable to patients on hemodialysis. Thus, we proposed a multicenter, prospective cohort study called "B-SAFE" to investigate the applicability of resting (123)I-labeled beta-methyl-iodophenylpentadecanoic acid ((123)I-BMIPP)-SPECT will be used to diagnose cardiac disease and evaluate the prognosis of hemodialysis patients by imaging myocardial fatty acid metabolism. B-SAFE began enrolling patients from June 2006 at 48 facilities. We performed (123)I-BMIPP-SPECT on 702 hemodialysis patients with risk factors for CAD until 30 November 2007 and plan to follow up for three years. The primary endpoints will be cardiac death and sudden death. This study should end in 2010.

[Tumor Data Interacted System Design Based on Grid Platform].

PubMed

Liu, Ying; Cao, Jiaji; Zhang, Haowei; Zhang, Ke

2016-06-01

In order to satisfy demands of massive and heterogeneous tumor clinical data processing and the multi-center collaborative diagnosis and treatment for tumor diseases,a Tumor Data Interacted System(TDIS)was established based on grid platform,so that an implementing virtualization platform of tumor diagnosis service was realized,sharing tumor information in real time and carrying on standardized management.The system adopts Globus Toolkit 4.0tools to build the open grid service framework and encapsulats data resources based on Web Services Resource Framework(WSRF).The system uses the middleware technology to provide unified access interface for heterogeneous data interaction,which could optimize interactive process with virtualized service to query and call tumor information resources flexibly.For massive amounts of heterogeneous tumor data,the federated stored and multiple authorized mode is selected as security services mechanism,real-time monitoring and balancing load.The system can cooperatively manage multi-center heterogeneous tumor data to realize the tumor patient data query,sharing and analysis,and compare and match resources in typical clinical database or clinical information database in other service node,thus it can assist doctors in consulting similar case and making up multidisciplinary treatment plan for tumors.Consequently,the system can improve efficiency of diagnosis and treatment for tumor,and promote the development of collaborative tumor diagnosis model.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Pilot Study Overview

NASA Technical Reports Server (NTRS)

Paloski, William H.; Young, L. R.

2007-01-01

Efficient, effective, multi-system countermeasures will likely be required to protect the health, safety, and performance of crews aboard planned exploration-class space flight missions to Mars and beyond. To that end, NASA, DLR, and IMBP initiated a multi-center international project to begin systematically exploring the utility of artificial gravity (AG) as a multi-system countermeasure in ground based venues using test subjects deconditioned by bed rest. The goal of this project is to explore the efficacy of short-radius, intermittent AG as a countermeasure to bone, muscle, cardiovascular, and sensory-motor adaptations to hypogravity. This session reports the results from a pilot study commissioned to validate a standardized protocol to be used by all centers involved in the project. Subject selection criteria, medical monitoring requirements, medical care procedures, experiment control procedures, and standardized dependent measures were established jointly. Testing was performed on 15 rigorously screened male volunteers subjected to 21 days of 6deg HDT bed rest. (All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them.) Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple tests of multiple dependent measures were made in each of the primary physiological systems of interest during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period was complete. Analyses of these data (presented in other papers in this session) suggest the AG prescription had salutary effects on aspects of the bone, muscle, and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Furthermore, treatment subjects were able to tolerate 153/160 centrifuge sessions over the 21 day deconditioning protocol, suggesting that tolerance was unaffected by deconditioning. These positive results set the stage for full implementation of the planned multi-center international AG project. Future work will be devoted to developing optimization techniques for AG prescriptions (likely supplemented by exercise) to provide maximum physiological protection across all systems subject to space flight deconditioning in both men and women with minimum time and/or side effects. While a continuous AG solution (rotating vehicle) would likely be more efficient, this study suggests that intermittent AG could be an effective multi-system countermeasure.

Socio-demographic and clinical profiles of paranoid and nonparanoid schizophrenia: a prospective, multicenter study in China.

PubMed

Xiang, Yu-Tao; Wang, Chuan-Yue; Chiu, Helen F K; Weng, Yong-Zhen; Bo, Qi-Jing; Chan, Sandra S M; Lee, Edwin H M; Ungvari, Gabor S

2011-07-01

This study aimed to explore the socio-demographic and clinical characteristics of paranoid and nonparanoid subtypes of schizophrenia. In a multicenter, randomized, controlled, longitudinal study, 374 clinically stable schizophrenia patients were interviewed at entry with standardized assessment instruments and followed for 12-26 months. In the multivariate analysis, male sex, married marital status, urban abode, and more frequent relapse over the study period were independently associated with paranoid schizophrenia. The socio-demographic and clinical characteristics of Chinese patients with the paranoid subtype of schizophrenia are different from those of their Caucasian counterparts who are more likely to be women and have a better outcome. © 2010 Wiley Periodicals, Inc.

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

PubMed

Bimczok, R; Gers-Barlag, H; Mundt, C; Klette, E; Bielfeldt, S; Rudolph, T; Pflucker, F; Heinrich, U; Tronnier, H; Johncock, W; Klebon, B; Westenfelder, H; Flosser-Muller, H; Jenni, K; Kockott, D; Lademann, J; Herzog, B; Rohr, M

2007-01-01

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

Exploring Women's Preferences for the Mode of Delivery in Twin Gestations: Results of the Twin Birth Study.

PubMed

Murray-Davis, Beth; McVittie, Jennifer; Barrett, Jon F; Hutton, Eileen K

2016-12-01

The Twin Birth Study, an international, multi-center randomized controlled trial was conducted to compare the risks of planned cesarean with planned vaginal delivery for twin pregnancies. The aim of this component of the trial was to understand participants' perspectives of study participation and preferences for the mode of delivery. A mixed-methods questionnaire was distributed to study participants 3 months after giving birth. The questionnaire contained Likert scales and open-ended questions about the experience of being enrolled in a clinical trial and of childbirth, including the mode of delivery. Quantitative data were analyzed using SAS to generate descriptive statistics. Qualitative data were analyzed to identify categories and themes. Ninety-one percent of trial participants completed the questionnaire. Across all groups, the majority of women would participate in a study like this one again if given the opportunity. Main benefits of participating were as follows: benefits to one and one's babies, altruism, and receiving quality care. Randomization for the mode of delivery was challenging for women because of the desire to be involved in decision-making. Findings related to childbirth experience and the mode of delivery demonstrated a preference for vaginal birth across all groups. Those who had a vaginal birth were more satisfied with their birth experience. This study provides evidence to inform practitioners about what women who have twin pregnancies like or dislike about birth and their desire for involvement in decision-making. Vaginal birth was preferred across all study groups and was associated with greater satisfaction with childbirth experience. © 2016 Wiley Periodicals, Inc.

DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity (DUTCH PEERS): rationale and study design of a randomized multicenter trial in a Dutch all-comers population.

PubMed

Tandjung, Kenneth; Basalus, Mounir W Z; Sen, Hanim; Jessurun, Gillian A J; Danse, Peter W; Stoel, Martin; Linssen, Gerard C M; Derks, Anita; van Loenhout, Ton T; Nienhuis, Mark B; Hautvast, Raymond W M; von Birgelen, Clemens

2012-04-01

Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES. Copyright © 2012 Mosby, Inc. All rights reserved.

Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study.

PubMed

Chung, Kevin K; Coates, Elsa C; Hickerson, William L; Arnold-Ross, Angela L; Caruso, Daniel M; Albrecht, Marlene; Arnoldo, Brett D; Howard, Christina; Johnson, Laura S; McLawhorn, Melissa M; Friedman, Bruce; Sprague, Amy M; Mosier, Michael J; Conrad, Peggie F; Smith, David J; Karlnoski, Rachel A; Aden, James K; Mann-Salinas, Elizabeth A; Wolf, Steven E

2018-06-20

Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been utilized in this population. The purpose of this multicenter study was to evaluate demographic, treatment and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial were included. Across 8 participating burn centers, 171 subjects were enrolled during a 4 year period. Complete data was available in 170 subjects with a mean age of 51±17, percent total body surface area (TBSA) burn of 38±26% and Injury Severity Score of 27±21. 80% of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37±19 (mL/kg/hr) and a treatment duration of 13±24 days. Overall, in hospital mortality was 50%. Among survivors, 21% required RRT upon discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multi-center cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

PubMed

Lee, Jong Woo; LaRoche, Suzette; Choi, Hyunmi; Rodriguez Ruiz, Andres A; Fertig, Evan; Politsky, Jeffrey M; Herman, Susan T; Loddenkemper, Tobias; Sansevere, Arnold J; Korb, Pearce J; Abend, Nicholas S; Goldstein, Joshua L; Sinha, Saurabh R; Dombrowski, Keith E; Ritzl, Eva K; Westover, Michael B; Gavvala, Jay R; Gerard, Elizabeth E; Schmitt, Sarah E; Szaflarski, Jerzy P; Ding, Kan; Haas, Kevin F; Buchsbaum, Richard; Hirsch, Lawrence J; Wusthoff, Courtney J; Hopp, Jennifer L; Hahn, Cecil D

2016-04-01

The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

A Multi-center Comparison of the Safety of Oral versus Intravenous Acetylcysteine for Treatment of Acetaminophen Overdose

PubMed Central

2010-01-01

Oral and intravenous (IV) acetylcysteine are used for treatment of acetaminophen poisoning. The objective of this multi-center study was to compare the safety of these two routes of administration. METHODS We conducted a multi-center chart review of all patients treated with acetylcysteine for acetaminophen poisoning. The primary safety outcome was the percentage of patients with of acetylcysteine-related adverse events. RESULTS A total of 503 subjects were included in the safety analysis (306 IV only, 145 oral only and 52 both routes).There were no serious adverse events related to acetylcysteine for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23% vs 9%). Anaphylactoid reactions were more common with IV administration (6% vs 2%). Conclusions Intravenous and oral acetylcysteine are both associated with minimal side effects and are safe for treatment of acetaminophen toxicity. PMID:20524832

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier.

PubMed

Trew, Geoffrey H; Pistofidis, George A; Brucker, Sara Y; Krämer, Bernhard; Ziegler, Nicole M; Korell, Matthias; Ritter, Henning; McConnachie, Alex; Ford, Ian; Crowe, Alison M; Estridge, Trudy D; Diamond, Michael P; De Wilde, Rudy L

2017-02-01

Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery. This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18-46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4-12 weeks. The first two patients of each surgeon received hydrogel, up to 30 mL sprayed over all sites of surgical trauma, and were assessed for safety and application only (n = 12). Subsequent subjects (n = 66) were randomized 1:1 to receive either hydrogel (Treatment, n = 35) or not (Control, n = 31); 63 completed the SLL. No adverse event was assessed as serious, or possibly device related. None was severe or fatal. Adverse events were reported for 17 treated subjects (17/47, 36.2%) and 13 Controls (13/31, 41.9%). For 95.7% of treated subjects, surgeons found the device "easy" or "very easy" to use; in 54.5%, some residual material was evident at SLL. For 63 randomized subjects who completed the SLL, adjusted between-group difference in the change from baseline adhesion score demonstrated a 41.4% reduction for Treatment compared with Controls (p = 0.017), with a 49.5% reduction (p = 0.008) among myomectomy subjects (n = 34). Spray application of a degradable hydrogel adhesion barrier during gynecologic laparoscopic abdominopelvic surgery was performed easily and safely, without evidence of clinically significant adverse outcomes. Data suggest the hydrogel was effective in reducing postoperative adhesion development, particularly following myomectomy.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

PubMed

Palacio, Montse; Bonet-Carne, Elisenda; Cobo, Teresa; Perez-Moreno, Alvaro; Sabrià, Joan; Richter, Jute; Kacerovsky, Marian; Jacobsson, Bo; García-Posada, Raúl A; Bugatto, Fernando; Santisteve, Ramon; Vives, Àngels; Parra-Cordero, Mauro; Hernandez-Andrade, Edgar; Bartha, José Luis; Carretero-Lucena, Pilar; Tan, Kai Lit; Cruz-Martínez, Rogelio; Burke, Minke; Vavilala, Suseela; Iruretagoyena, Igor; Delgado, Juan Luis; Schenone, Mauro; Vilanova, Josep; Botet, Francesc; Yeo, George S H; Hyett, Jon; Deprest, Jan; Romero, Roberto; Gratacos, Eduard

2017-08-01

Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique. Copyright © 2017. Published by Elsevier Inc.

Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study.

PubMed

Fruehauf, Stefan; Otremba, Burkhard; Stötzer, Oliver; Rudolph, Christine

2016-11-01

Febrile neutropenia (FN) is a serious and frequent complication of cytotoxic chemotherapy. Biosimilar filgrastim (Nivestim™, Hospira Inc, A Pfizer Company, Lake Forest, IL, USA) is a granulocyte-colony stimulating factor licensed for the treatment of neutropenia and FN induced by myelosuppressive chemotherapy. The primary goal of this VENICE study (ClinicalTrials.gov identifier, NCT01627990) was to observe the tolerability, safety and efficacy of biosimilar filgrastim in patients receiving cancer chemotherapy. This was a prospective, multicenter, non-interventional, longitudinal study. Consenting adult patients with solid tumors or hematologic malignancies for whom cytotoxic chemotherapy and treatment with biosimilar filgrastim was planned were enrolled. Among the enrolled patients (N = 386), 81% were female, with a median age (range) of 61 (22-92) years, with 39% >65 years old. Most patients (n = 338; 88%) had solid tumors and the remainder (n = 49; 13%) had hematological malignancies. The majority of the patients (64%) received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis. At the follow-up visits, for the majority of patients (95.6%) there had been no change in chemotherapy dose due to FN. For two patients (0.5%) the chemotherapy was discontinued due to FN and for four patients (1.0%) the chemotherapy dose was reduced due to FN. For the majority of patients (96.9%) the chemotherapy cycle following the first biosimilar filgrastim treatment was not delayed due to FN. For 3 patients (0.8%), the chemotherapy was delayed following the first biosimilar filgrastim treatment. Less than one-third (29.8%) of the patients experienced ≥1 adverse event that was at least potentially related to biosimilar filgrastim treatment. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic setting in patients undergoing chemotherapy for solid tumors and hematological malignancies. ClinicalTrials.gov identifier, NCT01627990. Hospira Inc, A Pfizer Company, Lake Forest, IL, USA.

Effects of a Patient-Provider, Collaborative, Medication-Planning Tool: A Randomized, Controlled Trial

PubMed Central

Wolf, Michael S.; Kaiser, Darren; Morrow, Daniel G.

2016-01-01

Among patients with various levels of health literacy, the effects of collaborative, patient-provider, medication-planning tools on outcomes relevant to self-management are uncertain. Objective. Among adult patients with type II diabetes mellitus, we tested the effectiveness of a medication-planning tool (Medtable™) implemented via an electronic medical record to improve patients' medication knowledge, adherence, and glycemic control compared to usual care. Design. A multicenter, randomized controlled trial in outpatient primary care clinics. 674 patients received either the Medtable tool or usual care and were followed up for up to 12 months. Results. Patients who received Medtable had greater knowledge about indications for medications in their regimens and were more satisfied with the information about their medications. Patients' knowledge of drug indication improved with Medtable regardless of their literacy status. However, Medtable did not improve patients' demonstrated medication use, regimen adherence, or glycemic control (HbA1c). Conclusion. The Medtable tool supported provider/patient collaboration related to medication use, as reflected in patient satisfaction with communication, but had limited impact on patient medication knowledge, adherence, and HbA1c outcomes. This trial is registered with ClinicalTrials.gov NCT01296633. PMID:27699179

Innovative measures to combat rare diseases in China: The national rare diseases registry system, larger-scale clinical cohort studies, and studies in combination with precision medicine research.

PubMed

Song, Peipei; He, Jiangjiang; Li, Fen; Jin, Chunlin

2017-02-01

China is facing the great challenge of treating the world's largest rare disease population, an estimated 16 million patients with rare diseases. One effort offering promise has been a pilot national project that was launched in 2013 and that focused on 20 representative rare diseases. Another government-supported special research program on rare diseases - the "Rare Diseases Clinical Cohort Study" - was launched in December 2016. According to the plan for this research project, the unified National Rare Diseases Registry System of China will be established as of 2020, and a large-scale cohort study will be conducted from 2016 to 2020. The project plans to develop 109 technical standards, to establish and improve 2 national databases of rare diseases - a multi-center clinical database and a biological sample library, and to conduct studies on more than 50,000 registered cases of 50 different rare diseases. More importantly, this study will be combined with the concept of precision medicine. Chinese population-specific basic information on rare diseases, clinical information, and genomic information will be integrated to create a comprehensive predictive model with a follow-up database system and a model to evaluate prognosis. This will provide the evidence for accurate classification, diagnosis, treatment, and estimation of prognosis for rare diseases in China. Numerous challenges including data standardization, protecting patient privacy, big data processing, and interpretation of genetic information still need to be overcome, but research prospects offer great promise.

Multicenter surveillance of species distribution and antifungal susceptibilities of Candida bloodstream isolates in South Korea.

PubMed

Jung, Sook-In; Shin, Jong Hee; Song, Jae-Hoon; Peck, Kyong Ran; Lee, Kyungwon; Kim, Mi-Na; Chang, Hyun Ha; Moon, Chi Sook

2010-06-01

Multicenter data on in vitro susceptibility of Candida bloodstream isolates to echinocandin antifungal agents is still lacking in South Korea. We performed a prospective multicenter study to determine the species distribution of Candida bloodstream isolates and their susceptibility to five antifungal agents, including caspofungin and micafungin. A total of 639 isolates were collected from 20 tertiary hospitals between September 2006 and August 2007. Antifungal susceptibilities were determined through the use of the CLSI broth microdilution method M27-A3. The overall species distribution was as follows; Candida albicans (38%), Candida parapsilosis (26%), Candia tropicalis (20%), Candida glabrata (11%), and miscellaneous Candida species (5%). Although C. parapsilosis and miscellaneous Candida species were less susceptible to both echinocandins, all 639 isolates were susceptible to both caspofungin and micafungin (MIC,

Engaging stakeholders to design a comparative effectiveness trial in children with uncontrolled asthma.

PubMed

Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A

2016-01-01

To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial.

Filgrastim mobilization and collection of allogeneic blood progenitor cells from adult family donors: first interim report of a prospective German multicenter study.

PubMed

Beelen, D W; Ottinger, H; Kolbe, K; Pönisch, W; Sayer, H G; Knauf, W; Stockschläder, M; Scheid, C; Schaefer, U W

2002-12-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study.

PubMed

Duque, A; Martínez, P-J; Giraldo, A; Gualtero, D-F; Ardila, C-M; Contreras, A; Duarte, S; Lafaurie, G-I

2017-07-01

The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study

PubMed Central

Duque, Andrés; Martínez, Paula-Juliana; Giraldo, Astrid; Gualtero, Diego F.; Ardila, Carlos-Martín; Contreras, Adolfo; Duarte, Silvia

2017-01-01

Background The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. Material and Methods 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. Results The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Conclusions Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate, complementary and more reliable methods to assess the patient’s smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. Clinical Relevance: The serum cotinine level is more reliable to make associations with the patient’s periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies. Key words:Biological markers, serum, cotinine, periodontitis, smoking. PMID:28578367

Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

PubMed

Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

2016-12-01

Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study.

PubMed

Zoet, Gerbrand A; Meun, Cindy; Benschop, Laura; Boersma, Eric; Budde, Ricardo P J; Fauser, Bart C J M; de Groot, Christianne J M; van der Lugt, Aad; Maas, Angela H E M; Moons, Karl G M; Roeters van Lennep, Jeanine E; Roos-Hesselink, Jolien W; Steegers, Eric A P; van Rijn, Bas B; Laven, Joop S E; Franx, Arie; Velthuis, Birgitta K

2017-08-07

Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). Women of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. Initial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. Netherlands Trial Register, NTR5531 . Date registered: October 21st, 2015.

Biomarker combinations for diagnosis and prognosis in multicenter studies: Principles and methods.

PubMed

Meisner, Allison; Parikh, Chirag R; Kerr, Kathleen F

2017-01-01

Many investigators are interested in combining biomarkers to predict a binary outcome or detect underlying disease. This endeavor is complicated by the fact that many biomarker studies involve data from multiple centers. Depending upon the relationship between center, the biomarkers, and the target of prediction, care must be taken when constructing and evaluating combinations of biomarkers. We introduce a taxonomy to describe the role of center and consider how a biomarker combination should be constructed and evaluated. We show that ignoring center, which is frequently done by clinical researchers, is often not appropriate. The limited statistical literature proposes using random intercept logistic regression models, an approach that we demonstrate is generally inadequate and may be misleading. We instead propose using fixed intercept logistic regression, which appropriately accounts for center without relying on untenable assumptions. After constructing the biomarker combination, we recommend using performance measures that account for the multicenter nature of the data, namely the center-adjusted area under the receiver operating characteristic curve. We apply these methods to data from a multicenter study of acute kidney injury after cardiac surgery. Appropriately accounting for center, both in construction and evaluation, may increase the likelihood of identifying clinically useful biomarker combinations.

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PubMed

Sargos, P; Charleux, T; Haas, R L; Michot, A; Llacer, C; Moureau-Zabotto, L; Vogin, G; Le Péchoux, C; Verry, C; Ducassou, A; Delannes, M; Mervoyer, A; Wiazzane, N; Thariat, J; Sunyach, M P; Benchalal, M; Laredo, J D; Kind, M; Gillon, P; Kantor, G

2018-04-01

The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Strategic Planning for Research in Pediatric Critical Care.

PubMed

Tamburro, Robert F; Jenkins, Tammara L; Kochanek, Patrick M

2016-11-01

To summarize the scientific priorities and potential future research directions for pediatric critical care research discussed by a panel of experts at the inaugural Strategic Planning Conference of the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Expert opinion expressed during the Strategic Planning Conference. Not applicable. Chaired by an experienced expert from the field, issues relevant to the conduct of pediatric critical care research were discussed and debated by the invited participants. Common themes and suggested priorities were identified and coalesced. Of the many pathophysiologic conditions discussed, the multiple organ dysfunction syndrome emerged as a topic in need of more study that is most relevant to the field. Additionally, the experts offered that the interrelationship and impact of critical illness on child development and family functioning are important research priorities. Consequently, long-term outcomes research was encouraged. The expert group also suggested that multidisciplinary conferences are needed to help identify key knowledge gaps to advance and direct research in the field. The Pediatric Critical Care and Trauma Scientist Development National K12 Program and the Collaborative Pediatric Critical Care Research Network were recognized as successful and important programs supported by the branch. The development of core data resources including biorepositories with robust phenotypic data using common data elements was also suggested to foster data sharing among investigators and to enhance disease diagnosis and discovery. Multicenter clinical trials and innovative study designs to address understudied and poorly understood conditions were considered important for field advancement. Finally, the growth of the pediatric critical care research workforce was offered as a priority that could be spawned in many ways including by expanded transdisciplinary and multiprofessional collaboration and diversity representation.

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

PubMed Central

Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

2017-01-01

Background The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). Objective To describe the data management process and statistical analysis plan. Methods The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. Conclusion According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. Trial registration ClinicalTrials.gov number, NCT01374022. PMID:28977255

Defibrillator implantations for primary prevention in the United States: Inappropriate care or inadequate documentation: Insights from the National Cardiovascular Data ICD Registry.

PubMed

Kaiser, Daniel W; Tsai, Vivian; Heidenreich, Paul A; Goldstein, Mary K; Wang, Yongfei; Curtis, Jeptha; Turakhia, Mintu P

2015-10-01

Prior studies have reported that more than 20% of implantable cardioverter-defibrillator (ICD) implantations in the United States do not adhere to trial-based criteria. We sought to investigate the patient characteristics associated with not meeting the inclusion criteria of the clinical trials that have demonstrated the efficacy of primary prevention ICDs. Using data from the National Cardiovascular Data Registry's ICD Registry, we identified patients who received ICDs for primary prevention from January 2006 to December 2008. We determined whether patients met the inclusion criteria of at least 1 of the 4 ICD primary prevention trials: Multicenter Automatic Defibrillator Implantation Trial (MADIT), MADIT-II, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), and the Multicenter Unsustained Tachycardia Trial (MUSTT). Among 150,264 patients, 86% met criteria for an ICD implantation based on trial data. The proportion of patients who did not meet trial-based criteria increased as age decreased. In multivariate analysis, the significant predictors for not meeting trial criteria included prior cardiac transplantation (odds ratio [OR] 2.1), pediatric electrophysiology operator (OR 2.0), and high-grade atrioventricular conduction disease (OR 1.4). Among National Cardiovascular Data Registry registrants receiving first-time ICDs for primary prevention, the majority met trial-based criteria. Multivariate analyses suggested that many patients who did not meet the trial-based criteria may have had clinical circumstances that warranted ICD implantation. These findings caution against the use of trial-based indications to determine site quality metrics that could penalize sites that care for younger patients. The planned incorporation of appropriate use criteria into the ICD registry may better characterize patient- and site-level quality and performance. Published by Elsevier Inc.

Stable Atlas-based Mapped Prior (STAMP) machine-learning segmentation for multicenter large-scale MRI data.

PubMed

Kim, Eun Young; Magnotta, Vincent A; Liu, Dawei; Johnson, Hans J

2014-09-01

Machine learning (ML)-based segmentation methods are a common technique in the medical image processing field. In spite of numerous research groups that have investigated ML-based segmentation frameworks, there remains unanswered aspects of performance variability for the choice of two key components: ML algorithm and intensity normalization. This investigation reveals that the choice of those elements plays a major part in determining segmentation accuracy and generalizability. The approach we have used in this study aims to evaluate relative benefits of the two elements within a subcortical MRI segmentation framework. Experiments were conducted to contrast eight machine-learning algorithm configurations and 11 normalization strategies for our brain MR segmentation framework. For the intensity normalization, a Stable Atlas-based Mapped Prior (STAMP) was utilized to take better account of contrast along boundaries of structures. Comparing eight machine learning algorithms on down-sampled segmentation MR data, it was obvious that a significant improvement was obtained using ensemble-based ML algorithms (i.e., random forest) or ANN algorithms. Further investigation between these two algorithms also revealed that the random forest results provided exceptionally good agreement with manual delineations by experts. Additional experiments showed that the effect of STAMP-based intensity normalization also improved the robustness of segmentation for multicenter data sets. The constructed framework obtained good multicenter reliability and was successfully applied on a large multicenter MR data set (n>3000). Less than 10% of automated segmentations were recommended for minimal expert intervention. These results demonstrate the feasibility of using the ML-based segmentation tools for processing large amount of multicenter MR images. We demonstrated dramatically different result profiles in segmentation accuracy according to the choice of ML algorithm and intensity normalization chosen. Copyright © 2014 Elsevier Inc. All rights reserved.

A multicenter observational study of US adults with acute asthma: who are the frequent users of the emergency department?

PubMed

Hasegawa, Kohei; Sullivan, Ashley F; Tovar Hirashima, Eva; Gaeta, Theodore J; Fee, Christopher; Turner, Stuart J; Massaro, Susan; Camargo, Carlos A

2014-01-01

Despite the substantial burden of asthma-related emergency department (ED) visits, there have been no recent multicenter efforts to characterize this high-risk population. We aimed to characterize patients with asthma according to their frequency of ED visits and to identify factors associated with frequent ED visits. A multicenter chart review study of 48 EDs across 23 US states. We identified ED patients ages 18 to 54 years with acute asthma during 2011 and 2012. Primary outcome was frequency of ED visits for acute asthma in the past year, excluding the index ED visit. Of the 1890 enrolled patients, 863 patients (46%) had 1 or more (frequent) ED visits in the past year. Specifically, 28% had 1 to 2 visits, 11% had 3 to 5 visits, and 7% had 6 or more visits. Among frequent ED users, guideline-recommended management was suboptimal. For example, of patients with 6 or more ED visits, 85% lacked evidence of prior evaluation by an asthma specialist, and 43% were not treated with inhaled corticosteroids. In a multivariable model, significant predictors of frequent ED visits were public insurance, no insurance, and markers for chronic asthma severity (all P < .05). Stronger associations were found among those with a higher frequency of asthma-related ED visits (eg, 6 or more ED visits). This multicenter study of US adults with acute asthma demonstrated many frequent ED users and suboptimal preventive management in this high-risk population. Future reductions in asthma morbidity and associated health care utilization will require continued efforts to bridge these major gaps in asthma care. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

PubMed

Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

2014-06-01

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Barriers to Clinical Research in Latin America

PubMed Central

Chomsky-Higgins, Kathryn; Miclau, Theodore A.; Mackechnie, Madeline C.; Aguilar, Dino; Avila, Jorge Rubio; dos Reis, Fernando Baldy; Balmaseda, Roberto; Barquet, Antonio; Ceballos, Alfredo; Contreras, Fernando; Escalante, Igor; Elias, Nelson; Vincenti, Sergio Iriarte; Lozano, Christian; Medina, Fryda; Merchan, Gavino; Segovia, Julio; Guerado, Enrique; Quintero, Jose Eduardo; Morshed, Saam; Bhandari, Mohit; Miclau, Theodore

2017-01-01

Enhancing health research capacity in developing countries is a global health priority. Understanding the orthopedic burden of disease in Latin America will require close partnership between more-developed and less-developed countries. To this end, the Osteosynthesis and Trauma Care Foundation assembled a research consortium of Latin-American orthopedic leaders. Prior to the meeting, we surveyed attendees on perceived barriers to conducting research at their institutions. During the event, working groups discussed these barriers, developed strategies for addressing them, and planned future steps for collaboration. The participants established the need for global relationships that allow colleagues from Latin America to access to training and established investigational infrastructure of North American centers to address research questions relevant to their communities. As a result of the discussion, the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care was initiated. Since then, an expanded international working group, Associación de Cirujanos Traumatológicos en las Americas (ACTUAR), has been created with the purpose of promoting increased global partnership for research capacity development. PMID:28459047

Barriers to Clinical Research in Latin America.

PubMed

Chomsky-Higgins, Kathryn; Miclau, Theodore A; Mackechnie, Madeline C; Aguilar, Dino; Avila, Jorge Rubio; Dos Reis, Fernando Baldy; Balmaseda, Roberto; Barquet, Antonio; Ceballos, Alfredo; Contreras, Fernando; Escalante, Igor; Elias, Nelson; Vincenti, Sergio Iriarte; Lozano, Christian; Medina, Fryda; Merchan, Gavino; Segovia, Julio; Guerado, Enrique; Quintero, Jose Eduardo; Morshed, Saam; Bhandari, Mohit; Miclau, Theodore

2017-01-01

Enhancing health research capacity in developing countries is a global health priority. Understanding the orthopedic burden of disease in Latin America will require close partnership between more-developed and less-developed countries. To this end, the Osteosynthesis and Trauma Care Foundation assembled a research consortium of Latin-American orthopedic leaders. Prior to the meeting, we surveyed attendees on perceived barriers to conducting research at their institutions. During the event, working groups discussed these barriers, developed strategies for addressing them, and planned future steps for collaboration. The participants established the need for global relationships that allow colleagues from Latin America to access to training and established investigational infrastructure of North American centers to address research questions relevant to their communities. As a result of the discussion, the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care was initiated. Since then, an expanded international working group, Associación de Cirujanos Traumatológicos en las Americas (ACTUAR), has been created with the purpose of promoting increased global partnership for research capacity development.

Advancing the evidence base in cancer: psychosocial multicenter trials

PubMed Central

2012-01-01

Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

Employment related productivity loss associated with herpes zoster and postherpetic neuralgia: a 6-month prospective study.

PubMed

Drolet, Mélanie; Levin, Myron J; Schmader, Kenneth E; Johnson, Robert; Oxman, Michael N; Patrick, David; Fournier, Simon Olivier; Mansi, James A; Brisson, Marc

2012-03-09

We conducted a prospective multi-center study to assess productivity loss associated with herpes zoster (HZ) and postherpetic neuralgia (PHN). From 10/2005 to 07/2006, we recruited immunocompetent subjects aged ≥50 years with HZ within 14 days of rash onset across Canada. Of the 249 patients recruited, 88 were employed. Data on employment status, absences from work, reasons for absence and effectiveness at work were documented at recruitment, 7-14-21-30-60-90-120-150 and 180 days later. The majority (64%) of employed subjects missed work because of HZ and 76% reported decreased effectiveness at work (i.e. presenteeism) because of HZ/PHN. Mean hours of absenteeism and presenteeism per working individual were 27 and 34 h, respectively. Pain severity and duration were associated with greater productivity loss. These results provide new information about the burden of HZ and PHN, which is useful for public health planning and cost-effectiveness analyses of HZ vaccination among individuals of working age. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome Blood and Marrow Transplant Clinical Trials Network #1102 Study Rationale, Design and Methods

PubMed Central

Saber, Wael; Le Rademacher, Jennifer; Sekeres, Mikkael; Logan, Brent; Lewis, Moira; Mendizabal, Adam; Leifer, Eric; Appelbaum, Frederick R.; Horowitz, Mary M; Nakamura, Ryotaro; Cutler, Corey S.

2014-01-01

The introduction of reduced intensity conditioning regimens (RIC) made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared to novel non-transplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT to non-transplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age & response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT. PMID:24972249

Treatment using oxaliplatin and S-1 adjuvant chemotherapy for pathological stage III gastric cancer: a multicenter phase II study (TOSA trial) protocol.

PubMed

Namikawa, Tsutomu; Maeda, Hiromichi; Kitagawa, Hiroyuki; Oba, Koji; Tsuji, Akihito; Yoshikawa, Takaki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2018-02-13

Recent studies demonstrated the efficacy of S-1-based adjuvant chemotherapy administered for six months after curative surgery for stage III gastric cancer; however, it is unproven whether this type of combination chemotherapy is more effective than the standard adjuvant chemotherapy of S-1 for one year. This multicenter phase II study evaluate the efficacy and safety of adjuvant chemotherapy using S-1 plus oxaliplatin followed by S-1 for up to one year for curatively resected stage III gastric cancer in patients aged over 20 years. Treatment initially comprises oral fluoropyrimidine S-1 (80 mg/m 2 ) administered twice daily for the first 2 weeks of a 3-week cycle. On day 1 of a second 3-week cycle, patients will receive 100 mg/m 2 of intravenous oxaliplatin followed by 80 mg/m 2 of S-1 (maximum 8 cycles). Then, the patients will receive 80 mg/m 2 of S-1 daily for 4 weeks, followed by 2 weeks of no chemotherapy. This 6-week cycle will be repeated during the first year after surgery. The primary endpoint is relapse-free survival for 3 years and secondary endpoints are safety, including the incidence of adverse events, and grading of neuropathy with each treatment cycle. The planned sample size of 75 patients is appropriate for this trial. The data will be analyzed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance. In contrast to previous trials, the current study involves administration of S-1 until one year after surgery in addition to prior S-1 plus oxaliplatin, and is the first study to evaluate the safety and efficacy of S-1 plus oxaliplatin followed by S-1 for up to one year in patients with curatively resected stage III gastric cancer. This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry (UMIN-CTR) registration number, R000029656  ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029656 ). Registered January 24, 2017.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. Via the inhibition of inflammatory reactions and of apoptosis, stem cell recruitment, advancement of angiogenesis and growth factor release, EPO enhances healing and thus restitutio ad integrum after trauma. Human skin contains EPO receptors and is able to synthesize EPO. We therefore hypothesize that EPO is able to optimize wound healing in thermally injured patients. Methods/Design This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. Discussion We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. Trial registration EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824. PMID:23782555

Methodological aspects of multicenter studies with quantitative PET.

PubMed

Boellaard, Ronald

2011-01-01

Quantification of whole-body FDG PET studies is affected by many physiological and physical factors. Much of the variability in reported standardized uptake value (SUV) data seen in the literature results from the variability in methodology applied among these studies, i.e., due to the use of different scanners, acquisition and reconstruction settings, region of interest strategies, SUV normalization, and/or corrections methods. To date, the variability in applied methodology prohibits a proper comparison and exchange of quantitative FDG PET data. Consequently, the promising role of quantitative PET has been demonstrated in several monocentric studies, but these published results cannot be used directly as a guideline for clinical (multicenter) trials performed elsewhere. In this chapter, the main causes affecting whole-body FDG PET quantification and strategies to minimize its inter-institute variability are addressed.

Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial.

PubMed

Spadafora, Marco; Pace, Leonardo; Evangelista, Laura; Mansi, Luigi; Del Prete, Francesco; Saladini, Giorgio; Miletto, Paolo; Fanti, Stefano; Del Vecchio, Silvana; Guerra, Luca; Pepe, Giovanna; Peluso, Giuseppina; Nicolai, Emanuele; Storto, Giovanni; Ferdeghini, Marco; Giordano, Alessandro; Farsad, Mohsen; Schillaci, Orazio; Gridelli, Cesare; Cuocolo, Alberto

2018-05-05

Diagnosis of solitary pulmonary nodule (SPN) is an important public health issue and 18 F-FDG PET/CT has proven to be more effective than CT alone. Pre-test risk stratification and clinical presentation of SPN could affect the diagnostic strategy. A relevant issue is whether thoracic segmental (s)-PET/CT could be implemented in patients with SPN. This retrospective multicenter study compared the results of FDG whole-body (wb)-PET/CT to those of s-PET/CT. 18 F-FDG PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. The thoracic part of wb-PET/CT, considered s-PET/CT, was compared to wb-PET/CT. Clinical and PET/CT variables were investigated for SPN characterization as well as for identification of patients in whom s-PET/CT could be performed. Histopathology or follow-up data were used as a reference. In the study population, 36% had malignant, 35% benign, and 29% indeterminate SPN. 18 F-FDG uptake indicative of thoracic and extra-thoracic lesions was detectable in 13% and 3% of the patients. All patients with extra-thoracic metastases (n = 13) had thoracic lymph node involvement and highest 18 F-FDG uptake at level of SPN (negative predictive value 100%). Compared to wb-PET/CT, s-PET/CT could save about 2/3 of 18 F-FDG dose, radiation exposure or scan-time, without affecting the clinical impact of PET/CT. Pre-test probability of malignancy can guide the diagnostic strategy of 18 FDG-PET/CT in patients with SPN. In subjects with low-intermediate pretest probability s-PET/CT imaging might be planned in advance, while in those at high risk and with thoracic lymph node involvement a wb-PET/CT is necessary.

Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial).

PubMed

Mandrioli, Jessica; D'Amico, Roberto; Zucchi, Elisabetta; Gessani, Annalisa; Fini, Nicola; Fasano, Antonio; Caponnetto, Claudia; Chiò, Adriano; Dalla Bella, Eleonora; Lunetta, Christian; Mazzini, Letizia; Marinou, Kalliopi; Sorarù, Gianni; de Biasi, Sara; Lo Tartaro, Domenico; Pinti, Marcello; Cossarizza, Andrea

2018-06-01

Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

PubMed

Bossi, P; Cortinovis, D; Fatigoni, S; Cossu Rocca, M; Fabi, A; Seminara, P; Ripamonti, C; Alfieri, S; Granata, R; Bergamini, C; Agustoni, F; Bidoli, P; Nolè, F; Pessi, M A; Macchi, F; Michellini, L; Montanaro, F; Roila, F

2017-10-01

The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A social media intervention to improve hypoglycemia management at a multicenter hospital: a quality improvement pilot for clinical nurses.

PubMed

De Sousa, Filomena; Jackson, Jennifer; Knight, Ruth; Cloutier, Edith; Basa, Rosemary; Fourney, Anne; Devecseri, Kathleen

2018-02-01

Hypoglycemia poses significant risk to inpatients. Nursing management of hypoglycemia is a challenge, despite established best practice guidelines. Social media is an effective tool for sharing information and could overcome barriers to clinical education at a multicenter hospital. The purpose of this quality improvement intervention was to create and disseminate social media posts about best practices in hypoglycemia management. An unmatched pre-and post-survey assessed nursing knowledge of hypoglycemia management. Social media posts were created to visually outline the steps for hypoglycemia management over 2 weeks, across a nursing social media platform. We assessed the reach of the posts via Facebook and a survey. The posts reached 2962 users during the first week, and 1491 users the second week. A social media intervention can have a substantial reach and distribute information across a multicenter hospital. Additional study is needed to determine what factors could support an increase in nursing knowledge through a social media campaign.

Conjugation in multi-tetrazole derivatives: a new design direction for energetic materials.

PubMed

Sun, Shuyang; Lu, Ming

2018-06-23

Multi-tetrazole derivatives with conjugated structures were designed and investigated in this study. Using quantum chemistry methods, the crystal structures, electrostatic potentials (ESPs), multicenter bond orders, HOMO-LUMO energy gaps, and detonation properties of the derivatives were calculated. As expected, these molecules with conjugated structures showed low energies of their crystal structures, molecular layering in their crystals, high average ESPs, high multicenter bond order values, and enhanced detonation properties. The derivative 1,2-di(1H-tetrazol-5-yl)diazene (N2) was predicted to have the best density (1.87 g/cm 3 ), detonation velocity (9006 m/s), and detonation pressure (36.8 GPa) of the designed molecules, while its total crystal energy was low, suggesting that it is relatively stable. Its sensitivity was also low, as the molecular stacking that occurs in its crystal allows external forces to be dissipated into movements of crystal layers. Finally, its multicenter bond order was high, indicating a highly conjugated structure.

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariados, Neil, E-mail: nmariados@ampofny.com; Sylvester, John; Shah, Dhiren

2015-08-01

Purpose: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Methods and Materials: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapymore » (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Results: Spacer application was rated as “easy” or “very easy” 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Conclusions: Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.« less

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy.

PubMed

Mariados, Neil; Sylvester, John; Shah, Dhiren; Karsh, Lawrence; Hudes, Richard; Beyer, David; Kurtzman, Steven; Bogart, Jeffrey; Hsi, R Alex; Kos, Michael; Ellis, Rodney; Logsdon, Mark; Zimberg, Shawn; Forsythe, Kevin; Zhang, Hong; Soffen, Edward; Francke, Patrick; Mantz, Constantine; Rossi, Peter; DeWeese, Theodore; Hamstra, Daniel A; Bosch, Walter; Gay, Hiram; Michalski, Jeff

2015-08-01

Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

PubMed

Brzheskiy, Vladimir V; Efimova, Elena L; Vorontsova, Tatiana N; Alekseev, Vladimir N; Gusarevich, Olga G; Shaidurova, Ksenia N; Ryabtseva, Alla A; Andryukhina, Olga M; Kamenskikh, Tatiana G; Sumarokova, Elena S; Miljudin, Eugeny S; Egorov, Eugeny A; Lebedev, Oleg I; Surov, Alexander V; Korol, Andrii R; Nasinnyk, Illia O; Bezditko, Pavel A; Muzhychuk, Olena P; Vygodin, Vladimir A; Yani, Elena V; Savchenko, Alla Y; Karger, Elena M; Fedorkin, Oleg N; Mironov, Alexander N; Ostapenko, Victoria; Popeko, Natalia A; Skulachev, Vladimir P; Skulachev, Maxim V

2015-12-01

This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. Mitotech LLC.

Engaging stakeholders to design a comparative effectiveness trial in children with uncontrolled asthma

PubMed Central

Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A

2016-01-01

Aim: To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. Methods: We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Results: Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Conclusion: Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial. PMID:26690579

Learning styles and teaching/learning strategy preferences: implications for educating nurses in critical care, the operating room, and infection control.

PubMed

Goldrick, B; Gruendemann, B; Larson, E

1993-01-01

To assess the learning styles and educational strategy preferences among critical care nurses, operating room nurses, and infection control practitioners. Descriptive multicenter survey using a self-report questionnaire. 108 hospitals from nine geographic regions of the United States. A random sample of 303 (93%) nurses in the three specialties responded to the survey questionnaires. The majority of participants (64%) had an abstract learning style and preferred the self-directed, discovery approach to learning. Nurses may be more abstract in their learning styles than previously reported. Experiential learning theory is an effective means of identifying nurses' learning styles and teaching/learning preferences, which can then be used to plan basic and continuing educational programs.

Spinal Cord Injury

MedlinePlus

... A recent prospective multicenter trial called STASCIS is exploring whether performing decompression surgery early (less than 24 ... A recent prospective multicenter trial called STASCIS is exploring whether performing decompression surgery early (less than 24 ...

Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach.

PubMed

Müller, Hans-Peter; Grön, Georg; Sprengelmeyer, Reiner; Kassubek, Jan; Ludolph, Albert C; Hobbs, Nicola; Cole, James; Roos, Raymund A C; Duerr, Alexandra; Tabrizi, Sarah J; Landwehrmeyer, G Bernhard; Süssmuth, Sigurd D

2013-01-01

Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale.

Use of psi(alpha)-ETOs in the unified treatment of electronic attraction, electric field and electric field gradient multicenter integrals of screened Coulomb potentials over Slater orbitals.

PubMed

Guseinov, Israfil

2004-02-01

In this study, using complete orthonormal sets of Psi(alpha)-ETOs (where alpha=1, 0, -1, -2, ...) introduced by the author, a large number of series expansion formulae for the multicenter electronic attraction (EA), electric field (EF) and electric field gradient (EFG) integrals of the Yukawa-like screened Coulomb potentials (SCPs) is presented through the new central and noncentral potentials and the overlap integrals with the same screening constants. The final results obtained are valid for arbitrary locations of STOs and their parameters.

Who benefit from school doctors' health checks: a prospective study of a screening method.

PubMed

Nikander, Kirsi; Kosola, Silja; Kaila, Minna; Hermanson, Elina

2018-06-27

School health services provide an excellent opportunity for the detection and treatment of children at risk of later health problems. However, the optimal use of school doctors' skills and expertise remains unknown. Furthermore, no validated method for screening children for school doctors' assessments exists. The aims of the study are 1) to evaluate the benefits or harm of school doctors' routine health checks in primary school grades 1 and 5 (at ages 7 and 11) and 2) to explore whether some of the school doctors' routine health checks can be omitted using study questionnaires. This is a prospective, multicenter observational study conducted in four urban municipalities in Southern Finland by comparing the need for a school doctor's assessment to the benefit gained from it. We will recruit a random sample of 1050 children from 21 schools from primary school grades 1 and 5. Before the school doctor's health check, parents, nurses and teachers fill a study questionnaire to identify any potential concerns about each child. Doctors, blinded to the questionnaire responses, complete an electronic report after the appointment, including given instructions and follow-up plans. The child, parent, doctor and researchers assess the benefit of the health check. The researchers compare the need for a doctor's appointment to the benefit gained from it. At one year after the health check, we will analyze the implementation of the doctors' interventions and follow-up plans. The study will increase our knowledge of the benefits of school doctors' routine health checks and assess the developed screening method. We hypothesize that targeting the health checks to the children in greatest need would increase the quality of school health services. ClinicalTrials.gov Identifier: NCT03178331 , date of registration June 6 th 2017.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Adjusted regression trend test for a multicenter clinical trial.

PubMed

Quan, H; Capizzi, T

1999-06-01

Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

[Attaching importance to study on acute health risk assessment and adaptation of air pollution and climate change].

PubMed

Shi, X M

2017-03-10

Air pollution and climate change have become key environmental and public health problems around the world, which poses serious threat to human health. How to assess and mitigate the health risks and increase the adaptation of the public have become an urgent topic of research in this area. The six papers in this issue will provide important and rich information on design, analysis method, indicator selection and setting about acute health risk assessment and adaptation study of air pollution and climate change in China, reflecting the advanced conceptions of multi-center and area-specific study and multi-pollutant causing acute effect study. However, the number and type of the cities included in these studies were still limited. In future, researchers should further expand detailed multi-center and multi-area study coverage, conduct area specific predicting and early warning study and strengthen adaptation study.

Multicenter Evaluation Of Coronary Dual-Source CT angiography in patients with intermediate Risk of Coronary Artery Stenoses (MEDIC): study design and rationale.

PubMed

Marwan, Mohamed; Hausleiter, Jörg; Abbara, Suhny; Hoffmann, Udo; Becker, Christoph; Ovrehus, Kristian; Ropers, Dieter; Bathina, Ravi; Berman, Dan; Anders, Katharina; Uder, Michael; Meave, Aloha; Alexánderson, Erick; Achenbach, Stephan

2014-01-01

The diagnostic performance of multidetector row CT to detect coronary artery stenosis has been evaluated in numerous single-center studies, with only limited data from large cohorts with low-to-intermediate likelihood of coronary disease and in multicenter trials. The Multicenter Evaluation of Coronary Dual-Source CT Angiography in Patients with Intermediate Risk of Coronary Artery Stenoses (MEDIC) trial determines the accuracy of dual-source CT (DSCT) to identify persons with at least 1 coronary artery stenosis among patients with low-to-intermediate pretest likelihood of disease. The MEDIC trial was designed as a prospective, multicenter, international trial to evaluate the diagnostic performance of DSCT for the detection of coronary artery stenosis compared with invasive coronary angiography. The study includes 8 sites in Germany, India, Mexico, the United States, and Denmark. The study population comprises patients referred for a diagnostic coronary angiogram because of suspected coronary artery disease with an intermediate pretest likelihood as determined by sex, age, and symptoms. All evaluations are performed by blinded core laboratory readers. The primary outcome of the MEDIC trial is the accuracy of DSCT to identify the presence of coronary artery stenoses with a luminal diameter narrowing of 50% or more on a per-vessel basis. Secondary outcome parameters include per-patient and per-segment diagnostic accuracy for 50% stenoses and accuracy to identify stenoses of 70% or more. Furthermore, secondary outcome parameters include the influence of heart rate, Agatston score, body weight, body mass index, image quality, and diagnostic confidence on the accuracy to detect coronary artery stenoses >50% on a per-vessel basis. The results of the MEDIC trial will assess the clinical utility of coronary CT angiography in the evaluation of patients with intermediate pretest likelihood of coronary artery disease. Copyright © 2014 Society of Cardiovascular Computed Tomography. All rights reserved.

Diagnostic performance of computed tomography coronary angiography (from the Prospective National Multicenter Multivendor EVASCAN Study).

PubMed

Gueret, Pascal; Deux, Jean-François; Bonello, Laurent; Sarran, Anthony; Tron, Christophe; Christiaens, Luc; Dacher, Jean-Nicolas; Bertrand, David; Leborgne, Laurent; Renard, Cedric; Caussin, Christophe; Cluzel, Philippe; Helft, Gerard; Crochet, Dominique; Vernhet-Kovacsik, Hélène; Chabbert, Valérie; Ferrari, Emile; Gilard, Martine; Willoteaux, Serge; Furber, Alain; Barone-Rochette, Gilles; Jankowski, Adrien; Douek, Philippe; Mousseaux, Elie; Sirol, Marc; Niarra, Ralph; Chatellier, Gilles; Laissy, Jean-Pierre

2013-02-15

Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study.

PubMed

Zabor, Emily C; Furberg, Helena; Lee, Byron; Campbell, Steven; Lane, Brian R; Thompson, R Houston; Antonio, Elvis Caraballo; Noyes, Sabrina L; Zaid, Harras; Jaimes, Edgar A; Russo, Paul

2018-04-01

We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma. A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event. This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preoperative estimated glomerular filtration rate had an increased chance of recovery. This study also suggested that larger tumor size and female gender were significantly associated with an increased chance of renal function recovery. In this multicenter retrospective study we confirmed that in the long term a large proportion of patients recover to preoperative renal function following radical nephrectomy for kidney tumors. Recovery is more likely among those with a lower preoperative estimated glomerular filtration rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

First report on the nationwide incidence of type 1 diabetes and ketoacidosis at onset in children in Serbia: a multicenter study.

PubMed

Vukovic, Rade; Jesic, Maja D; Vorgucin, Ivana; Stankovic, Sandra; Folic, Nevena; Milenkovic, Tatjana; Sajic, Silvija; Katanic, Dragan; Zivic, Sasa; Markovic, Slavica; Soldatovic, Ivan

2018-05-17

Data regarding incidence of type 1 diabetes (T1DM), as well as data on frequency and severity of diabetic ketoacidosis (DKA) at the time of T1DM diagnosis is of paramount importance for national and regional healthcare planning. The aim of present multicenter study was to provide the first report regarding nationwide annual incidence rates for T1DM in youth in Serbia, as well as prevalence of DKA at the time of diagnosis. Data on all pediatric patients with newly diagnosed T1DM was retrospectively collected from all 15 regional centers for pediatric diabetes in Serbia during the period 2007-2017. During the study period, average-standardized incidence of T1DM in youth < 19 years was 11.82/100,000, and 14.28/100,000 in 0-14 years age group, with an average yearly increase in incidence of 5.9%. High prevalence of DKA (35.1%) at the time of diagnosis was observed, with highest frequency in children aged < 5 years (47.2%). This is the first study reporting the nationwide incidence of T1DM and alarmingly high prevalence of DKA at diagnosis in youth in Serbia. The focus of public health preventive measures should be directed towards the preschoolers, considering the highest frequency and severity of DKA observed in this age group. What is Known: • Knowing regional T1DM incidence is of paramount importance for resource allocation and healthcare services provision. • DKA is the leading cause of acute mortality in youth with T1DM, and public health preventive educational measures could improve early diagnosis and reduce the frequency and severity of DKA at presentation. What is New: • Incidence of pediatric T1DM in Serbia is on the rise, with an average yearly increase of 5.9%. • Worryingly high prevalence of DKA (35.1%) at the time of T1DM diagnosis was observed, with the highest frequency of DKA in children aged < 5 years (47.2%).

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

PubMed

Qu, Jianhui; Yu, Zujiang; Li, Qin; Chen, Yongping; Xiang, Dedong; Tan, Lin; Lei, Chunliang; Bai, Wenlin; Li, Hongyan; Shang, Qinghua; Chen, Liang; Hu, Xiaoyu; Lu, Wei; Li, Zhiqin; Chen, Da; Wang, Xiaodong; Zhang, Changjiang; Xiao, Guangming; Qi, Xun; Chen, Jing; Zhou, Li; Chen, Guofeng; Li, Yonggang; Zeng, Zhen; Rong, Guanghua; Dong, Zheng; Chen, Yan; Lou, Min; Wang, Chunping; Lu, Yinying; Zhang, Cuihong; Yang, Yongping

2014-11-10

Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study

PubMed Central

Liang, Ying; Cao, Changan; Zhu, Cheng; Wang, Chuanyue; Zhang, Congpei; Dong, Fang; Yang, Fude; Deng, Hong; Yu, Jingjie; Tang, Jisheng; Su, Lei; Xin, Limin; Hong, Ling; Gao, Minglong; Tang, Muni; Xie, Shiping; Lu, Shuiping; Liu, Tiebang; Xu, Xiaojin; Wang, Xijin; Li, Xuanzi; Wang, Xueyi; Li, Yi; Zhang, Yong; Chen, Zhiyu

2016-01-01

Abstract Introduction This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. Methods A multicenter, single‐arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Results A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. Discussion Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia. PMID:27020720

Impact of the Cancer Prevention and Control Research Network

PubMed Central

Ribisl, Kurt M.; Fernandez, Maria E.; Friedman, Daniela B.; Hannon, Peggy; Leeman, Jennifer; Moore, Alexis; Olson, Lindsay; Ory, Marcia; Risendal, Betsy; Sheble, Laura; Taylor, Vicky; Williams, Rebecca; Weiner, Bryan J.

2018-01-01

The Cancer Prevention and Control Research Network (CPCRN) is a thematic network dedicated to accelerating the adoption of evidence-based cancer prevention and control practices in communities by advancing dissemination and implementation science. Funded by the Centers for Disease Control and Prevention and National Cancer Institute, CPCRN has operated at two levels: Each participating Network Center conducts research projects with primarily local partners as well as multicenter collaborative research projects with state and national partners. Through multicenter collaboration, thematic networks leverage the expertise, resources, and partnerships of participating centers to conduct research projects collectively that might not be feasible individually. Although multicenter collaboration often is advocated, it is challenging to promote and assess. Using bibliometric network analysis and other graphical methods, this paper describes CPCRN’s multicenter publication progression from 2004 to 2014. Searching PubMed, Scopus, and Web of Science in 2014 identified 249 peer-reviewed CPCRN publications involving two or more centers out of 6,534 total. The research and public health impact of these multicenter collaborative projects initiated by CPCRN during that 10-year period were then examined. CPCRN established numerous workgroups around topics such as: 2-1-1, training and technical assistance, colorectal cancer control, federally qualified health centers, cancer survivorship, and human papillomavirus. The paper discusses the challenges that arise in promoting multicenter collaboration and the strategies that CPCRN uses to address those challenges. The lessons learned should broadly interest those seeking to promote multisite collaboration to address public health problems, such as cancer prevention and control. PMID:28215371

The QUASAR reproducibility study, Part II: Results from a multi center Arterial Spin Labeling test-retest Study

PubMed Central

Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

2009-01-01

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed “The QUASAR reproducibility study”. Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87±0.95mm and rotations of 1.56±0.66°. Mean gray matter CBF was 47.4±7.5 [ml/100g/min] with a between subject standard variation SDb = 5.5 [ml/100g/min] and a within subject standard deviation SDw = 4.7 [ml/100g/min]. The corresponding repeatability was 13.0 [ml/100g/min] and was found to be within the range of previous studies. PMID:19660557

SUNSET: Stereotactic Radiation for Ultracentral Non-Small-Cell Lung Cancer-A Safety and Efficacy Trial.

PubMed

Giuliani, Meredith; Mathew, Ashwathy S; Bahig, Houda; Bratman, Scott V; Filion, Edith; Glick, Daniel; Louie, Alexander V; Raman, Srinivas; Swaminath, Anand; Warner, Andrew; Yau, Vivian; Palma, David

2018-04-18

Lung stereotactic body radiotherapy (SBRT) is considered a standard curative treatment for medically inoperable early stage non-small-cell lung cancer (NSCLC). Patients with ultracentral tumors (signifying tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, or pulmonary artery) may be at higher risk of serious toxicities such as bronchial stricture and collapse, esophageal strictures, tracheal-esophageal fistula, and hemorrhage. The primary objective of the study is to determine the maximum tolerated dose of radiotherapy for ultracentral NSCLC. This multicenter phase 1 dose-escalation study will use a time-to-event continual reassessment method (TITE-CRM). Accrual will start at level 1 (60 Gy in 8 fractions delivered daily). The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 30% or less. All patients with newly diagnosed stage T1-3 N0M0 NSCLC (International Union Against Cancer, 8th edition) with tumor size ≤ 6 cm and meeting the criteria for ultracentral location (ie, tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, pulmonary vein, or pulmonary artery) will be eligible for this study. It is important to identify a safe dose-fractionation regimen for treating ultracentral tumors with SBRT. In addition, the data from this study may be informative in guiding future studies on the use of SBRT in treating malignancies within the mediastinum-for example, for salvage treatment of mediastinal lymph nodes for recurrent NSCLC or mediastinal oligometastases. Copyright © 2018 Elsevier Inc. All rights reserved.

Anchor Trial Launch

Cancer.gov

NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

Emerging indications of endoscopic radiofrequency ablation

PubMed Central

Becq, Aymeric; Camus, Marine; Rahmi, Gabriel; de Parades, Vincent; Marteau, Philippe

2015-01-01

Introduction Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. Results Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. Conclusions Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases. PMID:26279839

[Information management in multicenter studies: the Brazilian longitudinal study for adult health].

PubMed

Duncan, Bruce Bartholow; Vigo, Álvaro; Hernandez, Émerson; Luft, Vivian Cristine; Ahlert, Hubert; Bergmann, Kaiser; Mota, Eduardo

2013-06-01

Information management in large multicenter studies requires a specialized approach. The Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil - Brazilian Longitudinal Study for Adult Health) has created a Datacenter to enter and manage its data system. The aim of this paper is to describe the steps involved, including the information entry, transmission and management methods. A web system was developed in order to allow, in a safe and confidential way, online data entry, checking and editing, as well as the incorporation of data collected on paper. Additionally, a Picture Archiving and Communication System was implemented and customized for echocardiography and retinography. It stores the images received from the Investigation Centers and makes them available at the Reading Centers. Finally, data extraction and cleaning processes were developed to create databases in formats that enable analyses in multiple statistical packages.

[The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire].

PubMed

Goebel, G; Hiller, W

1994-03-01

The clinical examination of patients with severe and chronic tinnitus must include associated psychological disturbances. The present paper describes traditional diagnostic methods of ENT practice as well as the Tinnitus Questionnaire (TQ) which has been evaluated in a number of studies. This instrument differentiates between emotional and cognitive distress, auditory perceptual difficulties and self-experienced intrusiveness produced by the tinnitus. The results of a German multicenter study are presented which show that the TQ can be used to demonstrate differences of tinnitus distress under different clinical conditions (e.g., ENT clinic vs psychosomatic clinic and in- vs out-patient care). The TQ can be employed for comparative studies in different tinnitus-related institutions and for the evaluation of the relative effects of different treatment approaches.

Reliability of 3-Dimensional Measures of Single-Leg Cross Drop Landing Across 3 Different Institutions

PubMed Central

DiCesare, Christopher A.; Bates, Nathaniel A.; Barber Foss, Kim D.; Thomas, Staci M.; Wordeman, Samuel C.; Sugimoto, Dai; Roewer, Benjamin D.; Medina McKeon, Jennifer M.; Di Stasi, Stephanie; Noehren, Brian W.; Ford, Kevin R.; Kiefer, Adam W.; Hewett, Timothy E.; Myer, Gregory D.

2015-01-01

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Study Design: Controlled laboratory study. Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Results: Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Conclusion: Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Clinical Relevance: Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated. PMID:26779550

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

PubMed

Oki, Eiji; Tokunaga, Shoji; Emi, Yasunori; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Ishigami, Sumiya; Tsuji, Akihito; Higashi, Hidefumi; Nakamura, Toshihiko; Saeki, Hiroshi; Shirabe, Ken; Kakeji, Yoshihiro; Sakai, Kenji; Baba, Hideo; Nishimaki, Tadashi; Natsugoe, Shoji; Maehara, Yoshihiko

2016-07-01

The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Application of the cultured epidermal autograft "JACE(®") for treatment of severe burns: Results of a 6-year multicenter surveillance in Japan.

PubMed

Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio

2016-06-01

In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Feasibility of the Atlas Unicompartmental Knee System Load Absorber in Improving Pain Relief and Function in Patients Needing Unloading of the Medial Compartment of the Knee: 1-Year Follow-Up of a Prospective, Multicenter, Single-Arm Pilot Study (PHANTOM High Flex Trial).

PubMed

Slynarski, Konrad; Walawski, Jacek; Smigielski, Robert; van der Merwe, Willem

2017-01-01

In young patients with medial knee osteoarthritis (OA), surgical intervention may not be desirable due to preferences to avoid bone cutting procedures, return to high activity levels, and prolong implant survival. The Atlas Knee System was designed to fill the gap between ineffective conservative treatments and invasive surgery. This single-arm study included 26 patients, aged 25 to 65 years, who completed 12 months of follow-up. All dimensions of the Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score significantly improved from baseline to 12 months. About 96.2% and 92.3% of patients experienced a ⩾20% improvement in their KOOS pain and WOMAC pain scores, respectively, at 12 months. This study highlights the potential benefit of a joint unloading device in the management of young patients with medial knee OA. The trial is still ongoing and another analysis is planned at 24 months.

Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

PubMed

Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

2016-07-01

With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation of standard operating procedures in a multicenter retrospective study to identify -omics biomarkers for chronic low back pain.

PubMed

Dagostino, Concetta; De Gregori, Manuela; Gieger, Christian; Manz, Judith; Gudelj, Ivan; Lauc, Gordan; Divizia, Laura; Wang, Wei; Sim, Moira; Pemberton, Iain K; MacDougall, Jane; Williams, Frances; Van Zundert, Jan; Primorac, Dragan; Aulchenko, Yurii; Kapural, Leonardo; Allegri, Massimo

2017-01-01

Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs) for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres) retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1) blood collection, (2) sample processing and storage, (3) shipping details and (4) cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson's disease.

PubMed

Müller, Thomas; Tolosa, Eduardo; Badea, Letitia; Asgharnejad, Mahnaz; Grieger, Frank; Markowitz, Michael; Nondonfaz, Xavier; Bauer, Lars; Timmermann, Lars

2018-06-01

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study.

PubMed

Rahbar, Mohammad H; Fox, Erin E; del Junco, Deborah J; Cotton, Bryan A; Podbielski, Jeanette M; Matijevic, Nena; Cohen, Mitchell J; Schreiber, Martin A; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah J; Reynolds, Robert J; Benjamin-Garner, Ruby; Holcomb, John B

2012-04-01

Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the US. PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1245 patients who received one or more blood transfusions within 6h of Emergency Department (ED) admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

PubMed Central

Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

2011-01-01

Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity.

PubMed

Sarrazin, Samuel; Poupon, Cyril; Linke, Julia; Wessa, Michèle; Phillips, Mary; Delavest, Marine; Versace, Amelia; Almeida, Jorge; Guevara, Pamela; Duclap, Delphine; Duchesnay, Edouard; Mangin, Jean-François; Le Dudal, Katia; Daban, Claire; Hamdani, Nora; D'Albis, Marc-Antoine; Leboyer, Marion; Houenou, Josselin

2014-04-01

Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI). To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes. A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants. Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for DSM-IV at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique. Generalized fractional anisotropy values along each reconstructed WM tract. Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing). In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.

Logistics and quality control for DNA sampling in large multicenter studies.

PubMed

Nederhand, R J; Droog, S; Kluft, C; Simoons, M L; de Maat, M P M

2003-05-01

To study associations between genetic variation and disease, large bio-banks need to be created in multicenter studies. Therefore, we studied the effects of storage time and temperature on DNA quality and quantity in a simulation experiment with storage up to 28 days frozen, at 4 degrees C and at room temperature. In the simulation experiment, the conditions did not influence the amount or quality of DNA to an unsatisfactory level. However, the amount of extracted DNA was decreased in frozen samples and in samples that were stored for > 7 days at room temperature. In a sample of patients from 24 countries of the EUROPA trial obtained by mail with transport times up to 1 month DNA yield and quality were adequate. From these results we conclude that transport of non-frozen blood by ordinary mail is usable and practical for DNA isolation for polymerase chain reaction in clinical and epidemiological studies.

Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: a multicenter clinical trial.

PubMed

Naydeck, B L; Sutton-Tyrrell, K; Burek, K; Sopko, G S

1996-06-01

Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization.

Prospective Validation of Objective Prognostic Score for Advanced Cancer Inpatients in South Korea: A Multicenter Study.

PubMed

Yoon, Seok Joon; Suh, Sang-Yeon; Lee, Yong Joo; Park, Jeanno; Hwang, Sunwook; Lee, Sanghee Shiny; Ahn, Hong Yup; Koh, Su-Jin; Park, Keon Uk

2017-01-01

Objective Prognostic Score (OPS) was developed as an easy and simple prognosticating tool in South Korea. It has been validated retrospectively in a single center in South Korea. We aimed to validate the OPS prospectively for advanced cancer inpatients in South Korea using a multicenter study. This was a prospective cohort study. We enrolled 243 advanced cancer patients admitted in five palliative care units in South Korea from May 2013 till March 2015. Seven members of the Korean Palliative Medicine Research Network who are experts of palliative care led the study. Clinical variables (dyspnea/anorexia/performance status) and laboratory variables (total leukocyte counts/serum total bilirubin/serum creatinine/lactate dehydrogenase) were collected at the enrollment. Survival time was calculated as days from enrollment to death during admission. A total of 217 patients were included in the final analysis (feasibility: 89.3%). Survival time of the higher OPS group (OPS ≥3) and the lower OPS group (OPS <3) was 10.0 (95% confidence interval (CI) 7.72-12.28) days and 32.0 (95% CI 25.44-38.56) days, respectively. There were significant differences between the 2 groups (p < 0.001). Overall accuracy of OPS ≥3 for predicting survival less than three weeks was 71.0%. OPS was successfully validated using a prospective multicenter study in South Korea. It is a useful method to predict three-week survival of Korean inpatients with advanced cancer.

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

PubMed

Tzimenatos, Leah; Kim, Emily; Kuppermann, Nathan

2014-12-01

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network (PECARN), and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future, but the growth of research in emergency medical services for children in general.

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

PubMed

Tzimenatos, Leah; Kim, Emily; Kuppermann, Nathan

2015-01-01

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future but the growth of research in emergency medical services for children in general.

Identification of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in Blood Cultures: a Multicenter Performance Evaluation of a Three-Color Peptide Nucleic Acid Fluorescence In Situ Hybridization Assay▿

PubMed Central

Della-Latta, Phyllis; Salimnia, Hossein; Painter, Theresa; Wu, Fann; Procop, Gary W.; Wilson, Deborah A.; Gillespie, Wendy; Mender, Alayna; Crystal, Benjamin S.

2011-01-01

A multicenter evaluation was undertaken to evaluate the performance of a new three-color peptide nucleic acid fluorescence in situ hybridization assay that identifies isolates directly from blood cultures positive for Gram-negative bacilli (GNB). The assay correctly identified 100% (186/186) of the Escherichia coli isolates, 99.1% (109/110) of the Klebsiella pneumoniae isolates, and 95.8% (46/48) of the Pseudomonas aeruginosa isolates in this study. Negative assay results were correctly obtained for 162 of 165 other GNB (specificity, 98.2%). PMID:21490185

A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer’s disease and loss of memory in women: design and baseline characteristics

PubMed Central

Sano, Mary; Jacobs, Diane; Andrews, Howard; Bell, Karen; Graff-Radford, Neill; Lucas, John; Rabins, Peter; Bolla, Karen; Tsai, Wei-Yan; Cross, Peter; Andrews, Karen; Costa, Rosann; Luo, Xiaodong

2012-01-01

Background Observational studies and small clinical trials suggested that hormone replacement therapy (HRT) decreases risk of cognitive loss and Alzheimer’s disease (AD) in postmenopausal women and may have value in primary prevention. Purpose A clinical trial was designed to determine if HRT delays AD or memory loss. This report describes the rationale and original design of the trial and details extensive modifications that were required to respond to unanticipated findings that emerged from other studies during the course of the trial. Methods The trial was designed as a multi-center, placebo-controlled primary prevention trial for women 65 years of age or older with a family history of dementia. Recruitment from local sites was supplemented by centralized efforts to use names of Medicare beneficiaries. Inclusion criteria included good general health and intact memory functioning. Participants were randomized to HRT or placebo in a 1:1 ratio. Assignment was stratified by hysterectomy status and site. The primary outcomes were incident AD and memory decline on neuropsychological testing. Results Enrollment began in March 1998. In response to the Women’s Health Initiative (WHI) May 2002 report of increased incidence of heart disease, stroke, pulmonary embolism, and breast cancer among women randomized to HRT, participants were re-consented with a revised consent form. Procedural modifications, including discontinuation of study medication and a modification of the planned primary outcome based on a final enrollment below the target enrollment (N = 477), were enacted in response to the subsequent WHI Memory Study report of increased risk of dementia and poorer cognitive function with HRT. The mean length of treatment exposure prior to discontinuation was 2.14 years. Participants’ mean age at baseline was 72.8; mean education was 14.2 years. Minority participation was 19% and 34% had a hysterectomy. The study continues to follow these participants for a total of 5 years blind to the original medication assignment. Limitations Results reported from the WHI during the course of this study mandated extensive procedural modifications, including discontinuing recruitment before completion and halting study medication. Alternative strategies for study redesign that were considered are discussed. PMID:18827045

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

PubMed

Geer, Eliza B; Shafiq, Ismat; Gordon, Murray B; Bonert, Vivien; Ayala, Alejandro; Swerdloff, Ronald S; Katznelson, Laurence; Lalazar, Yelena; Manuylova, Ekaterina; Pulaski-Liebert, Karen J; Carmichael, John D; Hannoush, Zeina; Surampudi, Vijaya; Broder, Michael S; Cherepanov, Dasha; Eagan, Marianne; Lee, Jackie; Said, Qayyim; Neary, Maureen P; Biller, Beverly M K

2017-08-01

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

PubMed

Davis, Stephanie D; Ratjen, Felix; Brumback, Lyndia C; Johnson, Robin C; Filbrun, Amy G; Kerby, Gwendolyn S; Panitch, Howard B; Donaldson, Scott H; Rosenfeld, Margaret

2016-05-01

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Development of a Multicenter Density Functional Tight Binding Model for Plutonium Surface Hydriding.

PubMed

Goldman, Nir; Aradi, Bálint; Lindsey, Rebecca K; Fried, Laurence E

2018-05-08

We detail the creation of a multicenter density functional tight binding (DFTB) model for hydrogen on δ-plutonium, using a framework of new Slater-Koster interaction parameters and a repulsive energy based on the Chebyshev Interaction Model for Efficient Simulation (ChIMES), where two- and three-center atomic interactions are represented by linear combinations of Chebyshev polynomials. We find that our DFTB/ChIMES model yields a total electron density of states for bulk δ-Pu that compares well to that from Density Functional Theory, as well as to a grid of energy calculations representing approximate H 2 dissociation paths on the δ-Pu (100) surface. We then perform molecular dynamics simulations and minimum energy pathway calculations to determine the energetics of surface dissociation and subsurface diffusion on the (100) and (111) surfaces. Our approach allows for the efficient creation of multicenter repulsive energies with a relatively small investment in initial DFT calculations. Our efforts are particularly pertinent to studies that rely on quantum calculations for interpretation and validation, such as experimental determination of chemical reactivity both on surfaces and in condensed phases.

Current concepts in cleft care: A multicenter analysis.

PubMed

Thiele, Oliver C; Kreppel, Matthias; Dunsche, Anton; Eckardt, Andre M; Ehrenfeld, Michael; Fleiner, Bernd; Gaßling, Volker; Gehrke, Gerd; Gerressen, Marcus; Gosau, Martin; Gröbe, Alexander; Haßfeld, Stefan; Heiland, Max; Hoffmeister, Bodo; Hölzle, Frank; Klein, Cornelius; Krüger, Maximilian; Kübler, Alexander C; Kübler, Norbert R; Kuttenberger, Johannes J; Landes, Constantin; Lauer, Günter; Martini, Markus; Merholz, Erich T; Mischkowski, Robert A; Al-Nawas, Bilal; Nkenke, Emeka; Piesold, Jörn U; Pradel, Winnie; Rasse, Michael; Rachwalski, Martin; Reich, Rudolf H; Rothamel, Daniel; Rustemeyer, Jan; Scheer, Martin; Schliephake, Henning; Schmelzeisen, Rainer; Schramm, Alexander; Schupp, Wiebke; Spitzer, Wolfgang J; Stocker, Erwin; Stoll, Christian; Terheyden, Hendrik; Voigt, Alexander; Wagner, Wilfried; Weingart, Dieter; Werkmeister, Richard; Wiltfang, Jörg; Ziegler, Christoph M; Zöller, Joachim E

2018-04-01

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

PubMed

Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

2015-06-01

A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Test-retest and between-site reliability in a multicenter fMRI study.

PubMed

Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

2008-08-01

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach☆

PubMed Central

Müller, Hans-Peter; Grön, Georg; Sprengelmeyer, Reiner; Kassubek, Jan; Ludolph, Albert C.; Hobbs, Nicola; Cole, James; Roos, Raymund A.C.; Duerr, Alexandra; Tabrizi, Sarah J.; Landwehrmeyer, G. Bernhard; Süssmuth, Sigurd D.

2013-01-01

Purpose Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. Materials and methods Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. Results The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. Conclusion Averaging FA-maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale. PMID:24179771

Prognostic values of common clinical parameters in advanced pancreatic ductal adenocarcinoma: a large multicenter cohort study of ten years.

PubMed

Zhang, Chenyue; Dong, Shu; Wang, Lei; Yu, Songlin; Zheng, Yuwei; Geng, Yanyan; Shen, Xiaoheng; Ying, Haifeng; Guo, Yuanbiao; Yu, Jinming; Deng, Qinglong; Meng, Zhiqiang; Li, Zhaoshen; Chen, Hao; Shen, Yehua; Chen, Qiwen

2018-03-01

We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and 28.5%, respectively. The median survival of stage IV patients was 5.4 months, with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%, respectively. In multivariate analyses, primary tumor diameter, low albumin, and elevated CA19-9 were associated with decreased survival for stage III patients. Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and elevated CA19-9 were associated with decreased survival for stage IV patients. Elevated CA19-9 level, decreased albumin level, and tumor size were associated with worse survival in stage III patients. Meanwhile, advanced age, smoking, and ALT or AST level were negatively correlated to prognosis in stage IV patients.

Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models.

PubMed

Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P

2012-01-01

In a phase III multi-center cancer clinical trial or a large public health study, sample size is predetermined to achieve desired power, and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date on the basis of the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment, and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B-38. The results showed that application of the proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.

Addressing data privacy in matched studies via virtual pooling.

PubMed

Saha-Chaudhuri, P; Weinberg, C R

2017-09-07

Data confidentiality and shared use of research data are two desirable but sometimes conflicting goals in research with multi-center studies and distributed data. While ideal for straightforward analysis, confidentiality restrictions forbid creation of a single dataset that includes covariate information of all participants. Current approaches such as aggregate data sharing, distributed regression, meta-analysis and score-based methods can have important limitations. We propose a novel application of an existing epidemiologic tool, specimen pooling, to enable confidentiality-preserving analysis of data arising from a matched case-control, multi-center design. Instead of pooling specimens prior to assay, we apply the methodology to virtually pool (aggregate) covariates within nodes. Such virtual pooling retains most of the information used in an analysis with individual data and since individual participant data is not shared externally, within-node virtual pooling preserves data confidentiality. We show that aggregated covariate levels can be used in a conditional logistic regression model to estimate individual-level odds ratios of interest. The parameter estimates from the standard conditional logistic regression are compared to the estimates based on a conditional logistic regression model with aggregated data. The parameter estimates are shown to be similar to those without pooling and to have comparable standard errors and confidence interval coverage. Virtual data pooling can be used to maintain confidentiality of data from multi-center study and can be particularly useful in research with large-scale distributed data.

Management of children with solid organ injuries after blunt torso trauma.

PubMed

Wisner, David H; Kuppermann, Nathan; Cooper, Arthur; Menaker, Jay; Ehrlich, Peter; Kooistra, Josh; Mahajan, Prashant; Lee, Lois; Cook, Lawrence J; Yen, Kenneth; Lillis, Kathy; Holmes, James F

2015-08-01

Management of children with intra-abdominal solid organ injuries has evolved markedly. We describe the current management of children with intra-abdominal solid organ injuries after blunt trauma in a large multicenter network. We performed a planned secondary analysis of a prospective, multicenter observational study of children (<18 years) with blunt torso trauma. We included children with spleen, liver, or kidney injuries identified by computed tomography, laparotomy/laparoscopy, or autopsy. Outcomes included disposition and interventions (blood transfusion for intra-abdominal hemorrhage, angiography, laparotomy/laparoscopy). We performed subanalyses of children with isolated injuries. A total of 12,044 children were enrolled; 605 (5.0%) had intra-abdominal solid organ injuries. The mean (SD) age was 10.7 (5.1) years, and injured organs included spleen 299 (49.4%), liver 282 (46.6%), and kidney 147 (24.3%). Intraperitoneal fluid was identified on computed tomography in 461 (76%; 95% confidence interval [CI], 73-80%), and isolated solid organ injuries were present in 418 (69%; 95% CI, 65-73%). Treatment included therapeutic laparotomy in 17 (4.1%), angiographic embolization in 6 (1.4%), and blood transfusion in 46 (11%) patients. Laparotomy rates for isolated injury were 11 (5.4%) of 205 (95% CI, 2.7-9.4%) at non-freestanding children's hospitals and 6 (2.8%) of 213 (95% CI, 1.0-6.0%) at freestanding children's hospitals (difference, 2.6%; 95% CI, -7.1% to 12.2%). Dispositions of the 212 children with isolated Grade I or II organ injuries were home in 6 (3%), emergency department observation in 9 (4%), ward in 114 (54%), intensive care unit in 73 (34%), operating suite in 7 (3%), and transferred in 3 (1%) patients. Intensive care unit admission for isolated Grade I or II injuries varied by center from 9% to 73%. Most children with solid organ injuries are managed with observation. Blood transfusion, while uncommon, is the most frequent therapeutic intervention; angiographic embolization and laparotomy are uncommon. Emergency department disposition of children with isolated Grade I to II solid organ injuries is highly variable and often differs from published guidelines. Prognostic/epidemiologic study, level III; therapeutic study, level IV.

Evaluation of time, attendance of medical staff, and resources during interstitial brachytherapy for prostate cancer : DEGRO-QUIRO trial.

PubMed

Tselis, N; Maurer, U; Popp, W; Sack, H; Zamboglou, N

2014-04-01

The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures. Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period. For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n = 112 measurements) and 6 min for LDR BRT (n = 21). Catheter implantation with intraoperative HDR real-time planning (n = 112), postimplantation HDR treatment planning (n = 112), and remotely controlled HDR afterloading irradiation (n = 112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n = 39) and LDR treatment postplanning (n = 32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT. In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

PubMed

Martínez-Sellés, M; Gómez Doblas, J J; Carro Hevia, A; García de la Villa, B; Ferreira-González, I; Alonso Tello, A; Andión Ogando, R; Ripoll Vera, T; Arribas Jiménez, A; Carrillo, P; Rodríguez Pascual, C; Casares i Romeva, M; Borras, X; Cornide, L; López-Palop, R

2014-06-01

To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. Transnational registry in Spain. We included 928 patients aged ≥80 years with severe symptomatic AS. Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. All-cause death. Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Dosimetric comparison of four different external beams for breast irradiation

NASA Astrophysics Data System (ADS)

Lee, Yoon Hee; Chung, Weon Kuu; Kim, Dong Wook; Kwon, Oh Young

2017-02-01

An intensity-modulated radiation-therapy (IMRT)-based technique, blocked single iso-centric IMRT (IMRT), is compared to multi-center IMRT (MIRT) and other conventional techniques such as three dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) for the treatment of breast cancer patients. Four different plans were devised and compared for 15 breast cancer patients, all of whom had early stage disease and had undergone breast conserving surgery. A total dose of 50.4 Gy in 28 fractions was prescribed as the planning target volume in all treatment plans. The doses to the ipsilateral lung, heart, and opposite breast were compared using a dose-volume histogram. The conformity index (CI), homogeneity index (HI), and coverage index (CoVI) were evaluated and compared among the four treatment techniques. The lifetime attributable risk (LAR) associated with each of the four techniques from age at exposure of 30 to 100 years was measured for the organs at risk. We found that MIRT had a better CoVI (1.02 ± 0.13 and 1.01 ± 0.04, respectively) and IMRT had a better CI (0.88 ± 0.04, and 0.87 ± 0.02, respectively) compared to the other three modalities. All four techniques had similar HIs. Moreover, we found that IMRT and MIRT were less likely to cause radiation induced-pneumonitis, 3D-CRT had the lowest LAR, IMRT and MIRT had similar LARs and VMAT had the highest LAR. In study we found that compared to the VMAT, MIRT and IMRT provided adequate the planning target volume (PTV) coverage and reduced the risk of secondary cancers in most of the organs at risk (OARs), while 3D-CRT had the lowest secondary-cancer risks. Therefore, 3D-CRT is still a reasonable choice for whole breast RT except for patients with complex PTV shapes, in which cases IMRT and MIRT may provide better target coverage.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Post-authorization safety study of Clottafact® , a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study.

PubMed

Négrier, C; Rothschild, C; Borg, J-Y; Lambert, T; Claeyssens, S; Sanhes, L; Stieltjes, N; Bertrand, A; André, M-H; Sié, P; Gruel, Y; Tellier, Z

2016-11-01

A new fibrinogen concentrate Clottafact ® was developed according to European guidelines on plasma-derived products. A post-authorization safety study was set up in 2009 as part of the risk management plan. This was a non-interventional, prospective, non-comparative, multicenter study of the use of fibrinogen concentrate for congenital afibrinogenemia in real-life medical practice in France. The analysis was descriptive and performed on 3 subgroups: prophylaxis vs. on-demand treatment, age (<6, <12 and ≥12) and severity of the deficiency. Fourteen patients [1-78 years] were included in 7 centres and followed for 1 year. Twenty-one adverse drug reactions (ADRs) classically reported with fibrinogen (pallor, chills, cough, vomiting, headache, urticaria and erythematous rash) were reported in 5 of 14 patients. Two ADRs were serious: an anaphylactic shock and a subclavian venous thrombosis with a favourable outcome without sequelae. In the nine patients under prophylaxis, 365 of 367 infusions were considered as successful (99·5%) and 2 as failures. For the five patients treated on-demand, the efficacy was rated as excellent for 27 of 48 infusions and good for the 21 others. This study confirms that the benefit/risk balance for this fibrinogen concentrate is favourable. © 2016 International Society of Blood Transfusion.

Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer.

PubMed

Bradley, Jeffrey; Thorstad, Wade L; Mutic, Sasa; Miller, Tom R; Dehdashti, Farrokh; Siegel, Barry A; Bosch, Walter; Bertrand, Rudi J

2004-05-01

Locoregional failure remains a significant problem for patients receiving definitive radiation therapy alone or combined with chemotherapy for non-small-cell lung cancer (NSCLC). Positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-d-glucose (FDG) has proven to be a valuable diagnostic and staging tool for NSCLC. This prospective study was performed to determine the impact of treatment simulation with FDG-PET and CT on radiation therapy target volume definition and toxicity profiles by comparison to simulation with computed tomography (CT) scanning alone. Twenty-six patients with Stages I-III NSCLC were studied. Each patient underwent sequential CT and FDG-PET simulation on the same day. Immobilization devices used for both simulations included an alpha cradle, a flat tabletop, 6 external fiducial markers, and a laser positioning system. A radiation therapist participated in both simulations to reproduce the treatment setup. Both the CT and fused PET/CT image data sets were transferred to the radiation treatment planning workstation for contouring. Each FDG-PET study was reviewed with the interpreting nuclear radiologist before tumor volumes were contoured. The fused PET/CT images were used to develop the three-dimensional conformal radiation therapy (3DCRT) plan. A second physician, blinded to the results of PET, contoured the gross tumor volumes (GTV) and planning target volumes (PTV) from the CT data sets, and these volumes were used to generate mock 3DCRT plans. The PTV was defined by a 10-mm margin around the GTV. The two 3DCRT plans for each patient were compared with respect to the GTV, PTV, mean lung dose, volume of normal lung receiving > or =20 Gy (V20), and mean esophageal dose. The FDG-PET findings altered the AJCC TNM stage in 8 of 26 (31%) patients; 2 patients were diagnosed with metastatic disease based on FDG-PET and received palliative radiation therapy. Of the 24 patients who were planned with 3DCRT, PET clearly altered the radiation therapy volume in 14 (58%), as follows. PET helped to distinguish tumor from atelectasis in all 3 patients with atelectasis. Unsuspected nodal disease was detected by PET in 10 patients, and 1 patient had a separate tumor focus detected within the same lobe of the lung. Increases in the target volumes led to increases in the mean lung dose, V20, and mean esophageal dose. Decreases in the target volumes in the patients with atelectasis led to decreases in these normal-tissue toxicity parameters. Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in over 50% of patients by comparison with CT targeting. The increasing availability of integrated PET/CT units will facilitate the use of this technology for radiation treatment planning. A confirmatory multicenter, cooperative group trial is planned within the Radiation Therapy Oncology Group.

Tug-of-war between classical and multicenter bonds in H-(Be)n-H species

NASA Astrophysics Data System (ADS)

Lundell, Katie A.; Boldyrev, Alexander I.

2018-05-01

Quantum chemical calculations were performed for beryllium homocatenated compounds [H-(Be)n-H]. Global minimum structures were found using machine searches (Coalescence Kick method) with density functional theory. Chemical bonding analysis was performed with the Adaptive Natural Density Partitioning method. It was found that H-(Be)2-H and H-(Be)3-H clusters are linear with classical two-center two-electron bonds, while for n > 3, three-dimensional structures are more stable with multicenter bonding. Thus, at n = 4, multicenter bonding wins the tug-of-war vs. the classical bonding.

Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study.

PubMed

Tazaki, Y; Sakai, F; Otomo, E; Kutsuzawa, T; Kameyama, M; Omae, T; Fujishima, M; Sakuma, A

1988-02-01

A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine (CDP-choline) was conducted to evaluate possible clinical benefits of the drug in patients with acute, moderate to severe cerebral infarction. The patients included also suffered from moderate to mild disturbances of consciousness, and all were admitted within 14 days of the ictus. Patients were allocated randomly to treatment with either CDP-choline (1,000 mg/day i.v. once daily for 14 days) or with placebo (physiological saline). One hundred thirty-three patients received CDP-choline treatment, and 139 received placebo. The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group, and CDP-choline was an entirely safe treatment.

A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India.

PubMed

Chandra, Praveen; Kumar, Tarun

2014-01-01

A prospective, multicenter, post marketing surveillance study to evaluate the safety and effectiveness of the Superia-Sirolimus Eluting Coronary Stent System (SSECSS) implanted during routine clinical practice in India. 1. To study the MACE and in stent and In-segment Loss at Six Months (in a pre selected group of 50 patients). 1. Clinical and procedural success. This is a prospective, open label, single-arm, multicenter (16 sites), post marketing observational study enrolling patients implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) in routine clinical practice in India. A total of 200 Patients of coronary Artery Disease (CAD) implanted with Superia-Sirolimus Eluting Coronary Stent (SSECS) were enrolled. Clinical assessments were done at 30 days, 180 days and at 1, 2 years either telephonically or office visit. A cohort of 50 pre-selected patients were followed up for angiographic evaluation at 180 days. MACE at 12 month of follow up was 1.71%.Late lumen loss, in segment was 0.14 and in stent was 0.10 mm at 6 month of follow-up. TLR was required only in 2 patients. Superia stent is as safe as other biodegradable polymer stent in the market and time has come for biodegradable polymer stent with thin struts. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

ECLAMC Study: prevalence patterns of hypospadias in South America: multi-national analysis over a 24-year period

PubMed Central

Fernández, Nicolás; Pérez, Jaime; Monterrey, Pedro; Poletta, Fernando A.; Bägli, Darius J.; Lorenzo, Armando J.; Zarante, Ignacio

2017-01-01

ABSTRACT Objective To evaluate prevalence trends of hypospadias in South-America it is essential to perform multicenter and multinational studies with the same methodology. Herein we present systematic data as part of an international multicenter initiative evaluating congenital malformations in South America over a 24-year period. Materials and Methods A nested case-control study was conducted using the Latin American Collaborative Study of Congenital Malformations (ECLAMC), between January 1989 and December 2012. Cases were stratified as isolated (IH) and non-isolated hypospadias (NIH). Global prevalence was calculated and discriminated by country. Associations between birth weight and gestational age, and NIH distribution by associated abnormality and severity of hypospadias, were analyzed. Results A total of 159 hospitals from six countries participated, reporting surveillance on 4.020.384 newborns. A total of 4.537 hypospadias cases were detected, with a global prevalence of 11.3/10.000 newborns. Trend analyses showed in Chile, Brazil and Uruguay a statistically significant increase in prevalence. Analysis of severity and associated anomalies did not to find an association for distal cases, but did for proximal (RR=1.64 [95% CI=1.33-2.03]). Conclusion This is one of only a few Latin American multicenter studies reporting on the epidemiology of hypospadias in South America in the last two decades. Our data adds to evidence suggesting an increase in some countries in the region at different times. There were also variations in prevalence according to severity. This study adds to literature describing associated anomalies at a hospital-based level. PMID:27802003

ECLAMC Study: Prevalence patterns of hypospadias in South America: Multi-national analysis over a 24-year period.

PubMed

Fernández, Nicolás; Pérez, Jaime; Monterrey, Pedro; Poletta, Fernando A; Bägli, Darius J; Lorenzo, Armando J; Zarante, Ignacio

2017-01-01

To evaluate prevalence trends of hypospadias in South-America it is essential to perform multicenter and multinational studies with the same methodology. Herein we present systematic data as part of an international multicenter initiative evaluating congenital malformations in South America over a 24-year period. A nested case-control study was conducted using the Latin American Collaborative Study of Congenital Malformations (ECLAMC), between January 1989 and December 2012. Cases were stratified as isolated (IH) and non-isolated hypospadias (NIH). Global prevalence was calculated and discriminated by country. Associations between birth weight and gestational age, and NIH distribution by associated abnormality and severity of hypospadias, were analyzed. A total of 159 hospitals from six countries participated, reporting surveillance on 4.020.384 newborns. A total of 4.537 hypospadias cases were detected, with a global prevalence of 11.3/10.000 newborns. Trend analyses showed in Chile, Brazil and Uruguay a statistically significant increase in prevalence. Analysis of severity and associated anomalies did not to find an association for distal cases, but did for proximal (RR=1.64 [95% CI=1.33-2.03]). This is one of only a few Latin American multicenter studies reporting on the epidemiology of hypospadias in South America in the last two decades. Our data adds to evidence suggesting an increase in some countries in the region at different times. There were also variations in prevalence according to severity. This study adds to literature describing associated anomalies at a hospital-based level. Copyright® by the International Brazilian Journal of Urology.

External validation of the Simplified Acute Physiology Score (SAPS) 3 in Spain.

PubMed

López-Caler, C; García-Delgado, M; Carpio-Sanz, J; Alvarez-Rodríguez, J; Aguilar-Alonso, E; Castillo-Lorente, E; Barrueco-Francioni, J E; Rivera-Fernández, R

2014-01-01

To evaluate SAPS 3 performance in Spain, assessing discrimination and calibration in a multicenter study. A prospective, multicenter study was carried out. A prospective cohort study was performed in Spanish hospitals between 2006 and 2011. A total of 2171 patients were included in the study. The mean age was 61.4±16.09 years, the ICU mortality was 11.6%, and hospital mortality 16.03%. The SAPS 3 score was 46.29±14.34 points, with a probability of death for our geographical area of 18.57%, and 17.97% for the general equation. The differences between observed-to-predicted mortality were analyzed with the Hosmer-Lemeshow test, which yielded H=31.71 (p<0.05) for our geographical area and H=20.05 (p<0.05) for the general equation. SAPS 3 discrimination with regard to hospital mortality, tested using the area under the ROC curve, was 0.845 (0.821-0.869). Our study shows good discrimination of the SAPS 3 system in Spain, but also inadequate calibration, with differences between predicted and observed mortality. There are more similarities with regard to the general equation than with respect to our geographical area equation, and in both cases the SAPS 3 system overestimates mortality. According to our results, Spanish ICU mortality is lower than in other hospitals included in the multicenter study that developed the SAPS 3 system, in patients with similar characteristics and severity of illness. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Reliability of Radiographic Assessments of Adolescent Midshaft Clavicle Fractures by the FACTS Multicenter Study Group.

PubMed

Li, Ying; Donohue, Kyna S; Robbins, Christopher B; Pennock, Andrew T; Ellis, Henry B; Nepple, Jeffrey J; Pandya, Nirav; Spence, David D; Willimon, Samuel Clifton; Heyworth, Benton E

2017-09-01

There is a recent trend toward increased surgical treatment of displaced midshaft clavicle fractures in adolescents. The primary purpose of this study was to evaluate the intrarater and interrater reliability of clavicle fracture classification systems and measurements of displacement, shortening, and angulation in adolescents. The secondary purpose was to compare 2 different measurement methods for fracture shortening. This study was performed by a multicenter study group conducting a prospective, comparative, observational cohort study of adolescent clavicle fractures. Eight raters evaluated 24 deidentified anteroposterior clavicle radiographs selected from patients 10-18 years of age with midshaft clavicle fractures. Two clavicle fracture classification systems were used, and 2 measurements for shortening, 1 measurement for superior-inferior displacement, and 2 measurements for fracture angulation were performed. A minimum of 2 weeks after the first round, the process was repeated. Intraclass correlation coefficients were calculated. Good to excellent intrarater and interrater agreement was achieved for the descriptive classification system of fracture displacement, direction of angulation, presence of comminution, and all continuous variables, including both measurements of shortening, superior-inferior displacement, and degrees of angulation. Moderate agreement was achieved for the Arbeitsgemeinschaft für Osteosynthesefragen classification system overall. Mean shortening by 2 different methods were significantly different from each other (P < 0.0001). Most radiographic measurements performed by investigators in a multicenter, prospective cohort study of adolescent clavicle fractures demonstrated good-to-excellent intrarater and interrater reliability. Future consensus on the most accurate and clinically appropriate measurement method for fracture shortening is critical.

Multicenter Outcomes After Hip Arthroscopy: Epidemiology (MASH Study Group). What Are We Seeing in the Office, and Who Are We Choosing to Treat?

PubMed

Kivlan, Benjamin R; Nho, Shane J; Christoforetti, John J; Ellis, Thomas J; Matsuda, Dean K; Salvo, John P; Wolff, Andrew B; Van Thiel, Geoffrey S; Stubbs, Allston J; Carreira, Dominic S

As the field of hip arthroscopy continues to grow rapidly, our understanding of the population of patients undergoing hip arthroscopy has led to improved diagnosis and management of hip joint pathologies. The Multicenter Arthroscopic Study of the Hip (MASH) Study Group conducts multicenter clinical studies in arthroscopic hip preservation surgery. Patients undergoing arthroscopic hip preservation surgery are enrolled in a large prospective longitudinal cohort at 10 separate sites nationwide by 10 fellowship-trained hip arthroscopists. In this study, we collected epidemiologic data on the 1738 patients who enrolled between January 2014 and November 2016. These data include demographics, pathologic entities treated, patient-reported measures of disease, and surgical treatment preferences. Our study results showed that patients who elected hip arthroscopy were younger to middle-aged white females with pain primarily located in the groin region. Most had pain for at least 1 year, and it was commonly exacerbated by sitting and athletic activities. Patients reported clinically significant pain and functional limitation and a decrease in physical and mental health. It was not uncommon for patients to have undergone another, related surgery and nonoperative treatments, including intra-articular injection and/or physical therapy, before surgery. There was a high incidence of abnormal hip morphology suggestive of a cam lesion, but the incidence of arthritic changes on radiographs was relatively low. Labral tear was the most common diagnosis, and most often it was addressed with repair. Many patients underwent femoroplasty, acetabuloplasty, and chondroplasty in addition to labral repair.

A Quality Improvement Collaborative to Improve the Discharge Process for Hospitalized Children.

PubMed

Wu, Susan; Tyler, Amy; Logsdon, Tina; Holmes, Nicholas M; Balkian, Ara; Brittan, Mark; Hoover, LaVonda; Martin, Sara; Paradis, Melisa; Sparr-Perkins, Rhonda; Stanley, Teresa; Weber, Rachel; Saysana, Michele

2016-08-01

To assess the impact of a quality improvement collaborative on quality and efficiency of pediatric discharges. This was a multicenter quality improvement collaborative including 11 tertiary-care freestanding children's hospitals in the United States, conducted between November 1, 2011 and October 31, 2012. Sites selected interventions from a change package developed by an expert panel. Multiple plan-do-study-act cycles were conducted on patient populations selected by each site. Data on discharge-related care failures, family readiness for discharge, and 72-hour and 30-day readmissions were reported monthly by each site. Surveys of each site were also conducted to evaluate the use of various change strategies. Most sites addressed discharge planning, quality of discharge instructions, and providing postdischarge support by phone. There was a significant decrease in discharge-related care failures, from 34% in the first project quarter to 21% at the end of the collaborative (P < .05). There was also a significant improvement in family perception of readiness for discharge, from 85% of families reporting the highest rating to 91% (P < .05). There was no improvement in unplanned 72-hour (0.7% vs 1.1%, P = .29) and slight worsening of the 30-day readmission rate (4.5% vs 6.3%, P = .05). Institutions that participated in the collaborative had lower rates of discharge-related care failures and improved family readiness for discharge. There was no significant improvement in unplanned readmissions. More studies are needed to evaluate which interventions are most effective and to assess feasibility in non-children's hospital settings. Copyright © 2016 by the American Academy of Pediatrics.

Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL).

PubMed

Rönö, Kristiina; Stach-Lempinen, Beata; Klemetti, Miira M; Kaaja, Risto J; Pöyhönen-Alho, Maritta; Eriksson, Johan G; Koivusalo, Saila B

2014-02-14

Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers.Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age.

Impact of the Cancer Prevention and Control Research Network: Accelerating the Translation of Research Into Practice.

PubMed

Ribisl, Kurt M; Fernandez, Maria E; Friedman, Daniela B; Hannon, Peggy A; Leeman, Jennifer; Moore, Alexis; Olson, Lindsay; Ory, Marcia; Risendal, Betsy; Sheble, Laura; Taylor, Vicky M; Williams, Rebecca S; Weiner, Bryan J

2017-03-01

The Cancer Prevention and Control Research Network (CPCRN) is a thematic network dedicated to accelerating the adoption of evidence-based cancer prevention and control practices in communities by advancing dissemination and implementation science. Funded by the Centers for Disease Control and Prevention and National Cancer Institute, CPCRN has operated at two levels: Each participating network center conducts research projects with primarily local partners as well as multicenter collaborative research projects with state and national partners. Through multicenter collaboration, thematic networks leverage the expertise, resources, and partnerships of participating centers to conduct research projects collectively that might not be feasible individually. Although multicenter collaboration is often advocated, it is challenging to promote and assess. Using bibliometric network analysis and other graphical methods, this paper describes CPCRN's multicenter publication progression from 2004 to 2014. Searching PubMed, Scopus, and Web of Science in 2014 identified 249 peer-reviewed CPCRN publications involving two or more centers out of 6,534 total. The research and public health impact of these multicenter collaborative projects initiated by CPCRN during that 10-year period were then examined. CPCRN established numerous workgroups around topics such as: 2-1-1, training and technical assistance, colorectal cancer control, federally qualified health centers, cancer survivorship, and human papillomavirus. This paper discusses the challenges that arise in promoting multicenter collaboration and the strategies that CPCRN uses to address those challenges. The lessons learned should broadly interest those seeking to promote multisite collaboration to address public health problems, such as cancer prevention and control. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

PubMed

Berwanger, Otavio; Santucci, Eliana Vieira; de Barros E Silva, Pedro Gabriel Melo; Jesuíno, Isabella de Andrade; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Santos, Renato Hideo Nakagawa; Laranjeira, Ligia Nasi; Egydio, Flávia de Mattos; Borges de Oliveira, Juliana Aparecida; Dall Orto, Frederico Toledo Campo; Beraldo de Andrade, Pedro; Bienert, Igor Ribeiro de Castro; Bosso, Carlos Eduardo; Mangione, José Armando; Polanczyk, Carisi Anne; Sousa, Amanda Guerra de Moraes Rego; Kalil, Renato Abdala Karam; Santos, Luciano de Moura; Sposito, Andrei Carvalho; Rech, Rafael Luiz; Sousa, Antônio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; Giraldez, Roberto Rocha Corrêa Veiga; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo Moraes Rego; Alexander, John Hunter; Granger, Christopher Bull; Lopes, Renato Delascio

2018-04-03

The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. clinicaltrials.gov Identifier: NCT01448642.

Protection of quality and innovation in radiation oncology: the prospective multicenter trial QUIRO of DEGRO: evaluation of time, attendance of medical staff, and resources during radiotherapy with tomotherapy.

PubMed

Winkler, Cornelia; Duma, M N; Popp, W; Sack, H; Budach, V; Molls, M; Kampfer, S

2014-10-01

The technical progress in radiotherapy in recent years has been tremendous. This also implies a change of human and time resources. However, there is a lack of data on this topic. Therefore, the DEGRO initiated several studies in the QUIRO project on this subject. The present publication focuses on results for tomotherapy systems and compares them with other IMRT techniques. Over a period of several months, time allocation was documented using a standard form at two university hospitals. The required time for individual steps in the treatment planning process was recorded for all involved professional groups (physicist, technician, and physician) by themselves. The time monitoring at the treatment machines was performed by auxiliary employees (student research assistants). Evaluation of the data was performed for all recorded data as well as by tumor site. A comparison was made between the two involved institutions. A total of 1,691 records were analyzed: 148 from head and neck (H&N) tumors, 460 from prostate cancer, 136 from breast cancer, and 947 from other tumor entities. The mean value of all data from both centers for the definition of the target volumes for H&N tumors took a radiation oncology specialist 75 min, while a physicist needed for the physical treatment planning 214 min. For prostate carcinomas, the times were 60 and 147 min, respectively, and for the group of other entities 63 and 192 min, respectively. For the first radiation treatment, the occupancy time of the linear accelerator room was 31, 26, and 30 min for each entity (H&N, prostate, other entities, respectively). For routine treatments 22, 18, and 21 min were needed for the particular entities. Major differences in the time required for the individual steps were observed between the two centers. This study gives an overview of the time and personnel requirements in radiation therapy using a tomotherapy system. The most representative analysis could be done for the room occupancy times during treatment in both centers. Due to the partly small amount of data and differing planning workflows between the two centers, it is problematic to draw a firm conclusion with regard to planning times. Overall, the time required for the tomotherapy treatment and planning is slightly higher compared to other IMRT techniques.

Effectiveness of a Medifast meal replacement program on weight, body composition and cardiometabolic risk factors in overweight and obese adults: a multicenter systematic retrospective chart review study.

PubMed

Coleman, Christopher D; Kiel, Jessica R; Mitola, Andrea H; Langford, Janice S; Davis, Kevin N; Arterburn, Linda M

2015-08-06

Recent medical guidelines emphasize the importance of actively treating overweight and obesity with diet and lifestyle intervention to achieve ≥ 5% weight loss in a 6-month period. Commercial programs offer one approach provided there is evidence of their efficacy and safety. This study was conducted to evaluate the effectiveness of the Medifast® 4 & 2 & 1 Plan™ on weight loss, body composition and cardiometabolic risk factors in overweight and obese adults. A systematic retrospective chart review of 310 overweight and obese clients following the Medifast 4 & 2 & 1 Plan at one of 21 Medifast Weight Control Centers® was conducted. Data were recorded electronically and key data points were independently verified. The primary endpoint was change from baseline body weight at 12 weeks. Within group paired t-tests were used to examine changes from baseline in a completers population. Differences between gender and age subgroups were examined using bivariate t-tests and mixed model regression analyses. For the primary endpoint at 12 weeks, body weight among completers (n = 185) was reduced by a mean of 10.9 ± 5.6 kg (-10.1%, p < 0.0001), and at 24 weeks (n = 81) mean weight was reduced by 16.0 ± 7.9 kg (-14.3%). At 12 and 24 weeks, 85% and 96% of those remaining on the plan, respectively, had lost ≥ 5% of their baseline body weight. Lean mass was preserved to within 5% of baseline throughout the 24 weeks, and fat mass represented ≥ 80% of the body weight lost from 12 weeks onward. Men, women, seniors (≥ 65 years), and non-seniors (<65 years) all had significant weight reductions with preservation of lean mass. Significant improvements in blood pressure, pulse and waist-to-hip ratio were observed. Mean weight regain among the subset who entered a formal maintenance phase was <2% during an average follow-up of 34 weeks. The meal plan was well tolerated, and program adherence was >85%. The 4 & 2 & 1 Plan used at Medifast Weight Control Centers was effective for weight loss, preservation of lean mass and improvement in cardiometabolic risk factors. The plan was generally well tolerated in a broad population of overweight and obese adults. #NCT02150837.

QIN. Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials

PubMed Central

Doot, Robert K.; Thompson, Tove; Greer, Benjamin E.; Allberg, Keith C.; Linden, Hannah M.; Mankoff, David A.; Kinahan, Paul E.

2012-01-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging is a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. PMID:22795929

Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials.

PubMed

Doot, Robert K; Thompson, Tove; Greer, Benjamin E; Allberg, Keith C; Linden, Hannah M; Mankoff, David A; Kinahan, Paul E

2012-11-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

PubMed Central

2014-01-01

Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Labeling for Big Data in radiation oncology: The Radiation Oncology Structures ontology.

PubMed

Bibault, Jean-Emmanuel; Zapletal, Eric; Rance, Bastien; Giraud, Philippe; Burgun, Anita

2018-01-01

Leveraging Electronic Health Records (EHR) and Oncology Information Systems (OIS) has great potential to generate hypotheses for cancer treatment, since they directly provide medical data on a large scale. In order to gather a significant amount of patients with a high level of clinical details, multicenter studies are necessary. A challenge in creating high quality Big Data studies involving several treatment centers is the lack of semantic interoperability between data sources. We present the ontology we developed to address this issue. Radiation Oncology anatomical and target volumes were categorized in anatomical and treatment planning classes. International delineation guidelines specific to radiation oncology were used for lymph nodes areas and target volumes. Hierarchical classes were created to generate The Radiation Oncology Structures (ROS) Ontology. The ROS was then applied to the data from our institution. Four hundred and seventeen classes were created with a maximum of 14 children classes (average = 5). The ontology was then converted into a Web Ontology Language (.owl) format and made available online on Bioportal and GitHub under an Apache 2.0 License. We extracted all structures delineated in our department since the opening in 2001. 20,758 structures were exported from our "record-and-verify" system, demonstrating a significant heterogeneity within a single center. All structures were matched to the ROS ontology before integration into our clinical data warehouse (CDW). In this study we describe a new ontology, specific to radiation oncology, that reports all anatomical and treatment planning structures that can be delineated. This ontology will be used to integrate dosimetric data in the Assistance Publique-Hôpitaux de Paris CDW that stores data from 6.5 million patients (as of February 2017).

Fulranumab in Patients With Pain Associated With Postherpetic Neuralgia and Postraumatic Neuropathy

PubMed Central

Wang, Hao; Romano, Gary; Fedgchin, Margaret; Russell, Lucille; Sanga, Panna; Kelly, Kathleen M.; Frustaci, Mary Ellen

2017-01-01

Objective: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. Methods: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3:2:2:3) to receive either placebo or one of 3 doses of fulranumab: 1 mg (1 mgQ4 wk), 3 mg (3 mgQ4 wk), or 10 mg (10 mgQ4 wk). PTN patients were randomized (1:1) to receive either placebo or fulranumab 10 mgQ4 wk. Results: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P>0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P>0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (>10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia. Discussion: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study. PMID:27153360

Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study.

PubMed

Ezeanolue, Echezona E; Nwizu, Chidi; Greene, Gregory S; Amusu, Olatilewa; Chukwuka, Chinwe; Ndembi, Nicaise; Smith, Rachel M; Chiller, Tom; Pharr, Jennifer; Kozel, Thomas R

2016-09-01

Worldwide, HIV-associated cryptococcal meningitis affects approximately 1 million persons and causes 600,000 deaths each year mostly in sub-Saharan Africa. Limited data exist on cryptococcal meningitis and antigenemia in Nigeria, and most studies are geographically restricted. We determined the prevalence of cryptococcal antigenemia (CrAg) among HIV-infected, treatment-naive individuals in Nigeria. This was a retrospective, cross-sectional study across 4 geographic regions in Nigeria. We performed CrAg testing using a lateral flow immunoassay on archived whole-blood samples collected from HIV-infected participants at US President's Emergency Plan for AIDS Relief (PEPFAR)-supported sites selected to represent the major geographical and ethnic diversity in Nigeria. Eligible samples were collected from consenting patients (>15 years) naive to antiretroviral therapy with CD4 count less than 200 cells per cubic millimeter and were stored in an -80°C freezer. A total of 2752 stored blood samples were retrospectively screened for CrAg. Most of the samples were from participants aged 30-44 years (57.6%), and 1570 (57.1%) were from women. The prevalence of CrAg positivity in specimens with CD4 <200 cells per cubic millimeter was 2.3% (95% confidence interval: 1.8% to 3.0%) and varied significantly across the 4 regions (P < 0.001). At 4.4% (3.2% to 5.9%), the South East contained the highest prevalence. The significant regional variation in CrAg prevalence found in Nigeria should be taken into consideration as plans are made to integrate routine screening into clinical care for HIV-infected patients.

Labeling for Big Data in radiation oncology: The Radiation Oncology Structures ontology

PubMed Central

Zapletal, Eric; Rance, Bastien; Giraud, Philippe; Burgun, Anita

2018-01-01

Purpose Leveraging Electronic Health Records (EHR) and Oncology Information Systems (OIS) has great potential to generate hypotheses for cancer treatment, since they directly provide medical data on a large scale. In order to gather a significant amount of patients with a high level of clinical details, multicenter studies are necessary. A challenge in creating high quality Big Data studies involving several treatment centers is the lack of semantic interoperability between data sources. We present the ontology we developed to address this issue. Methods Radiation Oncology anatomical and target volumes were categorized in anatomical and treatment planning classes. International delineation guidelines specific to radiation oncology were used for lymph nodes areas and target volumes. Hierarchical classes were created to generate The Radiation Oncology Structures (ROS) Ontology. The ROS was then applied to the data from our institution. Results Four hundred and seventeen classes were created with a maximum of 14 children classes (average = 5). The ontology was then converted into a Web Ontology Language (.owl) format and made available online on Bioportal and GitHub under an Apache 2.0 License. We extracted all structures delineated in our department since the opening in 2001. 20,758 structures were exported from our “record-and-verify” system, demonstrating a significant heterogeneity within a single center. All structures were matched to the ROS ontology before integration into our clinical data warehouse (CDW). Conclusion In this study we describe a new ontology, specific to radiation oncology, that reports all anatomical and treatment planning structures that can be delineated. This ontology will be used to integrate dosimetric data in the Assistance Publique—Hôpitaux de Paris CDW that stores data from 6.5 million patients (as of February 2017). PMID:29351341

[Drug consumption and occupational violence in working women, a multicenter study: Mexico, Peru, Brazil].

PubMed

Alonso Castillo, Maria Magdalena; Musayon Oblitas, Flor Yesenia; David, Helena Maria Scherlowski Leal; Gómez Meza, Marco Vinicio

2006-01-01

The purposes of the study were: 1) Determine the proportion of working women who consume drugs; 2) identify some occupational and personal risk factors that can predict drugs consumption; 3) identify the presence of occupational violence and its relation with drugs consumption; 4) identify differences and similarities in drugs consumption and occupational violence among women from three communities in Mexico (Monterrey), Peru (Lima) and Brazil (Rio de Janeiro). A multicenter, descriptive, correlational and comparative study was carried out, with a sample of 903 women. The results show that 11% of the participants in Mexico consume alcohol, 53% in Peru and 45% in Brazil. The consumption of illicit drugs corresponded to 5% in Mexico and 6% in Peru. The presence of occupational violence was found in 16% of the Mexican participants, 24% of the Peruvians and 39% of the Brazilians.

A multicenter prospective study to assess the effect of early cleavage on embryo quality, implantation, and live-birth rate.

PubMed

de los Santos, Maria José; Arroyo, Gemma; Busquet, Ana; Calderón, Gloria; Cuadros, Jorge; Hurtado de Mendoza, Maria Victoria; Moragas, Marta; Herrer, Raquel; Ortiz, Agueda; Pons, Carme; Ten, Jorge; Vilches, Miguel Angel; Figueroa, Maria José

2014-04-01

To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates. Prospective cross-sectional study. Multicenter study. Seven hundred embryo transfers and 1,028 early-stage human embryos. None. Implantation according to the presence of EC and embryo quality. The presence of EC is associated with embryo quality, especially in cycles with autologous oocytes. However, the use of EC as an additional criterion for selecting an embryo for transfer does not appear to significantly improve likelihood of implantation. Furthermore, embryos that presented EC had live-birth rates per implanted embryo similar to those that did not show any sign of cleavage. At least for conventional embryo culture and morphologic evaluations, the additional evaluation of EC in embryos may not be valuable to improve embryo implantation. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Spanish Multicenter Normative Studies (NEURONORMA Project): norms for Boston naming test and token test.

PubMed

Peña-Casanova, Jordi; Quiñones-Ubeda, Sonia; Gramunt-Fombuena, Nina; Aguilar, Miquel; Casas, Laura; Molinuevo, José Luis; Robles, Alfredo; Rodríguez, Dolores; Barquero, María Sagrario; Antúnez, Carmen; Martínez-Parra, Carlos; Frank-García, Anna; Fernández, Manuel; Molano, Ana; Alfonso, Verónica; Sol, Josep M; Blesa, Rafael

2009-06-01

As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the Boston naming test and Token test. The sample consists of 340 and 348 participants, respectively, who are cognitively normal, community-dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Age and education affected the score of the both tests, but sex was found to be unrelated to naming and verbal comprehension efficiency. Our norms should provide clinically useful data for evaluating elderly Spaniards. The normative data presented here were obtained from the same study sample as all the other NEURONORMA norms and the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.

Multicenter, double-blind, parallel group study investigating the non-inferiority of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2% ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.

PubMed

Buechner, Stanislaw A

2014-06-01

This study investigated the non-inferiority of efficacy and tolerance of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in the treatment of scalp seborrheic dermatitis. A randomized, double-blind, comparative, parallel group, multicenter study was done. A total of 274 patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice-weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global change [Clinical Global Impressions (CGIs) and Patient Global Impressions (PGIs)]. Miconazole shampoo is at least as effective and safe as ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

PubMed Central

Janz, David R.; Bernard, Gordon R.; May, Addison K.; Kangelaris, Kirsten N.; Matthay, Michael A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. METHODS: We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. RESULTS: In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. CONCLUSIONS: Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively. PMID:26033126

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

PubMed

Starling, R C; Stehlik, J; Baran, D A; Armstrong, B; Stone, J R; Ikle, D; Morrison, Y; Bridges, N D; Putheti, P; Strom, T B; Bhasin, M; Guleria, I; Chandraker, A; Sayegh, M; Daly, K P; Briscoe, D M; Heeger, P S

2016-01-01

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Short-term complications in intra- and extra-articular anterior cruciate ligament reconstruction. Comparison with the literature on isolated intra-articular reconstruction. A multicenter study by the French Arthroscopy Society.

PubMed

Panisset, J C; Pailhé, R; Schlatterer, B; Sigwalt, L; Sonnery-Cottet, B; Lutz, C; Lustig, S; Batailler, C; Bertiaux, S; Ehkirch, F P; Colombet, P; Steltzlen, C; Louis, M L; D'ingrado, P; Dalmay, F; Imbert, P; Saragaglia, D

2017-12-01

Lateral tenodesis (LT) is performed to limit the risk of iterative tear following anterior cruciate ligament (ACL) reconstruction in at-risk patients. By adding an extra procedure to isolated ACL graft, LT reconstruction increases operating time and may complicate postoperative course. The objective of the present study was to evaluate the rate of early complications. The study hypothesis was that associating ALL reconstruction to ACL reconstruction does not increase the complications rate found with isolated ACL reconstruction. A prospective multicenter study included 392 patients: 70% male; mean age, 29.9 years; treated by associated ACL and LT reconstruction. All adverse events were inventoried. Mean hospital stay was 2 days, with 46% day-surgery. Walking was resumed at a mean 27 days, with an advantage for patients treated by the hamstring technique. The early postoperative complications rate was 12%, with 1.7% specifically implicating LT reconstruction: pain, hematoma, stiffness in flexion and extension, and infection. There was a 5% rate of surgical revision during the first year, predominantly comprising arthrolysis for extension deficit. The 1-year recurrence rate was 2.8%. The complications rate for combined intra- and extra-articular reconstruction was no higher than for isolated intra-articular ACL reconstruction, with no increase in infection or stiffness rates. The rate of complications specific to ALL reconstruction was low, at 1.7%, and mainly involved fixation error causing lateral soft-tissue impingement. IV, prospective multicenter study. Copyright © 2017. Published by Elsevier Masson SAS.

Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies.

PubMed

Calfee, Carolyn S; Janz, David R; Bernard, Gordon R; May, Addison K; Kangelaris, Kirsten N; Matthay, Michael A; Ware, Lorraine B

2015-06-01

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

PubMed

Meretoja, Atte; Churilov, Leonid; Campbell, Bruce C V; Aviv, Richard I; Yassi, Nawaf; Barras, Christen; Mitchell, Peter; Yan, Bernard; Nandurkar, Harshal; Bladin, Christopher; Wijeratne, Tissa; Spratt, Neil J; Jannes, Jim; Sturm, Jonathan; Rupasinghe, Jayantha; Zavala, Jorge; Lee, Andrew; Kleinig, Timothy; Markus, Romesh; Delcourt, Candice; Mahant, Neil; Parsons, Mark W; Levi, Christopher; Anderson, Craig S; Donnan, Geoffrey A; Davis, Stephen M

2014-06-01

No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial

PubMed Central

2012-01-01

Background Anastomotic leakage is a major complication in colorectal surgery and with an incidence of 11% the most common cause of morbidity and mortality. In order to reduce the incidence of anastomotic leakage the C-seal is developed. This intraluminal biodegradable drain is stapled to the anastomosis with a circular stapler and prevents extravasation of intracolonic content in case of an anastomotic dehiscence. The aim of this study is to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses, as assessed by anastomotic leakage leading to invasive treatment within 30 days postoperative. Methods The C-seal trial is a prospective multi-center randomized controlled trial with primary endpoint, anastomotic leakage leading to re-intervention within 30 days after operation. In this trial 616 patients will be randomized to the C-seal or control group (1:1), stratified by center, anastomotic height (proximal or distal of peritoneal reflection) and the intention to create a temporary deviating ostomy. Interim analyses are planned after 50% and 75% of patient inclusion. Eligible patients are at least 18 years of age, have any colorectal disease requiring a colorectal anastomosis to be made with a circular stapler in an elective setting, with an ASA-classification < 4. Oral mechanical bowel preparation is mandatory and patients with signs of peritonitis are excluded. The C-seal student team will perform the randomization procedure, supports the operating surgeon during the C-seal application and achieves the monitoring of the trial. Patients are followed for one year after randomization en will be analyzed on an intention to treat basis. Discussion This Randomized Clinical trial is designed to evaluate the effectiveness of the C-seal in preventing clinical anastomotic leakage. Trial registration NTR3080 PMID:23153188

Double Kissing Crush Versus Provisional Stenting for Left Main Distal Bifurcation Lesions: DKCRUSH-V Randomized Trial.

PubMed

Chen, Shao-Liang; Zhang, Jue-Jie; Han, Yaling; Kan, Jing; Chen, Lianglong; Qiu, Chunguang; Jiang, Tiemin; Tao, Ling; Zeng, Hesong; Li, Li; Xia, Yong; Gao, Chuanyu; Santoso, Teguh; Paiboon, Chootopol; Wang, Yan; Kwan, Tak W; Ye, Fei; Tian, Nailiang; Liu, Zhizhong; Lin, Song; Lu, Chengzhi; Wen, Shangyu; Hong, Lang; Zhang, Qi; Sheiban, Imad; Xu, Yawei; Wang, Lefeng; Rab, Tanveer S; Li, Zhanquan; Cheng, Guanchang; Cui, Lianqun; Leon, Martin B; Stone, Gregg W

2017-11-28

Provisional stenting (PS) is the most common technique used to treat distal left main (LM) bifurcation lesions in patients with unprotected LM coronary artery disease undergoing percutaneous coronary intervention. The double kissing (DK) crush planned 2-stent technique has been shown to improve clinical outcomes in non-LM bifurcations compared with PS, and in LM bifurcations compared with culotte stenting, but has never been compared with PS in LM bifurcation lesions. The authors sought to determine whether a planned DK crush 2-stent technique is superior to PS for patients with true distal LM bifurcation lesions. The authors randomized 482 patients from 26 centers in 5 countries with true distal LM bifurcation lesions (Medina 1,1,1 or 0,1,1) to PS (n = 242) or DK crush stenting (n = 240). The primary endpoint was the 1-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Routine 13-month angiographic follow-up was scheduled after ascertainment of the primary endpoint. TLF within 1 year occurred in 26 patients (10.7%) assigned to PS, and in 12 patients (5.0%) assigned to DK crush (hazard ratio: 0.42; 95% confidence interval: 0.21 to 0.85; p = 0.02). Compared with PS, DK crush also resulted in lower rates of target vessel myocardial infarction I (2.9% vs. 0.4%; p = 0.03) and definite or probable stent thrombosis (3.3% vs. 0.4%; p = 0.02). Clinically driven target lesion revascularization (7.9% vs. 3.8%; p = 0.06) and angiographic restenosis within the LM complex (14.6% vs. 7.1%; p = 0.10) also tended to be less frequent with DK crush compared with PS. There was no significant difference in cardiac death between the groups. In the present multicenter randomized trial, percutaneous coronary intervention of true distal LM bifurcation lesions using a planned DK crush 2-stent strategy resulted in a lower rate of TLF at 1 year than a PS strategy. (Double Kissing and Double Crush Versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-Center Clinical Trial [DKCRUSH-V]; ChiCTR-TRC-11001213). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada - baseline findings of a multicenter trial.

PubMed

Umeh, Chizoba C; Pérez, Adriana; Augustine, Erika F; Dhall, Rohit; Dewey, Richard B; Mari, Zoltan; Simon, David K; Wills, Anne-Marie A; Christine, Chadwick W; Schneider, Jay S; Suchowersky, Oksana

2014-01-01

Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy - the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease.

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT

PubMed Central

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-01-01

Purpose A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Materials and Methods Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. Results In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT’s safety profile. Conclusion The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC. PMID:25410761

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT.

PubMed

Yang, James Chin-Hsin; Ahn, Myung-Ju; Nakagawa, Kazuhiko; Tamura, Tomohide; Barraclough, Helen; Enatsu, Sotaro; Cheng, Rebecca; Orlando, Mauro

2015-07-01

A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, post-marketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT's safety profile. The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.

ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

ClinicalTrials.gov

2017-12-08

Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Clinicopathologic analysis of 370 cases of vulvar intraepithelial neoplasia. Italian Study Group on Vulvar Disease.

PubMed

1996-09-01

To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN). A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) was performed by the Italian Study Group on Vulvar Disease. Of the 370 cases, 148 were VIN 1 (40.0%, 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370). The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.

Effective symptomatic treatment for severe and intractable pruritus associated with severe burn-induced hypertrophic scars: A prospective, multicenter, controlled trial.

PubMed

Wu, Jun; Xu, Rui; Zhan, Rixing; Luo, Gaoxing; Niu, Xihua; Liu, Yi; Lee, Benjamin Tak-Kwong; Flury, Meinrad; Wong, Chun-Ho; Fok, Manson; Lau, Johnson Yiu-Nam

2016-08-01

Burn-induced hypertrophic scars are disfiguring and can be associated with severe and intractable pruritus. No effective treatment modalities are currently available for symptomatic control of pruritus for most patients. We assessed the effect of the Antipruritic Hydrogel (CQ-01) in the symptomatic treatment of severe and intractable pruritus associated with burn-induced hypertrophic scars in a prospective, multicenter, controlled trial. A pilot study was conducted in healthy adult volunteers to identify the most appropriate hydrogel formulation. A selected preparation called Chongqing No. 1 (CQ-01; a guar gum-based hydrogel impregnated with peppermint oil, menthol, and methyl salicylate by a nanoemulsion), showed an excellent symptomatic relief in an exploratory study in 2 patients with intractable pruritus. A statistically powered, prospective, multicenter, controlled study was then conducted in 74 patients to evaluate the efficacy and safety of a 24-h application of CQ-01 compared to a gel control and a negative control on three separate areas in each patient. Symptom assessment was based on our visual analog JW scale (ranging from 0 to 100) at baseline and various time points up to 7 days after application. Follow-up studies were conducted to determine the reproducibility of CQ-01 in repeated applications. Of the 74 enrolled subjects, the only observed adverse event was skin irritation reported in 6 patients (8%) and resolved shortly after gel removal. Compared to the baseline, the gauze negative control had a mean JW score reduction of 7; while the gel control and CQ-01 had a drop of 18 (p<0.001) and 36 (p<0.001), respectively. The CQ-01 clinical effect was significant for up to 3 days and waned slowly from 3 to 7 days. There was no statistical correlation between the treatment response and any of the demographic, patient or burn-related factors. Further studies showed a trend that repeated applications might be more effective, suggesting the absence of tachyphylaxis. This prospective, multicenter, controlled study showed that this novel hydrogel CQ-01 is safe and provides significant symptomatic relief for severe and intractable pruritus associated with hypertrophic scars, an unmet medical need for these patients. This effect is independent of the etiology of the burn trauma, extent of the scarring, and duration of the scar formation. Copyright © 2016. Published by Elsevier Ltd.

Innate immune function and mortality in critically ill children with influenza: a multicenter study.

PubMed

Hall, Mark W; Geyer, Susan M; Guo, Chao-Yu; Panoskaltsis-Mortari, Angela; Jouvet, Philippe; Ferdinands, Jill; Shay, David K; Nateri, Jyotsna; Greathouse, Kristin; Sullivan, Ryan; Tran, Tram; Keisling, Shannon; Randolph, Adrienne G

2013-01-01

To prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection. Prospective, multicenter, observational study. Fifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network. Patients ≤18 yrs old admitted to a PICU with community-acquired influenza infection. A control group of outpatient children was also evaluated. ICU patients underwent sampling within 72 hrs of ICU admission for measurement of a panel of 31 serum cytokine levels and quantification of whole blood ex vivo lipopolysaccharide-stimulated tumor necrosis factor-α production capacity using a standardized stimulation protocol. Outpatient control subjects also underwent measurement of tumor necrosis factor-α production capacity. Fifty-two patients (44 survivors, eight deaths) were sampled. High levels of serum cytokines (granulocyte macrophage colony-stimulating factor, interleukin-6, interleukin-8, interferon-inducible protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α) were associated with mortality (p < 0.0016 for each comparison) as was the presence of secondary infection with Staphylococcus aureus (p = 0.007), particularly methicillin-resistant S. aureus (p < 0.0001). Nonsurvivors were immunosuppressed with leukopenia and markedly reduced tumor necrosis factor-α production capacity compared with outpatient control subjects (n = 21, p < 0.0001) and to ICU survivors (p < 0.0001). This association remained after controlling for multiple covariables. A tumor necrosis factor-α response <250 pg/mL was highly predictive of death and longer duration of ICU stay (p < 0.0001). Patients with S. aureus coinfection demonstrated the greatest degree of immunosuppression (p < 0.0001). High serum levels of cytokines can coexist with marked innate immune suppression in children with critical influenza. Severe, early innate immune suppression is highly associated with both S. aureus coinfection and mortality in this population. Multicenter innate immune function testing is feasible and can identify these high-risk children.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

PubMed Central

Papachristou, Georgios I.; Machicado, Jorge D.; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C.; Singh, Vikesh K.; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A.; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O.; Triantafyllou, Konstantinos; Barbu, Sorin T.; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A.; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch.; Nawaz, Haq; Park, Walter G.; de-Madaria, Enrique; Lee, Peter J.; Wu, Bechien U.; Greer, Phil J.; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials. PMID:28042246

Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy.

PubMed

Hacioglu, Sibel; Bilen, Yusuf; Eser, Ali; Sivgin, Serdar; Gurkan, Emel; Yildirim, Rahsan; Aydogdu, Ismet; Dogu, Mehmet Hilmi; Yilmaz, Mehmet; Kayikci, Omur; Tombak, Anil; Kuku, Irfan; Celebi, Harika; Akay, Meltem Olga; Esen, Ramazan; Korkmaz, Serdal; Keskin, Ali

2015-12-01

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population. Copyright © 2014 John Wiley & Sons, Ltd.

[Diagnostic imaging and interventional therapy in hepatocarcinoma. Multicenter study of 290 cases].

PubMed

Dalla Palma, L; Pozzi Mucelli, R; Sponza, M; Bartolozzi, C; Lencioni, R; Florio, F; De Santis, M; Gandini, G; Matricardi, L; Rossi, C; Simonetti, G; Pocek, M

1997-01-01

We report the results of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC). The first aim--diagnosis--was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in HCC detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning. Two hundred ninety patients underwent this imaging protocol. The patients were classified by tumor spread into three groups, namely group 1 (single HCCs < 5 cm), group 2 (multifocal HCCs with max. 3 nodules or tumor volume < 80 cc), group 3 (multifocal HCCs with more than 3 nodules and/or tumor volume > 80 cc). US and CT diagnosed more cases as group 1 and fewer cases as group 3 than DSA and LCT; the latter two techniques gave a similar classification. With LCT as the gold standard, US and CT understaged 27.9% and 26.5% of cases, respectively. Even though LCT is known to have 53% sensitivity, it is currently the most sensitive preoperative investigation and therefore the best tool for treatment planning. In surgical patients, however, intraoperative US, with its nearly 100% sensitivity, is suggested. The second aim--treatment--consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced HCC and of CEAT versus no treatment (NT) in advanced HCC. Treatment efficacy was evaluated with the following randomized protocols: PEI versus CEAT in group 1, PEI versus CEAT in group 2 and CEAT versus NT in group 3. The data were analyzed relative to 215 patients for 6 to 30 months. The Kaplan-Meier method was used to calculate survival rates, which were, at 24 and 30 months, 72% and 72% for PEI and 72% and 52% for CEAT in group 1, 52% and 28% for PEI and 70% and 50% for CEAT in group 2 and finally 30% and 20% for NT and 45% and 30% for CEAT in group 3. In group 1, PEI appeared markedly superior to CEAT. In group 2, the difference between PEI and CEAT was not statistically significant; the results in this group indicate that CEAT should be considered when three nodules are present because of PEI invasiveness in these cases. In group 3, CEAT results were definitely better in the first two years, but there was no difference with NT patients at the end of the third year. Therefore, CEAT is indicated in advanced HCC because it improves the survival rate in the first 24 months. After this period, the survival time is not modified by treatment.

Delaying Surgical Treatment of Penile Fracture Results in Poor Functional Outcomes: Results from a Large Retrospective Multicenter European Study.

PubMed

Bozzini, Giorgio; Albersen, Maarten; Otero, Javier Romero; Margreiter, Markus; Cruz, Eduard Garcia; Mueller, Alexander; Gratzke, Christian; Serefoglu, Ege Can; Salamanca, Juan Ignacio Martinez; Verze, Paolo

2018-01-01

Penile fracture is a rare clinical entity that represents a urologic emergency. It involves traumatic rupture of the tunica albuginea of the corpora cavernosa due to twisting or bending of the penile shaft during erection. To determine the differences in preoperative diagnostic evaluation patterns and outcomes of penile fracture patients to investigate the impact of surgical delay on functional outcomes. A retrospective analysis was performed using data obtained from 137 patients presenting with penile fracture at seven different European academic medical centers between 1996 and 2013. Age, imaging modalities used, timing of surgical intervention, length of tunica albuginea defect, and surgical technique were recorded. Postoperative erectile function outcomes were assessed with the International Index of Erectile Function (IIEF-5), and the presence of postoperative penile curvature was noted. The association between timing of surgical intervention and postoperative IIEF-5 results was evaluated with discriminant function analysis. The median age of the patients was 34.50 yr (interquartile range [IQR]: 28.0-46.5 yr). Of the 137 patients, 82 (59.85%) underwent penile Doppler ultrasound, and 5 patients (3.64%) were evaluated with magnetic resonance imaging. All patients were treated surgically, and the duration between emergency room admission and surgical intervention was 5.0h (IQR: 3.6-8.0h). The median length of tunica albuginea defect was 10mm (IQR: 8-20mm). Postoperative IIEF-5 scores were 21 (IQR: 12-23) and 23 (IQR: 15-24) at the first and third postoperative months, respectively. Discriminant function analysis revealed that if the surgical intervention was performed >8.23hours after emergency room admission, postoperative erectile function was significantly worse (p=0.0051 at first month and p=0.0057 at third month postoperatively). Our multicenter study showed that delaying surgical intervention results in significantly impaired erectile function. Surgical treatment must be planned as soon as possible to avoid postoperative erectile dysfunction. We looked at sexual outcomes following the repair of penile fracture in a large European population. We found that outcomes worsened if surgical repair was delayed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial.

PubMed

DeWitt, John M; Murthy, S Krishna; Ardhanari, Ramesh; DuVall, G Aaron; Wallner, Grzegorz; Litka, Paul; Daugherty, Claire; Fowers, Kirk

2017-07-01

OncoGel (Protherics Salt Lake City, Inc, Salt Lake City, UT) is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for focused cytotoxicity and radiosensitization. A phase 2a study suggested that EUS-guided PTX injection into esophageal tumors subsequently receiving radiotherapy was safe. In an international multicenter, prospective, randomized phase 2b study, patients with local or locoregional adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus/gastroesophageal junction and eligible for neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of care (SOC) plus EUS-guided PTX injection or SOC alone. PTX was injected in 0.5 to 1.0 mL aliquots throughout the tumor. Planned CRT as SOC was intravenous 5-fluorouracil for the first 4 days (weeks 1 and 5), intravenous cisplatin on the first day of each 5-fluorouracil course, and radiotherapy over 5.5 weeks. Patients were evaluated weekly during CRT and re-evaluated at 12 weeks for surgical eligibility and CT for change in overall tumor volume. The analysis included 137 patients (97 males; mean age, 58 ± 9.1 years) randomized to PTX + SOC (n = 72) and SOC (n = 65) by using a modified intention-to-treat approach. Overall response by tumor volume between the PTX (12.5%) and the SOC group (20.0%; P = .24; odds ratio, 0.57; 95% confidence interval, 0.23-1.44) was similar. Pathologic complete response was higher in the SOC group (26.2% vs 12.5%; P = .046); however, 12-month survival (P = .412) and the overall frequency of 1 or more adverse events (P = .17) were similar between the 2 groups. SOC + PTX is safe but does not improve overall survival or overall tumor response at the primary tumor site for patients with local or locoregional cancer of the esophagus/gastroesophageal junction. (Clinical trial registration number: NCT00573131.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Inter-vender and test-retest reliabilities of resting-state functional magnetic resonance imaging: Implications for multi-center imaging studies.

PubMed

An, Hyeong Su; Moon, Won-Jin; Ryu, Jae-Kyun; Park, Ju Yeon; Yun, Won Sung; Choi, Jin Woo; Jahng, Geon-Ho; Park, Jang-Yeon

2017-12-01

This prospective multi-center study aimed to evaluate the inter-vendor and test-retest reliabilities of resting-state functional magnetic resonance imaging (RS-fMRI) by assessing the temporal signal-to-noise ratio (tSNR) and functional connectivity. Study included 10 healthy subjects and each subject was scanned using three 3T MR scanners (GE Signa HDxt, Siemens Skyra, and Philips Achieva) in two sessions. The tSNR was calculated from the time course data. Inter-vendor and test-retest reliabilities were assessed with intra-class correlation coefficients (ICCs) derived from variant component analysis. Independent component analysis was performed to identify the connectivity of the default-mode network (DMN). In result, the tSNR for the DMN was not significantly different among the GE, Philips, and Siemens scanners (P=0.638). In terms of vendor differences, the inter-vendor reliability was good (ICC=0.774). Regarding the test-retest reliability, the GE scanner showed excellent correlation (ICC=0.961), while the Philips (ICC=0.671) and Siemens (ICC=0.726) scanners showed relatively good correlation. The DMN pattern of the subjects between the two sessions for each scanner and between three scanners showed the identical patterns of functional connectivity. The inter-vendor and test-retest reliabilities of RS-fMRI using different 3T MR scanners are good. Thus, we suggest that RS-fMRI could be used in multicenter imaging studies as a reliable imaging marker. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of Standardized, Quantitative Digital Photography in a Multicenter Web-based Study

PubMed Central

Molnar, Joseph A.; Lew, Wesley K.; Rapp, Derek A.; Gordon, E. Stanley; Voignier, Denise; Rushing, Scott; Willner, William

2009-01-01

Objective: We developed a Web-based, blinded, prospective, randomized, multicenter trial, using standardized digital photography to clinically evaluate hand burn depth and accurately determine wound area with digital planimetry. Methods: Photos in each center were taken with identical digital cameras with standardized settings on a custom backdrop developed at Wake Forest University containing a gray, white, black, and centimeter scale. The images were downloaded, transferred via the Web, and stored on servers at the principal investigator's home institution. Color adjustments to each photo were made using Adobe Photoshop 6.0 (Adobe, San Jose, Calif). In an initial pilot study, model hands marked with circles of known areas were used to determine the accuracy of the planimetry technique. Two-dimensional digital planimetry using SigmaScan Pro 5.0 (SPSS Science, Chicago, Ill) was used to calculate wound area from the digital images. Results: Digital photography is a simple and cost-effective method for quantifying wound size when used in conjunction with digital planimetry (SigmaScan) and photo enhancement (Adobe Photoshop) programs. The accuracy of the SigmaScan program in calculating predetermined areas was within 4.7% (95% CI, 3.4%–5.9%). Dorsal hand burns of the initial 20 patients in a national study involving several centers were evaluated with this technique. Images obtained by individuals denying experience in photography proved reliable and useful for clinical evaluation and quantification of wound area. Conclusion: Standardized digital photography may be used quantitatively in a Web-based, multicenter trial of burn care. This technique could be modified for other medical studies with visual endpoints. PMID:19212431

Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

PubMed

Kloimstein, Herwig; Likar, Rudolf; Kern, Michael; Neuhold, Josef; Cada, Miroslav; Loinig, Nadja; Ilias, Wilfried; Freundl, Brigitta; Binder, Heinrich; Wolf, Andreas; Dorn, Christian; Mozes-Balla, Eva Maria; Stein, Rolf; Lappe, Ivo; Sator-Katzenschlager, Sabine

2014-02-01

The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal. © 2013 International Neuromodulation Society.

Use of standardized, quantitative digital photography in a multicenter Web-based study.

PubMed

Molnar, Joseph A; Lew, Wesley K; Rapp, Derek A; Gordon, E Stanley; Voignier, Denise; Rushing, Scott; Willner, William

2009-01-01

We developed a Web-based, blinded, prospective, randomized, multicenter trial, using standardized digital photography to clinically evaluate hand burn depth and accurately determine wound area with digital planimetry. Photos in each center were taken with identical digital cameras with standardized settings on a custom backdrop developed at Wake Forest University containing a gray, white, black, and centimeter scale. The images were downloaded, transferred via the Web, and stored on servers at the principal investigator's home institution. Color adjustments to each photo were made using Adobe Photoshop 6.0 (Adobe, San Jose, Calif). In an initial pilot study, model hands marked with circles of known areas were used to determine the accuracy of the planimetry technique. Two-dimensional digital planimetry using SigmaScan Pro 5.0 (SPSS Science, Chicago, Ill) was used to calculate wound area from the digital images. Digital photography is a simple and cost-effective method for quantifying wound size when used in conjunction with digital planimetry (SigmaScan) and photo enhancement (Adobe Photoshop) programs. The accuracy of the SigmaScan program in calculating predetermined areas was within 4.7% (95% CI, 3.4%-5.9%). Dorsal hand burns of the initial 20 patients in a national study involving several centers were evaluated with this technique. Images obtained by individuals denying experience in photography proved reliable and useful for clinical evaluation and quantification of wound area. Standardized digital photography may be used quantitatively in a Web-based, multicenter trial of burn care. This technique could be modified for other medical studies with visual endpoints.

Factors predicting survival in ALS: a multicenter Italian study.

PubMed

Calvo, Andrea; Moglia, Cristina; Lunetta, Christian; Marinou, Kalliopi; Ticozzi, Nicola; Ferrante, Gianluca Drago; Scialo, Carlo; Sorarù, Gianni; Trojsi, Francesca; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Chiò, Adriano; Sansone, Valeria Ada; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Monsurrò, Maria Rosaria; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fini, Nicola; Mandrioli, Jessica

2017-01-01

The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

PubMed

Leal Reyna, Mariela; Gómez, Reynaldo M; Lupi, Susana N; Belli, Susana H; Fenili, Cecilia A; Martínez, Marcela S; Ruibal, Gabriela F; Rossi, María A; Chervin, Raúl A; Cornaló, Dora; Contreras, Liliana N; Costa, Liliana; Nofal, María T; Damilano, Sergio A; Pardes, Ester M

2015-10-01

Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.

PubMed

Musset, Lucile; Allenbach, Yves; Benveniste, Olivier; Boyer, Olivier; Bossuyt, Xavier; Bentow, Chelsea; Phillips, Joe; Mammen, Andrew; Van Damme, Philip; Westhovens, René; Ghirardello, Anna; Doria, Andrea; Choi, May Y; Fritzler, Marvin J; Schmeling, Heinrike; Muro, Yoshinao; García-De La Torre, Ignacio; Ortiz-Villalvazo, Miguel A; Bizzaro, Nicola; Infantino, Maria; Imbastaro, Tiziana; Peng, Qinglin; Wang, Guochun; Vencovský, Jiří; Klein, Martin; Krystufkova, Olga; Franceschini, Franco; Fredi, Micaela; Hue, Sophie; Belmondo, Thibaut; Danko, Katalin; Mahler, Michael

2016-10-01

In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria. Copyright © 2016. Published by Elsevier B.V.

Assessing the Knowledge, Attitudes and Behaviors of Human and Animal Health Students towards Antibiotic Use and Resistance: A Pilot Cross-Sectional Study in the UK.

PubMed

Dyar, Oliver James; Hills, Holly; Seitz, Lara-Turiya; Perry, Alex; Ashiru-Oredope, Diane

2018-01-30

The Global Action Plan on Antimicrobial Resistance highlights the importance of training all healthcare professionals. No study has assessed patterns of students' knowledge, attitudes and practices concerning antibiotic use simultaneously across different healthcare course types. We conducted a cross-sectional multi-center survey among UK students. The survey was advertised through local survey coordinators at 25 universities. The online survey was accessible from 10th October to 17th November 2016 (before European Antibiotic Awareness Day). A total of 255 students from 25 universities participated, including students on medicine, pharmacy, nursing, physician associate, dentistry and veterinary medicine courses. Antibiotic resistance was considered to be a more important global challenge than climate change, obesity or food security ( p < 0.001). Most students (95%) believed that antibiotic resistance will be a problem for their future practice, but fewer (69%) thought that the antibiotics they will prescribe, administer or dispense will contribute to the problem. A fifth of students felt they had sufficient knowledge of antibiotic use for their future work. Our exploratory study suggests that UK human and animal healthcare students are aware of the importance of antibiotic resistance, but many still have certain misconceptions. Campaigns and improved educational efforts applying behavioral insights methodology could address these.

Psychosocial and occupational risk perception among health care workers: a Moroccan multicenter study.

PubMed

Giurgiu, Doina Ileana; Jeoffrion, Christine; Grasset, Benjamin; Dessomme, Brigitte Keriven; Moret, Leila; Roquelaure, Yves; Caubet, Alain; Verger, Christian; Laraqui, Chakib El Houssine; Lombrail, Pierre; Geraut, Christian; Tripodi, Dominique

2015-09-04

International studies on occupational risks in public hospitals are infrequent and only few researchers have focused on psychosocial stress in Moroccan Health Care Workers (HCWs). The aim of this study was to present and analyze Moroccan HCWs occupational risk perception. Across nine public hospitals from three Moroccan regions (northern, central and southern), a 49 item French questionnaire with 4 occupational risks subscales, was distributed to 4746 HCWs. This questionnaire was based on the Job Content Questionnaire. Psychosocial job demand, job decision latitude and social support scores analysis were used to isolate high strain jobs. Occupational risks and high strain perception correlation were analyzed by univariate and multivariate logistic regression. 2863 HCWs (60%) answered the questionnaire (54% women; mean age 40 years; mean work seniority 11 years; 24% physicians; 45% nurses). 44% of Moroccan HCWs were at high strain. High strain was strongly associated with two occupational categories: midwives (2.33 OR; CI 1.41-3.85), full-time employment (1.65 OR; CI 1.24-2.19), hypnotics and sedatives use (1.41 OR; CI 1.11-1.79), analgesics use (1.37 OR; CI 1.13-1.66). Moroccan HCWs, physicians included, perceive their job as high strain. Moroccan HCWs use of hypnotics, sedatives and analgesics is high. Risk prevention plan implementation is highly recommended.

Cognitive Impairment after Severe Traumatic Brain Injury, Clinical Course and Impact on Outcome: A Swedish-Icelandic Study

PubMed Central

Stenberg, Maud; Godbolt, Alison K.; Nygren De Boussard, Catharina; Levi, Richard; Stålnacke, Britt-Marie

2015-01-01

Objective. To assess the clinical course of cognitive and emotional impairments in patients with severe TBI (sTBI) from 3 weeks to 1 year after trauma and to study associations with outcomes at 1 year. Methods. Prospective, multicenter, observational study of sTBI in Sweden and Iceland. Patients aged 18–65 years with acute Glasgow Coma Scale 3–8 were assessed with the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and the Hospital Anxiety and Depression Scale (HADS). Outcome measures were Glasgow Outcome Scale Extended (GOSE) and Rancho Los Amigos Cognitive Scale-Revised (RLAS-R). Results. Cognition was assessed with the BNIS assessed for 42 patients out of 100 at 3 weeks, 75 patients at 3 months, and 78 patients at 1 year. Cognition improved over time, especially from 3 weeks to 3 months. The BNIS subscales “orientation” and “visuospatial and visual problem solving” were associated with the GOSE and RLAS-R at 1 year. Conclusion. Cognition seemed to improve over time after sTBI and appeared to be rather stable from 3 months to 1 year. Since cognitive function was associated with outcomes, these results indicate that early screening of cognitive function could be of importance for rehabilitation planning in a clinical setting. PMID:26783381

Telephone-based mindfulness training to reduce stress in women with myocardial infarction: Rationale and design of a multicenter randomized controlled trial.

PubMed

Spruill, Tanya M; Reynolds, Harmony R; Dickson, Victoria Vaughan; Shallcross, Amanda J; Visvanathan, Pallavi D; Park, Chorong; Kalinowski, Jolaade; Zhong, Hua; Berger, Jeffrey S; Hochman, Judith S; Fishman, Glenn I; Ogedegbe, Gbenga

2018-04-21

Elevated stress is associated with adverse cardiovascular disease outcomes and accounts in part for the poorer recovery experienced by women compared with men after myocardial infarction (MI). Psychosocial interventions improve outcomes overall but are less effective for women than for men with MI, suggesting the need for different approaches. Mindfulness-based cognitive therapy (MBCT) is an evidence-based intervention that targets key psychosocial vulnerabilities in women including rumination (i.e., repetitive negative thinking) and low social support. This article describes the rationale and design of a multicenter randomized controlled trial to test the effects of telephone-delivered MBCT (MBCT-T) in women with MI. We plan to randomize 144 women reporting elevated perceived stress at least two months after MI to MBCT-T or enhanced usual care (EUC), which each involve eight weekly telephone sessions. Perceived stress and a set of patient-centered health outcomes and potential mediators will be assessed before and after the 8-week telephone programs and at 6-month follow-up. We will test the hypothesis that MBCT-T will be associated with greater 6-month improvements in perceived stress (primary outcome), disease-specific health status, quality of life, depression and anxiety symptoms, and actigraphy-based sleep quality (secondary outcomes) compared with EUC. Changes in mindfulness, rumination and perceived social support will be evaluated as potential mediators in exploratory analyses. If found to be effective, this innovative, scalable intervention may be a promising secondary prevention strategy for women with MI experiencing elevated perceived stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Social marketing-based communications to integrate and support the HEALTHY study intervention

USDA-ARS?s Scientific Manuscript database

The HEALTHY study was a randomized, controlled, multicenter, middle school-based, multifaceted intervention designed to reduce risk factors for the development of type 2 diabetes. The study randomized 42 middle schools to intervention or control, and followed students from the sixth to the eighth gr...

Calculation of multicenter electric field gradient integrals over Slater-type orbitals using unsymmetrical one-range addition theorems.

PubMed

Guseinov, Israfil I; Görgün, Nurşen Seçkin

2011-06-01

The electric field induced within a molecule by its electrons determines a whole series of important physical properties of the molecule. In particular, the values of the gradient of this field at the nuclei determine the interaction of their quadrupole moments with the electrons. Using unsymmetrical one-range addition theorems introduced by one of the authors, the sets of series expansion relations for multicenter electric field gradient integrals over Slater-type orbitals in terms of multicenter charge density expansion coefficients and two-center basic integrals are presented. The convergence of the series is tested by calculating concrete cases for different values of quantum numbers, parameters and locations of orbitals.

Challenges for conducting blood collection and biochemical analysis in a large multicenter school-based study with adolescents: lessons from ERICA in Brazil.

PubMed

Cureau, Felipe Vogt; Bloch, Katia Vergetti; Henz, Aline; Schaan, Camila W; Klein, Carlos Henrique; Oliveira, Cecília Lacroix de; Giannini, Denise Tavares; Leon, Elisa Brosina de; Abreu, Gabriela de Azevedo; Telo, Gabriela Heiden; Dias, Glauber Monteiro; Carvalho, Kênia Mara Baiocchi de; Barufaldi, Laura Augusta; Kuschnir, Maria Cristina Caetano; Szklo, Moyses; Montenegro, Renan; Silva, Thiago Luiz Nogueira da; Ekelund, Ulf; Schaan, Beatriz D

2017-05-18

The Study of Cardiovascular Risk in Adolescents (ERICA) is a pioneering study that aimed to assess the prevalence of cardiovascular risk factors, including metabolic syndrome components in Brazilian adolescents. This study aims to describe the methodological aspects related to blood collection as well as to report pertaining results of the preparation, transport, storage, and exams in ERICA. Exams in ERICA were performed in a single laboratory and blood samples were collected in schools in a standardized manner. Logistics involved air transportation of samples to the reference laboratory with controlled temperature since sample collection. The serum was stored in local biorepositories in four centers to be used in future analyses. During the study, 284,247 exams were performed and rate of participation in exams was 56.2%, thus involving 40,732 adolescents. From the total, 92.6% of the samples reached the reference laboratory maintaining the temperature between 0-10°C. No clinical significant changes in results due to temperature changes were identified. External quality control recorded satisfactory results in 98.7% of the evaluations. Four biorepositories with samples of 7,785 adolescents were created. Thus, we can consider that the logistics adopted in ERICA was fairly successful and description of this as well as the difficulties experienced in Brazil can inform and facilitate the planning of future studies, especially in developing countries.

Surgical site infection after surgery to repair femoral neck fracture: a French multicenter retrospective study.

PubMed

Merrer, Jacques; Girou, Emmanuelle; Lortat-Jacob, Alain; Montravers, Philippe; Lucet, Jean-Christophe

2007-10-01

Femoral neck fracture is the most frequent orthopedic emergency among elderly persons. Despite a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in this population, no multicenter study of antibiotic prophylaxis practices and the rate and microbiological characteristics of surgical site infection (SSI) has been performed in France. Retrospective, multicenter cohort study. Twenty-two university and community hospitals in France. Each center provided data on 25 consecutive patients who underwent surgery for femoral neck fracture during the first quarter of 2005. Demographic, clinical, and follow-up characteristics were recorded, and most patients had a follow-up office visit or were involved in a telephone survey 1 year after surgery. These 22 centers provided data on 541 patients, 396 (73%) of whom were followed up 1 year after surgery. Of 504 (93%) patients for whom antibiotic prophylaxis was recorded, 433 (86%) received a cephalosporin. Twenty-two patients had an SSI, for a rate of 5.6% (95% confidence interval, 3.7-8.0). SSI was reported for 15 (6.9%) of patients who had a prosthesis placed and for 7 (3.9%) who underwent osteosynthesis (P=.27). SSI was diagnosed a median of 30 days after surgery (interquartile range, 21-41 days); 7 (32%) of these SSIs were superficial infections, and 15 (68%) were deep or organ-space infections. MRSA caused 7 SSIs (32%), Pseudomonas aeruginosa caused 5 (23%), other staphylococci caused 4 (18%), and other bacteria caused 2 (9%); the etiologic pathogen was unknown in 4 cases (18%). Reoperation was performed for 14 patients with deep or organ-space SSI, including 6 of 7 patients with MRSA SSI. The mortality rate 1 year after surgery was 20% overall but 50% among patients with SSI. In univariate analysis, only the National Nosocomial Infections Surveillance System risk index score was significantly associated with SSI (P=.006). SSI after surgery for femoral neck fracture is severe, and MRSA is the most frequently encountered etiologic pathogen. A large, multicenter prospective trial is necessary to determine whether the use of antibiotic prophylaxis effective against MRSA would decrease the SSI rate in this population.

Lifestyle interventions and independence for elders study: Recruitment and baseline characteristics

USDA-ARS?s Scientific Manuscript database

Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate...

Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

PubMed

Cohen Aubart, Fleur; Abbara, Salam; Maisonobe, Thierry; Cottin, Vincent; Papo, Thomas; Haroche, Julien; Mathian, Alexis; Pha, Micheline; Gilardin, Laurent; Hervier, Baptiste; Soussan, Michael; Morlat, Philippe; Nunes, Hilario; Benveniste, Olivier; Amoura, Zahir; Valeyre, Dominique

2018-05-01

To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

Nonparametric estimation of median survival times with applications to multi-site or multi-center studies.

PubMed

Rahbar, Mohammad H; Choi, Sangbum; Hong, Chuan; Zhu, Liang; Jeon, Sangchoon; Gardiner, Joseph C

2018-01-01

We propose a nonparametric shrinkage estimator for the median survival times from several independent samples of right-censored data, which combines the samples and hypothesis information to improve the efficiency. We compare efficiency of the proposed shrinkage estimation procedure to unrestricted estimator and combined estimator through extensive simulation studies. Our results indicate that performance of these estimators depends on the strength of homogeneity of the medians. When homogeneity holds, the combined estimator is the most efficient estimator. However, it becomes inconsistent when homogeneity fails. On the other hand, the proposed shrinkage estimator remains efficient. Its efficiency decreases as the equality of the survival medians is deviated, but is expected to be as good as or equal to the unrestricted estimator. Our simulation studies also indicate that the proposed shrinkage estimator is robust to moderate levels of censoring. We demonstrate application of these methods to estimating median time for trauma patients to receive red blood cells in the Prospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study.

Use of biodegradable polylactic acid barrier materials in the treatment of grade II periodontal furcation defects in humans--Part I: A multicenter investigative clinical study.

PubMed

Vernino, A R; Ringeisen, T A; Wang, H L; Derhalli, M; Rapley, J; Nechamkin, S J; Brekke, J

1998-12-01

This study evaluated two bioresorbable polylactic acid barriers (Epi-Guide and Guidor) to determine if design differences were of therapeutic significance in the treatment of Grade II furcation defects in humans. Forty patients with bilaterally matched, Grade II furcation defects in maxillary or mandibular first or second molars were treated in a multicenter study. Comprehensive initial periodontal therapy, followed by defect debridement and root preparation, preceded randomized membrane placement. Data collected from all three investigative centers were pooled and analyzed using an analysis of variance appropriate for a counterbalancing design. Both barrier types produced measurable improvements of clinical probing values. Barrier exposure scores taken through the eighth week postoperative revealed that Epi-Guide was less likely to become exposed than Guidor. The findings of this study, which was conducted over a 12-month period, demonstrated that Epi-Guide and Guidor were comparable as measured by clinical probing determinations.

Intraorganizational Communication and Job Satisfaction Among Flemish Hospital Nurses: An Exploratory Multicenter Study.

PubMed

Vermeir, Peter; Downs, Cal; Degroote, Sophie; Vandijck, Dominique; Tobback, Els; Delesie, Liesbeth; Mariman, An; De Veugele, Myriam; Verhaeghe, Rik; Cambré, Bart; Vogelaers, Dirk

2018-01-01

Intraorganizational communication affects job satisfaction and turnover. The goal of this study was to explore relationships between communication and job satisfaction, intention to leave, and burnout among Flemish hospital nurses. A multicenter questionnaire study was conducted in three hospitals using the Communication Satisfaction Questionnaire, the Turnover Intention subscale of the Questionnaire on the Experience and Evaluation of Work, and the Maslach Burnout Inventory. A visual analog scale measured job satisfaction. The mean job satisfaction score was 7.49/10 (±1.43). Almost 7% of nurse participants (93/1,355) reported a high intent to leave, and 2.9% of the respondents (41/1,454) had a score indicative of burnout. All dimensions of communication were associated with job satisfaction. A low score on any dimension of communication satisfaction, except "Relationship With Employees," was associated with higher intent to leave and burnout. Study findings support the need for management interventions to enhance efficient communication and ensure high-quality care and patient safety.

Multicenter prospective study of treatment of Brucella melitensis brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks.

PubMed Central

Cisneros, J M; Viciana, P; Colmenero, J; Pachón, J; Martinez, C; Alarcón, A

1990-01-01

The effectiveness of treating human brucellosis caused by Brucella melitensis with a 6-week course of doxcycline plus streptomycin for 2 of those weeks was analyzed by a multicenter prospective study of 139 patients. Subjects with central nervous system involvement, endocarditis, or spondylitis were excluded from the study. All but 5 of the 139 patients completed the full treatment schedule and became afebrile in the first week of therapy. Four patients suffered relapses during the follow-up period. Of the five patients who did not complete the treatment, two left because of adverse secondary effects (1.4%), another two left for noncomplicance with the treatment (1.4%), and the remaining patient was considered a therapeutic failure because his symptoms persisted after the first week of therapy (0.7%). We concluded that the combination of doxycycline and streptomycin is an effective treatment for the types of brucellosis included in our study. PMID:2193624

Ocular Toxoplasmosis in Tropical Areas: Analysis and Outcome of 190 Patients from a Multicenter Collaborative Study.

PubMed

Huang, Philemon K; Jianping, Chen; Vasconcelos-Santos, Daniel Vitor; Arruda, Jacqueline Souza Dutra; Dutta Majumder, Parthopratim; Anthony, Eliza; Ganesh, Sudha K; Biswas, Jyotirmay; Ling, Ho Su; Teoh, Stephen C; Agrawal, Rupesh

2017-10-11

To describe clinical findings and outcomes for ocular toxoplasmosis in an international multicenter collaborative study. Retrospective analysis of 190 patients diagnosed with ocular toxoplasmosis from three study sites (Brazil, India, and Singapore). There were 93 (48.9%) females with a mean age of 32.8 years. The most common symptoms were isolated blurring of vision (36.8%), followed by blurring of vision with floaters (21.1%). Treatment regimens varied largely from monotherapy to multiple combination therapies. Final visual acuity of ≥20/40 was achieved in 106 (74.2%) patients. In a median follow-up period of 31 weeks (range 12-749 weeks), 83/190 (43.7%) patients suffered a relapse. There appears to be geographical variation in the presentation of ocular toxoplasmosis. Compared to previous studies, we did not observe the '"dual peak" phenomenon of chronic and active disease based on age at presentation, and there was less bilateral and macular involvement (but more peripheral involvement).

Nonparametric estimation of median survival times with applications to multi-site or multi-center studies

PubMed Central

Choi, Sangbum; Hong, Chuan; Zhu, Liang; Jeon, Sangchoon; Gardiner, Joseph C.

2018-01-01

We propose a nonparametric shrinkage estimator for the median survival times from several independent samples of right-censored data, which combines the samples and hypothesis information to improve the efficiency. We compare efficiency of the proposed shrinkage estimation procedure to unrestricted estimator and combined estimator through extensive simulation studies. Our results indicate that performance of these estimators depends on the strength of homogeneity of the medians. When homogeneity holds, the combined estimator is the most efficient estimator. However, it becomes inconsistent when homogeneity fails. On the other hand, the proposed shrinkage estimator remains efficient. Its efficiency decreases as the equality of the survival medians is deviated, but is expected to be as good as or equal to the unrestricted estimator. Our simulation studies also indicate that the proposed shrinkage estimator is robust to moderate levels of censoring. We demonstrate application of these methods to estimating median time for trauma patients to receive red blood cells in the Prospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study. PMID:29772007

Electronic medical record integration with a database for adult congenital heart disease: Early experience and progress in automating multicenter data collection.

PubMed

Broberg, Craig S; Mitchell, Julie; Rehel, Silven; Grant, Andrew; Gianola, Ann; Beninato, Peter; Winter, Christiane; Verstappen, Amy; Valente, Anne Marie; Weiss, Joseph; Zaidi, Ali; Earing, Michael G; Cook, Stephen; Daniels, Curt; Webb, Gary; Khairy, Paul; Marelli, Ariane; Gurvitz, Michelle Z; Sahn, David J

2015-10-01

The adoption of electronic health records (EHR) has created an opportunity for multicenter data collection, yet the feasibility and reliability of this methodology is unknown. The aim of this study was to integrate EHR data into a homogeneous central repository specifically addressing the field of adult congenital heart disease (ACHD). Target data variables were proposed and prioritized by consensus of investigators at five target ACHD programs. Database analysts determined which variables were available within their institutions' EHR and stratified their accessibility, and results were compared between centers. Data for patients seen in a single calendar year were extracted to a uniform database and subsequently consolidated. From 415 proposed target variables, only 28 were available in discrete formats at all centers. For variables of highest priority, 16/28 (57%) were available at all four sites, but only 11% for those of high priority. Integration was neither simple nor straightforward. Coding schemes in use for congenital heart diagnoses varied and would require additional user input for accurate mapping. There was considerable variability in procedure reporting formats and medication schemes, often with center-specific modifications. Despite the challenges, the final acquisition included limited data on 2161 patients, and allowed for population analysis of race/ethnicity, defect complexity, and body morphometrics. Large-scale multicenter automated data acquisition from EHRs is feasible yet challenging. Obstacles stem from variability in data formats, coding schemes, and adoption of non-standard lists within each EHR. The success of large-scale multicenter ACHD research will require institution-specific data integration efforts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

PubMed

Kavros, Steven J; Dutra, Timothy; Gonzalez-Cruz, Renier; Liden, Brock; Marcus, Belinda; McGuire, James; Nazario-Guirau, Luis

2014-08-01

The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Interrater reliability among epilepsy centers: multicenter study of epilepsy surgery.

PubMed

Haut, Sheryl R; Berg, Anne T; Shinnar, Shlomo; Cohen, Hillel W; Bazil, Carl W; Sperling, Michael R; Langfitt, John T; Pacia, Steven V; Walczak, Thaddeus S; Spencer, Susan S

2002-11-01

To measure the interrater reliability of presurgical testing and surgical decisions among epilepsy centers. Seven centers participating in an ongoing, prospective multicenter study of resective epilepsy surgery agreed to conform to a detailed protocol regarding presurgical evaluation and surgery. To assess quality assurance, each center independently reviewed 21 randomly selected surgical cases for preoperative study lateralization and localization, and surgical decisions. Interrater reliability was assessed by using intraclass correlation coefficients (ICCs), validated for use with multiple raters, and calculated in a two-way random model based on absolute agreement. Agreement for ICC values: > or = 0.75, excellent; 0.60-0.74, good; 0.40-0.59, fair; < or = 0.39, poor. One center was excluded for missing data. Agreement was excellent for extracranial EEG lateralization (0.8039), magnetic resonance imaging (MRI) lateralization (0.9521) and localization (0.9130), Wada lateralization (0.9453), and intracranial EEG localization (0.7905). Agreement was good for extracranial EEG localization (0.7384) and neuropsychological testing lateralization (0.7178) and localization (0.6891). Consensus about the decision to perform intracranial monitoring was fair (0.5397), in part reflecting one center's tendency toward intracranial monitoring. Overall agreements on whether to perform surgery (0.8311) and specific surgery recommended (0.8164) were excellent. High interrater reliability among six epilepsy centers was present for interpretation of most components of presurgical testing. Although consensus for the decision to perform intracranial monitoring was only fair, agreements for the ultimate decision about resective surgery and specific choice of resection were excellent. We believe that this study demonstrates the feasibility of implementing multicenter protocols for neurologic management, especially those involving localization, as well as protocols combining study results with clinical decision making.

The Italian dementia with Lewy bodies study group (DLB-SINdem): toward a standardization of clinical procedures and multicenter cohort studies design.

PubMed

Bonanni, L; Cagnin, A; Agosta, F; Babiloni, C; Borroni, B; Bozzali, M; Bruni, A C; Filippi, M; Galimberti, D; Monastero, R; Muscio, C; Parnetti, L; Perani, D; Serra, L; Silani, V; Tiraboschi, P; Padovani, A

2017-01-01

Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients' reduced quality of life and high mortality. Furthermore, DLB is often misdiagnosed as Alzheimer's disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer's disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.

Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study.

PubMed

Tsukamoto, Shunsuke; Nishizawa, Yuji; Ochiai, Hiroki; Tsukada, Yuichiro; Sasaki, Takeshi; Shida, Dai; Ito, Masaaki; Kanemitsu, Yukihide

2017-12-01

We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Identifying and collecting pertinent medical records for centralized abstraction in a multi-center randomized clinical trial: the model used by the American College of Radiology arm of the National Lung Screening Trial.

PubMed

Gareen, Ilana F; Sicks, JoRean D; Jain, Amanda Adams; Moline, Denise; Coffman-Kadish, Nancy

2013-01-01

In clinical trials and epidemiologic studies, information on medical care utilization and health outcomes is often obtained from medical records. For multi-center studies, this information may be gathered by personnel at individual sites or by staff at a central coordinating center. We describe the process used to develop a HIPAA-compliant centralized process to collect medical record information for a large multi-center cancer screening trial. The framework used to select, request, and track medical records incorporated a participant questionnaire with unique identifiers for each medical provider. De-identified information from the questionnaires was sent to the coordinating center indexed by these identifiers. The central coordinating center selected specific medical providers for abstraction and notified sites using these identifiers. The site personnel then linked the identifiers with medical provider information. Staff at the sites collected medical records and provided them for central abstraction. Medical records were successfully obtained and abstracted to ascertain information on outcomes and health care utilization in a study with over 18,000 study participants. Collection of records required for outcomes related to positive screening examinations and lung cancer diagnosis exceeded 90%. Collection of records for all aims was 87.32%. We designed a successful centralized medical record abstraction process that may be generalized to other research settings, including observational studies. The coordinating center received no identifying data. The process satisfied requirements imposed by the Health Insurance Portability and Accountability Act and concerns of site institutional review boards with respect to protected health information. Copyright © 2012 Elsevier Inc. All rights reserved.

Identifying and collecting pertinent medical records for centralized abstraction in a multi-center randomized clinical trial: The model used by the American College of Radiology arm of the National Lung Screening Trial

PubMed Central

Gareen, Ilana F.; Sicks, JoRean; Adams, Amanda; Moline, Denise; Coffman-Kadish, Nancy

2012-01-01

Background In clinical trials and epidemiologic studies, information on medical care utilization and health outcomes is often obtained from medical records. For multi-center studies, this information may be gathered by personnel at individual sites or by staff at a central coordinating center. We describe the process used to develop a HIPAA-compliant centralized process to collect medical record information for a large multi-center cancer screening trial. Methods The framework used to select, request, and track medical records incorporated a participant questionnaire with unique identifiers for each medical provider. De-identified information from the questionnaires was sent to the coordinating center indexed by these identifiers. The central coordinating center selected specific medical providers for abstraction and notified sites using these identifiers. The site personnel then linked the identifiers with medical provider information. Staff at the sites collected medical records and provided them for central abstraction. Results Medical records were successfully obtained and abstracted to ascertain information on outcomes and health care utilization in a study with over 18,000 study participants. Collection of records required for outcomes related to positive screening examinations and lung cancer diagnosis exceeded 90%. Collection of records for all aims was 87.32%. Conclusions We designed a successful centralized medical record abstraction process that may be generalized to other research settings, including observational studies. The coordinating center received no identifying data. The process satisfied requirements imposed by the Health Insurance Portability and Accountability Act and concerns of site institutional review boards with respect to protected health information. PMID:22982342

Integrating a Patient-Controlled Admission Program Into Mental Health Hospital Service: A Multicenter Grounded Theory Study.

PubMed

Ellegaard, Trine; Bliksted, Vibeke; Mehlsen, Mimi; Lomborg, Kirsten

2018-05-01

Patient-controlled admissions (PCAs) enable mental health patients by means of a contract to initiate an admission at a mental health hospital unit without using traditional admission procedures. This study was part of a 3-year Danish multicenter project, and we explored how mental health professionals experienced and managed the implementation of a PCA program. The methodology was grounded theory and the sample included 26 participants. We performed a constant comparative analysis to explore the concerns, attitudes, and strategies of mental health professionals. We developed a model of how the mental health professionals strived to integrate PCA into clinical practice. The process was motivated by the idea of establishing a partnership with patients and involved two interrelated strategies to manage (a) the patient-related duties and (b) the admission contracts. The professionals moved from a phase of professional discomfort to a phase of professional awareness, and ended up with professional comprehension.

Increasing complexity of clinical research in gastroenterology: implications for the training of clinician-scientists.

PubMed

Scott, Frank I; McConnell, Ryan A; Lewis, Matthew E; Lewis, James D

2012-04-01

Significant advances have been made in clinical and epidemiologic research methods over the past 30 years. We sought to demonstrate the impact of these advances on published gastroenterology research from 1980 to 2010. Twenty original clinical articles were randomly selected from each of three journals from 1980, 1990, 2000, and 2010. Each article was assessed for topic, whether the outcome was clinical or physiologic, study design, sample size, number of authors and centers collaborating, reporting of various statistical methods, and external funding. From 1980 to 2010, there was a significant increase in analytic studies, clinical outcomes, number of authors per article, multicenter collaboration, sample size, and external funding. There was increased reporting of P values, confidence intervals, and power calculations, and increased use of large multicenter databases, multivariate analyses, and bioinformatics. The complexity of clinical gastroenterology and hepatology research has increased dramatically, highlighting the need for advanced training of clinical investigators.

Safety and efficacy of a 10% intravenous immunoglobulin preparation in patients with immune thrombocytopenic purpura: results of two international, multicenter studies.

PubMed

Kovaleva, Lidia; Apte, Shashikant; Damodar, Sharat; Ramanan, Vijay; Loriya, Svetlana; Navarro-Puerto, Jordi; Khojasteh, Ali

2016-12-01

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma ® 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 9 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.

A 12-week, double-blind, multicenter study comparing diflunisal twice daily and ibuprofen four times daily in the treatment of rheumatoid arthritis.

PubMed

Bennett, R M

1986-01-01

Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule.

Development and Measurement of Guidelines-Based Quality Indicators of Caesarean Section Care in the Netherlands: A RAND-Modified Delphi Procedure and Retrospective Medical Chart Review

PubMed Central

de Boer, Karin; Burggraaf, Henriëtte; Derks, Jan B.; van Dijk, Det; van Dillen, Jeroen; Dirksen, Carmen D.; Duvekot, Johannes J.; Franx, Arie; Hasaart, Tom H. M.; Huisjes, Anjoke J. M.; Kolkman, Diny; Kwee, Anneke; Mol, Ben W.; van Pampus, Mariëlle G.; de Roon-Immerzeel, Alieke; van Roosmalen, Jos J. M.; Roumen, Frans J. M. E.; Smid-Koopman, Ellen; Spaans, Wilbert A.; Visser, Harry; van Wijngaarden, Wim J.; Willekes, Christine; Wouters, Maurice G. A. J.

2016-01-01

Background There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates. Method Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery. Results The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adherence 46%), 2) non-progressive labour (frequency 12%, CS performed too early in over 75%), 3) continuous support during labour (frequency 88%, adherence 37%) and 4) previous CS (frequency 12%), with adequate counselling in 15%. Conclusions We identified four concrete target groups for improvement of obstetrical care, which can be used as a starting point to reduce CS rates worldwide. PMID:26783742

The Treatment for Adolescents with Depression Study (TADS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

n/a; n/a

2005-01-01

Objective: The Treatment for Adolescents With Depression Study is a multicenter, randomized clinical trial sponsored by the NIMH. This study is designed to evaluate the short- and long-term effectiveness of four treatments for adolescents with major depressive disorder: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely,…

How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study

PubMed Central

Léger, Julie; Tandé, Didier; Plouzeau, Chloé; Valentin, Anne Sophie; Jolivet-Gougeon, Anne; Lemarié, Carole; Kempf, Marie; Héry-Arnaud, Geneviève; Bret, Laurent; Juvin, Marie Emmanuelle; Giraudeau, Bruno; Burucoa, Christophe

2015-01-01

Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI. PMID:26637380

How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study.

PubMed

Bémer, Pascale; Léger, Julie; Tandé, Didier; Plouzeau, Chloé; Valentin, Anne Sophie; Jolivet-Gougeon, Anne; Lemarié, Carole; Kempf, Marie; Héry-Arnaud, Geneviève; Bret, Laurent; Juvin, Marie Emmanuelle; Giraudeau, Bruno; Corvec, Stéphane; Burucoa, Christophe

2016-02-01

Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

PubMed

Fotopoulou, Christina; Sehouli, Jalid; Ewald-Riegler, Nina; de Gregorio, Nikolaus; Reuss, Alexander; Richter, Rolf; Mahner, Sven; Kommoss, Friedrich; Schmalfeldt, Barbara; Fehm, Tanja; Hanker, Lars; Wimberger, Pauline; Canzler, Ulrich; Pfisterer, Jacobus; Kommoss, Stefan; Hauptmann, Steffen; du Bois, Andreas

2015-09-01

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

PubMed Central

2012-01-01

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements. PMID:22928744

Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults

PubMed Central

Liang, Peipeng; Shi, Lin; Chen, Nan; Luo, Yishan; Wang, Xing; Liu, Kai; Mok, Vincent CT; Chu, Winnie CW; Wang, Defeng; Li, Kuncheng

2015-01-01

Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18–76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population-specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID:26678304

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

PubMed

Li, Yan; Ma, Hongli; Zhang, Yuehui; Kuang, Hongying; Ng, Ernest Hung Yu; Hou, Lihui; Wu, Xiaoke

2013-07-18

Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. We postulate that women with PCOS will have improved insulin resistance following berberine administration. This study is registered at ClinicalTrials.gov, NCT01138930.

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

PubMed

Wang, Limin; Wang, Qian; Li, Guimei; Liu, Wendong

2015-09-01

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

Assessing production characteristics, influential factors and administrative policies in a multicenter dental organization.

PubMed

Patterson, Charles W

2012-06-01

In multicenter service organizations, managers often make centralized decisions without considering the effects of differing production characteristics and influential factors on each center. In this study, the author examines differences in production characteristics and factors that influence production, as well as their likely effect on policy formulation, in a large, six-center dental group in the Chicago area. The results of the study show that the six centers (in two groups) exhibited two distinct production patterns, with three having logarithmic distributions and three having normal distributions. Production differences between the groups likely resulted from differences in managed care, staffing and dental procedures performed. Instead of being monolithic, the organization exhibited two types of centers, each with its own production characteristics and factors that influenced production. The study results suggest that large service corporations and }partnerships would benefit from conducting analyses of production characteristics and factors that influence production before making policy decisions that affect the entire organization.

77 FR 9665 - Submission for OMB Emergency Review; Comment Request: A Multi-Center International Hospital-Based...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... postulated risk factors for evaluation in this study are chemical exposures (i.e., organochlorines, trichloroethylene, and benzene) and genetic susceptibility. Other factors potentially related to lymphoma, such as... also be studied. Patterns of key risk factors, including range of exposures, prevalence of exposures...

Physical activity monitoring in COPD: compliance and associations with clinical characteristics in a multicenter study.

PubMed

Waschki, Benjamin; Spruit, Martijn A; Watz, Henrik; Albert, Paul S; Shrikrishna, Dinesh; Groenen, Miriam; Smith, Cayley; Man, William D-C; Tal-Singer, Ruth; Edwards, Lisa D; Calverley, Peter M A; Magnussen, Helgo; Polkey, Michael I; Wouters, Emiel F M

2012-04-01

Little is known about COPD patients' compliance with physical activity monitoring and how activity relates to disease characteristics in a multi-center setting. In a prospective study at three Northern European sites physical activity and clinical disease characteristics were measured in 134 COPD patients (GOLD-stage II-IV; BODE index 0-9) and 46 controls. Wearing time, steps per day, and the physical activity level (PAL) were measured by a multisensory armband over a period of 6 consecutive days (in total, 144 h). A valid measurement period was defined as ≥22 h wearing time a day on at least 5 days. The median wearing time was 142 h:17 min (99%), 141 h:1 min (98%), and 142 h:24 min (99%), respectively in the three centres. A valid measurement period was reached in 94%, 97%, and 94% of the patients and did not differ across sites (P = 0.53). The amount of physical activity did not differ across sites (mean steps per day, 4725 ± 3212, P = 0.58; mean PAL, 1.45 ± 0.20, P = 0.48). Multivariate linear regression analyses revealed significant associations of FEV1, 6-min walk distance, quadriceps strength, fibrinogen, health status, and dyspnoea with both steps per day and PAL. Previously unrecognized correlates of activity were grade of fatigue, degree of emphysema, and exacerbation rate. The excellent compliance with wearing a physical activity monitor irrespective of study site and consistent associations with relevant disease characteristics support the use of activity monitoring as a valid outcome in multi-center studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Utility of an Abbreviated Dizziness Questionnaire to Differentiate between Causes of Vertigo and Guide Appropriate Referral: A Multicenter Prospective Blinded Study

PubMed Central

Roland, Lauren T.; Kallogjeri, Dorina; Sinks, Belinda C.; Rauch, Steven D.; Shepard, Neil T.; White, Judith A.; Goebel, Joel A.

2015-01-01

Objective Test performance of a focused dizziness questionnaire’s ability to discriminate between peripheral and non-peripheral causes of vertigo. Study Design Prospective multi-center Setting Four academic centers with experienced balance specialists Patients New dizzy patients Interventions A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Main outcomes Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and non-peripheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. Results 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and non-peripheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central and other causes were considered good as measured by c-indices of 0.75, 0.7 and 0.78, respectively. Conclusions This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from non-peripheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed. PMID:26485598

Depressive Symptoms Correlate with Disability and Disease Course in Multiple Sclerosis Patients: An Italian Multi-Center Study Using the Beck Depression Inventory.

PubMed

Solaro, C; Trabucco, E; Signori, A; Martinelli, V; Radaelli, M; Centonze, D; Rossi, S; Grasso, M G; Clemenzi, A; Bonavita, S; D'Ambrosio, A; Patti, F; D'Amico, E; Cruccu, G; Truini, A

2016-01-01

Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0-8.5) and mean disease duration of 10.3 years (range 1-50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20-63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials.

PubMed

Kimberly, Michael B; Hoehn, K Sarah; Feudtner, Chris; Nelson, Robert M; Schreiner, Mark

2006-05-01

To systematically compare standards for compensation and child participant assent in informed permission, assent, and consent forms (IP-A-CFs) approved by 55 local institutional review boards (IRBs) reviewing 3 standardized multicenter research protocols. Sixty-nine principal investigators participating in any of 3 national, multicenter clinical trials submitted standardized research protocols for their trials to their local IRBs for approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to an academic clinical research organization. This collection of IRB-approved forms allowed for a quasiexperimental retrospective evaluation of the variation in informed permission, assent, and consent standards operationalized by the local IRBs. Standards for compensation and child participant assent varied substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering compensation, monetary compensation was offered by 33 as reimbursement for travel, parking, or food expenses, whereas monetary or material compensation was offered by 22 for subject inconvenience and by 13 for subject time. Compensation ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that included a form of assent documentation, 33 included a line for assent on the informed permission or consent form, whereas 35 included a separate form written in simplified language. Of the IP-A-CFs that stipulated the documentation of assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission or consent forms were addressed either to parents or child participants. In response to identical clinical trial protocols, local IRBs generate IP-A-CFs that vary considerably regarding compensation and child participant assent.

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

PubMed

Nicolini, A; Tonveronachi, E; Navalesi, P; Antonelli, M; Valentini, I; Melotti, R M; Pigna, A; Carrassi, A; Righini, P; Ferrari Bravo, M; Pelosi, P; Nicoli, F; Cosentini, R; Vaschetto, R; Faenza, S; Nava, S

2012-12-01

The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma.

PubMed

Yanamoto, Souichi; Umeda, Masahiro; Kioi, Mitomu; Kirita, Tadaaki; Yamashita, Tetsuro; Hiratsuka, Hiroyoshi; Yokoo, Satoshi; Tanzawa, Hideki; Uzawa, Narikazu; Shibahara, Takahiko; Ota, Yoshihide; Kurita, Hiroshi; Okura, Masaya; Hamakawa, Hiroyuki; Kusukawa, Jingo; Tohnai, Iwai

2018-03-01

The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC). We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m 2 ; subsequent weeks, 250 mg/m 2 ) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m 2 , day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m 2 /day, days 1-4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first. The median follow-up was 10.5 (range 1.2-34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3-4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal. The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.

A Multicenter Performance Evaluation of a Blood Glucose Monitoring System in 21 Leading Hospitals in Spain

PubMed Central

Bedini, José Luis; Wallace, Jane F.; Petruschke, Thorsten; Pardo, Scott

2015-01-01

Background: Self-monitoring of blood glucose is crucial for the effective self-management of diabetes. The present study evaluated the accuracy of the Contour® XT blood glucose monitoring system (BGMS) compared to the reference method in a large multicenter study under routine lab conditions at each hospital site. Methods: This study was conducted at 21 leading hospitals in Spain using leftover whole blood samples (n = 2100). Samples were tested with the BGMS using 1 commercial strip lot and the local laboratory hexokinase method. BGMS accuracy was assessed and results were compared to ISO 15197:2013 accuracy limit criteria and by using mean absolute relative difference analysis (MARD), consensus (Parkes) error grid (CEG), and surveillance error grid analyses (SEG). Results: Pooled analysis of 2100 measurements from all sites showed that 99.43% of the BGMS results were within the ranges accepted by the accuracy limit criteria. The overall MARD was 3.85%. MARD was 4.47% for glucose concentrations < 70 mg/dL and 3.81% for concentrations of 70-300 mg/dL. In CEG, most results (99.8%) were within zone A (“no effect on clinical action”); the remaining ones (0.2%) were in zone B (“little to no effect on clinical action”). The SEG analysis showed that most of the results (98.4%) were in the “no risk” zone, with the remaining results in the “slight, lower” risk zone. Conclusions: This is the largest multicenter study of Contour XT BGMS to date, and shows that this BGMS meets the ISO 15197:2013 accuracy limit criteria under local routine conditions in 21 leading Spanish hospitals. PMID:26253142

A Multicenter Performance Evaluation of a Blood Glucose Monitoring System in 21 Leading Hospitals in Spain.

PubMed

Bedini, José Luis; Wallace, Jane F; Petruschke, Thorsten; Pardo, Scott

2015-08-07

Self-monitoring of blood glucose is crucial for the effective self-management of diabetes. The present study evaluated the accuracy of the Contour® XT blood glucose monitoring system (BGMS) compared to the reference method in a large multicenter study under routine lab conditions at each hospital site. This study was conducted at 21 leading hospitals in Spain using leftover whole blood samples (n = 2100). Samples were tested with the BGMS using 1 commercial strip lot and the local laboratory hexokinase method. BGMS accuracy was assessed and results were compared to ISO 15197:2013 accuracy limit criteria and by using mean absolute relative difference analysis (MARD), consensus (Parkes) error grid (CEG), and surveillance error grid analyses (SEG). Pooled analysis of 2100 measurements from all sites showed that 99.43% of the BGMS results were within the ranges accepted by the accuracy limit criteria. The overall MARD was 3.85%. MARD was 4.47% for glucose concentrations < 70 mg/dL and 3.81% for concentrations of 70-300 mg/dL. In CEG, most results (99.8%) were within zone A ("no effect on clinical action"); the remaining ones (0.2%) were in zone B ("little to no effect on clinical action"). The SEG analysis showed that most of the results (98.4%) were in the "no risk" zone, with the remaining results in the "slight, lower" risk zone. This is the largest multicenter study of Contour XT BGMS to date, and shows that this BGMS meets the ISO 15197:2013 accuracy limit criteria under local routine conditions in 21 leading Spanish hospitals. © 2015 Diabetes Technology Society.

Safety of Endovascular Intervention for Stroke on Therapeutic Anticoagulation: Multicenter Cohort Study and Meta-Analysis.

PubMed

Kurowski, Donna; Jonczak, Karin; Shah, Qaisar; Yaghi, Shadi; Marshall, Randolph S; Ahmad, Haroon; McKinney, James; Torres, Jose; Ishida, Koto; Cucchiara, Brett

2017-05-01

Intravenous (IV) tissue plasminogen activator (tPA) is contraindicated in therapeutically anti-coagulated patients. Such patients may be considered for endovascular intervention. However, there are limited data on its safety. We performed a multicenter retrospective study of patients undergoing endovascular intervention for acute ischemic stroke while on therapeutic anticoagulation. We compared the observed rate of National Institute of Neurological Disorders and Stroke defined symptomatic intracerebral hemorrhage (sICH) with risk-adjusted historical control rates of sICH after IV tPA using weighted averages of the hemorrhage after thrombolysis (HAT) and Multicenter Stroke Survey (MSS) prediction scores. We also performed a metaanalysis of studies assessing risk of sICH with endovascular intervention in patients on anticoagulation. Of 94 cases, mean age was 73 years and median National Institutes of Health Stroke Scale was 19. Anticoagulation consisted of warfarin (n = 51), dabigatran (n = 6), rivaroxaban (n = 13), apixaban (n = 1), IV heparin (n = 19), low molecular weight heparin (n = 3), and combined warfarin and IV heparin (n = 3). sICH was seen in 7 patients (7%, 95% confidence interval 4-15), all on warfarin. Predicted sICH rates for the cohort based on HAT and MSS scoring were 12% and 7%, respectively. Meta-analysis of 6 studies showed no significant difference in sICH between patients undergoing endovascular intervention on anticoagulation and comparator groups. Endovascular intervention in subjects on therapeutic anticoagulation appears reasonably safe, with a sICH rate similar to patients not on anticoagulation receiving IV tPA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Prospective Multi-Center Audit of Nutrition Support Parameters Following Burn Injury.

PubMed

Kurmis, Rochelle; Heath, Kathryn; Ooi, Selena; Munn, Zachary; Forbes, Sharon; Young, Vicki; Rigby, Paul; Wood, Kate; Phillips, Frances; Greenwood, John

2015-01-01

The importance of nutrition support delivery to the severe burn-injured patient is well recognized, however, nutrition provision to the patient may be sub optimal in practice. The aim of this study was to conduct a prospective multi-center audit across Australia and New Zealand using the Joanna Briggs Institute Burns Node Nutrition audit criteria. Thirty-four patients with severe burn injury (≥20% TBSA in adults and ≥10% TBSA in children) were identified on admission or on referral to the Dietitian at the eight participating Burn Units between February 1, 2012 and April 30, 2012 for inclusion in the study. De-identified patient data was analyzed using the Joanna Briggs Institute, Practical Application of Clinical Evidence System. Compliance with individual audit criterion ranged from 33 to 100%. Provision of prescribed enteral feed volumes and weekly weighing of patients were highlighted as key areas for clinical improvement. Clinical audit is a valuable tool for evaluating current practice against best evidence to ensure that quality patient care is delivered. The use of the Joanna Briggs Institute Burns Node audit criteria has allowed for a standardized multi-center audit to be conducted. Improving nutrition support delivery in burn patients was identified as a key area requiring ongoing clinical improvement across Australia and New Zealand. Clinician feedback on use of the audit criteria will allow for future refinement of individual criterion, and presentation of results of this audit has resulted in a review of the Bi-National Burns Registry nutrition quality indicators.

A cooperative network of trained sites for the conduct of a complex clinical trial: a new concept in multicenter clinical research.

PubMed

Davidson, Robert M; McNeer, J Frederick; Logan, Leanne; Higginbotham, Michael B; Anderson, Jerome; Blackshear, Joseph; Chu, Alan; Hettleman, Bruce; McGrew, Frank; Meesse, Roderick; O'Connor, Christopher; Schneider, Ricky; Wagner, Galen S

2006-02-01

The purpose of this report is to present a model of physicians in full-time clinical practice participating as investigators in multicenter clinical trials, sponsored by a pharmaceutical or medical device company. This gas-exchange substudy was conducted as a pilot study to establish the feasibility of the 10-member EXERcise testing group of the Duke University Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex multicenter trial using cardiopulmonary exercise testing. An active interchange of information was established involving the principal investigator for the substudy, a dedicated full-time project coordinator, a medical director of the overall EXERDUCCS network site, the project coordinator for the sponsor, and all the participating EXERDUCCS investigators and coordinators. The sponsor set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met this goal. As a result of the successful enrollment and completion of the study and substudy by the EXERDUCCS sites, the sponsor subsequently increased the payment stipends to the sites to compensate for the extra work and expense incurred. This cooperative experience accomplished several goals: (1) it allowed a complex clinical trial to be successfully completed in a time frame which would not have been possible using only single unconnected sites; (2) it educated the physician-investigators (and their personnel) in exercise cardiopulmonary; and (3) it prepared the sites for future clinical trials involving this methodology.

Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

PubMed

Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

2015-02-01

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

GHPSS multicenter Italian survey: smoking prevalence, knowledge and attitudes, and tobacco cessation training among third-year medical students.

PubMed

Saulle, Rosella; Bontempi, Claudio; Baldo, Vincenzo; Boccia, Giovanni; Bonaccorsi, Guglielmo; Brusaferro, Silvio; Donato, Francesco; Firenze, Alberto; Gregorio, Pasquale; Pelissero, Gabriele; Sella, Alberto; Siliquini, Roberta; Boccia, Antonio; La Torre, Giuseppe

2013-01-01

Healthcare professionals have an important role to play both as advisers - influencing smoking cessation - and as role models. The aims of this study were to examine smoking prevalence, knowledge and attitudes among Italian university students attending medical schools using the Global Health Professions Student Survey (GHPSS) approach. A multicenter cross-sectional study was conducted among University students of 9 Italian medical schools (age ranging between 19 and 29 years). The GHPSS questionnaire was self-administered. A logistic regression model was used to identify possible factors associated with tobacco smoking status. Data were analyzed with the software SPSS 19.0 for Windows. Seven hundred thirty medical students (response rate 100%) were enrolled. The prevalence of current smokers was 20.4% (males 22.4%, females 19.1%). Of the total sample, 87.7% believed that health professionals should receive specific training in techniques to quit smoking, and 65% believed that health professionals had a role in giving advice or information about smoking cessation. However, 89.4% answered that they had not received specific training on smoking cessation techniques. Multivariate analysis showed that students belonging to universities in southern Italy were more likely to be smokers (OR = 2.00; 95% CI: 1.03-3.97). This Italian multicenter survey found that one fifth of future medical doctors are smokers. There is a need to adopt a standard undergraduate curriculum containing comprehensive tobacco prevention and cessation training to improve their effectiveness as role models.

Using 3D Printing to Create Personalized Brain Models for Neurosurgical Training and Preoperative Planning.

PubMed

Ploch, Caitlin C; Mansi, Chris S S A; Jayamohan, Jayaratnam; Kuhl, Ellen

2016-06-01

Three-dimensional (3D) printing holds promise for a wide variety of biomedical applications, from surgical planning, practicing, and teaching to creating implantable devices. The growth of this cheap and easy additive manufacturing technology in orthopedic, plastic, and vascular surgery has been explosive; however, its potential in the field of neurosurgery remains underexplored. A major limitation is that current technologies are unable to directly print ultrasoft materials like human brain tissue. In this technical note, the authors present a new technology to create deformable, personalized models of the human brain. The method combines 3D printing, molding, and casting to create a physiologically, anatomically, and tactilely realistic model based on magnetic resonance images. Created from soft gelatin, the model is easy to produce, cost-efficient, durable, and orders of magnitude softer than conventionally printed 3D models. The personalized brain model cost $50, and its fabrication took 24 hours. In mechanical tests, the model stiffness (E = 25.29 ± 2.68 kPa) was 5 orders of magnitude softer than common 3D printed materials, and less than an order of magnitude stiffer than mammalian brain tissue (E = 2.64 ± 0.40 kPa). In a multicenter surgical survey, model size (100.00%), visual appearance (83.33%), and surgical anatomy (81.25%) were perceived as very realistic. The model was perceived as very useful for patient illustration (85.00%), teaching (94.44%), learning (100.00%), surgical training (95.00%), and preoperative planning (95.00%). With minor refinements, personalized, deformable brain models created via 3D printing will improve surgical training and preoperative planning with the ultimate goal to provide accurate, customized, high-precision treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Demonstration of Nonlinearity Bias in the Measurement of the Apparent Diffusion Coefficient in Multicenter Trials

PubMed Central

Malyarenko, Dariya; Newitt, David; Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G.; Arlinghaus, Lori R.; Jacobs, Michael A.; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E.; Huang, Wei; Chenevert, Thomas L.

2015-01-01

Purpose Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Methods Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ±150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients and eddy currents were assessed independently. The observed bias errors were compared to numerical models. Results The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between −55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (±5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image co-registration of individual gradient directions. Conclusion The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. PMID:25940607

Optimization of a whole blood phenotyping assay for enumeration of peripheral blood leukocyte populations in multicenter clinical trials.

PubMed

Hensley-McBain, Tiffany; Heit, Antje; De Rosa, Stephen C; McElrath, M Juliana; Andersen-Nissen, Erica

2014-09-01

Vaccination with viral vectors or adjuvants can induce early changes in circulating peripheral blood leukocytes that are predictive of a protective immune response. In this study, we define an 11-color whole blood antibody staining Trucount Panel (TP1) to enumerate and phenotype the major leukocyte populations in a human vaccine experimental medicine trial setting. TP1 can be prepared up to 8weeks prior to use, enabling bulk preparation at a central laboratory and distribution to clinical sites. Cells in whole blood must be stained within 4h of draw to accurately detect the major cell populations. Staining of cells with TP1 followed by storage and shipping at -80°C to a central laboratory has little to no effect on the cell concentrations observed. We also present data from an HIV vaccine multicenter clinical trial obtained using the optimized TP1 assay protocol and show that the data produced accurately correlates with complete blood count (CBC) data. Taken together, these data indicate the optimized TP1 panel assay can be used in a multicenter clinical trial setting to increase our understanding of systemic responses to vaccination or disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Demonstration of nonlinearity bias in the measurement of the apparent diffusion coefficient in multicenter trials.

PubMed

Malyarenko, Dariya I; Newitt, David; J Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G; Arlinghaus, Lori R; Jacobs, Michael A; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E; Huang, Wei; Chenevert, Thomas L

2016-03-01

Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ± 150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients, and eddy currents were assessed independently. The observed bias errors were compared with numerical models. The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between -55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (± 5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image coregistration of individual gradient directions. The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. © 2015 Wiley Periodicals, Inc.

Most Common Publication Types in Radiology Journals:: What is the Level of Evidence?

PubMed

Rosenkrantz, Andrew B; Pinnamaneni, Niveditha; Babb, James S; Doshi, Ankur M

2016-05-01

This study aimed to assess the most common publication types in radiology journals, as well as temporal trends and association with citation frequency. PubMed was searched to extract all published articles having the following "Publication Type" indices: "validation studies," "meta-analysis," "clinical trial," "comparative study," "evaluation study," "guideline," "multicenter study," "randomized study," "review," "editorial," "case report," and "technical report." The percentage of articles within each category published within clinical radiology journals was computed. Normalized percentages for each category were also computed on an annual basis. Citation counts within a 2-year window following publication were obtained using Web of Science. Overall trends were assessed. Publication types with the highest fraction in radiology journals were technical reports, evaluation studies, and case reports (4.8% to 5.8%). Publication types with the lowest fraction in radiology journals were randomized trials, multicenter studies, and meta-analyses (0.8% to 1.5%). Case reports showed a significant decrease since 1999, with accelerating decline since 2007 (P = 0.002). Publication types with highest citation counts were meta-analyses, guidelines, and multicenter studies (8.1 ± 10.7 to 12.9 ± 5.1). Publication types with lowest citation counts were case reports, editorials, and technical reports (1.4 ± 2.4 to 2.9 ± 4.3). The representation in radiology journals and citation frequency of the publication types showed weak inverse correlation (r = -0.372). Radiology journals have historically had relatively greater representation of less frequently cited publication types. Various strategies, including methodological training, multidisciplinary collaboration, national support networks, as well as encouragement of higher level of evidence by funding agencies and radiology journals themselves, are warranted to improve the impact of radiological research. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

A review of the epidemiological methods used to investigate the health impacts of air pollution around major industrial areas.

PubMed

Pascal, Mathilde; Pascal, Laurence; Bidondo, Marie-Laure; Cochet, Amandine; Sarter, Hélène; Stempfelet, Morgane; Wagner, Vérène

2013-01-01

We performed a literature review to investigate how epidemiological studies have been used to assess the health consequences of living in the vicinity of industries. 77 papers on the chronic effects of air pollution around major industrial areas were reviewed. Major health themes were cancers (27 studies), morbidity (25 studies), mortality (7 studies), and birth outcome (7 studies). Only 3 studies investigated mental health. While studies were available from many different countries, a majority of papers came from the United Kingdom, Italy, and Spain. Several studies were motivated by concerns from the population or by previous observations of an overincidence of cases. Geographical ecological designs were largely used for studying cancer and mortality, including statistical designs to quantify a relationship between health indicators and exposure. Morbidity was frequently investigated through cross-sectional surveys on the respiratory health of children. Few multicenter studies were performed. In a majority of papers, exposed areas were defined based on the distance to the industry and were located from <2 km to >20 km from the plants. Improving the exposure assessment would be an asset to future studies. Criteria to include industries in multicenter studies should be defined.

Ultrasonic implant site preparation using piezosurgery: a multicenter case series study analyzing 3,579 implants with a 1- to 3-year follow-up.

PubMed

Vercellotti, Tomaso; Stacchi, Claudio; Russo, Crescenzo; Rebaudi, Alberto; Vincenzi, Giampaolo; Pratella, Umberto; Baldi, Domenico; Mozzati, Marco; Monagheddu, Chiara; Sentineri, Rosario; Cuneo, Tommaso; Di Alberti, Luca; Carossa, Stefano; Schierano, Gianmario

2014-01-01

This multicenter case series introduces an innovative ultrasonic implant site preparation (UISP) technique as an alternative to the use of traditional rotary instruments. A total of 3,579 implants were inserted in 1,885 subjects, and the sites were prepared using a specific ultrasonic device with a 1- to 3-year follow-up. No surgical complications related to the UISP protocol were reported for any of the implant sites. Seventy-eight implants (59 maxillary, 19 mandibular) failed within 5 months of insertion, for an overall osseointegration percentage of 97.82% (97.14% maxilla, 98.75% mandible). Three maxillary implants failed after 3 years of loading, with an overall implant survival rate of 97.74% (96.99% maxilla, 98.75% mandible).

The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED).

PubMed

Gold, Michael R; Knops, Reinoud; Burke, Martin C; Lambiase, Pier D; Russo, Andrea M; Bongiorni, Maria Grazia; Deharo, Jean-Claude; Aasbo, Johan; El Chami, Mikhael F; Husby, Michael; Carter, Nathan; Boersma, Lucas

2017-01-01

The UNTOUCHED study will assess the safety and efficacy of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the most common cohort of patients receiving ICDs. The primary goal is to evaluate the inappropriate shock (IAS)-free rate in primary prevention patients with a reduced ejection fraction (EF) and compare with a historical control of transvenous ICD patients with similar programming. The UNTOUCHED study is a global, multicenter, prospective, nonrandomized study of patients undergoing de novo S-ICD implantation for primary prevention of sudden cardiac death with a left ventricular EF ≤35%. The primary end point of this trial is freedom from IAS at 18 months. The lower 95% confidence bound of the observed incidence will be compared to a performance goal of 91.6%, which was derived from the IAS rate in MADIT-RIT. The secondary end points are all-cause shock-free rate at 18 months, and system- and procedure-related complication-free rate at 1 month and 6 months. Enrollment of a minimum of 1,100 subjects from up to 200 centers worldwide is planned based on power calculations of the primary and principal secondary end points. This trial will provide important data regarding the rates of inappropriate and appropriate shock therapy in real-world use of the S-ICD in the most common group of patients receiving ICDs. © 2016 Wiley Periodicals, Inc.

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

PubMed

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

The association between concomitant use of serotonergic antidepressants and lithium-induced polyuria. A multicenter medical chart review study.

PubMed

Wilting, I; Egberts, A C G; Movig, K L L; Laarhoven, J H M van; Heerdink, E R; Nolen, W A

2008-07-01

A previous study aimed at revealing the prevalence and determinants of lithium induced polyuria suggested an increased risk of polyuria (urine volume > or =3 L/24 h) in those using serotonergic antidepressants next to lithium. The objective of our study was to re-evaluate this secondary finding in another study population. We performed a multicenter medical chart review study in patients using lithium in whom a 24-hour urine volume had been determined. We included 116 patients, twelve (26%)of the 46 patients with polyuria used serotonergic antidepressants compared to ten (14%) of the 70 patients without polyuria. We found an increased risk of polyuria in lithium users concurrently using serotonergic antidepressants (oddsratio 2.86; 95% confidence interval 1.00-8.21), adjusted for age, gender, use of antiepileptics and thyreomimetics. Our results confirm the previous secondary finding of an increased risk of polyuria in patients using serotonergic antidepressants next to lithium. Physicians should take this into account when evaluating polyuria in patients using lithium and when choosing an antidepressant in patients using lithium.

HeartMate II left ventricular assist system: from concept to first clinical use.

PubMed

Griffith, B P; Kormos, R L; Borovetz, H S; Litwak, K; Antaki, J F; Poirier, V L; Butler, K C

2001-03-01

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Effectiveness of an interactive telerehabilitation system with home-based exercise training in patients after total hip or knee replacement: study protocol for a multicenter, superiority, no-blinded randomized controlled trial.

PubMed

Eichler, Sarah; Rabe, Sophie; Salzwedel, Annett; Müller, Steffen; Stoll, Josefine; Tilgner, Nina; John, Michael; Wegscheider, Karl; Mayer, Frank; Völler, Heinz

2017-09-21

Total hip or knee replacement is one of the most frequently performed surgical procedures. Physical rehabilitation following total hip or knee replacement is an essential part of the therapy to improve functional outcomes and quality of life. After discharge from inpatient rehabilitation, a subsequent postoperative exercise therapy is needed to maintain functional mobility. Telerehabilitation may be a potential innovative treatment approach. We aim to investigate the superiority of an interactive telerehabilitation intervention for patients after total hip or knee replacement, in comparison to usual care, regarding physical performance, functional mobility, quality of life and pain. This is an open, randomized controlled, multicenter superiority study with two prospective arms. One hundred and ten eligible and consenting participants with total knee or hip replacement will be recruited at admission to subsequent inpatient rehabilitation. After comprehensive, 3-week, inpatient rehabilitation, the intervention group performs a 3-month, interactive, home-based exercise training with a telerehabilitation system. For this purpose, the physiotherapist creates an individual training plan out of 38 different strength and balance exercises which were implemented in the system. Data about the quality and frequency of training are transmitted to the physiotherapist for further adjustment. Communication between patient and physiotherapist is possible with the system. The control group receives voluntary, usual aftercare programs. Baseline assessments are investigated after discharge from rehabilitation; final assessments 3 months later. The primary outcome is the difference in improvement between intervention and control group in 6-minute walk distance after 3 months. Secondary outcomes include differences in the Timed Up and Go Test, the Five-Times-Sit-to-Stand Test, the Stair Ascend Test, the Short-Form 36, the Western Ontario and McMaster Universities Osteoarthritis Index, the International Physical Activity Questionnaire, and postural control as well as gait and kinematic parameters of the lower limbs. Baseline-adjusted analysis of covariance models will be used to test for group differences in the primary and secondary endpoints. We expect the intervention group to benefit from the interactive, home-based exercise training in many respects represented by the study endpoints. If successful, this approach could be used to enhance the access to aftercare programs, especially in structurally weak areas. German Clinical Trials Register (DRKS), ID: DRKS00010009 . Registered on 11 May 2016.

Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

NASA Technical Reports Server (NTRS)

Landry, Steven J.; Farley, Todd; Hoang, Ty

2005-01-01

Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

Estimating relative risks in multicenter studies with a small number of centers - which methods to use? A simulation study.

PubMed

Pedroza, Claudia; Truong, Van Thi Thanh

2017-11-02

Analyses of multicenter studies often need to account for center clustering to ensure valid inference. For binary outcomes, it is particularly challenging to properly adjust for center when the number of centers or total sample size is small, or when there are few events per center. Our objective was to evaluate the performance of generalized estimating equation (GEE) log-binomial and Poisson models, generalized linear mixed models (GLMMs) assuming binomial and Poisson distributions, and a Bayesian binomial GLMM to account for center effect in these scenarios. We conducted a simulation study with few centers (≤30) and 50 or fewer subjects per center, using both a randomized controlled trial and an observational study design to estimate relative risk. We compared the GEE and GLMM models with a log-binomial model without adjustment for clustering in terms of bias, root mean square error (RMSE), and coverage. For the Bayesian GLMM, we used informative neutral priors that are skeptical of large treatment effects that are almost never observed in studies of medical interventions. All frequentist methods exhibited little bias, and the RMSE was very similar across the models. The binomial GLMM had poor convergence rates, ranging from 27% to 85%, but performed well otherwise. The results show that both GEE models need to use small sample corrections for robust SEs to achieve proper coverage of 95% CIs. The Bayesian GLMM had similar convergence rates but resulted in slightly more biased estimates for the smallest sample sizes. However, it had the smallest RMSE and good coverage across all scenarios. These results were very similar for both study designs. For the analyses of multicenter studies with a binary outcome and few centers, we recommend adjustment for center with either a GEE log-binomial or Poisson model with appropriate small sample corrections or a Bayesian binomial GLMM with informative priors.

Oral care with vancomycin paste for reduction in incidence of alpha-hemolytic streptococcal sepsis.

PubMed

Barker, G J; Call, S K; Gamis, A S

1995-05-01

alpha-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy. In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d. at the oncologists' discretion. A retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste. A total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without. AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06). Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09). There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients. Vancomycin resistance was not encountered. This analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance. A multicentered, placebo-controlled, double-blind study is currently planned.

Randomized comparison of deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents.

PubMed

Thuesen, Leif; Galløe, Anders; Thayssen, Per; Rasmussen, Klaus; Kelbæk, Henning; Lassen, Jens Flensted; Hansen, Peter Riis; Pedersen, Knud Erik; Ravkilde, Jan; Helquist, Steffen; Abildgaard, Ulrik; Andersen, Henning Rud; Bøtker, Hans Erik; Kristensen, Steen Dalby; Hjort, Jacob; Krusell, Lars Romer

2005-11-01

To compare deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents in a randomized multicenter trial in five Danish interventional centres. Patients with planned stenting of at least one stenotic lesion in a native coronary artery were included in the study. There were 494 (664) patients (treated lesions) in the BxSonic(R), 499 (657) in the Express(R) and 500 (658) in the Flexmaster(R) groups. The groups were well matched with regard to age, sex, diabetes, smoking, hypercholesterolemia, hypertension, indication for PCI and coronary artery lesion complexity. The study stents were implanted with or without predilatation according to ordinary -clinical practice.Rates of successful stent implantation and in-hospital stent thrombosis, re-intervention, non-fatal myocardial infarction or death. The BxSonic(R), Express(R) and Flexmaster(R) stents were successfully implanted in 92,2%, 89,3% and 91,6% of all lesions (ns). There were no in-hospital deaths and the rates of in-hospital complications were similar in the three stent groups. We found similar deliverability and in-hospital complication rates of the BxSonic(R), Express(R) and Flexmaster(R) stents.

Mexican registry of pulmonary hypertension: REMEHIP.

PubMed

Sandoval Zarate, Julio; Jerjes-Sanchez, Carlos; Ramirez-Rivera, Alicia; Zamudio, Tomas Pulido; Gutierrez-Fajardo, Pedro; Elizalde Gonzalez, Jose; Leon, Mario Seoane Garcia De; Gamez, Miguel Beltran; Abril, Francisco Moreno Hoyos; Michel, Rodolfo Parra; Aguilar, Humberto Garcia

REMEHIP is a prospective, multicentre registry on pulmonary hypertension. The main objective will be to identify the clinical profile, medical care, therapeutic trends and outcomes in adult and pediatric Mexican patients with well-characterized pulmonary hypertension. REMEHIP a multicenter registry began in 2015 with a planned recruitment time of 12 months and a 4-year follow-up. The study population will comprise a longitudinal cohort study, collecting data on patients with prevalent and incident pulmonary hypertension. Will be included patients of age >2 years and diagnosis of pulmonary hypertension by right heart catheterization within Group 1 and Group 4 of the World Health Organization classification. The structure, data collection and data analysis will be based on quality current recommendations for registries. The protocol has been approved by institutional ethics committees in all participant centers. All patients will sign an informed consent form. Currently in Mexico, there is a need of observational registries that include patients with treatment in the everyday clinical practice so the data could be validated and additional information could be obtained versus the one from the clinical trials. In this way, REMEHIP emerges as a link among randomized clinical trials developed by experts and previous Mexican experience. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST).

PubMed

Nigrovic, Peter A; Beukelman, Timothy; Tomlinson, George; Feldman, Brian M; Schanberg, Laura E; Kimura, Yukiko

2018-06-01

Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely. To describe a pragmatic, observational comparative effectiveness study that takes advantage of diversity in the management of a rare disease: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST), comparing non-biologic and biologic consensus treatment plans for new-onset systemic juvenile idiopathic arthritis within the 60-center Childhood Arthritis and Rheumatology Research Alliance Registry (CARRA). FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) is a multicenter, prospective, non-randomized study that compares four Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis: (1) glucocorticoids alone, (2) methotrexate, (3) interleukin-1 blockade, and (4) interleukin-6 blockade. Patients consenting to participation in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry are started on one of four Consensus Treatment Plans at the discretion of the treating physician. The outcome of primary interest is clinically inactive disease off glucocorticoids at 9 months, comparing non-biologic (Consensus Treatment Plans 1 + 2) versus biologic (Consensus Treatment Plans 3 + 4) strategies. Bayesian analytic methods will be employed to evaluate response rates, using propensity scoring to balance treatment groups for potential confounding. With 200 patients in a 2:1 ratio of biologic to non-biologic, there is a >90% probability of finding biologic consensus treatment plans more effective if the rate of clinically inactive disease is 30% higher than for non-biologic therapy. Additional outcomes include Patient-Reported Outcomes Measurement Information System measures and other parent-/patient-reported outcomes reported in real time using smartphone technology. Routine operation of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry will allow assessment of outcomes over at least 10 years. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) began enrollment in November 2016. The observational design may not provide balance in measured and unmeasured confounders. Use of consensus treatment plan (CTP) strategies at frequencies more unbalanced than predicted could reduce the chance of finding differences in efficacy. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) will provide the first prospective comparison of Childhood Arthritis and Rheumatology Research Alliance's (CARRA's) consensus-derived non-biologic versus biologic management strategies in systemic juvenile idiopathic arthritis, performed in a real-world setting wherein each patient receives standard-of-care treatment selected by the treating physician. Outcomes include clinician- and patient-/family-reported outcomes, empowering both physician and patient decision making in new-onset systemic juvenile idiopathic arthritis.

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

PubMed

Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

2015-11-10

A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result of the encryption, concatenated with the random number r, is the final NHash study identifier. We performed experiments using a large synthesized dataset comparing NHash with random strings, and demonstrated neglegible probability for collision. We implemented NHash for the Center for SUDEP Research (CSR), a National Institute for Neurological Disorders and Stroke-funded Center Without Walls for Collaborative Research in the Epilepsies. This multicenter collaboration involves 14 institutions across the United States and Europe, bringing together extensive and diverse expertise to understand sudden unexpected death in epilepsy patients (SUDEP). The CSR Data Repository has successfully used NHash to link deidentified multimodal clinical data collected in participating CSR institutions, meeting all desired objectives of NHash.

Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea.

PubMed

Song, Sanghyuk; Chang, Ji Hyun; Kim, Hak Jae; Kim, Yeon Sil; Kim, Jin Hee; Ahn, Yong Chan; Kim, Jae-Sung; Song, Si Yeol; Moon, Sung Ho; Cho, Moon June; Youn, Seon Min

2017-07-01

Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea. We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants' opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey. SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule. The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

A retrospective study of the impact of 21-gene recurrence score assay on treatment choice in node positive micrometastatic breast cancer.

PubMed

Frazier, Thomas G; Fox, Kevin R; Smith, J Stanley; Laronga, Christine; McSwain, Anita; Paul, Devchand; Schultz, Michael; Stilwill, Joseph; Teal, Christine; Weisberg, Tracey; Vacchino, Judith F; Sing, Amy P; Cherepanov, Dasha; Hsiao, Wendy; Chang, Eunice; Broder, Michael S

2015-03-17

To assess clinical utility of the 21-gene assay (Oncotype DX® Recurrence Score®), we determined whether women with HER2(-)/ER+ pN1mi breast cancer with low (<18) Recurrence Scores results are given adjuvant chemotherapy in a lower proportion than those with high scores (≥31). This was a multicenter chart review of ≥18 year old women with pN1mi breast cancer, HER2(-)/ER+ tumors, ductal/lobular/mixed histology, with the assay ordered on or after 1 January 2007. One hundred and eighty one patients had a mean age of 60.7 years; 82.9% had ECOG performance status 0; 33.7% had hypertension, 22.7% had osteoporosis, 18.8% had osteoarthritis, and 8.8% had type-2 diabetes. Mean Recurrence Score was 17.8 (range: 0-50). 48.6% had a mastectomy; 55.8% had a lumpectomy. 19.8% of low-risk group patients were recommended chemotherapy vs. 57.9% in the intermediate-risk group and 100% in the high-risk group (p < 0.001). A total of 80.2% of the low-risk group were recommended endocrine therapy alone, while 77.8% of the high-risk group were recommended both endocrine and chemotherapy (p < 0.001). The Oncotype DX Recurrence Score result provides actionable information that can be incorporated into treatment planning for women with HER2(-)/ER+ pN1mi breast cancer. The Recurrence Score result has clinical utility in treatment planning for HER2(-)/ER+ pN1mi breast cancer patients.

Relapse Prevention in Pediatric Patients with ADHD Treated with Atomoxetine: A Randomized, Double-Blind, Placebo-Controlled Study

ERIC Educational Resources Information Center

Michelson, David; Buitelaar, Jan K.; Danckaerts, Marina; Gillberg, Christopher; Spencer, Thomas J.; Zuddas, Alessandro; Faries, Douglas E.; Zhang, Shuyu; Biederman, Joseph

2004-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. Method: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a…

Incidence of Extrusion Following Type I Polypropylene Mesh “Kit” Repairs in the Correction of Pelvic Organ Prolapse

PubMed Central

Lukban, James C.; Beyer, Roger D.; Moore, Robert D.

2012-01-01

Introduction and Hypothesis. We sought to determine the mesh extrusion (vaginal exposure) rates and subject outcomes following IntePro (Type I polypropylene) mesh “kit” repairs for vaginal prolapse. Methods. Data were pooled from two prospective multicenter studies evaluating the safety and efficacy of the Perigee and Apogee (American Medical Systems, Minnetonka, Minn, USA) to treat anterior and posterior/apical prolapses, respectively. Extrusions involving the anterior compartment (AC) or posterior compartment/apex (PC/A) were recorded. Results. Two hundred sixty women underwent mesh placement, with a total of 368 mesh units inserted (173 in the AC and 195 in the PC/A). Extrusions were noted in 13 (7.5%) of AC implants and 27 (13.8%) of PC/A implants through 12 months. No difference was seen between those with and without extrusion in regard to anatomic cure, postoperative painor quality of life at 1 year. Conclusions. Extrusion had no apparent effect on short-term outcomes. Given the unknown long-term sequellae of vaginal mesh exposure, a thorough assessment of risks and benefits of transvaginal mesh placement should be considered at the time of preoperative planning. PMID:22190952

Impact of the National Institutes of Health Focal Segmental Glomerulosclerosis (NIH FSGS) clinical trial on the treatment of steroid-resistant FSGS.

PubMed

Canetta, Pietro A; Radhakrishnan, Jai

2013-03-01

Idiopathic focal segmental glomerulosclerosis (FSGS) is among the most common, morbid and treatment-resistant conditions faced by nephrologists. While glucocorticoids have traditionally been the mainstay of initial treatment, they induce remission in only a minority of patients. A variety of other immunosuppressants have been utilized against steroid-resistant FSGS, but few have been rigorously examined in well-controlled trials. Recently, the results were published from a National Institutes of Health (NIH)-sponsored multicenter randomized trial comparing cyclosporine (CSA) with a combination of mycophenolate mofetil (MMF) and pulse dexamethasone (DEX) for the treatment of steroid-resistant FSGS. No difference in treatment effectiveness was shown between the two groups, and adverse effects were comparable. This was the largest randomized trial ever undertaken in FSGS, but it was unfortunately underpowered to show clinically relevant differences in response rates. This shortcoming, along with particularities of the study population and outcome measures, makes it challenging to draw definitive conclusions from the trial results. Despite these limitations, the trial does provide valuable insights into treatment strategies for FSGS and offers important lessons for planning future research.

Quality control for quantitative multicenter whole-body PET/MR studies: A NEMA image quality phantom study with three current PET/MR systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boellaard, Ronald, E-mail: r.boellaard@vumc.nl; European Association of Nuclear Medicine Research Ltd., Vienna 1060; European Association of Nuclear Medicine Physics Committee, Vienna 1060

2015-10-15

Purpose: Integrated positron emission tomography/magnetic resonance (PET/MR) systems derive the PET attenuation correction (AC) from dedicated MR sequences. While MR-AC performs reasonably well in clinical patient imaging, it may fail for phantom-based quality control (QC). The authors assess the applicability of different protocols for PET QC in multicenter PET/MR imaging. Methods: The National Electrical Manufacturers Association NU 2 2007 image quality phantom was imaged on three combined PET/MR systems: a Philips Ingenuity TF PET/MR, a Siemens Biograph mMR, and a GE SIGNA PET/MR (prototype) system. The phantom was filled according to the EANM FDG-PET/CT guideline 1.0 and scanned for 5more » min over 1 bed. Two MR-AC imaging protocols were tested: standard clinical procedures and a dedicated protocol for phantom tests. Depending on the system, the dedicated phantom protocol employs a two-class (water and air) segmentation of the MR data or a CT-based template. Differences in attenuation- and SUV recovery coefficients (RC) are reported. PET/CT-based simulations were performed to simulate the various artifacts seen in the AC maps (μ-map) and their impact on the accuracy of phantom-based QC. Results: Clinical MR-AC protocols caused substantial errors and artifacts in the AC maps, resulting in underestimations of the reconstructed PET activity of up to 27%, depending on the PET/MR system. Using dedicated phantom MR-AC protocols, PET bias was reduced to −8%. Mean and max SUV RC met EARL multicenter PET performance specifications for most contrast objects, but only when using the dedicated phantom protocol. Simulations confirmed the bias in experimental data to be caused by incorrect AC maps resulting from the use of clinical MR-AC protocols. Conclusions: Phantom-based quality control of PET/MR systems in a multicenter, multivendor setting may be performed with sufficient accuracy, but only when dedicated phantom acquisition and processing protocols are used for attenuation correction.« less

Design Features of the Diabetes and Periodontal Therapy Trial (DPTT): A Multicenter Randomized Single-Masked Clinical Trial Testing the Effect of Non-surgical Periodontal Therapy on Glycosylated Hemoglobin (HbA1c) Levels in Subjects with Type 2 Diabetes and Chronic Periodontitis

PubMed Central

2013-01-01

Background Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. Purpose The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. Methods DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. Conclusion Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other. PMID:24080100

Candidacy for Bilateral Hearing Aids: A Retrospective Multicenter Study

ERIC Educational Resources Information Center

Boymans, Monique; Goverts, S. Theo; Kramer, Sophia E.; Festen, Joost M.; Dreschler, Wouter A.

2009-01-01

Purpose: The goal of this study was to find factors for refining candidacy criteria for bilateral hearing aid fittings. Clinical files of 1,000 consecutive hearing aid fittings were analyzed. Method: Case history, audiometric, and rehabilitation data were collected from clinical files, and an extensive questionnaire on long-term outcome measures…

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

Dialectical Effects on Nasalance: A Multicenter, Cross-Continental Study

ERIC Educational Resources Information Center

Awan, Shaheen N.; Bressmann, Tim; Poburka, Bruce; Roy, Nelson; Sharp, Helen; Watts, Christopher

2015-01-01

Purpose: This study investigated nasalance in speakers from six different dialectal regions across North America using recent versions of the Nasometer. It was hypothesized that many of the sound changes observed in regional dialects of North American English would have a significant impact on measures of nasalance. Method: Samples of the Zoo…

Bronchopulmonary infection-colonization patterns in Spanish cystic fibrosis patients: Results from a national multicenter study.

PubMed

de Dios Caballero, Juan; Del Campo, Rosa; Royuela, Ana; Solé, Amparo; Máiz, Luis; Olveira, Casilda; Quintana-Gallego, Esther; de Gracia, Javier; Cobo, Marta; de la Pedrosa, Elia Gómez G; Oliver, Antonio; Cantón, Rafael

2016-05-01

Clinical and demographical knowledge on Spanish cystic fibrosis (CF) patients is incomplete as no national registry exists. CF-microbiology has not been studied at national level. The results of the first Spanish multicenter study on CF microbiology are presented. 24 CF-Units for adult (n=12) and pediatric (n=12) patients from 17 hospitals provided sputa and clinical data from 15 consecutive patients. Cultures and susceptibility testing were performed. Colonization impact on pulmonary function was assessed. 341 patients [mean (SD) age 21 (11) years, 180≥18years, mean (SD) FEV1=68 (25)%] were included. Pseudomonas aeruginosa was reported as chronic, intermittent or absent in 46%, 22% and 32% of patients, respectively. The annual prevalence was 62%. Positive P. aeruginosa and methicillin-resistant Staphylococcus aureus cultures were significantly associated with lower FEV1 (p<0.001 and p=0.003, respectively). The representative subset of the Spanish CF-population which has been clinically, demographically and microbiologically characterized will serve as a reference for future CF studies in Spain. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Evaluation of a Teleform-based data collection system: a multi-center obesity research case study.

PubMed

Jenkins, Todd M; Wilson Boyce, Tawny; Akers, Rachel; Andringa, Jennifer; Liu, Yanhong; Miller, Rosemary; Powers, Carolyn; Ralph Buncher, C

2014-06-01

Utilizing electronic data capture (EDC) systems in data collection and management allows automated validation programs to preemptively identify and correct data errors. For our multi-center, prospective study we chose to use TeleForm, a paper-based data capture software that uses recognition technology to create case report forms (CRFs) with similar functionality to EDC, including custom scripts to identify entry errors. We quantified the accuracy of the optimized system through a data audit of CRFs and the study database, examining selected critical variables for all subjects in the study, as well as an audit of all variables for 25 randomly selected subjects. Overall we found 6.7 errors per 10,000 fields, with similar estimates for critical (6.9/10,000) and non-critical (6.5/10,000) variables-values that fall below the acceptable quality threshold of 50 errors per 10,000 established by the Society for Clinical Data Management. However, error rates were found to widely vary by type of data field, with the highest rate observed with open text fields. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coffin-Lowry syndrome: a multicenter study.

PubMed

Gilgenkrantz, S; Mujica, P; Gruet, P; Tridon, P; Schweitzer, F; Nivelon-Chevallier, A; Nivelon, J L; Couillault, G; David, A; Verloes, A

1988-10-01

The Coffin-Lowry syndrome is an inherited syndrome of mental retardation, characteristic facies and skeletal anomalies. The occurrence of severe manifestations in males, with no instance of male-to-male transmission, suggests an X-linked inheritance. The paper describes seven families from five European Centers.

Preoperative computer simulation for planning of vascular access surgery in hemodialysis patients.

PubMed

Zonnebeld, Niek; Huberts, Wouter; van Loon, Magda M; Delhaas, Tammo; Tordoir, Jan H M

2017-03-06

The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients. Unfortunately, 20-40% of all constructed AVFs fail to mature (FTM), and are therefore not usable for hemodialysis. AVF maturation importantly depends on postoperative blood volume flow. Predicting patient-specific immediate postoperative flow could therefore support surgical planning. A computational model predicting blood volume flow is available, but the effect of blood flow predictions on the clinical endpoint of maturation (at least 500 mL/min blood volume flow, diameter of the venous cannulation segment ≥4 mm) remains undetermined. A multicenter randomized clinical trial will be conducted in which 372 patients will be randomized (1:1 allocation ratio) between conventional healthcare and computational model-aided decision making. All patients are extensively examined using duplex ultrasonography (DUS) during preoperative assessment (12 venous and 11 arterial diameter measurements; 3 arterial volume flow measurements). The computational model will predict patient-specific immediate postoperative blood volume flows based on this DUS examination. Using these predictions, the preferred AVF configuration is recommended for the individual patient (radiocephalic, brachiocephalic, or brachiobasilic). The primary endpoint is FTM rate at six weeks in both groups, secondary endpoints include AVF functionality and patency rates at 6 and 12 months postoperatively. ClinicalTrials.gov (NCT02453412), and ToetsingOnline.nl (NL51610.068.14).

Multicenter Clinical Trial of the Nucleus® Hybrid™ S8 Cochlear Implant: Final Outcomes

PubMed Central

Gantz, Bruce J; Dunn, Camille; Oleson, Jacob; Hansen, Marlan; Parkinson, Aaron; Turner, Christopher

2015-01-01

Objective The concept expanding electrical speech processing to those with more residual acoustic hearing with a less invasive shorter cochlear implant has been ongoing since 1999. A multi-center study of the Nucleus Hybrid S8 CI took place between 2002–11. This report describes the final outcomes of this clinical trial. Study Design Multi-Center longitudinal single subject design Methods Eighty-seven subjects received a Nucleus® Hybrid™ S8 implant in their poorer ear. Speech perception in quiet (CNC words) and in noise (BKB-SIN) was collected pre- and post-operatively at 3, 6, and 12 months. Subjective questionnaire data using the APHAB was also collected. Results Some level of hearing preservation was accomplished in 98% subjects with 90% maintaining a functional low-frequency pure-tone average (LFPTA) at initial activation. By 12 months, 5 subjects had total hearing loss and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the Hybrid and Combined conditions. The majority of had improvements with BKB-SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the 4 subscales of the APHAB. Conclusion The concept of hybrid speech processing has significant advantages for subjects with residual low-frequency hearing. In this study, the Nucleus® Hybrid™ S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device. Level of evidence 2c PMID:26756395

Aortic valve sclerosis as a marker of coronary artery atherosclerosis; a multicenter study of a large population with a low prevalence of coronary artery disease.

PubMed

Rossi, Andrea; Gaibazzi, Nicola; Dandale, Raje; Agricola, Eustachio; Moreo, Antonella; Berlinghieri, Nicola; Sartorio, Daniele; Loffi, Marco; De Chiara, Benedetta; Rigo, Fausto; Vassanelli, Corrado; Faggiano, Pompilio

2014-03-15

There are no studies analyzing the association between aortic valve sclerosis (AVS) and coronary artery disease (CAD) in a large and multicenter patient population with an overall low prevalence of CAD. We hypothesized that AVS could predict the presence and degree of CAD in patients with severe organic mitral regurgitation. We retrospectively analyzed consecutive patients with flail mitral leaflet who had coronary angiography for pre-surgical screening and not because suspect of CAD. End-points were considered: 1) any degree of CAD (stenosis>20%) and 2) obstructive CAD (stenosis>75% of at least one coronary artery). AVS was defined as focal areas of increased echogenicity and thickening of the leaflets. Traditional clinical risk factors were considered: age, male gender, hypertension (>140/90 mmHg or medical therapy), hypercholesterolemia (total cholesterol>200 mg/dl or statin), diabetes, family history of CAD and smoking habit. 675 patients (mean age: 64±12; 27% female) formed the study population. Among patients with AVS, 60% and 39% had any-CAD and ob-CAD respectively, on the opposite among patients without AVS 12% and 7% had any-CAD and ob-cad. After adjustment for clinical risk factors, AVS was associated with a 22.7 fold increased risk of any degree of CAD (95% CI 8.1 63.6 p<0.0001) and with a 21.8 fold increased risk of obstructive-CAD (95% CI 6.6 71.9; p<0.0001). In a large and multicenter sample of patient with flail mitral leaflet, AVS was strongly associated with the presence and degree of CAD independently of clinical risk factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland.

PubMed

Simon, Arne; Ammann, Roland A; Bode, Udo; Fleischhack, Gudrun; Wenchel, Hans-Martin; Schwamborn, Dorothee; Gravou, Chara; Schlegel, Paul-Gerhardt; Rutkowski, Stefan; Dannenberg, Claudia; Körholz, Dieter; Laws, Hans Jürgen; Kramer, Michael H

2008-05-23

Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic. Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods. 7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis. Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

The Adult Respiratory Distress Syndrome Cognitive Outcomes Study

PubMed Central

Christie, Jason D.; Lanken, Paul N.; Biester, Rosette C.; Thompson, B. Taylor; Bellamy, Scarlett L.; Localio, A. Russell; Demissie, Ejigayehu; Hopkins, Ramona O.; Angus, Derek C.

2012-01-01

Rationale: Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking. Objectives: To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment. Methods: As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post–hospital discharge. Measurements and Main Results: Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02). Conclusions: Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation. PMID:22492988

Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

PubMed Central

López Furst, María José; de Vedia, Lautaro; Fernández, Silvina; Gardella, Noella; Ganaha, María Cristina; Prieto, Sergio; Carbone, Edith; Lista, Nicolás; Rotryng, Flavio; Morera, Graciana I.; Mollerach, Marta; Stryjewski, Martín E.

2013-01-01

Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Materials and Methods Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina. PMID:24324543

Utility of an Abbreviated Dizziness Questionnaire to Differentiate Between Causes of Vertigo and Guide Appropriate Referral: A Multicenter Prospective Blinded Study.

PubMed

Roland, Lauren T; Kallogjeri, Dorina; Sinks, Belinda C; Rauch, Steven D; Shepard, Neil T; White, Judith A; Goebel, Joel A

2015-12-01

Test performance of a focused dizziness questionnaire's ability to discriminate between peripheral and nonperipheral causes of vertigo. Prospective multicenter. Four academic centers with experienced balance specialists. New dizzy patients. A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and nonperipheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. In total, 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and nonperipheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central, and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central, and other causes was considered good as measured by c-indices of 0.75, 0.7, and 0.78, respectively. This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from nonperipheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

PubMed

Jans, Goele; Matthys, Christophe; Bel, Sarah; Ameye, Lieveke; Lannoo, Matthias; Van der Schueren, Bart; Dillemans, Bruno; Lemmens, Luc; Saey, Jean-Pierre; van Nieuwenhove, Yves; Grandjean, Pascale; De Becker, Ben; Logghe, Hilde; Coppens, Marc; Roelens, Kristien; Loccufier, Anne; Verhaeghe, Johan; Devlieger, Roland

2016-07-29

The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. Retrospectively registered (July 2015 - NCT02515214 ).

Low intensity vs. self-guided Internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study

PubMed Central

2013-01-01

Background Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. Methods The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. Discussion The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. Trial registration Clinical Trials NCT01611818 PMID:23312003

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

PubMed

DeVille, J Brian; Svinarich, J Thomas; Dan, Dan; Wickliffe, Andrew; Kantipudi, Charan; Lim, Hae W; Plummer, Lisa; Baker, James; Kowalski, Marcin; Baydoun, Hassan; Jenkins, Mark; Chang-Sing, Peter

2014-06-01

Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

Comparative effectiveness and cost-effectiveness of Chuna manual therapy versus conventional usual care for nonacute low back pain: study protocol for a pilot multicenter, pragmatic randomized controlled trial (pCRN study).

PubMed

Shin, Byung-Cheul; Kim, Me-Riong; Cho, Jae-Heung; Jung, Jae-Young; Kim, Koh-Woon; Lee, Jun-Hwan; Nam, Kibong; Lee, Min Ho; Hwang, Eui-Hyoung; Heo, Kwang-Ho; Kim, Namkwen; Ha, In-Hyuk

2017-01-17

While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce. This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment. This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial. Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016.

Assessing the Knowledge, Attitudes and Behaviors of Human and Animal Health Students towards Antibiotic Use and Resistance: A Pilot Cross-Sectional Study in the UK

PubMed Central

Hills, Holly; Seitz, Lara-Turiya; Perry, Alex

2018-01-01

The Global Action Plan on Antimicrobial Resistance highlights the importance of training all healthcare professionals. No study has assessed patterns of students’ knowledge, attitudes and practices concerning antibiotic use simultaneously across different healthcare course types. We conducted a cross-sectional multi-center survey among UK students. The survey was advertised through local survey coordinators at 25 universities. The online survey was accessible from 10th October to 17th November 2016 (before European Antibiotic Awareness Day). A total of 255 students from 25 universities participated, including students on medicine, pharmacy, nursing, physician associate, dentistry and veterinary medicine courses. Antibiotic resistance was considered to be a more important global challenge than climate change, obesity or food security (p < 0.001). Most students (95%) believed that antibiotic resistance will be a problem for their future practice, but fewer (69%) thought that the antibiotics they will prescribe, administer or dispense will contribute to the problem. A fifth of students felt they had sufficient knowledge of antibiotic use for their future work. Our exploratory study suggests that UK human and animal healthcare students are aware of the importance of antibiotic resistance, but many still have certain misconceptions. Campaigns and improved educational efforts applying behavioral insights methodology could address these. PMID:29385687

Toward a conditional approach to anonymity? An explorative multicenter longitudinal study among anonymous living kidney donors and recipients.

PubMed

Pronk, Mathilde C; Slaats, Dorthe; van der Pant, Karlijn A M I; Vervelde, Janneke; Dooper, Ine M; Dor, Frank J M F; Weimar, Willem; van de Wetering, Jacqueline; Zuidema, Willij C; Massey, Emma K

2017-12-01

Anonymity between living donors and recipients is a topic of discussion among transplant professionals. This longitudinal study explored living kidney donors' and patients' perspectives on anonymity. Prior to surgery (T0) and 3 months afterward (T1), participants in unspecified or specified indirect donation programs completed a questionnaire on their experiences with and attitudes toward anonymity as well as demographic and medical characteristics. Nonparametric tests were used to assess group differences and associations. Participants were content with anonymity at T0 and T1. Fourteen and 23% wanted to meet at T0 and T1, respectively. If the other party expressed the wish to meet, 50% (T0) and 55% (T1) would be willing to meet. Most participants agreed that meeting should be allowed if both parties agree. Attitude toward anonymity did not differ between donors/recipients, nor between T0/T1 and unspecified/specified indirect donation programs. This study showed that most donors and recipients who participated in anonymous donation schemes are in favor of a conditional approach to anonymity. Guidelines on how to revoke anonymity if both parties agree are needed and should include education about pros and cons of (non-) anonymity and a logistical plan on how, when, where, and by whom anonymity should be revoked. © 2017 Steunstichting ESOT.

Solution of multi-center molecular integrals of Slater-type orbitals

NASA Technical Reports Server (NTRS)

Tai, H.

1989-01-01

The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

A statistical analysis plan for the efficiency and safety of Chinese herbal medicine used concurrently with topical therapy for psoriasis vulgaris.

PubMed

Lu, Liming; Xuan, Meiling; Yan, Yuhong; Li, Geng; Zhou, Li; Wen, Zehuai; Lu, Chuanjian

2016-10-03

Psoriasis vulgaris (PV) has been causing increasing concern due to its highly prevalent, harmful and therapy-resistant characteristics. The YXBCM01 (Chinese herbal medicine) for PV trial evaluates the effects of YXBCM01 on relapse rate in patients suffering from PV. As an update to the published design and method for the trial, this paper presents the statistical plan for the main publication to avoid the risk of outcome reporting bias, selective reporting, and data-driven results. This trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 600 PV patients (300 in each group) will be randomized to one of two arms: participants in the experimental group will receive the YXBCM01 granule 5.5 g twice daily for 12 weeks. Placebo granules are given to patients in the control group at a dose of 5.5 g twice daily for 12 weeks. The sequential topical therapy is administrated simultaneously to all eligible patients by using calcipotriol betamethasone ointment once daily (a treatment area of up to 30 % body surface area (BSA), fingertip unit is recommended) in the first 4 weeks (maximum of 100 g weekly), followed by calcipotriol betamethasone ointment once daily for the remaining 8 weeks (maximum of 100 g weekly). The primary outcome measure is relapse rate in the treatment period and follow-up period. The secondary outcome measures include time to relapse, time to onset, rebound rate, cumulative consumption of topical medicine, visual analog scale (VAS), BSA, the Dermatology Life Quality Index (DLQI) and the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36). Application of this statistical analysis plan to the YXBCM01 for PV trial will facilitate unbiased evaluation of these important clinical data. This study will provide evidence regarding the value of YXBCM01 as an intervention for PV patients. Chinese Clinical Trial Registry: ChiCTR-TRC-13003233 , registered on 26 May 2013.

Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

PubMed Central

Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

2015-01-01

Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

["Notebook computer" in combination with WWW-technology in multicenter clinical trials and for chronic patient care].

PubMed

Koop, A; Gatermann, C; Mösges, R

2000-01-01

Our purpose was to determine conditions, under which the use of hand-held computers in the diagnosis and therapy of patients with chronic diseases seems to be handy. Two scenarios are presented showing the employment of these computers in a doctor's office and in multicenter clinical trials. Security-related aspects involved in transferring medical data via the internet are discussed.

Acute necrotizing pancreatitis: a multicenter study.

PubMed

Fernández-Cruz, L; Navarro, S; Valderrama, R; Sáenz, A; Guarner, L; Aparisi, L; Espi, A; Jaurietta, E; Marruecos, L; Gener, J

1994-04-01

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.

PubMed

Weil, E H; Eerdmans, P H; Dijkman, G A; Tamussino, K; Feyereisl, J; Vierhout, M E; Schmidbauer, C; Egarter, C; Kölle, D; Plasman, J E; Heidler, H; Abbühl, B E; Wein, W

1998-01-01

Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.

A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms.

PubMed

Van Leusden, H A; Albertyn, G; Verlaine, C; Van Ruymbeke, J

1993-01-01

Comparison of the effects of treatment of two transdermal therapeutic systems for estrogen replacement therapy with regard to efficacy, tolerability, and acceptance. Open randomized. Multicenter. A study population of 104 postmenopausal women was randomized on a 1:1 basis to treatment with one of two estradiol patches, System (Cilag) and Estraderm (Ciba-Geigy). Systolic and diastolic BP, hot flushes, night sweating, fatigue, insomnia, depression, nervousness, headache, vaginal discomfort (efficacy variables); bleeding, dermatological symptoms, comfort and adhesiveness of patch, and other possible causes of discontinuation (tolerability); general evaluation by patient (acceptance). Considering all efficacy variables, 53% of Systen and 46% of Estraderm patients found the therapy satisfactory. Tolerability was somewhat higher in the Systen group. Adhesiveness of the patch was significantly better for Systen. Overall, 79% of Systen patients and 62% of Estraderm patients evaluated treatment as "good" or "very good." The majority of patients in both groups found the patch very comfortable or only slightly obtrusive.

Multicenter Study of Prevalence of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis in France ▿

PubMed Central

Roux, Anne-Laure; Catherinot, Emilie; Ripoll, Fabienne; Soismier, Nathalie; Macheras, Edouard; Ravilly, Sophie; Bellis, Gil; Vibet, Marie-Anne; Le Roux, Evelyne; Lemonnier, Lydie; Gutierrez, Cristina; Vincent, Véronique; Fauroux, Brigitte; Rottman, Martin; Guillemot, Didier; Gaillard, Jean-Louis

2009-01-01

We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The “new” species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%). PMID:19846643

Management of venous thromboembolism in patients with acute leukemia at high bleeding risk: a multi-center study.

PubMed

Napolitano, Mariasanta; Valore, Luca; Malato, Alessandra; Saccullo, Giorgia; Vetro, Calogero; Mitra, Maria Enza; Fabbiano, Francesco; Mannina, Donato; Casuccio, Alessandra; Lucchesi, Alessandro; Del Principe, Maria Ilaria; Candoni, Anna; Di Raimondo, Francesco; Siragusa, Sergio

2016-01-01

In the last decades, evaluation of clinically relevant thrombotic complications in patients with acute leukemia (AL) has been poorly investigated. The authors performed a multi-center study to evaluate the management of symptomatic venous thromboembolism (VTE) in adult patients with AL. The intention was to find as clinically relevant the following: symptomatic Venous Thrombosis (VT) occurred in typical (lower limbs) and atypical (cerebral, upper limbs, abdominal, etc) sites with or without pulmonary embolism (PE). Over a population of 1461 patients with AL, 22 cases of symptomatic VTE were recorded in hospitalized patients with a mean age of 54.6 years. The absolute incidence of VTE was 1.5%. VTE occurred during chemotherapy in 17/22 (77.2%) cases, mainly (14/17, 82.3%) during the induction phase. Treatment of acute VTE was based on Low Molecular Weight Heparin (LMWH) at full dosage for the first month from diagnosis and reduced dosage (75%) for the following months.

Chymodiactin in patients with herniated lumbar intervertebral disc(s). An open-label, multicenter study.

PubMed

McDermott, D J; Agre, K; Brim, M; Demma, F J; Nelson, J; Wilson, R R; Thisted, R A

1985-04-01

To extent the safety information for Chymodiactin (chymopapain for injection), 37 neurologic and orthopedic surgeons conducted an open-label, multicenter, phase 3 clinical study. A total of 1,498 patients with one or two herniated lumbar intervertebral discs were enrolled. Therapeutic results were generally favorable, with the percentages of patients achieving either excellent or good (or successful) results ranging from 79.6% to 88.9%, depending on criteria employed in the tabulation. There were 13 cases of anaphylaxis, and 2 of these patients died of complications of anaphylaxis. Two additional patients experienced serious neurologic problems. The first of these two patients developed transverse myelitis and paraplegia approximately 3 weeks following chemonucleolysis. Transdural discograms at three levels had been done approximately 2 days prior to chemonucleolysis, in violation of the protocol. The second patient developed acute cauda equina syndrome, and, despite emergency laminectomy, had permanent neurologic sequelae. Back spasm and stiffness/soreness were the most frequently encountered adverse experiences.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

PubMed

Kor, Daryl J; Erlich, Jason; Gong, Michelle N; Malinchoc, Michael; Carter, Rickey E; Gajic, Ognjen; Talmor, Daniel S

2011-11-01

To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. This is a secondary analysis of a prospective multicenter international cohort investigation. Multicenter observational study including 20 US hospitals and two hospitals in Turkey. Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. None. Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

PubMed Central

Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

2017-01-01

Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

Dosimetric characterization of small fields using a plastic scintillator detector: A large multicenter study.

PubMed

Mancosu, Pietro; Pasquino, Massimo; Reggiori, Giacomo; Masi, Laura; Russo, Serenella; Stasi, Michele

2017-09-01

In modern radiation therapy accurate small fields dosimetry is a challenge and its standardization is fundamental to harmonize delivered dose in different institutions. This study presents a multicenter characterization of MLC-defined small field for Elekta and Varian linear accelerators. Measurements were performed using the Exradin W1 plastic scintillator detector. The project enrolled 24 Italian centers. Each center performed Tissue Phantom Ratio (TPR), in-plane and cross-plane dose profiles of 0.8×0.8cm 2 field, and Output Factor (OF) measurements for square field sizes ranging from 0.8 to 10cm. Set-up conditions were 10cm depth in water phantom at SSD 90cm. Measurements were performed using two twin Exradin W1 plastic scintillator detectors (PSD) correcting for the Cerenkov effect as proposed by the manufacturer. Data analysis from 12 Varian and 12 Elekta centers was performed. Measurements of 7 centers were not included due to cable problems. TPR measurements showed standard deviations (SD)<1%; SD<0.4mm for the profile penumbra was obtained, while FWHM measurements showed SD<0.5mm. OF measurements showed SD<1.5% for field size greater than 2×2cm 2 . Median OFs values were in agreement with the recent bibliography. High degree of consistency was registered for all the considered parameters. This work confirmed the importance of multicenter dosimetric intercomparison. W1 PSD could be considered as a good candidate for small field measurements. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): rationale and study design of the randomized TWENTE III multicenter trial.

PubMed

Lam, Ming Kai; Sen, Hanim; Tandjung, Kenneth; van Houwelingen, K Gert; de Vries, Arie G; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Löwik, Marije M; Linssen, Gerard C M; Ijzerman, Maarten J; van der Palen, Job; Doggen, Carine J M; von Birgelen, Clemens

2014-04-01

To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Personality Disorder Patients' Perspectives on the Introduction of Imagery within Schema Therapy: A Qualitative Study of Patients' Experiences

ERIC Educational Resources Information Center

ten Napel-Schutz, Marieke C.; Abma, Tineke A.; Bamelis, Lotte; Arntz, Arnoud

2011-01-01

A qualitative study was done on patients' perspectives on the first phases of imagery work in the context of schema therapy (ST) for personality disorders. Patients participated in a multi-center randomized controlled study of the effectiveness of ST. Patients' experiences and opinions were collected with semistructured in-depth interviews at the…

Severe postpartum hemorrhage from uterine atony: a multicentric study.

PubMed

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths.

Information on center characteristics as costs' determinants in multicenter clinical trials: is modeling center effect worth the effort?

PubMed

Petrinco, Michele; Pagano, Eva; Desideri, Alessandro; Bigi, Riccardo; Ghidina, Marco; Ferrando, Alberto; Cortigiani, Lauro; Merletti, Franco; Gregori, Dario

2009-01-01

Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

Multicentered black holes with a negative cosmological constant

NASA Astrophysics Data System (ADS)

Chimento, Samuele; Klemm, Dietmar

2014-01-01

We present a recipe that allows us to construct multicentered black holes embedded in an arbitrary Friedmann-Lemaître-Robertson-Walker (FLRW) universe. These solutions are completely determined by a function satisfying the conformal Laplace equation on the spatial slices E3, S3, or H3. Since anti-de Sitter (AdS) space can be written in FLRW coordinates, this includes as a special case multicentered black holes in AdS, in the sense that, far away from the black holes, the energy density and the pressure approach the values given by a negative cosmological constant. We study in some detail the physical properties of the single-centered asymptotically AdS case, which does not coincide with the usual Reissner-Nordström-AdS black hole, but is highly dynamical. In particular, we determine the curvature singularities and trapping horizons of this solution, compute the surface gravity of the trapping horizons, and show that the generalized first law of black hole dynamics proposed by Hayward holds in this case. It turns out that the spurious big bang/big crunch singularities that appear when one writes AdS in FLRW form become real in the presence of these dynamical black holes. This implies that actually only one point of the usual conformal boundary of AdS survives in the solutions that we construct. Finally, a generalization to arbitrary dimension is also presented.

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

PubMed Central

Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

2017-01-01

Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration ClinicalTrials.gov NCT01310738 PMID:28662034

Effects of a novel method for enteral nutrition infusion involving a viscosity-regulating pectin solution: A multicenter randomized controlled trial.

PubMed

Tabei, Isao; Tsuchida, Shigeru; Akashi, Tetsuro; Ookubo, Katsuichiro; Hosoda, Satoru; Furukawa, Yoshiyuki; Tanabe, Yoshiaki; Tamura, Yoshiko

2018-02-01

The initial complications associated with infusion of enteral nutrition (EN) for clinical and nutritional care are vomiting, aspiration pneumonia, and diarrhea. There are many recommendations to prevent these complications. A novel method involving a viscosity-regulating pectin solution has been demonstrated. In Japan, this method along with the other so-called "semi-solid EN" approaches has been widely used in practice. However, there has been no randomized clinical trial to prove the efficiency and safety of a viscosity-regulating pectin solution in EN management. Therefore, we planned and initiated a multicenter randomized controlled trial to determine the efficiency and safety. This study included 34 patients from 7 medical institutions who participated. Institutional review board (IRB) approval was obtained from all participating institutions. Patients who required EN management were enrolled and randomly assigned to the viscosity regulation of enteral feeding (VREF) group and control group. The VREF group (n = 15) was managed with the addition of a viscosity-regulating pectin solution. The control group (n = 12) was managed with conventional EN administration, usually in a gradual step-up method. Daily clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation frequency; and stool form were observed in the 2 week trial period. The dose of EN and duration of infusion were also examined. A favorable trend for clinical symptoms was noticed in the VREF group. No significant differences were observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2 groups. An apparent reduction in infusion duration and hardening of stool form were noted in the VREF group. The novel method involving a viscosity-regulating pectin solution with EN administration can be clinically performed safely and efficiently, similar to the conventional method. Moreover, there were benefits, such as improvement in stool form, a short time for EN infusion, and a reduction in vomiting episodes, with the use of the novel method. This indicates some potential advantages in the quality of life among patients receiving this novel method. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

PubMed

Filippi, Luca; Cavallaro, Giacomo; Berti, Elettra; Padrini, Letizia; Araimo, Gabriella; Regiroli, Giulia; Bozzetti, Valentina; De Angelis, Chiara; Tagliabue, Paolo; Tomasini, Barbara; Buonocore, Giuseppe; Agosti, Massimo; Bossi, Angela; Chirico, Gaetano; Aversa, Salvatore; Pasqualetti, Roberta; Fortunato, Pina; Osnaghi, Silvia; Cavallotti, Barbara; Vanni, Maurizio; Borsari, Giulia; Donati, Simone; Nascimbeni, Giuseppe; la Marca, Giancarlo; Forni, Giulia; Milani, Silvano; Cortinovis, Ivan; Bagnoli, Paola; Dal Monte, Massimo; Calvani, Anna Maria; Pugi, Alessandra; Villamor, Eduardo; Donzelli, Gianpaolo; Mosca, Fabio

2017-07-14

Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

A Review of the Epidemiological Methods Used to Investigate the Health Impacts of Air Pollution around Major Industrial Areas

PubMed Central

Pascal, Laurence; Bidondo, Marie-Laure; Cochet, Amandine; Sarter, Hélène; Stempfelet, Morgane; Wagner, Vérène

2013-01-01

We performed a literature review to investigate how epidemiological studies have been used to assess the health consequences of living in the vicinity of industries. 77 papers on the chronic effects of air pollution around major industrial areas were reviewed. Major health themes were cancers (27 studies), morbidity (25 studies), mortality (7 studies), and birth outcome (7 studies). Only 3 studies investigated mental health. While studies were available from many different countries, a majority of papers came from the United Kingdom, Italy, and Spain. Several studies were motivated by concerns from the population or by previous observations of an overincidence of cases. Geographical ecological designs were largely used for studying cancer and mortality, including statistical designs to quantify a relationship between health indicators and exposure. Morbidity was frequently investigated through cross-sectional surveys on the respiratory health of children. Few multicenter studies were performed. In a majority of papers, exposed areas were defined based on the distance to the industry and were located from <2 km to >20 km from the plants. Improving the exposure assessment would be an asset to future studies. Criteria to include industries in multicenter studies should be defined. PMID:23818910

The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth

ERIC Educational Resources Information Center

Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Liu, Jing; Lester, Barry M.

2007-01-01

Objective: Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development,…

Arthritis, Rheumatism and Aging Medical Information System Post-Marketing Surveillance Program.

PubMed

Singh, G

2001-05-01

The Arthritis, Rheumatism, and Aging Post-Marketing Surveillance Program (ARAMIS-PMS) is a collection of multicenter, prospective, noninterventional, observational longitudinal studies of patients with rheumatic diseases. The ARAMIS-PMS program aims to study patients in normal clinical setting to evaluate the real-life effectiveness, toxicity, and cost effectiveness of various medications used to treat rheumatic diseases.

A multicenter cohort study of spinal osteoid osteomas: results of surgical treatment and analysis of local recurrence.

PubMed

Quraishi, Nasir A; Boriani, Stefano; Sabou, Silviu; Varga, Peter P; Luzzati, Alessandro; Gokaslan, Ziya L; Fehlings, Michael G; Fisher, Charles G; Dekutoski, Mark B; Rhines, Laurence D; Reynolds, Jeremy J; Germscheid, Niccole M; Bettegowda, Chetan; Williams, Richard P

2017-03-01

Spinal osteoid osteomas are benign primary tumors arising predominantly from the posterior column of the spine. These "osteoblastic" lesions have traditionally been treated with intralesional excision. The purpose of the present study was to review the treatment and local recurrence rates for symptomatic spinal osteoid osteomas. Multicenter ambispective cross-sectional observational cohort study. During the study period, a total of 84 patients (65 males, 19 females) were diagnosed with a spinal osteoid osteoma and received surgical treatment. The mean age at surgery was 21.8 ± 9.0 years (range: 6.7-52.4 years) and the mean follow-up was 2.7 years (13 days-14.5 years). Local recurrence, perioperative morbidity, and cross-sectional survival. Using the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated osteoid osteoma cases were identified. Patient demographic, clinical and diagnostic, treatment, local recurrence, perioperative morbidity, and cross-sectional survival data were collected and retrieved. Descriptive statistics were summarized using mean/standard deviation or frequency/percentage. In our study, most of the tumors were localized in the mobile spine (81 of 84 [96%]); all patients reported pain as a symptom. According to the postoperative assessment, 10 (12%) patients received an en bloc resection with marginal or wide margins, whereas two (2%) patients received en bloc resections with intralesional margins, 69 (82%) patients were treated by piecemeal "intralesional" resection, and three (4%) patients were not assessed. A total of six patients (7%) experienced a local recurrence, all of which occurred in patients who had received an intralesional resection. Benign bone-forming tumors of the spine are uncommon. Most patients in our series underwent a piecemeal resection with intralesional margins. This remains safe with a low local recurrence rate. En bloc excision may provide more chance of complete excision of the nidus but is not mandatory. The importance of complete excision of the nidus cannot be overemphasized. Copyright © 2016 Elsevier Inc. All rights reserved.

Job Satisfaction and Associated Factors among Anesthetists Working in Amhara National Regional State, Northwest Ethiopia, May 2017: A Multicenter Cross-Sectional Study.

PubMed

Yilkal Fentie, Demeke; Enyew Ashagrie, Henos; Getinet Kasahun, Habtamu

2018-01-01

Job satisfaction is an important determinant of health staff's motivation, retention, and performance. Difficulties in critical decision-making and problems with lack of respect and recognition lead to lower job satisfaction level among anesthetists. It leads to high turnover intention, dropout from the profession, burnout, impaired health status of anesthetists, and lower work performance. The aim of this multicenter cross-sectional study was to assess the level of job satisfaction and associated factors among anesthetists working in Amhara National Regional State. A multicenter cross-sectional study was conducted from April 1 to June 30, 2017. Ninety-eight anesthetists that were working in Amhara National Regional State Hospitals were involved in this study. The structured questionnaire was scored on five-point Likert scales. Data were analyzed using Statistical Package for Social Sciences version 20. Binary logistic regression was used to measure statistical significance between dependent and each independent variable. Variables with P value of ≤0.2 on crude analysis were taken into multivariate analysis, and P value 0.05 and 95% CI was used as cut off point. 98 out of 104 participants were involved in this study with a response rate of 94.3%. The overall level of job satisfaction was 46.9%. Anesthetists in academic working position were satisfied with the odds of about 2.3 (AOR = 2.269; CI = 1.137-6.740) compared to those in clinical working position. Anesthetists were least satisfied with coworker relationships (37.8%), work schedule (43.9%), professional opportunity (46.9%), and recognition (49%) while they were most satisfied from their control of responsibility (59.2%), social interaction (55%), and salary and benefits (51%). Job satisfaction of anesthetists was low, and we suggest that facilitation of professional development, creation of smooth relationship in working environment, increasing the number of anesthetists, and recognition of the anesthesia professional are of paramount importance to increase job satisfaction of anesthetists.

Descriptive Epidemiology of the Multicenter ACL Revision Study (MARS) Cohort

PubMed Central

2013-01-01

Background Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. Purpose To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Study Design Cross-sectional study; Level of evidence, 2. Methods After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. Results As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (<1%), and no response (<1%). Previous graft present at the time of injury was 70% autograft, 27% allograft, 2% combination, and 1% unknown. Sixty-two percent were more than 2 years removed from their last reconstruction. Graft choice for revision ACL reconstruction was 45% autograft, 54% allograft, and more than 1% both allograft and autograft. Meniscus and/or chondral damage was found in 90% of patients. Conclusion The MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most common mode of failure. Allograft graft choice is more common in the revision setting than autograft. Concomitant knee injury is extremely common in this population. PMID:20889962

Long-term application of computer-based pleoptics in home therapy: selected results of a prospective multicenter study.

PubMed

Kämpf, Uwe; Shamshinova, Angelika; Kaschtschenko, Tamara; Mascolus, Wilfried; Pillunat, Lutz; Haase, Wolfgang

2008-01-01

The paper presents selected results of a prospective multicenter study. The reported study was aimed at the evaluation of a software-based stimulation method of computer training applied in addition to occlusion as a complementary treatment for therapy-resistant cases of amblyopia. The stimulus was a drifting sinusoidal grating of a spatial frequency of 0.3 cyc/deg and a temporal frequency of 1 cyc/sec, reciprocally coordinated with each other to a drift of 0.33 deg/sec. This pattern was implemented as a background stimulus into simple computer games to bind attention by sensory-motor coordination tasks. According to an earlier proposed hypothesis, the stimulation aims at the provocation of stimulus-induced phase-coupling in order to contribute to the refreshment of synchronization and coordination processes in the visual transmission channels. To assess the outcome of the therapy, we studied the development of the visual acuity during a period of 6 months. Our cooperating partners of this prospective multicenter study were strabologic departments in ophthalmic clinics and private practices as well. For the issue of therapy control, a partial sample of 55 patients from an overall sample of 198 patients was selected, according to the criterion of strong therapy resistance. The visual acuity was increased about two logarithmic steps by an occlusion combined with computer training in addition to the earlier obtained gain of the same amount by occlusion alone. Recalculated relatively to the duration of the therapy periods, the computer training combined with occlusion was found to be about twice as effective as the preceding occlusion alone. The results of combined computer training and occlusion show an additional increase of the same amount as the preceding occlusion alone, which yielded at its end no further advantage to the development of visual acuity in the selected sample of our 55 therapy-resistant patients. In a concluding theoretical note, a preliminary hypothesis about the neuronal mechanisms of the stimulus-induced treatment effect is discussed.

A Multicenter Approach Evaluating the Impact of Vitamin E-Blended Polyethylene in Cementless Total Hip Replacement

PubMed Central

Jäger, Marcus; van Wasen, Andrea; Warwas, Sebastian; Landgraeber, Stefan; Haversath, Marcel; Group, VITAS

2014-01-01

Since polyethylene is one of the most frequently used biomaterials as a liner in total hip arthroplasty, strong efforts have been made to improve design and material properties over the last 50 years. Antioxidants seems to be a promising alternative to further increase durability and reduce polyethylene wear in long term. As of yet, only in vitro results are available. While they are promising, there is yet no clinical evidence that the new material shows these advantages in vivo. To answer the question if vitamin-E enhanced ultra-high molecular weight polyethylene (UHMWPE) is able to improve long-term survivorship of cementless total hip arthroplasty we initiated a randomized long-term multicenter trial. Designed as a superiority study, the oxidation index assessed in retrieval analyses of explanted liners was chosen as primary parameter. Radiographic results (wear rate, osteolysis, radiolucency) and functional outcome (Harris Hip Scores, University of California-Los Angeles, Hip Disability and Osteoarthritis Outcome Score, Visual Analogue Scale) will serve as secondary parameters. Patients with the indication for a cementless total hip arthroplasty will be asked to participate in the study and will be randomized to either receive a standard hip replacement with a highly cross-linked UHMWPE-X liner or a highly cross-linked vitamin-E supplemented UHMWPE-XE liner. The follow-up will be 15 years, with evaluation after 5, 10 and 15 years. The controlled randomized study has been designed to determine if Vitamin-E supplemented highly cross-linked polyethylene liners are superior to standard XLPE liners in cementless total hip arthroplasty. While several studies have been started to evaluate the influence of vitamin-E, most of them evaluate wear rates and functional results. The approach used for this multicenter study, to analyze the oxidation status of retrieved implants, should make it possible to directly evaluate the ageing process and development of the implant material itself over a time period of 15 years. PMID:25002933

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions.

PubMed

Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

2015-01-01

Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients' medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012-2013) in the societal perspective was US$ 468 million (90% CL: 349-590) or US$ 1,212 million (90% CL: 904-1,526) after adjusting for under-reporting. Considering the time series of dengue (2009-2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). The economic burden associated with dengue in Brazil is substantial with large variations in reported cases and consequently costs reflecting the dynamic of dengue transmission.

Pain severity and mobility one year after spinal cord injury: a multicenter, cross-sectional study.

PubMed

Marcondes, Bianca F; Sreepathi, Shruti; Markowski, Justin; Nguyen, Dung; Stock, Shannon R; Carvalho, Sandra; Tate, Denise; Zafonte, Ross; Morse, Leslie R; Fregni, Felipe

2016-10-01

Following a spinal cord injury, patients are often burdened by chronic pain. Preliminary research points to activation of the motor cortex through increased mobility as a potential means of alleviating postinjury chronic pain. The aim of this study was to assess the relationship between pain severity and mobility among patients who have sustained a traumatic spinal cord injury while controlling for clinically-relevant covariates. A multi-center, cross-sectional study. The SCIMS is composed of 14 centers, all located in the United States and funded by the National Institute on Disability and Rehabilitation Research (NIDRR). The study cohort included 1980 patients who completed the one-year SCIMS follow-up assessment between October 2000- December 2013. A multi-center, cross-sectional study was performed to assess the impact of mobility on self-reported pain using information from 1980 subjects who sustained a traumatic spinal cord injury and completed a year-one follow-up interview between October 2000 and December 2013. Patient information was acquired using the Spinal Cord Injury National Database, compiled by the affiliated Spinal Cord Injury Model Systems. Analyses included a multivariable linear regression of patients' self-reported pain scores on mobility, quantified using the CHART-SF mobility total score, and other clinically relevant covariates. After controlling for potential confounders, a significant quadratic relationship between mobility and patients' self-reported pain was observed (P=0.016). Furthermore, female gender, "unemployed" occupational status, paraplegia, and the presence of depressive symptoms were associated with significantly higher pain scores (P<0.02 for all variables). Statistically significant quadratic associations between pain scores and age at injury, life satisfaction total score, and the CHART-SF occupational total subscale were also observed (P≤0.03 for all variables). Among patients with moderate to high levels of mobility, pain scores decreased with increasing mobility. Enhancing a patient's physical activity by increasing his or her mobility may reduce neuropathic pain if begun shortly after a spinal cord injury.

Effects of structured patient education in adults with atopic dermatitis: Multicenter randomized controlled trial.

PubMed

Heratizadeh, Annice; Werfel, Thomas; Wollenberg, Andreas; Abraham, Susanne; Plank-Habibi, Sibylle; Schnopp, Christina; Sticherling, Michael; Apfelbacher, Christian; Biedermann, Tilo; Breuer, Kristine; Fell, Isabel; Fölster-Holst, Regina; Heine, Guido; Grimm, Jennifer; Hennighausen, Lars; Kugler, Claudia; Reese, Imke; Ring, Johannes; Schäkel, Knut; Schmitt, Jochen; Seikowski, Kurt; von Stebut, Esther; Wagner, Nicola; Waßmann-Otto, Anja; Wienke-Graul, Ute; Weisshaar, Elke; Worm, Margitta; Gieler, Uwe; Kupfer, Joerg

2017-09-01

Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1% to 3% of adults in Western industrialized countries. We sought to investigate the effectiveness of educational training in an outpatient setting on coping with the disease, quality of life, symptoms, and severity in adults with AD. In this German prospective, randomized controlled multicenter study, adult patients with moderate-to-severe AD were educated by referring to a comprehensive 12-hour training manual consented by a multiprofessional study group from different centers (Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene [ARNE]). Patients were randomly allocated to the intervention or waiting control groups. Study visits were performed at baseline and after 1 year (1 year of follow-up). Primary outcomes were defined as a decrease in (1) "catastrophizing cognitions" with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire), (2) "social anxiety" (Marburger Hautfragebogen questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire), and (4) improvement of disease signs and symptoms assessed by using the SCORAD index at 1 year of follow-up. Data were analyzed on an intention-to-treat basis. At 1 year of follow-up, patients from the intervention group (n = 168) showed a significantly better improvement compared with the waiting group (n = 147) in the following defined primary study outcomes: coping behavior with respect to itching (P < .001), quality of life assessed by using the Skindex-29 questionnaire (P < .001), and the SCORAD index (P < .001). This is the first randomized, controlled multicenter study on patient education in adult AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters, as well as AD severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Dippel, Diederik W J; Dijkgraaf, Marcel G W; van der Poll, Tom; Prins, Jan M; Vermeij, Frederique H; Roos, Yvo B W E M; Brouwer, Matthijs C; Zwinderman, Aeilko H; van de Beek, Diederik; Nederkoorn, Paul J

2014-10-01

Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Labor force participation and health-related quality of life in HIV-positive men who have sex with men: The Multicenter AIDS Cohort Study

PubMed Central

Rueda, Sergio; Raboud, Janet; Plankey, Michael; Ostrow, David; Mustard, Cameron; Rourke, Sean B.; Jacobson, Lisa P.; Bekele, Tsegaye; Bayoumi, Ahmed; Lavis, John; Detels, Roger; Silvestre, Anthony J.

2013-01-01

Too many people with HIV have left the job market permanently and those with reduced work capacity have been unable to keep their jobs. There is a need to examine the health effects of labor force participation in people with HIV. This study presents longitudinal data from 1,415 HIV-positive men who have sex with men taking part in the Multicenter AIDS Cohort Study. Generalized Estimating Equations show that employment is associated with better physical and mental health quality of life and suggests that there may be an adaptation process to the experience of unemployment. Post-hoc analyses also suggest that people who are more physically vulnerable may undergo steeper health declines due to job loss than those who are generally healthier. However, this may also be the result of a selection effect whereby poor physical health contributes to unemployment. Policies that promote labor force participation may not only increase employment rates but also improve the health of people living with HIV. PMID:22814570

[Analysis of the results of total cervical disc arthroplasty using a M6-C prosthesis: a multicenter study].

PubMed

Byval'tsev, V A; Kalinin, A A; Stepanov, I A; Pestryakov, Yu Ya; Shepelev, V V

Cervical spondylosis and intervertebral disc (IVD) degeneration are the most common cause for compression of the spinal cord and/or its roots. Total IVD arthroplasty, as a modern alternative to surgical treatment of IVD degeneration, is gaining popularity in many neurosurgical clinics around the world. Aim - the study aim was to conduct a multicenter analysis of cervical spine arthroplasty with an IVD prosthesis M6-C ('Spinal Kinetics', USA). The study included 112 patients (77 males and 35 females). All patients underwent single-level discectomy with implantation of the artificial IVD prosthesis M6-C. The follow-up period was up to 36 months. Dynamic assessment of the prosthesis was based on clinical parameters (pain intensity in the cervical spine and upper extremities (visual analog scale - VAS); quality of life (Neck Disability Index - NDI)); and subjective satisfaction with the results of surgical treatment (Macnab scale) and instrumental data (range of motion in the operated spinal motion segment, degree of heterotopic ossification (McAfee-Suchomel classification), and time course of degenerative changes in the adjacent segments).

Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

PubMed Central

De Guio, François; Jouvent, Eric; Biessels, Geert Jan; Black, Sandra E; Brayne, Carol; Chen, Christopher; Cordonnier, Charlotte; De Leeuw, Frank-Eric; Dichgans, Martin; Doubal, Fergus; Duering, Marco; Dufouil, Carole; Duzel, Emrah; Fazekas, Franz; Hachinski, Vladimir; Ikram, M Arfan; Linn, Jennifer; Matthews, Paul M; Mazoyer, Bernard; Mok, Vincent; Norrving, Bo; O’Brien, John T; Pantoni, Leonardo; Ropele, Stefan; Sachdev, Perminder; Schmidt, Reinhold; Seshadri, Sudha; Smith, Eric E; Sposato, Luciano A; Stephan, Blossom; Swartz, Richard H; Tzourio, Christophe; van Buchem, Mark; van der Lugt, Aad; van Oostenbrugge, Robert; Vernooij, Meike W; Viswanathan, Anand; Werring, David; Wollenweber, Frank; Wardlaw, Joanna M

2016-01-01

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan–rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease. PMID:27170700

Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.

PubMed

Hesham, Mervat; Atfy, Mervat; Hassan, Tamer; Abdo, Mohamed; Morsy, Saed; El Malky, Mohamed; Latif, Dalia Abdel

2014-11-01

Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor and Hodgkin lymphoma and lower in patients with neuroblastoma. A larger multicenter study is required to further investigate the conclusions drawn from this study.

Rationale, design and methods of the HEALTHY study behavior intervention component

USDA-ARS?s Scientific Manuscript database

HEALTHY was a multi-center primary prevention trial designed to reduce risk factors for type 2 diabetes in adolescents. Seven centers each recruited six middle schools that were randomized to either intervention or control. The HEALTHY intervention integrated multiple components in nutrition, physic...

VISIBILITY AS A SURROGATE FOR PARTICLE POLLUTION IN MULTI-CENTER POPULATION-BASED STUDIES. (R827994)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Women with BRCA1 and BRCA2 mutations survive ovarian cancer at higher rates

Cancer.gov

Results from a National Cancer Institute (NCI) sponsored multicenter study published in the Journal of the American Medical Association on January 25, 2012, provides strong evidence that BRCA1 and BRCA2 gene mutation carriers with ovarian cancer were more

Early Enteral Nutrition in Burns: Compliance With Guidelines and Associated Outcomes in a Multicenter Study

PubMed Central

Mosier, Michael J.; Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.; Arnoldo, Brett D.; Gamelli, Richard L.; Tompkins, Ronald G.; Herndon, David N.

2013-01-01

Early nutritional support is an essential component of burn care to prevent ileus, stress ulceration, and the effects of hypermetabolism. The American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical. The authors sought to evaluate compliance with early enteral nutrition (EN) guidelines, associated complications, and hospitalization outcomes in a prospective multicenter observational study. They conducted a retrospective review of mechanically ventilated burn patients enrolled in the prospective observational multicenter study “Inflammation and the Host Response to Injury.” Timing of initiation of tube feedings was recorded, with early EN defined as being started within 24 hours of admission. Univariate and multivariate analyses were performed to distinguish barriers to initiation of EN and the impact of early feeding on development of multiple organ dysfunction syndrome, infectious complications, days on mechanical ventilation, intensive care unit (ICU) length of stay, and survival. A total of 153 patients met study inclusion criteria. The cohort comprised 73% men, with a mean age of 41 ± 15 years and a mean %TBSA burn of 46 ± 18%. One hundred twenty-three patients (80%) began EN in the first 24 hours and 145 (95%) by 48 hours. Age, sex, inhalation injury, and full-thickness burn size were similar between those fed by 24 hours vs after 24 hours, except for higher mean Acute Physiology and Chronic Health Evaluation II scores (26 vs 23, P = .03) and smaller total burn size (44 vs 54% TBSA burn, P = .01) in those fed early. There was no significant difference in rates of hyperglycemia, abdominal compartment syndrome, or gastrointestinal bleeding between groups. Patients fed early had shorter ICU length of stay (adjusted hazard ratio 0.57, P = 0.03, 95% confidence interval 0.35–0.94) and reduced wound infection risk (adjusted odds ratio 0.28, P = 0.01, 95% confidence interval 0.10–0.76). The investigators have found early EN to be safe, with no increase in complications and a lower rate of wound infections and shorter ICU length of stay. Across institutions, there has been high compliance with early EN as part of the standard operating procedure in this prospective multicenter observational trial. The investigators advocate that initiation of EN by 24 hours be used as a formal recommendation in nutrition guidelines for severe burns, and that nutrition guidelines be actively disseminated to individual burn centers to permit a change in practice. PMID:21116188

Assessment of the diagnostic value of a urinary adipsin rapid strip test for pre-eclampsia: A prospective multicenter study.

PubMed

Peng, Bing; Zhang, Li; Yan, Jianying; Qi, Hongbo; Zhang, Weiyuan; Fan, Ling; Hu, Yayi; Lin, Li; Li, Xiaotian; Hu, Rong; Xie, Lan; Zhang, Jianping; Wu, Yanqiao; Li, Li; Zhou, Rong

2017-01-01

The purpose of the present study was to evaluate the clinical value of the rapid strip test of urinary adipsin for the quick diagnosis of pre-eclampsia. In a multicenter diagnostic test study, we studied the diagnostic accuracy of the rapid strip test of urinary adipsin in women presenting with pre-eclampsia. A total of 204 pre-eclampsia patients and 254 healthy pregnant women were recruited for this study, respectively. The rapid strip test of urinary adipsin was used to detect the adipsin in the urine of each patient. The diagnostic value of the rapid strip test of urinary adipsin for pre-eclampsia was demonstrated by its high sensitivity and specificity (95.10% and 97.64%, respectively). The diagnostic accuracy was 96.51%. The consistency analysis showed that the kappa value was 0.93 compared with the gold standard diagnosis of pre-eclampsia. The rapid strip test of urinary adipsin is a non-invasive test for the diagnosis of pre-eclampsia with high sensitivity and specificity. It could help the quick diagnosis of pre-eclampsia in clinical practice greatly. © 2016 Japan Society of Obstetrics and Gynecology.

The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients.

PubMed

1998-07-01

The purpose of this report is to examine the differences at baseline in demographic, medical, and ophthalmic characteristics between blacks and whites enrolled in the Advanced Glaucoma Intervention Study (AGIS), a multicenter, randomized, clinical trial. Multicenter, randomized, controlled trial. A total of 332 black patients (451 eyes), 249 white patients (325 eyes), and 10 patients of other races (13 eyes) with open-angle glaucoma that could not be controlled by medical therapy alone participated. There was no intervention performed. The investigators compare the baseline demographic, medical, and ophthalmic characteristics of black and white patients, adjusting the comparisons for age and gender. Blacks in the study were younger than whites and had more systemic hypertension and diabetes than whites. The visual field defects of blacks on average were substantially more severe than those of whites. Intraocular pressures and visual acuity scores were similar in the two groups. Blacks were more hyperopic and had relatively fewer disk rim hemorrhages than whites. The findings of the current study concur with those of previous clinical studies of open-angle glaucoma that visual field defects are more severe in blacks than whites.

Multi-Center Traffic Management Advisor Operational Field Test Results

NASA Technical Reports Server (NTRS)

Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

2005-01-01

The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research

PubMed Central

Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D

2015-01-01

Background A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. Objective This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. Methods NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f 1, f 2, ..., f k. The input for each function f i has 3 components: a random number r, an integer n, and input data m. The result, f i(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f 1(r 1, n 1, m 1), f 2(r 2, n 2, m 2), ..., f k(r k, n k, m k). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result of the encryption, concatenated with the random number r, is the final NHash study identifier. Results We performed experiments using a large synthesized dataset comparing NHash with random strings, and demonstrated neglegible probability for collision. We implemented NHash for the Center for SUDEP Research (CSR), a National Institute for Neurological Disorders and Stroke-funded Center Without Walls for Collaborative Research in the Epilepsies. This multicenter collaboration involves 14 institutions across the United States and Europe, bringing together extensive and diverse expertise to understand sudden unexpected death in epilepsy patients (SUDEP). Conclusions The CSR Data Repository has successfully used NHash to link deidentified multimodal clinical data collected in participating CSR institutions, meeting all desired objectives of NHash. PMID:26554419

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

PubMed

Frank, Jonathan M; Kayupov, Erdan; Moric, Mario; Segreti, John; Hansen, Erik; Hartman, Curtis; Okroj, Kamil; Belden, Katherine; Roslund, Brian; Silibovsky, Randi; Parvizi, Javad; Della Valle, Craig J

2017-01-01

Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. Level I, therapeutic study.

OVERALL PROCEDURES PROTOCOL AND PATIENT ENROLLMENT PROTOCOL: TESTING FEASIBILITY OF 3D ULTRASOUND DATA ACQUISITION AND RELIABILITY OF DATA RETRIEVAL FROM STORED 3D IMAGES

EPA Science Inventory

The purpose of this study is to examine the feasibility of collecting, transmitting,

and analyzing 3-D ultrasound data in the context of a multi-center study of pregnant

women. The study will also examine the reliability of measurements obtained from 3-D

imag...

Conditions for exercising residents' voting rights in long-term care residences: a prospective multicenter study.

PubMed

Bosquet, Antoine; El Massioui, Farid; Mahé, Isabelle

2015-01-01

To assess voting conditions in long-term care settings, we conducted a multicenter survey after the 2009 European elections in France. A questionnaire about voting procedures and European elections was proposed in 146 out of 884 randomized facilities. Sixty-four percent of facilities answered the questionnaire. Four percent of residents voted (national turnout: 40%), by proxy (58%) or at polling places (42%). Abstention related to procedural issues was reported in 32% of facilities. Sixty-seven percent of establishments had voting procedures, and 53% declared that they assessed residents' capacity to vote. Assistance was proposed to residents for voter registration, for proxy voting, and for voting at polling places, respectively, in 33%, 87%, and 80% of facilities. This survey suggests that residents may be disenfranchised and that more progress should be made to protect the voting rights of residents in long-term care facilities.

Building a Community of Practice for Researchers: The International Network for Simulation-Based Pediatric Innovation, Research and Education.

PubMed

Cheng, Adam; Auerbach, Marc; Calhoun, Aaron; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay; Hunt, Elizabeth A; Duval-Arnould, Jordan; Peiris, Nicola; Kessler, David

2018-06-01

The scope and breadth of simulation-based research is growing rapidly; however, few mechanisms exist for conducting multicenter, collaborative research. Failure to foster collaborative research efforts is a critical gap that lies in the path of advancing healthcare simulation. The 2017 Research Summit hosted by the Society for Simulation in Healthcare highlighted how simulation-based research networks can produce studies that positively impact the delivery of healthcare. In 2011, the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE) was formed to facilitate multicenter, collaborative simulation-based research with the aim of developing a community of practice for simulation researchers. Since its formation, the network has successfully completed and published numerous collaborative research projects. In this article, we describe INSPIRE's history, structure, and internal processes with the goal of highlighting the community of practice model for other groups seeking to form a simulation-based research network.

Cardiac biomarkers in youth with type 2 diabetes mellitus: Results from the Today Study

USDA-ARS?s Scientific Manuscript database

To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 ...

The Handbook of Research Impact Assessment. Edition 7. Summer 1997.

DTIC Science & Technology

1997-01-01

Treatment of Patients with Chronic-Schizophrenia - A Multi-National, Multicenter, Double-Blind, Parallel-Group Study Versus Haloperidol ", BRITISH JOURNAL OF...34The Scientific Production and International Reputation of Travassos,Lauro", MEMORIAS DO INSTITUTO OSWALDO CRUZ,1992, Vol 87, Iss S1, pp R7-R10 Courtial

Design and Cohort Characteristics of the Social Spectrum Study: A Multicenter Study of the Autism Spectrum among Clinically Referred Children

ERIC Educational Resources Information Center

Duvekot, Jorieke; Hoopen, Leontine W.; Slappendel, Geerte; van der Ende, Jan; Verhulst, Frank C.; van der Sijde, Ad; Greaves-Lord, Kirstin

2017-01-01

This paper provides an overview of the design and cohort characteristics of the Social Spectrum Study: a clinical cohort study that used a two-phase sampling design to identify children at risk for ASD. After screening 1281 children aged 2.5-10 years who had been consecutively referred to one of six mental health services in the Netherlands,…

International consensus on a complications list after gastrectomy for cancer.

PubMed

Baiocchi, Gian Luca; Giacopuzzi, Simone; Marrelli, Daniele; Reim, Daniel; Piessen, Guillaume; Matos da Costa, Paulo; Reynolds, John V; Meyer, Hans-Joachim; Morgagni, Paolo; Gockel, Ines; Lara Santos, Lucio; Jensen, Lone Susanne; Murphy, Thomas; Preston, Shaun R; Ter-Ovanesov, Mikhail; Fumagalli Romario, Uberto; Degiuli, Maurizio; Kielan, Wojciech; Mönig, Stefan; Kołodziejczyk, Piotr; Polkowski, Wojciech; Hardwick, Richard; Pera, Manuel; Johansson, Jan; Schneider, Paul M; de Steur, Wobbe O; Gisbertz, Suzanne S; Hartgrink, Henk; van Sandick, Joanna W; Portolani, Nazario; Hölscher, Arnulf H; Botticini, Maristella; Roviello, Franco; Mariette, Christophe; Allum, William; De Manzoni, Giovanni

2018-05-30

Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Analysis of patients' willingness to be mobile, taking into account individual characteristics and two exemplary indications.

PubMed

Augustin, Jobst; Schäfer, Ines; Augustin, Matthias; Zander, Nicole

2017-04-01

With respect to health care planning, it is commonly assumed that patients consult the nearest physician. In reality, however, patients frequently accept great-er efforts/expenses than necessary to see a physician. The objective of the present study was to determine under which circumstances patients were willing to accept additional efforts/expenses, and which role sociodemographic and clinical characteristics play in this regard. Data collection was carried out in the context of a multicenter cross-sectional study among office-based and hospital-affiliated (University Medical Center Hamburg-Eppendorf) dermatologists. Patients (n = 309) with psoriasis and chronic wounds were surveyed about their mobility patterns and disease severity. Data analysis was performed using descriptive and multivariate methods. The willingness to accept additional efforts/expenses is primarily determined by a physician's expertise and service portfolio. Comparing both diagnoses showed that psoriasis patients usually traveled longer distances than wound patients. Among psoriasis patients, one significant predictor for accepting additional efforts/expenses was the level of education. With regard to wound patients, key factors included wound size (severity). The present study revealed complex mobility patterns among patients, which are affected by numerous personal as well as clinical factors. Depending on the diagnosis and individual preferences, additional efforts/expenses can - among other things - be explained by disease severity. Further studies are required to obtain more conclusive data. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Work schedule flexibility is associated with emotional exhaustion among registered nurses in Swiss hospitals: A cross-sectional study.

PubMed

Dhaini, Suzanne R; Denhaerynck, Kris; Bachnick, Stefanie; Schwendimann, René; Schubert, Maria; De Geest, Sabina; Simon, Michael

2018-06-01

Emotional exhaustion among healthcare workers is a widely investigated, well-recognized problem, the incidence of which has recently been linked to work environment factors, particularly work/family conflict. However, another environmental feature that may be equally influential, but that is more amenable to nurse manager action, remains less recognized: shift schedule flexibility. This study's main purposes were to assess variations in work schedule flexibility between Swiss acute care hospital units, and to investigate associations between psychosocial work environment (e.g. work schedule flexibility) and self-reported emotional exhaustion among registered nurses. This is a secondary analysis of data collected for the multi-center observational cross-sectional Match RN study, which included a national sample of 23 hospitals and 1833 registered nurses across Switzerland. Overall, self-reported work schedule flexibility among registered nurses was limited: 32% of participants reported little or no influence in planning their own shifts. Work schedule flexibility (β -0.11; CI -0.16; -0.06) and perceived nurse manager ability (β -0.30; CI -0.49; -0.10) were negatively related to self-reported emotional exhaustion. Work-family conflict (β 0.39; CI 0.33; 0.45) was positively correlated to emotional exhaustion. The study results indicate that managerial efforts to improve working environments, including special efforts to improve work schedule flexibility, might play an important role in promoting nurses' emotional health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial.

PubMed

Bartl, Christoph; Stengel, Dirk; Bruckner, Thomas; Rossion, Inga; Luntz, Steffen; Seiler, Christoph; Gebhard, Florian

2011-03-22

Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation.Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool.The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central statistical unit, an independent monitoring institute, and a data safety monitoring board. Following approval by the institutional review boards of all participating centers, conduct and reporting will strictly adhere to national and international rules, regulations, and recommendations (e.g., Good Clinical Practice, data safety laws, and EQUATOR/CONSORT proposals). To our knowledge, ORCHID is the first multicenter RCT designed to assess quality of life and functional outcomes following operative treatment compared to conservative treatment of complex, intra-articular fractures of the distal radius in elderly patients. The results are expected to influence future treatment recommendations and policies on an international level. ISRCTN: ISRCTN76120052 Registration date: 31.07.2008; Randomization of first patient: 15.09.2008.

Screening CT Colonography: Multicenter Survey of Patient Experience, Preference, and Potential Impact on Adherence

DTIC Science & Technology

2012-06-21

June 21. N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript this sizeable group . Although nearly 70% indicated on ...Screening CT Colonography: Multicenter Survey of Patient Experience, Preference, and Potential Impact on Adherence B. Dustin Pooler1, Mark J. Baumel2...MATERIALS AND METHODS—A 12-question survey instrument measuring pretest choice, experience, and satisfaction was given to a consecutive cohort of

[Costs of exacerbations of chronic obstructive pulmonary disease in primary and secondary care in 2007--results of multicenter Polish study].

PubMed

Jahnz-Rózyk, Karina; Targowski, Tomasz; From, Sławomir

2009-03-01

Exacerbations are the key drivers of the costs of chronic obstructive pulmonary disease (COPD). This was the multicenter study of patients with COPD aimed at evaluating direct and indirect cost of exacerbations under usual clinical practice in primary and secondary care form societal perspective. It was observational, multicenter study with participation of 196 subjects with moderate or severe COPD, defined according to the current GOLD criteria. Patients presenting at the selected health care centres were included into the study in the sequential manner if they fulfilled the inclusion criteria. Exacerbations were divided into three different severity types according to Anthonisen N.R. classification. The management of exacerbations followed the usual clinical practice. The number of exacerbations was 3.8 (3.2-4.4) in hospitalised patients and 1.7 (1.4-1.9) in ambulatory treated patients (1EURO was 3.85 PLN in 2007). The average direct health-care cost per exacerbation was PLN 5548 (95% CI = 4543; 6502) and PLN 524.1 (95% CI = 443; 614) in secondary and primary care respectively. In secondary care, the drug acquisition and oxygen therapy cost represented 18.3% of total direct costs, diagnostic tests costs accounted for 14.5%, the other hospital care and post-discharge followup visit costs 67%. Costs varied considerably with the severity of COPD before the exacerbation as well as the duration of COPD. In primary care the cost structure was as follows: diagnostic tests and medical devices 47.5%, drug acquisition costs 41% and doctors visits 11.4%. The average indirect costs per exacerbation were PLN 127.78 and PLN 100.56, in secondary and primary respectively (n.s) Exacerbations of COPD are costly. Cost of exacerbation managed in secondary care is almost 10-fold higher than in primary care. Prevention of moderate-to-severe exacerbations, requiring hospitalization could be very cost-effective strategy.

Challenges of local recurrence and cure in low grade malignant tumors of the spine.

PubMed

Boriani, Stefano; Saravanja, Davor; Yamada, Yoshiya; Varga, Peter Pal; Biagini, Roberto; Fisher, Charles G

2009-10-15

Systematic review and ambispective multicenter cohort study. 1. To compare the effects of wide/marginal (en bloc) resection with intralesional resection on local recurrence and survival for chordomas and chondrosarcomas of the spine. 2. To determine the influence of radiation therapy in the management of chordomas and chondrosarcomas. Chordomas and chondrosarcomas of the spine are prone to local recurrence and death despite being low-grade malignant tumors. No study to date has enough numbers or adequate scientific rigor to determine the influence of resection or radiation therapy on outcome. A systematic review was performed to evaluate the 2 objectives. In addition an ambispective multicenter cohort analysis of chordomas and chondrosarcomas was performed. The GRADE system of analysis integrating the results of the systematic review, the multicenter cohort study and the expert opinion of the Spine Oncology Study Group (SOSG) was used to arrive at treatment recommendations. A total of 63 articles were included in the systematic reviews. Evidence was low quality. En bloc resection appeared to improve both local recurrence and disease free survival in Chordoma and Chondrosarcoma. Radiation therapy had a positive impact on the management of Chordoma and Chondrosarcoma with predictably low side effects. The cohort analysis showed significantly decreased local recurrence for Chordoma (P < 0.0001) and Chondrosarcoma (P < 0.0001) with en bloc resection, and significantly decreased death for both Chordoma (P = 0.0001) and Chondrosarcoma (P = 0.0015) with en bloc resection. When wide or marginal margins (en bloc) are achieved in surgical resection of chordomas and chondrosarcomas of the spine there is a decrease in local recurrence and mortality. Therefore, en bloc resection should be undertaken for the treatment of chordomas and chondrosarcomas of the spine. Strong Recommendation, Moderate Quality Evidence.Radiation therapy of at least 60 to 65 Gy equivalents is indicated as an adjuvant treatment for chordoma and chondrosarcoma of the spine when there has been incomplete resection or an intralesional margin. Weak Recommendation, Low Quality Evidence.

The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study.

PubMed

Kozower, Benjamin D; Meyers, Bryan F; Smith, Michael A; De Oliveira, Nilto C; Cassivi, Stephen D; Guthrie, Tracey J; Wang, Honkung; Ryan, Beverly J; Shen, K Robert; Daniel, Thomas M; Jones, David R

2008-01-01

The lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation. A multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005). The study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 +/- 528.3 days to 445.6 +/- 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 +/- 6.7 days to 7.8 +/- 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6) This multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected.

The Prevalence and Clinical Features of Non-responsive Gastroesophageal Reflux Disease to Practical Proton Pump Inhibitor Dose in Korea: A Multicenter Study.

PubMed

Park, Hong Jun; Park, Soo Heon; Shim, Ki Nam; Kim, Yong Sung; Kim, Hyun Jin; Han, Jae Pil; Kim, Yong Sik; Bang, Byoung Wook; Kim, Gwang Ha; Baik, Gwang Ho; Kim, Hyung Hun; Park, Seon Young; Kim, Sung Soo

2016-07-25

In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients.

PubMed

Valões, C C M; Molinari, B C; Pitta, A C G; Gormezano, N W S; Farhat, S C L; Kozu, K; Sallum, A M E; Appenzeller, S; Sakamoto, A P; Terreri, M T; Pereira, R M R; Magalhães, C S; Ferreira, J C O A; Barbosa, C M; Gomes, F H; Bonfá, E; Silva, C A

2017-04-01

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

A prospective multicenter study on self-expandable metallic stents as a bridge to surgery for malignant colorectal obstruction in Japan: efficacy and safety in 312 patients.

PubMed

Saito, Shuji; Yoshida, Shuntaro; Isayama, Hiroyuki; Matsuzawa, Takeaki; Kuwai, Toshio; Maetani, Iruru; Shimada, Mamoru; Yamada, Tomonori; Tomita, Masafumi; Koizumi, Koichi; Hirata, Nobuto; Kanazawa, Hideki; Enomoto, Toshiyuki; Sekido, Hitoshi; Saida, Yoshihisa

2016-09-01

Endoscopic stenting with a self-expandable metallic stent (SEMS) is a widely accepted procedure for malignant colonic obstruction. The Colonic Stent Safe Procedure Research Group conducted the present prospective feasibility study. Our objectives were to estimate the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction. We conducted a prospective, observational, single-arm, multicenter clinical trial from March 2012 to October 2013. Each patient was treated with an uncovered WallFlex enteral colonic stent. Patients were followed up until discharge after surgery. A total of 518 consecutive patients were enrolled in this study. The cohort intended for BTS consisted of 312 patients (61 %), and the stent could be released in 305 patients. Technical and clinical success rates were 98 and 92 %, respectively. Elective surgery was performed in 297 patients, and emergency surgery was performed in eight patients for the treatment of complications. The overall preoperative complication rate was 7.2 %. Major complications, including perforation, occurred in 1.6 %, persistent colonic obstruction occurred in 1.0 %, and stent migration occurred in 1.3 % patients. The median time from SEMS to surgery was 16 days. Silent perforations were observed in 1.3 %. Open and laparoscopic surgery was performed in 121 and 184 patients, respectively. The tumor could be resected in 297 patients. The primary anastomosis rate was 92 %. The rate of anastomotic leakage was 4 %, and the overall stoma creation rate was 10 %. The median duration of hospitalization following surgery was 12 days. Overall postoperative morbidity and mortality rates were 16 and 0.7 %, respectively. This largest, multicenter, prospective study demonstrates the feasibility of SEMS placement as a BTS for malignant colorectal obstruction. SEMS serves as a safe and effective BTS with acceptable stoma creation and complication rates in patients with acute malignant colonic obstruction.

A Retrospective Study of the Impact of 21-Gene Recurrence Score Assay on Treatment Choice in Node Positive Micrometastatic Breast Cancer

PubMed Central

Frazier, Thomas G.; Fox, Kevin R.; Smith, J. Stanley; Laronga, Christine; McSwain, Anita; Paul, Devchand; Schultz, Michael; Stilwill, Joseph; Teal, Christine; Weisberg, Tracey; Vacchino, Judith F.; Sing, Amy P.; Cherepanov, Dasha; Hsiao, Wendy; Chang, Eunice; Broder, Michael S.

2015-01-01

To assess clinical utility of the 21-gene assay (Oncotype DX® Recurrence Score®), we determined whether women with HER2(−)/ER+ pN1mi breast cancer with low (<18) Recurrence Scores results are given adjuvant chemotherapy in a lower proportion than those with high scores (≥31). This was a multicenter chart review of ≥18 year old women with pN1mi breast cancer, HER2(−)/ER+ tumors, ductal/lobular/mixed histology, with the assay ordered on or after 1 January 2007. One hundred and eighty one patients had a mean age of 60.7 years; 82.9% had ECOG performance status 0; 33.7% had hypertension, 22.7% had osteoporosis, 18.8% had osteoarthritis, and 8.8% had type-2 diabetes. Mean Recurrence Score was 17.8 (range: 0–50). 48.6% had a mastectomy; 55.8% had a lumpectomy. 19.8% of low-risk group patients were recommended chemotherapy vs. 57.9% in the intermediate-risk group and 100% in the high-risk group (p < 0.001). A total of 80.2% of the low-risk group were recommended endocrine therapy alone, while 77.8% of the high-risk group were recommended both endocrine and chemotherapy (p < 0.001). The Oncotype DX Recurrence Score result provides actionable information that can be incorporated into treatment planning for women with HER2(−)/ER+ pN1mi breast cancer. The Recurrence Score result has clinical utility in treatment planning for HER2(−)/ER+ pN1mi breast cancer patients. PMID:25789420

Simulation Use for Global Away Rotations (SUGAR): preparing residents for emotional challenges abroad--a multicenter study.

PubMed

Butteris, Sabrina M; Gladding, Sophia P; Eppich, Walter; Hagen, Scott A; Pitt, Michael B

2014-01-01

Preparation for residents participating in global health (GH) experiences is critical. Active preparatory curricula allowing residents to experience and debrief emotional challenges they may encounter abroad are generally lacking. We sought to evaluate a novel simulation curriculum designed to prepare residents for emotions they may experience in response to challenges abroad. Pediatric GH educators from 7 institutions developed case vignettes incorporating common challenges residents experience abroad. Residents participating in a GH training track or planning to participate in a GH rotation from the 7 institutions were eligible to participate in the simulation curriculum. Participants and trained facilitators completed postsimulation evaluations that were analyzed using descriptive statistics and thematic analysis of written comments to assess the utility of the curriculum, emotions evoked, and changes residents anticipated making to their GH rotation preparation. Fifty-one residents and 16 facilitators completed 160 and 52 evaluations, respectively. Overall, respondents found the simulations useful (mean [SD] resident score 4.49 [0.82] and facilitator score 4.85 [0.36] on a 5-point scale [1 = completely useless, 5 = very useful]). Residents reported strong emotions in 153 (98%) of 156 comments. After the sessions, 131 (96%) of 137 comments reflected anticipated changes to GH rotation preparation plans. Active preparation for GH rotations using simulated cases appears to be a useful tool that can be implemented across a variety of sites with minimal facilitator training or simulation experience. The curriculum successfully elicited powerful emotions in residents and provided an opportunity to debrief these experiences before encountering them abroad. Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

International Collaboration between US and Thailand on a Clinical Trial of Treatment for HIV-associated Cryptococcal Meningitis

PubMed Central

Zimmer, LO; Nolen, TL; Pramanpol, S; Wallace, D; Walker, ME; Pappas, P; Chetchotisakd, P

2010-01-01

Background International clinical trials can provide scientific and logistic benefits in spite of the many challenges. Determining whether a country, especially a developing country, is an appropriate location for the research should include in-country consultation and partnering to assess its social value for the population; that treatments are relevant for the population under study; and that the research infrastructure and ethical oversight are adequate. Collaboration increases the likelihood of study success and helps ensure that benefits accrue to recruited populations and their community. Purpose This paper describes our experiences on a bi-national study and may provide guidance for those planning to engage in future collaborations. Methods A Thai and United States team collaborated to develop and implement a Phase II clinical trial for HIV-associated cryptococcal meningitis to assess safety and tolerability of combination therapy versus standard treatment. Clinical and cultural differences, regulatory hurdles and operational issues were addressed before and during the study to ensure a successful collaboration between the 2 groups. Results The international multicenter study allowed for more rapid enrollment, reduced costs to complete the study, sharing of the benefits of research, greater generalizability of results and capacity building in Thailand; quality metrics in Thailand were equivalent to or better than those in the U.S. Conclusions Conducting successful clinical trials internationally requires early and ongoing collaboration to ensure the study meets sites’ requirements and expectations, conforms to varying national regulations, adheres to data quality standards and is responsive to the health needs of studied populations. PMID:19897055

Impact of Zygomycosis on Microbiology Workload: a Survey Study in Spain▿

PubMed Central

Torres-Narbona, Marta; Guinea, Jesús; Martínez-Alarcón, José; Muñoz, Patricia; Gadea, Ignacio

2007-01-01

This multicenter, population-based study evaluated the laboratory workload produced by zygomycetes and the number of cases of zygomycosis in Spain during 2005. Less than 8% of the patients who harbored zygomycete isolates had zygomycosis. The incidence of zygomycosis (6 cases) was 0.43 cases/1,000,000 inhabitants and 0.62 cases/100,000 hospital admissions. PMID:17392438

Infants' Early Visual Attention and Social Engagement as Developmental Precursors to Joint Attention

ERIC Educational Resources Information Center

Salley, Brenda; Sheinkopf, Stephen J.; Neal-Beevers, A. Rebecca; Tenenbaum, Elena J.; Miller-Loncar, Cynthia L.; Tronick, Ed; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles; Whitaker, Toni; Hammond, Jane; Lester, Barry M.

2016-01-01

This study examined infants' early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n = 325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at 4 centers of the National Institute of Child Health and Human…

Epidemiology of acute promyelocytic leukemia.

PubMed

Mele, A; Stazi, M A; Pulsoni, A; Visani, G; Monarca, B; Castelli, G; Rocchi, L; Avvisati, G; Mandelli, F

1995-01-01

The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a polous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies.

Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PubMed

Fukushima, Kouhei; Sugita, Akira; Futami, Kitaro; Takahashi, Ken-Ichi; Motoya, Satoshi; Kimura, Hideaki; Yoshikawa, Shusaku; Kinouchi, Yoshitaka; Iijima, Hideki; Endo, Katsuya; Hibi, Toshihumi; Watanabe, Mamoru; Sasaki, Iwao; Suzuki, Yasuo

2018-06-01

The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

Adversity and Syndemic Production Among Men Participating in the Multicenter AIDS Cohort Study: A Life-Course Approach

PubMed Central

Lim, Sin How; Plankey, Michael W.; Chmiel, Joan S.; Guadamuz, Thomas T.; Kao, Uyen; Shoptaw, Steven; Carrico, Adam; Ostrow, David; Stall, Ron

2013-01-01

Objectives. We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study. Methods. Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland–Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production. Results. Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ2 = 247.94; P < .001; df = 22). Conclusions. We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM. PMID:23153154

Effect of Armodafinil on Cortical Activity and Working Memory in Patients with Residual Excessive Sleepiness Associated with CPAP-Treated OSA: A Multicenter fMRI Study

PubMed Central

Greve, Douglas N.; Duntley, Stephen P.; Larson-Prior, Linda; Krystal, Andrew D.; Diaz, Michele T.; Drummond, Sean P. A.; Thein, Stephen G.; Kushida, Clete A.; Yang, Ronghua; Thomas, Robert J.

2014-01-01

Study Objective: To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy. Methods: This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency. Results: No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%). Conclusions: Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness. Study Registration: Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea. ClinicalTrials.gov Identifier: NCT00711516. http://www.clinicaltrials.gov/ct2/show/study/NCT00711516 Citation: Greve DN; Duntley SP; Larson-Prior L; Krystal AD; Diaz MT; Drummond SP; Thein SG; Kushida CA; Yang R; Thomas RJ. Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-treated OSA: a multicenter fMRI study. J Clin Sleep Med 2014;10(2):143-153. PMID:24532997

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial.

PubMed

2012-08-28

Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. ClinicalTrials.gov Identifier: NCT01374022.

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method. Trial registration ClinicalTrials.gov Identifier: NCT01374022 PMID:22929542

Severe Postpartum Hemorrhage from Uterine Atony: A Multicentric Study

PubMed Central

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Objective. Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. Study Design. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Results. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. Conclusions. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths. PMID:24363935

Function Biomedical Informatics Research Network Recommendations for Prospective Multi-Center Functional Magnetic Resonance Imaging Studies

PubMed Central

Glover, Gary H.; Mueller, Bryon A.; Turner, Jessica A.; van Erp, Theo G.M.; Liu, Thomas T.; Greve, Douglas N.; Voyvodic, James T.; Rasmussen, Jerod; Brown, Gregory G.; Keator, David B.; Calhoun, Vince D.; Lee, Hyo Jong; Ford, Judith M.; Mathalon, Daniel H.; Diaz, Michele; O’Leary, Daniel S.; Gadde, Syam; Preda, Adrian; Lim, Kelvin O.; Wible, Cynthia G.; Stern, Hal S.; Belger, Aysenil; McCarthy, Gregory; Ozyurt, Burak; Potkin, Steven G.

2011-01-01

This report provides practical recommendations for the design and execution of Multi-Center functional Magnetic Resonance Imaging (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The paper was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multi-site aspects include: (1) establishing and verifying scan parameters including scanner types and magnetic fields, (2) establishing and monitoring of a scanner quality program, (3) developing task paradigms and scan session documentation, (4) establishing clinical and scanner training to ensure consistency over time, (5) developing means for uploading, storing, and monitoring of imaging and other data, (6) the use of a traveling fMRI expert and (7) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery. PMID:22314879

The oncologic outcome and immediate surgical complications of lipofilling in breast cancer patients: a multicenter study--Milan-Paris-Lyon experience of 646 lipofilling procedures.

PubMed

Petit, Jean Yves; Lohsiriwat, Visnu; Clough, Krishna B; Sarfati, Isabelle; Ihrai, Tarik; Rietjens, Mario; Veronesi, Paolo; Rossetto, Fabio; Scevola, Anna; Delay, Emmanuel

2011-08-01

Lipofilling is now performed to improve the breast contour, after both breast-conserving surgery and breast reconstruction. However, injection of fat into a previous tumor site may create a new environment for cancer and adjacent cells. There is also no international agreement regarding lipofilling after breast cancer treatment. The authors included three institutions specializing in both breast cancer treatment and breast reconstruction (European Institute of Oncology, Milan, Italy; Paris Breast Center, Paris, France; and Leon Berard Centre, Lyon, France) for a multicenter study. A collective chart review of all lipofilling procedures after breast cancer treatment was performed. From 2000 to 2010, the authors reviewed 646 lipofilling procedures from 513 patients. There were 370 mastectomy patients and 143 breast-conserving surgery patients. There were 405 patients (78.9 percent) with invasive carcinoma and 108 (21.1 percent) with carcinoma in situ. The average interval between oncologic surgical interventions and lipofilling was 39.7 months. Average follow-up after lipofilling was 19.2 months. The authors observed a complication rate of 2.8 percent (liponecrosis, 2.0 percent). Twelve radiologic images appeared after lipofilling in 119 breast-conserving surgery cases (10.1 percent). The overall oncologic event rate was 5.6 percent (3.6 percent per year). The locoregional event rate was 2.4 percent (1.5 percent per year). Lipofilling after breast cancer treatment leads to a low complication rate and does not affect radiologic follow-up after breast-conserving surgery. A prospective clinical registry including high-volume multicenter data with a long follow-up is warranted to demonstrate the oncologic safety. Until then, lipofilling should be performed in experienced hands, and a cautious oncologic follow-up protocol is advised. Therapeutic, IV [corrected].

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus.

PubMed

Sakamoto, Ana Paula; Silva, Clovis Artur; Silva, Marco Felipe Castro da; Lopes, Anandreia Simões; Russo, Gleice Clemente Souza; Sallum, Adriana Maluf Elias; Kozu, Katia; Bonfá, Eloisa; Saad-Magalhães, Claudia; Pereira, Rosa Maria Rodrigues; Len, Claudio Arnaldo; Terreri, Maria Teresa

To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p=0.008), discoid rash (16% vs. 4%, p=0.017), photosensitivity (76% vs. 45%, p=0.002) and other cutaneous vasculitides (80% vs. 19%, p<0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p=0.003), fever (32% vs. 56%, p=0.020) and hepatomegaly (4% vs. 23%, p=0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p>0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p=0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p=0.014) was significantly lower in the DV group. Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients. Copyright © 2017. Published by Elsevier Editora Ltda.

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

PubMed Central

Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

2015-01-01

Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform.

PubMed

Messroghli, Daniel R; Pickardt, Thomas; Fischer, Marcus; Opgen-Rhein, Bernd; Papakostas, Konstantin; Böcker, Dorothée; Jakob, André; Khalil, Markus; Mueller, Goetz C; Schmidt, Florian; Kaestner, Michael; Udink Ten Cate, Floris E A; Wagner, Robert; Ruf, Bettina; Kiski, Daniela; Wiegand, Gesa; Degener, Franziska; Bauer, Ulrike M M; Friede, Tim; Schubert, Stephan

2017-05-01

The aim of this registry is to provide data on age-related clinical features of suspected myocarditis and to create a study platform allowing for deriving diagnostic criteria and, at a later stage, testing therapeutic interventions in patients with myocarditis. After an initial 6-month pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry for patients from pediatric heart centers, university hospitals, and community hospitals with pediatric cardiology wards in Germany. Inclusion criteria consisted of age<18 years and hospitalization for suspected myocarditis as leading diagnosis at the discretion of the treating physician. By December 31, 2015, fifteen centers across Germany were actively participating and had enrolled 149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher proportions of males, and document a high prevalence of severe disease courses in pediatric patients with suspected myocarditis. Severe clinical courses and early adverse events were more prevalent in younger patients and were related to severely impaired leftventricular ejection fraction at initial presentation. MYKKE represents a multicenter registry and research platform for children and adolescents with suspected myocarditis that achieve steady recruitment and generate a wide range of real-world data on clinical course, diagnostic workup, and treatment of this group of patients. The baseline data reveal the presence of 2 age peaks and provide important insights into the severity of disease in children with suspected myocarditis. In the future, MYKKE might facilitate interventional substudies by providing an established collaborating network using common diagnostic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety aspects of lipidapheresis using DALI and MONET - Multicenter observational study.

PubMed

Kozik-Jaromin, Justyna; Röseler, Eberhard; Heigl, Franz; Spitthöver, Ralf; Ringel, Jens; Schmitz, Gerd; Heinzler, Rainer; Abdul-Rahman, Nadim; Leistikow, Frank; Himmelsbach, Frido; Schettler, Volker; Uhlenbusch-Körwer, Ingrid; Ramlow, Wolfgang

2017-11-01

Lipidapheresis was introduced for intractable hyperlipidemia as a more selective therapy than plasma exchange aiming to enhance efficacy and limit side-effects. Although this therapy is regarded safe, multicenter data from routine application are limited. We investigated direct adsorption of lipoproteins (DALI) and lipofiltration (MONET) regarding the short and the long-term safety aspects. This multicenter observational study prospectively evaluated 2154 DALI and 1297 MONET sessions of 122 patients during a period of 2 years. Safety parameters included clinical side-effects (adverse device effects, ADEs), technical complications, blood pressure and pulse rate. Also routinely performed laboratory parameters were documented. Analysis of laboratory parameters was not corrected for blood dilution. Overall 0.4% DALI and 0.5% MONET treatments were affected by ADE. Technical complications occurred in 2.1% and in 0.8% DALI and MONET sessions, respectively. The most frequent ADE was hypotension, and the majority of technical problems were related to vascular access. Both types of treatments led to a drop of thrombocytes in the range of 7-8%. Hematocrit and erythrocytes decreased only during the DALI treatments by about 6%. Leucocytes decreased during the DALI therapy (∼15%), whereas they increased during the MONET application (∼11%). MONET treatment was associated with a higher reduction of proteins (fibrinogen: 58% vs. 23%, albumin: 12% vs. 7%, CRP: 33% vs. 19% for MONET and DALI, respectively). Apart from severe thrombocytopenia in two DALI patients, changes of other parameters were typically transient. Under routine use the frequency of side-effects was low. Still, monitoring of blood count and proteins in chronic apheresis patients is recommended. Copyright © 2017. Published by Elsevier B.V.

Cubital tunnel syndrome: comparative results of a multicenter study of 4 surgical techniques with a mean follow-up of 92 months.

PubMed

Bacle, G; Marteau, E; Freslon, M; Desmoineaux, P; Saint-Cast, Y; Lancigu, R; Kerjean, Y; Vernet, E; Fournier, J; Corcia, P; Le Nen, D; Rabarin, F; Laulan, J

2014-06-01

Cubital tunnel syndrome is the second most frequent entrapment syndrome. Physiopathology is mixed, and treatment options are multiple, none having yet proved superior efficacy. The present retrospective multicenter study compared results and rates of complications and recurrence between the 4 main cubital tunnel syndrome treatments, to identify trends and optimize outcome. Patients presenting with primary clinical cubital tunnel syndrome diagnosed on electroneuromyography were included and operated on using 1 of the following 4 techniques: open or endoscopic in situ decompression, or subcutaneous or submuscular anterior transposition. Four specialized upper-limb surgery centers participated, each systematically performing 1 of the above procedures. Subjective and objective results and rates of complications and recurrence were compared at end of follow-up. Five hundred and two patients were included and 375 followed up for a mean 92 months (range, 9-144 months); 103 were lost to follow-up and 24 died. Whichever the procedure, more than 90% of patients were cured or showed improvement. There was a single case of scar pain at end of follow-up, managed by endoscopic decompression; there were no other long-term complications. None of the 4 techniques aggravated symptoms. There were 6 recurrences by end of follow-up: 1 associated with open in situ decompression and 5 with submuscular transposition. Surgery was effective in treating cubital tunnel syndrome. Submuscular anterior transposition was associated with recurrence. In contrast to literature reports, subcutaneous anterior transposition, which is a reliable and valid technique, was not associated with a higher complication rate than in situ decompression. Level IV. Multicenter retrospective. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study

PubMed Central

González, Hernán E.; Martínez, José R.; Vargas-Salas, Sergio; Solar, Antonieta; Veliz, Loreto; Cruz, Francisco; Arias, Tatiana; Loyola, Soledad; Horvath, Eleonora; Tala, Hernán; Traipe, Eufrosina; Meneses, Manuel; Marín, Luis; Wohllk, Nelson; Diaz, René E.; Véliz, Jesús; Pineda, Pedro; Arroyo, Patricia; Mena, Natalia; Bracamonte, Milagros; Miranda, Giovanna; Bruce, Elsa

2017-01-01

Background: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. Methods: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. Results: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64–82% and a negative predictive value of 97–99% in patients with a cancer prevalence range of 20–40%. Conclusions: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing. PMID:28521616

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

Clinical outcomes of atherectomy prior to percutaneous coronary intervention: A comparison of outcomes following rotational versus orbital atherectomy (COAP-PCI study).

PubMed

Meraj, Perwaiz M; Shlofmitz, Evan; Kaplan, Barry; Jauhar, Rajiv; Doshi, Rajkumar

2018-04-29

Because of the challenges in treating calcified coronary artery disease (CAD), lesion preparation has become increasingly important prior to percutaneous coronary intervention (PCI). Despite growing data for both rotational atherectomy (RA) and orbital atherectomy (OA), there have been no multicenter studies comparing the safety and efficacy of both. We sought to examine the clinical outcomes of patients with calcified CAD who underwent atherectomy. A total of 39 870 patients from five tertiary care hospitals who had PCI from January 2011 to January 2017 were identified. 907 patients who had RA or OA were included. This multicenter, prospectively collected observational analysis compared OA and RA. The primary end-point was myocardial infarction and safety outcomes including significant dissection, perforation, cardiac tamponade, and vascular complications. Propensity score matching (1:1) was performed to reduce selection bias. After matching, 546 patients were included in the final analysis. The primary endpoint, myocardial infarction occurred less frequently with OA compared to RA (6.7% vs 13.8%, P ≤ 0.01) in propensity score matched cohorts. Procedural safety outcomes were comparable between the groups. The secondary outcome of death on discharge occurred less in the OA group as compared with RA (0% vs 2.2%, P = 0.01). Fluoroscopy time was less in patients who were treated with OA (21.9 vs 25.6 min, P ≤ 0.01). Additional secondary outcomes were comparable between groups. In this non-randomized, multicenter comparison of contemporary atherectomy devices, OA was associated with significantly decreased in-hospital myocardial infarction and mortality after propensity score matching with decreased fluoroscopy time. © 2018, Wiley Periodicals, Inc.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Kay, Gary G; Schwartz, Howard I; Wingertzahn, Mark A; Jayawardena, Shyamalie; Rosenberg, Russell P

2016-05-01

Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Changes in sexual functioning from 6 to 12 months following traumatic brain injury: a prospective TBI model system multicenter study.

PubMed

Hanks, Robin A; Sander, Angelle M; Millis, Scott R; Hammond, Flora M; Maestas, Kacey L

2013-01-01

To investigate longitudinal changes in sexual functioning during the first year following moderate to severe traumatic brain injury (TBI). Prospective cohort study. Community. 182 persons (53 women and 129 men) with moderate to severe TBI who were admitted to 1 of 6 participating TBI Model System centers and followed in the community at 6 and 12 months after injury. Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR); Global Sexual Satisfaction Index (GSSI). Mean T-scores on the DISF-SR Arousal subscale demonstrated marginal improvement over time, with a 2.59-point increase (P = .05) from 6 to 12 months after injury. There were no significant differences over this 6-month period on the remaining DISF-SR subscales, including sexual cognition/fantasy, sexual behavior/experience, and orgasm. There was no significant change in satisfaction with sexual functioning on the GSSI from 6 months (72% satisfied) to 12 months (71% satisfied). Sexual function and satisfaction appears to be stable in those with moderate to severe TBI from 6 to 12 months after injury, with the exception of minimal improvement in arousal. These findings, to our knowledge, reflect the first evidence regarding prospective changes in sexual functioning in this population. Future research can go far to assist clinicians in treatment planning and managing patient expectations of recovery of sexual functioning after TBI.

The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

PubMed Central

Vose, Julie M.; Kelly, Jennifer L.; Young, Faith; Bernstein, Steven H.; Peterson, Derick; Rich, Lynn; Blumel, Susan; Proia, Nicole K.; Liesveld, Jane; Fisher, Richard I.; Armitage, James O.; Grant, Steven; Leonard, John P.

2011-01-01

Given the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534. PMID:21239695

Mentoring Interventions for Underrepresented Scholars in Biomedical and Behavioral Sciences: Effects on Quality of Mentoring Interactions and Discussions

PubMed Central

Lewis, Vivian; Martina, Camille A.; McDermott, Michael P.; Chaudron, Linda; Trief, Paula M.; LaGuardia, Jennifer G.; Sharp, Daryl; Goodman, Steven R.; Morse, Gene D.; Ryan, Richard M.

2017-01-01

Mentors rarely receive education about the unique needs of underrepresented scholars in the biomedical and behavioral sciences. We hypothesized that mentor-training and peer-mentoring interventions for these scholars would enrich the perceived quality and breadth of discussions between mentor–protégé dyads (i.e., mentor–protégé pairs). Our multicenter, randomized study of 150 underrepresented scholar–mentor dyads compared: 1) mentor training, 2) protégé peer mentoring, 3) combined mentor training and peer mentoring, and 4) a control condition (i.e., usual practice of mentoring). In this secondary analysis, the outcome variables were quality of dyad time and breadth of their discussions. Protégé participants were graduate students, fellows, and junior faculty in behavioral and biomedical research and healthcare. Dyads with mentor training were more likely than those without mentor training to have discussed teaching and work–life balance. Dyads with peer mentoring were more likely than those without peer mentoring to have discussed clinical care and career plans. The combined intervention dyads were more likely than controls to perceive that the quality of their time together was good/excellent. Our study supports the value of these mentoring interventions to enhance the breadth of dyad discussions and quality of time together, both important components of a good mentoring relationship. PMID:28747354

Accounting for center in the Early External Cephalic Version trials: an empirical comparison of statistical methods to adjust for center in a multicenter trial with binary outcomes.

PubMed

Reitsma, Angela; Chu, Rong; Thorpe, Julia; McDonald, Sarah; Thabane, Lehana; Hutton, Eileen

2014-09-26

Clustering of outcomes at centers involved in multicenter trials is a type of center effect. The Consolidated Standards of Reporting Trials Statement recommends that multicenter randomized controlled trials (RCTs) should account for center effects in their analysis, however most do not. The Early External Cephalic Version (EECV) trials published in 2003 and 2011 stratified by center at randomization, but did not account for center in the analyses, and due to the nature of the intervention and number of centers, may have been prone to center effects. Using data from the EECV trials, we undertook an empirical study to compare various statistical approaches to account for center effect while estimating the impact of external cephalic version timing (early or delayed) on the outcomes of cesarean section, preterm birth, and non-cephalic presentation at the time of birth. The data from the EECV pilot trial and the EECV2 trial were merged into one dataset. Fisher's exact method was used to test the overall effect of external cephalic version timing unadjusted for center effects. Seven statistical models that accounted for center effects were applied to the data. The models included: i) the Mantel-Haenszel test, ii) logistic regression with fixed center effect and fixed treatment effect, iii) center-size weighted and iv) un-weighted logistic regression with fixed center effect and fixed treatment-by-center interaction, iv) logistic regression with random center effect and fixed treatment effect, v) logistic regression with random center effect and random treatment-by-center interaction, and vi) generalized estimating equations. For each of the three outcomes of interest approaches to account for center effect did not alter the overall findings of the trial. The results were similar for the majority of the methods used to adjust for center, illustrating the robustness of the findings. Despite literature that suggests center effect can change the estimate of effect in multicenter trials, this empirical study does not show a difference in the outcomes of the EECV trials when accounting for center effect. The EECV2 trial was registered on 30 July 30 2005 with Current Controlled Trials: ISRCTN 56498577.

The Siblings With Ischemic Stroke Study (SWISS) Protocol

PubMed Central

Meschia, James F; Brown, Robert D; Brott, Thomas G; Chukwudelunzu, Felix E; Hardy, John; Rich, Stephen S

2002-01-01

Background Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. Methods Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. Discussion Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members. PMID:11882254

Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile-associated disease: An Eastern Association for the Surgery of Trauma multicenter trial.

PubMed

Ferrada, Paula; Callcut, Rachael; Zielinski, Martin D; Bruns, Brandon; Yeh, Daniel Dante; Zakrison, Tanya L; Meizoso, Jonathan P; Sarani, Babak; Catalano, Richard D; Kim, Peter; Plant, Valerie; Pasley, Amelia; Dultz, Linda A; Choudhry, Asad J; Haut, Elliott R

2017-07-01

The mortality of patients with Clostridium difficile-associated disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single-center study. To date, no reproducible results have been published. The objective of this study was to compare these two procedures in a multicentric approach to help the surgeon decide what procedure is best suited for the patient in need. This was a retrospective multicenter study conducted under the sponsorship of the Eastern Association for the Surgery of Trauma. Demographics, medical history, clinical presentation, APACHE score, and outcomes were collected. We used the Research Electronic Data Capture tool to store the data. Mann-Whitney (continuous data) and Fisher exact (categorical data) were used to compare TC with LI. Logistic regression was performed to determine predictors of mortality. A propensity score analysis was done to control for potential confounders and determine adjusted mortality rates by procedure type. We collected data from 10 centers of patients who presented with CDAD requiring surgery between July 1, 2010 and July 30, 2014. Two patients died during the surgical procedure, leaving 98 individuals in the study. The overall mortality was 32%, and 75% had postoperative complications. Median age was 64.5 years; 59% were male. Concerning preoperative patient conditions, 54% were on pressors, 47% had renal failure, and 36% had respiratory failure. When comparing TC and LI, there was no statistical difference regarding these conditions. Univariate preprocedure predictors of mortality were age, lactate, timing of operation, vasopressor use, and acute renal failure. There was no statistical difference between the APACHE score of patients undergoing either procedure (TC, 22 vs LI, 16). Adjusted mortality (controlled for preprocedure confounders) was significantly lower in the LI group (17.2% vs 39.7%; p = 0.002). This is the first multicenter study comparing TC with LI for the treatment of CDAD. In this study, LI carried less mortality than TC. In patients without contraindications, LI should be considered for the surgical treatment of CDAD. Therapeutic study, level III.

Fluid Lavage of Open Wounds (FLOW): A Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures

DTIC Science & Technology

2013-10-01

Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures PRINCIPAL...Solutions and Pressures in Patients with Open Fractures 5b. GRANT NUMBER W81XWH-12-1-0530 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kyle J. Jeray...important initial step in preventing infection in open fractures . However, there is little clinical evidence as to the best irrigation methods and additives

Rapid Detection of Staphylococcus aureus and Methicillin-Resistant S. aureus (MRSA) in Wound Specimens and Blood Cultures: Multicenter Preclinical Evaluation of the Cepheid Xpert MRSA/SA Skin and Soft Tissue and Blood Culture Assays▿

PubMed Central

Wolk, D. M.; Struelens, M. J.; Pancholi, P.; Davis, T.; Della-Latta, P.; Fuller, D.; Picton, E.; Dickenson, R.; Denis, O.; Johnson, D.; Chapin, K.

2009-01-01

A multicenter preclinical evaluation was conducted to evaluate the performance of two Cepheid Xpert assays for detection of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus. Sensitivity was 97.1% and 98.3% for MRSA in wound and blood culture specimens, respectively. Sensitivity was 100% for S. aureus from both specimen types. PMID:19144803

Multicenter Evaluation of a New Shortened Peptide Nucleic Acid Fluorescence In Situ Hybridization Procedure for Species Identification of Select Gram-Negative Bacilli from Blood Cultures▿

PubMed Central

Morgan, Margie; Marlowe, Elizabeth; Della-Latta, Phyllis; Salimnia, Hossein; Novak-Weekley, Susan; Wu, Fann; Crystal, Benjamin S.

2010-01-01

A shortened protocol for two peptide nucleic acid fluorescence in situ hybridization (PNA FISH) assays for the detection of Gram-negative bacilli from positive blood cultures was evaluated in a multicenter trial. There was 100% concordance between the two protocols for each assay (368 of 368 and 370 of 370 results) and 99.7% (367 of 368 and 369 of 370 results) agreement with routine laboratory techniques. PMID:20357212

Multicenter transversal two-phase study to determine a national prevalence of epilepsy in Algeria.

PubMed

Moualek, Dalila; Pacha, Lamia Ali; Abrouk, Samira; Kediha, Mohamed Islam; Nouioua, Sonia; Aissa, Leila Ait; Bellatache, Mounia; Belarbi, Soreya; Slimani, Saddek; Khennouf, Houria; Fellahi, Lynda; El Amine Hamimed, Mohamed; Benali, Nadia; Chekkour, Mohamed Chahine; Maamoun, Ramdane; Dameche, Rachida; Assami, Salima; Tazir, Meriem

2012-01-01

The prevalence of epilepsy in Algeria is unknown. The aims of this multicenter transversal study were to determine the national prevalence and clinical characteristics of epilepsy in the Algerian population. This two-phase study was conducted in 5 circumscriptions and included 8,046 subjects aged over 2 months who attended the randomly selected public and private primary care clinics. In the phase 1 study, a questionnaire was submitted to the sample of patients. In the phase 2 study, all potentially epileptic people were examined by neurologists and a second questionnaire was submitted, eventually assessed by appropriate investigations. Sixty-seven patients were identified as having active epilepsy, giving a crude prevalence ratio of 8.32 per 1,000 (95% CI, 6.34-10.3) and an age-adjusted prevalence ratio of 8.9 per 1,000. The highest age-specific ratio was found in patients aged 10-19 years (16.92 per 1,000). Generalized seizures (68.7%) were more common than partial seizures (29.8%). Perinatal injuries were the major leading putative causes (11.9%). The prevalence of epilepsy of 8.32 determined in this study is relatively high. These results provide new epidemiological data and suggest that epilepsy remains an important public health issue to consider in Algeria. Copyright © 2012 S. Karger AG, Basel.