ASCOT: a text mining-based web-service for efficient search and assisted creation of clinical trials.

PubMed

Korkontzelos, Ioannis; Mu, Tingting; Ananiadou, Sophia

2012-04-30

Clinical trials are mandatory protocols describing medical research on humans and among the most valuable sources of medical practice evidence. Searching for trials relevant to some query is laborious due to the immense number of existing protocols. Apart from search, writing new trials includes composing detailed eligibility criteria, which might be time-consuming, especially for new researchers. In this paper we present ASCOT, an efficient search application customised for clinical trials. ASCOT uses text mining and data mining methods to enrich clinical trials with metadata, that in turn serve as effective tools to narrow down search. In addition, ASCOT integrates a component for recommending eligibility criteria based on a set of selected protocols.

UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications, and Consent

PubMed Central

Horst, Jeremy A; Ellenikiotis, Hellene; Milgrom, Peter M

2016-01-01

The Food and Drug Administration recently cleared silver diamine fluoride for reducing tooth sensitivity. Clinical trials document arrest and prevention of dental caries by silver diamine fluoride; this off-label use is now permissible and appropriate under U.S. law. A CDT code was approved for caries arresting medicaments for 2016 to facilitate documentation and billing. We present a systematic review, clinical indications, clinical protocol, and consent procedure to guide application for caries arrest treatment. PMID:26897901

Cell engineering: spearheading the next generation in healthcare.

PubMed

Jayasinghe, Suwan N

2008-09-01

Manipulating living mammalian cells present fascinating possibilities for a plethora of applications within our healthcare. These imply several possibilities in tissue engineering and regenerative medicine, to those of a therapeutic nature. The physical sciences are increasingly playing a pivotal role in this endeavour by both advancing existing cell engineering technology and pioneering new protocols for the creation of biologically viable structures. In this paper, the author introduces several direct needle/channel/orifice-based cell engineering protocols, currently undergoing intense investigation for a whole host of bio-applications. Hence, each protocol's advantages and disadvantages are clearly identified, whilst recognizing their future biological and engineering challenges. In conclusion, a few selected biotechnological applications present possibilities where these protocols could undergo focused exploration. Successful development of these bio-protocols sees the emergence of unique future strategies within a clinical environment having far-reaching consequences for our healthcare.

A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor.

PubMed

Krug, Christian; Wiesinger, Manuel; Abken, Hinrich; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Schaft, Niels

2014-10-01

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 × 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.

Data Acquisition for a Patient-directed Intervention Protocol in the Dynamic Intensive Care Unit Setting

PubMed Central

Chlan, Linda; Patterson, Robert P.; Heiderscheit, Annie

2011-01-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicates data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. PMID:21382515

Data acquisition for a patient-directed intervention protocol in the dynamic intensive care unit setting.

PubMed

Chlan, Linda; Patterson, Robert P; Heiderscheit, Annie

2011-07-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicate data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. Copyright © 2011 Elsevier Inc. All rights reserved.

Evolution of a Patient Information Management System in a Local Area Network Environment at Loyola University of Chicago Medical Center

PubMed Central

Price, Ronald N; Chandrasekhar, Arcot J; Tamirisa, Balaji

1990-01-01

The Department of Medicine at Loyola University Medical Center (LUMC) of Chicago has implemented a local area network (LAN) based Patient Information Management System (PIMS) as part of its integrated departmental database management system. PIMS consists of related database applications encompassing demographic information, current medications, problem lists, clinical data, prior events, and on-line procedure results. Integration into the existing departmental database system permits PIMS to capture and manipulate data in other departmental applications. Standardization of clinical data is accomplished through three data tables that verify diagnosis codes, procedures codes and a standardized set of clinical data elements. The modularity of the system, coupled with standardized data formats, allowed the development of a Patient Information Protocol System (PIPS). PIPS, a userdefinable protocol processor, provides physicians with individualized data entry or review screens customized for their specific research protocols or practice habits. Physician feedback indicates that the PIMS/PIPS combination enhances their ability to collect and review specific patient information by filtering large amount of clinical data.

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

NASA Technical Reports Server (NTRS)

Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

2007-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

Clinical grade adult stem cell banking

PubMed Central

Thirumala, Sreedhar; Goebel, W Scott

2009-01-01

There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

Novel Application of a Reverse Triage Protocol Providing Increased Access to Care in an Outpatient, Primary Care Clinic Setting.

PubMed

Sacino, Amanda N; Shuster, Jonathan J; Nowicki, Kamil; Carek, Peter J; Wegman, Martin P; Listhaus, Alyson; Gibney, Joseph M; Chang, Ku-Lang

2016-02-01

As the number of patients with access to care increases, outpatient clinics will need to implement innovative strategies to maintain or enhance clinic efficiency. One viable alternative involves reverse triage. A reverse triage protocol was implemented during a student-run free clinic. Each patient's chief complaint(s) were obtained at the beginning of the clinic session and ranked by increasing complexity. "Complexity" was defined as the subjective amount of time required to provide a full, thorough evaluation of a patient. Less complex cases were prioritized first since they could be expedited through clinic processing and allow for more time and resources to be dedicated to complex cases. Descriptive statistics were used to characterize and summarize the data obtained. Categorical variables were analyzed using chi-square. A time series analysis of the outcome versus centered time in weeks was also conducted. The average number of patients seen per clinic session increased by 35% (9.5 versus 12.8) from pre-implementation of the reverse triage protocol to 6 months after the implementation of the protocol. The implementation of a reverse triage in an outpatient setting significantly increased clinic efficiency as noted by a significant increase in the number of patients seen during a clinic session.

SU-E-I-26: The CT Compatibility of a Novel Direction Modulated Brachytherapy (DMBT) Tandem Applicator for Cervical Cancer

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

Elzibak, A; Safigholi, H; Soliman, A

2015-06-15

Purpose: To examine CT metal image artifact from a novel direction-modulated brachytherapy (DMBT) tandem applicator (95% tungsten) for cervical cancer using a commercially available orthopedic metal artifact reduction (O-MAR) algorithm. Comparison to a conventional stainless steel applicator is also performed. Methods: Each applicator was placed in a water-filled phantom resembling the female pelvis and scanned in a Philips Brilliance 16-slice CT scanner using two pelvis protocols: a typical clinical protocol (120kVp, 16×0.75mm collimation, 0.692 pitch, 1.0s rotation, 350mm field of view (FOV), 600mAs, 1.5mm slices) and a protocol with a higher kVp and mAs setting useful for larger patients (140kVp,more » 16×0.75mm collimation, 0.688 pitch, 1.5s rotation, 350mm FOV, 870mAs, 1.5mm slices). Images of each tandem were acquired with and without the application of the O-MAR algorithm. Baseline scans of the phantom (no applicator) were also collected. CT numbers were quantified at distances from 5 to 30 mm away from the applicator’s edge (in increments of 5mm) using measurements at eight angles around the applicator, on three consecutive slices. Results: While the presence of both applicators degraded image quality, the DMBT applicator resulted in larger streaking artifacts and dark areas in the image compared to the stainless steel applicator. Application of the O-MAR algorithm improved all acquired images, both visually and quantitatively. The use of low and high kVp and mAs settings (120 kVp/600mAs and 140 kVp/870mAs) in conjunction with the O-MAR algorithm lead to similar CT numbers in the vicinity of the applicator and a similar reduction of the induced metal artifact. Conclusion: This work indicated that metal artifacts induced by the DMBT and the stainless steel applicator are greatly reduced when using the O-MAR algorithm, leading to better quality phantom images. The use of a high dose protocol provided similar improvements in metal artifacts compared to the clinical protocol.« less

Automated monitoring of medical protocols: a secure and distributed architecture.

PubMed

Alsinet, T; Ansótegui, C; Béjar, R; Fernández, C; Manyà, F

2003-03-01

The control of the right application of medical protocols is a key issue in hospital environments. For the automated monitoring of medical protocols, we need a domain-independent language for their representation and a fully, or semi, autonomous system that understands the protocols and supervises their application. In this paper we describe a specification language and a multi-agent system architecture for monitoring medical protocols. We model medical services in hospital environments as specialized domain agents and interpret a medical protocol as a negotiation process between agents. A medical service can be involved in multiple medical protocols, and so specialized domain agents are independent of negotiation processes and autonomous system agents perform monitoring tasks. We present the detailed architecture of the system agents and of an important domain agent, the database broker agent, that is responsible of obtaining relevant information about the clinical history of patients. We also describe how we tackle the problems of privacy, integrity and authentication during the process of exchanging information between agents.

The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders.

PubMed

Obeso, Ignacio; Cerasa, Antonio; Quattrone, Aldo

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe and painless method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment, and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols. The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson's disease (PD) with levodopa-induced dyskinesias (LIDs), essential tremor (ET) and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to "normalize" pathologically decreased or increased levels of cortical activity have given moderate progress in patient's quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.

Comparing Usual Care With a Warfarin Initiation Protocol After Mechanical Heart Valve Replacement.

PubMed

Roberts, Gregory; Razooqi, Rasha; Quinn, Stephen

2017-03-01

The immediate postoperative warfarin sensitivity for patients receiving heart valve prostheses is increased. Established warfarin initiation protocols may lack clinical applicability, resulting in dosing based on clinical judgment. To compare current practice for warfarin initiation with a known warfarin initiation protocol, with doses proportionally reduced to account for the increased postoperative sensitivity. We compared the Mechanical Heart Valve Warfarin Initiation Protocol (Protocol group) with current practice (clinical judgment-Empirical group) for patients receiving mechanical heart valves in an observational before-and-after format. End points were the time to achieve a stable therapeutic international normalized ratio (INR), doses held in the first 6 days, and overanticoagulation in the first 6 days. The Protocol group (n = 37) achieved a stable INR more rapidly than the Empirical group (n = 77; median times 5.1 and 8.7 days, respectively; P = 0.002). Multivariable analysis indicated that the Protocol group (hazard ratio [HR] = 2.22; P = 0.005) and men (HR = 1.76; P = 0.043) more rapidly achieved a stable therapeutic INR. Age, serum albumin, amiodarone, presence of severe heart failure, and surgery type had no impact. Protocol patients had fewer doses held (1.1% vs 10.1%, P < 0.001) and no difference in overanticoagulation (2.7% vs 9.1%, P = 0.27). The Mechanical Heart Valve Warfarin Initiation Protocol provided a reliable approach to initiating warfarin in patients receiving mechanical aortic or mitral valves.

Bringing DNA vaccines closer to commercial use.

PubMed

Carvalho, Joana A; Prazeres, Duarte M F; Monteiro, Gabriel A

2009-10-01

Progress in the application of DNA vaccines as an immunization protocol is evident from the increasing number of such vaccines under evaluation in clinical trials and by the recent approval of several DNA vaccine products for veterinary applications. DNA vaccine technology offers important therapeutic and commercial advantages compared with conventional approaches, including the opportunity to target pathogens characterized by significant genetic diversity using a safe immunization platform, and the ability to use a simple, rapid and well-characterized production method. However, further optimization of DNA vaccine technology through the use of improved constructs, delivery systems and immunization protocols is necessary to clinically achieve the promising results that have been demonstrated in preclinical models.

Applications of copolymer for rapid identification of bacteria in blood culture broths using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Ashizawa, Kazuho; Murata, Syota; Terada, Takashi; Ito, Daisuke; Bunya, Masaru; Watanabe, Koji; Teruuchi, Yoko; Tsuchida, Sachio; Satoh, Mamoru; Nishimura, Motoi; Matsushita, Kazuyuki; Sugama, Yuji; Nomura, Fumio

2017-08-01

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) can be used to identify pathogens in blood culture samples. However, sample pretreatment is needed for direct identification of microbes in blood culture bottles. Conventional protocols are complex and time-consuming. Therefore, in this study, we developed a method for collecting bacteria using polyallylamine-polystyrene copolymer for application in wastewater treatment technology. Using representative bacterial species Escherichia coli and Staphylococcus capitis, we found that polyallylamine-polystyrene can form visible aggregates with bacteria, which can be identified using MALDI-TOF MS. The processing time of our protocol was as short as 15min. Hemoglobin interference in MALDI spectra analysis was significantly decreased in our method compared with the conventional method. In a preliminary experiment, we evaluated the use of our protocol to identify clinical isolates from blood culture bottles. MALDI-TOF MS-based identification of 17 strains from five bacterial species (E. coli, Klebsiella pneumoniae, Enterococcus faecalis, S. aureus, and S. capitis) collected by our protocol was satisfactory. Prospective large-scale studies are needed to further evaluate the clinical application of this novel and simple method of collecting bacteria in blood culture bottles. Copyright © 2017 Elsevier B.V. All rights reserved.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases.  CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR), Office of Regulatory Affairs for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Protocol Coordinator II: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials Provides deployment of clinical support services for clinical research Streamlines protocol development timeline Provides data and document collection and compilation for regulatory filing with the FDA and other regulatory authorities Provides administrative coordination and general logistical support for regulatory activities Ensures the provision of training for investigators and associate staff to reinforce and enhance a GCP culture Provides quality assurance and quality control oversight Performs regulatory review of clinical protocols, informed consent and other clinical documents Tracks and facilitates a portfolio of protocols through each process step (IRB, RAC, DSMB, Office of Protocol Services) Assists clinical investigators in preparing clinical research protocols, including writing and formatting protocol documents and consent forms Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies Collaborates with investigators to resolve any protocol/data issues Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI Institutional Review Board (IRB) and the clinical trial sponsor or the FDA Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events Attends and prepares minutes for the Branch Protocol Review Committees For protocols that are performed with other research centers: contacts coordinators at other centers to obtain review committee approvals at these centers, maintains records of these approvals at the outside centers in the protocol files, and sends protocol amendments and other reports to the participating centers Maintains a schedule of all review committee submission deadline dates and meeting dates Assists clinical investigators in understanding and complying with the entire review process Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document management and tracking system for NCI protocols Converts protocols from Word format to PDF with bookmarks Maintains the PDF version of the most current approved version of each active clinical protocol on a central server    This position has the option to be located in Frederick or Rockville, Maryland.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR) Protocol Support Office (PSO) for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator III: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials. Provides deployment of clinical support services for clinical research. Streamlines the protocol development timeline. Provides data and documents collection and compilation for regulatory filing with the U.S. Food and Drug Administration (FDA) and other regulatory authorities.. Provides technical review and report preparation. Provides administrative coordination and general logistical support for regulatory activities. Ensures the provision of training for investigators and associate staff to reinforce and enhance a Good Clinical Practices (GCP) culture. Oversees quality assurance and quality control, performs regulatory review of clinical protocols, informed consent and other clinical documents. Tracks and facilitates a portfolio of protocols through each process step (Institutional Review Board [IRB], Regulatory Affairs Compliance [RAC], Data Safety Monitoring Board [DSMB], Office of Protocol Services). Assists clinical investigators in preparing clinical research protocols, including writing and formatting consent forms. Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies. Collaborates with investigators to resolve any protocol/data issues. Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI IRB, and the clinical trial sponsor or the FDA. Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events. Attends and prepares minutes for the Branch Protocol Review Committees. Contacts coordinators at other centers for protocols that are performed there to obtain review committee approvals at those centers, maintains records of these approvals and sends protocol amendments and other reports to the participating centers. Maintains a schedule of all review committee submission deadline dates and meeting dates. Assists clinical investigators in understanding and complying with the entire review process. Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document and tracking system for NCI protocols. Converts protocols from Word format to .pdf with bookmarks. Maintains the .pdf version of the most current approved version of each active clinical protocol on a central server. This position is located in Rockville, Maryland.

Integrating DXplain into a clinical information system using the World Wide Web.

PubMed

Elhanan, G; Socratous, S A; Cimino, J J

1996-01-01

The World Wide Web(WWW) offers a cross-platform environment and standard protocols that enable integration of various applications available on the Internet. The authors use the Web to facilitate interaction between their Web-based Clinical Information System and a decision-support system-DXplain, at the Massachusetts General Hospital-using local architecture and Common Gateway Interface programs. The current application translates patients laboratory test results into DXplain's terms to generate diagnostic hypotheses. Two different access methods are utilized for this model; Hypertext Transfer Protocol (HTTP) and TCP/IP function calls. While clinical aspects cannot be evaluated as yet, the model demonstrates the potential of Web-based applications for interaction and integration and how local architecture, with a controlled vocabulary server, can further facilitate such integration. This model serves to demonstrate some of the limitations of the current WWW technology and identifies issues such as control over Web resources and their utilization and liability issues as possible obstacles for further integration.

Minimally-invasive Ultrasound Devices for Treating Low Back Pain

NASA Astrophysics Data System (ADS)

Nau, William; Diederich, C.; Shu, R.; Kinsey, A.; Lotz, J.; Ferrier, W.; Sutton, J.; Pellegrino, R.

2006-05-01

Catheter-based ultrasound is being investigated for the potential to deliver heat to disc tissue for the treatment of discogenic low back pain. Two ultrasound applicator design configurations were tested: an intradiscal (IDUS) applicator which can be implanted directly within the disc, and an extradiscal (EDUS) applicator which is placed adjacent to the disc. In vitro heating trials were performed in human lumbar cadaveric disc segments instrumented with 24 thermocouples to obtain detailed maps of the temperature distributions. A low temperature elevation heating protocol in which the maximum temperature measured 5 mm away from the applicator is controlled to 52° C for the treatment period, and a high temperature elevation protocol (maximum temperature controlled to >70° C) were evaluated in this study. In vivo experiments were performed in sheep cervical spine using both applicator configurations, and both heating protocols. Steady-state temperature maps, and thermal doses (t43) calculated from the transient temperature data were used to assess regions of thermal damage within the disc. During the in vitro human disc studies using the high temperature protocol, temperatures were maintained at 71.5° ± 0.4°C 5 mm from an IDUS applicator implanted within the annular wall, with a maximum temperature (Tmax) of 78.6°C (t43 > 4.85 × 1010 min) measured 2 mm from the applicator. For the EDUS applicator, the temperature was maintained at 78.7° °C 5 mm from the applicator, with a Tmax of 86.3°C within 1 mm of the applicator surface. In the in vivo sheep studies, steady-state temperatures were maintained at 49.4° ± 0.3°C (t43 = 8.74 × 102 min) and 73.2° ± 0.6°C (t43 = 1.34 × 1010 min) with the IDUS applicator for the low and high temperature protocols, respectively. Using the EDUS applicator, temperatures were maintained at 54.4° ± 3.2°C (t43 = 4.11 × 104 min) and 69.4° ± 2.8°C (t43 = 2.81 × 109 min) for the two protocols. Directional heating was demonstrated with both applicator design configurations. Results from these studies demonstrated the capability to control temperature distributions within targeted regions of the disc using interstitial ultrasound with greater thermal penetration than can be achieved with the RF heating devices currently in clinical use. Thus interstitial ultrasound offers a potential alternative heating modality for the clinical management of low back pain.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator II: Provides comprehensive clinical and administrative support to the Brain Tumor Trial Collaborative, Neuro-Oncology Branch, NCI, National Institutes of Health Serves as a liaison with Principal Investigators (PIs), the associated study teams and a variety of offices associated with protocol development and approvals Orchestrates meetings with investigators and other key medical staff to identify required support Coordinates the writing and regulatory review processes that occur in tandem, facilitates the bi-directional dialogue and feedback between various teams, and assists investigators and medical writers on the production/revision of clinical research protocols Assists research staff in coordinating/navigating requirements for special circumstances and facilitates access to necessary services Facilitates initiation of intramural research by providing assistance in obtaining required approvals Coordinates with investigators and medical writers to ensure Institutional Review Board (IRB) and Food and Drug Administration (FDA) stipulations are appropriately addressed in a timely manner Provides consultation and assistance for all aspects of the protocol lifecycle including initial Investigational New Drug (IND) submission, IRB submission, continuing review applications, protocol amendments, annual reports, and protocol inactivation with IRB and FDA Tracks a portfolio of protocols through each lifecycle step; processes and tracks appropriate approvals (e.g., IRB, Data and Safety Monitoring Board, Radiation Safety, Office of Protocol Services, etc.) Provides administrative support to Scientific Review Committees (SRC), reviews proposed protocol documents to ensure they are complete, distributes to reviewers, documents meeting minutes, enters data into the IRIS database, facilitates processes to obtain approval to initiate and continue clinical research Creates, maintains and queries an IRB database of approved amendment descriptions Maintains records of the current protocol(s) version, current Informed Consent document(s), FDA Safe to Proceed designation, etc. for each IND Provides expertise in data management including data collection and analysis Develops procedural manuals for clinical trials protocols Participates in quality improvement and assurance involving International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines This position is located at the National Institutes of Health (NIH) in Bethesda, Maryland.

Application of a motivation-behavioral skills protocol in gingival lichen planus: a short-term study.

PubMed

López-Jornet, Pia; Camacho-Alonso, Fabio

2010-10-01

The main objective of the present study was to assess the efficacy of a motivation–behavioral skills protocol for plaque control in patients with gingival lichen planus. A pre- and post-test descriptive clinical study was made of 40 consecutive white patients with gingival lichen planus: five males (12.5%) and 35 females (87.5%); mean age: 57 years. A motivation–behavioral skills protocol for oral hygiene was applied, with the determination of gingival scores (gingival index, plaque extension, and Community Periodontal Index of Treatment Needs [CPITN]) and patient evaluation after 4 and 8 weeks. The clinical parameters in relation to the different forms of gingival lichen planus showed statistically significant improvements for gingival index, plaque extension, and CPITN (P <0.001) as determined 4 and 8 weeks after starting the program. The application of an active prevention program in patients with gingival lichen planus is important because it offers benefits for periodontal health. However, more long-term studies are needed to confirm the results obtained.

Adaptive change in electrically stimulated muscle: a framework for the design of clinical protocols.

PubMed

Salmons, Stanley

2009-12-01

Adult mammalian skeletal muscles have a remarkable capacity for adapting to increased use. Although this behavior is familiar from the changes brought about by endurance exercise, it is seen to a much greater extent in the response to long-term neuromuscular stimulation. The associated phenomena include a markedly increased resistance to fatigue, and this is the key to several clinical applications. However, a more rational basis is needed for designing regimes of stimulation that are conducive to an optimal outcome. In this review I examine relevant factors, such as the amount, frequency, and duty cycle of stimulation, the influence of force generation, and the animal model. From these considerations a framework emerges for the design of protocols that yield an overall functional profile appropriate to the application. Three contrasting examples illustrate the issues that need to be addressed clinically.

Development of a method for measuring femoral torsion using real-time ultrasound.

PubMed

Hafiz, Eliza; Hiller, Claire E; Nicholson, Leslie L; Nightingale, E Jean; Clarke, Jillian L; Grimaldi, Alison; Eisenhuth, John P; Refshauge, Kathryn M

2014-07-01

Excessive femoral torsion has been associated with various musculoskeletal and neurological problems. To explore this relationship, it is essential to be able to measure femoral torsion in the clinic accurately. Computerized tomography (CT) and magnetic resonance imaging (MRI) are thought to provide the most accurate measurements but CT involves significant radiation exposure and MRI is expensive. The aim of this study was to design a method for measuring femoral torsion in the clinic, and to determine the reliability of this method. Details of design process, including construction of a jig, the protocol developed and the reliability of the method are presented. The protocol developed used ultrasound to image a ridge on the greater trochanter, and a customized jig placed on the femoral condyles as reference points. An inclinometer attached to the customized jig allowed quantification of the degree of femoral torsion. Measurements taken with this protocol had excellent intra- and inter-rater reliability (ICC2,1 = 0.98 and 0.97, respectively). This method of measuring femoral torsion also permitted measurement of femoral torsion with a high degree of accuracy. This method is applicable to the research setting and, with minor adjustments, will be applicable to the clinical setting.

The clinical application of research utilization: amphotericin B.

PubMed

Reedy, A M; Shivnan, J C; Hanson, J L; Haisfield, M E; Gregory, R E

1994-05-01

To describe the first application of the research utilization process by clinical nurses using the Stetler-Marram Model of Research Utilization to the practice of amphotericin B administration; to share the findings; and to discuss issues encountered in the process and their solutions. Published articles identified through computerized literature searches, published abstracts and books, personal communication with one author, and an informal survey of other cancer centers' amphotericin B infusion practices; research articles were selected for review if studies included settings and patient populations similar to those of the authors and if they used experimental designs. Studies were reviewed for scientific merit and clinical applicability according to the Stetler-Marram model; findings were used to develop a specific nursing protocol for infusion times of amphotericin B based on clinical criteria. The Stetler-Marram model helped staff nurses decide how to apply research findings to practice, although using it was difficult and required mentorship. A research base exists for amphotericin B administration time but not for test doses or premedications to prevent or minimize side effects. Staff nurses can use the Stetler-Marram model but need resources and support from individuals, committees, and administration. A specific protocol representing a practice change was implemented and may be applicable to other settings.

MO-FG-207-03: Maximizing the Utility of Integrated PET/MRI in Clinical Applications

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

Behr, S.

2015-06-15

The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: To understand the technological advances of clinical PET/MRI systems To correctly identify clinical applicationsmore » that can benefit from PET/MRI To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.« less

Application of evidence-based dentistry: from research to clinical periodontal practice.

PubMed

Kwok, Vivien; Caton, Jack G; Polson, Alan M; Hunter, Paul G

2012-06-01

Dentists need to make daily decisions regarding patient care, and these decisions should essentially be scientifically sound. Evidence-based dentistry is meant to empower clinicians to provide the most contemporary treatment. The benefits of applying the evidence-based method in clinical practice include application of the most updated treatment and stronger reasoning to justify the treatment. A vast amount of information is readily accessible with today's digital technology, and a standardized search protocol can be developed to ensure that a literature search is valid, specific and repeatable. It involves developing a preset question (population, intervention, comparison and outcome; PICO) and search protocol. It is usually used academically to perform commissioned reviews, but it can also be applied to answer simple clinical queries. The scientific evidence thus obtained can then be considered along with patient preferences and values, clinical patient circumstances and the practitioner's experience and judgment in order to make the treatment decision. This paper describes how clinicians can incorporate evidence-based methods into patient care and presents a clinical example to illustrate the process. © 2012 John Wiley & Sons A/S.

Dosimetry applications in GATE Monte Carlo toolkit.

PubMed

Papadimitroulas, Panagiotis

2017-09-01

Monte Carlo (MC) simulations are a well-established method for studying physical processes in medical physics. The purpose of this review is to present GATE dosimetry applications on diagnostic and therapeutic simulated protocols. There is a significant need for accurate quantification of the absorbed dose in several specific applications such as preclinical and pediatric studies. GATE is an open-source MC toolkit for simulating imaging, radiotherapy (RT) and dosimetry applications in a user-friendly environment, which is well validated and widely accepted by the scientific community. In RT applications, during treatment planning, it is essential to accurately assess the deposited energy and the absorbed dose per tissue/organ of interest, as well as the local statistical uncertainty. Several types of realistic dosimetric applications are described including: molecular imaging, radio-immunotherapy, radiotherapy and brachytherapy. GATE has been efficiently used in several applications, such as Dose Point Kernels, S-values, Brachytherapy parameters, and has been compared against various MC codes which are considered as standard tools for decades. Furthermore, the presented studies show reliable modeling of particle beams when comparing experimental with simulated data. Examples of different dosimetric protocols are reported for individualized dosimetry and simulations combining imaging and therapy dose monitoring, with the use of modern computational phantoms. Personalization of medical protocols can be achieved by combining GATE MC simulations with anthropomorphic computational models and clinical anatomical data. This is a review study, covering several dosimetric applications of GATE, and the different tools used for modeling realistic clinical acquisitions with accurate dose assessment. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Enhanced protocol for real-time transmission of echocardiograms over wireless channels.

PubMed

Cavero, Eva; Alesanco, Alvaro; García, Jose

2012-11-01

This paper presents a methodology to transmit clinical video over wireless networks in real-time. A 3-D set partitioning in hierarchical trees compression prior to transmission is proposed. In order to guarantee the clinical quality of the compressed video, a clinical evaluation specific to each video modality has to be made. This evaluation indicates the minimal transmission rate necessary for an accurate diagnosis. However, the channel conditions produce errors and distort the video. A reliable application protocol is therefore proposed using a hybrid solution in which either retransmission or retransmission combined with forward error correction (FEC) techniques are used, depending on the channel conditions. In order to analyze the proposed methodology, the 2-D mode of an echocardiogram has been assessed. A bandwidth of 200 kbps is necessary to guarantee its clinical quality. The transmission using the proposed solution and retransmission and FEC techniques working separately have been simulated and compared in high-speed uplink packet access (HSUPA) and worldwide interoperability for microwave access (WiMAX) networks. The proposed protocol achieves guaranteed clinical quality for bit error rates higher than with the other protocols, being for a mobile speed of 60 km/h up to 3.3 times higher for HSUPA and 10 times for WiMAX.

Fundamentals of functional imaging II: emerging MR techniques and new methods of analysis.

PubMed

Luna, A; Martín Noguerol, T; Mata, L Alcalá

2018-05-01

Current multiparameter MRI protocols integrate structural, physiological, and metabolic information about cancer. Emerging techniques such as arterial spin-labeling (ASL), blood oxygen level dependent (BOLD), MR elastography, chemical exchange saturation transfer (CEST), and hyperpolarization provide new information and will likely be integrated into daily clinical practice in the near future. Furthermore, there is great interest in the study of tumor heterogeneity as a prognostic factor and in relation to resistance to treatment, and this interest is leading to the application of new methods of analysis of multiparametric protocols. In parallel, new oncologic biomarkers that integrate the information from MR with clinical, laboratory, genetic, and histologic findings are being developed, thanks to the application of big data and artificial intelligence. This review analyzes different emerging MR techniques that are able to evaluate the physiological, metabolic, and mechanical characteristics of cancer, as well as the main clinical applications of these techniques. In addition, it summarizes the most novel methods of analysis of functional radiologic information in oncology. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Reversal of rocuronium-induced neuromuscular blockade by sugammadex allows for optimization of neural monitoring of the recurrent laryngeal nerve.

PubMed

Lu, I-Cheng; Wu, Che-Wei; Chang, Pi-Ying; Chen, Hsiu-Ya; Tseng, Kuang-Yi; Randolph, Gregory W; Cheng, Kuang-I; Chiang, Feng-Yu

2016-04-01

The use of neuromuscular blocking agent may effect intraoperative neuromonitoring (IONM) during thyroid surgery. An enhanced neuromuscular-blockade (NMB) recovery protocol was investigated in a porcine model and subsequently clinically applied during human thyroid neural monitoring surgery. Prospective animal and retrospective clinical study. In the animal experiment, 12 piglets were injected with rocuronium 0.6 mg/kg and randomly allocated to receive normal saline, sugammadex 2 mg/kg, or sugammadex 4 mg/kg to compare the recovery of laryngeal electromyography (EMG). In a subsequent clinical application study, 50 patients who underwent thyroidectomy with IONM followed an enhanced NMB recovery protocol-rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the operation start. The train-of-four (TOF) ratio was used for continuous quantitative monitoring of neuromuscular transmission. In our porcine model, it took 49 ± 15, 13.2 ± 5.6, and 4.2 ± 1.5 minutes for the 80% recovery of laryngeal EMG after injection of saline, sugammadex 2 mg/kg, and sugammadex 4 mg/kg, respectively. In subsequent clinical human application, the TOF ratio recovered from 0 to >0.9 within 5 minutes after administration of sugammadex 2 mg/kg at the operation start. All patients had positive and high EMG amplitude at the early stage of the operation, and intubation was without difficulty in 96% of patients. Both porcine modeling and clinical human application demonstrated that sugammadex 2 mg/kg allows effective and rapid restoration of neuromuscular function suppressed by rocuronium. Implementation of this enhanced NMB recovery protocol assures optimal conditions for tracheal intubation as well as IONM in thyroid surgery. NA. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Recommendations on practice of conditioned pain modulation (CPM) testing.

PubMed

Yarnitsky, D; Bouhassira, D; Drewes, A M; Fillingim, R B; Granot, M; Hansson, P; Landau, R; Marchand, S; Matre, D; Nilsen, K B; Stubhaug, A; Treede, R D; Wilder-Smith, O H G

2015-07-01

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results. © 2014 European Pain Federation - EFIC®

Protocols for the Initial Treatment of Moderately Severe Juvenile Dermatomyositis: Results of a Children's Arthritis and Rheumatology Research Alliance Consensus Conference

PubMed Central

Huber, Adam M.; Giannini, Edward H.; Bowyer, Suzanne L.; Kim, Susan; Lang, Bianca; Lindsley, Carol B.; Pachman, Lauren M.; Pilkington, Clarissa; Reed, Ann M.; Rennebohm, Robert M.; Rider, Lisa G.; Wallace, Carol A.; Feldman, Brian M.

2010-01-01

Objective To use juvenile dermatomyositis (JDM) survey data and expert opinion to develop a small number of consensus treatment protocols which reflect current initial treatment of moderately severe JDM. Methods A consensus meeting was held in Toronto, Ontario, Canada on December 1-2, 2007. Nominal group technique was used to achieve consensus on treatment protocols which represented typical management of moderately severe JDM. Consensus was also reached on which patients these protocols would be applicable to (inclusion and exclusion criteria), initial investigations which should be done prior to initiating one of these protocols, data which should be collected to evaluate these protocols, concomitant interventions that would be required or recommended. Results Three protocols were developed which described the first 2 months of treatment. All protocols included corticosteroids and methotrexate. One protocol also included intravenous gammaglobulin. Consensus was achieved for all issues that were addressed by conference participants, although there were some areas of controversy Conclusions This study shows that it is possible to achieve consensus on the initial treatment of JDM, despite considerable variation in clinical practice. Once these protocols are extended beyond 2 months, these protocols will be available for clinical use. By using methods which account for differences between patients (confounding by indication), the comparative effectiveness of the protocols will be evaluated. In the future, the goal will be to identify the optimal treatment of moderately severe JDM. PMID:20191521

Supporting Tablet Configuration, Tracking, and Infection Control Practices in Digital Health Interventions: Study Protocol.

PubMed

Furberg, Robert D; Ortiz, Alexa M; Zulkiewicz, Brittany A; Hudson, Jordan P; Taylor, Olivia M; Lewis, Megan A

2016-06-27

Tablet-based health care interventions have the potential to encourage patient care in a timelier manner, allow physicians convenient access to patient records, and provide an improved method for patient education. However, along with the continued adoption of tablet technologies, there is a concomitant need to develop protocols focusing on the configuration, management, and maintenance of these devices within the health care setting to support the conduct of clinical research. Develop three protocols to support tablet configuration, tablet management, and tablet maintenance. The Configurator software, Tile technology, and current infection control recommendations were employed to develop three distinct protocols for tablet-based digital health interventions. Configurator is a mobile device management software specifically for iPhone operating system (iOS) devices. The capabilities and current applications of Configurator were reviewed and used to develop the protocol to support device configuration. Tile is a tracking tag associated with a free mobile app available for iOS and Android devices. The features associated with Tile were evaluated and used to develop the Tile protocol to support tablet management. Furthermore, current recommendations on preventing health care-related infections were reviewed to develop the infection control protocol to support tablet maintenance. This article provides three protocols: the Configurator protocol, the Tile protocol, and the infection control protocol. These protocols can help to ensure consistent implementation of tablet-based interventions, enhance fidelity when employing tablets for research purposes, and serve as a guide for tablet deployments within clinical settings.

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2018-01-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2017-05-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating and improving recruitment and retention in an mHealth clinical trial: an example of iterating methods during a trial.

PubMed

Pfammatter, Angela Fidler; Mitsos, Alexa; Wang, Shirlene; Hood, Susan Hammett; Spring, Bonnie

2017-01-01

Recruitment and retention strategy investigations in mHealth clinical trials are rare. Technology presents an opportunity to intensely and remotely evaluate recruitment, use of mobile apps, and retention, leading to new insights for continuous improvement of mHealth trials. The objective of this paper is to present a case study in which a trial evaluated and changed strategies during a clinical trial to improve recruitment, adherence to study protocols, and retention in the mHealth trial. In Fall 2015, the NUYou trial enrolled 150 college freshmen in an mHealth protocol. Three months after study initiation, NUYou struggled to meet recruitment goals and maintain anticipated usage levels of the study smartphone application. Two sets of data were collected to improve recruitment and retention: a survey about recruitment was sent to the target population and surveys regarding usability of the app was sent to the study sample. Survey results informed improvements in recruitment strategies, the study retention protocol, and the smartphone application. Survey results revealed several insights including misunderstanding components of the trial by potential participants, low perceived usefulness of the app, and little recall or impact of the incentive structure. After implementation of user-centered improvements, the second cohort of NUYou recruitment in the fall of 2016 produced an equal sample size in 4 weeks less time. Winter quarter of 2016 compared to 2017 demonstrated an improvement in retention via app use and completion of weekly in-app surveys. Recruitment and retention in clinical trials continues to be a critical challenge and mHealth trials may present both unique challenges and opportunities. To our knowledge, this is the first study to describe a systematic evaluation followed by changes and further evaluation to recruitment, use of the mHealth application, adherence to study protocol, and retention during an mHealth clinical trial. Future work should adopt and explicitly study these processes to optimize both enrollment and retention in these types of trials to preserve validity and reliability of research results.

21 CFR 312.320 - Treatment IND or treatment protocol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... clinical trial under an IND designed to support a marketing application for the expanded access use, or (ii) All clinical trials of the drug have been completed; and (2) Marketing status. The sponsor is actively pursuing marketing approval of the drug for the expanded access use with due diligence; and (3) Evidence...

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

Jansen, F.

The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: To understand the technological advances of clinical PET/MRI systems To correctly identify clinical applicationsmore » that can benefit from PET/MRI To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.« less

Dedicated dental volumetric and total body multislice computed tomography: a comparison of image quality and radiation dose

NASA Astrophysics Data System (ADS)

Strocchi, Sabina; Colli, Vittoria; Novario, Raffaele; Carrafiello, Gianpaolo; Giorgianni, Andrea; Macchi, Aldo; Fugazzola, Carlo; Conte, Leopoldo

2007-03-01

Aim of this work is to compare the performances of a Xoran Technologies i-CAT Cone Beam CT for dental applications with those of a standard total body multislice CT (Toshiba Aquilion 64 multislice) used for dental examinations. Image quality and doses to patients have been compared for the three main i-CAT protocols, the Toshiba standard protocol and a Toshiba modified protocol. Images of two phantoms have been acquired: a standard CT quality control phantom and an Alderson Rando ® anthropomorphic phantom. Image noise, Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR) and geometric accuracy have been considered. Clinical image quality was assessed. Effective dose and doses to main head and neck organs were evaluated by means of thermo-luminescent dosimeters (TLD-100) placed in the anthropomorphic phantom. A Quality Index (QI), defined as the ratio of squared CNR to effective dose, has been evaluated. The evaluated effective doses range from 0.06 mSv (i-CAT 10 s protocol) to 2.37 mSv (Toshiba standard protocol). The Toshiba modified protocol (halved tube current, higher pitch value) imparts lower effective dose (0.99 mSv). The conventional CT device provides lower image noise and better SNR, but clinical effectiveness similar to that of dedicated dental CT (comparable CNR and clinical judgment). Consequently, QI values are much higher for this second CT scanner. No geometric distortion has been observed with both devices. As a conclusion, dental volumetric CT supplies adequate image quality to clinical purposes, at doses that are really lower than those imparted by a conventional CT device.

Mobile phone-based clinical guidance for rural health providers in India.

PubMed

Gautham, Meenakshi; Iyengar, M Sriram; Johnson, Craig W

2015-12-01

There are few tried and tested mobile technology applications to enhance and standardize the quality of health care by frontline rural health providers in low-resource settings. We developed a media-rich, mobile phone-based clinical guidance system for management of fevers, diarrhoeas and respiratory problems by rural health providers. Using a randomized control design, we field tested this application with 16 rural health providers and 128 patients at two rural/tribal sites in Tamil Nadu, Southern India. Protocol compliance for both groups, phone usability, acceptability and patient feedback for the experimental group were evaluated. Linear mixed-model analyses showed statistically significant improvements in protocol compliance in the experimental group. Usability and acceptability among patients and rural health providers were very high. Our results indicate that mobile phone-based, media-rich procedural guidance applications have significant potential for achieving consistently standardized quality of care by diverse frontline rural health providers, with patient acceptance. © The Author(s) 2014.

Supporting Tablet Configuration, Tracking, and Infection Control Practices in Digital Health Interventions: Study Protocol

PubMed Central

Furberg, Robert D; Zulkiewicz, Brittany A; Hudson, Jordan P; Taylor, Olivia M; Lewis, Megan A

2016-01-01

Background Tablet-based health care interventions have the potential to encourage patient care in a timelier manner, allow physicians convenient access to patient records, and provide an improved method for patient education. However, along with the continued adoption of tablet technologies, there is a concomitant need to develop protocols focusing on the configuration, management, and maintenance of these devices within the health care setting to support the conduct of clinical research. Objective Develop three protocols to support tablet configuration, tablet management, and tablet maintenance. Methods The Configurator software, Tile technology, and current infection control recommendations were employed to develop three distinct protocols for tablet-based digital health interventions. Configurator is a mobile device management software specifically for iPhone operating system (iOS) devices. The capabilities and current applications of Configurator were reviewed and used to develop the protocol to support device configuration. Tile is a tracking tag associated with a free mobile app available for iOS and Android devices. The features associated with Tile were evaluated and used to develop the Tile protocol to support tablet management. Furthermore, current recommendations on preventing health care–related infections were reviewed to develop the infection control protocol to support tablet maintenance. Results This article provides three protocols: the Configurator protocol, the Tile protocol, and the infection control protocol. Conclusions These protocols can help to ensure consistent implementation of tablet-based interventions, enhance fidelity when employing tablets for research purposes, and serve as a guide for tablet deployments within clinical settings. PMID:27350013

MatMRI and MatHIFU: software toolboxes for real-time monitoring and control of MR-guided HIFU

PubMed Central

2013-01-01

Background The availability of open and versatile software tools is a key feature to facilitate pre-clinical research for magnetic resonance imaging (MRI) and magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) and expedite clinical translation of diagnostic and therapeutic medical applications. In the present study, two customizable software tools that were developed at the Thunder Bay Regional Research Institute are presented for use with both MRI and MR-HIFU. Both tools operate in a MATLAB®; environment. The first tool is named MatMRI and enables real-time, dynamic acquisition of MR images with a Philips MRI scanner. The second tool is named MatHIFU and enables the execution and dynamic modification of user-defined treatment protocols with the Philips Sonalleve MR-HIFU therapy system to perform ultrasound exposures in MR-HIFU therapy applications. Methods MatMRI requires four basic steps: initiate communication, subscribe to MRI data, query for new images, and unsubscribe. MatMRI can also pause/resume the imaging and perform real-time updates of the location and orientation of images. MatHIFU requires four basic steps: initiate communication, prepare treatment protocol, and execute treatment protocol. MatHIFU can monitor the state of execution and, if required, modify the protocol in real time. Results Four applications were developed to showcase the capabilities of MatMRI and MatHIFU to perform pre-clinical research. Firstly, MatMRI was integrated with an existing small animal MR-HIFU system (FUS Instruments, Toronto, Ontario, Canada) to provide real-time temperature measurements. Secondly, MatMRI was used to perform T2-based MR thermometry in the bone marrow. Thirdly, MatHIFU was used to automate acoustic hydrophone measurements on a per-element basis of the 256-element transducer of the Sonalleve system. Finally, MatMRI and MatHIFU were combined to produce and image a heating pattern that recreates the word ‘HIFU’ in a tissue-mimicking heating phantom. Conclusions MatMRI and MatHIFU leverage existing MRI and MR-HIFU clinical platforms to facilitate pre-clinical research. MatMRI substantially simplifies the real-time acquisition and processing of MR data. MatHIFU facilitates the testing and characterization of new therapy applications using the Philips Sonalleve clinical MR-HIFU system. Under coordination with Philips Healthcare, both MatMRI and MatHIFU are intended to be freely available as open-source software packages to other research groups. PMID:25512856

Design of a Clinical Information Management System to Support DNA Analysis Laboratory Operation

PubMed Central

Dubay, Christopher J.; Zimmerman, David; Popovich, Bradley

1995-01-01

The LabDirector system has been developed at the Oregon Health Sciences University to support the operation of our clinical DNA analysis laboratory. Through an iterative design process which has spanned two years, we have produced a system that is both highly tailored to a clinical genetics production laboratory and flexible in its implementation, to support the rapid growth and change of protocols and methodologies in use in the field. The administrative aspects of the system are integrated with an enterprise schedule management system. The laboratory side of the system is driven by a protocol modeling and execution system. The close integration between these two aspects of the clinical laboratory facilitates smooth operations, and allows management to accurately measure costs and performance. The entire application has been designed and documented to provide utility to a wide range of clinical laboratory environments.

Procalcitonin-guided antibiotic treatment in critically ill patients.

PubMed

Hohn, Andreas; Heising, Bernhard; Schütte, Jan-Karl; Schroeder, Olaf; Schröder, Stefan

2017-02-01

In critically ill patients, length of antibiotic treatment can be effectively guided by procalcitonin (PCT) protocols. International sepsis guidelines and guidelines on antibiotic stewardship strategies recommend PCT as helpful laboratory marker for a rational use of antibiotics. A number of studies and meta-analyses have confirmed the effectiveness of PCT-protocols for shortening antibiotic treatment without compromising clinical outcome in critically ill patients. But in clinical practice, there is still uncertainty how to interpret PCT levels and how to adjust antibiotic treatment in various infectious situations, especially in the perioperative period. This narrative review gives an overview on the application of PCT-protocols in critically ill patients with severe bacterial infections on the basis of 5 case reports and the available literature. Beside strengths and limitations of this biomarker, also varying kinetics and different maximum values with regard to the infectious focus and pathogens are discussed. PCT-guided antibiotic treatment appears to be safe and effective. Most of the studies revealed a shorter antibiotic treatment without negative clinical outcomes. Cost effectiveness is still a matter of debate and effects on bacterial resistance due to shorter treatments, possible lower rates of drug-related adverse events, or decreased rates of Clostridium difficile infections are not yet evaluated. Guidance of antibiotic treatment can effectively be supported by PCT-protocols. However, it is important to consider the limitations of this biomarker and to use PCT protocols along with antibiotic stewardship programmes and regular clinical rounds together with infectious diseases specialists.

XXIst century magnetotherapy.

PubMed

Markov, M

2015-09-01

This paper discusses the state of the art therapeutic application of magnetic and electromagnetic fields (EMF) in treatment of various medical problems - from pain relief to musculoskeletal trauma, to vascular and endocrine disorders. The paper describes problems related to physical parameters of used fields, biophysical dosimetry, clinical protocols, and safety of the device operators. Clinical benefits and mechanisms of action are also discussed.

Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens

PubMed Central

Loudig, Olivier; Wang, Tao; Ye, Kenny; Lin, Juan; Wang, Yihong; Ramnauth, Andrew; Liu, Christina; Stark, Azadeh; Chitale, Dhananjay; Greenlee, Robert; Multerer, Deborah; Honda, Stacey; Daida, Yihe; Spencer Feigelson, Heather; Glass, Andrew; Couch, Fergus J.; Rohan, Thomas; Ben-Dov, Iddo Z.

2017-01-01

Formalin-fixed paraffin-embedded (FFPE) specimens, when used in conjunction with patient clinical data history, represent an invaluable resource for molecular studies of cancer. Even though nucleic acids extracted from archived FFPE tissues are degraded, their molecular analysis has become possible. In this study, we optimized a laboratory-based next-generation sequencing barcoded cDNA library preparation protocol for analysis of small RNAs recovered from archived FFPE tissues. Using matched fresh and FFPE specimens, we evaluated the robustness and reproducibility of our optimized approach, as well as its applicability to archived clinical specimens stored for up to 35 years. We then evaluated this cDNA library preparation protocol by performing a miRNA expression analysis of archived breast ductal carcinoma in situ (DCIS) specimens, selected for their relation to the risk of subsequent breast cancer development and obtained from six different institutions. Our analyses identified six miRNAs (miR-29a, miR-221, miR-375, miR-184, miR-363, miR-455-5p) differentially expressed between DCIS lesions from women who subsequently developed an invasive breast cancer (cases) and women who did not develop invasive breast cancer within the same time interval (control). Our thorough evaluation and application of this laboratory-based miRNA sequencing analysis indicates that the preparation of small RNA cDNA libraries can reliably be performed on older, archived, clinically-classified specimens. PMID:28335433

Combining novel technologies with improved logistics to reduce hemodialysis vascular access dysfunction.

PubMed

Roy-Chaudhury, P; Lee, T; Duncan, H; El-Khatib, M

2009-01-01

Hemodialysis (HD) vascular access dysfunction is currently a huge clinical problem for which there are no effective therapies. There are, however, a number of promising technologies that are currently at the experimental or clinical trial stage. We believe that the application of these novel technologies in combination with better clinical protocols for vascular access care could significantly reduce the current problems associated with HD vascular access.

Expanding Role of Data Science and Bioinformatics in Drug Discovery and Development.

PubMed

Fingert, Howard J

2018-01-01

Numerous barriers have been identified which detract from successful applications of clinical trial data and platforms. Despite the challenges, opportunities are growing to advance compliance, quality, and practical applications through top-down establishment of guiding principles, coupled with bottom-up approaches to promote data science competencies among data producers. Recent examples of successful applications include modern treatments for hematologic malignancies, developed with support from public-private partnerships, guiding principles for data-sharing, standards for protocol designs and data management, digital technologies, and quality analytics. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Vestibular rehabilitation: clinical benefits to patients with Parkinson's disease.

PubMed

Zeigelboim, Bianca Simone; Klagenberg, Karlin Fabianne; Teive, Hélio A Ghizoni; Munhoz, Renato Puppi; Martins-Bassetto, Jackeline

2009-06-01

To evaluate the effectiveness of the vestibular rehabilitation (VR) exercises by means of an assessment before and after the application of the Brazilian version of the Dizziness Handicap Inventory (DHI) questionnaire. Twelve patients were studied, the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluation, and the application of the DHI before and after the VR. Clinically resting tremors and subjective postural instability were the motor complaints most frequently associated with complaints of vertigo in 12 cases (100%); in the vestibular exam, all the patients presented abnormalities, frequently from the uni and bilateral peripheral vestibular deficiency syndromes in 10 cases (83.3%); there was significant improvement in the physical, functional and emotional aspects of the DHI after the completion of the VR. The VR following the Cawthorne and Cooksey protocol were shown to be useful in managing subjective complaints of several aspects evaluated in this protocol.

Standardizing data exchange for clinical research protocols and case report forms: An assessment of the suitability of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM).

PubMed

Huser, Vojtech; Sastry, Chandan; Breymaier, Matthew; Idriss, Asma; Cimino, James J

2015-10-01

Efficient communication of a clinical study protocol and case report forms during all stages of a human clinical study is important for many stakeholders. An electronic and structured study representation format that can be used throughout the whole study life-span can improve such communication and potentially lower total study costs. The most relevant standard for representing clinical study data, applicable to unregulated as well as regulated studies, is the Operational Data Model (ODM) in development since 1999 by the Clinical Data Interchange Standards Consortium (CDISC). ODM's initial objective was exchange of case report forms data but it is increasingly utilized in other contexts. An ODM extension called Study Design Model, introduced in 2011, provides additional protocol representation elements. Using a case study approach, we evaluated ODM's ability to capture all necessary protocol elements during a complete clinical study lifecycle in the Intramural Research Program of the National Institutes of Health. ODM offers the advantage of a single format for institutions that deal with hundreds or thousands of concurrent clinical studies and maintain a data warehouse for these studies. For each study stage, we present a list of gaps in the ODM standard and identify necessary vendor or institutional extensions that can compensate for such gaps. The current version of ODM (1.3.2) has only partial support for study protocol and study registration data mainly because it is outside the original development goal. ODM provides comprehensive support for representation of case report forms (in both the design stage and with patient level data). Inclusion of requirements of observational, non-regulated or investigator-initiated studies (outside Food and Drug Administration (FDA) regulation) can further improve future revisions of the standard. Published by Elsevier Inc.

MO-FG-207-00: Technological Advances in PET/MR Imaging

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

NONE

2015-06-15

The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: To understand the technological advances of clinical PET/MRI systems To correctly identify clinical applicationsmore » that can benefit from PET/MRI To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.« less

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

PubMed

Zhang, Yan; Phy, Jennifer; Scott-Johnson, Chris; Garos, Sheila; Orlando, Jennie; Prien, Samuel; Huang, Jaou-Chen

2017-04-04

The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. ClinicalTrials NCT02591186 registered on October 7, 2015.

SU-F-R-11: Designing Quality and Safety Informatics Through Implementation of a CT Radiation Dose Monitoring Program

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

Wilson, JM; Samei, E; Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, NC

2016-06-15

Purpose: Recent legislative and accreditation requirements have driven rapid development and implementation of CT radiation dose monitoring solutions. Institutions must determine how to improve quality, safety, and consistency of their clinical performance. The purpose of this work was to design a strategy and meaningful characterization of results from an in-house, clinically-deployed dose monitoring solution. Methods: A dose monitoring platform was designed by our imaging physics group that focused on extracting protocol parameters, dose metrics, and patient demographics and size. Compared to most commercial solutions, which focus on individual exam alerts and global thresholds, the program sought to characterize overall consistencymore » and targeted thresholds based on eight analytic interrogations. Those were based on explicit questions related to protocol application, national benchmarks, protocol and size-specific dose targets, operational consistency, outliers, temporal trends, intra-system variability, and consistent use of electronic protocols. Using historical data since the start of 2013, 95% and 99% intervals were used to establish yellow and amber parameterized dose alert thresholds, respectively, as a function of protocol, scanner, and size. Results: Quarterly reports have been generated for three hospitals for 3 quarters of 2015 totaling 27880, 28502, 30631 exams, respectively. Four adult and two pediatric protocols were higher than external institutional benchmarks. Four protocol dose levels were being inconsistently applied as a function of patient size. For the three hospitals, the minimum and maximum amber outlier percentages were [1.53%,2.28%], [0.76%,1.8%], [0.94%,1.17%], respectively. Compared with the electronic protocols, 10 protocols were found to be used with some inconsistency. Conclusion: Dose monitoring can satisfy requirements with global alert thresholds and patient dose records, but the real value is in optimizing patient-specific protocols, balancing image quality trade-offs that dose-reduction strategies promise, and improving the performance and consistency of a clinical operation. Data plots that capture patient demographics and scanner performance demonstrate that value.« less

BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill.

PubMed

Lichtenstein, Daniel A

2015-06-01

This review article describes two protocols adapted from lung ultrasound: the bedside lung ultrasound in emergency (BLUE)-protocol for the immediate diagnosis of acute respiratory failure and the fluid administration limited by lung sonography (FALLS)-protocol for the management of acute circulatory failure. These applications require the mastery of 10 signs indicating normal lung surface (bat sign, lung sliding, A-lines), pleural effusions (quad and sinusoid sign), lung consolidations (fractal and tissue-like sign), interstitial syndrome (lung rockets), and pneumothorax (stratosphere sign and the lung point). These signs have been assessed in adults, with diagnostic accuracies ranging from 90% to 100%, allowing consideration of ultrasound as a reasonable bedside gold standard. In the BLUE-protocol, profiles have been designed for the main diseases (pneumonia, congestive heart failure, COPD, asthma, pulmonary embolism, pneumothorax), with an accuracy > 90%. In the FALLS-protocol, the change from A-lines to lung rockets appears at a threshold of 18 mm Hg of pulmonary artery occlusion pressure, providing a direct biomarker of clinical volemia. The FALLS-protocol sequentially rules out obstructive, then cardiogenic, then hypovolemic shock for expediting the diagnosis of distributive (usually septic) shock. These applications can be done using simple grayscale machines and one microconvex probe suitable for the whole body. Lung ultrasound is a multifaceted tool also useful for decreasing radiation doses (of interest in neonates where the lung signatures are similar to those in adults), from ARDS to trauma management, and from ICUs to points of care. If done in suitable centers, training is the least of the limitations for making use of this kind of visual medicine.

Novel Instruments for the Implementation of Electrochemotherapy Protocols: From Bench Side to Veterinary Clinic.

PubMed

Spugnini, Enrico P; Fais, Stefano; Azzarito, Tommaso; Baldi, Alfonso

2017-03-01

Electrochemotherapy (ECT) is a medical strategy that allows an increased efficacy of chemotherapy agents after the application of permeabilizing electric pulses having appropriate characteristics (form, voltage, frequency). In the past 10 years, the clinical efficacy of this therapeutic approach in several spontaneous models of tumors in animals has been shown. Moreover, some of the molecular and cellular mechanisms responsible for this phenomenon have been elucidated. Our group has been deeply involved in the development of new ECT protocols for companion animals, implementing the use of the technique as first line treatment, and evaluating different chemotherapy agents in laboratory animals as well as pets. This article summarizes the most important advances in veterinary ECT, including the development of novel equipment, therapeutic protocols, and their translation to humans. J. Cell. Physiol. 232: 490-495, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

University of Washington Prostate Cancer Clinical Trials Consortium Application

DTIC Science & Technology

2011-04-01

13-25 Appendix 1: Protocol Evaluation Form Appendix 2: Community Symposia Flyer Appendix 3: Publications...Network Affiliate partners in the community . These and selected local practices receive quarterly correspondence that reviews our open clinical...studies: 09-002 (COU 301), 09-003 (AFFIRM), 09-004 (S0421), 09-005 (COU 302), 09-006 (doc dasatinib). Task 3. Maintain Communications with Consortium

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

Using information technology to improve the management of chronic disease.

PubMed

Celler, Branko G; Lovell, Nigel H; Basilakis, Jim

2003-09-01

Information and communications technology (ICT) is increasingly being used in management of chronic illness to facilitate shared services (virtual health networks and electronic health records), knowledge management (care rules and protocols, scheduling, information directories), as well as consumer-based health education and evidence-based clinical protocols. Common applications of ICT include home monitoring of vital signs for patients with chronic disease, as well as replacing home visits by nurses in person with telemedicine videophone consultations. A patient-managed Home Telecare System with integrated clinical signs monitoring, automated scheduling and medication reminders, as well as access to health education and daily logs, is presented as an example of ICT use for chronic disease self-management. A clinical case study demonstrates how early identification of adverse trends in clinical signs recorded in the home can either avoid hospital readmission or reduce the length of hospital stay.

Using of WHO guidelines for the management of severe malnutrition to cases of marasmus and kwashiorkor in a Colombia children's hospital.

PubMed

Ramírez Prada, D; Delgado, G; Hidalgo Patiño, C A; Pérez-Navero, J; Gil Campos, M

2011-01-01

In 2007, the Hospital Infantil Los Ángeles (HILA) in Colombia implemented a slightly-modified version of the WHO guidelines for the diagnosis and management of malnutrition during childhood. To evaluate the efficacy of the WHO-HILA protocol in children hospitalized with severe, chronic marasmus and kwashiorkor malnutrition (MS-KWK) in 2007 and 2008. In this descriptive retrospective study the records of 100 children hospitalized with MSKWK were initially evaluated. Of these, 30 fulfilled the inclusion criteria: children of both sexes with a primary diagnosis of MS-KWK. Patients with any chronic disease liable to cause malnutrition were excluded. Anthropometric parameters, clinical signs and biochemical indicators of malnutrition were assessed upon admission and again at discharge following application of the WHO guidelines. Univariate analysis was performed for each study variable; serum hemoglobin and albumin levels on admission and at discharge were compared, and data were subjected to bivariate analysis. Marasmus was diagnosed in 23.3% of children, kwashiorkor in 73.3% and marasmic kwashiorkor in 3.3%. The major clinical findings were: edema (70%), emaciation (40%), "flag sign" hair (42.86%), low serum albumin (93%) and anemia (80%). Thirteen children following the WHO-HILA protocol showed a significant nutritional status improvement (p<0.05), whereas no improvement was noted in the 17 children not treated according to the protocol. Application of the WHO-HILA protocol was associated with reduced morbimortality in children with marasmus-kwashiorkor malnutrition. Implementation of this protocol should therefore be considered in all children´s hospitals in countries where this disease is prevalent.

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation.

PubMed

Lee, W P Andrew; Shores, Jaimie T; Brandacher, Gerald

2018-05-18

 To achieve a favorable risk-benefit balance for hand transplantation, an immunomodulatory protocol was developed in the laboratory and translated to clinical application.  Following donor bone marrow infusion into transplant recipients, hand and arm allografts have been maintained on low-dose tacrolimus monotherapy.  Good-to-excellent functional recovery has been achieved in patients compliant with medication and therapy, thus restoring autonomous and productive lives.  The risk-benefit balance can be tilted in favor of the hand transplant recipients by using an immunomodulatory protocol with minimum immunosuppression. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A protocol proposition of cell therapy for the treatment of chronic obstructive pulmonary disease.

PubMed

Ribeiro-Paes, J T; Stessuk, T; Marcelino, M; Faria, C; Marinelli, T; Ribeiro-Paes, M J

2014-01-01

The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Security analysis of standards-driven communication protocols for healthcare scenarios.

PubMed

Masi, Massimiliano; Pugliese, Rosario; Tiezzi, Francesco

2012-12-01

The importance of the Electronic Health Record (EHR), that stores all healthcare-related data belonging to a patient, has been recognised in recent years by governments, institutions and industry. Initiatives like the Integrating the Healthcare Enterprise (IHE) have been developed for the definition of standard methodologies for secure and interoperable EHR exchanges among clinics and hospitals. Using the requisites specified by these initiatives, many large scale projects have been set up for enabling healthcare professionals to handle patients' EHRs. The success of applications developed in these contexts crucially depends on ensuring such security properties as confidentiality, authentication, and authorization. In this paper, we first propose a communication protocol, based on the IHE specifications, for authenticating healthcare professionals and assuring patients' safety. By means of a formal analysis carried out by using the specification language COWS and the model checker CMC, we reveal a security flaw in the protocol thus demonstrating that to simply adopt the international standards does not guarantee the absence of such type of flaws. We then propose how to emend the IHE specifications and modify the protocol accordingly. Finally, we show how to tailor our protocol for application to more critical scenarios with no assumptions on the communication channels. To demonstrate feasibility and effectiveness of our protocols we have fully implemented them.

MO-FG-207-01: Technological Advances and Challenges: Experience with the First Integrated Whole-Body PET/MRI

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

Laforest, R.

2015-06-15

The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: To understand the technological advances of clinical PET/MRI systems To correctly identify clinical applicationsmore » that can benefit from PET/MRI To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.« less

DNA damage in blood cells exposed to low-level lasers.

PubMed

Sergio, Luiz Philippe da Silva; Silva, Ana Paula Almeida da; Amorim, Philipi Freitas; Campos, Vera Maria Araújo; Magalhães, Luis Alexandre Gonçalves; de Paoli, Flavia; de Souza da Fonseca, Adenilson

2015-04-01

In regenerative medicine, there are increasing applications of low-level lasers in therapeutic protocols for treatment of diseases in soft and in bone tissues. However, there are doubts about effects on DNA, and an adequate dosimetry could improve the safety of clinical applications of these lasers. This work aimed to evaluate DNA damage in peripheral blood cells of Wistar rats induced by low-level red and infrared lasers at different fluences, powers, and emission modes according to therapeutic protocols. Peripheral blood samples were exposed to lasers and DNA damage was accessed by comet assay. In other experiments, DNA damage was accessed in blood cells by modified comet assay using formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III enzymes. Data show that exposure to low-level red and infrared lasers induce DNA damage depending on fluence, power and emission mode, which are targeted by Fpg and endonuclease III. Oxidative DNA damage should be considered for therapeutic efficacy and patient safety in clinical applications based on low-level red and infrared lasers. © 2015 Wiley Periodicals, Inc.

Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

PubMed

Charvet, Leigh E; Kasschau, Margaret; Datta, Abhishek; Knotkova, Helena; Stevens, Michael C; Alonzo, Angelo; Loo, Colleen; Krull, Kevin R; Bikson, Marom

2015-01-01

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using (31)P magnetic resonance spectroscopy.

PubMed

Sleigh, Alison; Lupson, Victoria; Thankamony, Ajay; Dunger, David B; Savage, David B; Carpenter, T Adrian; Kemp, Graham J

2016-01-11

The growing recognition of diseases associated with dysfunction of mitochondria poses an urgent need for simple measures of mitochondrial function. Assessment of the kinetics of replenishment of the phosphocreatine pool after exercise using (31)P magnetic resonance spectroscopy can provide an in vivo measure of mitochondrial function; however, the wider application of this technique appears limited by complex or expensive MR-compatible exercise equipment and protocols not easily tolerated by frail participants or those with reduced mental capacity. Here we describe a novel in-scanner exercise method which is patient-focused, inexpensive, remarkably simple and highly portable. The device exploits an MR-compatible high-density material (BaSO4) to form a weight which is attached directly to the ankle, and a one-minute dynamic knee extension protocol produced highly reproducible measurements of post-exercise PCr recovery kinetics in both healthy subjects and patients. As sophisticated exercise equipment is unnecessary for this measurement, our extremely simple design provides an effective and easy-to-implement apparatus that is readily translatable across sites. Its design, being tailored to the needs of the patient, makes it particularly well suited to clinical applications, and we argue the potential of this method for investigating in vivo mitochondrial function in new cohorts of growing clinical interest.

Mapping Evidence-Based Treatments for Children and Adolescents: Application of the Distillation and Matching Model to 615 Treatments from 322 Randomized Trials

ERIC Educational Resources Information Center

Chorpita, Bruce F.; Daleiden, Eric L.

2009-01-01

This study applied the distillation and matching model to 322 randomized clinical trials for child mental health treatments. The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies, referred to as practice elements. Practice elements were then summarized in…

Publication trends of study protocols in rehabilitation.

PubMed

Jesus, Tiago S; Colquhoun, Heather L

2017-09-04

Growing evidence points for the need to publish study protocols in the health field. To observe whether the growing interest in publishing study protocols in the broader health field has been translated into increased publications of rehabilitation study protocols. Observational study using publication data and its indexation in PubMed. Not applicable. Not applicable. PubMed was searched with appropriate combinations of Medical Subject Headings up to December 2014. The effective presence of study protocols was manually screened. Regression models analyzed the yearly growth of publications. Two-sample Z-tests analyzed whether the proportion of Systematic Reviews (SRs) and Randomized Controlled Trials (RCTs) among study protocols differed from that of the same designs for the broader rehabilitation research. Up to December 2014, 746 publications of rehabilitation study protocols were identified, with an exponential growth since 2005 (r2=0.981; p<0.001). RCT protocols were the most common among rehabilitation study protocols (83%), while RCTs were significantly more prevalent among study protocols than among the broader rehabilitation research (83% vs. 35.8%; p<0.001). For SRs, the picture was reversed: significantly less common among study protocols (2.8% vs. 9.3%; p<0.001). Funding was more often reported by rehabilitation study protocols than the broader rehabilitation research (90% vs. 53.1%; p<0.001). Rehabilitation journals published a significantly lower share of rehabilitation study protocols than they did for the broader rehabilitation research (1.8% vs.16.7%; p<0.001). Identifying the reasons for these discrepancies and reverting unwarranted disparities (e.g. low rate of publication for rehabilitation SR protocols) are likely new avenues for rehabilitation research and its publication. SRs, particularly those aggregating RCT results, are considered the best standard of evidence to guide rehabilitation clinical practice; however, that standard can be improved in rigor and/or transparency if the publications of rehabilitation SRs protocols become more common.

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS).

PubMed

Kasschau, Margaret; Sherman, Kathleen; Haider, Lamia; Frontario, Ariana; Shaw, Michael; Datta, Abhishek; Bikson, Marom; Charvet, Leigh

2015-12-26

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.

Effectiveness of a mobile cooperation intervention during the clinical practicum of nursing students: a parallel group randomized controlled trial protocol.

PubMed

Strandell-Laine, Camilla; Saarikoski, Mikko; Löyttyniemi, Eliisa; Salminen, Leena; Suomi, Reima; Leino-Kilpi, Helena

2017-06-01

The aim of this study was to describe a study protocol for a study evaluating the effectiveness of a mobile cooperation intervention to improve students' competence level, self-efficacy in clinical performance and satisfaction with the clinical learning environment. Nursing student-nurse teacher cooperation during the clinical practicum has a vital role in promoting the learning of students. Despite an increasing interest in using mobile technologies to improve the clinical practicum of students, there is limited robust evidence regarding their effectiveness. A multicentre, parallel group, randomized, controlled, pragmatic, superiority trial. Second-year pre-registration nursing students who are beginning a clinical practicum will be recruited from one university of applied sciences. Eligible students will be randomly allocated to either a control group (engaging in standard cooperation) or an intervention group (engaging in mobile cooperation) for the 5-week the clinical practicum. The complex mobile cooperation intervention comprises of a mobile application-assisted, nursing student-nurse teacher cooperation and a training in the functions of the mobile application. The primary outcome is competence. The secondary outcomes include self-efficacy in clinical performance and satisfaction with the clinical learning environment. Moreover, a process evaluation will be undertaken. The ethical approval for this study was obtained in December 2014 and the study received funding in 2015. The results of this study will provide robust evidence on mobile cooperation during the clinical practicum, a research topic that has not been consistently studied to date. © 2016 John Wiley & Sons Ltd.

Automation in an addiction treatment research clinic: computerised contingency management, ecological momentary assessment and a protocol workflow system.

PubMed

Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H; Preston, Kenzie L

2009-01-01

A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients' treatment needs and to accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with the provision of seamless methods for exporting, mining and querying the data. We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialised applications: the Automated Contingency Management (ACM) system for the delivery of behavioural interventions, the transactional electronic diary (TED) system for the management of behavioural assessments and the Protocol Workflow System (PWS) for computerised workflow automation and guidance of each participant's daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorised staff. ACM and the TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80 patient capacity, having an annual average of 18,000 patient visits and 7300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarise participant safety data for research oversight. When developed in consultation with end users, automation in treatment research clinics can enable more efficient operations, better communication among staff and expansions in research methods.

Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology.

PubMed

Lefterova, Martina I; Suarez, Carlos J; Banaei, Niaz; Pinsky, Benjamin A

2015-11-01

Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Single-cell high resolution melting analysis: A novel, generic, pre-implantation genetic diagnosis (PGD) method applied to cystic fibrosis (HRMA CF-PGD).

PubMed

Destouni, A; Poulou, M; Kakourou, G; Vrettou, C; Tzetis, M; Traeger-Synodinos, J; Kitsiou-Tzeli, S

2016-03-01

Institutions offering CF-PGD face the challenge of developing and optimizing single cell genotyping protocols that should cover for the extremely heterogeneous CF mutation spectrum. Here we report the development and successful clinical application of a generic CF-PGD protocol to facilitate direct detection of any CFTR nucleotide variation(s) by HRMA and simultaneous confirmation of diagnosis through haplotype analysis. A multiplex PCR was optimized supporting co-amplification of any CFTR exon-region, along with 6 closely linked STRs. Single cell genotypes were established through HRM analysis following melting of the 2nd round PCR products and were confirmed by STR haplotype analysis of the 1st PCR products. The protocol was validated pre-clinically, by testing 208 single lymphocytes, isolated from whole blood samples from 4 validation family trios. Fifteen PGD cycles were performed and 103 embryos were biopsied. In 15 clinical PGD cycles, genotypes were achieved in 88/93 (94.6%) embryo biopsy samples, of which 57/88 (64.8%) were deemed genetically suitable for embryo transfer. Amplification failed at all loci for 10/103 blastomeres biopsied from poor quality embryos. Six clinical pregnancies were achieved (2 twin, 4 singletons). PGD genotypes were confirmed following conventional amniocentesis or chorionic villus sampling in all achieved pregnancies. The single cell HRMA CF-PGD protocol described herein is a flexible, generic, low cost and robust genotyping method, which facilitates the analysis of any CFTR genotype combination. Single-cell HRMA can be beneficial to other clinical settings, for example the detection of single nucleotide variants in single cells derived from clinical tumor samples. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Xeno-Free Strategies for Safe Human Mesenchymal Stem/Stromal Cell Expansion: Supplements and Coatings

PubMed Central

Gonçalves, R. M.; Barrias, C. C.

2017-01-01

Human mesenchymal stem/stromal cells (hMSCs) have generated great interest in regenerative medicine mainly due to their multidifferentiation potential and immunomodulatory role. Although hMSC can be obtained from different tissues, the number of available cells is always low for clinical applications, thus requiring in vitro expansion. Most of the current protocols for hMSC expansion make use of fetal bovine serum (FBS) as a nutrient-rich supplement. However, regulatory guidelines encourage novel xeno-free alternatives to define safer and standardized protocols for hMSC expansion that preserve their intrinsic therapeutic potential. Since hMSCs are adherent cells, the attachment surface and cell-adhesive components also play a crucial role on their successful expansion. This review focuses on the advantages/disadvantages of FBS-free media and surfaces/coatings that avoid the use of animal serum, overcoming ethical issues and improving the expansion of hMSC for clinical applications in a safe and reproducible way. PMID:29158740

SU-F-R-06: Traumatic Brachial Plexus Injury Imaging, Developing a Coherent Clinical Protocol From Literature Review Through Practice

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

Wu, D; France, E; Lambert, J

Purpose: Medical Physics teams can now play a critical role to help plan and provide studied approaches for traumatic brachial plexus MR imaging (tbpMRI). This is especially important for coordination with uncommon applications, since it is challenging to select the right modality, parameters, and train technologists on the essential components. For this work, we started with a review of the medical literature, performed crossover/volunteer studies to bring tbpMRI to practice with greater image QC and protocol management. Methods: To the best of our knowledge, we reviewed the known searchable domain for tbpMRI. We found 69 total articles since 2000. Articlesmore » were evaluated with our published protocol for literature management (LIMES3). Two physicists and two radiologists condensed the information from all articles into a knowledgebase. Results: The initial literature demonstrated great heterogeneity, which was a sign that this area needed greater consistency. Despite inconsistency and imprecision, we extracted the most relevant targets using our long-term experience with protocol development in MSK. We ran volunteers on six different magnets of various field strengths with multiple receiver coils, and rebuilt a coherent protocol for tbpMRI. Our radiologists rated LIMES3 work as superior. We have received referrals from the ER and have conducted four patient evaluations. Conclusion: Traumatic brachial plexus MRI has great possible benefits for patients. This work supports the complexity of tbpMRI scanning. As this is rarely performed, it requires a more diligent protocol workflow, coordination of caregivers, and education within multiple clinical departments. Choosing the correct imaging exam can be critical, as patients can have significant neuropathy and/or paralysis. The LIMES3 protocol is well liked at our institution, and forms the cornerstone of understanding for our work. Our literature management led to a better clinical protocol creation despite the diffuse and inconclusive information presented in the existing medical literature.« less

Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications

PubMed Central

Castro-Manrreza, Marta E.; Montesinos, Juan J.

2015-01-01

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD). PMID:25961059

Impact of telemedicine in hospital culture and its consequences on quality of care and safety

PubMed Central

Steinman, Milton; Morbeck, Renata Albaladejo; Pires, Philippe Vieira; Abreu, Carlos Alberto Cordeiro; Andrade, Ana Helena Vicente; Terra, Jose Claudio Cyrineu; Teixeira, José Carlos; Kanamura, Alberto Hideki

2015-01-01

ABSTRACT Objective To describe the impact of the telemedicine application on the clinical process of care and its different effects on hospital culture and healthcare practice. Methods The concept of telemedicine through real time audio-visual coverage was implemented at two different hospitals in São Paulo: a secondary and public hospital, Hospital Municipal Dr. Moysés Deutsch, and a tertiary and private hospital, Hospital Israelita Albert Einstein. Results Data were obtained from 257 teleconsultations records over a 12-month period and were compared to a similar period before telemedicine implementation. For 18 patients (7.1%) telemedicine consultation influenced in diagnosis conclusion, and for 239 patients (92.9%), the consultation contributed to clinical management. After telemedicine implementation, stroke thrombolysis protocol was applied in 11% of ischemic stroke patients. Telemedicine approach reduced the need to transfer the patient to another hospital in 25.9% regarding neurological evaluation. Sepsis protocol were adopted and lead to a 30.4% reduction mortality regarding severe sepsis. Conclusion The application is associated with differences in the use of health services: emergency transfers, mortality, implementation of protocols and patient management decisions, especially regarding thrombolysis. These results highlight the role of telemedicine as a vector for transformation of hospital culture impacting on the safety and quality of care. PMID:26676268

Patient and professional user experiences of simple telehealth for hypertension, medication reminders and smoking cessation: a service evaluation

PubMed Central

Cottrell, Elizabeth; Cox, Tracey; O'Connell, Phil; Chambers, Ruth

2015-01-01

Objectives To establish patient and professional user satisfaction with the Advice & Interactive Messaging (AIM) for Health programme delivered using a mobile phone-based, simple telehealth intervention, ‘Florence’. Design A service evaluation using data extracted from Florence and from a professional user electronic survey. Setting 425 primary care practices across 31 Clinical Commissioning Groups in England. Participants 3381 patients registered on 1 of 10 AIM protocols between March 2013 and January 2014 and 77 professional users. Intervention The AIM programme offered 10 clinical protocols, in three broad groups: (1) hypertension diagnosis/monitoring, (2) medication reminders and (3) smoking cessation. Florence sent patients prompts to submit clinical information, educational messages and user satisfaction questions. Patient responses were reviewed by their primary healthcare providers. Primary outcome measures Patients and professional user experiences of using AIM, and within this, Florence. Results Patient activity using Florence was generally good at month 1 for the hypertension protocols (71–80%), but reduced over 2–3 months (31–60%). For the other protocols, patient activity was 0–39% at 3 months. Minimum target days of texting were met for half the hypertension protocols. 1707/2304 (74%) patients sent evaluative texts responded at least once. Among responders, agreement with the adapted friends and family statement generally exceeded preproject aspirations. Professional responders were generally positive or equivocal about the programme. Conclusions Satisfaction with AIM appeared optimal when patients were carefully selected for the protocol; professional users were familiar with the system, the programme addressed a problem with the previous service delivery that was identified by users and users took an active approach to achieve clinical goals. However, there was a significant decrease in patients’ use of Florence over time. Future applications may be optimised by identifying and addressing reasons for the waning use of the service and enhancing support during implementation of the service. PMID:25795698

High-Throughput Screening Assay for Embryoid Body Differentiation of Human Embryonic Stem Cells

PubMed Central

Outten, Joel T.; Gadue, Paul; French, Deborah L.; Diamond, Scott L.

2012-01-01

Serum-free human pluripotent stem cell media offer the potential to develop reproducible clinically applicable differentiation strategies and protocols. The vast array of possible growth factor and cytokine combinations for media formulations makes differentiation protocol optimization both labor and cost-intensive. This unit describes a 96-well plate, 4-color flow cytometry-based screening assay to optimize pluripotent stem cell differentiation protocols. We provide conditions both to differentiate human embryonic stem cells (hESCs) to the three primary germ layers, ectoderm, endoderm, and mesoderm, and to utilize flow cytometry to distinguish between them. This assay exhibits low inter-well variability and can be utilized to efficiently screen a variety of media formulations, reducing cost, incubator space, and labor. Protocols can be adapted to a variety of differentiation stages and lineages. PMID:22415836

The role of advanced reconstruction algorithms in cardiac CT

PubMed Central

Halliburton, Sandra S.; Tanabe, Yuki; Partovi, Sasan

2017-01-01

Non-linear iterative reconstruction (IR) algorithms have been increasingly incorporated into clinical cardiac CT protocols at institutions around the world. Multiple IR algorithms are available commercially from various vendors. IR algorithms decrease image noise and are primarily used to enable lower radiation dose protocols. IR can also be used to improve image quality for imaging of obese patients, coronary atherosclerotic plaques, coronary stents, and myocardial perfusion. In this article, we will review the various applications of IR algorithms in cardiac imaging and evaluate how they have changed practice. PMID:29255694

A data-rich recruitment core to support translational clinical research.

PubMed

Kost, Rhonda G; Corregano, Lauren M; Rainer, Tyler-Lauren; Melendez, Caroline; Coller, Barry S

2015-04-01

Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. For protocols receiving recruitment services during 2009-2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first-time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real-time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. © 2014 Wiley Periodicals, Inc.

A Data‐Rich Recruitment Core to Support Translational Clinical Research

PubMed Central

Corregano, Lauren M.; Rainer, Tyler‐Lauren; Melendez, Caroline; Coller, Barry S.

2014-01-01

Abstract Background Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. Methods The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. Results For protocols receiving recruitment services during 2009–2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first‐time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Conclusions Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real‐time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. PMID:25381717

Echocardiographic evaluation after pediatric heart transplant in Chile: initial application of a functional protocol with global longitudinal strain.

PubMed

Trincado, Claudia; Molina, Víctor; Urcelay, Gonzalo; Dellepiane, Paulina

2018-02-01

The echocardiographic evaluation of patients after heart transplantation is a useful tool. However, it is still necessary to define an optimal follow-up protocol. To describe the results of the application of a functional echocardiographic protocol in patients being followed after pediatric heart transplantation. Alls patients being followed at our institution after pediatric heart transplantation underwent an echocardiographic examination with a functional protocol that included global longitudinal strain. Contemporaneous endomyocardial biopsy results and hemodynamic data were recorded. 9 patients were evaluated with our echocardiographic functional protocol. Of these patients, only 1 showed systolic left ventricular dysfunction according to classic parameters. However, almost all patients had an abnormal global longitudinal strain. Right ventricular systolic dysfunction was observed in all patients. No epidodes of moderate to severe rejectiom were recorded. No correlation was observed between these parameters and pulmonary artery pressure. Subclinical biventricular systolic dysfunction was observed in the majority of the patients in this study. No association with rejection episodes or pulmonary hypertension was observed, which may be related to the absence of moderate or severe rejection episodes during the study period, and to the small sample size. Long term follow-up of these patients may better define the clinical relevance of our findings.

Treatment algorithms and protocolized care.

PubMed

Morris, Alan H

2003-06-01

Excess information in complex ICU environments exceeds human decision-making limits and likely contributes to unnecessary variation in clinical care, increasing the likelihood of clinical errors. I reviewed recent critical care clinical trials searching for information about the impact of protocol use on clinically pertinent outcomes. Several recently published clinical trials illustrate the importance of distinguishing efficacy and effectiveness trials. One of these trials illustrates the danger of conducting effectiveness trials before the efficacy of an intervention is established. The trials also illustrate the importance of distinguishing guidelines and inadequately explicit protocols from adequately explicit protocols. Only adequately explicit protocols contain enough detail to lead different clinicians to the same decision when faced with the same clinical scenario. Differences between guidelines and protocols are important. Guidelines lack detail and provide general guidance that requires clinicians to fill in many gaps. Computerized or paper-based protocols are detailed and, when used for complex clinical ICU problems, can generate patient-specific, evidence-based therapy instructions that can be carried out by different clinicians with almost no interclinician variability. Individualization of patient therapy can be preserved by these protocols when they are driven by individual patient data. Explicit decision-support tools (eg, guidelines and protocols) have favorable effects on clinician and patient outcomes and can reduce the variation in clinical practice. Guidelines and protocols that aid ICU decision makers should be more widely distributed.

Nursing Students' Opinion on the Use of Smartphone Applications (Apps) in Clinical Education and Training: A Study Protocol.

PubMed

O'Connor, Siobhan; Andrews, Tom

2016-01-01

Nurse educators are exploring different mobile technologies to provide additional support to nursing students in clinical practice. However, the view of nursing students on the use of smartphone applications (apps) to enhance clinical education has not been explored. This proposed study will use a self-reported questionnaire to examine the opinions of nursing students on the current and potential use of smartphone apps when training in clinical settings. Descriptive and inferential statistics will be performed on the quantitative data. Qualitative data from open ended questions will be thematically analysed using the framework approach. This will be the first study to examine the use of smartphone apps as a support in clinical teaching from a students' perspective. Their opinion is vital if the right mobile technology is to be designed and implemented.

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis.

PubMed

Ali, Ather; Kahn, Janet; Rosenberger, Lisa; Perlman, Adam I

2012-10-04

Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists' clinical judgment and maintaining consistency with a prior pilot study. The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Clinicaltrials.gov NCT00970008 (18 August 2009).

Cryopreservation: Vitrification and Controlled Rate Cooling.

PubMed

Hunt, Charles J

2017-01-01

Cryopreservation is the application of low temperatures to preserve the structural and functional integrity of cells and tissues. Conventional cooling protocols allow ice to form and solute concentrations to rise during the cryopreservation process. The damage caused by the rise in solute concentration can be mitigated by the use of compounds known as cryoprotectants. Such compounds protect cells from the consequences of slow cooling injury, allowing them to be cooled at cooling rates which avoid the lethal effects of intracellular ice. An alternative to conventional cooling is vitrification. Vitrification methods incorporate cryoprotectants at sufficiently high concentrations to prevent ice crystallization so that the system forms an amorphous glass thus avoiding the damaging effects caused by conventional slow cooling. However, vitrification too can impose damaging consequences on cells as the cryoprotectant concentrations required to vitrify cells at lower cooling rates are potentially, and often, harmful. While these concentrations can be lowered to nontoxic levels, if the cells are ultra-rapidly cooled, the resulting metastable system can lead to damage through devitrification and growth of ice during subsequent storage and rewarming if not appropriately handled.The commercial and clinical application of stem cells requires robust and reproducible cryopreservation protocols and appropriate long-term, low-temperature storage conditions to provide reliable master and working cell banks. Though current Good Manufacturing Practice (cGMP) compliant methods for the derivation and banking of clinical grade pluripotent stem cells exist and stem cell lines suitable for clinical applications are available, current cryopreservation protocols, whether for vitrification or conventional slow freezing, remain suboptimal. Apart from the resultant loss of valuable product that suboptimal cryopreservation engenders, there is a danger that such processes will impose a selective pressure on the cells selecting out a nonrepresentative, freeze-resistant subpopulation. Optimizing this process requires knowledge of the fundamental processes that occur during the freezing of cellular systems, the mechanisms of damage and methods for avoiding them. This chapter draws together the knowledge of cryopreservation gained in other systems with the current state-of-the-art for embryonic and induced pluripotent stem cell preservation in an attempt to provide the background for future attempts to optimize cryopreservation protocols.

Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples

PubMed Central

Quick, Josh; Grubaugh, Nathan D; Pullan, Steven T; Claro, Ingra M; Smith, Andrew D; Gangavarapu, Karthik; Oliveira, Glenn; Robles-Sikisaka, Refugio; Rogers, Thomas F; Beutler, Nathan A; Burton, Dennis R; Lewis-Ximenez, Lia Laura; de Jesus, Jaqueline Goes; Giovanetti, Marta; Hill, Sarah; Black, Allison; Bedford, Trevor; Carroll, Miles W; Nunes, Marcio; Alcantara, Luiz Carlos; Sabino, Ester C; Baylis, Sally A; Faria, Nuno; Loose, Matthew; Simpson, Jared T; Pybus, Oliver G; Andersen, Kristian G; Loman, Nicholas J

2018-01-01

Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples without isolation remains challenging for viruses such as Zika, where metagenomic sequencing methods may generate insufficient numbers of viral reads. Here we present a protocol for generating coding-sequence complete genomes comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimised library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences. The MinION protocol does not require an internet connection for analysis, making it suitable for field applications with limited connectivity. Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction. Viral consensus sequences can be achieved starting with clinical samples in 1-2 days following a simple laboratory workflow. This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas. PMID:28538739

Does chlorhexidine prevent dry socket?

PubMed

Richards, Derek

2012-01-01

The BBO (Bibliografia Brasileira de Odontologia), Biomed Central, Cochrane Library, Directory of Open Access Journals, LILACS, Open-J-Gate, OpenSIGLE, PubMed, Sabinet and Science-Direct databases were searched. Articles were selected for review from the search results on the basis of their compliance with the broad inclusion criteria: relevant to the review question; and prospective two-arm (or more) clinical study. The primary outcome measure was the incidence of AO reported at the patient level. Two reviewers (VY and SM) independently extracted data and assessed the quality of the accepted articles. Individual dichotomous datasets for the control and test group were extracted from each article. Where possible, missing data were calculated from information given in the text or tables. In addition, authors were contacted in order to obtain missing information. Datasets were assessed for their clinical and methodological heterogeneity following Cochrane guidelines. Meta-analysis was conducted with homogeneous datasets. Publication bias was assessed by use of a funnel plot and Egger's regression. Ten randomised trials were included; almost all involved the removal of third molars. Only two of six identified application protocols (single application of chlorhexidine 0.2% gel or multiple application of 0.12% rinse versus placebo) were found to significantly decrease the incidence of AO. Within the limitations of this review, only two of six identified application protocols were found to significantly decrease the incidence of AO. The evidence for both protocols is weak and may be challenged on the grounds of high risk of selection, detection/performance and attrition bias. This systematic review could not identify sufficient evidence supporting the use of chlorhexidine for the prevention of AO. Chlorhexidine seems not to cause any significantly higher adverse reactions than placebo. Future high-quality randomised control trials are needed to provide conclusive evidence on this topic.

Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological Assessment Protocol for Older Adults with Low Formal Education

PubMed Central

de Paula, Jonas Jardim; Bertola, Laiss; Ávila, Rafaela Teixeira; Moreira, Lafaiete; Coutinho, Gabriel; de Moraes, Edgar Nunes; Bicalho, Maria Aparecida Camargos; Nicolato, Rodrigo; Diniz, Breno Satler; Malloy-Diniz, Leandro Fernandes

2013-01-01

Background and Objectives The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. Methods and Results A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. Conclusion The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education. PMID:24066031

Automation in an Addiction Treatment Research Clinic: Computerized Contingency Management, Ecological Momentary Assessment, and a Protocol Workflow System

PubMed Central

Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H.; Preston, Kenzie L.

2009-01-01

Issues A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients’ treatment needs and accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with provision of seamless methods for exporting, mining, and querying the data. Approach We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialized applications: the Automated Contingency Management (ACM) system for delivery of behavioral interventions, the Transactional Electronic Diary (TED) system for management of behavioral assessments, and the Protocol Workflow System (PWS) for computerized workflow automation and guidance of each participant’s daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorized staff. Key Findings ACM and TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80-patient capacity having an annual average of 18,000 patient-visits and 7,300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarize participant-safety data for research oversight. Implications and conclusion When developed in consultation with end users, automation in treatment-research clinics can enable more efficient operations, better communication among staff, and expansions in research methods. PMID:19320669

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes. © The Author 2016. 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.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Practice guidelines for music interventions with hospitalized pediatric patients.

PubMed

Stouffer, Janice W; Shirk, Beverly J; Polomano, Rosemary C

2007-12-01

Music therapy is an effective complementary approach that can achieve specific therapeutic outcomes in the clinical management of pediatric patients. Growing research on music interventions has generated scientific knowledge about how this modality benefits patients and has formed the basis for effective protocols that can be used in practice. Although it can be challenging to translate research-based protocols into routine clinical care at the bedside, it is essential that music therapy interventions be aligned with evidence-based information and that accepted standards be established by the music therapy discipline to achieve the greatest benefit. The importance of partnerships between nurses and music therapists is emphasized to enhance the success of music-based treatments. This discussion synthesizes research findings that can be used to design pediatric practice guidelines in the application of music therapy.

Tracheal decannulation protocol in patients affected by traumatic brain injury.

PubMed

Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

2014-04-01

Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing.

Tracheal Decannulation Protocol in Patients Affected by Traumatic Brain Injury

PubMed Central

Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

2014-01-01

Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing. PMID:25992074

The Ontology of Clinical Research (OCRe): An Informatics Foundation for the Science of Clinical Research

PubMed Central

Sim, Ida; Tu, Samson W.; Carini, Simona; Lehmann, Harold P.; Pollock, Brad H.; Peleg, Mor; Wittkowski, Knut M.

2013-01-01

To date, the scientific process for generating, interpreting, and applying knowledge has received less informatics attention than operational processes for conducting clinical studies. The activities of these scientific processes — the science of clinical research — are centered on the study protocol, which is the abstract representation of the scientific design of a clinical study. The Ontology of Clinical Research (OCRe) is an OWL 2 model of the entities and relationships of study design protocols for the purpose of computationally supporting the design and analysis of human studies. OCRe’s modeling is independent of any specific study design or clinical domain. It includes a study design typology and a specialized module called ERGO Annotation for capturing the meaning of eligibility criteria. In this paper, we describe the key informatics use cases of each phase of a study’s scientific lifecycle, present OCRe and the principles behind its modeling, and describe applications of OCRe and associated technologies to a range of clinical research use cases. OCRe captures the central semantics that underlies the scientific processes of clinical research and can serve as an informatics foundation for supporting the entire range of knowledge activities that constitute the science of clinical research. PMID:24239612

Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation: clinical feasibility and integration as an adjunct therapy.

PubMed

Hoermann, Simon; Ferreira Dos Santos, Luara; Morkisch, Nadine; Jettkowski, Katrin; Sillis, Moran; Devan, Hemakumar; Kanagasabai, Parimala S; Schmidt, Henning; Krüger, Jörg; Dohle, Christian; Regenbrecht, Holger; Hale, Leigh; Cutfield, Nicholas J

2017-07-01

New rehabilitation strategies for post-stroke upper limb rehabilitation employing visual stimulation show promising results, however, cost-efficient and clinically feasible ways to provide these interventions are still lacking. An integral step is to translate recent technological advances, such as in virtual and augmented reality, into therapeutic practice to improve outcomes for patients. This requires research on the adaptation of the technology for clinical use as well as on the appropriate guidelines and protocols for sustainable integration into therapeutic routines. Here, we present and evaluate a novel and affordable augmented reality system (Augmented Reflection Technology, ART) in combination with a validated mirror therapy protocol for upper limb rehabilitation after stroke. We evaluated components of the therapeutic intervention, from the patients' and the therapists' points of view in a clinical feasibility study at a rehabilitation centre. We also assessed the integration of ART as an adjunct therapy for the clinical rehabilitation of subacute patients at two different hospitals. The results showed that the combination and application of the Berlin Protocol for Mirror Therapy together with ART was feasible for clinical use. This combination was integrated into the therapeutic plan of subacute stroke patients at the two clinical locations where the second part of this research was conducted. Our findings pave the way for using technology to provide mirror therapy in clinical settings and show potential for the more effective use of inpatient time and enhanced recoveries for patients. Implications for Rehabilitation Computerised Mirror Therapy is feasible for clinical use Augmented Reflection Technology can be integrated as an adjunctive therapeutic intervention for subacute stroke patients in an inpatient setting Virtual Rehabilitation devices such as Augmented Reflection Technology have considerable potential to enhance stroke rehabilitation.

Histomorphometric assessment of bone necrosis produced by two cryosurgery protocols using liquid nitrogen: an experimental study on rat femurs.

PubMed

Costa, Fábio Wildson Gurgel; Brito, Gerly Anne de Castro; Pessoa, Rosana Maria Andrade; Studart-Soares, Eduardo Costa

2011-01-01

The aim of this study was to evaluate the effects of liquid nitrogen cryosurgery on the femoral diaphysis of rats. The femoral diaphyses of 42 Wistar rats were exposed to three local and sequential applications of liquid nitrogen for 1 or 2 min, intercalated with periods of 5 min of passive thawing. The animals were sacrificed after 1, 2, 4 and 12 weeks and the specimens obtained were processed and analyzed histomorphometrically. The depth and extent of peak bone necrosis were 124.509 µm and 2087.094 µm for the 1-min protocol, respectively, and 436.424 µm and 12046.426 µm for the 2-min protocol. Peak necrosis was observed in the second experimental week with both cryotherapy protocols. The present results indicate that the 2-min protocol produced more marked bone necrosis than the 1-min protocol. Although our results cannot be entirely extrapolated to clinical practice, they contribute to the understanding of the behavior of bone tissue submitted to different cycles of liquid nitrogen freezing and may serve as a basis for new studies.

Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.

PubMed

Ebile, Akoh Walter; Ateudjieu, Jerome; Yakum, Martin Ndinakie; Djuidje, Marceline Ngounoue; Watcho, Pierre

2015-09-29

International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.

Electronic protocol of respiratory physical therapy in patients with idiopathic adolescent scoliosis.

PubMed

Cano, Danila Vieira Baldini; Malafaia, Osvaldo; Alves, Vera Lúcia dos Santos; Avanzi, Osmar; Pinto, José Simão de Paula

2011-01-01

To create a clinical database of respiratory function in patients with adolescent idiopathic scoliosis; computerize and store this clinical data through the use of a software; incorporate this electronic protocol to the SINPE© (Integrated Electronic Protocols System) and analyze a pilot project with interpretation of results. From the literature review a computerized data bank of clinical data of postural deviations was set up (master protocol). Upon completion of the master protocol a specific protocol of respiratory function in patients with adolescent idiopathic scoliosis was designed and a pilot project was conducted to collect and analyze data from ten patients. It was possible to create the master protocol of postural deviations and the specific protocol of respiratory function in patients with adolescent idiopathic scoliosis. The data collected in the pilot project was processed by the SINPE ANALYZER©, generating charts and statistics. The establishment of the clinical database of adolescent idiopathic scoliosis was possible. Computerization and storage of clinical data using the software were viable. The electronic protocol of adolescent idiopathic scoliosis could be incorporated into the SINPE© and its use in the pilot project was successful.

Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

PubMed Central

Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

2015-01-01

Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329

Development of a digital clinical pathway for emergency medicine: Lessons from usability testing and implementation failure.

PubMed

Gutenstein, Marc; Pickering, John W; Than, Martin

2018-06-01

Clinical pathways are used to support the management of patients in emergency departments. An existing document-based clinical pathway was used as the foundation on which to design and build a digital clinical pathway for acute chest pain, with the aim of improving clinical calculations, clinician decision-making, documentation, and data collection. Established principles of decision support system design were used to build an application within the existing electronic health record, before testing with a multidisciplinary team of doctors using a think-aloud protocol. Technical authoring was successful, however, usability testing revealed that the user experience and the flexibility of workflow within the application were critical barriers to implementation. Emergency medicine and acute care decision support systems face particular challenges to existing models of linear workflow that should be deliberately addressed in digital pathway design. We make key recommendations regarding digital pathway design in emergency medicine.

A standards-based clinical information system for HIV/AIDS.

PubMed

Stitt, F W

1995-01-01

To create a clinical data repository to interface the Veteran's Administration (VA) Decentralized Hospital Computer Program (DHCP) and a departmental clinical information system for the management of HIV patients. This system supports record-keeping, decision-making, reporting, and analysis. The database development was designed to overcome two impediments to successful implementations of clinical databases: (i) lack of a standard reference data model, and; (ii) lack of a universal standard for medical concept representation. Health Level Seven (HL7) is a standard protocol that specifies the implementation of interfaces between two computer applications (sender and receiver) from different vendors or sources of electronic data exchange in the health care environment. This eliminates or substantially reduces the custom interface programming and program maintenance that would otherwise be required. HL7 defines the data to be exchanged, the timing of the interchange, and the communication of errors to the application. The formats are generic in nature and must be configured to meet the needs of the two applications involved. The standard conceptually operates at the seventh level of the ISO model for Open Systems Interconnection (OSI). The OSI simply defines the data elements that are exchanged as abstract messages, and does not prescribe the exact bit stream of the messages that flow over the network. Lower level network software developed according to the OSI model may be used to encode and decode the actual bit stream. The OSI protocols are not universally implemented and, therefore, a set of encoding rules for defining the exact representation of a message must be specified. The VA has created an HL7 module to assist DHCP applications in exchanging health care information with other applications using the HL7 protocol. The DHCP HL7 module consists of a set of utility routines and files that provide a generic interface to the HL7 protocol for all DHCP applications. The VA's DHCP core modules are in standard use at 169 hospitals, and the role of the VA system in health care delivery has been discussed elsewhere. This development was performed at the Miami VA Medical Center Special Immunology Unit, where a database was created for an HIV patient registry in 1987. Over 2,300 patient have been entered into a database that supports a problem-oriented summary of the patient's clinical record. The interface to the VA DHCP was designed and implemented to capture information from the patient treatment file, pharmacy, laboratory, radiology, and other modules. We obtained a suite of programs for implementing the HL7 encoding rules from Columbia-Presbyterian Medical Center in New York, written in ANSI C. This toolkit isolates our application programs from the details of the HL7 encoding rules, and allows them to deal with abstract messages and the programming level. While HL7 has become a standard for healthcare message exchange, SQL (Structured Query Language) is the standard for database definition, data manipulation, and query. The target database (Stitt F.W. The Problem-Oriented Medical Synopsis: a patient-centered clinical information system. Proc 17 SCAMC. 1993:88-93) provides clinical workstation functionality. Medical concepts are encoded using a preferred terminology derived from over 15 sources that include the Unified Medical Language System and SNOMed International ( Stitt F.W. The Problem-Oriented Medical Synopsis: coding, indexing, and classification sub-model. Proc 18 SCAMC, 1994: in press). The databases were modeled using the Information Engineering CASE tools, and were written using relational database utilities, including embedded SQL in C (ESQL/C). We linked ESQL/C programs to the HL7 toolkit to allow data to be inserted, deleted, or updated, under transaction control. A graphical format will be used to display the entity-rel

Research ethics board approval for an international thromboprophylaxis trial.

PubMed

Lutz, Kristina; Wilton, Kelly; Zytaruk, Nicole; Julien, Lisa; Hall, Richard; Harvey, Johanne; Skrobik, Yoanna; Vlahakis, Nicholas; Meade, Laurie; Matte, Andrea; Meade, Maureen; Burns, Karen; Albert, Martin; Cash, Bronwyn Barlow; Vallance, Shirley; Klinger, James; Heels-Ansdell, Diane; Cook, Deborah

2012-06-01

Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards. Copyright © 2012 Elsevier Inc. All rights reserved.

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

PubMed

Wright, Melanie C; Taekman, Jeffrey M; Barber, Linda; Hobbs, Gene; Newman, Mark F; Stafford-Smith, Mark

2005-12-01

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples.

PubMed

Quick, Joshua; Grubaugh, Nathan D; Pullan, Steven T; Claro, Ingra M; Smith, Andrew D; Gangavarapu, Karthik; Oliveira, Glenn; Robles-Sikisaka, Refugio; Rogers, Thomas F; Beutler, Nathan A; Burton, Dennis R; Lewis-Ximenez, Lia Laura; de Jesus, Jaqueline Goes; Giovanetti, Marta; Hill, Sarah C; Black, Allison; Bedford, Trevor; Carroll, Miles W; Nunes, Marcio; Alcantara, Luiz Carlos; Sabino, Ester C; Baylis, Sally A; Faria, Nuno R; Loose, Matthew; Simpson, Jared T; Pybus, Oliver G; Andersen, Kristian G; Loman, Nicholas J

2017-06-01

Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples (i.e., without isolation and culture) remains challenging for viruses such as Zika, for which metagenomic sequencing methods may generate insufficient numbers of viral reads. Here we present a protocol for generating coding-sequence-complete genomes, comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimized library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences. The MinION protocol does not require an Internet connection for analysis, making it suitable for field applications with limited connectivity. Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction. Viral consensus sequences can be achieved in 1-2 d by starting with clinical samples and following a simple laboratory workflow. This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas. The protocol can be used to sequence other viral genomes using the online Primal Scheme primer designer software. It is suitable for sequencing either RNA or DNA viruses in the field during outbreaks or as an inexpensive, convenient method for use in the lab.

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2015-12-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

PubMed Central

Chan, An-Wen; Tetzlaff, Jennifer M.; Altman, Douglas G.; Laupacis, Andreas; Gøtzsche, Peter C.; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A.; Doré, Caroline J.; Parulekar, Wendy R.; Summerskill, William S.M.; Groves, Trish; Schulz, Kenneth F.; Sox, Harold C.; Rockhold, Frank W.; Rennie, Drummond; Moher, David

2016-01-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:23295957

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2013-02-05

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

PubMed

Debruyne, Philip R; Johnson, Philip J; Pottel, Lies; Daniels, Susanna; Greer, Rachel; Hodgkinson, Elizabeth; Kelly, Stephen; Lycke, Michelle; Samol, Jens; Mason, Julie; Kimber, Donna; Loucaides, Eileen; Parmar, Mahesh Kb; Harvey, Sally

2015-06-01

Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research. © The Author(s) 2015.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

PubMed

Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

2017-06-01

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Electronic data collection for the analysis of surgical maneuvers on patients submitted to rhinoplasty

PubMed Central

Berger, Cezar; Freitas, Renato; Malafaia, Osvaldo; Pinto, José Simão de Paula; Mocellin, Marcos; Macedo, Evaldo; Fagundes, Marina Serrato Coelho

2012-01-01

Summary Introduction: In the health field, computerization has become increasingly necessary in professional practice, since it facilitates data recovery and assists in the development of research with greater scientific rigor. Objective: the present work aimed to develop, apply, and validate specific electronic protocols for patients referred for rhinoplasty. Methods: The prospective research had 3 stages: (1) preparation of theoretical data bases; (2) creation of a master protocol using Integrated System of Electronic Protocol (SINPE©); and (3) elaboration, application, and validation of a specific protocol for the nose and sinuses regarding rhinoplasty. Results: After the preparation of the master protocol, which dealt with the entire field of otorhinolaryngology, we idealized a specific protocol containing all matters related to the patient. In particular, the aesthetic and functional nasal complaints referred for surgical treatment (i.e., rhinoplasty) were organized into 6 main hierarchical categories: anamnesis, physical examination, complementary exams, diagnosis, treatment, and outcome. This protocol utilized these categories and their sub-items: finality; access; surgical maneuvers on the nasal dorsum, tip, and base; clinical evolution after 3, 6, and 12 months; revisional surgery; and quantitative and qualitative evaluations. Conclusion: The developed electronic-specific protocol is feasible and important for information registration from patients referred to rhinoplasty. PMID:25991979

The Effect of Coded Healing Abutments on Treatment Duration and Clinical Outcome: A Randomized Controlled Clinical Trial Comparing Encode and Conventional Impression Protocols.

PubMed

Abduo, Jaafar; Chen, Chen; Le Breton, Eugene; Radu, Alexandra; Szeto, Josephine; Judge, Roy; Darby, Ivan

To compare the Encode impression protocol (Biomet 3i) with the conventional impression protocol in terms of treatment duration, clinical accuracy, and outcome up to the first postplacement review of single-implant crowns. A total of 45 implants were included in this study. The implants were randomly allocated to the Encode group (23 implants) or the conventional group (22 implants). At the time of surgery, all implants received two-piece Encode healing abutments. The implants were restored 3 months after insertion. In the conventional protocol, open-tray implant-level impressions were taken and the implants were restored with prefabricated abutments and porcelain-fused-to-metal (PFM) crowns. For the implants in the Encode group, closed-tray impressions of the healing abutments were taken. The generated casts were sent to the Biomet 3i scanning/milling center for custom abutment manufacturing on which PFM crowns were fabricated. Treatment duration (laboratory and clinical), clinical accuracy of occlusal and proximal contacts, and outcome (esthetics, patient satisfaction, and crown contour) were evaluated with the aid of a series of questionnaires. The Encode protocol required significantly less laboratory time (18 minutes) than the conventional protocol for adjustment of the abutments. The impression pour time, time for the laboratory to return the crown, time for crown insertion at the final appointment, and total clinical time for crown insertion did not differ significantly between the two protocols. Likewise, clinical accuracy, esthetics, and patient satisfaction were similar for the two protocols. The two protocols were clinically comparable. The Encode protocol is advantageous in reducing the laboratory time before crown fabrication.

Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients.

PubMed

Dauti, Angela; Gerstl, Brigitte; Chong, Serena; Chisholm, Orin; Anazodo, Antoinette

2017-06-01

There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new trials.

Ultralow dose dentomaxillofacial CT imaging and iterative reconstruction techniques: variability of Hounsfield units and contrast-to-noise ratio

PubMed Central

Bischel, Alexander; Stratis, Andreas; Kakar, Apoorv; Bosmans, Hilde; Jacobs, Reinhilde; Gassner, Eva-Maria; Puelacher, Wolfgang; Pauwels, Ruben

2016-01-01

Objective: The aim of this study was to evaluate whether application of ultralow dose protocols and iterative reconstruction technology (IRT) influence quantitative Hounsfield units (HUs) and contrast-to-noise ratio (CNR) in dentomaxillofacial CT imaging. Methods: A phantom with inserts of five types of materials was scanned using protocols for (a) a clinical reference for navigated surgery (CT dose index volume 36.58 mGy), (b) low-dose sinus imaging (18.28 mGy) and (c) four ultralow dose imaging (4.14, 2.63, 0.99 and 0.53 mGy). All images were reconstructed using: (i) filtered back projection (FBP); (ii) IRT: adaptive statistical iterative reconstruction-50 (ASIR-50), ASIR-100 and model-based iterative reconstruction (MBIR); and (iii) standard (std) and bone kernel. Mean HU, CNR and average HU error after recalibration were determined. Each combination of protocols was compared using Friedman analysis of variance, followed by Dunn's multiple comparison test. Results: Pearson's sample correlation coefficients were all >0.99. Ultralow dose protocols using FBP showed errors of up to 273 HU. Std kernels had less HU variability than bone kernels. MBIR reduced the error value for the lowest dose protocol to 138 HU and retained the highest relative CNR. ASIR could not demonstrate significant advantages over FBP. Conclusions: Considering a potential dose reduction as low as 1.5% of a std protocol, ultralow dose protocols and IRT should be further tested for clinical dentomaxillofacial CT imaging. Advances in knowledge: HU as a surrogate for bone density may vary significantly in CT ultralow dose imaging. However, use of std kernels and MBIR technology reduce HU error values and may retain the highest CNR. PMID:26859336

Clinical Feasibility of Continuously Monitored Data for Heart Rate, Physical Activity, and Sleeping by Wearable Activity Trackers in Patients with Thyrotoxicosis: Protocol for a Prospective Longitudinal Observational Study.

PubMed

Lee, Jie-Eun; Lee, Dong Hwa; Oh, Tae Jung; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul; Moon, Jae Hoon

2018-02-21

Thyrotoxicosis is a common disease caused by an excess of thyroid hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis cases are caused by Graves' disease, an autoimmune disease, which has a high recurrence rate when treated with antithyroid drugs such as methimazole or propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include palpitation, weight loss, restlessness, and difficulty sleeping. Although these clinical changes in thyrotoxicosis can be detected by currently available wearable activity trackers, there have been few trials of the clinical application of wearable devices in patients with thyrotoxicosis. The aim of this study is to investigate the clinical applicability of wearable device-generated data to the management of thyrotoxicosis. We are analyzing continuously monitored data for heart rate, physical activity, and sleep in patients with thyrotoxicosis during their clinical course after treatment. Thirty thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul National University Bundang Hospital. Heart rate, physical activity, and sleep are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data including anthropometric measures, thyroid function test, and hyperthyroidism symptom scale are recorded. Study enrollment began in December 2016, and the intervention and follow-up phases are ongoing. The results of the data analysis are expected to be available by September 2017. This study will provide a foundational feasibility trial of the clinical applications of biosignal measurements to the differential diagnosis, prediction of clinical course, early detection of recurrence, and treatment in patients with thyrotoxicosis. ClinicalTrials.gov NCT03009357; https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at http://www.webcitation.org/6wh4MWPm2). ©Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.02.2018.

CT protocol management: simplifying the process by using a master protocol concept.

PubMed

Szczykutowicz, Timothy P; Bour, Robert K; Rubert, Nicholas; Wendt, Gary; Pozniak, Myron; Ranallo, Frank N

2015-07-08

This article explains a method for creating CT protocols for a wide range of patient body sizes and clinical indications, using detailed tube current information from a small set of commonly used protocols. Analytical expressions were created relating CT technical acquisition parameters which can be used to create new CT protocols on a given scanner or customize protocols from one scanner to another. Plots of mA as a function of patient size for specific anatomical regions were generated and used to identify the tube output needs for patients as a function of size for a single master protocol. Tube output data were obtained from the DICOM header of clinical images from our PACS and patient size was measured from CT localizer radiographs under IRB approval. This master protocol was then used to create 11 additional master protocols. The 12 master protocols were further combined to create 39 single and multiphase clinical protocols. Radiologist acceptance rate of exams scanned using the clinical protocols was monitored for 12,857 patients to analyze the effectiveness of the presented protocol management methods using a two-tailed Fisher's exact test. A single routine adult abdominal protocol was used as the master protocol to create 11 additional master abdominal protocols of varying dose and beam energy. Situations in which the maximum tube current would have been exceeded are presented, and the trade-offs between increasing the effective tube output via 1) decreasing pitch, 2) increasing the scan time, or 3) increasing the kV are discussed. Out of 12 master protocols customized across three different scanners, only one had a statistically significant acceptance rate that differed from the scanner it was customized from. The difference, however, was only 1% and was judged to be negligible. All other master protocols differed in acceptance rate insignificantly between scanners. The methodology described in this paper allows a small set of master protocols to be adapted among different clinical indications on a single scanner and among different CT scanners.

Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis

DTIC Science & Technology

2007-06-01

Protocol for Improved Specificity in Breast Cancer Diagnosis PRINCIPAL INVESTIGATOR: Luminita Alina Tudorica, Ph.D. CONTRACTING...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Clinically Practical Magnetic Resonance Protocol for Improved Specificity in Breast Cancer Diagnosis 5b... breast cancer study in a clinical setting. This study aims to improve specificity of breast cancer detection by using a combined MRI/MRS protocol. In

Practical Recommendations for Robot-Assisted Treadmill Therapy (Lokomat) in Children with Cerebral Palsy: Indications, Goal Setting, and Clinical Implementation within the WHO-ICF Framework.

PubMed

Aurich-Schuler, Tabea; Warken, Birgit; Graser, Judith V; Ulrich, Thilo; Borggraefe, Ingo; Heinen, Florian; Meyer-Heim, Andreas; van Hedel, Hubertus J A; Schroeder, A Sebastian

2015-08-01

Active participation and the highest level of independence during daily living are primary goals in neurorehabilitation. Therefore, standing and walking are key factors in many rehabilitation programs. Despite inconclusive evidence considering the best application and efficacy of robotic tools in the field of pediatric neurorehabilitation, robotic technologies have been implemented to complement conventional therapies in recent years. A group of experienced therapists and physicians joined in an "expert panel." They compared their clinical application protocols, discussed recurring open questions, and developed experience-based recommendations for robot-assisted treadmill therapy (exemplified by the Lokomat, Hocoma, Volketswil, Switzerland) with a focus on children with cerebral palsy. Specific indications and therapeutic goals were defined considering the severity of motor impairments and the International Classification of Functioning, Disability and Health framework (ICF). After five meetings, consensus was found and recommendations for the implementation of robot-assisted treadmill therapy including postsurgery rehabilitation were proposed. This article aims to provide a comprehensive overview on therapeutical applications in a fast developing field of medicine, where scientific evidence is still scarce. These recommendations can help physicians and therapists to plan the child's individual therapy protocol of robot-assisted treadmill therapy. Georg Thieme Verlag KG Stuttgart · New York.

Disaster management mobile protocols: a technology that will save lives.

PubMed

Williamson, Hope M

2011-01-01

Although training and education have long been accepted as integral to disaster preparedness, many currently taught practices are neither evidence based nor standardized. The need for effective evidence-based disaster education for healthcare workers at all levels in the multidisciplinary medical response to major events has been designated by the disaster response community as a high priority. This article describes a disaster management mobile application of systematic evidence-based practice. The application is interactive and comprises portable principles, algorithms, and emergency protocols that are agile, concise, comprehensive, and response relevant to all healthcare workers. Early recognition through clinical assessment versus laboratory and diagnostic procedures in chemical, biological, radiological, and nuclear (CBRNE) exposures grounded in an evidence-based skill set is especially important. During the immediate threat, the clinical diagnosis can get frustrating because CBRNE casualties can mimic everyday healthcare illnesses and initially present with nonspecific respiratory or flu-like symptoms. As there is minimal time in a catastrophic event for the medical provider to make accurate decisions, access to accurate, timely, and comprehensive information in these situations is critical. The CBRNE mobile application is intended to provide a credible source for treatment and management of numerous patients in an often intimidating environment with scarce resources and overwhelming tasks.

Interorganizational exchanges as performance markers in a community cancer network.

PubMed Central

McKinney, M M; Morrissey, J P; Kaluzny, A D

1993-01-01

OBJECTIVE. This study examines how "strategic partnerships" between community-based consortia of oncologists and hospitals (CCOPs) and clinical cooperative groups emerge, develop, and influence patient accruals (i.e., the number of patients enrolled in clinical trials) over time. DATA SOURCES AND STUDY SETTING. Study analyses are based on 65 pairwise relationships that 38 CCOPs established with eight clinical cooperative groups in September 1983 and maintained through February 1989. Data are drawn from grantee applications and progress reports. STUDY DESIGN. The study examines how different types of CCOP-cooperative group exchange relate to one another and to CCOP patient accruals over six time points. Key independent variables include resource dependence, information exchange (i.e., meeting attendance and committee membership), and protocol exchange (i.e., the number of different protocols used). DATA COLLECTION METHODS. Data extracted from secondary sources were entered in a data base. PRINCIPAL FINDINGS. The number of CCOP physicians and support staff who attend cooperative group meetings during the first two years of a clinical research partnership has a significant influence on meeting attendance and protocol use in later years. Two-thirds or more of the variance in patient accruals at each time point can be explained by the number of different protocols used and the number of CCOP representatives serving on cooperative group committees (or attending cooperative group meetings). CONCLUSIONS. The findings highlight the importance of historical relationships and anticipated resource dependence in shaping initial exchange patterns. They also suggest that strategic partnerships need to emphasize structures and processes that encourage early involvement in collaborative activities and that reward participants for maintaining high levels of interaction. PMID:8407338

Extravasation of radiographic contrast media: prevention, diagnosis, and treatment.

PubMed

Tonolini, Massimo; Campari, Alessandro; Bianco, Roberto

2012-01-01

Contrast media extravasation represents a not unusual problem in radiological practice. Incidence, patient-, and procedure-related risk factors, pathogenesis, and clinical manifestations of extravasation injuries are discussed with a review of recent literature, and a practical preventive approach is proposed. A diagnostic and therapeutic protocol, to be applied whenever contrast extravasation is detected, includes radiographic assessment of compartmentalization, antidote application, local care, and clinical follow-up; indications for surgical consultation and adverse event reporting are provided. Copyright © 2012 Mosby, Inc. All rights reserved.

SU-E-J-207: Effect of Pulse Sequence Parameters On Geometric Distortions Induced by a Titanium Brachytherapy Applicator

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

Shea, S; Diak, A; Surucu, M

2015-06-15

Purpose: To investigate the effect of readout bandwidth and voxel size on the appearance of distortion artifacts caused by a titanium brachytherapy applicator. Methods: An acrylic phantom was constructed to rigidly hold a MR conditional, titanium Fletcher-Suit-Delclos-style applicator set (Varian Medical Systems) for imaging on CT (Philips Brilliance) and 1.5T MRI (Siemens Magnetom Aera). Several variants of MRI parameters were tried for 2D T2-weighted turbo spin echo imaging in comparison against the standard clinical protocol with the criteria to keep relative SNR loss less than 20% and imaging time as short as possible. Two 3D sequences were also used formore » comparison with similar parameters. The applicator tandem was segmented on axial CT images (0.4×0.4×1.5mm {sup 3} resolution) and the CT images were registered to the 3D MR images in Eclipse (Varian). The applicator volume was then overlaid on all MRI sets in 3D-Slicer and distances were measured from the tandem tip to the MRI artifact edge in right/left/superior and anterior/posterior/superior directions from coronal and sagittal 2D acquisitions, respectively, or 3D data reformats. Artifact regions were also manually contoured in coronal/sagittal orientations for area measurements. Results: As would be expected, reductions in voxel size and increases in readout bandwidth reduced artifact size (average max artifact length decreased by 0.95 mm and average max area decrease by 0.27 cm{sup 2}). Interestingly, bandwidth increases yielded reductions in area (0.19 cm{sup 2}) and in distance measurements (1 mm) even with voxel increases, as compared to a standard protocol. This could be useful when high performance protocols are not feasible due to long imaging times. Conclusion: We have characterized artifacts caused by cervical brachytherapy applicator across multiple sequence parameters at 1.5T. Future work will focus on finalizing an optimal protocol that balances artifact reduction with imaging time and then testing this new protocol in patients.« less

Co-Designing Mobile Apps to Assist in Clinical Nursing Education: A Study Protocol.

PubMed

O'Connor, Siobhan; Andrews, Tom

2016-01-01

Mobile applications (apps) to train health professionals is gaining momentum as the benefits of mobile learning (mLearning) are becoming apparent in complex clinical environments. However, most educational apps are generic, off-the-shelf pieces of software that do not take into consideration the unique needs of nursing students. The proposed study will apply a user-centred design process to create a tailored mobile app for nursing students to learn and apply clinical skills in practice. The app will be piloted and evaluated to understand how nursing students use mobile technology in clinical settings to support their learning and educational needs.

Wireless medical sensor networks: design requirements and enabling technologies.

PubMed

Vallejos de Schatz, Cecilia H; Medeiros, Henry Ponti; Schneider, Fabio K; Abatti, Paulo J

2012-06-01

This article analyzes wireless communication protocols that could be used in healthcare environments (e.g., hospitals and small clinics) to transfer real-time medical information obtained from noninvasive sensors. For this purpose the features of the three currently most widely used protocols-namely, Bluetooth(®) (IEEE 802.15.1), ZigBee (IEEE 802.15.4), and Wi-Fi (IEEE 802.11)-are evaluated and compared. The important features under consideration include data bandwidth, frequency band, maximum transmission distance, encryption and authentication methods, power consumption, and current applications. In addition, an overview of network requirements with respect to medical sensor features, patient safety and patient data privacy, quality of service, and interoperability between other sensors is briefly presented. Sensor power consumption is also discussed because it is considered one of the main obstacles for wider adoption of wireless networks in medical applications. The outcome of this assessment will be a useful tool in the hands of biomedical engineering researchers. It will provide parameters to select the most effective combination of protocols to implement a specific wireless network of noninvasive medical sensors to monitor patients remotely in the hospital or at home.

Similarity-based modeling in large-scale prediction of drug-drug interactions.

PubMed

Vilar, Santiago; Uriarte, Eugenio; Santana, Lourdes; Lorberbaum, Tal; Hripcsak, George; Friedman, Carol; Tatonetti, Nicholas P

2014-09-01

Drug-drug interactions (DDIs) are a major cause of adverse drug effects and a public health concern, as they increase hospital care expenses and reduce patients' quality of life. DDI detection is, therefore, an important objective in patient safety, one whose pursuit affects drug development and pharmacovigilance. In this article, we describe a protocol applicable on a large scale to predict novel DDIs based on similarity of drug interaction candidates to drugs involved in established DDIs. The method integrates a reference standard database of known DDIs with drug similarity information extracted from different sources, such as 2D and 3D molecular structure, interaction profile, target and side-effect similarities. The method is interpretable in that it generates drug interaction candidates that are traceable to pharmacological or clinical effects. We describe a protocol with applications in patient safety and preclinical toxicity screening. The time frame to implement this protocol is 5-7 h, with additional time potentially necessary, depending on the complexity of the reference standard DDI database and the similarity measures implemented.

MRI vs. CT for orthodontic applications: comparison of two MRI protocols and three CT (multislice, cone-beam, industrial) technologies.

PubMed

Detterbeck, Andreas; Hofmeister, Michael; Hofmann, Elisabeth; Haddad, Daniel; Weber, Daniel; Hölzing, Astrid; Zabler, Simon; Schmid, Matthias; Hiller, Karl-Heinz; Jakob, Peter; Engel, Jens; Hiller, Jochen; Hirschfelder, Ursula

2016-07-01

To examine the relative usefulness and suitability of magnetic resonance imaging (MRI) in daily clinical practice as compared to various technologies of computed tomography (CT) in addressing questions of orthodontic interest. Three blinded raters evaluated 2D slices and 3D reconstructions created from scans of two pig heads. Five imaging modalities were used, including three CT technologies-multislice (MSCT), cone-beam CT (CBCT), and industrial (µCT)-and two MRI protocols with different scan durations. Defined orthodontic parameters were rated one by one on the 2D slices and the 3D reconstructions, followed by final overall ratings for each modality. A mixed linear model was used for statistical analysis. Based on the 2D slices, the parameter of visualizing tooth-germ topography did not yield any significantly different ratings for MRI versus any of the CT scans. While some ratings for the other parameters did involve significant differences, how these should be interpreted depends greatly on the relevance of each parameter. Based on the 3D reconstructions, the only significant difference between technologies was noted for the parameter of visualizing root-surface morphology. Based on the final overall ratings, the imaging performance of the standard MRI protocol was noninferior to the performance of the three CT technologies. On comparing the imaging performance of MRI and CT scans, it becomes clear that MRI has a huge potential for applications in daily clinical practice. Given its additional benefits of a good contrast ratio and complete absence of ionizing radiation, further studies are needed to explore this clinical potential in greater detail.

Comparative studies of mesenchymal stem cells derived from different cord tissue compartments - The influence of cryopreservation and growth media.

PubMed

Dulugiac, Magda; Moldovan, Lucia; Zarnescu, Otilia

2015-10-01

We have identified some critical aspects concerning umbilical cord tissue mesenchymal stem cells: the lack of standards for cell isolation, expansion and cryopreservation, the lack of unanimous opinions upon their multilineage differentiation potential and the existence of very few results related to the functional characterization of the cells isolated from cryopreserved umbilical cord tissue. Umbilical cord tissue cryopreservation appears to be the optimal solution for umbilical cord tissue mesenchymal stem cells storage for future clinical use. Umbilical cord tissue cryopreservation allows mesenchymal stem cells isolation before expected use, according with the specific clinical applications, by different customized isolation and expansion protocols agreed by cell therapy institutions. Using an optimized protocol for umbilical cord tissue cryopreservation in autologous cord blood plasma, isolation explant method and growth media supplemented with FBS or human serum, we performed comparative studies with respect to the characteristics of mesenchymal stem cells (MSC) isolated from different compartments of the same umbilical cord tissue such as Wharton's jelly, vein, arteries, before cryopreservation (pre freeze) and after cryopreservation (post thaw). Expression of histochemical and immunohistochemical markers as well as electron microscopy observations revealed similar adipogenic, chondrogenic and osteogenic differentiation capacity for cells isolated from pre freeze and corresponding post thaw tissue fragments of Wharton's jelly, vein or arteries of the same umbilical cord tissue, regardless growth media used for cells isolation and expansion. Our efficient umbilical cord tissue cryopreservation protocol is reliable for clinical applicability of mesenchymal stem cells that could next be isolated and expanded in compliance with future accepted standards. Copyright © 2015 Elsevier Ltd. All rights reserved.

Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease

NASA Astrophysics Data System (ADS)

Sillay, Karl; Schomberg, Dominic; Hinchman, Angelica; Kumbier, Lauren; Ross, Chris; Kubota, Ken; Brodsky, Ethan; Miranpuri, Gurwattan

2012-04-01

Convection-enhanced delivery (CED) is an advanced infusion technique used to deliver therapeutic agents into the brain. CED has shown promise in recent clinical trials. Independent verification of published parameters is warranted with benchmark testing of published parameters in applicable models such as gel phantoms, ex vivo tissue and in vivo non-human animal models to effectively inform planned and future clinical therapies. In the current study, specific performance characteristics of two CED infusion catheter systems, such as backflow, infusion cloud morphology, volume of distribution (mm3) versus the infused volume (mm3) (Vd/Vi) ratios, rate of infusion (µl min-1) and pressure (mmHg), were examined to ensure published performance standards for the ERG valve-tip (VT) catheter. We tested the hypothesis that the ERG VT catheter with an infusion protocol of a steady 1 µl min-1 functionality is comparable to the newly FDA approved MRI Interventions Smart Flow (SF) catheter with the UCSF infusion protocol in an agarose gel model. In the gel phantom models, no significant difference was found in performance parameters between the VT and SF catheter. We report, for the first time, such benchmark characteristics in CED between these two otherwise similar single-end port VT with stylet and end-port non-stylet infusion systems. Results of the current study in agarose gel models suggest that the performance of the VT catheter is comparable to the SF catheter and warrants further investigation as a tool in the armamentarium of CED techniques for eventual clinical use and application.

Nuclear medicine in clinical urology and nephrology

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

Tauxe, W.N.; Dubousky, E.V.

This book presents explanations of current procedures involving the kidney with information of the performance of each test, its rationale, and interpretation. The information covers all currently used radiopharmaceuticals, radiation dosimetry, instrumentation, test protocols, and mathematical principles of pathophysiology as they relate to nuclear medicine studies. Information is provided on which radiopharmaceutical, instrument, or computer application to use, and when.

Reducing the Indication for Ventilatory Support in the Severely Burned Patient: Results of a New Protocol Approach at a Regional Burn Center.

PubMed

Gille, Jochen; Bauer, Nicole; Malcharek, Michael J; Dragu, Adrian; Sablotzki, Armin; Taha, Hischam; Czeslick, Elke

2016-01-01

Initial management of the severely injured routinely includes sedation and mechanical ventilatory support. However, nonjudiciously applied mechanical ventilatory support can itself lead to poorer patient outcomes. In an attempt to reduce this iatrogenic risk, a standardized, in-house, five-point protocol providing clinical guidance on the use and duration of ventilation was introduced and analyzed, and the impact on patient outcomes was assessed. In 2007, a protocol for early spontaneous breathing was introduced and established in clinical practice. This protocol included: 1) early extubation (≤6 hours after admission) in the absence of absolute ventilatory indication; 2) avoidance of "routine intubation" in spontaneously breathing patients; 3) early postoperative extubation, including patients requiring multiple surgical interventions; 4) intensive chest and respiratory physiotherapy with routine application of expectorants; and 5) early active mobilization. A retrospective clinical study compared patients (group A) over a 2-year period admitted under the new protocol with a historical patient group (group B). Patients in group A (n = 38) had fewer ventilator days over the time-course of treatment (3 [1; 5.8] vs 18.5 days [0.5; 20.5]; P = .0001) with a lower rate of tracheostomies (15.8 vs 54%; P = .0003). Patients on ventilation at admission in group A had shorter ventilation periods after admission (4.75 [4; 22.25] vs 378 hours [8.5; 681.5]; P = .0003), and 66.7% of these patients were extubated within 6 hours of admission (vs 9.1% in group B). No patients fulfilling the inclusion criteria required re- or emergency intubation. In the first 5 days of treatment, significantly lower Sequential Organ Failure Assessment scores were recorded in group A. There was also a trend for lower mortality rates (0 [0%] vs 6 [14%]), sepsis rates (24 [63.2%] vs 37 [88.1%]), and cumulative fluid balance on days 3 and 7 in group A. In contrast, group A demonstrated an elevated rate of pneumonia (15 [39.5%] vs 8 [19%]). These trends, however, lacked statistical significance. Our five-point protocol was safe and easily translated into clinical practice. In the authors experience, this protocol significantly reduced the ventilatory period in severely injured. Furthermore, this study suggests that many injured may be over-treated with routine ventilation, which carries accompanying risks.

Detection of Bacterial Pathogens from Broncho-Alveolar Lavage by Next-Generation Sequencing.

PubMed

Leo, Stefano; Gaïa, Nadia; Ruppé, Etienne; Emonet, Stephane; Girard, Myriam; Lazarevic, Vladimir; Schrenzel, Jacques

2017-09-20

The applications of whole-metagenome shotgun sequencing (WMGS) in routine clinical analysis are still limited. A combination of a DNA extraction procedure, sequencing, and bioinformatics tools is essential for the removal of human DNA and for improving bacterial species identification in a timely manner. We tackled these issues with a broncho-alveolar lavage (BAL) sample from an immunocompromised patient who had developed severe chronic pneumonia. We extracted DNA from the BAL sample with protocols based either on sequential lysis of human and bacterial cells or on the mechanical disruption of all cells. Metagenomic libraries were sequenced on Illumina HiSeq platforms. Microbial community composition was determined by k-mer analysis or by mapping to taxonomic markers. Results were compared to those obtained by conventional clinical culture and molecular methods. Compared to mechanical cell disruption, a sequential lysis protocol resulted in a significantly increased proportion of bacterial DNA over human DNA and higher sequence coverage of Mycobacterium abscessus , Corynebacterium jeikeium and Rothia dentocariosa , the bacteria reported by clinical microbiology tests. In addition, we identified anaerobic bacteria not searched for by the clinical laboratory. Our results further support the implementation of WMGS in clinical routine diagnosis for bacterial identification.

Transdiagnostic and Transcultural: Pilot Study of Unified Protocol for Depressive and Anxiety Disorders in Japan.

PubMed

Ito, Masaya; Horikoshi, Masaru; Kato, Noriko; Oe, Yuki; Fujisato, Hiroko; Nakajima, Shun; Kanie, Ayako; Miyamae, Mitsuhiro; Takebayashi, Yoshitake; Horita, Ryo; Usuki, Masato; Nakagawa, Atsuo; Ono, Yutaka

2016-05-01

Unified protocol (UP) is a transdiagnostic cognitive behavior therapy for emotional disorders. It remains unknown whether UP is applicable for use in non-Western countries and for depressive disorders. We therefore examined its feasibility for a Japanese clinical population using this clinical trial design, which is multicentered, open-labeled, and single-armed (Clinical registry: UMIN000008322). The primary outcome was severity of anxiety symptoms, as assessed using Structured Interview Guide for the Hamilton Anxiety Rating Scale. Secondary outcomes were depressive symptoms, clinical global impression, functioning, quality of life, affectivity, emotion regulation, and adverse events. Of the 28 prospective participants, 17 were eligible and enrolled (depressive disorders=9, anxiety disorders=8). Severity of anxiety symptoms, which decreased significantly after the intervention, remained low for 3months (Hedges' g=1.29, 95% CI=0.56-2.06). Similar tendencies were observed for secondary outcome measures. No severe adverse event occurred. Two participants dropped out of the intervention. High treatment adherence and interrater reliability were confirmed. Results suggest the feasibility of UP in the Japanese context sufficient to warrant a larger clinical trial. Copyright © 2016. Published by Elsevier Ltd.

Micropulsed diode laser therapy: evolution and clinical applications.

PubMed

Sivaprasad, Sobha; Elagouz, Mohammed; McHugh, Dominic; Shona, Olajumoke; Dorin, Giorgio

2010-01-01

Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparative assessment of different recycling methods of orthodontic brackets for clinical use.

PubMed

de Oliveira Correia, Ayla M; de Souza Matos, Felipe; Pilli Jóias, Renata; de Mello Rode, Sigmar; Cesar, Paulo F; Paranhos, Luiz R

2017-06-01

This study aimed to assess bond strength of the resin/bracket interface, under in-vitro shear stress, of metal brackets recycled by different clinical protocols. Sixty stainless steel orthodontic brackets were bonded on acrylic resin. The Transbond XT™ resin was applied at the base of the bracket aided by a matrix, obtaining 1 mm of thickness, and photoactivated with a LED device (40 s; 500 mW/cm2). Samples were randomly divided into four groups (N.=15) according to the reconditioning/recycling protocol: aluminum oxide (AO) 90 µm; hydrofluoric acid 60 s (HA60); hydrofluoric acid 120 s (HA120); hydrofluoric acid 60 s + silane (HA60S). After recycling, the resin was applied at the base of the bracket for shear testing in a universal testing machine (0.5 mm/min). After reconditioning/recycling, the surfaces were analyzed by Scanning Electron Microscopy. Data obtained after the shear test were subjected to ANOVA and Tukey's test (P<0.05). The AO group presented higher values of shear bond strength compared to the other reconditioning/recycling protocols (P<0.05). The HA120 and HA60S groups presented statistically similar results, but HA120 presented strength below the recommended limit. The recycling technique by aluminum oxide sandblasting was more effective for reconditioning orthodontic brackets when compared to the other protocols. The reconditioning technique with 10% hydrofluoric acid followed by the application of silane bonding agent may be used as an alternative protocol.

Decreased intra-lymphocyte cytokines measurement in septic shock patients: A proof of concept study in whole blood.

PubMed

Letessier, Wilfried; Demaret, Julie; Gossez, Morgane; Allam, Camille; Venet, Fabienne; Rimmelé, Thomas; Monneret, Guillaume

2018-04-01

Functional testing protocols are thought to be the gold standard for the exploration of the immune system. However, in terms of routine analysis, they present numerous drawbacks and consequently their use is mainly limited to research applications. In the clinical context of septic shock, characterized by marked lymphocyte alterations, a new approach for lymphocyte intracellular cytokine measurement in whole blood upon was evaluated in a proof-of-concept study. Following lymphocyte activation, simultaneous intracellular labeling of Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), and Interleukin-2 (IL-2) was performed in CD4 + and CD8 + T cells (identified by surface marking). The analysis was carried out by flow cytometry (6 colors). Results obtained in septic patients (n=22) were compared to those of healthy volunteers (n=8). Independently of lymphopenia, there were significant differences between groups. In particular there was significant decrease in the production of IL-2 and TNF-α in septic patients, while the production of IFN-γ was not significantly altered. Polyfunctional results showed that patients presented with increased percentages of triple negative lymphocytes. In contrast, volunteers had higher proportions of triple positive cells. The approach could be performed in a robust and consistent way, taking 4.5h to complete. Moreover, clear differences could be observed between clinical groups with this modified method. These characteristics illustrate the potential of this novel whole blood protocol for clinical applications. However, further research is required to determine the applicability compared to alternative test and to evaluate clinical performances in larger cohorts of patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical implementation and failure mode and effects analysis of HDR skin brachytherapy using Valencia and Leipzig surface applicators.

PubMed

Sayler, Elaine; Eldredge-Hindy, Harriet; Dinome, Jessie; Lockamy, Virginia; Harrison, Amy S

2015-01-01

The planning procedure for Valencia and Leipzig surface applicators (VLSAs) (Nucletron, Veenendaal, The Netherlands) differs substantially from CT-based planning; the unfamiliarity could lead to significant errors. This study applies failure modes and effects analysis (FMEA) to high-dose-rate (HDR) skin brachytherapy using VLSAs to ensure safety and quality. A multidisciplinary team created a protocol for HDR VLSA skin treatments and applied FMEA. Failure modes were identified and scored by severity, occurrence, and detectability. The clinical procedure was then revised to address high-scoring process nodes. Several key components were added to the protocol to minimize risk probability numbers. (1) Diagnosis, prescription, applicator selection, and setup are reviewed at weekly quality assurance rounds. Peer review reduces the likelihood of an inappropriate treatment regime. (2) A template for HDR skin treatments was established in the clinic's electronic medical record system to standardize treatment instructions. This reduces the chances of miscommunication between the physician and planner as well as increases the detectability of an error. (3) A screen check was implemented during the second check to increase detectability of an error. (4) To reduce error probability, the treatment plan worksheet was designed to display plan parameters in a format visually similar to the treatment console display, facilitating data entry and verification. (5) VLSAs are color coded and labeled to match the electronic medical record prescriptions, simplifying in-room selection and verification. Multidisciplinary planning and FMEA increased detectability and reduced error probability during VLSA HDR brachytherapy. This clinical model may be useful to institutions implementing similar procedures. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

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

Soliman, A; Elzibak, A; Fatemi, A

Purpose: To quantitatively evaluate the MR image quality of a novel direction modulated brachytherapy (DMBT) tandem applicator for cervical cancer, using the clinical MRI scanning protocol for image guided brachytherapy. Methods: The tungsten alloy-based applicator was placed in a water phantom and clinical imaging protocol was performed. Axial images were acquired using 2D turbo-spin echo (TSE) T2-weighted sequence on a 1.5T GE 450w MR scanner and an 8-channel body coil. As multi-channel receiver coil was used, inhomogeneities in the B1 receive field must be considered before performing the quantification process. Therefore the applicator was removed from the phantom and themore » whole imaging session was performed again for the water phantom with the same parameters. Images from the two scans were then subtracted, resulting in a difference image that only shows the applicator with its surrounding magnetic susceptibility dipole artifact. Line profiles were drawn and plotted on the difference image at various angles and locations along the tandem. Full width at half maximum (FWHM) was measured at all the line profiles to quantify the extent of the artifact. Additionally, the extent of the artifact along the diameter of the tandem was measured at various angles and locations. Results: After removing the background inhomogeneities of the receiver coil, FWHM of the tandem measured 5.75 ± 0.35 mm (the physical tandem diameter is 5.4 mm). The average extent of the artifacts along the diameter of the tandem measured is 2.14 ± 0.56 mm. In contrast to CT imaging of the same applicator (not shown here), the tandem can be easily identified without additional correction algorithms. Conclusion: This work demonstrated that the novel DMBT tandem applicator has minimal susceptibility artifact in T2-weighted images employed in clinical practice for MRI-guided brachytherapy of cervical cancer.« less

Mouse Models Applied to the Research of Pharmacological Treatments in Asthma.

PubMed

Marqués-García, Fernando; Marcos-Vadillo, Elena

2016-01-01

Models developed for the study of asthma mechanisms can be used to investigate new compounds with pharmacological activity against this disease. The increasing number of compounds requires a preclinical evaluation before starting the application in humans. Preclinical evaluation in animal models reduces the number of clinical trials positively impacting in the cost and in safety. In this chapter, three protocols for the study of drugs are shown: a model to investigate corticoids as a classical treatment of asthma; a protocol to test the effects of retinoic acid (RA) on asthma; and a mouse model to test new therapies in asthma as monoclonal antibodies.

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

PubMed Central

Diehl, Rita; Ferrara, Fabienne; Müller, Claudia; Dreyer, Antje Y; McLeod, Damian D; Fricke, Stephan; Boltze, Johannes

2017-01-01

Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies. PMID:27721455

The reliable multicast protocol application programming interface

NASA Technical Reports Server (NTRS)

Montgomery , Todd; Whetten, Brian

1995-01-01

The Application Programming Interface for the Berkeley/WVU implementation of the Reliable Multicast Protocol is described. This transport layer protocol is implemented as a user library that applications and software buses link against.

CT protocol management: simplifying the process by using a master protocol concept

PubMed Central

Bour, Robert K.; Rubert, Nicholas; Wendt, Gary; Pozniak, Myron; Ranallo, Frank N.

2015-01-01

This article explains a method for creating CT protocols for a wide range of patient body sizes and clinical indications, using detailed tube current information from a small set of commonly used protocols. Analytical expressions were created relating CT technical acquisition parameters which can be used to create new CT protocols on a given scanner or customize protocols from one scanner to another. Plots of mA as a function of patient size for specific anatomical regions were generated and used to identify the tube output needs for patients as a function of size for a single master protocol. Tube output data were obtained from the DICOM header of clinical images from our PACS and patient size was measured from CT localizer radiographs under IRB approval. This master protocol was then used to create 11 additional master protocols. The 12 master protocols were further combined to create 39 single and multiphase clinical protocols. Radiologist acceptance rate of exams scanned using the clinical protocols was monitored for 12,857 patients to analyze the effectiveness of the presented protocol management methods using a two‐tailed Fisher's exact test. A single routine adult abdominal protocol was used as the master protocol to create 11 additional master abdominal protocols of varying dose and beam energy. Situations in which the maximum tube current would have been exceeded are presented, and the trade‐offs between increasing the effective tube output via 1) decreasing pitch, 2) increasing the scan time, or 3) increasing the kV are discussed. Out of 12 master protocols customized across three different scanners, only one had a statistically significant acceptance rate that differed from the scanner it was customized from. The difference, however, was only 1% and was judged to be negligible. All other master protocols differed in acceptance rate insignificantly between scanners. The methodology described in this paper allows a small set of master protocols to be adapted among different clinical indications on a single scanner and among different CT scanners. PACS number: 87.57.Q PMID:26219005

Security architecture for HL/7 message interchange.

PubMed

Chen, T S; Liao, B S; Lin, M G; Gough, T G

2001-01-01

The promotion of quality medical treatment is very important to the healthcare providers as well as to patients. It requires that the medical resources of different hospitals be combined to ensure that medical information is shared and that resources are not wasted. A computer-based patient record is one of the best methods to accomplish the interchange of the patient's clinical data. In our system, the Health Level/Seven (HL/7) format is used for the interchange of the clinical data, as it has been supported by many healthcare providers and become a â standard'. The security of the interchange of clinical data is a serious issue for people using the Internet for data communication. Several international well-developed security algorithms, models and secure policies are adopted in the design of a security handler for an HL/7 architecture. The goal of our system is to combine our security system with the end-to-end communication systems constructed from the HL/7 format to establish a safe delivery channel. A suitable security interchange environment is implemented to address some shortcomings in clinical data interchange. located at the application layer of the ISO/OSI reference model. The medical message components, sub-components, and related types of message event are the primary goals of the HL/7 protocols. The patient management system, the doctor's system for recording his advice, examination and diagnosis as well as any financial management system are all covered by the HL/7 protocols. Healthcare providers and hospitals in Taiwan are very interested in developing the HL/7 protocols as a common standard for clinical data interchange.

Recent Innovations in Collagen Corneal Cross-linking; a Mini Review.

PubMed

Vastardis, Iraklis; Pajic-Eggspuehler, Brigitte; Nichorlis, Charis; Mueller, Jörg; Pajic, Bojan

2017-01-01

The introduction of corneal cross-linking (CXL) with ultraviolet-A (UVA) and Riboflavin photosensitizer (Vit B 2 ) from Seiler et al. , revolutionized the treatment of Keratoconus and other corneal ectatic diseases. Today, the commonly known epithelium off Dresden protocol is in clinical use for the last 15 years with great success and regarded by many as the golden standard. With several studies demonstrating its simplicity, efficacy and safety this revolutionary method, paved the way for new therapies and strategies in the treatment of corneal ectatic diseases and changed our understanding in corneal biomechanics. Recent scientific and technological advances enabled the creation of various modifications of the initial CXL protocol and the formation of new ones. This work highlights the recent advances of CXL, such as the role of oxygen, higher fluence and shorter irradiation times as well as the various clinical applications and updates of this method.

Transdiagnostic Treatment of Bipolar Disorder and Comorbid Anxiety with the Unified Protocol: A Clinical Replication Series

PubMed Central

Ellard, Kristen K.; Deckersbach, Thilo; Sylvia, Louisa G.; Nierenberg, Andrew A.; Barlow, David H.

2013-01-01

Bipolar disorder (BD) is a chronic, debilitating disorder with recurrent manic and depressive episodes. Over 75% of bipolar patients have a current or lifetime diagnosis of a comorbid anxiety disorder. Comorbid anxiety in BD is associated with greater illness severity, greater functional impairment, and poorer illness-related outcomes. Effectively treating comorbid anxiety in individuals with BD has been recognized as one of the biggest unmet needs in the field of bipolar disorder. Recently, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) was developed to be applicable to the full range of anxiety and mood disorders, based upon converging evidence from genetics, cognitive and affective neuroscience, and behavioral research suggesting common, core emotion-related pathology. Here, we present a preliminary evaluation of the efficacy of the UP for the treatment of BD with comorbid anxiety, in a clinical replication series consisting of three cases. PMID:22822175

Workflow based framework for life science informatics.

PubMed

Tiwari, Abhishek; Sekhar, Arvind K T

2007-10-01

Workflow technology is a generic mechanism to integrate diverse types of available resources (databases, servers, software applications and different services) which facilitate knowledge exchange within traditionally divergent fields such as molecular biology, clinical research, computational science, physics, chemistry and statistics. Researchers can easily incorporate and access diverse, distributed tools and data to develop their own research protocols for scientific analysis. Application of workflow technology has been reported in areas like drug discovery, genomics, large-scale gene expression analysis, proteomics, and system biology. In this article, we have discussed the existing workflow systems and the trends in applications of workflow based systems.

Overcoming recruitment challenges in palliative care clinical trials.

PubMed

LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

2013-11-01

Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

Bilateral robots for upper-limb stroke rehabilitation: State of the art and future prospects.

PubMed

Sheng, Bo; Zhang, Yanxin; Meng, Wei; Deng, Chao; Xie, Shengquan

2016-07-01

Robot-assisted bilateral upper-limb training grows abundantly for stroke rehabilitation in recent years and an increasing number of devices and robots have been developed. This paper aims to provide a systematic overview and evaluation of existing bilateral upper-limb rehabilitation devices and robots based on their mechanisms and clinical-outcomes. Most of the articles studied here were searched from nine online databases and the China National Knowledge Infrastructure (CNKI) from year 1993 to 2015. Devices and robots were categorized as end-effectors, exoskeletons and industrial robots. Totally ten end-effectors, one exoskeleton and one industrial robot were evaluated in terms of their mechanical characteristics, degrees of freedom (DOF), supported control modes, clinical applicability and outcomes. Preliminary clinical results of these studies showed that all participants could gain certain improvements in terms of range of motion, strength or physical function after training. Only four studies supported that bilateral training was better than unilateral training. However, most of clinical results cannot definitely verify the effectiveness of mechanisms and clinical protocols used in robotic therapies. To explore the actual value of these robots and devices, further research on ingenious mechanisms, dose-matched clinical protocols and universal evaluation criteria should be conducted in the future. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

PubMed

Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

2014-05-06

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

OSI Upper Layers Support for Applications.

ERIC Educational Resources Information Center

Davison, Wayne

1990-01-01

Discusses how various Open Systems Interconnection (OSI) application layer protocols can be used together, along with the Presentation and Session protocols, to support the interconnection requirements of applications. Application layer protocol standards that are currently available or under development are reviewed, and the File, Transfer,…

Human albumin solders for clinical application during laser tissue welding.

PubMed

Poppas, D P; Wright, E J; Guthrie, P D; Shlahet, L T; Retik, A B

1996-01-01

Fifty percent human albumin solder significantly improves weld strength when compared to lower concentrations [Wright et al., ASLMS meeting, April, 1995]. We developed a method for preparing 50% human albumin that may be considered compatible for clinical applications. Fifty percent human albumin solder was prepared from 25% commercially available human albumin using a lyophilization technique. Assessment of sterility, viscosity, pH, and peak absorption wavelength were performed. This report describes the methodology used to prepare a 50% human albumin solder that is compatible with clinical use. Maintenance of the structural integrity of the albumin was confirmed by polyacrylamide gel electrophoresis. This solder preparation can be used alone or with the addition of exogenous chromophores. The final product is sterile, incorporates viral free protocols, maintains high viscosity, and can be applied easily during open or laparoscopic procedures.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

PubMed Central

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-01-01

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID:26811365

JPRS Report, Science & Technology. Europe: Economic Competitiveness

DTIC Science & Technology

1992-02-24

Health Systems This area covers the harmonisation of methodologies and protocols in epidemiological, biological , clinical and technological...substances and biological agents on human health; and the application and enhancement of biomedical tech- nology to medical health care. Major Health...Work will cover the completion and integration of the genetic and physical maps; the genetic basis for biolog - ical functions; and the setting up a

Generation of Neural Progenitor Spheres from Human Pluripotent Stem Cells in a Suspension Bioreactor.

PubMed

Yan, Yuanwei; Song, Liqing; Tsai, Ang-Chen; Ma, Teng; Li, Yan

2016-01-01

Conventional two-dimensional (2-D) culture systems cannot provide large numbers of human pluripotent stem cells (hPSCs) and their derivatives that are demanded for commercial and clinical applications in in vitro drug screening, disease modeling, and potentially cell therapy. The technologies that support three-dimensional (3-D) suspension culture, such as a stirred bioreactor, are generally considered as promising approaches to produce the required cells. Recently, suspension bioreactors have also been used to generate mini-brain-like structure from hPSCs for disease modeling, showing the important role of bioreactor in stem cell culture. This chapter describes a detailed culture protocol for neural commitment of hPSCs into neural progenitor cell (NPC) spheres using a spinner bioreactor. The basic steps to prepare hPSCs for bioreactor inoculation are illustrated from cell thawing to cell propagation. The method for generating NPCs from hPSCs in the spinner bioreactor along with the static control is then described. The protocol in this study can be applied to the generation of NPCs from hPSCs for further neural subtype specification, 3-D neural tissue development, or potential preclinical studies or clinical applications in neurological diseases.

Clinical Application of Standardized Cognitive Assessment Using fMRI. I. Matrix Reasoning

PubMed Central

Allen, Mark D.; Fong, Alina K.

2008-01-01

Functional MRI is increasingly recognized for its potential as a powerful new tool in clinical neuropsychology. This is likely due to the fact that, with some degree of innovation, it is possible to convert practically any familiar cognitive test into one that can be performed in the MRI scanning environment. However, like any assessment approach, meaningful interpretation of fMRI data for the purpose of patient evaluation crucially requires normative data derived from a sample of unimpaired persons, against which individual patients may be compared. Currently, no such normative data are available for any fMRI-based cognitive testing protocol. In this paper, we report the first of a series of fMRI-compatible cognitive assessment protocols, a matrix reasoning test (f-MRT), for which normative samples of functional activation have been collected from unimpaired control subjects and structured in a manner that makes individual patient evaluation possible in terms of familiar z-score distributions. Practical application of the f-MRT is demonstrated via a contrastive case-study of two individuals with cognitive impairment in which fMRI data identifies subtleties in patient deficits otherwise missed by conventional measures of performance. PMID:19641250

How to implement a clinical pathway for intensive glucose regulation in acute coronary syndromes.

PubMed

de Mulder, Maarten; Zwaan, Esther; Wielinga, Yvonne; Stam, Frank; Umans, Victor A W M

2009-06-01

Hyperglycemia upon admission of myocardial infarction patients predicts inferior clinical outcomes. Current strategies investigating hyperglycemia correction mostly use glucose-driven protocols. Implementation of these often labor-intensive protocols might be facilitated with the approach of a clinical pathway. Therefore, we evaluated the implementation of our glucose-driven protocol.We adapted a protocol for use in our coronary care unit (CCU), which was implemented according to the steps of a clinical pathway. To compensate for carbohydrates in meals we additionally developed a regimen of subcutaneous insulin.Protocol adherence was facilitated with a Web-based insulin calculator. All hyperglycemic patients admitted to the CCU were eligible for treatment according to this protocol.In a 4-month period, 643 glucose measurements were obtained in hyperglycemic patients admitted to our CCU. Patients were treated intensively with IV insulin for 35 hours and had 23 glucose measurements in this time span on average. This regimen achieved a median glucose of 6.2 mmol/L. Severe hypoglycemia occurred in only 1.1% of measurements and was without severe clinical side effects.Introduction of new intensive insulin protocol according to the steps of a clinical pathway is safe and feasible. The presence of a clinical pathway coordinator and sound communication are important conditions for successful introduction, which can be further aided with a computerized calculator.

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions: an iliac angioplasty exemplar case study.

PubMed

Fernández-Gutiérrez, Fabiola; Martínez, Santiago; Rube, Martin A; Cox, Benjamin F; Fatahi, Mahsa; Scott-Brown, Kenneth C; Houston, J Graeme; McLeod, Helen; White, Richard D; French, Karen; Gueorguieva, Mariana; Immel, Erwin; Melzer, Andreas

2015-10-01

A methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics. Three clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages' durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated. Significant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries. This work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education.

Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic Framework

PubMed Central

Yavari, Fatemeh; Nitsche, Michael A.; Ekhtiari, Hamed

2017-01-01

During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future. PMID:28450832

Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application.

PubMed

Karakatsanis, Nicolas A; Lodge, Martin A; Tahari, Abdel K; Zhou, Y; Wahl, Richard L; Rahmim, Arman

2013-10-21

Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ~15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ~45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole body. In addition, the total acquisition length can be reduced from 45 to ~35 min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error and the CNR metrics, resulting in enhanced task-based imaging.

Dynamic whole body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

PubMed Central

Karakatsanis, Nicolas A.; Lodge, Martin A.; Tahari, Abdel K.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

2013-01-01

Static whole body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single bed-coverage limiting the axial field-of-view to ~15–20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole body PET acquisition protocol of ~45min total length is presented, composed of (i) an initial 6-min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (6 passes x 7 bed positions, each scanned for 45sec). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares (OLS) Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of 10 different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole-body. In addition, the total acquisition length can be reduced from 45min to ~35min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error (MSE) and the CNR metrics, resulting in enhanced task-based imaging. PMID:24080962

Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Lodge, Martin A.; Tahari, Abdel K.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

2013-10-01

Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ˜15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ˜45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole body. In addition, the total acquisition length can be reduced from 45 to ˜35 min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error and the CNR metrics, resulting in enhanced task-based imaging.

The applicability of real-time PCR in the diagnostic of cutaneous leishmaniasis and parasite quantification for clinical management: Current status and perspectives.

PubMed

Moreira, Otacilio C; Yadon, Zaida E; Cupolillo, Elisa

2017-09-29

Cutaneous leishmaniasis (CL) is spread worldwide and is the most common manifestation of leishmaniasis. Diagnosis is performed by combining clinical and epidemiological features, and through the detection of Leishmania parasites (or DNA) in tissue specimens or trough parasite isolation in culture medium. Diagnosis of CL is challenging, reflecting the pleomorphic clinical manifestations of this disease. Skin lesions vary in severity, clinical appearance, and duration, and in some cases, they can be indistinguishable from lesions related to other diseases. Over the past few decades, PCR-based methods, including real-time PCR assays, have been developed for Leishmania detection, quantification and species identification, improving the molecular diagnosis of CL. This review provides an overview of many real-time PCR methods reported for the diagnostic evaluation of CL and some recommendations for the application of these methods for quantification purposes for clinical management and epidemiological studies. Furthermore, the use of real-time PCR for Leishmania species identification is also presented. The advantages of real-time PCR protocols are numerous, including increased sensitivity and specificity and simpler standardization of diagnostic procedures. However, despite the numerous assays described, there is still no consensus regarding the methods employed. Furthermore, the analytical and clinical validation of CL molecular diagnosis has not followed international guidelines so far. A consensus methodology comprising a DNA extraction protocol with an exogenous quality control and an internal reference to normalize parasite load is still needed. In addition, the analytical and clinical performance of any consensus methodology must be accurately assessed. This review shows that a standardization initiative is essential to guide researchers and clinical laboratories towards the achievement of a robust and reproducible methodology, which will permit further evaluation of parasite load as a surrogate marker of prognosis and monitoring of aetiological treatment, particularly in multi-centric observational studies and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

A Guide to Writing a Qualitative Systematic Review Protocol to Enhance Evidence-Based Practice in Nursing and Health Care.

PubMed

Butler, Ashleigh; Hall, Helen; Copnell, Beverley

2016-06-01

The qualitative systematic review is a rapidly developing area of nursing research. In order to present trustworthy, high-quality recommendations, such reviews should be based on a review protocol to minimize bias and enhance transparency and reproducibility. Although there are a number of resources available to guide researchers in developing a quantitative review protocol, very few resources exist for qualitative reviews. To guide researchers through the process of developing a qualitative systematic review protocol, using an example review question. The key elements required in a systematic review protocol are discussed, with a focus on application to qualitative reviews: Development of a research question; formulation of key search terms and strategies; designing a multistage review process; critical appraisal of qualitative literature; development of data extraction techniques; and data synthesis. The paper highlights important considerations during the protocol development process, and uses a previously developed review question as a working example. This paper will assist novice researchers in developing a qualitative systematic review protocol. By providing a worked example of a protocol, the paper encourages the development of review protocols, enhancing the trustworthiness and value of the completed qualitative systematic review findings. Qualitative systematic reviews should be based on well planned, peer reviewed protocols to enhance the trustworthiness of results and thus their usefulness in clinical practice. Protocols should outline, in detail, the processes which will be used to undertake the review, including key search terms, inclusion and exclusion criteria, and the methods used for critical appraisal, data extraction and data analysis to facilitate transparency of the review process. Additionally, journals should encourage and support the publication of review protocols, and should require reference to a protocol prior to publication of the review results. © 2016 Sigma Theta Tau International.

Detection and identification of Leishmania spp.: application of two hsp70-based PCR-RFLP protocols to clinical samples from the New World.

PubMed

Montalvo, Ana M; Fraga, Jorge; Tirado, Dídier; Blandón, Gustavo; Alba, Annia; Van der Auwera, Gert; Vélez, Iván Darío; Muskus, Carlos

2017-07-01

Leishmaniasis is highly prevalent in New World countries, where several methods are available for detection and identification of Leishmania spp. Two hsp70-based PCR protocols (PCR-N and PCR-F) and their corresponding restriction fragment length polymorphisms (RFLP) were applied for detection and identification of Leishmania spp. in clinical samples recruited in Colombia, Guatemala, and Honduras. A total of 93 cases were studied. The samples were classified into positive or suspected of leishmaniasis according to parasitological criteria. Molecular amplification of two different hsp70 gene fragments and further RFLP analysis for identification of Leishmania species was done. The detection in parasitologically positive samples was higher using PCR-N than PCR-F. In the total of samples studied, the main species identified were Leishmania panamensis, Leishmania braziliensis, and Leishmania infantum (chagasi). Although RFLP-N was more efficient for the identification, RFLP-F is necessary for discrimination between L. panamensis and Leishmania guyanesis, of great importance in Colombia. Unexpectedly, one sample from this country revealed an RFLP pattern corresponding to Leishmania naiffi. Both molecular variants are applicable for the study of clinical samples originated in Colombia, Honduras, and Guatemala. Choosing the better tool for each setting depends on the species circulating. More studies are needed to confirm the presence of L. naiffi in Colombian territory.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects present for a specific study phase may have been masked by combining protocols into phase groupings. Presence of informative censoring, such as withdrawal of some protocols from development if they began showing signs of lost interest among investigators, complicates interpretation of Kaplan-Meier estimates. Because this study constitutes a retrospective examination over an extended period of time, it does not allow for the precise identification of relative factors impacting timing. Conclusions Delays not only increase the time and cost to complete clinical trials, but they also diminish their usefulness by failing to answer research questions in time. We believe that research analyzing the time spent traversing defined intervals across the clinical trial protocol development and implementation continuum can stimulate business process analyses and reengineering efforts that could lead to reductions in the time from clinical trial concept to results, thereby accelerating progress in clinical research. PMID:24980279

How to write a surgical clinical research protocol: literature review and practical guide.

PubMed

Rosenthal, Rachel; Schäfer, Juliane; Briel, Matthias; Bucher, Heiner C; Oertli, Daniel; Dell-Kuster, Salome

2014-02-01

The study protocol is the core document of every clinical research project. Clinical research in studies involving surgical interventions presents some specific challenges, which need to be accounted for and described in the study protocol. The aim of this review is to provide a practical guide for developing a clinical study protocol for surgical interventions with a focus on methodologic issues. On the basis of an in-depth literature search of methodologic literature and on some cardinal published surgical trials and observational studies, the authors provides a 10-step guide for developing a clinical study protocol in surgery. This practical guide outlines key methodologic issues important when planning an ethically and scientifically sound research project involving surgical interventions, with the ultimate goal of providing high-level evidence relevant for health care decision making in surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

[Contemplation on the application of big data in clinical medicine].

PubMed

Lian, Lei

2015-01-01

Medicine is another area where big data is being used. The link between clinical treatment and outcome is the key step when applying big data in medicine. In the era of big data, it is critical to collect complete outcome data. Patient follow-up, comprehensive integration of data resources, quality control and standardized data management are the predominant approaches to avoid missing data and data island. Therefore, establishment of systemic patients follow-up protocol and prospective data management strategy are the important aspects of big data in medicine.

Application of FTA sample collection and DNA purification system on the determination of CTG trinucleotide repeat size by PCR-based Southern blotting.

PubMed

Hsiao, K M; Lin, H M; Pan, H; Li, T C; Chen, S S; Jou, S B; Chiu, Y L; Wu, M F; Lin, C C; Li, S Y

1999-01-01

Myotonic dystrophy (DM) is caused by a CTG trinucleotide expansion mutation at exon 15 of the myotonic dystrophy protein kinase gene. The clinical severity of this disease correlates with the length of the CTG trinucleotide repeats. Determination of the CTG repeat length has been primarily relied on by Southern blot analysis of restriction enzyme-digested genomic DNA. The development of PCR-based Southern blotting methodology provides a much more sensitive and simpler protocol for DM diagnosis. However, the quality of the template and the high (G+C) ratio of the amplified region hamper the use of PCR on the diagnosis of DM. A modified PCR protocol to amplify different lengths of CTG repeat region using various concentrations of 7deaza-dGTP has been reported (1). Here we describe a procedure including sample collection, DNA purification, and PCR analysis of CTG repeat length without using 7-deaza-dGTP. This protocol is very sensitive and convenient because only a small number of nucleate cells are needed for detection of CTG expansion. Therefore, it could be very useful in clinical and prenatal diagnosis as well as in prevalence study of DM.

Manufacture of a human mesenchymal stem cell population using an automated cell culture platform.

PubMed

Thomas, Robert James; Chandra, Amit; Liu, Yang; Hourd, Paul C; Conway, Paul P; Williams, David J

2007-09-01

Tissue engineering and regenerative medicine are rapidly developing fields that use cells or cell-based constructs as therapeutic products for a wide range of clinical applications. Efforts to commercialise these therapies are driving a need for capable, scaleable, manufacturing technologies to ensure therapies are able to meet regulatory requirements and are economically viable at industrial scale production. We report the first automated expansion of a human bone marrow derived mesenchymal stem cell population (hMSCs) using a fully automated cell culture platform. Differences in cell population growth profile, attributed to key methodological differences, were observed between the automated protocol and a benchmark manual protocol. However, qualitatively similar cell output, assessed by cell morphology and the expression of typical hMSC markers, was obtained from both systems. Furthermore, the critical importance of minor process variation, e.g. the effect of cell seeding density on characteristics such as population growth kinetics and cell phenotype, was observed irrespective of protocol type. This work highlights the importance of careful process design in therapeutic cell manufacture and demonstrates the potential of automated culture for future optimisation and scale up studies required for the translation of regenerative medicine products from the laboratory to the clinic.

OC ToGo: bed site image integration into OpenClinica with mobile devices

NASA Astrophysics Data System (ADS)

Haak, Daniel; Gehlen, Johan; Jonas, Stephan; Deserno, Thomas M.

2014-03-01

Imaging and image-based measurements nowadays play an essential role in controlled clinical trials, but electronic data capture (EDC) systems insufficiently support integration of captured images by mobile devices (e.g. smartphones and tablets). The web application OpenClinica has established as one of the world's leading EDC systems and is used to collect, manage and store data of clinical trials in electronic case report forms (eCRFs). In this paper, we present a mobile application for instantaneous integration of images into OpenClinica directly during examination on patient's bed site. The communication between the Android application and OpenClinica is based on the simple object access protocol (SOAP) and representational state transfer (REST) web services for metadata, and secure file transfer protocol (SFTP) for image transfer, respectively. OpenClinica's web services are used to query context information (e.g. existing studies, events and subjects) and to import data into the eCRF, as well as export of eCRF metadata and structural information. A stable image transfer is ensured and progress information (e.g. remaining time) visualized to the user. The workflow is demonstrated for a European multi-center registry, where patients with calciphylaxis disease are included. Our approach improves the EDC workflow, saves time, and reduces costs. Furthermore, data privacy is enhanced, since storage of private health data on the imaging devices becomes obsolete.

Positron Emission Tomography: Principles, Technology, and Recent Developments

NASA Astrophysics Data System (ADS)

Ziegler, Sibylle I.

2005-04-01

Positron emission tomography (PET) is a nuclear medical imaging technique for quantitative measurement of physiologic parameters in vivo (an overview of principles and applications can be found in [P.E. Valk, et al., eds. Positron Emission Tomography. Basic Science and Clinical Practice. 2003, Springer: Heidelberg]), based on the detection of small amounts of posi-tron-emitter-labelled biologic molecules. Various radiotracers are available for neuro-logical, cardiological, and oncological applications in the clinic and in research proto-cols. This overview describes the basic principles, technology, and recent develop-ments in PET, followed by a section on the development of a tomograph with ava-lanche photodiodes dedicated for small animal imaging as an example of efforts in the domain of high resolution tomographs.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

PubMed

Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

2016-01-01

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

Application development environment for advanced digital workstations

NASA Astrophysics Data System (ADS)

Valentino, Daniel J.; Harreld, Michael R.; Liu, Brent J.; Brown, Matthew S.; Huang, Lu J.

1998-06-01

One remaining barrier to the clinical acceptance of electronic imaging and information systems is the difficulty in providing intuitive access to the information needed for a specific clinical task (such as reaching a diagnosis or tracking clinical progress). The purpose of this research was to create a development environment that enables the design and implementation of advanced digital imaging workstations. We used formal data and process modeling to identify the diagnostic and quantitative data that radiologists use and the tasks that they typically perform to make clinical decisions. We studied a diverse range of radiology applications, including diagnostic neuroradiology in an academic medical center, pediatric radiology in a children's hospital, screening mammography in a breast cancer center, and thoracic radiology consultation for an oncology clinic. We used object- oriented analysis to develop software toolkits that enable a programmer to rapidly implement applications that closely match clinical tasks. The toolkits support browsing patient information, integrating patient images and reports, manipulating images, and making quantitative measurements on images. Collectively, we refer to these toolkits as the UCLA Digital ViewBox toolkit (ViewBox/Tk). We used the ViewBox/Tk to rapidly prototype and develop a number of diverse medical imaging applications. Our task-based toolkit approach enabled rapid and iterative prototyping of workstations that matched clinical tasks. The toolkit functionality and performance provided a 'hands-on' feeling for manipulating images, and for accessing textual information and reports. The toolkits directly support a new concept for protocol based-reading of diagnostic studies. The design supports the implementation of network-based application services (e.g., prefetching, workflow management, and post-processing) that will facilitate the development of future clinical applications.

Systematic Evaluation of the Patient-Reported Outcome (PRO) Content of Clinical Trial Protocols

PubMed Central

Kyte, Derek; Duffy, Helen; Fletcher, Benjamin; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; King, Madeleine; Draper, Heather; Ives, Jonathan; Brundage, Michael; Blazeby, Jane; Calvert, Melanie

2014-01-01

Background Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. Methods and Findings We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the ‘Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16–41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4–18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively ‘complete’ using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. Conclusions The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols. PMID:25333349

Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues.

PubMed

Meints, Lisa M; Poston, Anne W; Piligian, Brent F; Olson, Claire D; Badger, Katherine S; Woodruff, Peter J; Swarts, Benjamin M

2017-02-17

Chemically modified versions of trehalose, or trehalose analogues, have applications in biology, biotechnology, and pharmaceutical science, among other fields. For instance, trehalose analogues bearing detectable tags have been used to detect Mycobacterium tuberculosis and may have applications as tuberculosis diagnostic imaging agents. Hydrolytically stable versions of trehalose are also being pursued due to their potential for use as non-caloric sweeteners and bioprotective agents. Despite the appeal of this class of compounds for various applications, their potential remains unfulfilled due to the lack of a robust route for their production. Here, we report a detailed protocol for the rapid and efficient one-step biocatalytic synthesis of trehalose analogues that bypasses the problems associated with chemical synthesis. By utilizing the thermostable trehalose synthase (TreT) enzyme from Thermoproteus tenax, trehalose analogues can be generated in a single step from glucose analogues and uridine diphosphate glucose in high yield (up to quantitative conversion) in 15-60 min. A simple and rapid non-chromatographic purification protocol, which consists of spin dialysis and ion exchange, can deliver many trehalose analogues of known concentration in aqueous solution in as little as 45 min. In cases where unreacted glucose analogue still remains, chromatographic purification of the trehalose analogue product can be performed. Overall, this method provides a "green" biocatalytic platform for the expedited synthesis and purification of trehalose analogues that is efficient and accessible to non-chemists. To exemplify the applicability of this method, we describe a protocol for the synthesis, all-aqueous purification, and administration of a trehalose-based click chemistry probe to mycobacteria, all of which took less than 1 hour and enabled fluorescence detection of mycobacteria. In the future, we envision that, among other applications, this protocol may be applied to the rapid synthesis of trehalose-based probes for tuberculosis diagnostics. For instance, short-lived radionuclide-modified trehalose analogues (e.g., 18 F-modified trehalose) could be used for advanced clinical imaging modalities such as positron emission tomography-computed tomography (PET-CT).

What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial.

PubMed

de Oliveira, Adriano Rodrigues; Vanin, Adriane Aver; De Marchi, Thiago; Antonialli, Fernanda Colella; Grandinetti, Vanessa dos Santos; de Paiva, Paulo Roberto Vicente; Albuquerque Pontes, Gianna Móes; Santos, Larissa Aline; Aleixo Junior, Ivo de Oliveira; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal-Junior, Ernesto Cesar Pinto

2014-02-27

Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose-response pattern. The protocol for this study is registered with the Protocol Registry System, ClinicalTrials.gov identifier NCT01844271.

Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification.

PubMed

Ren, Zi; Zeng, Hai-tao; Xu, Yan-wen; Zhuang, Guang-lun; Deng, Jie; Zhang, Cheng; Zhou, Can-quan

2009-02-01

To evaluate the use of multiple displacement amplification (MDA) in preimplantation genetic diagnosis (PGD) for female carriers with Duchenne muscular dystrophy (DMD). MDA was used to amplify a whole genome of single cells. Following the setup on single cells, the test was applied in two clinical cases of PGD. One mutant exon, six short tandem repeats (STR) markers within the dystrophin gene, and amelogenin were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products of single blastomeres. Center for reproductive medicine in First Affiliated Hospital, Sun Yat-sen University, China. Two female carriers with a duplication of exons 3-11 and a deletion of exons 47-50, respectively. The MDA of single cells and fluorescent PCR assays for PGD. The ability to analyze single blastomeres for DMD using MDA. The protocol setup previously allowed for the accurate diagnosis of each embryo. Two clinical cases resulted in a healthy girl, which was the first successful clinical application of MDA in PGD for DMD. We suggest that this protocol is reliable to increase the accuracy of the PGD for DMD.

Clinical examination of subjects with halitosis.

PubMed

Donaldson, A C; Riggio, M P; Rolph, H J; Bagg, J; Hodge, P J

2007-01-01

To develop and apply a detailed clinical protocol for screening and assessing subjects with a complaint of halitosis. Cross-sectional. Several methods were used to recruit subjects with a complaint of halitosis, including a newspaper advertisement. A definition of halitosis arising from within the oral cavity, which is not related to generalized chronic gingivitis, chronic periodontitis or pathology of the oral mucosa was used. An extensive list of exclusion criteria was applied at the initial visit. Eligible subjects were asked to follow strict instructions and complete a questionnaire prior to their second visit for data collection. The clinical examination consisted of an organoleptic assessment, Halimeter reading and periodontal examination. The best method of recruiting subjects was advertising. Of 66 individuals recruited, four failed to attend the screening visit and 25 were excluded. The main reasons for exclusion were poor oral hygiene and existing periodontal disease. Thirty-seven completed the full protocol, resulting in identification of 18 with halitosis and 19 controls. Application of the exclusion criteria resulted in significant attrition of eligible participants. Our results suggest that organoleptic assessment should be regarded as a useful standard for defining subjects with halitosis.

Efficiency Improvement in a Busy Radiology Practice: Determination of Musculoskeletal Magnetic Resonance Imaging Protocol Using Deep-Learning Convolutional Neural Networks.

PubMed

Lee, Young Han

2018-04-04

The purposes of this study are to evaluate the feasibility of protocol determination with a convolutional neural networks (CNN) classifier based on short-text classification and to evaluate the agreements by comparing protocols determined by CNN with those determined by musculoskeletal radiologists. Following institutional review board approval, the database of a hospital information system (HIS) was queried for lists of MRI examinations, referring department, patient age, and patient gender. These were exported to a local workstation for analyses: 5258 and 1018 consecutive musculoskeletal MRI examinations were used for the training and test datasets, respectively. The subjects for pre-processing were routine or tumor protocols and the contents were word combinations of the referring department, region, contrast media (or not), gender, and age. The CNN Embedded vector classifier was used with Word2Vec Google news vectors. The test set was tested with each classification model and results were output as routine or tumor protocols. The CNN determinations were evaluated using the receiver operating characteristic (ROC) curves. The accuracies were evaluated by a radiologist-confirmed protocol as the reference protocols. The optimal cut-off values for protocol determination between routine protocols and tumor protocols was 0.5067 with a sensitivity of 92.10%, a specificity of 95.76%, and an area under curve (AUC) of 0.977. The overall accuracy was 94.2% for the ConvNet model. All MRI protocols were correct in the pelvic bone, upper arm, wrist, and lower leg MRIs. Deep-learning-based convolutional neural networks were clinically utilized to determine musculoskeletal MRI protocols. CNN-based text learning and applications could be extended to other radiologic tasks besides image interpretations, improving the work performance of the radiologist.

Satellite Communications Using Commercial Protocols

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

2000-01-01

NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

Changes in co-contraction during stair descent after manual therapy protocol in knee osteoarthritis: A pilot, single-blind, randomized study.

PubMed

Cruz-Montecinos, Carlos; Flores-Cartes, Rodrigo; Montt-Rodriguez, Agustín; Pozo, Esteban; Besoaín-Saldaña, Alvaro; Horment-Lara, Giselle

2016-10-01

Manual therapy has shown clinical results in patients with knee osteoarthritis. However, the biomechanical aspects during functional tasks have not been explored in depth. Through surface electromyography, the medial and lateral co-contractions of the knee were measured while descending stairs, prior and posterior to applying a manual therapy protocol in the knee, with emphasis on techniques of joint mobilization and soft-tissue management. Sixteen females with slight or moderate knee osteoarthritis were recruited (eight experimental, eight control). It was observed that the lateral co-contraction index of the experimental group, posterior to intervention, increased by 11.7% (p = 0.014). The application of a manual therapy protocol with emphasis on techniques of joint mobilization and soft-tissue management modified lateral co-contraction, which would have a protective effect on the joint. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent advances in corneal collagen cross-linking

PubMed Central

Sachdev, Gitansha Shreyas; Sachdev, Mahipal

2017-01-01

Corneal collagen cross-linking has become the preferred modality of treatment for corneal ectasia since its inception in late 1990s. Numerous studies have demonstrated the safety and efficacy of the conventional protocol. Our understanding of the cross-linking process is ever evolving, with its wide implications in the form of accelerated and pulsed protocols. Newer advancements in technology include various riboflavin formulations and the ability to deliver higher fluence protocols with customised irradiation patterns. A greater degree of customisation is likely the path forward, which will aim at achieving refractive improvements along with disease stability. The use of cross-linking for myopic correction is another avenue under exploration. Combination of half fluence cross-linking with refractive correction for high errors to prevent post LASIK regression is gaining interest. This review aims to highlight the various advancements in the cross-linking technology and its clinical applications. PMID:28905820

Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications.

PubMed

Meier, Raphael P H; Montanari, Elisa; Morel, Philippe; Pimenta, Joël; Schuurman, Henk-Jan; Wandrey, Christine; Gerber-Lemaire, Sandrine; Mahou, Redouan; Bühler, Leo H

2017-01-01

Encapsulated hepatocyte transplantation and encapsulated mesenchymal stem cell transplantation are newly developed potential treatments for acute and chronic liver diseases, respectively. Cells are microencapsulated in biocompatible semipermeable alginate-based hydrogels. Microspheres protect cells against antibodies and immune cells, while allowing nutrients, small/medium size proteins and drugs to diffuse inside and outside the polymer matrix. Microencapsulated cells are assessed in vitro and designed for experimental transplantation and for future clinical applications.Here, we describe the protocol for microencapsulation of hepatocytes and mesenchymal stem cells within hybrid poly(ethylene glycol)-alginate hydrogels.

Pretreatment with low-energy shock waves induces renal vasoconstriction during standard shock wave lithotripsy (SWL): a treatment protocol known to reduce SWL-induced renal injury.

PubMed

Handa, Rajash K; Bailey, Michael R; Paun, Marla; Gao, Sujuan; Connors, Bret A; Willis, Lynn R; Evan, Andrew P

2009-05-01

To test the hypothesis that the pretreatment of the kidney with low-energy shock waves (SWs) will induce renal vasoconstriction sooner than a standard clinical dose of high-energy SWs, thus providing a potential mechanism by which the pretreatment SW lithotripsy (SWL) protocol reduces tissue injury. Female farm pigs (6-weeks-old) were anaesthetized with isoflurane and the lower pole of the right kidney treated with SWs using a conventional electrohydraulic lithotripter (HM3, Dornier GmbH, Germany). Pulsed Doppler ultrasonography was used to measure renal resistive index (RI) in blood vessels as a measure of resistance/impedance to blood flow. RI was recorded from one intralobar artery located in the targeted pole of the kidney, and measurements taken from pigs given sham SW treatment (Group 1; no SWs, four pigs), a standard clinical dose of high-energy SWs (Group 2; 2000 SWs, 24 kV, 120 SWs/min, seven pigs), low-energy SW pretreatment followed by high-energy SWL (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, eight pigs) and low-energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, six pigs). Baseline RI (approximately 0.61) was similar for all groups. Pigs receiving sham SW treatment (Group 1) had no significant change in RI. A standard clinical dose of high-energy SWs (Group 2) did not significantly alter RI during treatment, but did increase RI at 45 min after SWL. Low-energy SWs did not alter RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of high-energy SWs resulted in a significantly earlier (at 1000 SWs) and greater (two-fold) rise in RI than that in Group 2 pigs. This rise in RI during the low/high-energy SWL protocol was not due to a delayed vasoconstrictor response of pretreatment, as low-energy SW treatment alone (Group 4) did not increase RI until 65 min after SWL. The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring after SWL. Thus, the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury.

CareTrack Kids—part 1. Assessing the appropriateness of healthcare delivered to Australian children: study protocol for clinical indicator development

PubMed Central

Wiles, Louise K; Hooper, Tamara D; Hibbert, Peter D; White, Les; Mealing, Nicole; Jaffe, Adam; Cowell, Christopher T; Runciman, William B; Goldstein, Stan; Hallahan, Andrew R; Wakefield, John G; Murphy, Elisabeth; Lau, Annie; Wheaton, Gavin; Williams, Helena M; Hughes, Clifford; Braithwaite, Jeffrey

2015-01-01

Introduction Despite the widespread availability of clinical guidelines, considerable gaps remain between the care that is recommended (appropriate care) and the care provided. This protocol describes a research methodology to develop clinical indicators for appropriate care for common paediatric conditions. Methods and analysis We will identify conditions amenable to population-level appropriateness of care research and develop clinical indicators for each condition. Candidate conditions have been identified from published research; burden of disease, prevalence and frequency of presentation data; and quality of care priority lists. Clinical indicators will be developed through searches of national and international guidelines, and formatted with explicit criteria for inclusion, exclusion, time frame and setting. Experts will review the indicators using a wiki-based approach and modified Delphi process. A formative evaluation of the wiki process will be undertaken. Ethics and dissemination Human Research Ethics Committee approvals have been received from Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service, and the Women's and Children's Health Network (South Australia). Applications are under review with Macquarie University and the Royal Australian College of General Practitioners. We will submit the results of the study to relevant journals and offer national and international presentations. PMID:25854976

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

PubMed

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-04-01

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Establishing treatment protocols for clinical mastitis.

PubMed

Roberson, Jerry R

2003-03-01

Each farm has a unique mix of mastitis pathogens and management procedures that have evolved over time. The herd veterinarian should work with the manager/owner to systematically develop treatment protocols that meet the needs and management of the farm. To establish a mastitis treatment protocol, it is necessary to develop a system to routinely identify clinical mastitis cases, develop a herd-specific severity level assessment system, manage the clinical mastitis cases based on severity level and culture result (when available), avoid antibiotic residues, and monitor the success of the system and alter the protocol as necessary.

IRB Process Improvements: A Machine Learning Analysis.

PubMed

Shoenbill, Kimberly; Song, Yiqiang; Cobb, Nichelle L; Drezner, Marc K; Mendonca, Eneida A

2017-06-01

Clinical research involving humans is critically important, but it is a lengthy and expensive process. Most studies require institutional review board (IRB) approval. Our objective is to identify predictors of delays or accelerations in the IRB review process and apply this knowledge to inform process change in an effort to improve IRB efficiency, transparency, consistency and communication. We analyzed timelines of protocol submissions to determine protocol or IRB characteristics associated with different processing times. Our evaluation included single variable analysis to identify significant predictors of IRB processing time and machine learning methods to predict processing times through the IRB review system. Based on initial identified predictors, changes to IRB workflow and staffing procedures were instituted and we repeated our analysis. Our analysis identified several predictors of delays in the IRB review process including type of IRB review to be conducted, whether a protocol falls under Veteran's Administration purview and specific staff in charge of a protocol's review. We have identified several predictors of delays in IRB protocol review processing times using statistical and machine learning methods. Application of this knowledge to process improvement efforts in two IRBs has led to increased efficiency in protocol review. The workflow and system enhancements that are being made support our four-part goal of improving IRB efficiency, consistency, transparency, and communication.

Comparing the World Health Organization-versus China-recommended protocol for first-trimester medical abortion: a retrospective analysis.

PubMed

Ngo, Thoai D; Park, Min Hae; Xiao, Yuanhong

2012-01-01

To compare the effectiveness, in terms of complete abortion, of the World Health Organization (WHO)- and the China-recommended protocol for first-trimester medical abortion. A retrospective analysis of clinical data from women presenting for first trimester medical abortion between January 2009 and August 2010 at reproductive health clinics in Qingdao, Xi'an, Nanjing, Nanning, and Zhengzhou was conducted. One clinic in Qingdao administered the WHO-recommended protocol (200 mg mifepristone orally followed by 0.8 mg misoprostol buccally 36-48 hours later). Four clinics in the other locations provided the China-recommended procedure (Day 1: 50 mg of mifepristone in the morning, 25 mg in the afternoon; Day 2: 50 mg of mifepristone in the morning, 25 mg in the afternoon; Day 3: 0.6 mg oral misoprostol). Data on reproductive and demographic characteristics were extracted from clinic records, and complete termination was determined on day 14 (post-mifepristone administration). A total of 337 women underwent early medical abortion (167 WHO- and 170 China-recommended procedures). Complete abortion was significantly higher among women who had the WHO protocol than those who received the China protocol (91.0% vs 77.7%, respectively; P < 0.001). Women using the China-recommended protocol were three times more likely to require an additional dose of misoprostol than women using the WHO protocol (21.8% vs 7.8%, respectively; P < 0.001), and had significantly more bleeding on the day of misoprostol administration (12.5 mL vs 18.5 mL; P < 0.001). This clinical audit provides preliminary evidence suggesting the WHO-recommended protocol may be more effective than the China-recommended protocol for early medical abortion. A larger scale study is necessary to compare the methods' effectiveness and acceptability.

Wound-healing outcomes using standardized assessment and care in clinical practice.

PubMed

Bolton, Laura; McNees, Patrick; van Rijswijk, Lia; de Leon, Jean; Lyder, Courtney; Kobza, Laura; Edman, Kelly; Scheurich, Anne; Shannon, Ron; Toth, Michelle

2004-01-01

Wound-healing outcomes applying standardized protocols have typically been measured within controlled clinical trials, not natural settings. Standardized protocols of wound care have been validated for clinical use, creating an opportunity to measure the resulting outcomes. Wound-healing outcomes were explored during clinical use of standardized validated protocols of care based on patient and wound assessments. This was a prospective multicenter study of wound-healing outcomes management in real-world clinical practice. Healing outcomes from March 26 to October 31, 2001, were recorded on patients in 3 long-term care facilities, 1 long-term acute care hospital, and 12 home care agencies for wounds selected by staff to receive care based on computer-generated validated wound care algorithms. After diagnosis, wound dimensions and status were assessed using a tool adapted from the Pressure Sore Status Toolfor use on all wounds. Wound, ostomy, and continence nursing professionals accessed consistent protocols of care, via telemedicine in home care or paper forms in long-term care. A physician entered assessments into a desktop computer in the wound clinic. Based on evidence that healing proceeds faster with fewer infections in environments without gauze, the protocols generally avoided gauze dressings. Most of the 767 wounds selected to receive the standardized-protocols of care were stage III-IV pressure ulcers (n = 373; mean healing time 62 days) or full-thickness venous ulcers (n = 124; mean healing time 57 days). Partial-thickness wounds healed faster than same-etiology full-thickness wounds. These results provide benchmarks for natural-setting healing outcomes and help to define and address wound care challenges. Outcomes primarily using nongauze protocols of care matched or surpassed best previously published results on similar wounds using gauze-based protocols of care, including protocols applying gauze impregnated with growth factors or other agents.

Intracytoplasmic sperm injection: a state of the art technique.

PubMed

Mansour, R

1998-01-01

Of the micromanipulation techniques developed in the twentieth century, intracytoplasmic sperm injection (ICSI) has been the major breakthrough in the field of assisted fertilization. This article reviews the indications for the use of ICSI, its clinical application, the establishment of an ICSI programme including protocol and the results obtained since the introduction of ICSI and the potential risks. In addition, intracytoplasmic spermatid injection is briefly discussed.

Principles and Application of Hydrotherapy for Equine Athletes.

PubMed

King, Melissa R

2016-04-01

Hydrotherapy has become a key element within equine rehabilitation protocols and is used to address range of motion, proprioception, strength, neuromotor control, pain, and inflammation. Various forms of hydrotherapy can be tailored to the individual's injury and the expected return to athletic performance. This article describes the mechanisms of action of hydrotherapies and potential use in the clinical management of equine musculoskeletal injuries. Published by Elsevier Inc.

Networking and Information Technology Research and Development. Supplement to the President’s Budget for FY 2002

DTIC Science & Technology

2001-07-01

Web-based applications to improve health data systems and quality of care; innovative strategies for data collection in clinical settings; approaches...research to increase interoperability and integration of software in distributed systems ; protocols and tools for data annotation and management; and...Generation National Defense and National Security Systems .......................... 27 Improved Health Care Systems for All Citizens

Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization?

PubMed

Londra, Laura; Moreau, Caroline; Strobino, Donna; Bhasin, Aarti; Zhao, Yulian

2016-09-01

To evaluate the association between different ovarian hyperstimulation protocols and ectopic pregnancy (EP) in in vitro fertilization (IVF) cycles in fresh autologous embryo transfer cycles in the United States between 2008 and 2011 as reported to the Society of Assisted Reproductive Technology (SART). Historical cohort study. Not applicable. None. None. All autologous cycles that resulted in a clinical pregnancy after a fresh, intrauterine embryo transfer and described characteristics of cycles according to protocol were included: luteal GnRH agonist, GnRH agonist flare, or GnRH antagonist. Multivariate logistic regression was conducted to investigate the association between type of protocol and EP. Among 136,605 clinical pregnancies, 2,645 (1.94%) were EP. Ectopic pregnancy was more frequent with GnRH antagonist (2.4%) cycles than with GnRH agonist flare (2.1%) or luteal GnRH agonist (1.6%) cycles. After adjusting for maternal and treatment characteristics, the GnRH antagonist and the GnRH agonist flare protocols were associated with increased odds of EP (adjusted odds ratio [aOR] 1.52; 95% confidence interval [CI], 1.39-1.65; and aOR 1.25; 95% CI, 1.09-1.44, respectively) compared with luteal GnRH agonist. Analysis of differences in the factors related to EP in luteal GnRH agonist versus GnRH antagonist protocols indicated that diminished ovarian reserve was associated with an increased risk of EP in luteal GnRH agonist but not in GnRH antagonist cycles. The type of protocol used during ovarian hyperstimulation in fresh autologous cycles was associated with EP. This finding suggests a role for extrapituitary GnRH on the tubal and uterine environment during ovarian hyperstimulation treatment for IVF. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A software defined RTU multi-protocol automatic adaptation data transmission method

NASA Astrophysics Data System (ADS)

Jin, Huiying; Xu, Xingwu; Wang, Zhanfeng; Ma, Weijun; Li, Sheng; Su, Yong; Pan, Yunpeng

2018-02-01

Remote terminal unit (RTU) is the core device of the monitor system in hydrology and water resources. Different devices often have different communication protocols in the application layer, which results in the difficulty in information analysis and communication networking. Therefore, we introduced the idea of software defined hardware, and abstracted the common feature of mainstream communication protocols of RTU application layer, and proposed a uniformed common protocol model. Then, various communication protocol algorithms of application layer are modularized according to the model. The executable codes of these algorithms are labeled by the virtual functions and stored in the flash chips of embedded CPU to form the protocol stack. According to the configuration commands to initialize the RTU communication systems, it is able to achieve dynamic assembling and loading of various application layer communication protocols of RTU and complete the efficient transport of sensor data from RTU to central station when the data acquisition protocol of sensors and various external communication terminals remain unchanged.

Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors.

PubMed

Kutner, Robert H; Zhang, Xian-Yang; Reiser, Jakob

2009-01-01

Over the past decade, lentiviral vectors have emerged as powerful tools for transgene delivery. The use of lentiviral vectors has become commonplace and applications in the fields of neuroscience, hematology, developmental biology, stem cell biology and transgenesis are rapidly emerging. Also, lentiviral vectors are at present being explored in the context of human clinical trials. Here we describe improved protocols to generate highly concentrated lentiviral vector pseudotypes involving different envelope glycoproteins. In this protocol, vector stocks are prepared by transient transfection using standard cell culture media or serum-free media. Such stocks are then concentrated by ultracentrifugation and/or ion exchange chromatography, or by precipitation using polyethylene glycol 6000, resulting in vector titers of up to 10(10) transducing units per milliliter and above. We also provide reliable real-time PCR protocols to titrate lentiviral vectors based on proviral DNA copies present in genomic DNA extracted from transduced cells or on vector RNA. These production/concentration methods result in high-titer vector preparations that show reduced toxicity compared with lentiviral vectors produced using standard protocols involving ultracentrifugation-based methods. The vector production and titration protocol described here can be completed within 8 d.

State of the art: dual-energy CT of the abdomen.

PubMed

Marin, Daniele; Boll, Daniel T; Mileto, Achille; Nelson, Rendon C

2014-05-01

Recent technologic advances in computed tomography (CT)--enabling the nearly simultaneous acquisition of clinical images using two different x-ray energy spectra--have sparked renewed interest in dual-energy CT. By interrogating the unique characteristics of different materials at different x-ray energies, dual-energy CT can be used to provide quantitative information about tissue composition, overcoming the limitations of attenuation-based conventional single-energy CT imaging. In the past few years, intensive research efforts have been devoted to exploiting the unique and powerful opportunities of dual-energy CT for a variety of clinical applications. This has led to CT protocol modifications for radiation dose reduction, improved diagnostic performance for detection and characterization of diseases, as well as image quality optimization. In this review, the authors discuss the basic principles, instrumentation and design, examples of current clinical applications in the abdomen and pelvis, and future opportunities of dual-energy CT.

Feasibility of using interstitial ultrasound for intradiscal thermal therapy: a study in human cadaver lumbar discs

NASA Astrophysics Data System (ADS)

Nau, William H.; Diederich, Chris J.; Shu, Richard

2005-06-01

Application of heat in the spine using resistive wire heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. In this study, interstitial ultrasound was evaluated for the potential to heat intradiscal tissue more precisely by directing energy towards the posterior annular wall while avoiding vertebral bodies. Two single-element directional applicator design configurations were tested: a 1.5 mm OD direct-coupled (DC) applicator which can be implanted directly within the disc, and a catheter-cooled (CC) applicator which is inserted in a 2.4 mm OD catheter with integrated water cooling and implanted within the disc. The transducers were sectored to produce 90° spatial heating patterns for directional control. Both applicator configurations were evaluated in four human cadaver lumbar disc motion segments. Two heating protocols were employed in this study in which the temperature measured 5 mm away from the applicator was controlled to either T = 52 °C, or T > 70 °C for the treatment period. These temperatures (thermal doses) are representative of those required for thermal necrosis of in-growing nociceptor nerve fibres and disc cellularity alone, or with coagulation and restructuring of annular collagen in the high-temperature case. Steady-state temperature maps, and thermal doses (t43) were used to assess the thermal treatments. Results from these studies demonstrated the capability of controlling temperature distributions within selected regions of the disc and annular wall using interstitial ultrasound, with minimal vertebral end-plate heating. While directional heating was demonstrated with both applicator designs, the CC configuration had greater directional heating capabilities and offered better temperature control than the DC configuration, particularly during the high-temperature protocol. Further, ultrasound energy was capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain.

Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept.

PubMed

Almeida, Afonso R; Correia, Daniel V; Fernandes-Platzgummer, Ana; da Silva, Cláudia L; da Silva, Maria Gomes; Anjos, Diogo Remechido; Silva-Santos, Bruno

2016-12-01

The Vδ1 + subset of γδ T lymphocytes is a promising candidate for cancer immunotherapy, but the lack of suitable expansion/differentiation methods has precluded therapeutic application. We set out to develop and test (preclinically) a Vδ1 + T-cell-based protocol that is good manufacturing practice compatible and devoid of feeder cells for prompt clinical translation. We tested multiple combinations of clinical-grade agonist antibodies and cytokines for their capacity to expand and differentiate (more than 2-3 weeks) Vδ1 + T cells from the peripheral blood of healthy donors and patients with chronic lymphocytic leukemia (CLL). We characterized the phenotype and functional potential of the final cellular product, termed Delta One T (DOT) cells, in vitro and in vivo (xenograft models of CLL). We describe a very robust two-step protocol for the selective expansion (up to 2,000-fold in large clinical-grade cell culture bags) and differentiation of cytotoxic Vδ1 + (DOT) cells. These expressed the natural cytotoxicity receptors, NKp30 and NKp44, which synergized with the T-cell receptor to mediate leukemia cell targeting in vitro When transferred in vivo, DOT cells infiltrated tumors and peripheral organs, and persisted until the end of the analysis without showing signs of loss of function; indeed, DOT cells proliferated and produced abundant IFNγ and TNFα, but importantly no IL17, in vivo Critically, DOT cells were capable of inhibiting tumor growth and preventing dissemination in xenograft models of CLL. We provide a clinical-grade method and the preclinical proof of principle for application of a new cellular product, DOT cells, in adoptive immunotherapy of CLL. Clin Cancer Res; 22(23); 5795-804. ©2016 AACR. ©2016 American Association for Cancer Research.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

PubMed

Šišić, Ibrahim; Pojskić, Belma; Mekić Abazović, Alma; Kovčin, Vladimir

2015-08-01

To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Influence of LCD color reproduction accuracy on observer performance using virtual pathology slides

NASA Astrophysics Data System (ADS)

Krupinski, Elizabeth A.; Silverstein, Louis D.; Hashmi, Syed F.; Graham, Anna R.; Weinstein, Ronald S.; Roehrig, Hans

2012-02-01

The use of color LCDs in medical imaging is growing as more clinical specialties use digital images as a resource in diagnosis and treatment decisions. Telemedicine applications such as telepathology, teledermatology and teleophthalmology rely heavily on color images. However, standard methods for calibrating, characterizing and profiling color displays do not exist, resulting in inconsistent presentation. To address this, we developed a calibration, characterization and profiling protocol for color-critical medical imaging applications. Physical characterization of displays calibrated with and without the protocol revealed high color reproduction accuracy with the protocol. The present study assessed the impact of this protocol on observer performance. A set of 250 breast biopsy virtual slide regions of interest (half malignant, half benign) were shown to 6 pathologists, once using the calibration protocol and once using the same display in its "native" off-the-shelf uncalibrated state. Diagnostic accuracy and time to render a decision were measured. In terms of ROC performance, Az (area under the curve) calibrated = 0.8640; uncalibrated = 0.8558. No statistically significant difference (p = 0.2719) was observed. In terms of interpretation speed, mean calibrated = 4.895 sec, mean uncalibrated = 6.304 sec which is statistically significant (p = 0.0460). Early results suggest a slight advantage diagnostically for a properly calibrated and color-managed display and a significant potential advantage in terms of improved workflow. Future work should be conducted using different types of color images that may be more dependent on accurate color rendering and a wider range of LCDs with varying characteristics.

Evaluation of Quality Assessment Protocols for High Throughput Genome Resequencing Data

PubMed Central

Chiara, Matteo; Pavesi, Giulio

2017-01-01

Large-scale initiatives aiming to recover the complete sequence of thousands of human genomes are currently being undertaken worldwide, concurring to the generation of a comprehensive catalog of human genetic variation. The ultimate and most ambitious goal of human population scale genomics is the characterization of the so-called human “variome,” through the identification of causal mutations or haplotypes. Several research institutions worldwide currently use genotyping assays based on Next-Generation Sequencing (NGS) for diagnostics and clinical screenings, and the widespread application of such technologies promises major revolutions in medical science. Bioinformatic analysis of human resequencing data is one of the main factors limiting the effectiveness and general applicability of NGS for clinical studies. The requirement for multiple tools, to be combined in dedicated protocols in order to accommodate different types of data (gene panels, exomes, or whole genomes) and the high variability of the data makes difficult the establishment of a ultimate strategy of general use. While there already exist several studies comparing sensitivity and accuracy of bioinformatic pipelines for the identification of single nucleotide variants from resequencing data, little is known about the impact of quality assessment and reads pre-processing strategies. In this work we discuss major strengths and limitations of the various genome resequencing protocols are currently used in molecular diagnostics and for the discovery of novel disease-causing mutations. By taking advantage of publicly available data we devise and suggest a series of best practices for the pre-processing of the data that consistently improve the outcome of genotyping with minimal impacts on computational costs. PMID:28736571

Passive fMRI mapping of language function for pediatric epilepsy surgical planning: validation using Wada, ECS, and FMAER.

PubMed

Suarez, Ralph O; Taimouri, Vahid; Boyer, Katrina; Vega, Clemente; Rotenberg, Alexander; Madsen, Joseph R; Loddenkemper, Tobias; Duffy, Frank H; Prabhu, Sanjay P; Warfield, Simon K

2014-12-01

In this study we validate passive language fMRI protocols designed for clinical application in pediatric epilepsy surgical planning as they do not require overt participation from patients. We introduced a set of quality checks that assess reliability of noninvasive fMRI mappings utilized for clinical purposes. We initially compared two fMRI language mapping paradigms, one active in nature (requiring participation from the patient) and the other passive in nature (requiring no participation from the patient). Group-level analysis in a healthy control cohort demonstrated similar activation of the putative language centers of the brain in the inferior frontal (IFG) and temporoparietal (TPG) regions. Additionally, we showed that passive language fMRI produced more left-lateralized activation in TPG (LI=+0.45) compared to the active task; with similarly robust left-lateralized IFG (LI=+0.24) activations using the passive task. We validated our recommended fMRI mapping protocols in a cohort of 15 pediatric epilepsy patients by direct comparison against the invasive clinical gold-standards. We found that language-specific TPG activation by fMRI agreed to within 9.2mm to subdural localizations by invasive functional mapping in the same patients, and language dominance by fMRI agreed with Wada test results at 80% congruency in TPG and 73% congruency in IFG. Lastly, we tested the recommended passive language fMRI protocols in a cohort of very young patients and confirmed reliable language-specific activation patterns in that challenging cohort. We concluded that language activation maps can be reliably achieved using the passive language fMRI protocols we proposed even in very young (average 7.5 years old) or sedated pediatric epilepsy patients. Copyright © 2014 Elsevier B.V. All rights reserved.

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

PubMed Central

Tetzlaff, Jennifer M; Gøtzsche, Peter C; Altman, Douglas G; Mann, Howard; Berlin, Jesse A; Dickersin, Kay; Hróbjartsson, Asbjørn; Schulz, Kenneth F; Parulekar, Wendy R; Krleža-Jerić, Karmela; Laupacis, Andreas; Moher, David

2013-01-01

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders. PMID:23303884

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Gøtzsche, Peter C; Altman, Douglas G; Mann, Howard; Berlin, Jesse A; Dickersin, Kay; Hróbjartsson, Asbjørn; Schulz, Kenneth F; Parulekar, Wendy R; Krleza-Jeric, Karmela; Laupacis, Andreas; Moher, David

2013-01-08

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model

PubMed Central

Marcuzzo, Stefania; Bonanno, Silvia; Padelli, Francesco; Moreno-Manzano, Victoria; García-Verdugo, José Manuel; Bernasconi, Pia; Mantegazza, Renato; Bruzzone, Maria Grazia; Zucca, Ileana

2016-01-01

Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the optimization of acquisition protocols for preclinical and clinical dMRI studies on the spinal cord. PMID:27560686

A Versatile Microarray Platform for Capturing Rare Cells

NASA Astrophysics Data System (ADS)

Brinkmann, Falko; Hirtz, Michael; Haller, Anna; Gorges, Tobias M.; Vellekoop, Michael J.; Riethdorf, Sabine; Müller, Volkmar; Pantel, Klaus; Fuchs, Harald

2015-10-01

Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or incubation protocol, allows virtual arbitrary targeting of capture species and therefore wide spread applications in biomedical sciences.

Pretreatment with low-energy shock waves induces renal vasoconstriction during standard SWL: a treatment protocol known to reduce lithotripsy-induced renal injury

PubMed Central

Handa, Rajash K.; Bailey, Michael R.; Paun, Marla; Gao, Sujuan; Connors, Bret A.; Willis, Lynn R.; Evan, Andrew P.

2008-01-01

Introduction and Objective A great deal of effort has been focused on developing new treatment protocols to reduce tissue injury to improve the safety of shock wave lithotripsy. This has led to the discovery that pretreatment of the kidney with a series of low-energy shock waves (SWs) will substantially reduce the hemorrhagic lesion that normally results from a standard clinical dose of high-energy SWs. Because renal blood flow is reduced following low- or high-energy SWL, and may therefore contribute to this effect, this study was designed to test the hypothesis that the pretreatment protocol induces renal vasoconstriction sooner than the standard protocol for SW delivery. Methods Female farm pigs (6-weeks old) were anesthetized with isoflurane and the lower pole of the right kidney treated with SWs using the HM3 lithotripter. Pulsed Doppler sonography was used to measure resistive index (RI) in blood vessels as a reflection of resistance/impedance to blood flow. RI was recorded from a single intralobar artery located in the targeted pole of the kidney, and measurements taken from pigs given sham SW treatment (Group 1; no SWs, n = 4), a standard clinical dose of high-energy SWs (Group 2; 2000 SWs, 24 kV, 120 SWs/min, n = 7), low-energy SW pretreatment followed by high-energy SWL (Group 3; 500 SWs, 12 kV, 120 SWs/min + 2000 SWs, 24 kV, 120 SWs/min, n = 8) and low-energy SW pretreatment alone (Group 4; 500 SWs, 12 kV, 120 SWs/min, n = 6). Results Baseline RI (~ 0.61) was similar for all groups. Pigs receiving sham SW treatment (Group 1) had no significant change in RI. A standard clinical dose of high-energy SWs (Group 2) did not significantly alter RI during treatment, but did increase RI at 45-min into the post-SWL period. Low-energy SWs did not alter RI in Group 3 pigs, but subsequent treatment with a standard clinical dose of high-energy SWs resulted in a significantly earlier (at 1000 SWs) and greater (two-fold) rise in RI than that observed in Group 2 pigs. This rise in RI during the low/high-energy SWL treatment protocol was not due to a delayed vasoconstrictor response of pretreatment, as low-energy SW treatment alone (Group 4) did not increase RI until 65 min into the post-SWL period. Conclusions The pretreatment protocol induces renal vasoconstriction during the period of SW application whereas the standard protocol shows vasoconstriction occurring only during the post-SWL period. Thus the earlier and greater rise in RI during the pretreatment protocol may be causally associated with a reduction in tissue injury. PMID:19154458

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

PubMed

Karády, Júlia; Panajotu, Alexisz; Kolossváry, Márton; Szilveszter, Bálint; Jermendy, Ádám L; Bartykowszki, Andrea; Károlyi, Mihály; Celeng, Csilla; Merkely, Béla; Maurovich-Horvat, Pál

2017-11-01

Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Optimization of protocol design: a path to efficient, lower cost clinical trial execution

PubMed Central

Malikova, Marina A

2016-01-01

Managing clinical trials requires strategic planning and efficient execution. In order to achieve a timely delivery of important clinical trials’ outcomes, it is useful to establish standardized trial management guidelines and develop robust scoring methodology for evaluation of study protocol complexity. This review will explore the challenges clinical teams face in developing protocols to ensure that the right patients are enrolled and the right data are collected to demonstrate that a drug is safe and efficacious, while managing study costs and study complexity based on proposed comprehensive scoring model. Key factors to consider when developing protocols and techniques to minimize complexity will be discussed. A methodology to identify processes at planning phase, approaches to increase fiscal return and mitigate fiscal compliance risk for clinical trials will be addressed. PMID:28031939

Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension.

PubMed

Komaroff, A L; Flatley, M; Browne, C; Sherman, H; Fineberg, S E; Knopp, R H

1976-04-01

Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The care rendered by the protocol system was compared with care rendered by a "traditional" system in the same clinic in which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.

MR efficiency using automated MRI-desktop eProtocol

NASA Astrophysics Data System (ADS)

Gao, Fei; Xu, Yanzhe; Panda, Anshuman; Zhang, Min; Hanson, James; Su, Congzhe; Wu, Teresa; Pavlicek, William; James, Judy R.

2017-03-01

MRI protocols are instruction sheets that radiology technologists use in routine clinical practice for guidance (e.g., slice position, acquisition parameters etc.). In Mayo Clinic Arizona (MCA), there are over 900 MR protocols (ranging across neuro, body, cardiac, breast etc.) which makes maintaining and updating the protocol instructions a labor intensive effort. The task is even more challenging given different vendors (Siemens, GE etc.). This is a universal problem faced by all the hospitals and/or medical research institutions. To increase the efficiency of the MR practice, we designed and implemented a web-based platform (eProtocol) to automate the management of MRI protocols. It is built upon a database that automatically extracts protocol information from DICOM compliant images and provides a user-friendly interface to the technologists to create, edit and update the protocols. Advanced operations such as protocol migrations from scanner to scanner and capability to upload Multimedia content were also implemented. To the best of our knowledge, eProtocol is the first MR protocol automated management tool used clinically. It is expected that this platform will significantly improve the radiology operations efficiency including better image quality and exam consistency, fewer repeat examinations and less acquisition errors. These protocols instructions will be readily available to the technologists during scans. In addition, this web-based platform can be extended to other imaging modalities such as CT, Mammography, and Interventional Radiology and different vendors for imaging protocol management.

A "building block" approach to application development for education and decision support in radiology: implications for integrated clinical information systems environments.

PubMed

Greenes, R A

1991-11-01

Education and decision-support resources useful to radiologists are proliferating for the personal computer/workstation user or are potentially accessible via high-speed networks. These resources are typically made available through a set of application programs that tend to be developed in isolation and operate independently. Nonetheless, there is a growing need for an integrated environment for access to these resources in the context of professional work, during clinical problem-solving and decision-making activities, and for use in conjunction with other information resources. New application development environments are required to provide these capabilities. One such architecture for applications, which we have implemented in a prototype environment called DeSyGNER, is based on separately delineating the component information resources required for an application, termed entities, and the user interface and organizational paradigms, or composition methods, by which the entities are used to provide particular kinds of capability. Examples include composition methods to support query, book browsing, hyperlinking, tutorials, simulations, or question/answer testing. Future steps must address true integration of such applications with existing clinical information systems. We believe that the most viable approach for evolving this capability is based on the use of new software engineering methodologies, open systems, client-server communication, and delineation of standard message protocols.

[Clinical outcomes and economic analysis of two ovulation induction protocols in patients undergoing repeated IVF/ICSI cycles].

PubMed

Chen, Xiao; Geng, Ling; Li, Hong

2014-04-01

To compare the clinical outcomes and cost-effectiveness of luteal phase down-regulation with gonadotrophin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol in patients undergoing repeated in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) cycles. A retrospective analysis of clinical outcomes and costs was conducted among 198 patients undergoing repeated IVF-ICSI cycles, including 109 receiving luteal phase down-regulation with GnRH agonist protocol (group A) and 89 receiving GnRH antagonist protocol (group B). The numbers of oocytes retrieved and good embryos, clinical pregnancy rate, abortion rate, the live birth rate, mean total cost, and the cost-effective ratio were compared between the two groups. In patients undergoing repeated IVF-ICSI cycles, the two protocols produced no significant differences in the number of good embryos, clinical pregnancy rate, abortion rate, or twin pregnancy rate. Compared with group B, group A had better clinical outcomes though this difference was not statistically significant. The number of retrieved oocytes was significantly greater and live birth rate significantly higher in group A than in group B (9.13=4.98 vs 7.11=4.74, and 20.2% vs 9.0%, respectively). Compared with group B, group A had higher mean total cost per cycle but lower costs for each oocyte retrieved (2729.11 vs 3038.60 RMB yuan), each good embryo (8867.19 vs 9644.85 RMB yuan), each clinical pregnancy (77598.06 vs 96139.85 RMB yuan). For patients undergoing repeated IVF/ICSI cycle, luteal phase down-regulation with GnRH agonist protocol produces good clinical outcomes with also good cost-effectiveness in spite an unsatisfactory ovarian reserve.

Impact of continuous positive airway pressure on the pulmonary changes promoted by immersion in water

PubMed Central

Rizzetti, Danize Aparecida; Quadros, Janayna Rodembuch Borba; Ribeiro, Bruna Esmerio; Callegaro, Letícia; Veppo, Aline Arebalo; Wiggers, Giulia Alessandra; Peçanha, Franck Maciel

2017-01-01

ABSTRACT Objective: To determine whether different levels of CPAP improve the lung volumes and capacities of healthy subjects immersed in water. Methods: This was a randomized clinical trial, conducted between April and June of 2016, involving healthy female volunteers who were using oral contraceptives. Three 20-min immersion protocols were applied: control (no CPAP); CPAP5 (CPAP at 5 cmH2O); and CPAP10 (CPAP at 10 cmH2O). We evaluated HR, SpO2, FVC, FEV1, the FEV1/FVC ratio, peak expiratory flow rate (PEFR), and FEF25-75%) at three time points: pre-immersion; 10 min after immersion; and 10 min after the end of each protocol. Results: We evaluated 13 healthy volunteers. The CPAP10 protocol reversed the restrictive pattern of lung function induced by immersion in water, maintaining pulmonary volumes and capacities for a longer period than did the CPAP5 protocol. Conclusions: When the hemodynamic change causing a persistent lung disorder, only the application of higher positive pressures is effective in maintaining long-term improvements in the pulmonary profile. PMID:29340488

Impact of continuous positive airway pressure on the pulmonary changes promoted by immersion in water.

PubMed

Rizzetti, Danize Aparecida; Quadros, Janayna Rodembuch Borba; Ribeiro, Bruna Esmerio; Callegaro, Letícia; Veppo, Aline Arebalo; Wiggers, Giulia Alessandra; Peçanha, Franck Maciel

2017-01-01

To determine whether different levels of CPAP improve the lung volumes and capacities of healthy subjects immersed in water. This was a randomized clinical trial, conducted between April and June of 2016, involving healthy female volunteers who were using oral contraceptives. Three 20-min immersion protocols were applied: control (no CPAP); CPAP5 (CPAP at 5 cmH2O); and CPAP10 (CPAP at 10 cmH2O). We evaluated HR, SpO2, FVC, FEV1, the FEV1/FVC ratio, peak expiratory flow rate (PEFR), and FEF25-75%) at three time points: pre-immersion; 10 min after immersion; and 10 min after the end of each protocol. We evaluated 13 healthy volunteers. The CPAP10 protocol reversed the restrictive pattern of lung function induced by immersion in water, maintaining pulmonary volumes and capacities for a longer period than did the CPAP5 protocol. When the hemodynamic change causing a persistent lung disorder, only the application of higher positive pressures is effective in maintaining long-term improvements in the pulmonary profile.

Combined experimental and Monte Carlo verification of brachytherapy plans for vaginal applicators

NASA Astrophysics Data System (ADS)

Sloboda, Ron S.; Wang, Ruqing

1998-12-01

Dose rates in a phantom around a shielded and an unshielded vaginal applicator containing Selectron low-dose-rate sources were determined by experiment and Monte Carlo simulation. Measurements were performed with thermoluminescent dosimeters in a white polystyrene phantom using an experimental protocol geared for precision. Calculations for the same set-up were done using a version of the EGS4 Monte Carlo code system modified for brachytherapy applications into which a new combinatorial geometry package developed by Bielajew was recently incorporated. Measured dose rates agree with Monte Carlo estimates to within 5% (1 SD) for the unshielded applicator, while highlighting some experimental uncertainties for the shielded applicator. Monte Carlo calculations were also done to determine a value for the effective transmission of the shield required for clinical treatment planning, and to estimate the dose rate in water at points in axial and sagittal planes transecting the shielded applicator. Comparison with dose rates generated by the planning system indicates that agreement is better than 5% (1 SD) at most positions. The precision thermoluminescent dosimetry protocol and modified Monte Carlo code are effective complementary tools for brachytherapy applicator dosimetry.

Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

PubMed

Maher, Dermot P; Chen, Lucy; Mao, Jianren

2017-02-01

Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied.

An investigation into the bacterial contamination of goniolenses in use in clinical practice.

PubMed

Grundon, Rachael; Scurrell, Emma; Mould, John; Hayton-Lee, Emma; Heinrich, Christine

2017-12-18

Objectives To report the incidence and evaluate the clinical significance of goniolens bacterial contamination in clinical use in dogs with three different usage protocols and one with an added cleaning protocol. Animals Studied and Methods Three groups of twenty dogs undergoing gonioscopy at a private practice in the UK had the goniolenses swabbed for bacteriology culture and identification prior to placement on the cornea. Three protocols of lens use, with 2 different types of goniolens, were studied. One protocol was then repeated with 21 dogs with a lens cleaning protocol prior to storage. Results Low levels of bacterial contamination were found in all 3 initial groups (10-15%). No correlation was found between usage protocol used and rate of contamination and no correlation was found between length of storage between use and contamination. All bacteria cultured were considered naturally occurring commensals for the canine eye and environment. The group with a cleaning protocol had a 4.7% contamination rate. This was not statistically different from the non-cleaning groups. Conclusions The rate of bacterial contamination of goniolenses in clinical practice is low and the bacterial contaminants consist of commensal bacteria, unlikely to be of detriment to the eye. Minimal contamination of the goniolenses was found and this did not appear to be of clinical significance. The introduction of a simple cleaning protocol did not produce a statistically significant reduction in bacterial contamination. © 2017 American College of Veterinary Ophthalmologists.

Clinical applications of dynamic infrared thermography in plastic surgery: a systematic review

PubMed Central

John, Hannah Eliza; Niumsawatt, Vachara; Whitaker, Iain S.

2016-01-01

Background Infrared thermography (IRT) has become an increasingly utilized adjunct to more expensive and/or invasive investigations in a range of surgical fields, no more so than in plastic surgery. The combination of functional assessment, flow characteristics and anatomical localization has led to increasing applications of this technology. This article aims to perform a systematic review of the clinical applications of IRT in plastic surgery. Methods A systematic literature search using the keywords ‘IRT’ and ‘dynamic infrared thermography (DIRT)’ has been accomplished. A total of 147 papers were extracted from various medical databases, of which 34 articles were subjected to a full read by two independent reviewers, to ensure the papers satisfied the inclusion and exclusion criteria. Studies focusing on the use of IRT in breast cancer diagnosis were excluded. Results A systematic review of 29 publications demonstrated the clinical applications of IRT in plastic surgery today. They include preoperative planning of perforators for free flaps, post operative monitoring of free flaps, use of IRT as an adjunct in burns depth analysis, in assessment of response to treatment in hemangioma and as a diagnostic test for cutaneous melanoma and carpal tunnel syndrome (CTS). Conclusions Modern infrared imaging technology with improved standardization protocols is now a credible, useful non-invasive tool in clinical practice. PMID:27047781

Screening protocol for dysphagia in adults: comparison with videofluoroscopic findings.

PubMed

Sassi, Fernanda C; Medeiros, Gisele C; Zilberstein, Bruno; Jayanthi, Shri Krishna; de Andrade, Claudia R F

2017-12-01

To compare the videofluoroscopic findings of patients with suspected oropharyngeal dysphagia with the results of a clinical screening protocol. A retrospective observational cohort study was conducted on all consecutive patients with suspected oropharyngeal dysphagia between March 2015 and February 2016 who were assigned to receive a videofluoroscopic assessment of swallowing. All patients were first submitted to videofluoroscopy and then to the clinical assessment of swallowing. The clinical assessment was performed within the first 24 hours after videofluoroscopy. The videofluoroscopy results were analyzed regarding penetration/aspiration using an 8-point multidimensional perceptual scale. The accuracy of the clinical protocol was analyzed using the sensitivity, specificity, likelihood ratios and predictive values. The selected sample consisted of 50 patients. The clinical protocol presented a sensitivity of 50% and specificity of 95%, with an accuracy of 88%. "Cough" and "wet-hoarse" vocal quality after/during swallowing were clinical indicators that appeared to correctly identify the presence of penetration/aspiration risk. The clinical protocol used in the present study is a simple, rapid and reliable clinical assessment. Despite the absence of a completely satisfactory result, especially in terms of the sensitivity and positive predictive values, we suggest that lower rates of pneumonia can be achieved using a formal dysphagia screening method.

Development of a cross-disciplinary continuous insulin infusion protocol for non-critically ill patients in a French university hospital.

PubMed

Bernard, Lise; Roche, Béatrice; Batisse, Marie; Maqdasy, Salwan; Terral, Daniel; Sautou, Valérie; Tauveron, Igor

2016-10-01

In non-critically ill patients, the use of an insulin syringe pump allows the management of temporary situations during which other therapies cannot be used (failure of subcutaneous injections, awaiting advice from the diabetes team, emergency situations, prolonged corticosteroid therapy, initiation of an artificial nutrition, need for a fasting status, etc.). To manage the risks related to this «never event», the use of a standard validated protocol for insulin administration and monitoring is an essential prerequisite. To this end, a multidisciplinary approach is recommended. With the support of our subcommission «Endocrinology-Diabetology», we proceeded with a «step-by-step process» to create such a standardized protocol: (1) review of all existing protocols in our hospital; (2) overview of the literature data concerning insulin infusion protocols developed by multidisciplinary teams in France and abroad; (3) development of a standardized protocol for non-intensive care unit patients, respecting the current recommendations and adapting it to the working habits of health teams; and (4) validation of the protocol Two protocols based on the same structure but adapted to the health status of the patient have been developed. The protocols are divided in to three parts: (1) golden rules to make the use of the protocol appropriate and safe; (2) the algorithm (a double entry table) corresponding to a dynamic adaptation of insulin doses, clearly defining the target and the 'at risk situations'; and (3) practical aspects of the protocol: preparation of the syringe, treatment initiation and traceability. The protocols have been validated by the institution. Our standardized insulin infusion protocol is simple, easy to implement, safe and is likely to be applicable in diverse care units. However, the efficiency, safety and the workability of our protocols have to be clinically evaluated. © 2016 John Wiley & Sons, Ltd.

MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses

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

Nakayasu, Ernesto S.; Nicora, Carrie D.; Sims, Amy C.

2016-05-03

ABSTRACT Integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. Despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. Here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-omics measurements. Themetabolite,protein, andlipidextraction (MPLEx) protocol proved to be robust and applicable to a diverse set of sample types, including cell cultures, microbial communities, and tissues. To illustrate the utility of thismore » protocol, an integrative multi-omics analysis was performed using a lung epithelial cell line infected with Middle East respiratory syndrome coronavirus, which showed the impact of this virus on the host glycolytic pathway and also suggested a role for lipids during infection. The MPLEx method is a simple, fast, and robust protocol that can be applied for integrative multi-omic measurements from diverse sample types (e.g., environmental,in vitro, and clinical). IMPORTANCEIn systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated broad applicability and robustness, which enabled comprehensive proteomics, metabolomics, and lipidomics analyses from the same sample.« less

Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.

PubMed

Calvert, Melanie; Kyte, Derek; Mercieca-Bebber, Rebecca; Slade, Anita; Chan, An-Wen; King, Madeleine T; Hunn, Amanda; Bottomley, Andrew; Regnault, Antoine; Chan, An-Wen; Ells, Carolyn; O'Connor, Daniel; Revicki, Dennis; Patrick, Donald; Altman, Doug; Basch, Ethan; Velikova, Galina; Price, Gary; Draper, Heather; Blazeby, Jane; Scott, Jane; Coast, Joanna; Norquist, Josephine; Brown, Julia; Haywood, Kirstie; Johnson, Laura Lee; Campbell, Lisa; Frank, Lori; von Hildebrand, Maria; Brundage, Michael; Palmer, Michael; Kluetz, Paul; Stephens, Richard; Golub, Robert M; Mitchell, Sandra; Groves, Trish

2018-02-06

Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.

Concise Review: The Clinical Application of Mesenchymal Stem Cells for Musculoskeletal Regeneration: Current Status and Perspectives

PubMed Central

Steinert, Andre F.; Rackwitz, Lars; Gilbert, Fabian; Nöth, Ulrich

2012-01-01

Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a “standard of care” treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments. PMID:23197783

Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study.

PubMed

Mellgren, Marianne; Bergvall, Kerstin

2008-01-02

A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice. Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200-476 microg kg-1 subcutaneously 2-3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618-2185 microgkg-1) and oral ivermectin (range 616-2732 microgkg-1) administered by the owners, 3-6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2-20,0 mgkg-1, 1-3 times with an interval of 2-4 weeks. Follow-up time was 4 months-4.5 years. Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively. All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols.

Evaluating the Process of Generating a Clinical Trial Protocol

PubMed Central

Franciosi, Lui G.; Butterfield, Noam N.; MacLeod, Bernard A.

2002-01-01

The research protocol is the principal document in the conduct of a clinical trial. Its generation requires knowledge about the research problem, the potential experimental confounders, and the relevant Good Clinical Practices for conducting the trial. However, such information is not always available to authors during the writing process. A checklist of over 80 items has been developed to better understand the considerations made by authors in generating a protocol. It is based on the most cited requirements for designing and implementing the randomised controlled trial. Items are categorised according to the trial's research question, experimental design, statistics, ethics, and standard operating procedures. This quality assessment tool evaluates the extent that a generated protocol deviates from the best-planned clinical trial.

The use of autologous platelet-rich plasma in the orthopedic setting.

PubMed

Cohn, Claudia S; Lockhart, Evelyn; McCullough, J Jeffrey

2015-07-01

Autologous platelet-rich plasma (aPRP) is widely used with orthopedic patients to help treat injuries to tendons, cartilage, ligaments, and muscle. A comprehensive review of the literature was conducted to evaluate aPRP's efficacy and compare available methods. In addition, the production and administration of aPRP were explored. A literature search was performed. Randomized controlled clinical trials (RCTs) in orthopedic procedures on adult patients were included and assessed for methodologic quality. The main outcomes were pain relief, increase in function, structural integrity, and "healing" based on various validated scales. Twelve RCTs and one controlled cohort were included (four lateral epicondylitis, two chronic Achilles tendinopathy, two anterior cruciate ligament injury, and five rotator cuff injuries). Four trials reported some benefit from aPRP versus controls while eight trials found no benefit from aPRP applications versus control. One study had too many patients withdraw from the control arm for acceptable data interpretation. All protocols used a different aPRP formulation or method of delivery or application. Despite its popularity, there are no standardized criteria that define aPRP. Different techniques yield wide variability in terms of platelet count and concentration. These variations make it difficult to compare clinical trials that use aPRP or draw conclusions concerning its clinical efficacy in orthopedic procedures. Blood bankers have experience in the production of standardized blood components. This expertise may be used to develop and implement protocols for the production and administration of aPRP, as well as quality control measures. © 2015 AABB.

A semi-automatic method for left ventricle volume estimate: an in vivo validation study

NASA Technical Reports Server (NTRS)

Corsi, C.; Lamberti, C.; Sarti, A.; Saracino, G.; Shiota, T.; Thomas, J. D.

2001-01-01

This study aims to the validation of the left ventricular (LV) volume estimates obtained by processing volumetric data utilizing a segmentation model based on level set technique. The validation has been performed by comparing real-time volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation protocol has been defined. The validation protocol was applied to twenty-four estimates (range 61-467 ml) obtained from normal and pathologic subjects, which underwent both RT3DE and MRI. A statistical analysis was performed on each estimate and on clinical parameters as stroke volume (SV) and ejection fraction (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was found with volume measured by utilizing the segmentation procedure (y) (y=0.89x + 13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%. This study demonstrated that the segmentation technique is reliably applicable on human hearts in clinical practice.

Mesenchymal stem cells: biological characteristics and potential clinical applications.

PubMed

Kassem, Moustapha

2004-01-01

Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal-like cells. Several methods are currently available for isolation of the MSC based on their physical and physico-chemical characteristics, for example, adherence to plastics or other extracellular matrix components. Because of the ease of their isolation and their extensive differentiation potential, MSC are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.

From embryonic stem cells to functioning germ cells: science, clinical and ethical perspectives.

PubMed

Kiatpongsan, Sorapop

2007-10-01

Embryonic stem cells have been well recognized as cells having a versatile potential to differentiate into all types of cells in the body including germ cells. There are many research studies focusing on the differentiation processes and protocols to derive various types of somatic cells from embryonic stem cells. However, germ cells have unique differentiation process and developmental pathway compared with somatic cells. Consequently, they will require different differentiation protocols and special culture techniques. More understanding and established in vitro systems for gametogenesis will greatly contribute to further progression of knowledge and technology in germ cell biology, reproductive biology and reproductive medicine. Moreover if oocytes can be efficiently produced in vitro, this will play an important role on progression in nuclear transfer and nuclear reprogramming technology. The present article will provide concise review on past important discoveries, current ongoing studies and future views of this challenging research area. An ethical perspective has also been proposed to give comprehensive summary and viewpoint for future clinical application.

An overview of interstitial brachytherapy and hyperthermia

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

Brandt, B.B.; Harney, J.

Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less

Stigma and Barriers to Care Caring for Those Exposed to War, Disaster and Terrorism

DTIC Science & Technology

2012-03-06

behaviors, and injury. There is a paucity of qualitative study of the narratives of injured soldiers who successfully negotiated barriers to care...Develop qualitative methods to examine the narratives of successful treat- ment across the trajectories of accessing care. • Examine technologies... study and randomize them." Thirty patients consented to this protocol. It is the application of ethnographic methods . It is clinical ethnography . We

DoD Alcohol and Substance Abuse Consortium Award

DTIC Science & Technology

2016-10-01

opiate use disorder (OUD) also has developed significant clinical importance due to prolonged pain treatments with opiates. FDA approved...2) behaviors other than amount of alcohol consumed will be examined, such as anxiety-like behavior, sensitivity to pain and avoidance of an...The prospectus will be reviewed by the entire SRPP Committee and a subset of applications will be approved to develop a 10- to 20-page mini -protocol

Human Cognitive Limitations. Broad, Consistent, Clinical Application of Physiological Principles Will Require Decision Support.

PubMed

Morris, Alan H

2018-02-01

Our education system seems to fail to enable clinicians to broadly understand core physiological principles. The emphasis on reductionist science, including "omics" branches of research, has likely contributed to this decrease in understanding. Consequently, clinicians cannot be expected to consistently make clinical decisions linked to best physiological evidence. This is a large-scale problem with multiple determinants, within an even larger clinical decision problem: the failure of clinicians to consistently link their decisions to best evidence. Clinicians, like all human decision-makers, suffer from significant cognitive limitations. Detailed context-sensitive computer protocols can generate personalized medicine instructions that are well matched to individual patient needs over time and can partially resolve this problem.

A JAVA-based multimedia tool for clinical practice guidelines.

PubMed

Maojo, V; Herrero, C; Valenzuela, F; Crespo, J; Lazaro, P; Pazos, A

1997-01-01

We have developed a specific language for the representation of Clinical Practice Guidelines (CPGs) and Windows C++ and platform independent JAVA applications for multimedia presentation and edition of electronically stored CPGs. This approach facilitates translation of guidelines and protocols from paper to computer-based flowchart representations. Users can navigate through the algorithm with a friendly user interface and access related multimedia information within the context of each clinical problem. CPGs can be stored in a computer server and distributed over the World Wide Web, facilitating dissemination, local adaptation, and use as a reference element in medical care. We have chosen the Agency for Health Care and Policy Research's heart failure guideline to demonstrate the capabilities of our tool.

Hyperbaric oxygen therapy and preconditioning for ischemic and hemorrhagic stroke.

PubMed

Hu, Sheng-Li; Feng, Hua; Xi, Guo-Hua

2016-01-01

To date, the therapeutic methods for ischemic and hemorrhagic stroke are still limited. The lack of oxygen supply is critical for brain injury following stroke. Hyperbaric oxygen (HBO), an approach through a process in which patients breathe in 100% pure oxygen at over 101 kPa, has been shown to facilitate oxygen delivery and increase oxygen supply. Hence, HBO possesses the potentials to produce beneficial effects on stroke. Actually, accumulated basic and clinical evidences have demonstrated that HBO therapy and preconditioning could induce neuroprotective functions via different mechanisms. Nevertheless, the lack of clinical translational study limits the application of HBO. More translational studies and clinical trials are needed in the future to develop effective HBO protocols.

Microcomputer Nurse-Practitioner Protocols

PubMed Central

Way, Anthony B.; Rowley, Blair A.; White, Melanie A.

1982-01-01

We have developed a set of protocols on a microcomputer to assist in the management of a geographically isolated nurse practitioner. If a mid-level practitioner is supervised by a physician, some system is needed to ensure that approved care is being provided. The currently available paper-based protocols do not adequately serve all the needs for training, auditing, and record keeping. Conversely, adequate systems based on large computers are not feasible for small clinics. We have therefore developed a microcomputer-based system of protocols for a small rural nurse-practitioner's clinic. Our programs are designed for direct use by the practitioners while the patient is in the clinic. The user is given immediate feedback about any errors. The supervisor is later provided with a summary of the protocol uses and errors, and a copy of any erroneous records. The system appears to be easy to use by the nurse practitioner. The protocols are quickly learned and auditing is facilitated.

Psychological treatment of Comorbid Asthma and Panic Disorder: A Pilot Study

PubMed Central

Lehrer, Paul M.; Karavidas, Maria Katsamanis; Lu, Shou-En; Feldman, Jonathan; Kranitz, Linda; Abraham, Smrithy; Sanderson, William; Reynolds, Russ

2008-01-01

We evaluated two protocols for treating adults with comorbid asthma and panic disorder. The protocols included elements of Barlow’s “panic control therapy” and several asthma education programs, as well as modules designed to teach participants how to differentiate asthma and panic symptoms, and how to apply specific home management strategies for each. Fifty percent of subjects dropped out of a 14-session protocol by the eighth session; however, 83% of patients were retained in an eight-session protocol. Clinical results were mostly equivalent: significant decreases of >50% in panic symptoms, clinically significant decreases in asthma symptoms, improvement in asthma quality of life, and maintenance of clinical stability in asthma. Albuterol use decreased significantly in the 14-session protocol and at a borderline level in the 8-session protocol, while pulmonary function was maintained. A controlled evaluation of this procedure is warranted. PMID:17693054

Standardized protocols for quality control of MRM-based plasma proteomic workflows.

PubMed

Percy, Andrew J; Chambers, Andrew G; Smith, Derek S; Borchers, Christoph H

2013-01-04

Mass spectrometry (MS)-based proteomics is rapidly emerging as a viable technology for the identification and quantitation of biological samples, such as human plasma--the most complex yet commonly employed biofluid in clinical analyses. The transition from a qualitative to quantitative science is required if proteomics is going to successfully make the transition to a clinically useful technique. MS, however, has been criticized for a lack of reproducibility and interlaboratory transferability. Currently, the MS and plasma proteomics communities lack standardized protocols and reagents to ensure that high-quality quantitative data can be accurately and precisely reproduced by laboratories across the world using different MS technologies. Toward addressing this issue, we have developed standard protocols for multiple reaction monitoring (MRM)-based assays with customized isotopically labeled internal standards for quality control of the sample preparation workflow and the MS platform in quantitative plasma proteomic analyses. The development of reference standards and their application to a single MS platform is discussed herein, along with the results from intralaboratory tests. The tests highlighted the importance of the reference standards in assessing the efficiency and reproducibility of the entire bottom-up proteomic workflow and revealed errors related to the sample preparation and performance quality and deficits of the MS and LC systems. Such evaluations are necessary if MRM-based quantitative plasma proteomics is to be used in verifying and validating putative disease biomarkers across different research laboratories and eventually in clinical laboratories.

Resting-State Functional Magnetic Resonance Imaging for Language Preoperative Planning

PubMed Central

Branco, Paulo; Seixas, Daniela; Deprez, Sabine; Kovacs, Silvia; Peeters, Ronald; Castro, São L.; Sunaert, Stefan

2016-01-01

Functional magnetic resonance imaging (fMRI) is a well-known non-invasive technique for the study of brain function. One of its most common clinical applications is preoperative language mapping, essential for the preservation of function in neurosurgical patients. Typically, fMRI is used to track task-related activity, but poor task performance and movement artifacts can be critical limitations in clinical settings. Recent advances in resting-state protocols open new possibilities for pre-surgical mapping of language potentially overcoming these limitations. To test the feasibility of using resting-state fMRI instead of conventional active task-based protocols, we compared results from fifteen patients with brain lesions while performing a verb-to-noun generation task and while at rest. Task-activity was measured using a general linear model analysis and independent component analysis (ICA). Resting-state networks were extracted using ICA and further classified in two ways: manually by an expert and by using an automated template matching procedure. The results revealed that the automated classification procedure correctly identified language networks as compared to the expert manual classification. We found a good overlay between task-related activity and resting-state language maps, particularly within the language regions of interest. Furthermore, resting-state language maps were as sensitive as task-related maps, and had higher specificity. Our findings suggest that resting-state protocols may be suitable to map language networks in a quick and clinically efficient way. PMID:26869899

An Enhanced LoRaWAN Security Protocol for Privacy Preservation in IoT with a Case Study on a Smart Factory-Enabled Parking System.

PubMed

You, Ilsun; Kwon, Soonhyun; Choudhary, Gaurav; Sharma, Vishal; Seo, Jung Taek

2018-06-08

The Internet of Things (IoT) utilizes algorithms to facilitate intelligent applications across cities in the form of smart-urban projects. As the majority of devices in IoT are battery operated, their applications should be facilitated with a low-power communication setup. Such facility is possible through the Low-Power Wide-Area Network (LPWAN), but at a constrained bit rate. For long-range communication over LPWAN, several approaches and protocols are adopted. One such protocol is the Long-Range Wide Area Network (LoRaWAN), which is a media access layer protocol for long-range communication between the devices and the application servers via LPWAN gateways. However, LoRaWAN comes with fewer security features as a much-secured protocol consumes more battery because of the exorbitant computational overheads. The standard protocol fails to support end-to-end security and perfect forward secrecy while being vulnerable to the replay attack that makes LoRaWAN limited in supporting applications where security (especially end-to-end security) is important. Motivated by this, an enhanced LoRaWAN security protocol is proposed, which not only provides the basic functions of connectivity between the application server and the end device, but additionally averts these listed security issues. The proposed protocol is developed with two options, the Default Option (DO) and the Security-Enhanced Option (SEO). The protocol is validated through Burrows⁻Abadi⁻Needham (BAN) logic and the Automated Validation of Internet Security Protocols and Applications (AVISPA) tool. The proposed protocol is also analyzed for overheads through system-based and low-power device-based evaluations. Further, a case study on a smart factory-enabled parking system is considered for its practical application. The results, in terms of network latency with reliability fitting and signaling overheads, show paramount improvements and better performance for the proposed protocol compared with the two handshake options, Pre-Shared Key (PSK) and Elliptic Curve Cryptography (ECC), of Datagram Transport Layer Security (DTLS).

Healthy individuals' perspectives on clinical research protocols and influences on enrollment decisions.

PubMed

Roberts, Laura Weiss; Kim, Jane Paik

2017-01-01

Understanding the perspectives of healthy individuals is important ethically and for the advancement of science. We assessed perceptions of risk associated with research procedures, comparing views of healthy individuals with and without experience in clinical research, and the respondents' reported willingness to volunteer. Semistructured interviews and written surveys were conducted. Study participants were healthy individuals, half of whom were currently enrolled in clinical research and half of whom had no prior experience in clinical research. Participants were queried regarding seven "minimal risk" or "greater than minimal risk" protocol vignettes with procedures of three types: routine diagnostic tests, more burdensome (i.e., more effort or potential harm) diagnostic tests, and pharmacologic interventions. Views of influences on enrollment decisions were also assessed. Most healthy individuals indicated that protocols with more burdensome or pharmacologic interventions were very risky (59%, 58%), as opposed to routine diagnostic test procedures (32%). Respondents' willingness to enroll in protocols varied by type of protocol (p value < .001) and was inversely correlated with risk assessments (regression coefficients from GEE = -0.4; -0.5; -0.7). The odds of healthy individuals with research experience expressing strong willingness to enroll in the depicted protocols were twice the odds of healthy individuals without research experience expressing the same level of willingness (OR = 2.0 95% CI: [1.1, 3.9]). Respondents did not assign risk categories as institutional review boards (IRBs) would, as indicated by low agreement (26%) between respondent and expert opinion on minimal risk protocols. Perceptions of procedure risk appear to influence healthy individuals' willingness to enroll in protocols. Participants with experience in clinical research were far more likely to express willingness to enroll, a finding with important scientific and ethical implications. The lack of alignment between healthy individuals' views of protocol risk and IRB categorization warrants further study.

Bioreactor expansion of human mesenchymal stem cells according to GMP requirements.

PubMed

Elseberg, Christiane L; Salzig, Denise; Czermak, Peter

2015-01-01

In cell therapy, the use of autologous and allogenic human mesenchymal stem cells is rising. Accordingly, the supply of cells for clinical applications in highest quality is required. As hMSCs are considered as an advanced therapy medicinal products (ATMP), they underlie the requirements of GMP and PAT according to the authorities (FDA and EMA). The production process of these cells must therefore be documented according to GMP, which is usually performed via a GMP protocol based on standard operating procedures. This chapter provides an example of such a GMP protocol for hMSC, here a genetically modified allogenic cell line, based on a production process in a microcarrier-based stirred tank reactor including process monitoring according to PAT and final product quality assurance.

Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy

PubMed Central

2017-01-01

Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies. PMID:28122047

TH-C-18A-08: A Management Tool for CT Dose Monitoring, Analysis, and Protocol Review

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

Wang, J; Chan, F; Newman, B

2014-06-15

Purpose: To develop a customizable tool for enterprise-wide managing of CT protocols and analyzing radiation dose information of CT exams for a variety of quality control applications Methods: All clinical CT protocols implemented on the 11 CT scanners at our institution were extracted in digital format. The original protocols had been preset by our CT management team. A commercial CT dose tracking software (DoseWatch,GE healthcare,WI) was used to collect exam information (exam date, patient age etc.), scanning parameters, and radiation doses for all CT exams. We developed a Matlab-based program (MathWorks,MA) with graphic user interface which allows to analyze themore » scanning protocols with the actual dose estimates, and compare the data to national (ACR,AAPM) and internal reference values for CT quality control. Results: The CT protocol review portion of our tool allows the user to look up the scanning and image reconstruction parameters of any protocol on any of the installed CT systems among about 120 protocols per scanner. In the dose analysis tool, dose information of all CT exams (from 05/2013 to 02/2014) was stratified on a protocol level, and within a protocol down to series level, i.e. each individual exposure event. This allows numerical and graphical review of dose information of any combination of scanner models, protocols and series. The key functions of the tool include: statistics of CTDI, DLP and SSDE, dose monitoring using user-set CTDI/DLP/SSDE thresholds, look-up of any CT exam dose data, and CT protocol review. Conclusion: our inhouse CT management tool provides radiologists, technologists and administration a first-hand near real-time enterprise-wide knowledge on CT dose levels of different exam types. Medical physicists use this tool to manage CT protocols, compare and optimize dose levels across different scanner models. It provides technologists feedback on CT scanning operation, and knowledge on important dose baselines and thresholds.« less

Comparing the World Health Organization-versus China-recommended protocol for first-trimester medical abortion: a retrospective analysis

PubMed Central

Ngo, Thoai D; Park, Min Hae; Xiao, Yuanhong

2012-01-01

Objective To compare the effectiveness, in terms of complete abortion, of the World Health Organization (WHO)- and the China-recommended protocol for first-trimester medical abortion. Methods A retrospective analysis of clinical data from women presenting for first trimester medical abortion between January 2009 and August 2010 at reproductive health clinics in Qingdao, Xi’an, Nanjing, Nanning, and Zhengzhou was conducted. One clinic in Qingdao administered the WHO-recommended protocol (200 mg mifepristone orally followed by 0.8 mg misoprostol buccally 36–48 hours later). Four clinics in the other locations provided the China-recommended procedure (Day 1: 50 mg of mifepristone in the morning, 25 mg in the afternoon; Day 2: 50 mg of mifepristone in the morning, 25 mg in the afternoon; Day 3: 0.6 mg oral misoprostol). Data on reproductive and demographic characteristics were extracted from clinic records, and complete termination was determined on day 14 (post-mifepristone administration). Results A total of 337 women underwent early medical abortion (167 WHO- and 170 China-recommended procedures). Complete abortion was significantly higher among women who had the WHO protocol than those who received the China protocol (91.0% vs 77.7%, respectively; P < 0.001). Women using the China-recommended protocol were three times more likely to require an additional dose of misoprostol than women using the WHO protocol (21.8% vs 7.8%, respectively; P < 0.001), and had significantly more bleeding on the day of misoprostol administration (12.5 mL vs 18.5 mL; P < 0.001). Conclusion This clinical audit provides preliminary evidence suggesting the WHO-recommended protocol may be more effective than the China-recommended protocol for early medical abortion. A larger scale study is necessary to compare the methods’ effectiveness and acceptability. PMID:22505831

Standardized patient walkthroughs in the National Drug Abuse Treatment Clinical Trials Network: common challenges to protocol implementation.

PubMed

Fussell, Holly E; Kunkel, Lynn E; McCarty, Dennis; Lewy, Colleen S

2011-09-01

Training research staff to implement clinical trials occurring in community-based addiction treatment programs presents unique challenges. Standardized patient walkthroughs of study procedures may enhance training and protocol implementation. Examine and discuss cross-site and cross-study challenges of participant screening and data collection procedures identified during standardized patient walkthroughs of multi-site clinical trials. Actors portrayed clients and "walked through" study procedures with protocol research staff. The study completed 57 walkthroughs during implementation of 4 clinical trials. Observers and walkthrough participants identified three areas of concern (consent procedures, screening and assessment processes, and protocol implementation) and made suggestions for resolving the concerns. Standardized patient walkthroughs capture issues with study procedures previously unidentified with didactic training or unscripted rehearsals. Clinical trials within the National Drug Abuse Treatment Clinical Trials Network are conducted in addiction treatment centers that vary on multiple dimensions. Based on walkthrough observations, the national protocol team and local site leadership modify standardized operating procedures and resolve cross-site problems prior to recruiting study participants. The standardized patient walkthrough improves consistency across study sites and reduces potential site variation in study outcomes.

Biophysical Approaches for Oral Wound Healing: Emphasis on Photobiomodulation

PubMed Central

Khan, Imran; Arany, Praveen

2015-01-01

Significance: Oral wounds can lead to significant pain and discomfort as well as affect overall general health due to poor diet and inadequate nutrition. Besides many biological and pharmaceutical methods being investigated, there is growing interest in exploring various biophysical devices that utilize electric, magnetic, ultrasound, pressure, and light energy. Recent Advances: Significant insight into mechanisms of these biophysical devices could provide a clear rationale for their clinical use. Preclinical studies are essential precursors in determining physiological mechanisms and elucidation of causal pathways. This will lead to development of safe and effective therapeutic protocols for clinical wound management. Critical Issues: Identification of precise events initiated by biophysical devices, specifically photobiomodulation—the major focus of this review, offers promising avenues in improving oral wound management. The primary phase responses initiated by the interventions that distinctly contribute to the therapeutic response must be clearly delineated from secondary phase responses. The latter events are a consequence of the wound healing process and must not be confused with causal mechanisms. Future Direction: Clinical adoption of these biophysical devices needs robust and efficacious protocols that can be developed by well-designed preclinical and clinical studies. Elucidation of the precise molecular mechanisms of these biophysical approaches could determine optimization of their applications for predictive oral wound care. PMID:26634185

Feeder-free reprogramming of human fibroblasts with messenger RNA.

PubMed

Warren, Luigi; Wang, Jiwu

2013-11-13

This unit describes a feeder-free protocol for deriving induced pluripotent stem cells (iPSCs) from human fibroblasts by transfection of synthetic mRNA. The reprogramming of somatic cells requires transient expression of a set of transcription factors that collectively activate an endogenous gene regulatory network specifying the pluripotent phenotype. The necessary ectopic factor expression was first effected using retroviruses; however, as viral integration into the genome is problematic for cell therapy applications, the use of footprint-free vectors such as mRNA is increasingly preferred. Strong points of the mRNA approach include high efficiency, rapid kinetics, and obviation of a clean-up phase to purge the vector. Still, the method is relatively laborious and has, up to now, involved the use of feeder cells, which brings drawbacks including poor applicability to clinically oriented iPSC derivation. Using the methods described here, mRNA reprogramming can be performed without feeders at much-reduced labor and material costs relative to established protocols. Copyright © 2013 John Wiley & Sons, Inc.

Plasmid fermentation process for DNA immunization applications.

PubMed

Carnes, Aaron E; Williams, James A

2014-01-01

Plasmid DNA for immunization applications must be of the highest purity and quality. The ability of downstream purification to efficiently produce a pure final product is directly influenced by the performance of the upstream fermentation process. While several clinical manufacturing facilities already have validated fermentation processes in place to manufacture plasmid DNA for use in humans, a simple and inexpensive laboratory-scale fermentation process can be valuable for in-house production of plasmid DNA for use in animal efficacy studies. This chapter describes a simple fed-batch fermentation process for producing bacterial cell paste enriched with high-quality plasmid DNA. A constant feeding strategy results in a medium cell density culture with continuously increasing plasmid amplification towards the end of the process. Cell banking and seed culture preparation protocols, which can dramatically influence final product yield and quality, are also described. These protocols are suitable for production of research-grade plasmid DNA at the 100 mg-to-1.5 g scale from a typical 10 L laboratory benchtop fermentor.

Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

PubMed

Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

2010-12-14

The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

Developing an evidence-based practice protocol: implications for midwifery practice.

PubMed

Carr, K C

2000-01-01

Evidence-based practice is defined and its importance to midwifery practice is presented. Guidelines are provided for the development of an evidence-based practice protocol. These include: identifying the clinical question, obtaining the evidence, evaluating the validity and importance of the evidence, synthesizing the evidence and applying it to the development of a protocol or clinical algorithm, and, finally, developing an evaluation plan or measurement strategy to see if the new protocol is effective.

SPOT: Optimization Tool for Network Adaptable Security

NASA Astrophysics Data System (ADS)

Ksiezopolski, Bogdan; Szalachowski, Pawel; Kotulski, Zbigniew

Recently we have observed the growth of the intelligent application especially with its mobile character, called e-anything. The implementation of these applications provides guarantee of security requirements of the cryptographic protocols which are used in the application. Traditionally the protocols have been configured with the strongest possible security mechanisms. Unfortunately, when the application is used by means of the mobile devices, the strongest protection can lead to the denial of services for them. The solution of this problem is introducing the quality of protection models which will scale the protection level depending on the actual threat level. In this article we would like to introduce the application which manages the protection level of the processes in the mobile environment. The Security Protocol Optimizing Tool (SPOT) optimizes the cryptographic protocol and defines the protocol version appropriate to the actual threat level. In this article the architecture of the SPOT is presented with a detailed description of the included modules.

Intensive care window: real-time monitoring and analysis in the intensive care environment.

PubMed

Stylianides, Nikolas; Dikaiakos, Marios D; Gjermundrød, Harald; Panayi, George; Kyprianou, Theodoros

2011-01-01

This paper introduces a novel, open-source middleware framework for communication with medical devices and an application using the middleware named intensive care window (ICW). The middleware enables communication with intensive care unit bedside-installed medical devices over standard and proprietary communication protocol stacks. The ICW application facilitates the acquisition of vital signs and physiological parameters exported from patient-attached medical devices and sensors. Moreover, ICW provides runtime and post-analysis procedures for data annotation, data visualization, data query, and analysis. The ICW application can be deployed as a stand-alone solution or in conjunction with existing clinical information systems providing a holistic solution to inpatient medical condition monitoring, early diagnosis, and prognosis.

Orthodontic treatment outcomes obtained by application of a finishing protocol

PubMed Central

Carvajal-Flórez, Alvaro; Barbosa-Lis, Diana María; Zapata-Noreña, Oscar Arturo; Marín-Velásquez, Julissa Andrea; Afanador-Bayona, Sergio Andrés

2016-01-01

ABSTRACT Objective: To evaluate the results of a finishing protocol implemented in patients treated in the Orthodontics graduate program at Universidad de Antioquia. Evaluation was carried out by means of the criteria set by the Objective Grading System (OGS) of the American Board of Orthodontics (ABO). Methods: Cast models and panoramic radiographs of 34 patients were evaluated. The intervention group (IG) consisted of 17 patients (19.88 ± 4.4 years old) treated under a finishing protocol. This protocol included training in finishing, application of a finishing guide, brackets repositioning and patient's follow-up. Results of the IG were compared to a control group of 17 patients (21.88 ± 7.0 years old) selected by stratified randomization without finishing intervention (CG). Results: The scores for both CG and IG were 38.00 ± 9.0 and 31.41 ± 9.6 (p = 0.048), respectively. The score improved significantly in the IG group, mainly regarding marginal ridges (CG: 5.59 ± 2.2; IG: 3.65 ± 1.8) (p = 0.009) and root angulation (CG: 7.59 ± 2.8; IG: 4.88 ± 2.6) (p = 0.007). Criteria that did not improve, but had the highest scores were: alignment (CG: 6.35 ± 2.7; IG: 6.82 ± 2.8) (p = 0.62) and buccolingual inclination (CG: 3.6 ± 5.88; IG: 5.29 ± 3.9) (p = 0.65). Conclusions: Standardization and implementation of a finishing protocol contributed to improve clinical performance in the Orthodontics graduate program, as expressed by occlusal outcomes. Greater emphasis should be given on the finishing phase to achieve lower scores in the ABO grading system. PMID:27275620

Development of an alcohol withdrawal protocol: CNS collaborative exemplar.

PubMed

Phillips, Susan; Haycock, Camille; Boyle, Deborah

2006-01-01

The purpose of this process improvement project was to develop an Alcohol Withdrawal Syndrome (AWS) management protocol for acute care. The prevalence of alcohol abuse in our society presents challenges for health professionals, and few nurses have received formal education on the identification and treatment of AWS, which has frequently resulted in ineffective, nonstandardized care. However, nurses practicing in medical-surgical, emergency, trauma, and critical care settings must be astute in the assessment and management of AWS. DESIGN/BACKGROUND/RATIONALE: Following an analysis of existing management protocols, a behavioral health clinical nurse specialist was asked to lead a work team composed of physicians, pharmacists, and nurses to develop a new evidence-based alcohol withdrawal protocol for acute care. By implementing a standardized assessment tool and treatment protocol, clinical nurse specialists empowered nursing staff with strategies to prevent the serious medical complications associated with AWS. FINDINGS/OUTCOMES: The development and integration of a safe and effective treatment protocol to manage AWS was facilitated by collaborative, evidence-based decision making. Clinical experience and specialty expertise were integrated by clinical nurse specialists skilled in group dynamics, problem-solving, and the implementation of change. Improving care of patients in AWS is an exemplar for clinical nurse specialist roles as change agent and patient advocate.

Comparison of eye lens dose on neuroimaging protocols between 16- and 64-section multidetector CT: achieving the lowest possible dose.

PubMed

Tan, J S P; Tan, K-L; Lee, J C L; Wan, C-M; Leong, J-L; Chan, L-L

2009-02-01

To our knowledge, there has been no study that compares the radiation dose delivered to the eye lens by 16- and 64-section multidetector CT (MDCT) for standard clinical neuroimaging protocols. Our aim was to assess radiation-dose differences between 16- and 64-section MDCT from the same manufacturer, by using near-identical neuroimaging protocols. Three cadaveric heads were scanned on 16- and 64-section MDCT by using standard neuroimaging CT protocols. Eye lens dose was measured by using thermoluminescent dosimeters (TLD), and each scanning was repeated to reduce random error. The dose-length product, volume CT dose index (CTDI(vol)), and TLD readings for each imaging protocol were averaged and compared between scanners and protocols, by using the paired Student t test. Statistical significance was defined at P < .05. The radiation dose delivered and eye lens doses were lower by 28.1%-45.7% (P < .000) on the 64-section MDCT for near-identical imaging protocols. On the 16-section MDCT, lens dose reduction was greatest (81.1%) on a tilted axial mode, compared with a nontilted helical mode for CT brain scans. Among the protocols studied, CT of the temporal bone delivered the greatest radiation dose to the eye lens. Eye lens radiation doses delivered by the 64-section MDCT are significantly lower, partly due to improvements in automatic tube current modulation technology. However, where applicable, protection of the eyes from the radiation beam by either repositioning the head or tilting the gantry remains the best way to reduce eye lens dose.

Development of a Decision Support System to Predict Physicians' Rehabilitation Protocols for Patients with Knee Osteoarthritis

ERIC Educational Resources Information Center

Hawamdeh, Ziad M.; Alshraideh, Mohammad A.; Al-Ajlouni, Jihad M.; Salah, Imad K.; Holm, Margo B.; Otom, Ali H.

2012-01-01

To design a medical decision support system (MDSS) that would accurately predict the rehabilitation protocols prescribed by the physicians for patients with knee osteoarthritis (OA) using only their demographic and clinical characteristics. The demographic and clinical variables for 170 patients receiving one of three treatment protocols for knee…

Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

PubMed

Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

2016-05-01

Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. © The Author(s) 2015.

Favourably effective formulation of sodium iodide and salicylic acid plus professional hygiene in patients affected by desquamative gingivitis.

PubMed

Carcieri, P; Broccoletti, R; Giacometti, S; Gambino, A; Conrotto, D; Cabras, M; Arduino, P G

2016-01-01

The aim of this prospective pilot study was to evaluate the efficiency of an oral hygiene protocol, in combination with a solution of sodium iodide associated to salicylic acid (SISA), in patients affected by desquamative gingivitis (DG). Twenty patients not totally responding to conventional topical therapies, were selected. They received oral hygiene instructions with non-surgical periodontal therapy in a 21-day cohort study (during 3 weekly appointments). The SISA was used at the end of each session, with an impregnated gauze (with 5 ml of the solution) applied for 15 minutes for the upper jaw, and for a further 15 minutes with a new gauze for the lower. Evaluated clinical outcome variables included the full mouth plaque (FMPS) and bleeding (FMBS) scores, probing depth, patient related outcome and clinical gingival signs. Two months after concluding the planned protocol, a statistically significant reduction was observed for FMPS (P=0.032), FMBS (P=0.038), reported pain (P=0.000) and gingival clinical improvement (P=0.005). Topical application of SISA and professional oral hygiene procedures are connected with improvement of gum status, and decrease of related pain in subjects affected by severe DG.

DEVELOPING AN IPAD® APPLICATION FOR DATA COLLECTION IN A RHEUMATOLOGY RESEARCH CLINIC.

PubMed

Kaka, Hussam; Ayearst, Renise; Tran, Maithy; Touma, Zahi; Bagovich, Maria; Vinik, Ophir; Somaily, Mansour; Haddad, Amir; Gladman, Dafna D; Chandran, Vinod

2015-01-01

Clinical research data are often collected on paper and later inputted onto an electronic database. This method is time consuming and potentially introduces errors. Therefore, to make primary data collection more efficient and less error prone we aimed to develop a touch-screen application for data collection in a psoriatic arthritis research clinic and compared it with the pre-existing paper-based system. We developed a Web application using Java and optimized it for the iPad®. It highlights missing fields for physicians in real time, and only permits submission of data collection form after corrections are made. For its evaluation, seven physicians participated, and before each patient visit they were randomly assigned paper or iPad® data entry. Number of errors, length of visit, and time between clinic visit and completion of data entry were measured. A total of 106 patients seen in the clinic who agreed to participate were randomly assigned to be evaluated by clinic physicians using the iPad® (fifty-three patients) or a paper protocol (fifty-three patients). On average, 3.34 omissions were found per paper form, of which 2.24 would have been detected on the iPad®. The iPad® increased the mean patient encounter time from 37.2 minutes to 46.5 minutes, but eliminated delay between a clinic visit and its data entry. Entering data using the iPad® application makes the patient encounter slightly longer, but reduces "missing fields." It also eliminates the delay between clinic visit and data entry thus improving the efficiency of clinical data capture in a research setting.

Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

PubMed

Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

Application Level Protocol Development for Library and Information Science Applications. Volume 1: Service Definition. Volume 2: Protocol Specification. Report No. TG.1.5; TG.50.

ERIC Educational Resources Information Center

Aagaard, James S.; And Others

This two-volume document specifies a protocol that was developed using the Reference Model for Open Systems Interconnection (OSI), which provides a framework for communications within a heterogeneous network environment. The protocol implements the features necessary for bibliographic searching, record maintenance, and mail transfer between…

Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

PubMed

Gilaberte, Y; Aguilar, M; Almagro, M; Correia, O; Guillén, C; Harto, A; Pérez-García, B; Pérez-Pérez, L; Redondo, P; Sánchez-Carpintero, I; Serra-Guillén, C; Valladares, L M

2015-10-01

Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Microbiological effects and recolonization patterns after adjunctive subgingival debridement with Er:YAG laser.

PubMed

Sanz-Sánchez, Ignacio; Ortiz-Vigón, Alberto; Herrera, David; Sanz, Mariano

2016-07-01

The objective of this study was to assess the microbiological effects and recolonization patterns after non-surgical periodontal treatment protocol based on the adjunctive use of erbium-doped yttrium aluminium garnet (Er:YAG) laser. Patients diagnosed with chronic periodontitis were randomly assigned to two different treatment protocols: test, full-mouth subgingival ultrasonic instrumentation followed by Er-YAG laser application 1 week later to sites with initial probing pocket depth ≥4.5 mm; and control, full-mouth ultrasonic subgingival instrumentation within 1 week. Clinical (at sampled sites) and microbiological (culture-based) parameters were recorded at baseline and 3 and 12 months. Microbiological variables included total counts, frequency of detection, proportions and counts of target species. Results from 19 test and 21 control patients were compared. Minor changes were observed for total colony-forming units, with no differences between groups. For the frequency of detection, a limited and similar impact in both groups was observed for the most prevalent (over 80 %) periodontal pathogens (Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum). For proportions, reductions in P. gingivalis occurred at 3 months, both in the test and control groups (from 16.3 to 10 % and 16 to 14.8 %, respectively), although these differences were not statistically significant. At 12 months, the test group showed a statistically significant greater reduction in probing depth for the sampled sites. The adjunctive use of Er:YAG laser when compared with conventional ultrasonic debridement did not provide a microbiological added benefit. Even though some clinical benefits with the adjunctive laser application were identified when comparing both treatment protocols, there were no differences in microbiological outcomes or in the bacterial recolonization patterns.

Extracorporeal shockwave therapy versus exercise program in patients with low back pain: short-term results of a randomised controlled trial.

PubMed

Notarnicola, A; Maccagnano, G; Gallone, M F; Mastromauro, L; Rifino, F; Pesce, V; Covelli, I; Moretti, B

2018-01-01

The physiotherapy treatment of low back pain (LBP) with physical stimulation offers different possibilities of application. Until now, the physical therapies used in LBP are laser therapy, ultrasonotherapy and currents. We conducted a clinical trial in order to verify whether shockwave therapy, which is very effective in treating tendinopathies and fracture consolidation delays, leads to clinical and electromyographic improvement in patients affected by LBP. We randomized thirty patients affected by LBP treated with shock waves (shockwave group) or a standard protocol characterized by rehabilitative exercises (control group). At one and three months, the patients treated with shockwave therapy showed clinical improvement measured by VAS scales (p=0.002; p= 0.02), and disability evaluated with Roland scales (p=0.002; p=0.002) and Oswestry (p=0.002; p=0.002). At three months, the patients treated with shock waves, showed a significant improvement in terms of values of amplitude of the sensory nerve conduction velocity (SNCV) of the plantar medialis nerve (left: p=0.007; right: p=0.04), the motor nerve muscular conduction (MNCV) of the deep peroneal nerve (left: p=0.28; right: p=0.01) and recruitment of motor units of finger brevis extensor (left: p = 0.02; right: p=0.006). In the control group, there was a trend to increase the clinical and electromyographic results without statistical significance. The preliminary results suggest a good applicability of shockwave therapy in the treatment of LBP, in accordance with the antiinflammatory, antalgic, decontracting effects and remodeling of the nerve fiber damage verified in previous studies conducted on other pathological models. Future research will allow us to verify the integration of this therapy into a rehabilitation protocol combined with other physical therapies.

UK quantitative WB-DWI technical workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer.

PubMed

Barnes, Anna; Alonzi, Roberto; Blackledge, Matthew; Charles-Edwards, Geoff; Collins, David J; Cook, Gary; Coutts, Glynn; Goh, Vicky; Graves, Martin; Kelly, Charles; Koh, Dow-Mu; McCallum, Hazel; Miquel, Marc E; O'Connor, James; Padhani, Anwar; Pearson, Rachel; Priest, Andrew; Rockall, Andrea; Stirling, James; Taylor, Stuart; Tunariu, Nina; van der Meulen, Jan; Walls, Darren; Winfield, Jessica; Punwani, Shonit

2018-01-01

Application of whole body diffusion-weighted MRI (WB-DWI) for oncology are rapidly increasing within both research and routine clinical domains. However, WB-DWI as a quantitative imaging biomarker (QIB) has significantly slower adoption. To date, challenges relating to accuracy and reproducibility, essential criteria for a good QIB, have limited widespread clinical translation. In recognition, a UK workgroup was established in 2016 to provide technical consensus guidelines (to maximise accuracy and reproducibility of WB-MRI QIBs) and accelerate the clinical translation of quantitative WB-DWI applications for oncology. A panel of experts convened from cancer centres around the UK with subspecialty expertise in quantitative imaging and/or the use of WB-MRI with DWI. A formal consensus method was used to obtain consensus agreement regarding best practice. Questions were asked about the appropriateness or otherwise on scanner hardware and software, sequence optimisation, acquisition protocols, reporting, and ongoing quality control programs to monitor precision and accuracy and agreement on quality control. The consensus panel was able to reach consensus on 73% (255/351) items and based on consensus areas made recommendations to maximise accuracy and reproducibly of quantitative WB-DWI studies performed at 1.5T. The panel were unable to reach consensus on the majority of items related to quantitative WB-DWI performed at 3T. This UK Quantitative WB-DWI Technical Workgroup consensus provides guidance on maximising accuracy and reproducibly of quantitative WB-DWI for oncology. The consensus guidance can be used by researchers and clinicians to harmonise WB-DWI protocols which will accelerate clinical translation of WB-DWI-derived QIBs.

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

PubMed

Krishnan, Rahul; Ko, David; Foster, Clarence E; Liu, Wendy; Smink, A M; de Haan, Bart; De Vos, Paul; Lakey, Jonathan R T

2017-01-01

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

Cryopreservation and Revival of Human Mesenchymal Stromal Cells.

PubMed

Haack-Sørensen, Mandana; Ekblond, Annette; Kastrup, Jens

2016-01-01

Cell-based therapy is a promising and innovative new treatment for different degenerative and autoimmune diseases, and mesenchymal stromal cells (MSCs) from the bone marrow have demonstrated great therapeutic potential due to their immunosuppressive and regenerative capacities.The establishment of methods for large-scale expansion of clinical-grade MSCs in vitro has paved the way for their therapeutic use in clinical trials. However, the clinical application of MSCs also requires cryopreservation and banking of the cell products. To preserve autologous or allogeneic MSCs for future clinical applications, a reliable and effective cryopreservation method is required.Developing a successful cryopreservation protocol for clinical stem cell products, cryopreservation media, cryoprotectant agents (CPAs), the freezing container, the freezing temperature, and the cooling and warming rate are all aspects which should be considered.A major challenge is the selection of a suitable cryoprotectant which is able to penetrate the cells and yet has low toxicity.This chapter focuses on recent technological developments relevant for the cryopreservation of MSCs using the most commonly used cryopreservation medium containing DMSO and animal serum or human-derived products for research use and the animal protein-free cryopreservation media CryoStor (BioLife Solutions) for clinical use.

A universal data access and protocol integration mechanism for smart home

NASA Astrophysics Data System (ADS)

Shao, Pengfei; Yang, Qi; Zhang, Xuan

2013-03-01

With the lack of standardized or completely missing communication interfaces in home electronics, there is no perfect solution to address every aspect in smart homes based on existing protocols and technologies. In addition, the central control unit (CCU) of smart home system working point-to-point between the multiple application interfaces and the underlying hardware interfaces leads to its complicated architecture and unpleasant performance. A flexible data access and protocol integration mechanism is required. The current paper offers a universal, comprehensive data access and protocol integration mechanism for a smart home. The universal mechanism works as a middleware adapter with unified agreements of the communication interfaces and protocols, offers an abstraction of the application level from the hardware specific and decoupling the hardware interface modules from the application level. Further abstraction for the application interfaces and the underlying hardware interfaces are executed based on adaption layer to provide unified interfaces for more flexible user applications and hardware protocol integration. This new universal mechanism fundamentally changes the architecture of the smart home and in some way meets the practical requirement of smart homes more flexible and desirable.

[Ingestion of caustic substances: An analysis of the safety and benefit of a less aggressive protocol].

PubMed

Ripoll Trujillo, Noelia; Martínez Sánchez, Lidia; Habimana Jordana, Anna; Trenchs Sainz de La Maza, Victoria; Vila Miravet, Víctor; Luaces Cubells, Carles

2018-04-14

The ingestion of a caustic agent is the most common cause of admission after being in contact with a domestic product. A group of patients could be considered low risk and not require aggressive procedures such a corticosteroid administration and endoscopy, especially in the paediatric population. To evaluate the safety and benefit of a less aggressive protocol for patients defined as low risk. An analytical-observational study conducted on patients who consulted for caustic ingestion between January 2011 and December 2015. Two periods were differentiated according to the current protocol. Period-1: usual protocol (which included admission and parenteral corticosteroid and antibiotic administration) and Period-2: less aggressive protocol for the low risk patients (oral intake test after 6hours and discharged if they remained asymptomatic). Low risk patients were considered as those who met the following criteria: unintentional intake, absence of symptoms and oral lesions. In the rest of the patients the usual protocol was performed. Re-admission with a diagnosis of digestive lesions was considered as a complication. Forty-eight patients were included in period 1, and 35 in period 2. In period 2, thirteen patients met low risk criteria. The adherence to the less aggressive protocol was 100%. None of the low risk patients required admission or endoscopy after discharge. In period 1 the adherence to the usual protocol was 60.4%. Six patients would have benefited from the application of the less aggressive protocol. Adopting a more conservative attitude in low risk patients is safe. These patients benefit from clinical observation, without performing more aggressive measures with their possible iatrogenic adverse effects. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Development and validation of a remote home safety protocol.

PubMed

Romero, Sergio; Lee, Mi Jung; Simic, Ivana; Levy, Charles; Sanford, Jon

2018-02-01

Environmental assessments and subsequent modifications conducted by healthcare professionals can enhance home safety and promote independent living. However, travel time, expense and the availability of qualified professionals can limit the broad application of this intervention. Remote technology has the potential to increase access to home safety evaluations. This study describes the development and validation of a remote home safety protocol that can be used by a caregiver of an elderly person to video-record their home environment for later viewing and evaluation by a trained professional. The protocol was developed based on literature reviews and evaluations from clinical and content experts. Cognitive interviews were conducted with a group of six caregivers to validate the protocol. The final protocol included step-by-step directions to record indoor and outdoor areas of the home. The validation process resulted in modifications related to safety, clarity of the protocol, readability, visual appearance, technical descriptions and usability. Our final protocol includes detailed instructions that a caregiver should be able to follow to record a home environment for subsequent evaluation by a home safety professional. Implications for Rehabilitation The results of this study have several implications for rehabilitation practice The remote home safety evaluation protocol can potentially improve access to rehabilitation services for clients in remote areas and prevent unnecessary delays for needed care. Using our protocol, a patient's caregiver can partner with therapists to quickly and efficiently evaluate a patient's home before they are released from the hospital. Caregiver narration, which reflects a caregiver's own perspective, is critical to evaluating home safety. In-home safety evaluations, currently not available to all who need them due to access barriers, can enhance a patient's independence and provide a safer home environment.

Translating evidence-based protocol of wound drain management for total joint arthroplasty into practice: A quasi-experimental study.

PubMed

Tsang, Lap Fung; Cheng, Hang Cheong; Ho, Hon Shuen; Hsu, Yung Chak; Chow, Chiu Man; Law, Heung Wah; Fong, Lup Chau; Leung, Lok Ming; Kong, Ivy Ching Yan; Chan, Chi Wai; Sham, Alice So Yuen

2016-05-01

Although various drains have long been used in total joint replacement, evidence suggests inconsistent practice exists in the use of drainage systems including intermittently applying suction or free of drainage suction, and variations in the optimal timing for wound drain removal. A comprehensive systematic review of available evidence up to 2013 was conducted in a previous study and a protocol was adapted for clinical application according to the summary of the retrieved information (Tsang, 2015). To determine if the protocol could reduce blood loss and blood transfusion after operation and to develop a record form so as to enhance communication of drainage record amongst surgeons and nurses. A quasi-experimental time-series design was undertaken. In the conventional group, surgeons ordered free drainage if the drain output was more than 300 ml. The time of removal of the drain was based on their professional judgement. In the protocol group the method of drainage was dependant of the drainage output as was the timing of the removal of the drain. A standardized record form was developed to guide operating room and orthopaedic ward nurses to manage the drainage system. The drain was removed significantly earlier in the protocol group. Blood loss rate at the first hour of post-operation was extremely low in the protocol group due to clamping effect. Blood loss in volume during the first three hours in the protocol group was significantly lower than that in the conventional group. Only in 11.1% and 4% of cases was it necessary to clamp at the three and four hour post-operative hours. No clamping was required at the two and eight hour postoperative period. There was no significant difference in blood loss during the removal of the drain and during blood transfusion, which was required for patients upon removal of the drain in the two groups. This is the first clinical study to develop an evidence-based protocol to manage wound drain effectively in Hong Kong. Total blood loss and blood transfusions were not significantly different between the conventional and protocol groups. A standard documentation document is beneficial to enhance communication between doctors and nurses as well as to monitor and observe drainage effectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stem cell transplantation in neurodegenerative disorders of the gastrointestinal tract: future or fiction?

PubMed Central

Kulkarni, Subhash; Becker, Laren; Pasricha, Pankaj Jay

2014-01-01

Current advances in our understanding of stem and precursor cell biology and in the protocols of stem cell isolation and transplantation have opened up the possibility of transplanting neural stem cells for the treatment of gastrointestinal motility disorders. This review summarises the current status of research in this field, identifies the major gaps in our knowledge and discusses the potential opportunities and hurdles for clinical application. PMID:21816959

Development of an Inter-Service Complex Wound and Limb Salvage Center within the DoD (Briefing charts)

DTIC Science & Technology

2010-10-15

CWLSC Patient Growth: 2008-2010  Complex soft-tissue wound management in austere settings  NPWT/VAC application and management  Ostomy , fistula, and...acute and chronic wounds Complex Wound Limb Salvage Program WRAMC/NNMC Inpatient Care Wound and Ostomy NNMC and WRAMC Outpatient Care 2 Clinics...Standardization Ostomy Wound care Skin Care Cleansers Research / EBP Pressure ulcer protocol CPG development Wound education research grant WRNMMC

Federated Web-accessible Clinical Data Management within an Extensible NeuroImaging Database

PubMed Central

Keator, David B.; Wei, Dingying; Fennema-Notestine, Christine; Pease, Karen R.; Bockholt, Jeremy; Grethe, Jeffrey S.

2010-01-01

Managing vast datasets collected throughout multiple clinical imaging communities has become critical with the ever increasing and diverse nature of datasets. Development of data management infrastructure is further complicated by technical and experimental advances that drive modifications to existing protocols and acquisition of new types of research data to be incorporated into existing data management systems. In this paper, an extensible data management system for clinical neuroimaging studies is introduced: The Human Clinical Imaging Database (HID) and Toolkit. The database schema is constructed to support the storage of new data types without changes to the underlying schema. The complex infrastructure allows management of experiment data, such as image protocol and behavioral task parameters, as well as subject-specific data, including demographics, clinical assessments, and behavioral task performance metrics. Of significant interest, embedded clinical data entry and management tools enhance both consistency of data reporting and automatic entry of data into the database. The Clinical Assessment Layout Manager (CALM) allows users to create on-line data entry forms for use within and across sites, through which data is pulled into the underlying database via the generic clinical assessment management engine (GAME). Importantly, the system is designed to operate in a distributed environment, serving both human users and client applications in a service-oriented manner. Querying capabilities use a built-in multi-database parallel query builder/result combiner, allowing web-accessible queries within and across multiple federated databases. The system along with its documentation is open-source and available from the Neuroimaging Informatics Tools and Resource Clearinghouse (NITRC) site. PMID:20567938

Federated web-accessible clinical data management within an extensible neuroimaging database.

PubMed

Ozyurt, I Burak; Keator, David B; Wei, Dingying; Fennema-Notestine, Christine; Pease, Karen R; Bockholt, Jeremy; Grethe, Jeffrey S

2010-12-01

Managing vast datasets collected throughout multiple clinical imaging communities has become critical with the ever increasing and diverse nature of datasets. Development of data management infrastructure is further complicated by technical and experimental advances that drive modifications to existing protocols and acquisition of new types of research data to be incorporated into existing data management systems. In this paper, an extensible data management system for clinical neuroimaging studies is introduced: The Human Clinical Imaging Database (HID) and Toolkit. The database schema is constructed to support the storage of new data types without changes to the underlying schema. The complex infrastructure allows management of experiment data, such as image protocol and behavioral task parameters, as well as subject-specific data, including demographics, clinical assessments, and behavioral task performance metrics. Of significant interest, embedded clinical data entry and management tools enhance both consistency of data reporting and automatic entry of data into the database. The Clinical Assessment Layout Manager (CALM) allows users to create on-line data entry forms for use within and across sites, through which data is pulled into the underlying database via the generic clinical assessment management engine (GAME). Importantly, the system is designed to operate in a distributed environment, serving both human users and client applications in a service-oriented manner. Querying capabilities use a built-in multi-database parallel query builder/result combiner, allowing web-accessible queries within and across multiple federated databases. The system along with its documentation is open-source and available from the Neuroimaging Informatics Tools and Resource Clearinghouse (NITRC) site.

ABM Clinical Protocol #2: Guidelines for Hospital Discharge of the Breastfeeding Term Newborn and Mother: “The Going Home Protocol,” Revised 2014

PubMed Central

Evans, Amy; Taylor, Julie Scott

2014-01-01

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID:24456024

Data standards for clinical research data collection forms: current status and challenges.

PubMed

Richesson, Rachel L; Nadkarni, Prakash

2011-05-01

Case report forms (CRFs) are used for structured-data collection in clinical research studies. Existing CRF-related standards encompass structural features of forms and data items, content standards, and specifications for using terminologies. This paper reviews existing standards and discusses their current limitations. Because clinical research is highly protocol-specific, forms-development processes are more easily standardized than is CRF content. Tools that support retrieval and reuse of existing items will enable standards adoption in clinical research applications. Such tools will depend upon formal relationships between items and terminological standards. Future standards adoption will depend upon standardized approaches for bridging generic structural standards and domain-specific content standards. Clinical research informatics can help define tools requirements in terms of workflow support for research activities, reconcile the perspectives of varied clinical research stakeholders, and coordinate standards efforts toward interoperability across healthcare and research data collection.

Engineering the next generation of clinical deep brain stimulation technology.

PubMed

McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R; Lempka, Scott F

2015-01-01

Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of two clinical protocols for the management of women with vaginal discharge in southern Thailand.

PubMed

Chandeying, V; Skov, S; Kemapunmanus, M; Law, M; Geater, A; Rowe, P

1998-06-01

(1) To compare the effectiveness of two clinical protocols for the management of vaginal discharge in the situations where no laboratory facilities are available but speculum examination is possible and where basic laboratory facilities are available. (2) To determine clinical and simple laboratory indicators for diagnosis of patients with vaginal discharge in the local setting. Alternate allocation of subjects to one of two management protocols. Women presenting to university gynaecology outpatients department with a complaint of vaginal discharge. Subjects were alternately allocated management according to one of two protocols: one without (group A) and one with (group B) immediate access to results of basic laboratory tests. Full clinical assessment including speculum examination and microbiological assessment for infection with gonorrhoea, chlamydia, candida, trichomonas, and bacterial vaginosis was performed on all women. Follow up assessment of clinical and microbiological response was performed 1-2 weeks later. At initial assessment, both groups were similar in all respects except that more group B women had inflammation of the vulva. The prevalences of various conditions were: candidiasis 22%, bacterial vaginosis 38%, trichomoniasis 4%, chlamydia 4%, gonorrhoea 0.4%. There was no association between any demographic characteristic and diagnosis of cause of the discharge. Both protocols resulted in clinically and statistically significant improvements for women with candidiasis, bacterial vaginosis, and trichomoniasis. There were no clinically important differences in outcomes between the two protocols. The sensitivities and specificities of various indicators were: curd-like vaginal discharge for candidiasis, 72% and 100%; homogeneous vaginal discharge for bacterial vaginosis or trichomoniasis, 94% and 88%; absent or scanty lactobacilli for bacterial vaginosis, 99% and 68%; > 20% clue cells for bacterial vaginosis, 81% and 99%; visible endocervical mucopus for chlamydia or gonorrhoea, 36% and 86%; microscopic endocervical mucopus for chlamydia or gonorrhoea, 64% and 69%. Both protocols were equally effective in managing women with abnormal vaginal discharge. Simple clinical indicators for candidiasis, bacterial vaginosis, or trichomonas as in protocol A are sufficiently sensitive and specific for use in situations with no laboratory support. A modification to protocol A could increase detection of bacterial vaginosis at basic health service level. Further work is needed to identify appropriate indicators for infection with chlamydia or gonorrhoea.

Evaluation of two clinical protocols for the management of women with vaginal discharge in southern Thailand

PubMed Central

Chandeying, V.; Skov, S.; Kemapunmanus, M.; Law, M.; Geater, A.; Rowe, P.

1998-01-01

OBJECTIVES: (1) To compare the effectiveness of two clinical protocols for the management of vaginal discharge in the situations where no laboratory facilities are available but speculum examination is possible and where basic laboratory facilities are available. (2) To determine clinical and simple laboratory indicators for diagnosis of patients with vaginal discharge in the local setting. DESIGN: Alternate allocation of subjects to one of two management protocols. SUBJECTS: Women presenting to university gynaecology outpatients department with a complaint of vaginal discharge. METHODS: Subjects were alternately allocated management according to one of two protocols: one without (group A) and one with (group B) immediate access to results of basic laboratory tests. Full clinical assessment including speculum examination and microbiological assessment for infection with gonorrhoea, chlamydia, candida, trichomonas, and bacterial vaginosis was performed on all women. Follow up assessment of clinical and microbiological response was performed 1-2 weeks later. RESULTS: At initial assessment, both groups were similar in all respects except that more group B women had inflammation of the vulva. The prevalences of various conditions were: candidiasis 22%, bacterial vaginosis 38%, trichomoniasis 4%, chlamydia 4%, gonorrhoea 0.4%. There was no association between any demographic characteristic and diagnosis of cause of the discharge. Both protocols resulted in clinically and statistically significant improvements for women with candidiasis, bacterial vaginosis, and trichomoniasis. There were no clinically important differences in outcomes between the two protocols. The sensitivities and specificities of various indicators were: curd-like vaginal discharge for candidiasis, 72% and 100%; homogeneous vaginal discharge for bacterial vaginosis or trichomoniasis, 94% and 88%; absent or scanty lactobacilli for bacterial vaginosis, 99% and 68%; > 20% clue cells for bacterial vaginosis, 81% and 99%; visible endocervical mucopus for chlamydia or gonorrhoea, 36% and 86%; microscopic endocervical mucopus for chlamydia or gonorrhoea, 64% and 69%. CONCLUSIONS: Both protocols were equally effective in managing women with abnormal vaginal discharge. Simple clinical indicators for candidiasis, bacterial vaginosis, or trichomonas as in protocol A are sufficiently sensitive and specific for use in situations with no laboratory support. A modification to protocol A could increase detection of bacterial vaginosis at basic health service level. Further work is needed to identify appropriate indicators for infection with chlamydia or gonorrhoea. 


 PMID:9849555

Clinical Trials Management | Division of Cancer Prevention

Cancer.gov

Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230

Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document.

PubMed

Nguyen, S M; Thamm, D H; Vail, D M; London, C A

2015-09-01

In veterinary medical oncology, there is currently no standardized protocol for assessing response to therapy in solid tumours. The lack of such a formalized guideline makes it challenging to critically compare outcome measures across various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG) membership consensus document presented here is based on the recommendations of a subcommittee of American College of Veterinary Internal Medicine (ACVIM) board-certified veterinary oncologists. This consensus paper has used the human response evaluation criteria in solid tumours (RECIST v1.1) as a framework to establish standard procedures for response assessment in canine solid tumours that is meant to be easy to use, repeatable and applicable across a variety of clinical trial structures in veterinary oncology. It is hoped that this new canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology community and thereby facilitate the comparison of current and future treatment protocols used for companion animals with cancer. © 2013 Blackwell Publishing Ltd.

Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa

PubMed Central

Roemhild, Roderich; Barbosa, Camilo; Beardmore, Robert E; Jansen, Gunther; Schulenburg, Hinrich

2015-01-01

Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human pathogen Pseudomonas aeruginosa PA14 and two pairs of clinically relevant antibiotics (doripenem/ciprofloxacin and cefsulodin/gentamicin). Our results consistently show that the sequential application of two antibiotics decelerates resistance evolution relative to monotherapy. Sequential treatment enhanced population extinction although we applied antibiotics at sublethal dosage. In both experiments, we identified an order effect of the antibiotics used in the sequential protocol, leading to significant variation in the long-term efficacy of the tested protocols. These variations appear to be caused by asymmetric evolutionary constraints, whereby adaptation to one drug slowed down adaptation to the other drug, but not vice versa. An understanding of such asymmetric constraints may help future development of evolutionary robust treatments against infectious disease. PMID:26640520

ICONE: An International Consortium of Neuro Endovascular Centres.

PubMed

Raymond, J; White, P; Kallmes, D F; Spears, J; Marotta, T; Roy, D; Guilbert, F; Weill, A; Nguyen, T; Molyneux, A J; Cloft, H; Cekirge, S; Saatci, I; Bracard, S; Meder, J F; Moret, J; Cognard, C; Qureshi, A I; Turk, A S; Berenstein, A

2008-06-30

The proliferation of new endovascular devices and therapeutic strategies calls for a prudentand rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisation a land methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the designand execution of basic science, device developmentand clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across aspectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or pre clinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from clientsponsored financial agreements will be redirected to the academic and research objectives of the organization. The Consortium wishes to work inconcert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Developing a guideline for clinical trial protocol content: Delphi consensus survey

PubMed Central

2012-01-01

Background Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. PMID:23006145

[The factors that influence the use of clinical protocols according to the opinion of health center coordinators. The Research Group on the Evaluation and Improvement of Clinical Protocols].

PubMed

Saura-Llamas, J; Saturno Hernández, P J; Gaona Ramón, J M; Romero Román, J R; González Barberá, M

1999-11-15

To find the factors that affect the use of clinical protocols in primary care, in the view of primary care team coordinators, and the reasons why they are little followed, and to bring together suggestions for improvement. An opinion study, through a telephone survey. Primary health care. The health centres in Murcia with protocolized activity: 31 at the start of the project. The coordinators and those in charge of nursing, 62 people in all. After a pilot study, a structured telephone survey was carried out, administered by a trained interviewer who posed two open questions: why do you think that the professionals at your centre do not use the existing protocols more often? and: what suggestions would you make to improve the protocols and have them used more? A specialist company did the field-work in June and July 1996. There was a 98% reply rate. To the first question, coordinators thought that low use could be explained by excess demand and lack of time for consultations (33% of all replies), although they also cited other organisational problems in the centre, defects in protocols and lack of training. Those in charge of nursing gave very similar replies, with excess demand (39%) predominating. To the second question, on increasing the use of protocols, coordinators suggested that the protocols needed to be improved (44.8% of replies), and also cited the need for improvements in organisation and on-going training. Very similar answers came from the nursing side, where 43.5% highlighted the need to improve the protocol documents. The coordinators assumed that the clinical protocols were used little and could be improved. In their view the basic reason for their low use is excessive pressure from the patient-load. The key to using them more is improvement in the protocol documents.

Health care access for rural youth on equal terms? A mixed methods study protocol in northern Sweden.

PubMed

Goicolea, Isabel; Carson, Dean; San Sebastian, Miguel; Christianson, Monica; Wiklund, Maria; Hurtig, Anna-Karin

2018-01-11

The purpose of this paper is to propose a protocol for researching the impact of rural youth health service strategies on health care access. There has been no published comprehensive assessment of the effectiveness of youth health strategies in rural areas, and there is no clearly articulated model of how such assessments might be conducted. The protocol described here aims to gather information to; i) Assess rural youth access to health care according to their needs, ii) Identify and understand the strategies developed in rural areas to promote youth access to health care, and iii) Propose actions for further improvement. The protocol is described with particular reference to research being undertaken in the four northernmost counties of Sweden, which contain a widely dispersed and diverse youth population. The protocol proposes qualitative and quantitative methodologies sequentially in four phases. First, to map youth access to health care according to their health care needs, including assessing horizontal equity (equal use of health care for equivalent health needs,) and vertical equity (people with greater health needs should receive more health care than those with lesser needs). Second, a multiple case study design investigates strategies developed across the region (youth clinics, internet applications, public health programs) to improve youth access to health care. Third, qualitative comparative analysis of the 24 rural municipalities in the region identifies the best combination of conditions leading to high youth access to health care. Fourth, a concept mapping study involving rural stakeholders, care providers and youth provides recommended actions to improve rural youth access to health care. The implementation of this research protocol will contribute to 1) generating knowledge that could contribute to strengthening rural youth access to health care, as well as to 2) advancing the application of mixed methods to explore access to health care.

Taking the Politics Out of Satellite and Space-Based Communications Protocols

NASA Technical Reports Server (NTRS)

Ivancic, William D.

2006-01-01

After many years of studies, experimentation, and deployment, large amounts of misinformation and misconceptions remain regarding applicability of various communications protocols for use in satellite and space-based networks. This paper attempts to remove much of the politics, misconceptions, and misinformation that have plagued spacebased communications protocol development and deployment. This paper provides a common vocabulary for communications; a general discussion of the requirements for various communication environments; an evaluation of tradeoffs between circuit and packet-switching technologies, and the pros and cons of various link, network, transport, application, and security protocols. Included is the applicability of protocol enhancing proxies to NASA, Department of Defense (DOD), and commercial space communication systems.

Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

PubMed Central

Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2015-01-01

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

Positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: do we need a personalized approach?

PubMed Central

Paolini, Valentina; Faverio, Paola; Aliberti, Stefano; Messinesi, Grazia; Foti, Giuseppe; Sibila, Oriol; Monzani, Anna; Stainer, Anna; Pesci, Alberto

2018-01-01

Background Acute respiratory failure (ARF) is a life-threatening complication in patients with community acquired pneumonia (CAP). The use of non-invasive ventilation is controversial. With this prospective, observational study we aimed to describe a protocol to assess whether a patient with moderate-to-severe hypoxemic ARF secondary to CAP benefits, in clinical and laboratoristic terms, from the application of a positive end expiratory pressure (PEEP) + oxygen vs oxygen alone. Methods Patients who benefit from PEEP application (PEEP-responders) were defined as those with partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increase >20% and/or reduction of respiratory distress during PEEP + oxygen therapy compared to oxygen therapy alone. Clinical characteristics and outcomes were compared between PEEP-responders and PEEP-non responders. Results Out of 41 patients, 27 (66%) benefit from PEEP application (PEEP-responders), the best response was obtained with a PEEP of 10 cmH2O in 13 patients, 7.5 cmH2O in eight and 5 cmH2O in six. PEEP-responders were less likely to present comorbidities compared to PEEP-non responders. No differences between groups were found in regards to endotracheal intubation criteria fullfillment, intensive care unit admission and in-hospital mortality, while PEEP-responders had a shorter length of hospital stay. Discussion The application of a protocol to evaluate PEEP responsiveness might be useful in patients with moderate-to-severe hypoxemic ARF due to CAP in order to personalize and maximize the effectiveness of therapy, and prevent the inappropriate PEEP use. PEEP responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay. PMID:29404202

HIV patient retention: the implementation of a North Carolina clinic-based protocol.

PubMed

Keller, Jennifer; Heine, Amy; LeViere, Anna Finestone; Donovan, Jenna; Wilkin, Aimee; Sullivan, Kristen; Quinlivan, Evelyn Byrd

2017-05-01

Decreased visit attendance leads to poor health outcomes, decreased viral suppression, and higher mortality rates for persons living with HIV. Retention in care is an important factor in improving health status for people living with HIV but continues to be a challenge in clinical settings. This paper details the development and implementation of the NC-LINK Retention Protocol, a clinic-based protocol to locate and reengage out-of-care patients, as part of overall clinic retention efforts. The protocol was implemented as one of four interventions of the NC-LINK Systems and Linkages Project, a multi-site initiative funded by the HIV/AIDS Bureau and the Special Projects of National Significance. Lists of out-of-care patients who had not received HIV medical care in over nine months and did not have a future appointment were created each month. Patient navigators, case managers, and other staff then followed a standardized protocol to locate and reengage these patients in care. A total of 452 patients were identified for reengagement services. Of those, 194 (43%) returned to care, 108 (24%) had another definitive outcome (incarcerated, deceased, or relocated) and 150 (33%) were referred for additional follow-up to locate and reengage in care. In summary, 67% of patients were located through the efforts of the clinic staff. The results of this intervention indicate that it is possible to successfully integrate a protocol into the existing infrastructure of a clinic and reengage a majority of out-of-care patients into medical care.

Optimization Manufacture of Virus- and Tumor-Specific T Cells

PubMed Central

Lapteva, Natalia; Vera, Juan F.

2011-01-01

Although ex vivo expanded T cells are currently widely used in pre-clinical and clinical trials, the complexity of manufacture remains a major impediment for broader application. In this review we discuss current protocols for the ex vivo expansion of virus- and tumor-specific T cells and describe our experience in manufacture optimization using a gas-permeable static culture flask (G-Rex). This innovative device has revolutionized the manufacture process by allowing us to increase cell yields while decreasing the frequency of cell manipulation and in vitro culture time. It is now being used in good manufacturing practice (GMP) facilities for clinical cell production in our institution as well as many others in the US and worldwide. PMID:21915183

Pediatric oncology clinical trial participation where the geography is vast: Development of a clinical research system for tertiary and satellite centers in Ontario, Canada.

PubMed

Alexander, Sarah; Greenberg, Mark; Malkin, David; Portwine, Carol; Johnston, Donna; Silva, Mariana; Zelcer, Shayna; Sonshine, Samantha; Manzo, Janet; Bennett, Carla; Brodeur-Robb, Kathy; Deveault, Catherine; Ramachandran, Nivetha; Gibson, Paul

2018-04-01

Opportunities for participation in clinical trials are a core component of the care of children with cancer. In Ontario, many pediatric patients live long distances from their cancer center. This paper describes the work that was done in order to allow patients participating in Children's Oncology Group trials to receive care, including research protocol related care, jointly between the tertiary pediatric cancer center and the closer-to-home satellite center. The system is a pragmatic risk-based model, supporting excellence in care while ensuring good conduct of the research in compliance with applicable regulations and guidelines, including ethics oversight. © 2017 Wiley Periodicals, Inc.

Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-involved Diabetic Macular Edema

PubMed Central

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M.; Browning, David J.; Chalam, KV; Davis, Matthew; Ferris, Frederick L; Glassman, Adam; Maturi, Raj; Stockdale, Cynthia R.; Topping, Trexler

2011-01-01

Objective Describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design Discussion of treatment protocol for DME. Participants Subjects with vision loss from DME involving the center of the macula. Methods The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser in eyes with vision loss from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes, compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. In order to share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures Clinical guidelines based on a DRCR.net protocol. Results The treatment protocol required real time feedback from a web-based data entry system for intravitreal injections, focal/grid laser, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month, or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. PMID:22136692

Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

PubMed

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M; Browning, David J; Chalam, K V; Davis, Matthew; Ferris, Frederick L; Glassman, Adam R; Maturi, Raj K; Stockdale, Cynthia R; Topping, Trexler M

2011-12-01

To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Discussion of treatment protocol for DME. Subjects with vision loss resulting from DME involving the center of the macula. The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Clinical guidelines based on a DRCR.net protocol. The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Multidisciplinary approaches to stimulate wound healing.

PubMed

Businaro, Rita; Corsi, Mariangela; Di Raimo, Tania; Marasco, Sergio; Laskin, Debra L; Salvati, Bruno; Capoano, Raffaele; Ricci, Serafino; Siciliano, Camilla; Frati, Giacomo; De Falco, Elena

2016-08-01

New civil wars and waves of terrorism are causing crucial social changes, with consequences in all fields, including health care. In particular, skin injuries are evolving as an epidemic issue. From a physiological standpoint, although wound repair takes place more rapidly in the skin than in other tissues, it is still a complex organ to reconstruct. Genetic and clinical variables, such as diabetes, smoking, and inflammatory/immunological pathologies, are also important risk factors limiting the regenerative potential of many therapeutic applications. Therefore, optimization of current clinical strategies is critical. Here, we summarize the current state of the field by focusing on stem cell therapy applications in wound healing, with an emphasis on current clinical approaches being developed. These involve protocols for the ex vivo expansion of adipose tissue-derived mesenchymal stem cells by means of a patented Good Manufacturing Practice-compliant platelet lysate. Combinations of multiple strategies, including genetic modifications and stem cells, biomimetic scaffolds, and novel vehicles, such as nanoparticles, are also discussed as future approaches. © 2016 New York Academy of Sciences.

A new approach for the quantitative evaluation of drawings in children with learning disabilities.

PubMed

Galli, Manuela; Vimercati, Sara Laura; Stella, Giacomo; Caiazzo, Giorgia; Norveti, Federica; Onnis, Francesca; Rigoldi, Chiara; Albertini, Giorgio

2011-01-01

A new method for a quantitative and objective description of drawing and for the quantification of drawing ability in children with learning disabilities (LD) is hereby presented. Twenty-four normally developing children (N) (age 10.6 ± 0.5) and 18 children with learning disabilities (LD) (age 10.3 ± 2.4) took part to the study. The drawing tasks were chosen among those already used in clinical daily experience (Denver Developmental Screening Test). Some parameters were defined in order to quantitatively describe the features of the children's drawings, introducing new objective measurements beside the subjective standard clinical evaluation. The experimental set-up revealed to be valid for clinical application with LD children. The parameters highlighted the presence of differences in the drawing features of N and LD children. This paper suggests the applicability of this protocol to other fields of motor and cognitive valuation, as well as the possibility to study the upper limbs position and muscle activation during drawing. Copyright © 2011 Elsevier Ltd. All rights reserved.

The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

PubMed

Lorch, U; Berelowitz, K; Ozen, C; Naseem, A; Akuffo, E; Taubel, J

2012-05-01

The interest in adaptive study design is evident from the growing amount of clinical research employing this model in the mid to later stages of medicines development. Little has been published on the practical application and merits of adaptive study design in early phase clinical research. This paper describes a retrospective analysis performed on a sample of 29 industry lead adaptive early phase studies commencing between 1 January 2006 and 31 December 2010 in a clinical trials unit in London, England. All studies containing at least one adaptive feature in the original protocol were included in the analysis. The scope of the analysis was to assess whether the use of adaptive study designs provided tangible benefits over the use of conventional study designs using time savings as the main measure. We conclude that the use of adaptive study design saves time in early phase research programs. This is achieved by abolishing the need for substantial amendments or by mitigating their impact on timelines and by using adaptive scheduling efficiencies.

Recommended Implementation of Arterial Spin Labeled Perfusion MRI for Clinical Applications: A consensus of the ISMRM Perfusion Study Group and the European Consortium for ASL in Dementia

PubMed Central

Alsop, David C.; Detre, John A.; Golay, Xavier; Günther, Matthias; Hendrikse, Jeroen; Hernandez-Garcia, Luis; Lu, Hanzhang; MacIntosh, Bradley J.; Parkes, Laura M.; Smits, Marion; van Osch, Matthias J. P.; Wang, Danny JJ; Wong, Eric C.; Zaharchuk, Greg

2014-01-01

This article provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ‘ASL in Dementia’ consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this article we describe the major considerations and tradeoffs in implementing an ASL protocol, and provide specific recommendations for a standard approach. Our conclusions are that, as an optimal default implementation we recommend: pseudo-continuous labeling, background suppression, a segmented 3D readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. PMID:24715426

The use of bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.

PubMed

Kagami, Hideaki; Agata, Hideki; Inoue, Minoru; Asahina, Izumi; Tojo, Arinobu; Yamashita, Naohide; Imai, Kohzoh

2014-06-01

Bone tissue engineering is a promising field of regenerative medicine in which cultured cells, scaffolds, and osteogenic inductive signals are used to regenerate bone. Human bone marrow stromal cells (BMSCs) are the most commonly used cell source for bone tissue engineering. Although it is known that cell culture and induction protocols significantly affect the in vivo bone forming ability of BMSCs, the responsible factors of clinical outcome are poorly understood. The results from recent studies using human BMSCs have shown that factors such as passage number and length of osteogenic induction significantly affect ectopic bone formation, although such differences hardly affected the alkaline phosphatase activity or gene expression of osteogenic markers. Application of basic fibroblast growth factor helped to maintain the in vivo osteogenic ability of BMSCs. Importantly, responsiveness of those factors should be tested under clinical circumstances to improve the bone tissue engineering further. In this review, clinical application of bone tissue engineering was reviewed with putative underlying mechanisms.

Network protocols for real-time applications

NASA Technical Reports Server (NTRS)

Johnson, Marjory J.

1987-01-01

The Fiber Distributed Data Interface (FDDI) and the SAE AE-9B High Speed Ring Bus (HSRB) are emerging standards for high-performance token ring local area networks. FDDI was designed to be a general-purpose high-performance network. HSRB was designed specifically for military real-time applications. A workshop was conducted at NASA Ames Research Center in January, 1987 to compare and contrast these protocols with respect to their ability to support real-time applications. This report summarizes workshop presentations and includes an independent comparison of the two protocols. A conclusion reached at the workshop was that current protocols for the upper layers of the Open Systems Interconnection (OSI) network model are inadequate for real-time applications.

Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study

PubMed Central

Mellgren, Marianne; Bergvall, Kerstin

2008-01-01

Background A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice. Methods Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200–476 μg kg-1 subcutaneously 2–3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618–2185 μgkg-1) and oral ivermectin (range 616–2732 μgkg-1) administered by the owners, 3–6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2–20,0 mgkg-1, 1–3 times with an interval of 2–4 weeks. Follow-up time was 4 months–4.5 years. Results Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively. Conclusion All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols. PMID:18171479

Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

PubMed

Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

2016-08-01

Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs. In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

[Cognitive therapy of trauma related guilt in patients with PTSD].

PubMed

Popiel, Agnieszka

2014-01-01

Various aspects of guilt are frequent problems of patients suffering from PTSD, though they have been included into the diagnostic criteria for PTSD just in the present version DSM-5. Some studies indicate limitation of effectiveness of exposure therapy in PTSD patients with predominant emotions of anger or guilt. The aim of this paper is to present cognitive conceptualization of guilt in PTSD proposed by Kubany, and a treatment protocol resulting from this conceptualization. The clinical application of the protocol is illustrated with preliminary results of systematic observation of 8 patients with moderate to severe PTSD who were treated with cognitive therapy for guilt followed by a standard prolonged exposure protocol. The cognitive therapy of guilt can be a valuable supplement for treatment of PTSD. This protocol can also be an inspiration for therapists working with patients with dysfunctional guilt as a problem in other than PTSD disorders--like depression or adjustment disorders. In discussion the place of guilt in treatment according to different (PE-Foa et al.; CPT-Resick et al.; CT-Ehlers and Clark) trauma focused therapy approaches is addressed, and the need for further studies is underlined.

Surgical treatment and a unique management of rostral mandibular fracture with cerclage wire in a horse.

PubMed

Naddaf, Hadi; Sabiza, Soroush; Kavosi, Narges

2015-01-01

A 3-year-old Arabian colt was presented for a major gingiva wound at the right rostral part of mandible. After clinical assessments, rostral mandibular fracture was determined. Stabilization of fractured region was achieved via cerclage wire application under general anesthesia. Fixation wires were left in place for 6 weeks. A 3 -month follow up revealed complete fracture healing. The purpose of this case report was to give clinical information about rostral mandibular fractures and treatment of these fractures and nutrition protocol in a horse, as this fracture is of the most common type of jaw fracture sustained by young horses.

Regulatory considerations in application of encapsulated cell therapies.

PubMed

van Zanten, J; de Vos, Paul

2010-01-01

The encapsulation of tissue in semi-permeable membranes is a technology with high potential and in due time several new therapies based on this technology will be tested in clinical trials. Recent, new legislation requires that these investigational medicinal products used in clinical trials Phase I must be produced according to Good Manufacturing Practice (GMP). Consequently, the activities of GMP are expanding to the field of research and researchers might need to change developed protocols in order to meet GMP legislation. This chapters gives an overview of the overall guidelines covering GMP and more specific guidelines dealing with cell based therapies and gene therapy.

CT myocardial perfusion imaging: current status and future perspectives.

PubMed

Yang, Dong Hyun; Kim, Young-Hak

2017-07-01

Computed tomography myocardial perfusion (CTP) combined with coronary computed tomography angiography (CCTA) may constitute a "1-stop shop" for the noninvasive diagnosis of hemodynamically significant coronary stenosis during a single CT examination. CTP shows high diagnostic performance and provides incremental value over CCTA for the detection of hemodynamically significant coronary stenosis in patients with a high Agatston calcium score or coronary artery stents. Future studies should determine the optimal protocol and clinical value of CTP for guiding revascularization strategy and prognostication. In this article, we review the current status and future perspectives of CTP, focusing on technical considerations, clinical applications, and future research topics.

Template protocol for clinical trials investigating vaccines--focus on safety elements.

PubMed

Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2013-11-12

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Balancing patient care and student education: learning to deliver bad news in an optometry teaching clinic.

PubMed

Spafford, Marlee M; Schryer, Catherine F; Creutz, Stefan

2009-05-01

Learning to counsel patients in a teaching clinic or hospital occurs in the presence of the competing agendas of patient care and student education. We wondered about the challenges that these tensions create for clinical novices learning to deliver bad news to patients. In this preliminary study, we audio-taped and transcribed the interviews of seven senior optometry students and six optometrist instructors at a Canadian optometry teaching clinic. The participants described their experiences in learning to deliver bad news. Using a grounded theory approach, our analysis was informed by situated learning and activity theory. Optometry students received formal classroom training regarding how to deliver bad news, including exposure to the medically-based six-step SPIKES protocol (Baile et al. The Oncologist, 5, 302-311, 2000). Yet, application of this protocol to the teaching clinic was limited by the lack of exposure most instructors had received to this strategy. Determinants of the students' complex learning process during their clinical apprenticeship, included: (i) knowing one's place, (ii) knowing one's audience, (iii) knowing through feedback, and (iv) knowing who speaks. The experiences of these participants pointed toward the need for: (1) more instructional "scaffolding" (Bruner and Sherwood Play: Its role in development and evolution, p. 280, 1976) in the clinical setting when the learning task is complex, and (2) explicit discussions about the impacts that unfold when the activities of patient care and student education overlap. We reflect on the possible consequences to student education and patient care in the absence of these changes.

Analysis of different therapeutic protocols for osteonecrosis of the jaw associated with oral and intravenous bisphpsphonates

PubMed Central

Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis; Machuca-Portillo, Guillermo

2017-01-01

Introduction Chemotherapy-associated osteonecrosis of the jaw caused by bisphosphonates is an exposure of necrotic bone with more than eight weeks of evolution that is attributable to bisphosphonates and no prior radiation therapy. Its etiopathogenesis remains unknown, although there are two hypotheses that may explain it: the drug’s mechanism of action, and the risk factors that can lead to osteonecrosis. There is a wide range of treatment options for managing chemotherapy-associated osteonecrosis of the jaw, from conservative treatments to surgical procedures of varying levels of invasiveness, which are sometimes supplemented with adjuvant therapies. Objectives The objective of this article is to group the therapeutic options for osteonecrosis of the jaw (ONJ) into seven different protocols and to evaluate their effectiveness in relation to stage of ONJ. Material and Methods A literature review was carried out in PubMed following the PRISMA criteria. A total of 47 were collected after compiling a series of variables that define ONJ, applied treatments, and the clinical results obtained. Results and Discussion The 47 articles selected have a low to average estimated risk of bias and are of moderate to good quality. According to the data obtained, Protocol 3 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and adjuvant therapies) is the most favorable approach for ONJ lesions caused by oral bisphosphonates. For lesions caused by intravenous bisphosphonates, Protocol 2 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and no adjuvant therapies) is the best approach. When comparing the different stages of ONJ, Protocol 1 (conservative treatment, clinical and radiological follow-up) promotes better healing of Stage 1 ONJ lesions caused by orally administered bisphosphonates, and Protocol 3 is recommended for Stage II. For ONJ lesions attributable to intravenous bisphosphonates, Protocol 7 (conservative treatment, clinical and radiological follow-up, and adjuvant therapies) provides the best results in Stage 0; in Stages I, II, and III, Protocol 1 gives better results. Key words:Bisphosphonates, bronj, therapeutic protocol, clinical result. PMID:27918742

Automation of sample preparation for mass cytometry barcoding in support of clinical research: protocol optimization.

PubMed

Nassar, Ala F; Wisnewski, Adam V; Raddassi, Khadir

2017-03-01

Analysis of multiplexed assays is highly important for clinical diagnostics and other analytical applications. Mass cytometry enables multi-dimensional, single-cell analysis of cell type and state. In mass cytometry, the rare earth metals used as reporters on antibodies allow determination of marker expression in individual cells. Barcode-based bioassays for CyTOF are able to encode and decode for different experimental conditions or samples within the same experiment, facilitating progress in producing straightforward and consistent results. Herein, an integrated protocol for automated sample preparation for barcoding used in conjunction with mass cytometry for clinical bioanalysis samples is described; we offer results of our work with barcoding protocol optimization. In addition, we present some points to be considered in order to minimize the variability of quantitative mass cytometry measurements. For example, we discuss the importance of having multiple populations during titration of the antibodies and effect of storage and shipping of labelled samples on the stability of staining for purposes of CyTOF analysis. Data quality is not affected when labelled samples are stored either frozen or at 4 °C and used within 10 days; we observed that cell loss is greater if cells are washed with deionized water prior to shipment or are shipped in lower concentration. Once the labelled samples for CyTOF are suspended in deionized water, the analysis should be performed expeditiously, preferably within the first hour. Damage can be minimized if the cells are resuspended in phosphate-buffered saline (PBS) rather than deionized water while waiting for data acquisition.

From design to implementation--the Joint Asia Diabetes Evaluation (JADE) program: a descriptive report of an electronic web-based diabetes management program.

PubMed

Ko, Gary T; So, Wing-Yee; Tong, Peter C; Le Coguiec, Francois; Kerr, Debborah; Lyubomirsky, Greg; Tamesis, Beaver; Wolthers, Troels; Nan, Jennifer; Chan, Juliana

2010-05-13

The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care. The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose. The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions. The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes.

A Natural Language Processing-based Model to Automate MRI Brain Protocol Selection and Prioritization.

PubMed

Brown, Andrew D; Marotta, Thomas R

2017-02-01

Incorrect imaging protocol selection can contribute to increased healthcare cost and waste. To help healthcare providers improve the quality and safety of medical imaging services, we developed and evaluated three natural language processing (NLP) models to determine whether NLP techniques could be employed to aid in clinical decision support for protocoling and prioritization of magnetic resonance imaging (MRI) brain examinations. To test the feasibility of using an NLP model to support clinical decision making for MRI brain examinations, we designed three different medical imaging prediction tasks, each with a unique outcome: selecting an examination protocol, evaluating the need for contrast administration, and determining priority. We created three models for each prediction task, each using a different classification algorithm-random forest, support vector machine, or k-nearest neighbor-to predict outcomes based on the narrative clinical indications and demographic data associated with 13,982 MRI brain examinations performed from January 1, 2013 to June 30, 2015. Test datasets were used to calculate the accuracy, sensitivity and specificity, predictive values, and the area under the curve. Our optimal results show an accuracy of 82.9%, 83.0%, and 88.2% for the protocol selection, contrast administration, and prioritization tasks, respectively, demonstrating that predictive algorithms can be used to aid in clinical decision support for examination protocoling. NLP models developed from the narrative clinical information provided by referring clinicians and demographic data are feasible methods to predict the protocol and priority of MRI brain examinations. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Comparison and uncertainty evaluation of different calibration protocols and ionization chambers for low-energy surface brachytherapy dosimetry

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

Candela-Juan, C., E-mail: ccanjuan@gmail.com; Vijande, J.; García-Martínez, T.

2015-08-15

Purpose: A surface electronic brachytherapy (EBT) device is in fact an x-ray source collimated with specific applicators. Low-energy (<100 kVp) x-ray beam dosimetry faces several challenges that need to be addressed. A number of calibration protocols have been published for x-ray beam dosimetry. The media in which measurements are performed are the fundamental difference between them. The aim of this study was to evaluate the surface dose rate of a low-energy x-ray source with small field applicators using different calibration standards and different small-volume ionization chambers, comparing the values and uncertainties of each methodology. Methods: The surface dose rate ofmore » the EBT unit Esteya (Elekta Brachytherapy, The Netherlands), a 69.5 kVp x-ray source with applicators of 10, 15, 20, 25, and 30 mm diameter, was evaluated using the AAPM TG-61 (based on air kerma) and International Atomic Energy Agency (IAEA) TRS-398 (based on absorbed dose to water) dosimetry protocols for low-energy photon beams. A plane parallel T34013 ionization chamber (PTW Freiburg, Germany) calibrated in terms of both absorbed dose to water and air kerma was used to compare the two dosimetry protocols. Another PTW chamber of the same model was used to evaluate the reproducibility between these chambers. Measurements were also performed with two different Exradin A20 (Standard Imaging, Inc., Middleton, WI) chambers calibrated in terms of air kerma. Results: Differences between surface dose rates measured in air and in water using the T34013 chamber range from 1.6% to 3.3%. No field size dependence has been observed. Differences are below 3.7% when measurements with the A20 and the T34013 chambers calibrated in air are compared. Estimated uncertainty (with coverage factor k = 1) for the T34013 chamber calibrated in water is 2.2%–2.4%, whereas it increases to 2.5% and 2.7% for the A20 and T34013 chambers calibrated in air, respectively. The output factors, measured with the PTW chambers, differ by less than 1.1% for any applicator size when compared to the output factors that were measured with the A20 chamber. Conclusions: Measurements using both dosimetric protocols are consistent, once the overall uncertainties are considered. There is also consistency between measurements performed with both chambers calibrated in air. Both the T34013 and A20 chambers have negligible stem effect. Any x-ray surface brachytherapy system, including Esteya, can be characterized using either one of these calibration protocols and ionization chambers. Having less correction factors, lower uncertainty, and based on measurements, performed in closer to clinical conditions, the TRS-398 protocol seems to be the preferred option.« less

Protocol for the management of psychiatric patients with psychomotor agitation.

PubMed

Vieta, Eduard; Garriga, Marina; Cardete, Laura; Bernardo, Miquel; Lombraña, María; Blanch, Jordi; Catalán, Rosa; Vázquez, Mireia; Soler, Victòria; Ortuño, Noélia; Martínez-Arán, Anabel

2017-09-08

Psychomotor agitation (PMA) is a state of motor restlessness and mental tension that requires prompt recognition, appropriate assessment and management to minimize anxiety for the patient and reduce the risk for escalation to aggression and violence. Standardized and applicable protocols and algorithms can assist healthcare providers to identify patients at risk of PMA, achieve timely diagnosis and implement minimally invasive management strategies to ensure patient and staff safety and resolution of the episode. Spanish experts in PMA from different disciplines (psychiatrists, psychologists and nurses) convened in Barcelona for a meeting in April 2016. Based on recently issued international consensus guidelines on the standard of care for psychiatric patients with PMA, the meeting provided the opportunity to address the complexities in the assessment and management of PMA from different perspectives. The attendees worked towards producing a consensus for a unified approach to PMA according to the local standards of care and current local legislations. The draft protocol developed was reviewed and ratified by all members of the panel prior to its presentation to the Catalan Society of Psychiatry and Mental Health, the Spanish Society of Biological Psychiatry (SEPB) and the Spanish Network Centre for Research in Mental Health (CIBERSAM) for input. The final protocol and algorithms were then submitted to these organizations for endorsement. The protocol presented here provides guidance on the appropriate selection and use of pharmacological agents (inhaled/oral/IM), seclusion, and physical restraint for psychiatric patients suspected of or presenting with PMA. The protocol is applicable within the Spanish healthcare system. Implementation of the protocol and the constituent algorithms described here should ensure the best standard of care of patients at risk of PMA. Episodes of PMA could be identified earlier in their clinical course and patients could be managed in the least invasive and coercive manner, ensuring their own safety and that of others around them. Establishing specialized teams in agitation and providing them with continued training on the identification of agitation, patient management and therapeutic alternatives might reduce the burden of PMA for both the patient and the healthcare system.

Department of Clinical Investigation, Annual Research Progress Report, Fiscal Year 2006 (Madigan Army Medical Center)

DTIC Science & Technology

2006-09-30

45(4): p. 227-34, 2006. Roukis TS, Zgonis T. The management of acute Charcot fracture -dislocations with the Taylor’s spatial external fixation...Protocol No. S T Title Johnston GM #206028 C L Application of the Wells Criteria to determine Pretest Probability of Pulmonary Embolism ...Evaluation of Pulmonary Embolism - An Examination of Hospital-Wide Referral Practices Kwon HP #206087 O L Hemoptysis in Young Adults Kwon HP #206069

Implementing an intravenous insulin protocol in your practice: practical advice to overcome clinical, administrative, and financial barriers.

PubMed

Kelly, Janet L; Hirsch, Irl B; Furnary, Anthony P

2006-01-01

Diabetes mellitus is the fourth most common comorbid condition among hospitalized patients, and 30% of patients undergoing open-heart surgery have diabetes. The link between hyperglycemia and poor outcome has been well described, and large clinical trials have shown that aggressive control of blood glucose with an insulin infusion can improve these outcomes. The barriers to implementing an insulin infusion protocol are numerous, despite the fact that doing so is paramount to clinical success. Barriers include safety concerns, such as fear of hypoglycemia, insufficient nursing staff to patient ratios, lack of administrative and physician support, various system and procedural issues, and resistance to change. Key steps to overcome the barriers include building support with multidisciplinary champions, involving key staff, educating staff, and administrators of the clinical and economic benefits of improving glycemic control, setting realistic goals, selecting a validated insulin infusion protocol, and internally marketing the success of the protocol.

Using generalizability theory to develop clinical assessment protocols.

PubMed

Preuss, Richard A

2013-04-01

Clinical assessment protocols must produce data that are reliable, with a clinically attainable minimal detectable change (MDC). In a reliability study, generalizability theory has 2 advantages over classical test theory. These advantages provide information that allows assessment protocols to be adjusted to match individual patient profiles. First, generalizability theory allows the user to simultaneously consider multiple sources of measurement error variance (facets). Second, it allows the user to generalize the findings of the main study across the different study facets and to recalculate the reliability and MDC based on different combinations of facet conditions. In doing so, clinical assessment protocols can be chosen based on minimizing the number of measures that must be taken to achieve a realistic MDC, using repeated measures to minimize the MDC, or simply based on the combination that best allows the clinician to monitor an individual patient's progress over a specified period of time.

Clinical and Radiologic Outcomes of Submerged and Nonsubmerged Bone-Level Implants with Internal Hexagonal Connections in Immediate Implantation: A 5-Year Retrospective Study.

PubMed

Wu, Shiyu; Wu, Xiayi; Shrestha, Rachana; Lin, Jinying; Feng, Zhicai; Liu, Yudong; Shi, Yunlin; Huang, Baoxin; Li, Zhipeng; Liu, Quan; Zhang, Xiaocong; Hu, Mingxuan; Chen, Zhuofan

2018-02-01

To evaluate the 5-year clinical and radiologic outcome of immediate implantation using submerged and nonsubmerged techniques with bone-level implants and internal hexagonal connections and the effects of potential influencing factors. A total of 114 bone-level implants (XiVE S plus) with internal hexagonal connections inserted into 72 patients were included. Patients were followed up for 5 years. A t-test was used to statistically evaluate the marginal bone loss between the submerged and nonsubmerged groups. The cumulative survival rate (CSR) was calculated according to the life table method and illustrated with Kaplan-Meier survival curves. Comparisons of the CSR between healing protocols, guided bone regeneration, implants with different sites, lengths, and diameters were performed using log-rank tests. The 5-year cumulative implant survival rates with submerged and nonsubmerged healing were 94% and 96%, respectively. No statistically significant differences in terms of marginal bone loss, healing protocol, application of guided bone regeneration, implant site, or length were observed. High CSRs and good marginal bone levels were achieved 5 years after immediate implantation of bone-level implants with internal hexagonal connections using both the submerged and nonsubmerged techniques. Factors such as implant length, site, and application of guided bone regeneration did not have an impact on the long-term success of the implants. © 2017 by the American College of Prosthodontists.

Cryopreservation of Human Stem Cells for Clinical Application: A Review

PubMed Central

Hunt, Charles J.

2011-01-01

Summary Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell. PMID:21566712

Cryopreservation of Human Stem Cells for Clinical Application: A Review.

PubMed

Hunt, Charles J

2011-01-01

SUMMARY: Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell.

Near-infrared fluorescence image-guidance in plastic surgery: A systematic review.

PubMed

Cornelissen, Anouk J M; van Mulken, Tom J M; Graupner, Caitlin; Qiu, Shan S; Keuter, Xavier H A; van der Hulst, René R W J; Schols, Rutger M

2018-01-01

Near-infrared fluorescence (NIRF) imaging technique, after administration of contrast agents with fluorescent characteristics in the near-infrared (700-900 nm) range, is considered to possess great potential for the future of plastic surgery, given its capacity for perioperative, real-time anatomical guidance and identification. This study aimed to provide a comprehensive literature review concerning current and potential future applications of NIRF imaging in plastic surgery, thereby guiding future research. A systematic literature search was performed in databases of Cochrane Library CENTRAL, MEDLINE, and EMBASE (last search Oct 2017) regarding NIRF imaging in plastic surgery. Identified articles were screened and checked for eligibility by two authors independently. Forty-eight selected studies included 1166 animal/human subjects in total. NIRF imaging was described for a variety of (pre)clinical applications in plastic surgery. Thirty-two articles used NIRF angiography, i.e., vascular imaging after intravenous dye administration. Ten articles reported on NIRF lymphography after subcutaneous dye administration. Although currently most applied, general protocols for dosage and timing of dye administration for NIRF angiography and lymphography are still lacking. Three articles applied NIRF to detect nerve injury, and another three studies described other novel applications in plastic surgery. Future standard implementation of novel intraoperative optical techniques, such as NIRF imaging, could significantly contribute to perioperative anatomy guidance and facilitate critical decision-making in plastic surgical procedures. Further investigation (i.e., large multicenter randomized controlled trials) is mandatory to establish the true value of this innovative surgical imaging technique in standard clinical practice and to aid in forming consensus on protocols for general use.Level of Evidence: Not ratable.

Clinically applied procedures for human ovarian tissue cryopreservation result in different levels of efficacy and efficiency.

PubMed

Bastings, Lobke; Westphal, Johan R; Beerendonk, Catharina C M; Bekkers, Ruud L M; Zusterzeel, Petra L M; Hendriks, Jan C M; Braat, Didi D M; Peek, Ronald

2016-12-01

Different protocols are being used worldwide for the cryopreservation of human ovarian tissue for fertility preservation purposes. The efficiency and efficacy of the majority of these protocols has not been extensively evaluated, possibly resulting in sub-optimally cryopreserved ovarian tissue. To address the impact of this issue, we assessed the effects of two clinically successful human ovarian tissue slow-freezing cryopreservation procedures on the quality of the cryopreserved tissue. To differentiate between cryopreservation ( C ) versus thawing ( T ) related effects, four combinations of these two (A and B) very different cryopreservation/thawing protocols (A C A T , A C B T , B C A T , B C B T ) were studied. Before and after cryopreservation and thawing, the percentage of living and morphologically normal follicles, as well as the overall tissue viability, was assessed. Our experiments revealed that the choice of the cryopreservation protocol noticeably affected the overall tissue viability and percentage of living follicles, with a higher viability after protocol B C when compared to A C . No statistically significant differences in tissue viability were observed between the two thawing protocols, but thawing protocol B T required considerably more human effort and materials than thawing protocol A T . Tissue morphology was best retained using the B C A T combination. Our results indicate that extensive and systematical evaluation of clinically used protocols is warranted.

Comparison of Bruce treadmill exercise test protocols: is ramped Bruce equal or superior to standard bruce in producing clinically valid studies for patients presenting for evaluation of cardiac ischemia or arrhythmia with body mass index equal to or greater than 30?

PubMed

Bires, Angela Macci; Lawson, Dori; Wasser, Thomas E; Raber-Baer, Donna

2013-12-01

Clinically valid cardiac evaluation via treadmill stress testing requires patients to achieve specific target heart rates and to successfully complete the cardiac examination. A comparison of the standard Bruce protocol and the ramped Bruce protocol was performed using data collected over a 1-y period from a targeted patient population with a body mass index (BMI) equal to or greater than 30 to determine which treadmill protocol provided more successful examination results. The functional capacity, metabolic equivalent units achieved, pressure rate product, and total time on the treadmill as measured for the obese patients were clinically valid and comparable to normal-weight and overweight patients (P < 0.001). Data gathered from each protocol demonstrated that the usage of the ramped Bruce protocol achieved more consistent results in comparison across all BMI groups in achieving 80%-85% of their age-predicted maximum heart rate. This study did not adequately establish that the ramped Bruce protocol was superior to the standard Bruce protocol for the examination of patients with a BMI equal to or greater than 30.

Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols.

PubMed

Ji, Gong-Jun; Yu, Fengqiong; Liao, Wei; Wang, Kai

2017-04-01

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Planning oral health and clinical discharge in primary care: the comprehensive dental care protocol outcome.

PubMed

Cavalcanti, Yuri Wanderley; Dantas de Almeida, Leopoldina de Fátima; Barbosa, Ailma de Souza; Nascimento Padilha, Wilton Wilney

2015-03-01

The dental care must be driven by preventive and curative measures that can contribute to the population's oral health promotion. To evaluate the impact of the actions proposed by a comprehensive dental care protocol (CDCP) on the oral health condition of primary care users. The sample consisted of 32 volunteers, assisted throughout the six phases proposed by the CDCP: diagnosis of dental needs; resolution of urgencies; restorative interventions; application of promotional measures; evaluation of the achieved health level; and periodic controls. Data were collected through clinical exams, which measured the simplified oral hygiene index (OHI-S), gingival bleeding index (GBI) and the decayed, missing and filled teeth (DMFT) Index, before and after the CDCP was implemented. Statistical analysis consisted of the Wilcoxon test, at 5% significance level (α = 0.05). The OHI-S and GBI indices showed a significant reduction (p < 0.05) from the initial (1.4 ± 0.6 and 46.3 ± 19.9) to final condition (0.9 ± 0.3 and 21.5 ± 7.5). The decayed, missing and filled teeth and the missing teeth component were not significantly altered (p > 0.05), showing final values equal to 12.7 ± 9.6 and 5.6 ± 7.8, respectively. Decayed elements were fully converted into filled elements, and the final values of the decayed and filled elements were, respectively, 0.0 ± 0.0 and 7.3 ± 5.7 (p < 0.05). The enactment of the CDCP had a beneficial effect on the oral health of the population assisted by the dental services offered in primary care and this protocol seems to ft the public dental service demands. The CDCP can be useful to public dental service planning since it showed an efficient clinical outcome to the patients. We consider that this protocol should be employed in primary care oral health services in order to achieve overall upgrade, access enlargement and public oral health promotion.

Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study.

PubMed

Piek, Christine J; van Spil, Willem Evert; Junius, Greet; Dekker, Aldo

2011-04-13

Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149) and dogs treated according to the prednisolone protocol (P protocol; n = 73). At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77%) in the P protocol group and 69% (95% CI 59-80%) in the AP protocol group, respectively. Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

Universal neonatal hearing screening: applications for a developing country in the Asia-Pacific region.

PubMed

Navarro-Locsin, C Gretchen

2003-01-01

Various centers around the world have implemented and evaluated universal hearing screening programs as a response to the US National Institute of Health policy statement on early identification of hearing loss. Several well conducted clinical trials have been devised to examine and evaluate various factors relevant to establishing a UNHS program. This paper aims to describe some of these factors and analyze their applications and implications for a UNHS program for a developing country in the Asia-Pacific Region. Specifically, three main issues will be discussed: hospital vs community based programs, choice of technology, and choice of screening protocol.

[Adeno-associated viral vectors: methods for production and purification for gene therapy applications].

PubMed

Mena-Enriquez, Mayra; Flores-Contreras, Lucia; Armendáriz-Borunda, Juan

2012-01-01

Viral vectors based on adeno-associated virus (AAV) are widely used in gene therapy protocols, because they have characteristics that make them valuable for the treatment of genetic and chronic degenerative diseases. AAV2 serotype had been the best characterized to date. However, the AAV vectors developed from other serotypes is of special interest, since they have organ-specific tropism which increases their potential for transgene delivery to target cells for performing their therapeutic effects. This article summarizes AAV generalities, methods for their production and purification. It also discusses the use of these vectors in vitro, in vivo and their application in gene therapy clinical trials.

Fluorine-19 Labeling of Stromal Vascular Fraction Cells for Clinical Imaging Applications

PubMed Central

Rose, Laura C.; Kadayakkara, Deepak K.; Wang, Guan; Bar-Shir, Amnon; Helfer, Brooke M.; O’Hanlon, Charles F.; Kraitchman, Dara L.; Rodriguez, Ricardo L.

2015-01-01

Stromal vascular fraction (SVF) cells are used clinically for various therapeutic targets. The location and persistence of engrafted SVF cells are important parameters for determining treatment failure versus success. We used the GID SVF-1 platform and a clinical protocol to harvest and label SVF cells with the fluorinated (19F) agent CS-1000 as part of a first-in-human phase I trial (clinicaltrials.gov identifier NCT02035085) to track SVF cells with magnetic resonance imaging during treatment of radiation-induced fibrosis in breast cancer patients. Flow cytometry revealed that SVF cells consisted of 25.0% ± 15.8% CD45+, 24.6% ± 12.5% CD34+, and 7.5% ± 3.3% CD31+ cells, with 2.1 ± 0.7 × 105 cells per cubic centimeter of adipose tissue obtained. Fluorescent CS-1000 (CS-ATM DM Green) labeled 87.0% ± 13.5% of CD34+ progenitor cells compared with 47.8% ± 18.5% of hematopoietic CD45+ cells, with an average of 2.8 ± 2.0 × 1012 19F atoms per cell, determined using nuclear magnetic resonance spectroscopy. The vast majority (92.7% ± 5.0%) of CD31+ cells were also labeled, although most coexpressed CD34. Only 16% ± 22.3% of CD45−/CD31−/CD34− (triple-negative) cells were labeled with CS-ATM DM Green. After induction of cell death by either apoptosis or necrosis, >95% of 19F was released from the cells, indicating that fluorine retention can be used as a surrogate marker for cell survival. Labeled-SVF cells engrafted in a silicone breast phantom could be visualized with a clinical 3-Tesla magnetic resonance imaging scanner at a sensitivity of approximately 2 × 106 cells at a depth of 5 mm. The current protocol can be used to image transplanted SVF cells at clinically relevant cell concentrations in patients. Significance Stromal vascular fraction (SVF) cells harvested from adipose tissue offer great promise in regenerative medicine, but methods to track such cell therapies are needed to ensure correct administration and monitor survival. A clinical protocol was developed to harvest and label SVF cells with the fluorinated (19F) agent CS-1000, allowing cells to be tracked with 19F magnetic resonance imaging (MRI). Flow cytometry evaluation revealed heterogeneous 19F uptake in SVF cells, confirming the need for careful characterization. The proposed protocol resulted in sufficient 19F uptake to allow imaging using a clinical MRI scanner with point-of-care processing. PMID:26511652

[Donation protocol following controlled cardiac death (Maastricht type III donation). First experience].

PubMed

Rubio-Muñoz, J J; Pérez-Redondo, M; Alcántara-Carmona, S; Lipperheide-Vallhonrat, I; Fernández-Simón, I; Valdivia-de la Fuente, M; Villanueva-Fernández, H; Balandín-Moreno, B; Ortega-López, A; Romera-Ortega, M A; Galdos-Anuncibay, P

2014-03-01

To present our experience with the implementation of a donation protocol following controlled cardiac death (Maastricht type III donation). A retrospective descriptive and observational study was made. Intensive Care Unit of a third-level university hospital. Eight patients in an irreversible state, in which withdrawal of all life support had been agreed, were evaluated as potential donors. Application of the adopted protocol. Clinical data of donors, evaluation of a donation protocol following cardiac death, warm ischemia times, and short-term outcome of the recipients. Eight patients were evaluated. In one case donation was not possible because no cardiac arrest developed in the 120 minutes after extubation. The 7 remaining patients were effective kidney donors. Warm ischemia times were less than 23 minutes in all cases. Although 7 of the 14 recipients suffered delayed graft function, all of them achieved good renal function. Donation after cardiac death in patients in an overwhelming and irreversible state represents a potential source of donors not previously considered in this country. The prior development of a consensus-based protocol can help increase the number of organs in combination with those obtained after brain death. In our experience, the results of kidney transplants obtained from donors after cardiac death are good, and the success of these types of protocols could be extended to other organs such as the liver and lungs. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

The development and role of megavoltage cone beam computerized tomography in radiation oncology

NASA Astrophysics Data System (ADS)

Morin, Olivier

External beam radiation therapy has now the ability to deliver doses that conform tightly to a tumor volume. The steep dose gradients planned in these treatments make it increasingly important to reproduce the patient position and anatomy at each treatment fraction. For this reason, considerable research now focuses on in-room three-dimensional imaging. This thesis describes the first clinical megavoltage cone beam computed tomography (MVCBCT) system, which utilizes a conventional linear accelerator equipped with an amorphous silicon flat panel detector. The document covers the system development and investigation of its clinical applications over the last 4-5 years. The physical performance of the system was evaluated and optimized for soft-tissue contrast resolution leading to recommendations of imaging protocols to use for specific clinical applications and body sites. MVCBCT images can resolve differences of 5% in electron density for a mean dose of 9 cGy. Hence, the image quality of this system is sufficient to differentiate some soft-tissue structures. The absolute positioning accuracy with MVCBCT is better than 1 mm. The accuracy of isodose lines calculated using MVCBCT images of head and neck patients is within 3% and 3 mm. The system shows excellent stability in image quality, CT# calibration, radiation exposure and absolute positioning over a period of 8 months. A procedure for MVCBCT quality assurance was developed. In our clinic, MVCBCT has been used to detect non rigid spinal cord distortions, to position a patient with a paraspinous tumor close to metallic hardware, to position prostate cancer patients using gold markers or soft-tissue landmarks, to monitor head and neck anatomical changes and their dosimetric consequences, and to complement the convention CT for treatment planning in presence of metallic implants. MVCBCT imaging is changing the clinical practice of our department by increasingly revealing patient-specific errors. New verification protocols are being developed to minimize those errors thus moving the practice of radiation therapy one step closer to personalized medicine.

Development of Uniform Protocol for Alopecia Areata Clinical Trials.

PubMed

Solomon, James A

2015-11-01

Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts.

PubMed

Gary, Regina; Aigner, Michael; Moi, Stephanie; Schaffer, Stefanie; Gottmann, Anja; Maas, Stefanie; Zimmermann, Robert; Zingsem, Jürgen; Strobel, Julian; Mackensen, Andreas; Mautner, Josef; Moosmann, Andreas; Gerbitz, Armin

2018-05-09

A major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts. We have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population. CMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis. Our protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.

The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI Methods

PubMed Central

Jack, Clifford R.; Bernstein, Matt A.; Fox, Nick C.; Thompson, Paul; Alexander, Gene; Harvey, Danielle; Borowski, Bret; Britson, Paula J.; Whitwell, Jennifer L.; Ward, Chadwick; Dale, Anders M.; Felmlee, Joel P.; Gunter, Jeffrey L.; Hill, Derek L.G.; Killiany, Ron; Schuff, Norbert; Fox-Bosetti, Sabrina; Lin, Chen; Studholme, Colin; DeCarli, Charles S.; Krueger, Gunnar; Ward, Heidi A.; Metzger, Gregory J.; Scott, Katherine T.; Mallozzi, Richard; Blezek, Daniel; Levy, Joshua; Debbins, Josef P.; Fleisher, Adam S.; Albert, Marilyn; Green, Robert; Bartzokis, George; Glover, Gary; Mugler, John; Weiner, Michael W.

2008-01-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorode-oxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquiredat multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications thatguided protocol development. A major effort was devoted toevaluating 3D T1-weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B1-calibration scans when applicable; and an axial proton density-T2 dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials. PMID:18302232

Simulation as a Tool to Facilitate Practice Changes in Teams Taking Care of Patients Under Investigation for Ebola Virus Disease in Spain.

PubMed

Rojo, Elena; Oruña, Clara; Sierra, Dolores; García, Gema; Del Moral, Ignacio; Maestre, Jose M

2016-04-01

We analyzed the impact of simulation-based training on clinical practice and work processes on teams caring for patients with possible Ebola virus disease (EVD) in Cantabria, Spain. The Government of Spain set up a special committee for the management of EVD, and the Spanish Ministry of Health and foreign health services created an action protocol. Each region is responsible for selecting a reference hospital and an in-house care team to care for patients under investigation. Laboratory-confirmed cases of EVD have to be transferred to the Carlos III Health Institute in Madrid. Predeployment training and follow-up support are required to help personnel work safely and effectively. Simulation-based scenarios were designed to give staff the opportunity to practice before encountering a real-life situation. Lessons learned by each team during debriefings were listed, and a survey administered 3 months later assessed the implementation of practice and system changes. Implemented changes were related to clinical practice (eg, teamwork principles application), protocol implementation (eg, addition of new processes and rewriting of confusing parts), and system and workflow (eg, change of shift schedule and rearrangement of room equipment). Simulation can be used to detect needed changes in protocol or guidelines or can be adapted to meet the needs of a specific team.

ABM clinical protocol #4: Mastitis, revised March 2014.

PubMed

Amir, Lisa H

2014-06-01

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

A Pediatric Intensive Care Unit Bedside Computer Clinical Decision Support Protocol for Hyperglycemia Is Feasible, Safe and Offers Advantages

PubMed Central

Lanspa, Michael J.; Wilson, Emily L.; Sward, Katherine A.; Jephson, Al; Larsen, Gitte Y.; Morris, Alan H.

2017-01-01

Abstract Background: Computer clinical decision support (CDS) systems are uncommon in the pediatric intensive care unit (PICU), despite evidence suggesting they improve outcomes in adult ICUs. We reasoned that a bedside CDS protocol for intravenous insulin titration, eProtocol-insulin, would be feasible and safe in critically ill children. Methods: We retrospectively reviewed data from non-diabetic children admitted to the PICU with blood glucose (BG) ≥140 mg/dL who were managed with intravenous insulin by either unaided clinician titration or eProtocol-insulin. Primary outcomes were BG measurements in target range (80–110 mg/dL) and severe hypoglycemia (BG ≤40 mg/dL); secondary outcomes were 60-day mortality and PICU length of stay. We assessed bedside nurse satisfaction with the eProtocol-insulin protocol by using a 5-point Likert scale and measured clinician compliance with eProtocol-insulin recommendations. Results: Over 5 years, 69 children were titrated with eProtocol-insulin versus 104 by unaided clinicians. eProtocol-insulin achieved target range more frequently than clinician titration (41% vs. 32%, P < 0.001). Severe hypoglycemia was uncommon in both groups (4.3% of patients in eProtocol-insulin, 8.7% in clinician titration, P = 0.37). There were no differences in mean time to BG target or median BG between the groups. Mortality was 23% in both groups. Clinician compliance with eProtocol-insulin recommendations was 89%. Nurses believed that eProtocol-insulin was easy to understand and safer than clinician titration. Conclusions: eProtocol-insulin is safe for titration of intravenous insulin in critically ill children. Clinical research protocols and quality improvement initiatives aimed at optimizing BG control should utilize detailed computer protocols that enable replicable clinician decisions. PMID:28248127

4D pressure MRI: validation through in-vitro experiments and simulations

NASA Astrophysics Data System (ADS)

Schiavazzi, Daniele; Amili, Omid; Coletti, Filippo

2017-11-01

Advances in MRI scan technology and recently developed acquisition sequences have led to the development of 4D flow MRI, a protocol capable of characterizing in-vivo hemodynamics in patients. Thus, the availability of phase-averaged time-resolved three-dimensional blood velocities has opened new opportunities for computing a wide spectrum of totally non-invasive hemodynamic indicators. In this regard, relative pressures play a particularly important role, as they are routinely employed in the clinic to detect cardiovascular abnormalities (e.g., in peripheral artery disease, valve stenosis, hypertension, etc.). In the first part of the talk, we discuss how the relative pressures can be robustly computed through the solution of a pressure Poisson equation and how noise in the velocities affects their estimate. Routine application of these techniques in the clinic, require however a thorough validation on multiple patients/anatomies and systematic comparisons with in-vitro and simulated representations. Thus, the second part of the talk illustrates the use of numerical simulation and in-vitro experimental protocols to validate these indicators with reference to aortic and cerebral vascular anatomies.

Evaluation of neurofeedback in ADHD: the long and winding road.

PubMed

Arns, Martijn; Heinrich, Hartmut; Strehl, Ute

2014-01-01

Among the clinical applications of neurofeedback, most research has been conducted in ADHD. As an introduction a short overview of the general history of neurofeedback will be given, while the main part of the paper deals with a review of the current state of neurofeedback in ADHD. A meta-analysis on neurofeedback from 2009 found large effect sizes for inattention and impulsivity and medium effects sizes for hyperactivity. Since 2009 several new studies, including 4 placebo-controlled studies, have been published. These latest studies are reviewed and discussed in more detail. The review focuses on studies employing (1) semi-active, (2) active, and (3) placebo-control groups. The assessment of specificity of neurofeedback treatment in ADHD is discussed and it is concluded that standard protocols such as theta/beta, SMR and slow cortical potentials neurofeedback are well investigated and have demonstrated specificity. The paper ends with an outlook on future questions and tasks. It is concluded that future controlled clinical trials should, in a next step, focus on such known protocols, and be designed along the lines of learning theory. Copyright © 2013 Elsevier B.V. All rights reserved.

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis.

PubMed

Salinas-Jazmín, Nohemi; González-González, Edith; Vásquez-Bochm, Luz X; Pérez-Tapia, Sonia M; Velasco-Velázquez, Marco A

2017-05-04

Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab. The protocols allow the side-to-side comparison of a reference rituximab and a marketed rituximab biosimilar. The evaluated products showed differences both in target binding and CDC induction, suggesting that there are underlying physicochemical differences and highlighting the need to analyze the impact of those differences in the clinical setting. The methods reported here constitute simple and inexpensive in vitro models for the evaluation of the activity of rituximab biosimilars. Thus, they can be useful during biosimilar development, as well as for quality control in biosimilar production. Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.

Pediatric sepsis.

PubMed

Mathias, Brittany; Mira, Juan C; Larson, Shawn D

2016-06-01

Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. The definition of pediatric sepsis is currently in a state of evolution, and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become a commonplace.

77 FR 5492 - Magnuson-Stevens Act Provisions; General Provisions for Domestic Fisheries; Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

... assess the performance of an approved sampling protocol and to allow for continued sample collection and... developmental sampling protocol. While this application was being reviewed and was available for public comment, the sampling protocol being tested was adopted into the National Shellfish Sanitation Program by the...

Clinical Simulation: A Protocol for Evaluation of Mobile Technology.

PubMed

Mather, Carey; Jensen, Sanne; Cummings, Elizabeth

2017-01-01

For mobile technology to be accepted at point of care in healthcare environments there is a need to demonstrate benefits whilst ameliorating the risks and challenges. To provide a standardised approach to evaluation of mobile technology a simulation protocol was developed to provide guidance for its use in healthcare environments. Simulated conditions provide the opportunity to assess intended and unintended consequences and identify potential workarounds when using technology. The protocol can also be used to demonstrate the importance of the development of digital professionalism by end-users prior to students entering the clinical practice setting. The mobile technology protocol was adapted from a health information systems protocol developed and used at the ITX Lab, Denmark for use in other simulation laboratories. Use case scenarios were developed to enable evaluation of mobile technology for mobile learning of nurses, nurse supervisors, students and patients. The scenarios can be used in a range of simulated environments including hospital bedside, outpatient clinic or community settings. A case study exemplar of a nurse and patient is included to demonstrate how the mobile technology protocol can be applied.

Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy.

PubMed

Weiss, Jakob; Martirosian, Petros; Notohamiprodjo, Mike; Kaufmann, Sascha; Othman, Ahmed E; Grosse, Ulrich; Nikolaou, Konstantin; Gatidis, Sergios

2018-03-01

The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach. Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board-approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard. Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol. A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.

Medical Images Remote Consultation

NASA Astrophysics Data System (ADS)

Ferraris, Maurizio; Frixione, Paolo; Squarcia, Sandro

Teleconsultation of digital images among different medical centers is now a reality. The problem to be solved is how to interconnect all the clinical diagnostic devices in a hospital in order to allow physicians and health physicists, working in different places, to discuss on interesting clinical cases visualizing the same diagnostic images at the same time. Applying World Wide Web technologies, the proposed system can be easily used by people with no specific computer knowledge providing a verbose help to guide the user through the right steps of execution. Diagnostic images are retrieved from a relational database or from a standard DICOM-PACS through the DICOM-WWW gateway allowing connection of the usual Web browsers to DICOM applications via the HTTP protocol. The system, which is proposed for radiotherapy implementation, where radiographies play a fundamental role, can be easily converted to different field of medical applications where a remote access to secure data are compulsory.

Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

PubMed

Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

2015-01-01

Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

DNA microarrays: a powerful genomic tool for biomedical and clinical research

PubMed Central

Trevino, Victor; Falciani, Francesco; Barrera-Saldaña, Hugo A.

2007-01-01

Among the many benefits of the Human Genome Project are new and powerful tools such as the genome-wide hybridization devices referred as microarrays. Initially designed to measure gene transcriptional levels, microarray technologies are now used for comparing other genome features among individuals and their tissues and cells. Results provide valuable information on disease subcategories, disease prognosis, and treatment outcome. Likewise, reveal differences in genetic makeup, regulatory mechanisms and subtle variations are approaching the era of personalized medicine. To understand this powerful tool, its versatility and how it is dramatically changing the molecular approach to biomedical and clinical research, this review describes the technology, its applications, a didactic step-by-step review of a typical microarray protocol, and a real experiment. Finally, it calls the attention of the medical community to integrate multidisciplinary teams, to take advantage of this technology and its expanding applications that in a slide reveals our genetic inheritance and destiny. PMID:17660860

Development of a Multi-Agent m-Health Application Based on Various Protocols for Chronic Disease Self-Management.

PubMed

Park, Hyun Sang; Cho, Hune; Kim, Hwa Sun

2016-01-01

The purpose of this study was to develop and evaluate a mobile health application (Self-Management mobile Personal Health Record: "SmPHR") to ensure the interoperability of various personal health devices (PHDs) and electronic medical record systems (EMRs) for continuous self-management of chronic disease patients. The SmPHR was developed for Android 4.0.3, and implemented according to the optimized standard protocol for each interface of healthcare services adopted by the Continua Health Alliance (CHA). That is, the Personal Area Network (PAN) interface between the application and PHD implements ISO/IEEE 11073-20,601, 10,404, 10,407, 10,415, 10,417, and Bluetooth Health Device Profile (HDP), and EMRs with a wide area network (WAN) interface implement HL7 V2.6; the Health Record Network (HRN) interface implements Continuity of Care Document (CCD) and Continuity of Care Record (CCR). Also, for SmPHR, we evaluated the transmission error rate between the interface using four PHDs and personal health record systems (PHRs) from previous research, with 611 users and elderly people after receiving institutional review board (IRB) approval. In the evaluation, the PAN interface showed 15 (2.4 %) errors, and the WAN and HRN interface showed 13 (2.1 %) errors in a total of 611 transmission attempts. Also, we received opinions regarding SmPHR from 15 healthcare professionals who took part in the clinical trial. Thus, SmPHR can be provided as an interconnected PHR mobile health service to patients, allowing 'plug and play' of PHDs and EMRs through various standard protocols.

Development of an open metadata schema for prospective clinical research (openPCR) in China.

PubMed

Xu, W; Guan, Z; Sun, J; Wang, Z; Geng, Y

2014-01-01

In China, deployment of electronic data capture (EDC) and clinical data management system (CDMS) for clinical research (CR) is in its very early stage, and about 90% of clinical studies collected and submitted clinical data manually. This work aims to build an open metadata schema for Prospective Clinical Research (openPCR) in China based on openEHR archetypes, in order to help Chinese researchers easily create specific data entry templates for registration, study design and clinical data collection. Singapore Framework for Dublin Core Application Profiles (DCAP) is used to develop openPCR and four steps such as defining the core functional requirements and deducing the core metadata items, developing archetype models, defining metadata terms and creating archetype records, and finally developing implementation syntax are followed. The core functional requirements are divided into three categories: requirements for research registration, requirements for trial design, and requirements for case report form (CRF). 74 metadata items are identified and their Chinese authority names are created. The minimum metadata set of openPCR includes 3 documents, 6 sections, 26 top level data groups, 32 lower data groups and 74 data elements. The top level container in openPCR is composed of public document, internal document and clinical document archetypes. A hierarchical structure of openPCR is established according to Data Structure of Electronic Health Record Architecture and Data Standard of China (Chinese EHR Standard). Metadata attributes are grouped into six parts: identification, definition, representation, relation, usage guides, and administration. OpenPCR is an open metadata schema based on research registration standards, standards of the Clinical Data Interchange Standards Consortium (CDISC) and Chinese healthcare related standards, and is to be publicly available throughout China. It considers future integration of EHR and CR by adopting data structure and data terms in Chinese EHR Standard. Archetypes in openPCR are modularity models and can be separated, recombined, and reused. The authors recommend that the method to develop openPCR can be referenced by other countries when designing metadata schema of clinical research. In the next steps, openPCR should be used in a number of CR projects to test its applicability and to continuously improve its coverage. Besides, metadata schema for research protocol can be developed to structurize and standardize protocol, and syntactical interoperability of openPCR with other related standards can be considered.

An Efficient and QoS Supported Multichannel MAC Protocol for Vehicular Ad Hoc Networks

PubMed Central

Tan, Guozhen; Yu, Chao

2017-01-01

Vehicular Ad Hoc Networks (VANETs) employ multichannel to provide a variety of safety and non-safety (transport efficiency and infotainment) applications, based on the IEEE 802.11p and IEEE 1609.4 protocols. Different types of applications require different levels Quality-of-Service (QoS) support. Recently, transport efficiency and infotainment applications (e.g., electronic map download and Internet access) have received more and more attention, and this kind of applications is expected to become a big market driver in a near future. In this paper, we propose an Efficient and QoS supported Multichannel Medium Access Control (EQM-MAC) protocol for VANETs in a highway environment. The EQM-MAC protocol utilizes the service channel resources for non-safety message transmissions during the whole synchronization interval, and it dynamically adjusts minimum contention window size for different non-safety services according to the traffic conditions. Theoretical model analysis and extensive simulation results show that the EQM-MAC protocol can support QoS services, while ensuring the high saturation throughput and low transmission delay for non-safety applications. PMID:28991217

Physician Assistant/Sr. Nurse Practitioner | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides quality Physician Assistant and/or Nurse Practitioner clinical research services in support of the Urologic Oncology Branch (UOB), National Cancer Institute’s (NCI’s), Center for Cancer Research (CCR). KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Physician Extender: Provides clinical care in collaboration with physicians and health care professionals. Performs a comprehensive physical assessment and documents findings in the appropriate format following institutional and protocol standards. Assesses the patient's general health status through observation and the use of appropriate screening procedures. Acquires patient data through health history taking that includes family history and significant social information. Explains the care management/discharge plan to all members of the covering team (inpatient NPs, attendings) at sign-out. Provides teaching and guidance related to the patient's current state of health and understanding of his/her disease to promote optimal performance. Coordinates study enrollment, collaborates with nursing staff to provide protocol treatment, and provides follow-up care for patients participating in clinical trials. Assists the Principal Investigator (PI) in assuring informed consent forms have been signed, obtaining written consent for treatment, pharmacokinetics, and assessing patients on the study for complications. Calculates the dose of and prescribes chemotherapy, investigational agents, medications, intravenous fluids and blood products according to established protocol, institutional, and practice guidelines. Provides guidance in the management of specific problems for the patient resulting from chemotherapy, immunotherapy or other treatments. Manages appropriate referrals to other specialists as indicated. Screens new patient calls and provides phone triage for active patients. Orders radiological studies, following protocols and patient care guidelines. Orders and interprets lab studies. Attends new patient consultations with the patient and family for the purpose of explaining the diagnosis, protocol, and treatment program, and establishing a rapport. Completes initial and follow-up assessment(s), progress notes and written correspondence to multidisciplinary personnel. Serves as a clinical liaison to area hospices and/or home care agencies as needed or as appropriate. Acts as a clinical liaison between inpatient and outpatient nurses in order to provide continuity of care to the hospitalized patient. Maintains documented evidence of weekly case review with the collaborating physician. Attends and participates in multidisciplinary meetings. Practices within boundaries established by the Nurse Practice Act, State of Maryland and Medical Board of the Clinical Center. Liaises with Leidos Biomed and various NCI staff to initiate and complete tasks relating to medicine and clinical protocols, and all activities related to nursing. Performs clinical data recording and medical chart entries. Dictates admission and discharge summaries. This position is located in Bethesda, Maryland.

Variability of human pluripotent stem cell lines.

PubMed

Ortmann, Daniel; Vallier, Ludovic

2017-10-01

Human pluripotent stem cells derived from embryos (human Embryonic Stem Cells or hESCs) or generated by direct reprogramming of somatic cells (human Induced Pluripotent Stem Cells or hiPSCs) can proliferate almost indefinitely in vitro while maintaining the capacity to differentiate into a broad diversity of cell types. These two properties (self-renewal and pluripotency) confers human pluripotent stem cells a unique interest for clinical applications since they could allow the production of infinite quantities of cells for disease modelling, drug screening and cell based therapy. However, recent studies have clearly established that human pluripotent stem cell lines can display variable capacity to differentiate into specific lineages. Consequently, the development of universal protocols of differentiation which could work efficiently with any human pluripotent cell line is complicated substantially. As a consequence, each protocol needs to be adapted to every cell line thereby limiting large scale applications and precluding personalised therapies. Here, we summarise our knowledge concerning the origin of this variability and describe potential solutions currently available to bypass this major challenge. Copyright © 2017 Elsevier Ltd. All rights reserved.

ABM Clinical Protocol #21: Guidelines for Breastfeeding and the Drug-Dependent Woman

PubMed Central

2009-01-01

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID:19835481

ABM Clinical Protocol #19: Breastfeeding Promotion in the Prenatal Setting, Revision 2015

PubMed Central

Rosen-Carole, Casey; Hartman, Scott

2015-01-01

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID:26651541

MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses

PubMed Central

Nakayasu, Ernesto S.; Nicora, Carrie D.; Sims, Amy C.; Burnum-Johnson, Kristin E.; Kim, Young-Mo; Kyle, Jennifer E.; Matzke, Melissa M.; Shukla, Anil K.; Chu, Rosalie K.; Schepmoes, Athena A.; Jacobs, Jon M.; Baric, Ralph S.; Webb-Robertson, Bobbie-Jo; Smith, Richard D.

2016-01-01

ABSTRACT Integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. Despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. Here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-omics measurements. The metabolite, protein, and lipid extraction (MPLEx) protocol proved to be robust and applicable to a diverse set of sample types, including cell cultures, microbial communities, and tissues. To illustrate the utility of this protocol, an integrative multi-omics analysis was performed using a lung epithelial cell line infected with Middle East respiratory syndrome coronavirus, which showed the impact of this virus on the host glycolytic pathway and also suggested a role for lipids during infection. The MPLEx method is a simple, fast, and robust protocol that can be applied for integrative multi-omic measurements from diverse sample types (e.g., environmental, in vitro, and clinical). IMPORTANCE In systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated broad applicability and robustness, which enabled comprehensive proteomics, metabolomics, and lipidomics analyses from the same sample. Author Video: An author video summary of this article is available. PMID:27822525

Individual researcher liability for clinical research on humans.

PubMed

Miller, Ruth K

2003-01-01

Despite international guidelines and federal regulations, a recent rash of problems in clinical trials have highlighted weaknesses in the oversight process. The federal regulatory system depends on self-policing by researchers and institutions. Because the existing system is overworked, applying common law forms of liability to clinical researchers may encourage improvements in this self-regulation. While research necessarily involves uncertainties, researchers have the greatest direct control over the implementation of the research protocol and the most extensive direct contact with subjects, and must bear corresponding responsibility for acts which fall below the standard of care. This paper argues that the existing FDA patient protections should be adopted as the standards of care for researchers. It examines the possible application of negligence, negligence per se, and fraud and misrepresentation claims against researchers.

21 CFR 58.120 - Protocol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... FOR NONCLINICAL LABORATORY STUDIES Protocol for and Conduct of a Nonclinical Laboratory Study § 58.120 Protocol. (a) Each study shall have an approved written protocol that clearly indicates the objectives and all methods for the conduct of the study. The protocol shall contain, as applicable, the following...

Preparation and Application of an Innovative Thrombocyte/Leukocyte-Enriched Plasma to Promote Tissue Repair in Chelonians

PubMed Central

Di Ianni, Francesco; Merli, Elisa; Burtini, Francesca; Conti, Virna; Pelizzone, Igor; Di Lecce, Rosanna; Parmigiani, Enrico; Squassino, Gian Paolo; Del Bue, Maurizio; Lucarelli, Enrico; Ramoni, Roberto; Grolli, Stefano

2015-01-01

Platelet concentrates are widely used in mammalian regenerative medicine to improve tissue healing. Chelonians (Testudines) would benefit from the application of thrombocyte preparations to regenerate damaged tissues, since traumatic injuries are leading causes of morbidity and mortality for both wild-living and domesticated animals. The aim of this study was to establish a protocol that optimized the recovery of the thrombocytes from blood samples and to show the efficacy of thrombocyte-enriched plasma in chelonians. Peripheral blood samples were obtained from Testudo spp. (n = 12) and Trachemys scripta elegans (n = 10). Blood cells were fractionated by sodium diatrizoate-sodium polysucrose density gradient using a two-step centrifugation protocol. Thrombocytes and leukocytes were isolated and resuspended to obtain thrombocyte-leucocyte rich plasma (TLRP). The mean recovery of leukocytes and thrombocytes was 48.9% (±4.0 SEM, n = 22) of the whole blood cell content. No statistically significant difference was observed between blood samples collected from different turtle species. The ability of TLRP to form a gel was evaluated by adding variable concentrations of calcium gluconate at room temperature and at 37°C. A reliable and consistent clotting of the TLRP was obtained in glass tubes and dishes by adding 5-20% v/v of a 100 mg/ml solution of calcium gluconate. Furthermore, in order to test the clinical efficacy of TLRP, a preliminary evaluation was performed on four turtles (Testudo spp.) with traumatic injuries. In all the four animals, a successful clinical outcome was observed. The results demonstrated that a thrombocyte-enriched plasma, comparable to mammalian platelet rich plasma, can be prepared from chelonian blood samples. Furthermore, although the low number of cases presented does not allow definitive conclusions from a clinical point of view, their outcome suggests that TLRP application could be further investigated to improve the healing process of both soft and hard tissue injuries in chelonians. PMID:25901960

Detection of Trypanosoma cruzi by Polymerase Chain Reaction.

PubMed

Márquez, María Elizabeth; Concepción, Juan Luis; González-Marcano, Eglys; Mondolfi, Alberto Paniz

2016-01-01

American Trypanosomiasis (Chagas disease) is an infectious disease caused by the hemoflagellate parasite Trypanosoma cruzi which is transmitted by reduviid bugs. T. cruzi infection occurs in a broad spectrum of reservoir animals throughout North, Central, and South America and usually evolves into an asymptomatic chronic clinical stage of the disease in which diagnosis is often challenging. This chapter describes the application of polymerase chain reaction (PCR) for the detection of Trypanosoma cruzi DNA including protocols for sample preparation, DNA extraction, and target amplification methods.

Esthetic considerations for the treatment of the edentulous maxilla based on current informatic alternatives: a case report.

PubMed

Rodríguez-Tizcareño, Mario H; Barajas, Lizbeth; Pérez-Gásque, Marisol; Gómez, Salvador

2012-06-01

This report presents a protocol used to transfer the virtual treatment plan data to the surgical and prosthetic reality and its clinical application, bone site augmentation with computer-custom milled bovine bone graft blocks to their ideal architecture form, implant insertion based on image-guided stent fabrication, and the restorative manufacturing process through computed tomography-based software programs and navigation systems and the computer-aided design and manufacturing techniques for the treatment of the edentulous maxilla.

Performance assessment of two lysis methods for direct identification of yeasts from clinical blood cultures using MALDI-TOF mass spectrometry.

PubMed

Jeddi, Fakhri; Yapo-Kouadio, Gisèle Cha; Normand, Anne-Cécile; Cassagne, Carole; Marty, Pierre; Piarroux, Renaud

2017-02-01

In cases of fungal infection of the bloodstream, rapid species identification is crucial to provide adapted therapy and thereby ameliorate patient outcome. Currently, the commercial Sepsityper kit and the sodium-dodecyl sulfate (SDS) method coupled with MALDI-TOF mass spectrometry are the most commonly reported lysis protocols for direct identification of fungi from positive blood culture vials. However, the performance of these two protocols has never been compared on clinical samples. Accordingly, we performed a two-step survey on two distinct panels of clinical positive blood culture vials to identify the most efficient protocol, establish an appropriate log score (LS) cut-off, and validate the best method. We first compared the performance of the Sepsityper and the SDS protocols on 71 clinical samples. For 69 monomicrobial samples, mass spectrometry LS values were significantly higher with the SDS protocol than with the Sepsityper method (P < .0001), especially when the best score of four deposited spots was considered. Next, we established the LS cut-off for accurate identification at 1.7, based on specimen DNA sequence data. Using this LS cut-off, 66 (95.6%) and 46 (66.6%) isolates were correctly identified at the species level with the SDS and the Sepsityper protocols, respectively. In the second arm of the survey, we validated the SDS protocol on an additional panel of 94 clinical samples. Ninety-two (98.9%) of 93 monomicrobial samples were correctly identified at the species level (median LS = 2.061). Overall, our data suggest that the SDS method yields more accurate species identification of yeasts, than the Sepsityper protocol. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

PubMed Central

Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

2014-01-01

Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. PMID:25333995

[Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

PubMed

Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

2010-08-01

The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

Using mobile technology to deliver a cognitive behaviour therapy-informed intervention in early psychosis (Actissist): study protocol for a randomised controlled trial.

PubMed

Bucci, Sandra; Barrowclough, Christine; Ainsworth, John; Morris, Rohan; Berry, Katherine; Machin, Matthew; Emsley, Richard; Lewis, Shon; Edge, Dawn; Buchan, Iain; Haddock, Gillian

2015-09-10

Cognitive behaviour therapy (CBT) is recommended for the treatment of psychosis; however, only a small proportion of service users have access to this intervention. Smartphone technology using software applications (apps) could increase access to psychological approaches for psychosis. This paper reports the protocol development for a clinical trial of smartphone-based CBT. We present a study protocol that describes a single-blind randomised controlled trial comparing a cognitive behaviour therapy-informed software application (Actissist) plus Treatment As Usual (TAU) with a symptom monitoring software application (ClinTouch) plus TAU in early psychosis. The study consists of a 12-week intervention period. We aim to recruit and randomly assign 36 participants registered with early intervention services (EIS) across the North West of England, UK in a 2:1 ratio to each arm of the trial. Our primary objective is to determine whether in people with early psychosis the Actissist app is feasible to deliver and acceptable to use. Secondary aims are to determine whether Actissist impacts on predictors of first episode psychosis (FEP) relapse and enhances user empowerment, functioning and quality of life. Assessments will take place at baseline, 12 weeks (post-treatment) and 22-weeks (10 weeks post-treatment) by assessors blind to treatment condition. The trial will report on the feasibility and acceptability of Actissist and compare outcomes between the randomised arms. The study also incorporates semi-structured interviews about the experience of participating in the Actissist trial that will be qualitatively analysed to inform future developments of the Actissist protocol and app. To our knowledge, this is the first controlled trial to test the feasibility, acceptability, uptake, attrition and potential efficacy of a CBT-informed smartphone app for early psychosis. Mobile applications designed to deliver a psychologically-informed intervention offer new possibilities to extend the reach of traditional mental health service delivery across a range of serious mental health problems and provide choice about available care. ISRCTN34966555. Date of first registration: 12 June 2014.

[A security protocol for the exchange of personal medical data via Internet: monitoring treatment and drug effects].

PubMed

Viviani, R; Fischer, J; Spitzer, M; Freudenmann, R W

2004-04-01

We present a security protocol for the exchange of medical data via the Internet, based on the type/domain model. We discuss two applications of the protocol: in a system for the exchange of data for quality assurance, and in an on-line database of adverse reactions to drug use. We state that a type/domain security protocol can successfully comply with the complex requirements for data privacy and accessibility typical of such applications.

How to design and write a clinical research protocol in Cosmetic Dermatology*

PubMed Central

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

A Novel Combination Therapy for Patients With Dry Eye Disease: A Pilot Study.

PubMed

Smith, Will; McMahon, David; Nymark, Maria

2018-05-01

Context • Approximately 25% of the US population suffers from dry eyes or some abnormality of the exposed ocular surface. Investigation of effective modalities for their management is needed. Objective • The study intended to examine the efficacy of a proprietary, daily, Dry Eye Protocol consisting of daily use of a moist, heated, ocular compress and intake of an omega-3 dietary supplement in treatment of ocular surface disease. Design • The research team designed a 4-wk, clinically based, open-label, multicenter cohort study. Setting • The study took place at 6 private eye care practices throughout the United States: Beverly Hills, CA, USA; San Diego, CA, USA; Sunnyvale, CA, USA; Park City, UT, USA; Tarpon Spring, FL, USA; and Kennewick, WA, USA. Participants • Participants were adults between 18 and 75 y of age who had established ocular surface disease based on clinical findings and the results of testing using the ocular surface disease index (OSDI). Intervention • For period of 30 d, participants used a combined daily protocol that included (1) application of a moist, heated, eye compress and (2) a nutritional therapy via an omega-3 supplement in an oral triglyceride form. Outcome Measures • Measures included the OSDI and a test of tear break-up time (TBUT). Results • Of the original 35 participants, 33 completed the 4-wk protocol. The participants using the proprietary Dry Eye Protocol showed significant improvements from baseline, demonstrated by a 49% decrease in OSDI scores (P = .0015); and 46% of participants reported becoming asymptomatic of dry eye symptoms. A significant improvement was also observed in TBUT, increasing from 3.0 to 5.4 s. Conclusions • Daily use of the proprietary Dry Eye Protocol that included a high dosage of triglyceride omega-3 and use of a moist, heated, compress daily showed significant improvement for participants in OSDI and TBUT and should be considered to be a first-line therapy for patients with dry eye disease.

Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

PubMed

Shannahoff-Khalsa, David S

2005-03-01

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Techniques for physicochemical characterization of nanomaterials

PubMed Central

Lin, Ping-Chang; Lin, Stephen; Wang, Paul C.; Sridhar, Rajagopalan

2014-01-01

Advances in nanotechnology have opened up a new era of diagnosis, prevention and treatment of diseases and traumatic injuries. Nanomaterials, including those with potential for clinical applications, possess novel physicochemical properties that have an impact on their physiological interactions, from the molecular level to the systemic level. There is a lack of standardized methodologies or regulatory protocols for detection or characterization of nanomaterials. This review summarizes the techniques that are commonly used to study the size, shape, surface properties, composition, purity and stability of nanomaterials, along with their advantages and disadvantages. At present there are no FDA guidelines that have been developed specifically for nanomaterial based formulations for diagnostic or therapeutic use. There is an urgent need for standardized protocols and procedures for the characterization of nanoparticles, especially those that are intended for use as theranostics. PMID:24252561

Patient-derived Models of Human Breast Cancer: Protocols for In vitro and In vivo Applications in Tumor Biology and Translational Medicine

PubMed Central

DeRose, Yoko S.; Gligorich, Keith M.; Wang, Guoying; Georgelas, Ann; Bowman, Paulette; Courdy, Samir J.; Welm, Alana L.; Welm, Bryan E.

2013-01-01

Research models that replicate the diverse genetic and molecular landscape of breast cancer are critical for developing the next generation therapeutic entities that can target specific cancer subtypes. Patient-derived tumorgrafts, generated by transplanting primary human tumor samples into immune-compromised mice, are a valuable method to model the clinical diversity of breast cancer in mice, and are a potential resource in personalized medicine. Primary tumorgrafts also enable in vivo testing of therapeutics and make possible the use of patient cancer tissue for in vitro screens. Described in this unit are a variety of protocols including tissue collection, biospecimen tracking, tissue processing, transplantation, and 3-dimensional culturing of xenografted tissue, that enable use of bona fide uncultured human tissue in designing and validating cancer therapies. PMID:23456611

Development of a calibration protocol for quantitative imaging for molecular radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Wevrett, J.; Fenwick, A.; Scuffham, J.; Nisbet, A.

2017-11-01

Within the field of molecular radiotherapy, there is a significant need for standardisation in dosimetry, in both quantitative imaging and dosimetry calculations. Currently, there are a wide range of techniques used by different clinical centres and as a result there is no means to compare patient doses between centres. To help address this need, a 3 year project was funded by the European Metrology Research Programme, and a number of clinical centres were involved in the project. One of the required outcomes of the project was to develop a calibration protocol for three dimensional quantitative imaging of volumes of interest. Two radionuclides were selected as being of particular interest: iodine-131 (131I, used to treat thyroid disorders) and lutetium-177 (177Lu, used to treat neuroendocrine tumours). A small volume of activity within a scatter medium (water), representing a lesion within a patient body, was chosen as the calibration method. To ensure ease of use in clinical centres, an "off-the-shelf" solution was proposed - to avoid the need for in-house manufacturing. The BIODEX elliptical Jaszczak phantom and 16 ml fillable sphere were selected. The protocol was developed for use on SPECT/CT gamma cameras only, where the CT dataset would be used to correct the imaging data for attenuation of the emitted photons within the phantom. The protocol corrects for scatter of emitted photons using the triple energy window correction technique utilised by most clinical systems. A number of clinical systems were tested in the development of this protocol, covering the major manufacturers of gamma camera generally used in Europe. Initial imaging was performed with 131I and 177Lu at a number of clinical centres, but due to time constraints in the project, some acquisitions were performed with 177Lu only. The protocol is relatively simplistic, and does not account for the effects of dead-time in high activity patients, the presence of background activity surrounding volumes of interest or the partial volume effect of imaging lesions smaller than 16 ml. The development of this simple protocol demonstrates that it is possible to produce a standardised quantitative imaging protocol for molecular radiotherapy dosimetry. However, the protocol needs further development to expand it to incorporate other radionuclides, and to account for the effects that have been disregarded in this initial version.

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Update on the MRI Core of the Alzheimer's Disease Neuroimaging Initiative

PubMed Central

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; DeCarli, Charles S; Dale, Anders M; Weiner, Michael W

2010-01-01

Functions of the ADNI MRI core fall into three categories: (1) those of the central MRI core lab at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data, and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present (“ADNI-GO”) and future (“ADNI-2”, if funded) MRI protocol will be to maintain MRI methodological consistency in previously enrolled “ADNI-1” subjects who are followed longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor specific pilot sub-studies of arterial spin labeling perfusion, resting state functional connectivity and diffusion tensor imaging. One each of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multi-center (but single vendor) setting for these three emerging MRI applications. PMID:20451869

Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience.

PubMed

Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco

2018-05-02

The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.

Update on the magnetic resonance imaging core of the Alzheimer's disease neuroimaging initiative.

PubMed

Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; Decarli, Charles S; Dale, Anders M; Carmichael, Owen W; Tosun, Duygu; Weiner, Michael W

2010-05-01

Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications. Copyright 2010 The Alzheimer

Isolation of tumor antigen-specific single-chain variable fragments using a chimeric antigen receptor bicistronic retroviral vector in a Mammalian screening protocol.

PubMed

Lipowska-Bhalla, Grazyna; Gilham, David E; Hawkins, Robert E; Rothwell, Dominic G

2013-12-01

The clinical potential of chimeric antigen receptors in adoptive cellular therapy is beginning to be realized with several recent clinical trials targeting CD19 showing promising results in advanced B cell malignancies. This increased efficacy corresponds with improved engineering of the chimeric receptors with the latest-generation receptors eliciting greater signaling and proliferation potential. However, the antigen-binding single-chain variable fragment (scFv) domain of the receptors is critical in determining the activity of the chimeric receptor-expressing T cells, as this determines specificity and affinity to the tumor antigen. In this study, we describe a mammalian T cell line screening protocol employing a 2A-based bicistronic retroviral vector to isolate functional scFvs. This approach involves expression of the scFv library in a chimeric antigen receptor, and is based on selection of clones capable of stimulating CD69 upregulation in a T cell line and has a number of advantages over previously described methods in that the use of a 2A cassette ensures the exclusion of nonexpressing scFvs and the screening using a chimeric receptor in a mammalian T cell line ensures selection in the optimum context for therapeutic use. Proof-of-principle experiments show that the protocol was capable of a 10(5)-fold enrichment of positive clones after three rounds of selection. Furthermore, an antigen-specific clone was successfully isolated from a partially enriched scFv library, confirming the strength of the protocol. This approach has the potential to identify novel scFvs of use in adoptive T cell therapy and, potentially, wider antibody-based applications.

Ultrafast Brain MRI: Clinical Deployment and Comparison to Conventional Brain MRI at 3T.

PubMed

Prakkamakul, Supada; Witzel, Thomas; Huang, Susie; Boulter, Daniel; Borja, Maria J; Schaefer, Pamela; Rosen, Bruce; Heberlein, Keith; Ratai, Eva; Gonzalez, Gilberto; Rapalino, Otto

2016-09-01

To compare an ultrafast brain magnetic resonance imaging (MRI) protocol to the conventional protocol in motion-prone inpatient clinical settings. This retrospective study was HIPAA compliant and approved by the Institutional Review Board with waived inform consent. Fifty-nine inpatients (30 males, 29 females; mean age 55.1, range 23-93 years)who underwent 3-Tesla brain MRI using ultrafast and conventional protocols, both including five sequences, were included in the study. The total scan time for five ultrafast sequences was 4 minutes 59 seconds. The ideal conventional acquisition time was 10 minutes 32 seconds but the actual acquisition took 15-20 minutes. The average scan times for ultrafast localizers, T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, T2*-weighted sequences were 14, 41, 62, 96, 80, 6 seconds, respectively. Two blinded neuroradiologists independently assessed three aspects: (1) image quality, (2) gray-white matter (GM-WM) differentiation, and (3) diagnostic concordance for the detection of six clinically relevant imaging findings. Wilcoxon signed-rank test was used to compare image quality and GM-WM scores. Interobserver reproducibility was calculated. The ultrafast T1-weighted sequence demonstrated significantly better image quality (P = .005) and GM-WM differentiation (P < .001) compared to the conventional sequence. There was high agreement (>85%) between both protocols for the detection of mass-like lesion, hemorrhage, diffusion restriction, WM FLAIR hyperintensities, subarachnoid FLAIR hyperintensities, and hydrocephalus. The ultrafast protocol achieved at least comparable image quality and high diagnostic concordance compared to the conventional protocol. This fast protocol can be a viable option to replace the conventional protocol in motion-prone inpatient clinical settings. Copyright © 2016 by the American Society of Neuroimaging.

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

An energy-aware routing protocol for query-based applications in wireless sensor networks.

PubMed

Ahvar, Ehsan; Ahvar, Shohreh; Lee, Gyu Myoung; Crespi, Noel

2014-01-01

Wireless sensor network (WSN) typically has energy consumption restriction. Designing energy-aware routing protocol can significantly reduce energy consumption in WSNs. Energy-aware routing protocols can be classified into two categories, energy savers and energy balancers. Energy saving protocols are used to minimize the overall energy consumed by a WSN, while energy balancing protocols attempt to efficiently distribute the consumption of energy throughout the network. In general terms, energy saving protocols are not necessarily good at balancing energy consumption and energy balancing protocols are not always good at reducing energy consumption. In this paper, we propose an energy-aware routing protocol (ERP) for query-based applications in WSNs, which offers a good trade-off between traditional energy balancing and energy saving objectives and supports a soft real time packet delivery. This is achieved by means of fuzzy sets and learning automata techniques along with zonal broadcasting to decrease total energy consumption.

An Energy-Aware Routing Protocol for Query-Based Applications in Wireless Sensor Networks

PubMed Central

Crespi, Noel

2014-01-01

Wireless sensor network (WSN) typically has energy consumption restriction. Designing energy-aware routing protocol can significantly reduce energy consumption in WSNs. Energy-aware routing protocols can be classified into two categories, energy savers and energy balancers. Energy saving protocols are used to minimize the overall energy consumed by a WSN, while energy balancing protocols attempt to efficiently distribute the consumption of energy throughout the network. In general terms, energy saving protocols are not necessarily good at balancing energy consumption and energy balancing protocols are not always good at reducing energy consumption. In this paper, we propose an energy-aware routing protocol (ERP) for query-based applications in WSNs, which offers a good trade-off between traditional energy balancing and energy saving objectives and supports a soft real time packet delivery. This is achieved by means of fuzzy sets and learning automata techniques along with zonal broadcasting to decrease total energy consumption. PMID:24696640

Regenerative Endodontics: A Road Less Travelled

PubMed Central

Bansal, Ramta; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

2014-01-01

Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering. PMID:25478476

Automatic Determination of the Need for Intravenous Contrast in Musculoskeletal MRI Examinations Using IBM Watson's Natural Language Processing Algorithm.

PubMed

Trivedi, Hari; Mesterhazy, Joseph; Laguna, Benjamin; Vu, Thienkhai; Sohn, Jae Ho

2018-04-01

Magnetic resonance imaging (MRI) protocoling can be time- and resource-intensive, and protocols can often be suboptimal dependent upon the expertise or preferences of the protocoling radiologist. Providing a best-practice recommendation for an MRI protocol has the potential to improve efficiency and decrease the likelihood of a suboptimal or erroneous study. The goal of this study was to develop and validate a machine learning-based natural language classifier that can automatically assign the use of intravenous contrast for musculoskeletal MRI protocols based upon the free-text clinical indication of the study, thereby improving efficiency of the protocoling radiologist and potentially decreasing errors. We utilized a deep learning-based natural language classification system from IBM Watson, a question-answering supercomputer that gained fame after challenging the best human players on Jeopardy! in 2011. We compared this solution to a series of traditional machine learning-based natural language processing techniques that utilize a term-document frequency matrix. Each classifier was trained with 1240 MRI protocols plus their respective clinical indications and validated with a test set of 280. Ground truth of contrast assignment was obtained from the clinical record. For evaluation of inter-reader agreement, a blinded second reader radiologist analyzed all cases and determined contrast assignment based on only the free-text clinical indication. In the test set, Watson demonstrated overall accuracy of 83.2% when compared to the original protocol. This was similar to the overall accuracy of 80.2% achieved by an ensemble of eight traditional machine learning algorithms based on a term-document matrix. When compared to the second reader's contrast assignment, Watson achieved 88.6% agreement. When evaluating only the subset of cases where the original protocol and second reader were concordant (n = 251), agreement climbed further to 90.0%. The classifier was relatively robust to spelling and grammatical errors, which were frequent. Implementation of this automated MR contrast determination system as a clinical decision support tool may save considerable time and effort of the radiologist while potentially decreasing error rates, and require no change in order entry or workflow.

Translational microsurgery. A new platform for transplantation research.

PubMed

Kobayashi, Eiji; Haga, Junko

2016-03-01

Clinical microsurgery has been introduced in many fields, while experimental microsurgery has the cross-disciplinary features of the sciences and techniques for growth of medicine, pharmacology, veterinary, engineering etc. Training protocol, proposing a new name as Translational Microsurgery, was introduced. Reconstructive skills of hepatic artery in pediatric living donor liver transplantation were summarized. Ex vivo training protocol using artificial blood vessel for surgeons was proposed. Clinical microsurgery requires anastomosis with delicate arteries and limited field of view. Our training protocol revealed that the relation between the score and speed was seen, while not all the surgeons with enough experience got high score. This training led to muster clinical skills and to apply excellent experimental works. Our microsurgical training protocol has been planned from the points of clinical setting. Training for vascular anastomosis led to rodent transplantation models. These models were used for immunology and immunosuppressant research. Microsurgical techniques led to master catheter technique and to inject various drugs or gene vectors.

Use of an android phone application for automated text messages in international settings: A case study in an HIV clinical trial in St. Petersburg, Russia.

PubMed

Forman, Leah S; Patts, Gregory J; Coleman, Sharon M; Blokhina, Elena; Lu, John; Yaroslavtseva, Tatiana; Gnatienko, Natalia; Krupitsky, Evgeny; Samet, Jeffrey H; Chaisson, Christine E

2018-02-01

Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings. To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan. The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.

ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Use or Substance Use Disorder, Revised 2015

PubMed Central

2015-01-01

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID:25836677

Research into alternative network approaches for space operations

NASA Technical Reports Server (NTRS)

Kusmanoff, Antone L.; Barton, Timothy J.

1990-01-01

The main goal is to resolve the interoperability problem of applications employing DOD TCP/IP (Department of Defence Transmission Control Protocol/Internet Protocol) family of protocols on a CCITT/ISO based network. The objective is to allow them to communicate over the CCITT/ISO protocol GPLAN (General Purpose Local Area Network) network without modification to the user's application programs. There were two primary assumptions associated with the solution that was actually realized. The first is that the solution had to allow for future movement to the exclusive use of the CCITT/ISO standards. The second is that the solution had to be software transparent to the currently installed TCP/IP and CCITT/ISO user application programs.

Effectiveness of Serious Games for Leap Motion on the Functionality of the Upper Limb in Parkinson's Disease: A Feasibility Study.

PubMed

Oña, Edwin Daniel; Balaguer, Carlos; Cano-de la Cuerda, Roberto; Collado-Vázquez, Susana; Jardón, Alberto

2018-01-01

The design and application of Serious Games (SG) based on the Leap Motion sensor are presented as a tool to support the rehabilitation therapies for upper limbs. Initially, the design principles and their implementation are described, focusing on improving both unilateral and bilateral manual dexterity and coordination. The design of the games has been supervised by specialized therapists. To assess the therapeutic effectiveness of the proposed system, a protocol of trials with Parkinson's patients has been defined. Evaluations of the physical condition of the participants in the study, at the beginning and at the end of the treatment, are carried out using standard tests. The specific measurements of each game give the therapist more detailed information about the patients' evolution after finishing the planned protocol. The obtained results support the fact that the set of developed video games can be combined to define different therapy protocols and that the information obtained is richer than the one obtained through current clinical metrics, serving as method of motor function assessment.

Effectiveness of Serious Games for Leap Motion on the Functionality of the Upper Limb in Parkinson's Disease: A Feasibility Study

PubMed Central

Balaguer, Carlos; Collado-Vázquez, Susana; Jardón, Alberto

2018-01-01

The design and application of Serious Games (SG) based on the Leap Motion sensor are presented as a tool to support the rehabilitation therapies for upper limbs. Initially, the design principles and their implementation are described, focusing on improving both unilateral and bilateral manual dexterity and coordination. The design of the games has been supervised by specialized therapists. To assess the therapeutic effectiveness of the proposed system, a protocol of trials with Parkinson's patients has been defined. Evaluations of the physical condition of the participants in the study, at the beginning and at the end of the treatment, are carried out using standard tests. The specific measurements of each game give the therapist more detailed information about the patients' evolution after finishing the planned protocol. The obtained results support the fact that the set of developed video games can be combined to define different therapy protocols and that the information obtained is richer than the one obtained through current clinical metrics, serving as method of motor function assessment. PMID:29849550

A biochemical protocol for the isolation and identification of current species of Vibrio in seafood.

PubMed

Ottaviani, D; Masini, L; Bacchiocchi, S

2003-01-01

We report a biochemical method for the isolation and identification of the current species of vibrios using just one operative protocol. The method involves an enrichment phase with incubation at 30 degrees C for 8-24 h in alkaline peptone water and an isolation phase on thiosulphate-citrate-salt sucrose agar plates incubating at 30 degrees C for 24 h. Four biochemical tests and Alsina's scheme were performed for genus and species identification, respectively. All biochemical tests were optimized as regards conditions of temperature, time of incubation and media composition. The whole standardized protocol was always able to give a correct identification when applied to 25 reference strains of Vibrio and 134 field isolates. The data demonstrated that the assay method allows an efficient recovery, isolation and identification of current species of Vibrio in seafood obtaining results within 2-7 days. This method based on biochemical tests could be applicable even in basic microbiology laboratories, and can be used simultaneously to isolate and discriminate all clinically relevant species of Vibrio.

Comparative Study on Various Authentication Protocols in Wireless Sensor Networks.

PubMed

Rajeswari, S Raja; Seenivasagam, V

2016-01-01

Wireless sensor networks (WSNs) consist of lightweight devices with low cost, low power, and short-ranged wireless communication. The sensors can communicate with each other to form a network. In WSNs, broadcast transmission is widely used along with the maximum usage of wireless networks and their applications. Hence, it has become crucial to authenticate broadcast messages. Key management is also an active research topic in WSNs. Several key management schemes have been introduced, and their benefits are not recognized in a specific WSN application. Security services are vital for ensuring the integrity, authenticity, and confidentiality of the critical information. Therefore, the authentication mechanisms are required to support these security services and to be resilient to distinct attacks. Various authentication protocols such as key management protocols, lightweight authentication protocols, and broadcast authentication protocols are compared and analyzed for all secure transmission applications. The major goal of this survey is to compare and find out the appropriate protocol for further research. Moreover, the comparisons between various authentication techniques are also illustrated.

Comparative Study on Various Authentication Protocols in Wireless Sensor Networks

PubMed Central

Rajeswari, S. Raja; Seenivasagam, V.

2016-01-01

Wireless sensor networks (WSNs) consist of lightweight devices with low cost, low power, and short-ranged wireless communication. The sensors can communicate with each other to form a network. In WSNs, broadcast transmission is widely used along with the maximum usage of wireless networks and their applications. Hence, it has become crucial to authenticate broadcast messages. Key management is also an active research topic in WSNs. Several key management schemes have been introduced, and their benefits are not recognized in a specific WSN application. Security services are vital for ensuring the integrity, authenticity, and confidentiality of the critical information. Therefore, the authentication mechanisms are required to support these security services and to be resilient to distinct attacks. Various authentication protocols such as key management protocols, lightweight authentication protocols, and broadcast authentication protocols are compared and analyzed for all secure transmission applications. The major goal of this survey is to compare and find out the appropriate protocol for further research. Moreover, the comparisons between various authentication techniques are also illustrated. PMID:26881272

Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE® bioreactor

PubMed Central

2012-01-01

Background To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. Methods We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols. Results TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype. Conclusions The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols. PMID:22475724

Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.

PubMed

Amsterdam, Ezra A; Kirk, J Douglas; Bluemke, David A; Diercks, Deborah; Farkouh, Michael E; Garvey, J Lee; Kontos, Michael C; McCord, James; Miller, Todd D; Morise, Anthony; Newby, L Kristin; Ruberg, Frederick L; Scordo, Kristine Anne; Thompson, Paul D

2010-10-26

The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.

From design to implementation - The Joint Asia Diabetes Evaluation (JADE) program: A descriptive report of an electronic web-based diabetes management program

PubMed Central

2010-01-01

Background The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care. Methods The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose. Results The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions. Conclusions The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes. PMID:20465815

A protocol for the Hamilton Rating Scale for Depression: Item scoring rules, Rater training, and outcome accuracy with data on its application in a clinical trial.

PubMed

Rohan, Kelly J; Rough, Jennifer N; Evans, Maggie; Ho, Sheau-Yan; Meyerhoff, Jonah; Roberts, Lorinda M; Vacek, Pamela M

2016-08-01

We present a fully articulated protocol for the Hamilton Rating Scale for Depression (HAM-D), including item scoring rules, rater training procedures, and a data management algorithm to increase accuracy of scores prior to outcome analyses. The latter involves identifying potentially inaccurate scores as interviews with discrepancies between two independent raters on the basis of either scores >=5-point difference) or meeting threshold for depression recurrence status, a long-term treatment outcome with public health significance. Discrepancies are resolved by assigning two new raters, identifying items with disagreement per an algorithm, and reaching consensus on the most accurate scores for those items. These methods were applied in a clinical trial where the primary outcome was the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder version (SIGH-SAD), which includes the 21-item HAM-D and 8 items assessing atypical symptoms. 177 seasonally depressed adult patients were enrolled and interviewed at 10 time points across treatment and the 2-year followup interval for a total of 1589 completed interviews with 1535 (96.6%) archived. Inter-rater reliability ranged from ICCs of .923-.967. Only 86 (5.6%) interviews met criteria for a between-rater discrepancy. HAM-D items "Depressed Mood", "Work and Activities", "Middle Insomnia", and "Hypochondriasis" and Atypical items "Fatigability" and "Hypersomnia" contributed most to discrepancies. Generalizability beyond well-trained, experienced raters in a clinical trial is unknown. Researchers might want to consider adopting this protocol in part or full. Clinicians might want to tailor it to their needs. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-E-P-03: Implementing a Low Dose Lung Screening CT Program Meeting Regulatory Requirements

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

LaFrance, M; Marsh, S; O'Donnell, G

Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Purpose: Provide guidance to the Radiology Departments with the intent of implementing a Low Dose CT Screening Program using different CT Scanners with multiple techniques within the framework of the required state regulations. Method: State Requirements for the purpose of implementing a Low Dose CT Lung Protocol required working with the Radiology and Pulmonary Department in setting up a Low Dose Screening Protocol designed to reduce the radiation burden to the patients enrolled. Radiation dose measurements (CTDIvol) for various CTmore » manufacturers (Siemens16, Siemens 64, Philips 64, and Neusoft128) for three different weight based protocols. All scans were reviewed by the Radiologist. Prior to starting a low dose lung screening protocol, information had to be submitted to the state for approval. Performing a Healing Arts protocol requires extensive information. This not only includes name and address of the applicant but a detailed description of the disease, the x-ray examination and the population to be examined. The unit had to be tested by a qualified expert using the technique charts. The credentials of all the operators, the supervisors and the Radiologists had to be submitted to the state. Results: All the appropriate documentation was sent to the state for review. The measured results between the Low Dose Protocol versus the default Adult Chest Protocol showed that there was a dose reduction of 65% for small (100-150 lb.) patient, 75% for the Medium patient (151-250 lbs.), and a 55% reduction for the Large patient ( over 250 lbs.). Conclusion: Measured results indicated that the Low Dose Protocol indeed lowered the screening patient's radiation dose and the institution was able to submit the protocol to the State's regulators.« less

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation.

PubMed

Giovanni, Assenza; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets.

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation

PubMed Central

Assenza, Giovanni; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets. PMID:28659788

Reliability, validity and sensitivity of a computerized visual analog scale measuring state anxiety.

PubMed

Abend, Rany; Dan, Orrie; Maoz, Keren; Raz, Sivan; Bar-Haim, Yair

2014-12-01

Assessment of state anxiety is frequently required in clinical and research settings, but its measurement using standard multi-item inventories entails practical challenges. Such inventories are increasingly complemented by paper-and-pencil, single-item visual analog scales measuring state anxiety (VAS-A), which allow rapid assessment of current anxiety states. Computerized versions of VAS-A offer additional advantages, including facilitated and accurate data collection and analysis, and applicability to computer-based protocols. Here, we establish the psychometric properties of a computerized VAS-A. Experiment 1 assessed the reliability, convergent validity, and discriminant validity of the computerized VAS-A in a non-selected sample. Experiment 2 assessed its sensitivity to increase in state anxiety following social stress induction, in participants with high levels of social anxiety. Experiment 1 demonstrated the computerized VAS-A's test-retest reliability (r = .44, p < .001); convergent validity with the State-Trait Anxiety Inventory's state subscale (STAI-State; r = .60, p < .001); and discriminant validity as indicated by significantly lower correlations between VAS-A and different psychological measures relative to the correlation between VAS-A and STAI-State. Experiment 2 demonstrated the VAS-A's sensitivity to changes in state anxiety via a significant pre- to during-stressor rise in VAS-A scores (F(1,48) = 25.13, p < .001). Set-order administration of measures, absence of clinically-anxious population, and gender-unbalanced samples. The adequate psychometric characteristics, combined with simple and rapid administration, make the computerized VAS-A a valuable self-rating tool for state anxiety. It may prove particularly useful for clinical and research settings where multi-item inventories are less applicable, including computer-based treatment and assessment protocols. The VAS-A is freely available: http://people.socsci.tau.ac.il/mu/anxietytrauma/visual-analog-scale/. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation of a real-time wireless telemedicine system, using bluetooth protocol and a mobile phone, for remote monitoring patient in medical practice.

PubMed

Yousef, Jasemian; Lars, A N

2005-06-22

This paper validates the integration of a generic real-time wireless telemedicine system utilising Global System for Mobile Communications (GSM), BLUETOOTH protocol and General Packet Radio Service (GPRS) for cellular network in clinical practice. In the first experiment, the system was tested on 24 pacemaker patients at Aalborg Hospital (Denmark), in order to see if the pacemaker implant would be affected by the system. I the second experiment, the system was tested on 15 non risky arrhythmia heart patients, in order to evaluate and validate the system application in clinical practice, for patient monitoring. Electrocardiograms were selected as the continuously monitored parameter in the present study. The results showed that the system had no negative effects on the pacemaker implants. The experiment results showed, that in a realistic environment for the patients, the system had 96.1 % up-time, 3.2 (kbps) throughput, 10(-3) (packet/s) Packet Error Rate and 10(-3) (packet/s) Packet Lost Rate. During 24 hours test the network did not respond for 57 minutes, from which 83.1 % was in the range of 0-3 minutes, 15.4 % was in the range of 3-5 minutes, and only 0.7 % of the down-time was > or = 5 and < or = 6 minutes. By a subjective evaluation, it was demonstrated that the system is applicable and the patients as well as the healthcare personals were highly confident with the system. Moreover, the patients had high degree of mobility and freedom, employing the system. In conclusion, this generic telemedicine system showed a high reliability, quality and performance, and the design can provide a basic principle for real-time wireless remote monitoring systems used in clinical practice.

γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material.

PubMed

Menegakis, Apostolos; von Neubeck, Cläre; Yaromina, Ala; Thames, Howard; Hering, Sandra; Hennenlotter, Joerg; Scharpf, Marcus; Noell, Susan; Krause, Mechthild; Zips, Daniel; Baumann, Michael

2015-09-01

To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after >12h following ex vivo irradiation. Fitting the dose-response of residual γH2AX foci yielded slopes comparable with in situ irradiation of FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient-derived tumour samples were found. A novel clinically applicable method to quantify residual γH2AX foci in ex vivo irradiated tumour samples was established. The first clinical results suggest that this method allows to distinguish between radiosensitive and radioresistant tumour types. These findings support further translational evaluation of this assay to individualise radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

PubMed

Liedert, B; Bassus, S; Schneider, C K; Kalinke, U; Löwer, J

2007-01-01

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.

The Rockefeller University Navigation Program: A Structured Multidisciplinary Protocol Development and Educational Program to Advance Translational Research

PubMed Central

Kost, Rhonda G.; Dowd, Kathleen A.; Hurley, Arlene M.; Rainer, Tyler‐Lauren; Coller, Barry S.

2014-01-01

Abstract The development of translational clinical research protocols is complex. To assist investigators, we developed a structured supportive guidance process (Navigation) to expedite protocol development to the standards of good clinical practice (GCP), focusing on research ethics and integrity. Navigation consists of experienced research coordinators leading investigators through a concerted multistep protocol development process from concept initiation to submission of the final protocol. To assess the effectiveness of Navigation, we collect data on the experience of investigators, the intensity of support required for protocol development, IRB review outcomes, and protocol start and completion dates. One hundred forty‐four protocols underwent Navigation and achieved IRB approval since the program began in 2007, including 37 led by trainee investigators, 26 led by MDs, 9 by MD/PhDs, 57 by PhDs, and 12 by investigators with other credentials (e.g., RN, MPH). In every year, more than 50% of Navigated protocols were approved by the IRB within 30 days. For trainees who had more than one protocol navigated, the intensity of Navigation support required decreased over time. Navigation can increase access to translational studies for basic scientists, facilitate GCP training for investigators, and accelerate development and approval of protocols of high ethical and scientific quality. PMID:24405608

SAMP, the Simple Application Messaging Protocol: Letting applications talk to each other

NASA Astrophysics Data System (ADS)

Taylor, M. B.; Boch, T.; Taylor, J.

2015-06-01

SAMP, the Simple Application Messaging Protocol, is a hub-based communication standard for the exchange of data and control between participating client applications. It has been developed within the context of the Virtual Observatory with the aim of enabling specialised data analysis tools to cooperate as a loosely integrated suite, and is now in use by many and varied desktop and web-based applications dealing with astronomical data. This paper reviews the requirements and design principles that led to SAMP's specification, provides a high-level description of the protocol, and discusses some of its common and possible future usage patterns, with particular attention to those factors that have aided its success in practice.

The release of Doxorubicin from liposomes monitored by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model.

PubMed

Rizzitelli, S; Giustetto, P; Faletto, D; Delli Castelli, D; Aime, S; Terreno, E

2016-05-28

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. Copyright © 2016 Elsevier B.V. All rights reserved.

Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.

PubMed

Lian, Qizhou; Zhang, Yuelin; Liang, Xiaoting; Gao, Fei; Tse, Hung-Fat

2016-01-01

Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Cells generated with this protocol express typical MSCs surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to adult bone marrow-derived MSCs (BM-MSCs). Nonetheless, compared with adult BM-MSCs, iPSC-MSCs display a higher proliferative capacity, up to 120 passages, without obvious loss of self-renewal potential and constitutively express MSCs surface antigens. MSCs generated with this protocol have numerous applications, including expansion to large scale cell numbers for tissue engineering and the development of cellular therapeutics. This approach has been used to rescue limb ischemia, allergic disorders, and cigarette smoke-induced lung damage and to model mesenchymal and vascular disorders of Hutchinson-Gilford progeria syndrome (HGPS).

Infrared thermal imaging in medicine.

PubMed

Ring, E F J; Ammer, K

2012-03-01

This review describes the features of modern infrared imaging technology and the standardization protocols for thermal imaging in medicine. The technique essentially uses naturally emitted infrared radiation from the skin surface. Recent studies have investigated the influence of equipment and the methods of image recording. The credibility and acceptance of thermal imaging in medicine is subject to critical use of the technology and proper understanding of thermal physiology. Finally, we review established and evolving medical applications for thermal imaging, including inflammatory diseases, complex regional pain syndrome and Raynaud's phenomenon. Recent interest in the potential applications for fever screening is described, and some other areas of medicine where some research papers have included thermal imaging as an assessment modality. In certain applications thermal imaging is shown to provide objective measurement of temperature changes that are clinically significant.

Progeria 101/FAQ

MedlinePlus

... Culture Protocols Immortalized Cell Culture Protocols Induced Pluripotent Stem Cells PRF Cell and Tissue Bank Publications Research Funding Opportunities Grant Application Application Deadlines Grants Funded Close Meet The Kids Meet The Kids Our Ambassadors Find The Other ...

Objective Assessment of Joint Stiffness: A Clinically Oriented Hardware and Software Device with an Application to the Shoulder Joint.

PubMed

McQuade, Kevin; Price, Robert; Liu, Nelson; Ciol, Marcia A

2012-08-30

Examination of articular joints is largely based on subjective assessment of the "end-feel" of the joint in response to manually applied forces at different joint orientations. This technical report aims to describe the development of an objective method to examine joints in general, with specific application to the shoulder, and suitable for clinical use. We adapted existing hardware and developed laptop-based software to objectively record the force/displacement behavior of the glenohumeral joint during three common manual joint examination tests with the arm in six positions. An electromagnetic tracking system recorded three-dimensional positions of sensors attached to a clinician examiner and a patient. A hand-held force transducer recorded manually applied translational forces. The force and joint displacement were time-synchronized and the joint stiffness was calculated as a quantitative representation of the joint "end-feel." A methodology and specific system checks were developed to enhance clinical testing reproducibility and precision. The device and testing protocol were tested on 31 subjects (15 with healthy shoulders, and 16 with a variety of shoulder impairments). Results describe the stiffness responses, and demonstrate the feasibility of using the device and methods in clinical settings.

The wreathing protocol: the imbrication of hypnosis and EMDR in the treatment of dissociative identity disorder and other dissociative responses. Eye Movement Desensitization Reprocessing.

PubMed

Fine, C G; Berkowitz, A S

2001-01-01

Dissociative Identity Disorder (DID), a chronic childhood onset posttraumatic stress disorder, is currently recognized as a treatable condition. It is considered the paradigmatic dissociative condition and carries with it extreme posttraumatic symptomatology. Therapists skilled in the treatment of DID are typically fluent in the uses of hypnosis for stabilization, affect management, building a safe place and grounding to name of few. EMDR, which has come to the forefront of clinical awareness in the last ten years, seems aptly suited for the treatment of trauma, but can be destabilizing. This paper proposes a protocol, called Wreathing Protocol, for the imbricated use of EMDR and hypnosis in the treatment of not only DID (though this will be the primary focus of the paper), but also Dissociative Disorder Not Otherwise Specified (DDNOS) and chronic Posttraumatic Stress Disorder (PTSD). This protocol is useful to advanced clinicians skilled in both modalities independently. The sequential steps of the Wreathing Protocol will be described and illustrated by a clinical vignette on DID. The clinical implications of the use of the Wreathing Protocol will be discussed in DID as well as the chronic post traumatic spectrum.

Assisted closed-loop optimization of SSVEP-BCI efficiency

PubMed Central

Fernandez-Vargas, Jacobo; Pfaff, Hanns U.; Rodríguez, Francisco B.; Varona, Pablo

2012-01-01

We designed a novel assisted closed-loop optimization protocol to improve the efficiency of brain-computer interfaces (BCI) based on steady state visually evoked potentials (SSVEP). In traditional paradigms, the control over the BCI-performance completely depends on the subjects' ability to learn from the given feedback cues. By contrast, in the proposed protocol both the subject and the machine share information and control over the BCI goal. Generally, the innovative assistance consists in the delivery of online information together with the online adaptation of BCI stimuli properties. In our case, this adaptive optimization process is realized by (1) a closed-loop search for the best set of SSVEP flicker frequencies and (2) feedback of actual SSVEP magnitudes to both the subject and the machine. These closed-loop interactions between subject and machine are evaluated in real-time by continuous measurement of their efficiencies, which are used as online criteria to adapt the BCI control parameters. The proposed protocol aims to compensate for variability in possibly unknown subjects' state and trait dimensions. In a study with N = 18 subjects, we found significant evidence that our protocol outperformed classic SSVEP-BCI control paradigms. Evidence is presented that it takes indeed into account interindividual variabilities: e.g., under the new protocol, baseline resting state EEG measures predict subjects' BCI performances. This paper illustrates the promising potential of assisted closed-loop protocols in BCI systems. Probably their applicability might be expanded to innovative uses, e.g., as possible new diagnostic/therapeutic tools for clinical contexts and as new paradigms for basic research. PMID:23443214

Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective.

PubMed

Wehler, Thomas C; Graf, Claudine; Möhler, Markus; Herzog, Jutta; Berger, Martin R; Gockel, Ines; Lang, Hauke; Theobald, Matthias; Galle, Peter R; Schimanski, Carl C

2013-10-01

Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9-19 % of patients with the necessity of cetuximab dose reduction or cessation. The study presented was a retrospective analysis of 50 gastrointestinal cancer patients treated with cetuximab in combination with either FOLFIRI or FOLFOX. One cohort of 15 patients received an in-house reactive skin protocol upon development of an exanthema. A second cohort of 15 patients received a skin prophylaxis starting with the first dose of cetuximab before clinical signs of toxicity. A third historic group of 20 patients had received no skin prophylaxis or reactive treatment. 19/20 patients of the historic group developed a skin exanthema. Grade III/IV exanthema was observed six times. Forty percent discontinued cetuximab therapy. The average time to exanthema onset was 14.7 days. Applying the reactive skin protocol after the first occurrence of an exanthema, the exanthema was downgraded as follows: No patients developed grade IV° exanthema, and two patients developed a grade II/III exanthema. In the majority of cases, the reactive skin protocol controlled the exanthema (grade 0-I°). No dose reductions in cetuximab were necessary. Applying the prophylactic skin protocol starting at the beginning of cetuximab application was not superior to the reactive skin protocol. Cetuximab-induced skin exanthema can be coped with a reactive protocol equally effective as compared to a prophylactic skin treatment. A prospective study with higher patient numbers is planned.

Developing an Optimum Protocol for Thermoluminescence Dosimetry with GR-200 Chips using Taguchi Method.

PubMed

Sadeghi, Maryam; Faghihi, Reza; Sina, Sedigheh

2017-06-15

Thermoluminescence dosimetry (TLD) is a powerful technique with wide applications in personal, environmental and clinical dosimetry. The optimum annealing, storage and reading protocols are very effective in accuracy of TLD response. The purpose of this study is to obtain an optimum protocol for GR-200; LiF: Mg, Cu, P, by optimizing the effective parameters, to increase the reliability of the TLD response using Taguchi method. Taguchi method has been used in this study for optimization of annealing, storage and reading protocols of the TLDs. A number of 108 GR-200 chips were divided into 27 groups, each containing four chips. The TLDs were exposed to three different doses, and stored, annealed and read out by different procedures as suggested by Taguchi Method. By comparing the signal-to-noise ratios the optimum dosimetry procedure was obtained. According to the results, the optimum values for annealing temperature (°C), Annealing Time (s), Annealing to Exposure time (d), Exposure to Readout time (d), Pre-heat Temperature (°C), Pre-heat Time (s), Heating Rate (°C/s), Maximum Temperature of Readout (°C), readout time (s) and Storage Temperature (°C) are 240, 90, 1, 2, 50, 0, 15, 240, 13 and -20, respectively. Using the optimum protocol, an efficient glow curve with low residual signals can be achieved. Using optimum protocol obtained by Taguchi method, the dosimetry can be effectively performed with great accuracy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assisted closed-loop optimization of SSVEP-BCI efficiency.

PubMed

Fernandez-Vargas, Jacobo; Pfaff, Hanns U; Rodríguez, Francisco B; Varona, Pablo

2013-01-01

We designed a novel assisted closed-loop optimization protocol to improve the efficiency of brain-computer interfaces (BCI) based on steady state visually evoked potentials (SSVEP). In traditional paradigms, the control over the BCI-performance completely depends on the subjects' ability to learn from the given feedback cues. By contrast, in the proposed protocol both the subject and the machine share information and control over the BCI goal. Generally, the innovative assistance consists in the delivery of online information together with the online adaptation of BCI stimuli properties. In our case, this adaptive optimization process is realized by (1) a closed-loop search for the best set of SSVEP flicker frequencies and (2) feedback of actual SSVEP magnitudes to both the subject and the machine. These closed-loop interactions between subject and machine are evaluated in real-time by continuous measurement of their efficiencies, which are used as online criteria to adapt the BCI control parameters. The proposed protocol aims to compensate for variability in possibly unknown subjects' state and trait dimensions. In a study with N = 18 subjects, we found significant evidence that our protocol outperformed classic SSVEP-BCI control paradigms. Evidence is presented that it takes indeed into account interindividual variabilities: e.g., under the new protocol, baseline resting state EEG measures predict subjects' BCI performances. This paper illustrates the promising potential of assisted closed-loop protocols in BCI systems. Probably their applicability might be expanded to innovative uses, e.g., as possible new diagnostic/therapeutic tools for clinical contexts and as new paradigms for basic research.

Is the "sterile cockpit" concept applicable to cardiovascular surgery critical intervals or critical events? The impact of protocol-driven communication during cardiopulmonary bypass.

PubMed

Wadhera, Rishi K; Parker, Sarah Henrickson; Burkhart, Harold M; Greason, Kevin L; Neal, James R; Levenick, Katherine M; Wiegmann, Douglas A; Sundt, Thoralf M

2010-02-01

There is general enthusiasm for applying strategies from aviation directly to medical care; the application of the "sterile cockpit" rule to surgery has accordingly been suggested. An implicit prerequisite to the evidence-based transfer of such a concept to the clinical domain, however, is definition of periods of high mental workload analogous to takeoff and landing. We measured cognitive demands among operating room staff, mapped critical events, and evaluated protocol-driven communication. With the National Aeronautics and Space Administration Task Load Index and semistructured focus groups, we identified common critical stages of cardiac surgical cases. Intraoperative communication was assessed before (n = 18) and after (n = 16) introduction of a structured communication protocol. Cognitive workload measures demonstrated high temporal diversity among caregivers in various roles. Eight critical events during cardiopulmonary bypass were then defined. A structured, unambiguous verbal communication protocol for these events was then implemented. Observations of 18 cases before implementation including 29.6 hours of cardiopulmonary bypass with 632 total communication exchanges (average 35.1 exchanges/case) were compared with observations of 16 cases after implementation including 23.9 hours of cardiopulmonary bypass with 748 exchanges (average 46.8 exchanges/case, P = .06). Frequency of communication breakdowns per case decreased significantly after implementation (11.5 vs 7.3 breakdowns/case, P = .008). Because of wide variations is cognitive workload among caregivers, effective communication can be structured around critical events rather than defined intervals analogous to the sterile cockpit, with reduction in communication breakdowns. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

PubMed

Mitchell, Marc; Hedt, Bethany L; Eshun-Wilson, Ingrid; Fraser, Hamish; John, Melanie-Anne; Menezes, Colin; Grobusch, Martin P; Jackson, Jonathan; Taljaard, Jantjie; Lesh, Neal

2012-03-01

The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Application of mass spectrometry in mycology].

PubMed

Quiles Melero, Inmaculada; Peláez, Teresa; Rezusta López, Antonio; Garcia-Rodríguez, Julio

2016-06-01

MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) is becoming an essential tool in most microbiology laboratories. At present, by using a characteristic fungal profile obtained from whole cells or through simple extraction protocols, MALDI-TOF MS allows the identification of pathogenic fungi with a high performance potential. This methodology decreases the laboratory turnaround time, optimizing the detection of mycoses. This article describes the state-of-the-art of the use of MALDI-TOF MS for the detection of human clinical fungal pathogens in the laboratory and discusses the future applications of this technology, which will further improve routine mycological diagnosis. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Implementation of a Prototype Generalized Network Technology for Hospitals *

PubMed Central

Tolchin, S. G.; Stewart, R. L.; Kahn, S. A.; Bergan, E. S.; Gafke, G. P.; Simborg, D. W.; Whiting-O'Keefe, Q. E.; Chadwick, M. G.; McCue, G. E.

1981-01-01

A demonstration implementation of a distributed data processing hospital information system using an intelligent local area communications network (LACN) technology is described. This system is operational at the UCSF Medical Center and integrates four heterogeneous, stand-alone minicomputers. The applications systems are PID/Registration, Outpatient Pharmacy, Clinical Laboratory and Radiology/Medical Records. Functional autonomy of these systems has been maintained, and no operating system changes have been required. The LACN uses a fiber-optic communications medium and provides extensive communications protocol support within the network, based on the ISO/OSI Model. The architecture is reconfigurable and expandable. This paper describes system architectural issues, the applications environment and the local area network.

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping.

PubMed

Wu, Shih-Ying; Aurup, Christian; Sanchez, Carlos Sierra; Grondin, Julien; Zheng, Wenlan; Kamimura, Hermes; Ferrera, Vincent P; Konofagou, Elisa E

2018-05-22

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Trends in the number and the quality of trial protocols involving children submitted to a French Institutional Review Board.

PubMed

Gautier, Isabelle; Janiaud, Perrine; Rollet, Nelly; André, Nicolas; Tsimaratos, Michel; Cornu, Catherine; Malik, Salma; Gentile, Stéphanie; Kassaï, Behrouz

2017-08-23

There is a great need for high quality clinical research for children. The European Pediatric Regulation aimed to improve the quality of clinical trials in order to increase the availability of treatments for children. The main purpose of this study was to assess the evolution of both the number and the quality of pediatric trial protocols that were submitted to a French Institutional Review Board (IRB00009118) before and after the initiation of the EU Pediatric Regulation. All protocols submitted to the IRB00009118 between 2003 and 2014 and conducting research on subjects under eighteen years of age were eligible. The quality of randomized clinical trials was assessed according to the guidelines developed by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network and ranked using the Jadad score. Out of 622 protocols submitted to the Institutional Review Board (IRB), 21% (133/622) included children. Among these 133 pediatric protocols, the number of submitted pediatric protocols doubled between the two studied periods. From 2003 to 2008, 47 protocols including 21 institutionally sponsored were submitted to the IRB and from 2009 until 2014, 86 protocols including 48 institutionally sponsored were submitted. No significant trend was observed on the quality of RCTs. The overall median score of RCTs on the Jadad scale was high (3.5), 70.0% of protocols had a Jadad score ≥ 3, and 30.0% had a score < 3. Following the EU Pediatric Regulation, the number of pediatric protocols submitted to the IRB00009118 tends to increase, but no change was noticed regarding their quality.

[Perinatal bioethics: euthanasia or end-of-life decisions? Analysis of the Groningen Protocol].

PubMed

Halac, Jacobo; Halac, Eduardo; Moya, Martín P; Olmas, José M; Dopazo, Silvina L; Dolagaray, Nora

2009-12-01

The so called "Groningen Protocol" was conceived as a framework to discuss the euthanasia in neonates. Originally, it presents three groups of babies who might be candidates to this option. We analyzed the protocol in its original context and that of the Dutch society in which it was created. The analysis started with a careful reading of the protocol in both English and Dutch versions, translated later into Spanish. The medical and nursing staff participated in discussing it. A final consensus was reached. The Institutional Ethics Committee at our hospital discussed it freely and made recommendations for its application as a guideline to honestly discuss with parents the clinical condition of their babies, without permitting the option included literally in the word euthanasia. We selected four extremely ill infants. Their parents were interviewed at least twice daily: three stages were identified: the initial one of promoting all possible treatments; a second one of guarded and cautious request for the staff to evaluate "suffering", and a last one where requests were made to reduce therapeutic efforts to provide dignified death. A week after the death of their infants, they were presented with the facts of the protocol and the limits of our legal system. In all four cases the parents suggested that they would have chosen ending the life of their infants, in order to avoid them undue suffering. They clearly pointed out that this option emerged as a viable one to them once the ultimate outcome was evident. The protocol must not be viewed as a guideline for euthanasia in newborns, but rather as a mean to discuss the critical condition of an infant with the parents. Its direct implementation in our setting remains difficult. As a clear limitation for its overall application remains the definition of what is considered "unbearable suffering" in newborns, and how to certify when the infant has "no prospect". We emphasize the benefits of securing the help of the Ethics Committee and of "second opinions" from authorized physicians.

ABM Clinical Protocol #1: Guidelines for Blood Glucose Monitoring and Treatment of Hypoglycemia in Term and Late-Preterm Neonates, Revised 2014

PubMed Central

Wight, Nancy

2014-01-01

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID:24823918

Modifying the ECC-based grouping-proof RFID system to increase inpatient medication safety.

PubMed

Ko, Wen-Tsai; Chiou, Shin-Yan; Lu, Erl-Huei; Chang, Henry Ker-Chang

2014-09-01

RFID technology is increasingly used in applications that require tracking, identification, and authentication. It attaches RFID-readable tags to objects for identification and execution of specific RFID-enabled applications. Recently, research has focused on the use of grouping-proofs for preserving privacy in RFID applications, wherein a proof of two or more tags must be simultaneously scanned. In 2010, a privacy-preserving grouping proof protocol for RFID based on ECC in public-key cryptosystem was proposed but was shown to be vulnerable to tracking attacks. A proposed enhancement protocol was also shown to have defects which prevented proper execution. In 2012, Lin et al. proposed a more efficient RFID ECC-based grouping proof protocol to promote inpatient medication safety. However, we found this protocol is also vulnerable to tracking and impersonation attacks. We then propose a secure privacy-preserving RFID grouping proof protocol for inpatient medication safety and demonstrate its resistance to such attacks.

Rationale, Scenarios, and Profiles for the Application of the Internet Protocol Suite (IPS) in Space Operations

NASA Technical Reports Server (NTRS)

Benbenek, Daniel B.; Walsh, William

2010-01-01

This greenbook captures some of the current, planned and possible future uses of the Internet Protocol (IP) as part of Space Operations. It attempts to describe how the Internet Protocol is used in specific scenarios. Of primary focus is low-earth-orbit space operations, which is referred to here as the design reference mission (DRM). This is because most of the program experience drawn upon derives from this type of mission. Application profiles are provided. This includes parameter settings programs have proposed for sending IP datagrams over CCSDS links, the minimal subsets and features of the IP protocol suite and applications expected for interoperability between projects, and the configuration, operations and maintenance of these IP functions. Of special interest is capturing the lessons learned from the Constellation Program in this area, since that program included a fairly ambitious use of the Internet Protocol.

Developing an organizing framework to guide nursing research in the Children’s Oncology Group (COG)

PubMed Central

Kelly, Katherine Patterson; Hooke, Mary C.; Ruccione, Kathleen; Landier, Wendy; Haase, Joan

2014-01-01

Objectives To describe the development and application of an organizing research framework to guide COG Nursing research. Data Sources Research articles, reports and meeting minutes Conclusion An organizing research framework helps to outline research focus and articulate the scientific knowledge being produced by nurses in the pediatric cooperative group. Implication for Nursing Practice The use of an organizing framework for COG nursing research can facilitate clinical nurses’ understanding of how children and families sustain or regain optimal health when faced with a pediatric cancer diagnosis through interventions designed to promote individual and family resilience. The Children’s Oncology Group (COG) is the sole National Cancer Institute (NCI)-supported cooperative pediatric oncology clinical trials group and the largest organization in the world devoted exclusively to pediatric cancer research. It was founded in 2000 following the merger of the four legacy NCI-supported pediatric clinical trials groups (Children’s Cancer Group [CCG], Pediatric Oncology Group [POG], National Wilms Tumor Study Group, and Intergroup Rhabdomyosarcoma Study Group). The COG currently has over 200 member institutions across North America, Australia, New Zealand and Europe and a multidisciplinary membership of over 8,000 pediatric, radiation, and surgical oncologists, nurses, clinical research associates, pharmacists, behavioral scientists, pathologists, laboratory scientists, patient/parent advocates and other pediatric cancer specialists. The COG Nursing Discipline was formed from the merger of the legacy CCG and POG Nursing Committees, and current membership exceeds 2000 registered nurses. The discipline has a well-developed infrastructure that promotes nursing involvement throughout all levels of the organization, including representation on disease, protocol, scientific, executive and other administrative committees (e.g., nominating committee, data safety monitoring boards). COG nurses facilitate delivery of protocol-based treatments for children enrolled on COG protocols, and Nursing Discipline initiatives support nursing research, professional and patient/family education, evidence-based practice, and a patient-reported outcomes resource center. The research agenda of the Nursing Discipline is enacted through a well-established nursing scholar program. PMID:24559776

Progeria Research Foundation Diagnostic Testing Program

MedlinePlus

... Culture Protocols Immortalized Cell Culture Protocols Induced Pluripotent Stem Cells PRF Cell and Tissue Bank Publications Research Funding Opportunities Grant Application Application Deadlines Grants Funded Close Meet The Kids Meet The Kids Our Ambassadors Find The Other ...

HIS-Based Support of Follow-Up Documentation – Concept and Implementation for Clinical Studies

PubMed Central

Herzberg, S.; Fritz, F.; Rahbar, K.; Stegger, L.; Schäfers, M.; Dugas, M.

2011-01-01

Objective Follow-up data must be collected according to the protocol of each clinical study, i.e. at certain time points. Missing follow-up information is a critical problem and may impede or bias the analysis of study data and result in delays. Moreover, additional patient recruitment may be necessary due to incomplete follow-up data. Current electronic data capture (EDC) systems in clinical studies are usually separated from hospital information systems (HIS) and therefore can provide limited functionality to support clinical workflow. In two case studies, we assessed the feasibility of HIS-based support of follow-up documentation. Methods We have developed a data model and a HIS-based workflow to provide follow-up forms according to clinical study protocols. If a follow-up form was due, a database procedure created a follow-up event which was translated by a communication server into an HL7 message and transferred to the import interface of the clinical information system (CIS). This procedure generated the required follow-up form and enqueued a link to it in a work list of the relating study nurses and study physicians, respectively. Results A HIS-based follow-up system automatically generated follow-up forms as defined by a clinical study protocol. These forms were scheduled into work lists of study nurses and study physicians. This system was integrated into the clinical workflow of two clinical studies. In a study from nuclear medicine, each scenario from the test concept according to the protocol of the single photon emission computer tomography/computer tomography (SPECT/CT) study was simulated and each scenario passed the test. For a study in psychiatry, 128 follow-up forms were automatically generated within 27 weeks, on average five forms per week (maximum 12, minimum 1 form per week). Conclusion HIS-based support of follow-up documentation in clinical studies is technically feasible and can support compliance with study protocols. PMID:23616857

Natural zwitterionic l-Carnitine as efficient cryoprotectant for solvent-free cell cryopreservation.

PubMed

Zhai, Hongwen; Yang, Jing; Zhang, Jiamin; Pan, Chao; Cai, Nana; Zhu, Yingnan; Zhang, Lei

2017-07-15

Organic solvents, such as dimethyl sulfoxide (DMSO) and glycerol, have been commonly used as cryoprotectants (CPAs) in cell cryopreservation. However, their cytotoxicity and need of complex freezing protocols have impeded their applications especially in clinical cell therapy and regenerative medicine. Trehalose has been explored as a natural CPA to cryopreserve cells, but its poor cell permeability frequently results in low cryopreservation efficacy. In this work, we presented that a natural zwitterionic molecule-l-carnitine-could serve as a promising CPA for solvent-free cryopreservation. We demonstrated that l-carnitine possessed strong ability to depress water freezing point, and with ultrarapid freezing protocol, we studied the post-thaw survival efficiency of four cell lines (GLC-82 cells, MCF-7 cells, NIH-3T3 cells and Sheep Red Blood Cells) using l-carnitine without addition of any organic solvents. At the optimum l-carnitine concentration, all four cell lines could achieve above 80% survival efficiency, compared with the significantly lower efficiency using organic CPAs and trehalose. After cryopreservation, the recovered cell behaviors including cell attachment and proliferation were found to be similar to the normal cells, indicating that the cell functionalities were not affected. Moreover, l-carnitine showed no observable cytotoxicity, which was superior to the organic CPAs. This work offered an attractive alternative to traditional CPAs and held great promise to revolutionize current cryopreservation technologies, to benefit the patients in various cell-based clinical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Human Clinical-Grade Parthenogenetic ESC-Derived Dopaminergic Neurons Recover Locomotive Defects of Nonhuman Primate Models of Parkinson's Disease.

PubMed

Wang, Yu-Kai; Zhu, Wan-Wan; Wu, Meng-Hua; Wu, Yi-Hui; Liu, Zheng-Xin; Liang, Ling-Min; Sheng, Chao; Hao, Jie; Wang, Liu; Li, Wei; Zhou, Qi; Hu, Bao-Yang

2018-06-07

Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD (ClinicalTrials.gov number NCT03119636). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical research: business opportunities for pharmacy-based investigational drug services.

PubMed

Marnocha, R M

1999-02-01

The application by an academic health center of business principles to the conduct of clinical research is described. Re-engineering of the infrastructure for clinical research at the University of Wisconsin and University of Wisconsin Hospital and Clinics began in 1990 with the creation of the Center for Clinical Trials (CCT) and the restructuring of the investigational drug services (IDS). Strategies to further improve the institution's clinical research activities have been continually assessed and most recently have centered on the adaptation of a business philosophy within the institution's multidisciplinary research infrastructure. Toward that end, the CCT and IDS have introduced basic business principles into operational activities. Four basic business concepts have been implemented: viewing the research protocol as a commodity, seeking payment for services rendered, tracking investments, and assessing performance. It is proposed that incorporation of these basic business concepts is not only compatible with the infrastructure for clinical research but beneficial to that infrastructure. The adaptation of a business mindset is likely to enable an academic health center to reach its clinical research goals.

A virtual experimenter to increase standardization for the investigation of placebo effects.

PubMed

Horing, Bjoern; Newsome, Nathan D; Enck, Paul; Babu, Sabarish V; Muth, Eric R

2016-07-18

Placebo effects are mediated by expectancy, which is highly influenced by psychosocial factors of a treatment context. These factors are difficult to standardize. Furthermore, dedicated placebo research often necessitates single-blind deceptive designs where biases are easily introduced. We propose a study protocol employing a virtual experimenter - a computer program designed to deliver treatment and instructions - for the purpose of standardization and reduction of biases when investigating placebo effects. To evaluate the virtual experimenter's efficacy in inducing placebo effects via expectancy manipulation, we suggest a partially blinded, deceptive design with a baseline/retest pain protocol (hand immersions in hot water bath). Between immersions, participants will receive an (actually inert) medication. Instructions pertaining to the medication will be delivered by one of three metaphors: The virtual experimenter, a human experimenter, and an audio/text presentation (predictor "Metaphor"). The second predictor includes falsely informing participants that the medication is an effective pain killer, or correctly informing them that it is, in fact, inert (predictor "Instruction"). Analysis will be performed with hierarchical linear modelling, with a sample size of N = 50. Results from two pilot studies are presented that indicate the viability of the pain protocol (N = 33), and of the virtual experimenter software and placebo manipulation (N = 48). It will be challenging to establish full comparability between all metaphors used for instruction delivery, and to account for participant differences in acceptance of their virtual interaction partner. Once established, the presence of placebo effects would suggest that the virtual experimenter exhibits sufficient cues to be perceived as a social agent. He could consequently provide a convenient platform to investigate effects of experimenter behavior, or other experimenter characteristics, e.g., sex, age, race/ethnicity or professional status. More general applications are possible, for example in psychological research such as bias research, or virtual reality research. Potential applications also exist for standardizing clinical research by documenting and communicating instructions used in clinical trials.

European Network of Bipolar Research Expert Centre (ENBREC): a network to foster research and promote innovative care.

PubMed

Henry, Chantal; Andreassen, Ole A; Barbato, Angelo; Demotes-Mainard, Jacques; Goodwin, Guy; Leboyer, Marion; Vieta, Eduard; Nolen, Willem A; Kessing, Lars Vedel; Scott, Jan; Bauer, Michael

2013-01-01

Bipolar disorders rank as one of the most disabling illnesses in working age adults worldwide. Despite this, the quality of care offered to patients with this disorder is suboptimal, largely due to limitations in our understanding of the pathology. Improving this scenario requires the development of a critical mass of expertise and multicentre collaborative projects. Within the framework of the European FP7 programme, we developed a European Network of Bipolar Research Expert Centres (ENBREC) designed specifically to facilitate EU-wide studies. ENBREC provides an integrated support structure facilitating research on disease mechanisms and clinical outcomes across six European countries (France, Germany, Italy, Norway, Spain and the UK). The centres are adopting a standardised clinical assessment that explores multiple aspects of bipolar disorder through a structured evaluation designed to inform clinical decision-making as well as being applicable to research. Reliable, established measures have been prioritised, and instruments have been translated and validated when necessary. An electronic healthcare record and monitoring system (e-ENBREC©) has been developed to collate the data. Protocols to conduct multicentre clinical observational studies and joint studies on cognitive function, biomarkers, genetics, and neuroimaging are in progress; a pilot study has been completed on strategies for routine implementation of psycho-education. The network demonstrates 'proof of principle' that expert centres across Europe can collaborate on a wide range of basic science and clinical programmes using shared protocols. This paper is to describe the network and how it aims to improve the quality and effectiveness of research in a neglected priority area.

Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

PubMed

de Saussure, P; Soravia, C; Morel, P; Hadengue, A

2005-08-01

The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

The Clinical Utilisation of Respiratory Elastance Software (CURE Soft): a bedside software for real-time respiratory mechanics monitoring and mechanical ventilation management.

PubMed

Szlavecz, Akos; Chiew, Yeong Shiong; Redmond, Daniel; Beatson, Alex; Glassenbury, Daniel; Corbett, Simon; Major, Vincent; Pretty, Christopher; Shaw, Geoffrey M; Benyo, Balazs; Desaive, Thomas; Chase, J Geoffrey

2014-09-30

Real-time patient respiratory mechanics estimation can be used to guide mechanical ventilation settings, particularly, positive end-expiratory pressure (PEEP). This work presents a software, Clinical Utilisation of Respiratory Elastance (CURE Soft), using a time-varying respiratory elastance model to offer this ability to aid in mechanical ventilation treatment. CURE Soft is a desktop application developed in JAVA. It has two modes of operation, 1) Online real-time monitoring decision support and, 2) Offline for user education purposes, auditing, or reviewing patient care. The CURE Soft has been tested in mechanically ventilated patients with respiratory failure. The clinical protocol, software testing and use of the data were approved by the New Zealand Southern Regional Ethics Committee. Using CURE Soft, patient's respiratory mechanics response to treatment and clinical protocol were monitored. Results showed that the patient's respiratory elastance (Stiffness) changed with the use of muscle relaxants, and responded differently to ventilator settings. This information can be used to guide mechanical ventilation therapy and titrate optimal ventilator PEEP. CURE Soft enables real-time calculation of model-based respiratory mechanics for mechanically ventilated patients. Results showed that the system is able to provide detailed, previously unavailable information on patient-specific respiratory mechanics and response to therapy in real-time. The additional insight available to clinicians provides the potential for improved decision-making, and thus improved patient care and outcomes.

SU-C-BRD-02: A Team Focused Clinical Implementation and Failure Mode and Effects Analysis of HDR Skin Brachytherapy Using Valencia and Leipzig Surface Applicators

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

Sayler, E; Harrison, A; Eldredge-Hindy, H

Purpose: and Leipzig applicators (VLAs) are single-channel brachytherapy surface applicators used to treat skin lesions up to 2cm diameter. Source dwell times can be calculated and entered manually after clinical set-up or ultrasound. This procedure differs dramatically from CT-based planning; the novelty and unfamiliarity could lead to severe errors. To build layers of safety and ensure quality, a multidisciplinary team created a protocol and applied Failure Modes and Effects Analysis (FMEA) to the clinical procedure for HDR VLA skin treatments. Methods: team including physicists, physicians, nurses, therapists, residents, and administration developed a clinical procedure for VLA treatment. The procedure wasmore » evaluated using FMEA. Failure modes were identified and scored by severity, occurrence, and detection. The clinical procedure was revised to address high-scoring process nodes. Results: Several key components were added to the clinical procedure to minimize risk probability numbers (RPN): -Treatments are reviewed at weekly QA rounds, where physicians discuss diagnosis, prescription, applicator selection, and set-up. Peer review reduces the likelihood of an inappropriate treatment regime. -A template for HDR skin treatments was established in the clinical EMR system to standardize treatment instructions. This reduces the chances of miscommunication between the physician and planning physicist, and increases the detectability of an error during the physics second check. -A screen check was implemented during the second check to increase detectability of an error. -To reduce error probability, the treatment plan worksheet was designed to display plan parameters in a format visually similar to the treatment console display. This facilitates data entry and verification. -VLAs are color-coded and labeled to match the EMR prescriptions, which simplifies in-room selection and verification. Conclusion: Multidisciplinary planning and FMEA increased delectability and reduced error probability during VLA HDR Brachytherapy. This clinical model may be useful to institutions implementing similar procedures.« less

Mandibular molar uprighting using mini-implants: different approaches for different clinical cases--two case reports.

PubMed

Derton, Nicola; Perini, Alessandro; Mutinelli, Sabrina; Gracco, Antonio

2012-01-01

To detail two different clinical protocols and case studies using mini-implant anchorage developed to respond to certain clinical conditions. Two clinical protocols are described to upright mesially tilted mandibular molars. In the first protocol, a single mini-implant is inserted distally to the molar to be uprighted, and an elastic traction chain is applied to the tooth. In the second clinical approach, two mini-implants are inserted mesially. A screw-suspended TMA sectional archwire is applied (Derton-Perini technique). Two cases, descriptive of the two different treatment protocols, are described. In the first case, the mandibular right second premolar was missing and the adjacent first molar needed to be uprighted. A single screw was inserted distally to the first molar, and an elastic chain was applied. In the second case, the mandibular left second molar was missing and the third molar needed to be uprighted. Two mini-implants were inserted mesially and a fully screw-supported sectional archwire was used to upright and bodily mesialize the third molar. Both uprighting approaches uprighted the molar axis without loss of anchorage. The two approaches to mandibular molar uprighting, developed as rational responses to different clinical cases, were both found to be effective.

Development of a dynamic quality assurance testing protocol for multisite clinical trial DCE-CT accreditation

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

Driscoll, B.; Keller, H.; Jaffray, D.

2013-08-15

Purpose: Credentialing can have an impact on whether or not a clinical trial produces useful quality data that is comparable between various institutions and scanners. With the recent increase of dynamic contrast enhanced-computed tomography (DCE-CT) usage as a companion biomarker in clinical trials, effective quality assurance, and control methods are required to ensure there is minimal deviation in the results between different scanners and protocols at various institutions. This paper attempts to address this problem by utilizing a dynamic flow imaging phantom to develop and evaluate a DCE-CT quality assurance (QA) protocol.Methods: A previously designed flow phantom, capable of producingmore » predictable and reproducible time concentration curves from contrast injection was fully validated and then utilized to design a DCE-CT QA protocol. The QA protocol involved a set of quantitative metrics including injected and total mass error, as well as goodness of fit comparison to the known truth concentration curves. An additional region of interest (ROI) sensitivity analysis was also developed to provide additional details on intrascanner variability and determine appropriate ROI sizes for quantitative analysis. Both the QA protocol and ROI sensitivity analysis were utilized to test variations in DCE-CT results using different imaging parameters (tube voltage and current) as well as alternate reconstruction methods and imaging techniques. The developed QA protocol and ROI sensitivity analysis was then applied at three institutions that were part of clinical trial involving DCE-CT and results were compared.Results: The inherent specificity of robustness of the phantom was determined through calculation of the total intraday variability and determined to be less than 2.2 ± 1.1% (total calculated output contrast mass error) with a goodness of fit (R{sup 2}) of greater than 0.99 ± 0.0035 (n= 10). The DCE-CT QA protocol was capable of detecting significant deviations from the expected phantom result when scanning at low mAs and low kVp in terms of quantitative metrics (Injected Mass Error 15.4%), goodness of fit (R{sup 2}) of 0.91, and ROI sensitivity (increase in minimum input function ROI radius by 146 ± 86%). These tests also confirmed that the ASIR reconstruction process was beneficial in reducing noise without substantially increasing partial volume effects and that vendor specific modes (e.g., axial shuttle) did not significantly affect the phantom results. The phantom and QA protocol were finally able to quickly (<90 min) and successfully validate the DCE-CT imaging protocol utilized at the three separate institutions of a multicenter clinical trial; thereby enhancing the confidence in the patient data collected.Conclusions: A DCE QA protocol was developed that, in combination with a dynamic multimodality flow phantom, allows the intrascanner variability to be separated from other sources of variability such as the impact of injection protocol and ROI selection. This provides a valuable resource that can be utilized at various clinical trial institutions to test conformance with imaging protocols and accuracy requirements as well as ensure that the scanners are performing as expected for dynamic scans.« less

Spontaneous Swallow Frequency Compared with Clinical Screening in the Identification of Dysphagia in Acute Stroke

PubMed Central

Crary, Michael A.; Carnaby, Giselle D.; Sia, Isaac

2017-01-01

Background The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. Methods In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Results Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Conclusions Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. PMID:25088166

Spontaneous swallow frequency compared with clinical screening in the identification of dysphagia in acute stroke.

PubMed

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac

2014-09-01

The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Prospects for pluripotent stem cell therapies: into the clinic and back to the bench.

PubMed

Grabel, Laura

2012-02-01

Pluripotent stem cells, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, both hold great promise for the understanding and treatment of disease. They can be used for drug testing, as in vitro models for human disease progression, and for transplantation therapies. Research in this area has been influenced by the ever-changing political landscape, particularly in the United States. In this review, we discuss the prospects for clinical application using pluripotent cells, focusing on an evaluation of iPS cell potential, the continuing concern of tumor formation, and a summary of in vitro differentiation protocols and animal models used. We also describe the current clinical trials underway in the United States, as well as the ups and downs of funding for ES cell work. Copyright © 2011 Wiley Periodicals, Inc.

Clinical-Grade Manufacturing of Therapeutic Human Mesenchymal Stem/Stromal Cells in Microcarrier-Based Culture Systems.

PubMed

Fernandes-Platzgummer, Ana; Carmelo, Joana G; da Silva, Cláudia Lobato; Cabral, Joaquim M S

2016-01-01

The therapeutic potential of mesenchymal stem/stromal cells (MSC) has triggered the need for high cell doses in a vast number of clinical applications. This demand requires the development of good manufacturing practices (GMP)-compliant ex vivo expansion protocols that should be effective to deliver a robust and reproducible supply of clinical-grade cells in a safe and cost-effective manner. Controlled stirred-tank bioreactor systems under xenogeneic (xeno)-free culture conditions offer ideal settings to develop and optimize cell manufacturing to meet the standards and needs of human MSC for cellular therapies. Herein we describe two microcarrier-based stirred culture systems using spinner flasks and controlled stirred-tank bioreactors under xeno-free conditions for the efficient ex vivo expansion of human bone marrow and adipose tissue-derived MSC.

Functional neuroimaging applications for assessment and rehabilitation planning in patients with disorders of consciousness.

PubMed

Giacino, Joseph T; Hirsch, Joy; Schiff, Nicholas; Laureys, Steven

2006-12-01

To describe the theoretic framework, design, and potential clinical applications of functional neuroimaging protocols in patients with disorders of consciousness. Recent published literature and authors' own work. Studies using functional neuroimaging techniques to investigate cognitive processing in patients diagnosed with vegetative and minimally conscious state. Not applicable. Positron-emission tomography activation studies suggest that the vegetative state represents a global disconnection syndrome in which higher order association cortices are functionally disconnected from primary cortical areas. In contrast, patterns of activation in functional magnetic resonance imaging studies of patients in the minimally conscious state show preservation of large-scale cortical networks associated with language and visual processing. Novel applications of functional neuroimaging in patients with disorders of consciousness may aid in differential diagnosis, prognostic assessment and identification of pathophysiologic mechanisms. Improvements in patient characterization may, in turn, provide new opportunities for restoration of function through interventional neuromodulation.

Conducting Clinically Based Intimate Partner Violence Research: Safety Protocol Recommendations.

PubMed

Anderson, Jocelyn C; Glass, Nancy E; Campbell, Jacquelyn C

Maintaining safety is of utmost importance during research involving participants who have experienced intimate partner violence (IPV). Limited guidance on safety protocols to protect participants is available, particularly information related to technology-based approaches to informed consent, data collection, and contacting participants during the course of a study. The purpose of the article is to provide details on the safety protocol developed and utilized with women receiving care at an urban HIV clinic and who were taking part in an observational study of IPV, mental health symptoms, and substance abuse and their relationship to HIV treatment adherence. The protocol presents the technological strategies to promote safety and allow autonomy in participant decision-making throughout the research process, including Voice over Internet Protocol telephone numbers, and tablet-based eligibility screening and data collection. Protocols for management of participants at risk for suicide and/or intimate partner homicide that included automated high-risk messaging to participants and research staff and facilitated disclosure of risk to clinical staff based on participant preferences are discussed. Use of technology and partnership with clinic staff helped to provide an environment where research regarding IPV could be conducted without undue burden or risk to participants. Utilizing tablet-based survey administration provided multiple practical and safety benefits for participants. Most women who screened into high-risk categories for suicide or intimate partner homicide did not choose to have their results shared with their healthcare providers, indicating the importance of allowing participants control over information sharing whenever possible.

Applications of ultrasensitive magnetic measurement technologies (invited) (abstract)

NASA Astrophysics Data System (ADS)

Hirschkoff, Eugene C.

1993-05-01

The development of reliable, easy-to-use magnetic measurement systems with significantly enhanced levels of sensitivity has opened up a number of broad new areas of application for magnetic sensing. Magnetometers based on optical pumping offer sensitivities at the picotesla level, while those that utilize superconducting quantum interference devices can operate at the femtotesla level. These systems are finding applications in areas as diverse as geophysical exploration, communications, and medical diagnostics. This review briefly surveys the capabilities and application areas for a number of magnetic sensing technologies. The emphasis then focuses on the application of the most sensitive of these to the field of medical diagnostics and functional imaging. Protocols for specific applications to noninvasive presurgical planning and to the noninvasive assay of cortical dysfunction in diseases ranging from epilepsy to migraine and schizophrenia will be described in detail. Data will be presented reporting independent validation of these techniques in ten patients who subsequently underwent surgery. Routine and reliable utilization of this ultrasensitive magnetic sensing technology in the clinic is now feasible and practical.

Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients.

PubMed

Casati, Anna; Varghaei-Nahvi, Azam; Feldman, Steven Alexander; Assenmacher, Mario; Rosenberg, Steven Aaron; Dudley, Mark Edward; Scheffold, Alexander

2013-10-01

The adoptive transfer of lymphocytes genetically engineered to express tumor-specific antigen receptors is a potent strategy to treat cancer patients. T lymphocyte subsets, such as naïve or central memory T cells, selected in vitro prior to genetic engineering have been extensively investigated in preclinical mouse models, where they demonstrated improved therapeutic efficacy. However, so far, this is challenging to realize in the clinical setting, since good manufacturing practices (GMP) procedures for complex cell sorting and genetic manipulation are limited. To be able to directly compare the immunological attributes and therapeutic efficacy of naïve (T(N)) and central memory (T(CM)) CD8(+) T cells, we investigated clinical-scale procedures for their parallel selection and in vitro manipulation. We also evaluated currently available GMP-grade reagents for stimulation of T cell subsets, including a new type of anti-CD3/anti-CD28 nanomatrix. An optimized protocol was established for the isolation of both CD8(+) T(N) cells (CD4(-)CD62L(+)CD45RA(+)) and CD8(+) T(CM) (CD4(-)CD62L(+)CD45RA(-)) from a single patient. The highly enriched T cell subsets can be efficiently transduced and expanded to large cell numbers, sufficient for clinical applications and equivalent to or better than current cell and gene therapy approaches with unselected lymphocyte populations. The GMP protocols for selection of T(N) and T(CM) we reported here will be the basis for clinical trials analyzing safety, in vivo persistence and clinical efficacy in cancer patients and will help to generate a more reliable and efficacious cellular product.

The Brustkrebs-Studien.de website for breast cancer patients: User acceptance of a German internet portal offering information on the disease and treatment options, and a clinical trials matching service

PubMed Central

2010-01-01

Background The internet portal http://www.brustkrebs-studien.de (BKS) was launched in 2000 by the German Society of Senology (DGS) and the Baden-Württemberg Institute for Women's Health (IFG) to provide expert-written information on breast cancer online and to encourage and facilitate the participation of breast cancer patients in clinical trials. We describe the development of BKS and its applications, and report on website statistics and user acceptance. Methods Existing registries, including ClinicalTrials.gov, were analysed before we designed BKS, which combines a trial registry, a knowledge portal, and an online second opinion service. An advisory board guided the process. Log files and patient enquiries for trial participation and second opinions were analysed. A two-week user satisfaction survey was conducted online. Results During 10/2005-06/2010, the portal attracted 702,655 visitors, generating 15,507,454 page views. By 06/2010, the website's active scientific community consisted of 189 investigators and physicians, and the registry covered 163 clinical trial protocols. In 2009, 143 patients requested trial enrolment and 119 sought second opinions or individual treatment advice from the expert panel. During the two-week survey in 2008, 5,702 BKS visitors submitted 507 evaluable questionnaires. Portal acceptance was high. Respondents trusted information correctness (80%), welcomed self-matching to clinical trials (79%) and planned to use the portal in the future (76%) and recommend it to others (81%). Conclusions BKS is an established and trusted breast cancer information platform offering up-to-date resources and protocols to the growing physician and patient community to encourage participation in clinical trials. Further studies are needed to assess potential increases in trial enrolment by eligibility matching services. PMID:21126358

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication.

PubMed

Casati, Costanza; Colombo, Valeriana Giuseppina; Perrino, Marialuisa; Rossetti, Ornella Marina; Querques, Marialuisa; Giacomoni, Alessandro; Binaggia, Agnese; Colussi, Giacomo

2018-01-01

Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKT pre ) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT ( n = 48), SKT biopsy-based protocol ("high-risk", SKT hr , n = 51), or SKT clinically based protocol ("low-risk", SKT lr , n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKT hr showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication

PubMed Central

Casati, Costanza; Colombo, Valeriana Giuseppina; Perrino, Marialuisa; Rossetti, Ornella Marina; Querques, Marialuisa; Giacomoni, Alessandro; Binaggia, Agnese

2018-01-01

Background Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. Methods A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT (n = 48), SKT biopsy-based protocol (“high-risk”, SKThr, n = 51), or SKT clinically based protocol (“low-risk”, SKTlr, n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. Results Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60–69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKThr showed worst graft and overall survival in the 60–69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Conclusions Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time. PMID:29862061

Proteomics boosts translational and clinical microbiology.

PubMed

Del Chierico, F; Petrucca, A; Vernocchi, P; Bracaglia, G; Fiscarelli, E; Bernaschi, P; Muraca, M; Urbani, A; Putignani, L

2014-01-31

The application of proteomics to translational and clinical microbiology is one of the most advanced frontiers in the management and control of infectious diseases and in the understanding of complex microbial systems within human fluids and districts. This new approach aims at providing, by dedicated bioinformatic pipelines, a thorough description of pathogen proteomes and their interactions within the context of human host ecosystems, revolutionizing the vision of infectious diseases in biomedicine and approaching new viewpoints in both diagnostic and clinical management of the patient. Indeed, in the last few years, many laboratories have matured a series of advanced proteomic applications, aiming at providing individual proteome charts of pathogens, with respect to their morph and/or cell life stages, antimicrobial or antimycotic resistance profiling, epidemiological dispersion. Herein, we aim at reviewing the current state-of-the-art on proteomic protocols designed and set-up for translational and diagnostic microbiological purposes, from axenic pathogens' characterization to microbiota ecosystems' full description. The final goal is to describe applications of the most common MALDI-TOF MS platforms to advanced diagnostic issues related to emerging infections, increasing of fastidious bacteria, and generation of patient-tailored phylotypes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. © 2013. Published by Elsevier B.V. All rights reserved.

Building a Protocol Expressway: The Case of Mayo Clinic Cancer Center

PubMed Central

McJoynt, Terre A.; Hirzallah, Muhanad A.; Satele, Daniel V.; Pitzen, Jason H.; Alberts, Steven R.; Rajkumar, S. Vincent

2009-01-01

Purpose Inconsistencies and errors resulting from nonstandard processes, together with redundancies, rework, and excess workload, lead to extended time frames for clinical trial protocol development. This results in dissatisfaction among sponsors, investigators, and staff and restricts the availability of novel treatment options for patients. Methods A team of experts from Mayo Clinic formed, including Protocol Development Unit staff and management from the three Mayo Clinic campuses (Florida, Minnesota, and Arizona), a systems and procedures analyst, a quality office analyst, and two physician members to address the identified deficiencies. The current-state process was intensively reviewed, and improvement steps were taken to accelerate the development and approval of cancer-related clinical trials. The primary goal was to decrease the time from receipt of a new protocol through submission to an approving authority, such as the National Cancer Institute or institutional review board. Results Using the Define, Measure, Analyze, Improve, Control (DMAIC) framework infused with Lean waste-reduction methodologies, areas were identified for improvement, including enhancing first-time quality and processing new studies on a first-in/first-out basis. The project was successful in improving the mean turnaround time for internally authored protocols (P < .001) from 25.00 weeks (n = 41; range, 3.43 to 94.14 weeks) to 10.15 weeks (n = 14; range, 4.00 to 22.14 weeks). The mean turnaround time for externally authored protocols was improved (P < .001) from 20.61 weeks (n = 85; range, 3.29 to 108.57 weeks) to 7.79 weeks (n = 50; range, 2.00 to 20.86 weeks). Conclusion DMAIC framework combined with Lean methodologies is an effective tool to structure the definition, planning, analysis, and implementation of significant process changes. PMID:19564529

Building a protocol expressway: the case of Mayo Clinic Cancer Center.

PubMed

McJoynt, Terre A; Hirzallah, Muhanad A; Satele, Daniel V; Pitzen, Jason H; Alberts, Steven R; Rajkumar, S Vincent

2009-08-10

Inconsistencies and errors resulting from nonstandard processes, together with redundancies, rework, and excess workload, lead to extended time frames for clinical trial protocol development. This results in dissatisfaction among sponsors, investigators, and staff and restricts the availability of novel treatment options for patients. A team of experts from Mayo Clinic formed, including Protocol Development Unit staff and management from the three Mayo Clinic campuses (Florida, Minnesota, and Arizona), a systems and procedures analyst, a quality office analyst, and two physician members to address the identified deficiencies. The current-state process was intensively reviewed, and improvement steps were taken to accelerate the development and approval of cancer-related clinical trials. The primary goal was to decrease the time from receipt of a new protocol through submission to an approving authority, such as the National Cancer Institute or institutional review board. Using the Define, Measure, Analyze, Improve, Control (DMAIC) framework infused with Lean waste-reduction methodologies, areas were identified for improvement, including enhancing first-time quality and processing new studies on a first-in/first-out basis. The project was successful in improving the mean turnaround time for internally authored protocols (P < .001) from 25.00 weeks (n = 41; range, 3.43 to 94.14 weeks) to 10.15 weeks (n = 14; range, 4.00 to 22.14 weeks). The mean turnaround time for externally authored protocols was improved (P < .001) from 20.61 weeks (n = 85; range, 3.29 to 108.57 weeks) to 7.79 weeks (n = 50; range, 2.00 to 20.86 weeks). DMAIC framework combined with Lean methodologies is an effective tool to structure the definition, planning, analysis, and implementation of significant process changes.

Giving Voice to Study Volunteers: Comparing views of mentally ill, physically ill, and healthy protocol participants on ethical aspects of clinical research

PubMed Central

Roberts, Laura Weiss; Kim, Jane Paik

2014-01-01

Motivation Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable. Methods Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation. Results Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives regarding the ethical acceptability of clinical research participation by potentially vulnerable subpopulations (difference in acceptability perceived by mentally ill - healthy=−0.04, CI [−0.46, 0.39]; physically ill – healthy= −0.13, CI [−0.62, −.36]). Conclusions Clinical research volunteers and healthy clinical research-“naive” individuals view studies involving ill people as ethically acceptable, and their responses reflect concern regarding research that poses considerable burdens and risks and research involving vulnerable subpopulations. Physically ill research volunteers may be more willing to see burdensome and risky research as acceptable. Mentally ill research volunteers and healthy individuals expressed similar perspectives in this study, helping to dispel a misconception that those with mental illness should be presumed to hold disparate views. PMID:24931849

Giving voice to study volunteers: comparing views of mentally ill, physically ill, and healthy protocol participants on ethical aspects of clinical research.

PubMed

Roberts, Laura Weiss; Kim, Jane Paik

2014-09-01

Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable. Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation. Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives regarding the ethical acceptability of clinical research participation by potentially vulnerable subpopulations (difference in acceptability perceived by mentally ill - healthy = -0.04, CI [-0.46, 0.39]; physically ill - healthy = -0.13, CI [-0.62, -.36]). Clinical research volunteers and healthy clinical research-"naïve" individuals view studies involving ill people as ethically acceptable, and their responses reflect concern regarding research that poses considerable burdens and risks and research involving vulnerable subpopulations. Physically ill research volunteers may be more willing to see burdensome and risky research as acceptable. Mentally ill research volunteers and healthy individuals expressed similar perspectives in this study, helping to dispel a misconception that those with mental illness should be presumed to hold disparate views. Copyright © 2014 Elsevier Ltd. All rights reserved.

Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification.

PubMed

Stephens, John R; Liles, E Allen; Dancel, Ria; Gilchrist, Michael; Kirsch, Jonathan; DeWalt, Darren A

2014-04-01

Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates. To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol's implementation. Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation. Patients presenting for alcohol detoxification. Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification. Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation. We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p = 0.037). There was no difference in readmission rate or length of stay. Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions.

A Real-World Setting Study: Which Glucose Meter Could Be the Best for POCT Use? An Easy and Applicable Protocol During the Hospital Routine.

PubMed

Mancini, Alessio; Esposto, Giampaolo; Manfrini, Silvana; Rilli, Silvia; Tinti, Gessica; Carta, Giuseppe; Petrolati, Laura; Vidali, Matteo; Barocci, Simone

2018-05-01

The aim of this retrospective study is to evaluate the reliability and robustness of six glucose meters for point-of-care testing in our wards using a brand-new protocol. During a 30-days study period a total of 50 diabetes patients were subjected to venous blood sampling and glucose meter blood analysis. The results of six glucose meters were compared with our laboratory reference assay. GlucoMen Plus (Menarini) with the 82% of acceptable results was the most robust glucose meter. Even if the Passing-Bablok analysis demonstrates the presence of constant systematic errors and the Bland-Altman test highlighted a possible overestimation, the surveillance error grid analysis showed that this glucose meter can be used safely. We proved that portable glucose meters are not always reliable in routinely clinical settings.

Combined DNA-RNA Fluorescent In situ Hybridization (FISH) to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells

PubMed Central

Barakat, Tahsin Stefan; Gribnau, Joost

2014-01-01

Fluorescent in situ hybridization (FISH) is a molecular technique which enables the detection of nucleic acids in cells. DNA FISH is often used in cytogenetics and cancer diagnostics, and can detect aberrations of the genome, which often has important clinical implications. RNA FISH can be used to detect RNA molecules in cells and has provided important insights in regulation of gene expression. Combining DNA and RNA FISH within the same cell is technically challenging, as conditions suitable for DNA FISH might be too harsh for fragile, single stranded RNA molecules. We here present an easily applicable protocol which enables the combined, simultaneous detection of Xist RNA and DNA encoded by the X chromosomes. This combined DNA-RNA FISH protocol can likely be applied to other systems where both RNA and DNA need to be detected. PMID:24961515

Expression microdissection adapted to commercial laser dissection instruments

PubMed Central

Hanson, Jeffrey C; Tangrea, Michael A; Kim, Skye; Armani, Michael D; Pohida, Thomas J; Bonner, Robert F; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R

2016-01-01

Laser-based microdissection facilitates the isolation of specific cell populations from clinical or animal model tissue specimens for molecular analysis. Expression microdissection (xMD) is a second-generation technology that offers considerable advantages in dissection capabilities; however, until recently the method has not been accessible to investigators. This protocol describes the adaptation of xMD to commonly used laser microdissection instruments and to a commercially available handheld laser device in order to make the technique widely available to the biomedical research community. The method improves dissection speed for many applications by using a targeting probe for cell procurement in place of an operator-based, cell-by-cell selection process. Moreover, xMD can provide improved dissection precision because of the unique characteristics of film activation. The time to complete the protocol is highly dependent on the target cell population and the number of cells needed for subsequent molecular analysis. PMID:21412274

Determination of Minimum Training Sample Size for Microarray-Based Cancer Outcome Prediction–An Empirical Assessment

PubMed Central

Cheng, Ningtao; Wu, Leihong; Cheng, Yiyu

2013-01-01

The promise of microarray technology in providing prediction classifiers for cancer outcome estimation has been confirmed by a number of demonstrable successes. However, the reliability of prediction results relies heavily on the accuracy of statistical parameters involved in classifiers. It cannot be reliably estimated with only a small number of training samples. Therefore, it is of vital importance to determine the minimum number of training samples and to ensure the clinical value of microarrays in cancer outcome prediction. We evaluated the impact of training sample size on model performance extensively based on 3 large-scale cancer microarray datasets provided by the second phase of MicroArray Quality Control project (MAQC-II). An SSNR-based (scale of signal-to-noise ratio) protocol was proposed in this study for minimum training sample size determination. External validation results based on another 3 cancer datasets confirmed that the SSNR-based approach could not only determine the minimum number of training samples efficiently, but also provide a valuable strategy for estimating the underlying performance of classifiers in advance. Once translated into clinical routine applications, the SSNR-based protocol would provide great convenience in microarray-based cancer outcome prediction in improving classifier reliability. PMID:23861920

Optimization of oncological {sup 18}F-FDG PET/CT imaging based on a multiparameter analysis

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

Menezes, Vinicius O., E-mail: vinicius@radtec.com.br; Machado, Marcos A. D.; Queiroz, Cleiton C.

2016-02-15

Purpose: This paper describes a method to achieve consistent clinical image quality in {sup 18}F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. Methods: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. Results: The adoption of different schemes for three body mass ranges (<60 kg, 60–90 kg, >90 kg) allows improved image quality with both point spread functionmore » and ordered-subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. Conclusions: Consistent oncological PET/CT image quality on a high-performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations.« less

From skin biopsy to neurons through a pluripotent intermediate under Good Manufacturing Practice protocols.

PubMed

Karumbayaram, Saravanan; Lee, Peiyee; Azghadi, Soheila F; Cooper, Aaron R; Patterson, Michaela; Kohn, Donald B; Pyle, April; Clark, Amander; Byrne, James; Zack, Jerome A; Plath, Kathrin; Lowry, William E

2012-01-01

The clinical application of human-induced pluripotent stem cells (hiPSCs) requires not only the production of Good Manufacturing Practice-grade (GMP-grade) hiPSCs but also the derivation of specified cell types for transplantation under GMP conditions. Previous reports have suggested that hiPSCs can be produced in the absence of animal-derived reagents (xenobiotics) to ease the transition to production under GMP standards. However, to facilitate the use of hiPSCs in cell-based therapeutics, their progeny should be produced not only in the absence of xenobiotics but also under GMP conditions requiring extensive standardization of protocols, documentation, and reproducibility of methods and product. Here, we present a successful framework to produce GMP-grade derivatives of hiPSCs that are free of xenobiotic exposure from the collection of patient fibroblasts, through reprogramming, maintenance of hiPSCs, identification of reprogramming vector integration sites (nrLAM-PCR), and finally specification and terminal differentiation of clinically relevant cells. Furthermore, we developed a primary set of Standard Operating Procedures for the GMP-grade derivation and differentiation of these cells as a resource to facilitate widespread adoption of these practices.

Examining the use of constraint-induced movement therapy in canadian neurological occupational and physical therapy.

PubMed

Fleet, Alana; Che, Marion; Mackay-Lyons, Marilyn; Mackenzie, Diane; Page, Stephen; Eskes, Gail; McDonald, Alison; Boyce, Joy; Boe, Shaun

2014-01-01

To investigate the use of constraint-induced movement therapy (CIMT) in Canadian neurological occupational and physical therapy. An online survey was completed by occupational and physical therapists practising in Canadian adult neurological rehabilitation. We measured participants' practices, perceptions, and opinions in relation to their use of CIMT in clinical practice. A total of 338 surveys were returned for a 13% response rate; 92% of respondents knew of CIMT, and 43% reported using it. The majority (88%) of respondents using CIMT employed a non-traditional protocol. Self-rating of level of CIMT knowledge was found to be a significant predictor of CIMT use (p≤0.001). Commonly identified barriers to use included "patients having cognitive challenges that prohibit use of this treatment" and "lack of knowledge regarding treatment." Although the majority of respondents knew about CIMT, less than half reported using it. Barriers to CIMT use include lack of knowledge about the treatment and institutional resources to support its use. Identifying and addressing barriers to CIMT use-for example, by using continuing professional education to remediate knowledge gaps or developing new protocols that require fewer institutional resources-can help improve the feasibility of CIMT, and thus promote its clinical application.

Pediatric Sepsis

PubMed Central

Mathias, Brittany; Mira, Juan; Larson, Shawn D.

2016-01-01

Purpose of Review Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72,000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. Recent Findings The definition of pediatric sepsis is currently in a state of evolution and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. Summary Current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become commonplace. PMID:26983000

Validation of a Monte Carlo simulation of the Philips Allegro/GEMINI PET systems using GATE

NASA Astrophysics Data System (ADS)

Lamare, F.; Turzo, A.; Bizais, Y.; Cheze LeRest, C.; Visvikis, D.

2006-02-01

A newly developed simulation toolkit, GATE (Geant4 Application for Tomographic Emission), was used to develop a Monte Carlo simulation of a fully three-dimensional (3D) clinical PET scanner. The Philips Allegro/GEMINI PET systems were simulated in order to (a) allow a detailed study of the parameters affecting the system's performance under various imaging conditions, (b) study the optimization and quantitative accuracy of emission acquisition protocols for dynamic and static imaging, and (c) further validate the potential of GATE for the simulation of clinical PET systems. A model of the detection system and its geometry was developed. The accuracy of the developed detection model was tested through the comparison of simulated and measured results obtained with the Allegro/GEMINI systems for a number of NEMA NU2-2001 performance protocols including spatial resolution, sensitivity and scatter fraction. In addition, an approximate model of the system's dead time at the level of detected single events and coincidences was developed in an attempt to simulate the count rate related performance characteristics of the scanner. The developed dead-time model was assessed under different imaging conditions using the count rate loss and noise equivalent count rates performance protocols of standard and modified NEMA NU2-2001 (whole body imaging conditions) and NEMA NU2-1994 (brain imaging conditions) comparing simulated with experimental measurements obtained with the Allegro/GEMINI PET systems. Finally, a reconstructed image quality protocol was used to assess the overall performance of the developed model. An agreement of <3% was obtained in scatter fraction, with a difference between 4% and 10% in the true and random coincidence count rates respectively, throughout a range of activity concentrations and under various imaging conditions, resulting in <8% differences between simulated and measured noise equivalent count rates performance. Finally, the image quality validation study revealed a good agreement in signal-to-noise ratio and contrast recovery coefficients for a number of different volume spheres and two different (clinical level based) tumour-to-background ratios. In conclusion, these results support the accurate modelling of the Philips Allegro/GEMINI PET systems using GATE in combination with a dead-time model for the signal flow description, which leads to an agreement of <10% in coincidence count rates under different imaging conditions and clinically relevant activity concentration levels.

A secure distributed logistic regression protocol for the detection of rare adverse drug events

PubMed Central

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-01-01

Background There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. Objective To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. Methods We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. Results The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. Conclusion The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models. PMID:22871397

A secure distributed logistic regression protocol for the detection of rare adverse drug events.

PubMed

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-05-01

There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models.

Exploitation of Existing Voice Over Internet Protocol Technology for Department of the Navy Application

DTIC Science & Technology

2002-09-01

Protocol LAN Local Area Network LDAP Lightweight Directory Access Protocol LLQ Low Latency Queuing MAC Media Access Control MarCorSysCom Marine...Description Protocol SIP Session Initiation Protocol SMTP Simple Mail Transfer Protocol SPAWAR Space and Naval Warfare Systems Center SS7 ...PSTN infrastructure previously required to carry the conversation. The cost of accessing the PSTN is thereby eliminated. In cases where Internet

TU-G-BRD-02: Automated Systematic Quality Assurance Program for Radiation Oncology Information System Upgrades

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

Zhang, B; Yi, B; Eley, J

Purpose: To: (1) describe an independent, automated, systematic software-based protocol for verifying clinical data accuracy/integrity for mitigation of data corruption/loss risks following radiation oncology information system (ROIS) upgrades; and (2) report on application of this approach in an academic/community practice environment. Methods: We propose a robust approach to perform quality assurance on the ROIS after an upgrade, targeting four data sources: (1) ROIS relational database; (2) ROIS DICOM interface; (3) ROIS treatment machine data configuration; and (4) ROIS-generated clinical reports. We investigated the database schema for differences between pre-/post-upgrade states. Paired DICOM data streams for the same object (such asmore » RT-Plan/Treatment Record) were compared between pre-/post-upgrade states for data corruption. We examined machine configuration and related commissioning data files for changes and corruption. ROIS-generated treatment appointment and treatment parameter reports were compared to ensure patient encounter and treatment plan accuracy. This protocol was supplemented by an end-to-end clinical workflow test to verify essential ROI functionality and integrity of components interfaced during patient care chain of activities. We describe the implementation of this protocol during a Varian ARIA system upgrade at our clinic. Results: We verified 1,638 data tables with 2.4 billion data records. For 222 under-treatment patients, 605 DICOM RT plans and 13,480 DICOM treatment records retrieved from the ROIS DICOM interface were compared, with no differences in fractions, doses delivered, or treatment parameters. We identified 82 new data tables and 78 amended/deleted tables consistent with the upgrade. Reports for 5,073 patient encounters over a 2-week horizon were compared and were identical to those before the upgrade. Content in 12,237 xml machine files was compared, with no differences identified. Conclusion: An independent QA/validation approach for ROIS upgrades was developed and implemented at our clinic. The success of this approach ensures a robust QA of ROIS upgrades without manual paper/electronic checks and associated intensive labor.« less

A Method of Managing Severe Traumatic Brain Injury in the Absence of Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol.

PubMed

Chesnut, Randall M; Temkin, Nancy; Dikmen, Sureyya; Rondina, Carlos; Videtta, Walter; Petroni, Gustavo; Lujan, Silvia; Alanis, Victor; Falcao, Antonio; de la Fuenta, Gustavo; Gonzalez, Luis; Jibaja, Manuel; Lavarden, Arturo; Sandi, Freddy; Mérida, Roberto; Romero, Ricardo; Pridgeon, Jim; Barber, Jason; Machamer, Joan; Chaddock, Kelley

2018-01-01

The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) monitoring. As the default literature standard, it warrants careful evaluation. We present the ICE protocol in detail and analyze the demographics, outcome, treatment intensity, frequency of intervention usage, and related adverse events in the ICE-protocol cohort. The 167 ICE protocol patients were young (median 29 years) with a median Glasgow Coma Scale motor score of 4 but with anisocoria or abnormal pupillary reactivity in 40%. This protocol produced outcomes not significantly different from those randomized to the monitor-based protocol (favorable 6-month extended Glasgow Outcome Score in 39%; 41% mortality rate). Agents commonly employed to treat suspected intracranial hypertension included low-/moderate-dose hypertonic saline (72%) and mannitol (57%), mild hyperventilation (adjusted partial pressure of carbon dioxide 30-35 mm Hg in 73%), and pressors to maintain cerebral perfusion (62%). High-dose hyperosmotics or barbiturates were uncommonly used. Adverse event incidence was low and comparable to the BEST TRIP monitored group. Although this protocol should produce similar/acceptable results under circumstances comparable to those in the trial, influences such as longer pre-hospital times and non-specialist transport personnel, plus an intensive care unit model of aggressive physician-intensive care by small groups of neurotrauma-focused intensivists, which differs from most high-resource models, support caution in expecting the same results in dissimilar settings. Finally, this protocol's ICP-titration approach to suspected intracranial hypertension (vs. crisis management for monitored ICP) warrants further study.

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

A privacy preserving protocol for tracking participants in phase I clinical trials.

PubMed

El Emam, Khaled; Farah, Hanna; Samet, Saeed; Essex, Aleksander; Jonker, Elizabeth; Kantarcioglu, Murat; Earle, Craig C

2015-10-01

Some phase 1 clinical trials offer strong financial incentives for healthy individuals to participate in their studies. There is evidence that some individuals enroll in multiple trials concurrently. This creates safety risks and introduces data quality problems into the trials. Our objective was to construct a privacy preserving protocol to track phase 1 participants to detect concurrent enrollment. A protocol using secure probabilistic querying against a database of trial participants that allows for screening during telephone interviews and on-site enrollment was developed. The match variables consisted of demographic information. The accuracy (sensitivity, precision, and negative predictive value) of the matching and its computational performance in seconds were measured under simulated environments. Accuracy was also compared to non-secure matching methods. The protocol performance scales linearly with the database size. At the largest database size of 20,000 participants, a query takes under 20s on a 64 cores machine. Sensitivity, precision, and negative predictive value of the queries were consistently at or above 0.9, and were very similar to non-secure versions of the protocol. The protocol provides a reasonable solution to the concurrent enrollment problems in phase 1 clinical trials, and is able to ensure that personal information about participants is kept secure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effectiveness of a smartphone application for improving healthy lifestyles, a randomized clinical trial (EVIDENT II): study protocol.

PubMed

Recio-Rodríguez, José I; Martín-Cantera, Carlos; González-Viejo, Natividad; Gómez-Arranz, Amparo; Arietaleanizbeascoa, Maria S; Schmolling-Guinovart, Yolanda; Maderuelo-Fernandez, Jose A; Pérez-Arechaederra, Diana; Rodriguez-Sanchez, Emiliano; Gómez-Marcos, Manuel A; García-Ortiz, Luis

2014-03-15

New technologies could facilitate changes in lifestyle and improve public health. However, no large randomized, controlled studies providing scientific evidence of the benefits of their use have been made. The aims of this study are to develop and validate a smartphone application, and to evaluate the effect of adding this tool to a standardized intervention designed to improve adherence to the Mediterranean diet and to physical activity. An evaluation is also made of the effect of modifying habits upon vascular structure and function, and therefore on arterial aging. A randomized, double-blind, multicenter, parallel group clinical trial will be carried out. A total of 1215 subjects under 70 years of age from the EVIDENT trial will be included. Counseling common to both groups (control and intervention) will be provided on adaptation to the Mediterranean diet and on physical activity. The intervention group moreover will receive training on the use of a smartphone application designed to promote a healthy diet and increased physical activity, and will use the application for three months. The main study endpoints will be the changes in physical activity, assessed by accelerometer and the 7-day Physical Activity Recall (PAR) interview, and adaptation to the Mediterranean diet, as evaluated by an adherence questionnaire and a food frequency questionnaire (FFQ). Evaluation also will be made of vascular structure and function based on central arterial pressure, the radial augmentation index, pulse velocity, the cardio-ankle vascular index, and carotid intima-media thickness. Confirmation that the new technologies are useful for promoting healthier lifestyles and that their effects are beneficial in terms of arterial aging will have important clinical implications, and may contribute to generalize their application in favor of improved population health. Clinical Trials.gov Identifier: NCT02016014.