Clinical applicability of nursing outcomes in the evolution of orthopedic patients with Impaired Physical Mobility.

PubMed

da Silva, Marcos Barragan; Almeida, Miriam de Abreu; Panato, Bruna Paulsen; Siqueira, Ana Paula de Oliveira; da Silva, Mariana Palma; Reisderfer, Letícia

2015-01-01

to evaluate the clinical applicability of outcomes, according to the Nursing Outcomes Classification (NOC) in the evolution of orthopedic patients with Impaired Physical Mobility longitudinal study conducted in 2012 in a university hospital, with 21 patients undergoing Total Hip Arthroplasty, evaluated daily by pairs of trained data collectors. Data were collected using an instrument containing five Nursing Outcomes, 16 clinical indicators and a five point Likert scale, and statistically analyzed. The outcomes Body Positioning: self-initiated, Mobility, Knowledge: prescribed activity, and Fall Prevention Behavior presented significant increases in mean scores when comparing the first and final evaluations (p<0.001) and (p=0.035). the use of the NOC outcomes makes it possible to demonstrate the clinical progression of orthopedic patients with Impaired Physical Mobility, as well as its applicability in this context.

Estimating the cost of blood: past, present, and future directions.

PubMed

Shander, Aryeh; Hofmann, Axel; Gombotz, Hans; Theusinger, Oliver M; Spahn, Donat R

2007-06-01

Understanding the costs associated with blood products requires sophisticated knowledge about transfusion medicine and is attracting the attention of clinical and administrative healthcare sectors worldwide. To improve outcomes, blood usage must be optimized and expenditures controlled so that resources may be channeled toward other diagnostic, therapeutic, and technological initiatives. Estimating blood costs, however, is a complex undertaking, surpassing simple supply versus demand economics. Shrinking donor availability and application of a precautionary principle to minimize transfusion risks are factors that continue to drive the cost of blood products upward. Recognizing that historical accounting attempts to determine blood costs have varied in scope, perspective, and methodology, new approaches have been initiated to identify all potential cost elements related to blood and blood product administration. Activities are also under way to tie these elements together in a comprehensive and practical model that will be applicable to all single-donor blood products without regard to practice type (e.g., academic, private, multi- or single-center clinic). These initiatives, their rationale, importance, and future directions are described.

Computer-Based Intepretation of the Marital Satisfaction Inventory: Use in Treatment Planning.

ERIC Educational Resources Information Center

Snyder, Douglas K.; And Others

1988-01-01

Describes computer-based interpretive system for Marital Satisfaction Inventory (MSI) and application in initial phases of clinical assessment and treatment planning. Provides case study. Compares clinical findings at intake with MSI profiles for one couple obtained at termination and follow-up. Considers strengths and limitations of self-report…

Laboratory and clinical trials of cocamide diethanolamine lotion against head lice

PubMed Central

Brunton, Elizabeth R.; Brown, Christine M.

2015-01-01

Context. During the late 1990s, insecticide resistance had rendered a number of treatment products ineffective; some companies saw this as an opportunity to develop alternative types of treatment. We investigated the possibility that a surfactant-based lotion containing 10% cocamide diethanolamine (cocamide DEA) was effective to eliminate head louse infestation. Settings and Design. Initial in vitro testing of the lotion formulation versus laboratory reared body/clothing lice, followed by two randomised, controlled, community-based, assessor blinded, clinical studies. Materials and Methods. Preliminary laboratory tests were performed by exposing lice or louse eggs to the product using a method that mimicked the intended use. Clinical Study 1: Children and adults with confirmed head louse infestation were treated by investigators using a single application of aqueous 10% cocamide DEA lotion applied for 60 min followed by shampooing or a single 1% permethrin creme rinse treatment applied to pre-washed hair for 10 min. Clinical Study 2: Compared two treatment regimens using 10% cocamide DEA lotion that was concentrated by hair drying. A single application left on for 8 h/overnight was compared with two applications 7 days apart of 2 h duration, followed by a shampoo wash. Results. The initial laboratory tests showed a pediculicidal effect for a 60 min application but limited ovicidal effect. A longer application time of 8 h or overnight was found capable of killing all eggs but this differed between batches of test material. Clinical Study 1: Both treatments performed badly with only 3/23 (13%) successful treatments using cocamide DEA and 5/25 (23.8%) using permethrin. Clinical Study 2: The single overnight application of cocamide DEA concentrated by hair drying gave 10/56 (17.9%) successes compared with 19/56 (33.9%) for the 2 h application regimen repeated after 1 week. Intention to treat analysis showed no significant difference (p = 0.0523) between the treatments. Over the two studies, there were 18 adverse events possibly or probably associated with treatment, most of which were increased pruritus after treatment. Conclusions. Cocamide DEA 10% lotion, even when concentrated by hair drying, showed limited activity to eliminate head louse infestation. PMID:26557439

Learning Surgically Oriented Anatomy in a Student-Run Extracurricular Club: An Education through Recreation Initiative

ERIC Educational Resources Information Center

Ullah, Shahnoor M.; Bodrogi, Andrew; Cristea, Octav; Johnson, Marjorie; McAlister, Vivian C.

2012-01-01

Didactic and laboratory anatomical education have seen significant reductions in the medical school curriculum due, in part, to the current shift from basic science to more clinically based teaching in North American medical schools. In order to increase medical student exposure to anatomy, with clinical applicability, a student-run initiative…

21 CFR 56.103 - Circumstances in which IRB review is required.

Code of Federal Regulations, 2010 CFR

2010-04-01

... is required. (a) Except as provided in §§ 56.104 and 56.105, any clinical investigation which must... support of an application for a research or marketing permit any data or information that has been derived from a clinical investigation that has not been approved by, and that was not subject to initial and...

An Integrated Computerized Triage System in the Emergency Department

PubMed Central

Aronsky, Dominik; Jones, Ian; Raines, Bill; Hemphill, Robin; Mayberry, Scott R; Luther, Melissa A; Slusser, Ted

2008-01-01

Emergency department (ED) triage is a fast-paced process that prioritizes the allocation of limited health care resources to patients in greatest need. This paper describes the experiences with an integrated, computerized triage application. The system exchanges information with other information systems, including the ED patient tracking board, the longitudinal electronic medical record, the computerized provider order entry, and the medication reconciliation application. The application includes decision support capabilities such as assessing the patient’s acuity level, age-dependent alerts for vital signs, and clinical reminders. The browser-based system utilizes the institution’s controlled vocabulary, improves data completeness and quality, such as compliance with capturing required data elements and screening questions, initiates clinical processes, such as pneumococcal vaccination ordering, and reminders to start clinical pathways, issues alerts for clinical trial eligibility, and facilitates various reporting needs. The system has supported the triage documentation of >290,000 pediatric and adult patients. PMID:18999190

Clinical applicability of nursing outcomes in the evolution of orthopedic patients with Impaired Physical Mobility 1

PubMed Central

da Silva, Marcos Barragan; Almeida, Miriam de Abreu; Panato, Bruna Paulsen; Siqueira, Ana Paula de Oliveira; da Silva, Mariana Palma; Reisderfer, Letícia

2015-01-01

AIM: to evaluate the clinical applicability of outcomes, according to the Nursing Outcomes Classification (NOC) in the evolution of orthopedic patients with Impaired Physical Mobility METHOD: longitudinal study conducted in 2012 in a university hospital, with 21 patients undergoing Total Hip Arthroplasty, evaluated daily by pairs of trained data collectors. Data were collected using an instrument containing five Nursing Outcomes, 16 clinical indicators and a five point Likert scale, and statistically analyzed. RESULTS: The outcomes Body Positioning: self-initiated, Mobility, Knowledge: prescribed activity, and Fall Prevention Behavior presented significant increases in mean scores when comparing the first and final evaluations (p<0.001) and (p=0.035). CONCLUSION: the use of the NOC outcomes makes it possible to demonstrate the clinical progression of orthopedic patients with Impaired Physical Mobility, as well as its applicability in this context. PMID:25806631

Quantitative assessment of orthodontic mini-implant displacement: the effect of initial force application.

PubMed

Holst, Alexandra Ioana; Karl, Matthias; Karolczak, Marek; Goellner, Matthias; Holst, Stefan

2010-01-01

Primary stability and micromovement of orthodontic mini-implants depends on a number of factors and influences clinical success or failure. The purpose of this study was to assess the behavior of orthodontic mini-implants upon initial load application. Orthodontic mini-implants (n = 39) were inserted in the alveolar process of maxillary human cadaver specimens (n = 10). Increasing horizontal forces (up to 2.5 N) were applied, and triggered images were taken in 0.5-N load intervals. Additionally, peri-implant parameters based on micro-CT volume data were recorded. Data were subjected to a two-sided nonparametric Wilcoxon signed rank test, and between-group comparisons were assessed with a Mann-Whitney test (alpha = .05). Initial load application led to displacement beyond elastic recovery of the surrounding bone after force release (P < .001). Cortical thickness and insertion depth, despite numeric differences, did not reveal any statistical differences, while displacement of mini-implants was significantly affected by contact to neighboring teeth (P < .001). Insertion technique and initial load application on orthodontic mini-implants may be regarded as two crucial factors for success, while repeated application of orthodontic force does not seem to increase screw mobility.

Regenerative medicine for the respiratory system: distant future or tomorrow's treatment?

PubMed

Brouwer, Katrien M; Hoogenkamp, Henk R; Daamen, Willeke F; van Kuppevelt, Toin H

2013-03-01

Regenerative medicine (RM) is a new field of biomedical science that focuses on the regeneration of tissues and organs and the restoration of organ function. Although regeneration of organ systems such as bone, cartilage, and heart has attracted intense scientific research over recent decades, RM research regarding the respiratory system, including the trachea, the lung proper, and the diaphragm, has lagged behind. However, the last 5 years have witnessed novel approaches and initial clinical applications of tissue-engineered constructs to restore organ structure and function. In this regard, this article briefly addresses the basics of RM and introduces the key elements necessary for tissue regeneration, including (stem) cells, biomaterials, and extracellular matrices. In addition, the current status of the (clinical) application of RM to the respiratory system is discussed, and bottlenecks and recent approaches are identified. For the trachea, several initial clinical studies have been reported and have used various combinations of cells and scaffolds. Although promising, the methods used in these studies require optimization and standardization. For the lung proper, only (stem) cell-based approaches have been probed clinically, but it is becoming apparent that combinations of cells and scaffolds are required to successfully restore the lung's architecture and function. In the case of the diaphragm, clinical applications have focused on the use of decellularized scaffolds, but novel scaffolds, with or without cells, are clearly needed for true regeneration of diaphragmatic tissue. We conclude that respiratory treatment with RM will not be realized tomorrow, but its future looks promising.

Lower limb ice application alters ground reaction force during gait initiation.

PubMed

Muniz, Thiago B; Moraes, Renato; Guirro, Rinaldo R J

2015-01-01

Cryotherapy is a widely used technique in physical therapy clinics and sports. However, the effects of cryotherapy on dynamic neuromuscular control are incompletely explained. To evaluate the effects of cryotherapy applied to the calf, ankle and sole of the foot in healthy young adults on ground reaction forces during gait initiation. This study evaluated the gait initiation forces, maximum propulsion, braking forces and impulses of 21 women volunteers through a force platform, which provided maximum and minimum ground reaction force values. To assess the effects of cooling, the task--gait initiation--was performed before ice application, immediately after and 30 minutes after removal of the ice pack. Ice was randomly applied on separate days to the calf, ankle and sole of the foot of the participants. It was demonstrated that ice application for 30 minutes to the sole of the foot and calf resulted in significant changes in the vertical force variables, which returned to their pre-application values 30 minutes after the removal of the ice pack. Ice application to the ankle only reduced propulsion impulse. These results suggest that although caution is necessary when performing activities that require good gait control, the application of ice to the ankle, sole of the foot or calf in 30-minute intervals may be safe even preceding such activities.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Hai, Mary T Thanh; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-02-27

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. © 2018 American Heart Association, Inc.

Application of Viscoelastic Fracture Model and Non-uniform Crack Initiation at Clinically Relevant Notches in Crosslinked UHMWPE

PubMed Central

Sirimamilla, P. Abhiram; Furmanski, Jevan; Rimnac, Clare M.

2012-01-01

The mechanism of crack initiation from a clinically relevant notch is not well-understood for crosslinked ultra high molecular weight polyethylene (UHMWPE) used in total joint replacement components. Static mode driving forces, rather than the cyclic mode conditions typically associated with fatigue processes, have been shown to drive crack propagation in this material. Thus, in this study, crack initiation in a notched specimen under a static load was investigated. A video microscope was used to monitor the notch surface of the specimen and crack initiation time was measured from the video by identifying the onset of crack initiation at the notch. Crack initiation was considered using a viscoelastic fracture theory. It was found that the mechanism of crack initiation involved both single layer and a distributed multi-layer phenomenon and that multi-layer crack initiation delayed the crack initiation time for all loading conditions examined. The findings of this study support that the viscoelastic fracture theory governs fracture mechanics in crosslinked UHMWPE. The findings also support that crack initiation from a notch in UHMWPE is a more complex phenomenon than treated by traditional fracture theories for polymers. PMID:23127638

Development and Application of a Computer Simulation Program to Enhance the Clinical Problem-Solving Skills of Students.

ERIC Educational Resources Information Center

Boh, Larry E.; And Others

1987-01-01

A project to (1) develop and apply a microcomputer simulation program to enhance clinical medication problem solving in preclerkship and clerkship students and (2) perform an initial formative evaluation of the simulation is described. A systematic instructional design approach was used in applying the simulation to the disease state of rheumatoid…

Clinical proteomics in kidney disease as an exponential technology: heading towards the disruptive phase.

PubMed

Sanchez-Niño, Maria Dolores; Sanz, Ana B; Ramos, Adrian M; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

2017-04-01

Exponential technologies double in power or processing speed every year, whereas their cost halves. Deception and disruption are two key stages in the development of exponential technologies. Deception occurs when, after initial introduction, technologies are dismissed as irrelevant, while they continue to progress, perhaps not as fast or with so many immediate practical applications as initially thought. Twenty years after the first publications, clinical proteomics is still not available in most hospitals and some clinicians have felt deception at unfulfilled promises. However, there are indications that clinical proteomics may be entering the disruptive phase, where, once refined, technologies disrupt established industries or procedures. In this regard, recent manuscripts in CKJ illustrate how proteomics is entering the clinical realm, with applications ranging from the identification of amyloid proteins in the pathology lab, to a new generation of urinary biomarkers for chronic kidney disease (CKD) assessment and outcome prediction. Indeed, one such panel of urinary peptidomics biomarkers, CKD273, recently received a Food and Drug Administration letter of support, the first ever in the CKD field. In addition, a must-read resource providing information on kidney disease-related proteomics and systems biology databases and how to access and use them in clinical decision-making was also recently published in CKJ .

[Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

PubMed

Renisch, B; Lauer, W

2014-12-01

An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

Clinical applications of the functional connectome

PubMed Central

Castellanos, F. Xavier; Di Martino, Adriana; Craddock, R. Cameron; Mehta, Ashesh D.; Milham, Michael P.

2013-01-01

Central to the development of clinical applications of functional connectomics for neurology and psychiatry is the discovery and validation of biomarkers. Resting state fMRI (R-fMRI) is emerging as a mainstream approach for imaging-based biomarker identification, detecting variations in the functional connectome that can be attributed to clinical variables (e.g., diagnostic status). Despite growing enthusiasm, many challenges remain. Here, we assess evidence of the readiness of R-fMRI based functional connectomics to lead to clinically meaningful biomarker identification through the lens of the criteria used to evaluate clinical tests (i.e., validity, reliability, sensitivity, specificity, and applicability). We focus on current R-fMRI-based prediction efforts, and survey R-fMRI used for neurosurgical planning. We identify gaps and needs for R-fMRI-based biomarker identification, highlighting the potential of emerging conceptual, analytical and cultural innovations (e.g., the Research Domain Criteria Project (RDoC), open science initiatives, and Big Data) to address them. Additionally, we note the need to expand future efforts beyond identification of biomarkers for disease status alone to include clinical variables related to risk, expected treatment response and prognosis. PMID:23631991

International models of investigator-initiated trials: implications for Japan

PubMed Central

Trimble, E. L.; Ledermann, J.; Law, K.; Miyata, T.; Imamura, C. K.; Nam, B.-H.; Kim, Y.H.; Bang, Y.-J.; Michaels, M.; Ardron, D.; Amano, S.; Ando, Y.; Tominaga, T.; Kurokawa, K.; Takebe, N.

2012-01-01

Background Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. Materials In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. Results In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. Conclusions To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval. PMID:22843420

Ultrasonic propulsion of kidney stones.

PubMed

May, Philip C; Bailey, Michael R; Harper, Jonathan D

2016-05-01

Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application. Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the ureteropelvic junction with relief of pain, and differentiating large stones from a collection of small fragments. Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing ureteropelvic junction stones into the kidney to alleviate acute renal colic.

Ultrasonic propulsion of kidney stones

PubMed Central

May, Philip C.; Bailey, Michael R.; Harper, Jonathan D.

2016-01-01

Purpose of review Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application. Recent findings Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the UPJ with relief of pain, and differentiating large stones from a collection of small fragments. Summary Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing UPJ stones into the kidney to alleviate acute renal colic. PMID:26845428

Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future.

PubMed

Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

2016-05-12

The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a "Mayo Model" of HIV care that exceeds national outcomes and may be applicable in other settings.

Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future

PubMed Central

Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

2016-01-01

The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a “Mayo Model” of HIV care that exceeds national outcomes and may be applicable in other settings. PMID:27175350

Postconditioning hormesis put in perspective: an overview of experimental and clinical studies.

PubMed

Wiegant, F A C; Prins, H A B; Van Wijk, R

2011-01-01

A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

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…

Evolution in Clinical Knowledge Management Strategy at Intermountain Healthcare

PubMed Central

Hulse, Nathan C.; Galland, Joel; Borsato, Emerson P.

2012-01-01

In this manuscript, we present an overview of the clinical knowledge management strategy at Intermountain Healthcare in support of our electronic medical record systems. Intermountain first initiated efforts in developing a centralized enterprise knowledge repository in 2001. Applications developed, areas of emphasis served, and key areas of focus are presented. We also detail historical and current areas of emphasis, in response to business needs. PMID:23304309

The Computer-Based Writing Program: A Clinical Teaching Experience for Education Interns to Develop Professional Knowledge and Skills in Effective Instructional Writing Practices

ERIC Educational Resources Information Center

Painter, Diane D.

2016-01-01

The four-week university-sponsored summer Computer-based Writing (CBW) Program directed by the head of a special education initial teacher licensure program gave teaching interns opportunities to work with young struggling writers in a supervised clinical setting to address keyboarding skills, writing conventions and knowledge and application of…

Cardiovascular tissue engineering: where we come from and where are we now?

PubMed

Smit, Francis E; Dohmen, Pascal M

2015-01-27

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

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.

Proteases as therapeutics

PubMed Central

Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

2015-01-01

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

Lower limb ice application alters ground reaction force during gait initiation

PubMed Central

Muniz, Thiago B.; Moraes, Renato; Guirro, Rinaldo R. J.

2015-01-01

BACKGROUND: Cryotherapy is a widely used technique in physical therapy clinics and sports. However, the effects of cryotherapy on dynamic neuromuscular control are incompletely explained. OBJECTIVES: To evaluate the effects of cryotherapy applied to the calf, ankle and sole of the foot in healthy young adults on ground reaction forces during gait initiation. METHOD: This study evaluated the gait initiation forces, maximum propulsion, braking forces and impulses of 21 women volunteers through a force platform, which provided maximum and minimum ground reaction force values. To assess the effects of cooling, the task - gait initiation - was performed before ice application, immediately after and 30 minutes after removal of the ice pack. Ice was randomly applied on separate days to the calf, ankle and sole of the foot of the participants. RESULTS: It was demonstrated that ice application for 30 minutes to the sole of the foot and calf resulted in significant changes in the vertical force variables, which returned to their pre-application values 30 minutes after the removal of the ice pack. Ice application to the ankle only reduced propulsion impulse. CONCLUSIONS: These results suggest that although caution is necessary when performing activities that require good gait control, the application of ice to the ankle, sole of the foot or calf in 30-minute intervals may be safe even preceding such activities. PMID:25993625

Induced pluripotent stem cells--alchemist's tale or clinical reality?

PubMed

Rashid, S Tamir; Vallier, Ludovic

2010-08-13

Following Shinya Yamanaka's first report describing the reprogramming of fibroblasts into stem cells over three years ago, some sceptics initially drew analogies between this new field of research and the quasi-mystical practice of 'alchemy'. Unlike the alchemist, however, stem cell researchers have rigorously tested and repeated experiments, proving their very own brand of cellular 'alchemy' to be a reality, with potentially massive implications for the study of human biology and clinical medicine. These investigations have resulted in an explosion of related publications and initiated the field of stem cell research known as 'induced pluripotency'. In this review, we give an account of the historical development, current technologies and potential clinical applications of induced pluripotency and conclude with a perspective on the possible future directions for this dynamic field.

Therapeutic hypothermia: applications in pediatric cardiac arrest.

PubMed

Kochanek, Patrick M; Fink, Ericka L; Bell, Michael J; Bayir, Hülya; Clark, Robert S B

2009-03-01

There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.

Parameters for measurement of oxidative stress in diabetes mellitus: applicability of enzyme-linked immunosorbent assay for clinical evaluation.

PubMed

Noiri, Eisei; Tsukahara, Hirokazu

2005-05-01

Investigations of the mechanisms involved in the onset and progression of diabetes have recently confronted the role of reactive oxygen species (ROS) and oxidative stress. Prolonged exposure to hyperglycemic conditions induces nonenzymatic glycation of protein via the so-called Maillard reaction, resulting in Schiff-base products and Amadori products that engender ROS production. These processes initiate and exacerbate micro- and macrovascular complications in diabetes. Increased oxidative stress is induced by excessive ROS production and inadequate antioxidant defenses. Recently, oxidative stress status markers have been associated directly with the severity and prognosis of diabetes. To examine oxidative stress, reliable and high-throughput methods are needed to examine large numbers of clinical samples. The emerging availability of enzyme-linked immunosorbent assay (ELISA) for oxidative stress status markers allows its application to assessment of various pathophysiologic conditions, including diabetes. This review outlines the recent achievements of ELISA application for clinical studies elucidating oxidative stress. It introduces the potential applicability of ELISA for investigating oxidative stress in diabetes.

The SALOME study: recruitment experiences in a clinical trial offering injectable diacetylmorphine and hydromorphone for opioid dependency.

PubMed

Oviedo-Joekes, Eugenia; Marchand, Kirsten; Lock, Kurt; MacDonald, Scott; Guh, Daphne; Schechter, Martin T

2015-01-26

The Study to Assess Long-term Opioid Medication Effectiveness (SALOME) is a two-stage phase III, single site (Vancouver, Canada), randomized, double blind controlled trial designed to test if hydromorphone is as effective as diacetylmorphine for the treatment of long-term illicit opioid injection. Recruiting participants for clinical trials continues to be a challenge in medical and addiction research, with many studies not being able to reach the planned sample size in a timely manner. The aim of this study is to describe the recruitment strategies in SALOME, which offered appealing treatments but had limited clinic capacity and no guaranteed post-trial continuation of the treatments. SALOME included chronic opioid-dependent, current illicit injection opioid users who had at least one previous episode of opioid maintenance treatment. Regulatory approvals were received in June 2011 and recruitment strategies were implemented over the next 5 months. Recruitment strategies included ongoing open communication with the community, a consistent and accessible team and participant-centered screening. All applicants completed a pre-screening checklist to assess prerequisites. Applicants meeting these prerequisites were later contacted to commence the screening process. A total of 598 applications were received over the two-year recruitment period; 130 were received on the first day of recruitment. Of these applicants, 485 met prerequisites; however, many could not be found or were not reached before recruitment ended. For the 253 candidates who initiated the screening process, the average time lapse between application and screening date was 8.3 months (standard deviation [SD] = 4.44) and for the 202 randomized to the study, the average processing time from initial screen to randomization was 25.9 days (SD = 37.48; Median = 15.0). As in prior trials offering injectable diacetylmorphine within a supervised model, recruiting participants for this study took longer than planned. The recruitment challenges overcome in SALOME were due to the high number of applicants compared with the limited number that could be randomized and treated. Our study emphasizes the value of integrating these strategies into clinical addiction research to overcome study-specific barriers. ClinicalTrials.gov: NCT01447212.

A clinical information systems strategy for a large integrated delivery network.

PubMed Central

Kuperman, G. J.; Spurr, C.; Flammini, S.; Bates, D.; Glaser, J.

2000-01-01

Integrated delivery networks (IDNs) are an emerging class of health care institutions. IDNs are formed from the affiliation of individual health care institutions and are intended to be more efficient in the current fiscal health care environment. To realize efficiencies and support their strategic visions, IDNs rely critically on excellent information technology (IT). Because of its importance to the mission of the IDN, strategic decisions about IT are made by the top leadership of the IDN. At Partners HealthCare System, a large IDN in Boston, MA, a clinical information systems strategy has been created to support the Partners clinical vision. In this paper, we discuss the Partners' structure, clinical vision, and current IT initiatives in place to address the clinical vision. The initiatives are: a clinical data repository, inpatient process support, electronic medical records, a portal strategy, referral applications, knowledge resources, support for product lines, patient computing, confidentiality, and clinical decision support. We address several of the issues encountered in trying to bring excellent information technology to a large IDN. PMID:11079921

Harvard Catalyst | The Clinical Translational Science Center IND/IDE Consult Service: providing an IND/IDE consult service in a decentralized network of academic healthcare centers.

PubMed

Kim, Min J; Winkler, Sabune J; Bierer, Barbara E; Wolf, Delia

2014-04-01

The Food and Drug Administration (FDA) regulations require sponsors of clinical investigations involving an investigational drug or device to submit an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application. Strict adherence to applicable regulations is vital to the success of clinical research. Unlike most major pharmaceutical sponsors, investigator sponsors often do not fully appreciate their regulatory obligations nor have resources to ensure compliance. As a result they can place themselves and their institutions at risk. Nevertheless, investigator-initiated clinical trials are vital to the further development of innovative drugs, biologics, and medical devices. The IND/IDE Subcommittee under the Regulatory Knowledge and Support Program at Harvard Catalyst, The Harvard Clinical and Translational Science Center worked in collaboration with Harvard and Harvard affiliated institutions to create and launch an IND/IDE Consult Service in a decentralized network of collaborating Academic Healthcare Centers (AHC). The IND/IDE Consult Service offers expertise, resources, and shared experiences to assist sponsor-investigators and IRBs in meeting regulatory requirements for conducting and reviewing investigator-initiated IND/IDE studies. The scope of the services provided by the Harvard Catalyst IND/IDE Consult Service are described, including the specifics of the service, lessons learned, and challenges faced, in a scalable model that builds inter-institutional capacity. © 2014 Wiley Periodicals, Inc.

Harvard Catalyst | The Clinical Translational Science Center IND/IDE Consult Service: Providing an IND/IDE Consult Service in a Decentralized Network of Academic Healthcare Centers

PubMed Central

Winkler, Sabune J.; Bierer, Barbara E.; Wolf, Delia

2014-01-01

Abstract The Food and Drug Administration (FDA) regulations require sponsors of clinical investigations involving an investigational drug or device to submit an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application. Strict adherence to applicable regulations is vital to the success of clinical research. Unlike most major pharmaceutical sponsors, investigator sponsors often do not fully appreciate their regulatory obligations nor have resources to ensure compliance. As a result they can place themselves and their institutions at risk. Nevertheless, investigator‐initiated clinical trials are vital to the further development of innovative drugs, biologics, and medical devices. The IND/IDE Subcommittee under the Regulatory Knowledge and Support Program at Harvard Catalyst, The Harvard Clinical and Translational Science Center worked in collaboration with Harvard and Harvard affiliated institutions to create and launch an IND/IDE Consult Service in a decentralized network of collaborating Academic Healthcare Centers (AHC). The IND/IDE Consult Service offers expertise, resources, and shared experiences to assist sponsor‐investigators and IRBs in meeting regulatory requirements for conducting and reviewing investigator‐initiated IND/IDE studies. The scope of the services provided by the Harvard Catalyst IND/IDE Consult Service are described, including the specifics of the service, lessons learned, and challenges faced, in a scalable model that builds inter‐institutional capacity. PMID:24455986

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Thanh Hai, Mary T; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-03-06

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. Copyright © 2018 American College of Cardiology Foundation and American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications

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

Acharya, Sahaja; Fischer-Valuck, Benjamin W.; Kashani, Rojano

Purpose: To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. Methods and Materials: The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped {sup 60}Co heads. The unit is supported by a Monte Carlo–based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient atmore » the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. Results: The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. Conclusion: Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.« less

WhatsApp: a telemedicine platform for facilitating remote oral medicine consultation and improving clinical examinations.

PubMed

Petruzzi, Massimo; De Benedittis, Michele

2016-03-01

Increased use of smartphone and related software applications has created a new era in clinical data exchange among patients and clinicians. This study describes use of the smartphone-based application WhatsApp to share clinical oral medicine information. Clinical images and related questions were submitted by general dentists, physicians, dental hygienists, and patients to the authors via WhatsApp. For each submission, a clinical impression was made and categorized as traumatic, infective, neoplastic, autoimmune, or unclassified. Submissions were summarized by sender type, number of photographs per sender, and category of question. Patients were invited to undergo a clinical examination with biopsy, when indicated. The telemedicine impression was compared to the clinicopathologic diagnosis. Three hundred and thirty-nine images were received for 96 patients; 92 (95.8%) patients underwent clinicopathologic examination, and 45 (49%) received a biopsy. General dentists (62%) and dental hygienists (26%) were the most frequent senders. The most common question was related to diagnosis (56%). The telemedicine impression agreed with the clinicopathologic assessment for 82% of cases. Telemedicine applications, such as WhatsApp, can support communication about oral conditions among clinicians and patients. Telemedicine consultation reduced geographic barriers to initial clinical consultation and encouraged the significant majority of patients to pursue expert clinical examination. Copyright © 2016 Elsevier Inc. All rights reserved.

Initial Clinical Trial of Robot of Endovascular Treatment with Force Feedback and Cooperating of Catheter and Guidewire.

PubMed

Jiang, Yuhua; Liu, Keyun; Li, Youxiang

2018-01-01

To evaluate the feasibility and safety of the robot of endovascular treatment (RobEnt) in clinical practice, we carried out a cerebral angiography using this robot system. We evaluated the performance of application of the robot system to clinical practice through using this robotic system to perform the digital subtraction angiography for a patient who was suspected of suffering intracranial aneurysm. At the same time, through comparing the postoperative head nuclear magnetic and blood routine with the preoperative examination, we evaluated the safety of application of the robot system to clinical practice. We performed the robot system to complete the bilateral carotid artery and bilateral vertebral arteriography. The results indicate that there was no obvious abnormality in the patient's cerebral artery. No obvious abnormality was observed in the examination of patients' check-up, head nuclear magnetism, and blood routine after the digital subtraction angiography. From this clinical trial, it can be observed that the robot system can perform the operation of cerebral angiography. The robot system can basically complete the related observation indexes, and its accuracy, effectiveness, stability, and safety basically meet the requirements of clinical application in neurointerventional surgery.

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

PubMed Central

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

The Johns Hopkins model of psychological first aid (RAPID-PFA): curriculum development and content validation.

PubMed

Everly, George S; Barnett, Daniel J; Links, Jonathan M

2012-01-01

There appears to be virtual universal endorsement of the need for and value of acute "psychological first aid" (PFA) in the wake of trauma and disasters. In this paper, we describe the development of the curriculum for The Johns Hopkins RAPID-PFA model of psychological first aid. We employed an adaptation of the basic framework for the development of a clinical science as recommended by Millon which entailed: historical review, theoretical development, and content validation. The process of content validation of the RAPID-PFA curriculum entailed the assessment of attitudes (confidence in the application of PFA interventions, preparedness in the application of PFA); knowledge related to the application of immediate mental health interventions; and behavior (the ability to recognize clinical markers in the field as assessed via a videotape recognition exercise). Results of the content validation phase suggest the six-hour RAPID-PFA curriculum, initially based upon structural modeling analysis, can improve confidence in the application of PFA interventions, preparedness in the application of PFA, knowledge related to the application of immediate mental health interventions, and the ability to recognize clinical markers in the field as assessed via a videotape recognition exercise.

CaP CURE Initiatives and Projects

PubMed Central

Soule, Howard R

2003-01-01

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization’s Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE’s efforts have resulted in a significant increase in federal funding of prostate cancer research programs. PMID:16986049

Remote magnetic actuation using a clinical scale system

PubMed Central

Stehning, Christian; Gleich, Bernhard

2018-01-01

Remote magnetic manipulation is a powerful technique for controlling devices inside the human body. It enables actuation and locomotion of tethered and untethered objects without the need for a local power supply. In clinical applications, it is used for active steering of catheters in medical interventions such as cardiac ablation for arrhythmia treatment and for steering of camera pills in the gastro-intestinal tract for diagnostic video acquisition. For these applications, specialized clinical-scale field applicators have been developed, which are rather limited in terms of field strength and flexibility of field application. For a general-purpose field applicator, flexible field generation is required at high field strengths as well as high field gradients to enable the generation of both torques and forces on magnetic devices. To date, this requirement has only been met by small-scale experimental systems. We have built a highly versatile clinical-scale field applicator that enables the generation of strong magnetic fields as well as strong field gradients over a large workspace. We demonstrate the capabilities of this coil-based system by remote steering of magnetic drills through gel and tissue samples with high torques on well-defined curved trajectories. We also give initial proof that, when equipped with high frequency transmit-receive coils, the machine is capable of real-time magnetic particle imaging while retaining a clinical-scale bore size. Our findings open the door for image-guided radiation-free remote magnetic control of devices at the clinical scale, which may be useful in minimally invasive diagnostic and therapeutic medical interventions. PMID:29494647

Welcome to EDRN — EDRN Public Portal

Cancer.gov

The Early Detection Research Network (EDRN), an initiative of the National Cancer Institute (NCI), brings together dozens of institutions to help accelerate the translation of biomarker information into clinical applications and to evaluate new ways of testing cancer in its earliest stages and for cancer risk.

78 FR 63228 - Determination That Potassium Citrate, 10 Milliequivalents/Packet and 20 Milliequivalents/Packet...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain... mEq/packet and 20 mEq/packet, is the subject of NDA 19-647, held by Nova-K LLC, and initially...

Acoustic Droplet Vaporization in Biology and Medicine

PubMed Central

Pitt, William G.

2013-01-01

This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, and high intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has been explored in rodents and dogs and may be approaching clinical use. ADV for drug delivery is still in preclinical stages with initial applications to treat tumors in mice. Other techniques are still in preclinical studies but have potential for clinical use in specialty applications. Overall, ADV has a bright future in clinical application because the small size of nanodroplets greatly reduces the rate of clearance compared to larger contrast agent bubbles and yet provides the advantages of ultrasonographic contrast, acoustic cavitation, and nontoxicity of conventional perfluorocarbon contrast agent bubbles. PMID:24350267

Managing and Communicating Operational Workflow: Designing and Implementing an Electronic Outpatient Whiteboard.

PubMed

Steitz, Bryan D; Weinberg, Stuart T; Danciu, Ioana; Unertl, Kim M

2016-01-01

Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

PubMed

Lansky, Alexandra J; Messé, Steven R; Brickman, Adam M; Dwyer, Michael; Bart van der Worp, H; Lazar, Ronald M; Pietras, Cody G; Abrams, Kevin J; McFadden, Eugene; Petersen, Nils H; Browndyke, Jeffrey; Prendergast, Bernard; Ng, Vivian G; Cutlip, Donald E; Kapadia, Samir; Krucoff, Mitchell W; Linke, Axel; Scala Moy, Claudia; Schofer, Joachim; van Es, Gerrit-Anne; Virmani, Renu; Popma, Jeffrey; Parides, Michael K; Kodali, Susheel; Bilello, Michel; Zivadinov, Robert; Akar, Joseph; Furie, Karen L; Gress, Daryl; Voros, Szilard; Moses, Jeffrey; Greer, David; Forrest, John K; Holmes, David; Kappetein, Arie P; Mack, Michael; Baumbach, Andreas

2018-05-14

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

A regional assessment of information technology sophistication in Missouri nursing homes.

PubMed

Alexander, Gregory L; Madsen, Richard; Wakefield, Douglas

2010-08-01

To provide a state profile of information technology (IT) sophistication in Missouri nursing homes. Primary survey data were collected from December 2006 to August 2007. A descriptive, exploratory cross-sectional design was used to investigate dimensions of IT sophistication (technological, functional, and integration) related to resident care, clinical support, and administrative processes. Each dimension was used to describe the clinical domains and demographics (ownership, regional location, and bed size). The final sample included 185 nursing homes. A wide range of IT sophistication is being used in administrative and resident care management processes, but very little in clinical support activities. Evidence suggests nursing homes in Missouri are expanding use of IT beyond traditional administrative and billing applications to patient care and clinical applications. This trend is important to provide support for capabilities which have been implemented to achieve national initiatives for meaningful use of IT in health care settings.

Stem Cell Sciences plc.

PubMed

Daniels, Sebnem

2006-09-01

Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

Successes & Failures of Digital Libraries. Papers Presented at the Annual Clinic on Library Applications of Data Processing (35th, Champaign, Illinois, March 22-24, 1998).

ERIC Educational Resources Information Center

Harum, Susan, Ed.; Twidale, Michael, Ed.

This clinic's goal was to address questions arising during the process of transition from theory and research development to deployed useful and usable (and used) digital library systems. The idea was to use the Digital Libraries Initiative (DLI) based at the University of Illinois at Urbana-Champaign and entering its final year, as a detailed…

Clinical Transition Framework: Integrating Coaching Plans, Sampling, and Accountability in Clinical Practice Development.

PubMed

Boyer, Susan A; Mann-Salinas, Elizabeth A; Valdez-Delgado, Krystal K

The clinical transition framework (CTF) is a competency-based practice development system used by nursing professional development practitioners to support nurses' initial orientation or transition to a new specialty. The CTF is applicable for both new graduate and proficient nurses. The current framework and tools evolved from 18 years of performance improvement and research projects engaged in both acute and community care environments in urban and rural settings. This article shares core CTF concepts, a description of coaching plans, and a professional accountability statement as experienced within the framework.

Application of an Electronic Medical Record in Space Medicine

NASA Technical Reports Server (NTRS)

McGinnis, Patrick J.

2000-01-01

Electronic Medical Records (EMR) have been emerging over the past decade. Today, they are replacing the paper chart in clinics throughout the nation. Approximately three years ago, the NASA-JSC Flight Medicine Clinic initiated an assessment of the EMRs available on the market. This assessment included comparing these products with the particular scope of practice at JSC. In 1998, the Logician EMR from Medicalogic was selected for the JSC Flight Medicine Clinic. This presentation reviews the process of selection and implementation of the EMR into the unique practice of aerospace medicine at JSC.

Liberating the Oppressed: Research Knowledge Differentials and Ethical Investigation in Special Operations Forces Clinical Science.

PubMed

Kemplin, Kate Rocklein; Bowling, F Young

Special Operations Forces (SOF) medics do not have preparation in research knowledge that enables them to independently initiate or generate their own studies. Thus, medics rely on evidence generated by others, who are removed from medics' practice environment. Here, salient literature on research self-efficacy and the genesis of institutional review boards (IRBs) are reviewed and interpreted for contextual applications to medics' practice and initiation of studies. More publications delving into research methods are warranted to promote medics' participation and initiation of selfdirected scientific investigation, in collaboration with research scientists. 2017.

76 FR 57064 - National Institute on Aging; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute on Aging... personal privacy. Name of Committee: National Institute on Aging Initial Review Group, Clinical Aging... applications. Place: National Institute on Aging, Gateway Building, 7201 Wisconsin Avenue, Suite 2C212...

Implementation of Consolidated HIS: Improving Quality and Efficiency of Healthcare

PubMed Central

Choi, Jinwook; Seo, Jeong-Wook; Chung, Chun Kee; Kim, Kyung-Hwan; Kim, Ju Han; Kim, Jong Hyo; Chie, Eui Kyu; Cho, Hyun-Jai; Goo, Jin Mo; Lee, Hyuk-Joon; Wee, Won Ryang; Nam, Sang Mo; Lim, Mi-Sun; Kim, Young-Ah; Yang, Seung Hoon; Jo, Eun Mi; Hwang, Min-A; Kim, Wan Suk; Lee, Eun Hye; Choi, Su Hi

2010-01-01

Objectives Adoption of hospital information systems offers distinctive advantages in healthcare delivery. First, implementation of consolidated hospital information system in Seoul National University Hospital led to significant improvements in quality of healthcare and efficiency of hospital management. Methods The hospital information system in Seoul National University Hospital consists of component applications: clinical information systems, clinical research support systems, administrative information systems, management information systems, education support systems, and referral systems that operate to generate utmost performance when delivering healthcare services. Results Clinical information systems, which consist of such applications as electronic medical records, picture archiving and communication systems, primarily support clinical activities. Clinical research support system provides valuable resources supporting various aspects of clinical activities, ranging from management of clinical laboratory tests to establishing care-giving procedures. Conclusions Seoul National University Hospital strives to move its hospital information system to a whole new level, which enables customized healthcare service and fulfills individual requirements. The current information strategy is being formulated as an initial step of development, promoting the establishment of next-generation hospital information system. PMID:21818449

Ngi and Internet2: accelerating the creation of tomorrow's internet.

PubMed

Kratz, M; Ackerman, M; Hanss, T; Corbato, S

2001-01-01

Internet2 is a consortium of leading U.S. universities working in partnership with industry and the U.S. government's Next Generation Internet (NGI) initiative to develop a faster, more reliable Internet for research and education including enhanced, high-performance networking services and the advanced applications that are enabled by those services [1]. By facilitating and coordinating the development, deployment, operation, and technology transfer of advanced, network-based applications and network services, Internet2 and NGI are working together to fundamentally change the way scientists, engineers, clinicians, and others work together. [http://www.internet2.edu] The NGI Program has three tracks: research, network testbeds, and applications. The aim of the research track is to promote experimentation with the next generation of network technologies. The network testbed track aims to develop next generation network testbeds to connect universities and federal research institutions at speeds that are sufficient to demonstrate new technologies and support future research. The aim of the applications track is to demonstrate new applications, enabled by the NGI networks, to meet important national goals and missions [2]. [http://www.ngi.gov/] The Internet2/NGI backbone networks, Abilene and vBNS (very high performance Backbone Network Service), provide the basis of collaboration and development for a new breed of advanced medical applications. Academic medical centers leverage the resources available throughout the Internet2 high-performance networking community for high-capacity broadband and selectable quality of service to make effective use of national repositories. The Internet2 Health Sciences Initiative enables a new generation of emerging medical applications whose architecture and development have been restricted by or are beyond the constraints of traditional Internet environments. These initiatives facilitate a variety of activities to foster the development and deployment of emerging applications that meet the requirements of clinical practice, medical and related biological research, education, and medical awareness throughout the public sector. Medical applications that work with high performance networks and supercomputing capabilities offer exciting new solutions for the medical industry. Internet2 and NGI,strive to combine the expertise of their constituents to establish a distributed knowledge system for achieving innovation in research, teaching, learning, and clinical care.

Biothermal Model of Patient for Brain Hypothermia Treatment

NASA Astrophysics Data System (ADS)

Wakamatsu, Hidetoshi; Gaohua, Lu

A biothermal model of patient is proposed and verified for the brain hypothermia treatment, since the conventionally applied biothermal models are inappropriate for their unprecedented application. The model is constructed on the basis of the clinical practice of the pertinent therapy and characterized by the mathematical relation with variable ambient temperatures, in consideration of the clinical treatments such as the vital cardiopulmonary regulation. It has geometrically clear representation of multi-segmental core-shell structure, database of physiological and physical parameters with a systemic state equation setting the initial temperature of each compartment. Its step response gives the time constant about 3 hours in agreement with clinical knowledge. As for the essential property of the model, the dynamic temperature of its face-core compartment is realized, which corresponds to the tympanic membrane temperature measured under the practical anesthesia. From the various simulations consistent with the phenomena of clinical practice, it is concluded that the proposed model is appropriate for the theoretical analysis and clinical application to the brain hypothermia treatment.

Latest status of the clinical and industrial applications of cell sheet engineering and regenerative medicine.

PubMed

Egami, Mime; Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2014-01-01

Cell sheet engineering, which allows tissue engineering to be realized without the use of biodegradable scaffolds as an original approach, using a temperature-responsive intelligent surface, has been applied in regenerative medicine for various tissues, and a number of clinical studies have been already performed for life-threatening diseases. By using the results and findings obtained from the initial clinical studies, additional investigative clinical studies in several tissues with cell sheet engineering are currently in preparation stage. For treating many patients effectively by cell sheet engineering, an automated system integrating cell culture, cell-sheet fabrication, and layering is essential, and the system should include an advanced three-dimensional suspension cell culture system and an in vitro bioreactor system to scale up the production of cultured cells and fabricate thicker vascularized tissues. In this paper, cell sheet engineering, its clinical application, and further the authors' challenge to develop innovative cell culture systems under newly legislated regulatory platform in Japan are summarized and discussed.

Asthma in pregnancy: association between the Asthma Control Test and the Global Initiative for Asthma classification and comparisons with spirometry.

PubMed

de Araujo, Georgia Véras; Leite, Débora F B; Rizzo, José A; Sarinho, Emanuel S C

2016-08-01

The aim of this study was to identify a possible association between the assessment of clinical asthma control using the Asthma Control Test (ACT) and the Global Initiative for Asthma (GINA) classification and to perform comparisons with values of spirometry. Through this cross-sectional study, 103 pregnant women with asthma were assessed in the period from October 2010 to October 2013 in the asthma pregnancy clinic at the Clinical Hospital of the Federal University of Pernambuco. Questionnaires concerning the level of asthma control were administered using the Global Initiative for Asthma classification, the Asthma Control Test validated for asthmatic expectant mothers and spirometry; all three methods of assessing asthma control were performed during the same visit between the twenty-first and twenty-seventh weeks of pregnancy. There was a significant association between clinical asthma control assessment using the Asthma Control Test and the Global Initiative for Asthma classification (p<0.001). There were also significant associations between the results of the subjective instruments of asthma (the GINA classification and the ACT) and evidence of lung function by spirometry. This study shows that both the Global Initiative for Asthma classification and the Asthma Control Test can be used for asthmatic expectant mothers to assess the clinical control of asthma, especially at the end of the second trimester, which is assumed to be the period of worsening asthma exacerbations during pregnancy. We highlight the importance of the Asthma Control Test as a subjective instrument with easy application, easy interpretation and good reproducibility that does not require spirometry to assess the level of asthma control and can be used in the primary care of asthmatic expectant mothers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fluorescence In Situ Hybridization Probe Validation for Clinical Use.

PubMed

Gu, Jun; Smith, Janice L; Dowling, Patricia K

2017-01-01

In this chapter, we provide a systematic overview of the published guidelines and validation procedures for fluorescence in situ hybridization (FISH) probes for clinical diagnostic use. FISH probes-which are classified as molecular probes or analyte-specific reagents (ASRs)-have been extensively used in vitro for both clinical diagnosis and research. Most commercially available FISH probes in the United States are strictly regulated by the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), the Centers for Medicare & Medicaid Services (CMS) the Clinical Laboratory Improvement Amendments (CLIA), and the College of American Pathologists (CAP). Although home-brewed FISH probes-defined as probes made in-house or acquired from a source that does not supply them to other laboratories-are not regulated by these agencies, they too must undergo the same individual validation process prior to clinical use as their commercial counterparts. Validation of a FISH probe involves initial validation and ongoing verification of the test system. Initial validation includes assessment of a probe's technical specifications, establishment of its standard operational procedure (SOP), determination of its clinical sensitivity and specificity, development of its cutoff, baseline, and normal reference ranges, gathering of analytics, confirmation of its applicability to a specific research or clinical setting, testing of samples with or without the abnormalities that the probe is meant to detect, staff training, and report building. Ongoing verification of the test system involves testing additional normal and abnormal samples using the same method employed during the initial validation of the probe.

Comprehensive Psychopathological Assessment Based on the Association for Methodology and Documentation in Psychiatry (AMDP) System: Development, Methodological Foundation, Application in Clinical Routine, and Research.

PubMed

Stieglitz, Rolf-Dieter; Haug, Achim; Fähndrich, Erdmann; Rösler, Michael; Trabert, Wolfgang

2017-01-01

The documentation of psychopathology is core to the clinical practice of the psychiatrist and clinical psychologist. However, both in initial as well as further training and specialization in their fields, this particular aspect of their work receives scanty attention only. Yet, for the past 50 years, the Association for Methodology and Documentation in Psychiatry (AMDP) System has been in existence and available as a tool to serve precisely the purpose of offering a systematic introduction to the terminology and documentation of psychopathology. The motivation for its development was based on the need for an assessment procedure for the reliable documentation of the effectiveness of newly developed psychopharmacological substances. Subsequently, the AMDP-System began to be applied in the context of investigations into a number of methodological issues in psychiatry (e.g., the frequency and specificity of particular symptoms, the comparison of rating scales). The System then became increasingly important also in clinical practice and, today, represents the most used instrument for the documentation of psychopathology in the German-speaking countries of Europe. This paper intends to offer an overview of the AMDP-System, its origins, design, and functionality. After an initial account of the history and development of the AMDP-System, the discussion will in turn focus on the System's underlying methodological principles, the transfer of clinical skills and competencies in its practical application, and its use in research and clinical practice. Finally, potential future areas of development in relation to the AMDP-System are explored.

Comprehensive Psychopathological Assessment Based on the Association for Methodology and Documentation in Psychiatry (AMDP) System: Development, Methodological Foundation, Application in Clinical Routine, and Research

PubMed Central

Stieglitz, Rolf-Dieter; Haug, Achim; Fähndrich, Erdmann; Rösler, Michael; Trabert, Wolfgang

2017-01-01

The documentation of psychopathology is core to the clinical practice of the psychiatrist and clinical psychologist. However, both in initial as well as further training and specialization in their fields, this particular aspect of their work receives scanty attention only. Yet, for the past 50 years, the Association for Methodology and Documentation in Psychiatry (AMDP) System has been in existence and available as a tool to serve precisely the purpose of offering a systematic introduction to the terminology and documentation of psychopathology. The motivation for its development was based on the need for an assessment procedure for the reliable documentation of the effectiveness of newly developed psychopharmacological substances. Subsequently, the AMDP-System began to be applied in the context of investigations into a number of methodological issues in psychiatry (e.g., the frequency and specificity of particular symptoms, the comparison of rating scales). The System then became increasingly important also in clinical practice and, today, represents the most used instrument for the documentation of psychopathology in the German-speaking countries of Europe. This paper intends to offer an overview of the AMDP-System, its origins, design, and functionality. After an initial account of the history and development of the AMDP-System, the discussion will in turn focus on the System’s underlying methodological principles, the transfer of clinical skills and competencies in its practical application, and its use in research and clinical practice. Finally, potential future areas of development in relation to the AMDP-System are explored. PMID:28439242

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

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

Hoffman, D; Nair, C Kumaran; Wright, C

2016-06-15

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generatedmore » for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and investigate other cross-platform treatment delivery options.« less

Secondary Use of Patients’ Electronic Records (SUPER): An Approach for Meeting Specific Data Needs of Clinical and Translational Researchers

PubMed Central

Sholle, Evan T.; Kabariti, Joseph; Johnson, Stephen B.; Leonard, John P.; Pathak, Jyotishman; Varughese, Vinay I.; Cole, Curtis L.; Campion, Thomas R.

2017-01-01

Academic medical centers commonly approach secondary use of electronic health record (EHR) data by implementing centralized clinical data warehouses (CDWs). However, CDWs require extensive resources to model data dimensions and harmonize clinical terminology, which can hinder effective support of the specific and varied data needs of investigators. We hypothesized that an approach that aggregates raw data from source systems, ignores initial modeling typical of CDWs, and transforms raw data for specific research purposes would meet investigator needs. The approach has successfully enabled multiple tools that provide utility to the institutional research enterprise. To our knowledge, this is the first complete description of a methodology for electronic patient data acquisition and provisioning that ignores data harmonization at the time of initial storage in favor of downstream transformation to address specific research questions and applications. PMID:29854228

Dental Cements for Luting and Bonding Restorations: Self-Adhesive Resin Cements.

PubMed

Manso, Adriana P; Carvalho, Ricardo M

2017-10-01

Self-adhesive resin cements combine easy application of conventional luting materials with improved mechanical properties and bonding capability of resin cements. The presence of functional acidic monomers, dual cure setting mechanism, and fillers capable of neutralizing the initial low pH of the cement are essential elements of the material and should be understood when selecting the ideal luting material for each clinical situation. This article addresses the most relevant aspects of self-adhesive resin cements and their potential impact on clinical performance. Although few clinical studies are available to establish solid clinical evidence, the information presented provides clinical guidance in the dynamic environment of material development. Copyright © 2017 Elsevier Inc. All rights reserved.

Computer-aided navigation in dental implantology: 7 years of clinical experience.

PubMed

Ewers, Rolf; Schicho, Kurt; Truppe, Michael; Seemann, Rudolf; Reichwein, Astrid; Figl, Michael; Wagner, Arne

2004-03-01

This long-term study gives a review over 7 years of research, development, and routine clinical application of computer-aided navigation technology in dental implantology. Benefits and disadvantages of up-to-date technologies are discussed. In the course of the current advancement, various hardware and software configurations are used. In the initial phase, universally applicable navigation software is adapted for implantology. Since 2001, a special software module for dental implantology is available. Preoperative planning is performed on the basis of prosthetic aspects and requirements. In clinical routine use, patient and drill positions are intraoperatively registered by means of optoelectronic tracking systems; during preclinical tests, electromagnetic trackers are also used. In 7 years (1995 to 2002), 55 patients with 327 dental implants were successfully positioned with computer-aided navigation technology. The mean number of implants per patient was 6 (minimum, 1; maximum, 11). No complications were observed; the preoperative planning could be exactly realized. The average expenditure of time for the preparation of a surgical intervention with navigation decreased from 2 to 3 days in the initial phase to one-half day in clinical routine use with software that is optimized for dental implantology. The use of computer-aided navigation technology can contribute to considerable quality improvement. Preoperative planning is exactly realized and intraoperative safety is increased, because damage to nerves or neighboring teeth can be avoided.

Evolving technologies drive the new roles of Biomedical Engineering.

PubMed

Frisch, P H; St Germain, J; Lui, W

2008-01-01

Rapidly changing technology coupled with the financial impact of organized health care, has required hospital Biomedical Engineering organizations to augment their traditional operational and business models to increase their role in developing enhanced clinical applications utilizing new and evolving technologies. The deployment of these technology based applications has required Biomedical Engineering organizations to re-organize to optimize the manner in which they provide and manage services. Memorial Sloan-Kettering Cancer Center has implemented a strategy to explore evolving technologies integrating them into enhanced clinical applications while optimally utilizing the expertise of the traditional Biomedical Engineering component (Clinical Engineering) to provide expanded support in technology / equipment management, device repair, preventive maintenance and integration with legacy clinical systems. Specifically, Biomedical Engineering is an integral component of the Medical Physics Department which provides comprehensive and integrated support to the Center in advanced physical, technical and engineering technology. This organizational structure emphasizes the integration and collaboration between a spectrum of technical expertise for clinical support and equipment management roles. The high cost of clinical equipment purchases coupled with the increasing cost of service has driven equipment management responsibilities to include significant business and financial aspects to provide a cost effective service model. This case study details the dynamics of these expanded roles, future initiatives and benefits for Biomedical Engineering and Memorial Sloan Kettering Cancer Center.

Systematization of Nursing Care in undergraduate training: the perspective of Complex Thinking.

PubMed

da Silva, Josilaine Porfírio; Garanhani, Mara Lucia; Peres, Aida Maris

2015-01-01

to evaluate the clinical applicability of outcomes, according to the Nursing Outcomes Classification (NOC) in the evolution of orthopedic patients with Impaired Physical Mobility longitudinal study conducted in 2012 in a university hospital, with 21 patients undergoing Total Hip Arthroplasty, evaluated daily by pairs of trained data collectors. Data were collected using an instrument containing five Nursing Outcomes, 16 clinical indicators and a five point Likert scale, and statistically analyzed. The outcomes Body Positioning: self-initiated, Mobility, Knowledge: prescribed activity, and Fall Prevention Behavior presented significant increases in mean scores when comparing the first and final evaluations (p<0.001) and (p=0.035). the use of the NOC outcomes makes it possible to demonstrate the clinical progression of orthopedic patients with Impaired Physical Mobility, as well as its applicability in this context.

Comparison of mechanical and biological properties of zirconia and titanium alloy orthodontic micro-implants.

PubMed

Choi, Hae Won; Park, Young Seok; Chung, Shin Hye; Jung, Min Ho; Moon, Won; Rhee, Sang Hoon

2017-07-01

The aim of this study was to compare the initial stability as insertion and removal torque and the clinical applicability of novel orthodontic zirconia micro-implants made using a powder injection molding (PIM) technique with those parameters in conventional titanium micro-implants. Sixty zirconia and 60 titanium micro-implants of similar design (diameter, 1.6 mm; length, 8.0 mm) were inserted perpendicularly in solid polyurethane foam with varying densities of 20 pounds per cubic foot (pcf), 30 pcf, and 40 pcf. Primary stability was measured as maximum insertion torque (MIT) and maximum removal torque (MRT). To investigate clinical applicability, compressive and tensile forces were recorded at 0.01, 0.02, and 0.03 mm displacement of the implants at angles of 0°, 10°, 20°, 30°, and 40°. The biocompatibility of zirconia micro-implants was assessed via an experimental animal study. There were no statistically significant differences between zirconia micro-implants and titanium alloy implants with regard to MIT, MRT, or the amount of movement in the angulated lateral displacement test. As angulation increased, the mean compressive and tensile forces required to displace both types of micro-implants increased substantially at all distances. The average bone-to-implant contact ratio of prototype zirconia micro-implants was 56.88 ± 6.72%. Zirconia micro-implants showed initial stability and clinical applicability for diverse orthodontic treatments comparable to that of titanium micro-implants under compressive and tensile forces.

[Understanding the advantages and disadvantages of femtosecond laser comprehensive applications in ophthalmology].

PubMed

Xie, Li-xin; Gao, Hua

2013-04-01

The femtosecond (FS) laser is a novel laser technology, and is approved clinical application by FDA in 2000. FS laser initially mainly used in corneal refractive surgery to replace the mechanical microkeratome. Since the accuracy and controllability of the FS laser is very high, it shows superiority in the field of corneal refractive surgery. And with the development of the relative hard and software, FS laser is began to used in other fields of ophthalmology, such as corneal transplants, cataract surgery, as well as assisted diagnosis et al., although still have some limitations, the preliminary clinical results have been shown a very good prospects in the ophthalmology fields. Therefore, we reviewed the alternative applications, challenges and limitations, research direction in the future of FS laser, so that provide a reference and revelations for the peers.

Potential Applications of the National Institute of Mental Health's Research Domain Criteria (RDoC) to Clinical Psychiatric Practice: How RDoC Might Be Used in Assessment, Diagnostic Processes, Case Formulation, Treatment Planning, and Clinical Notes.

PubMed

Yager, Joel; Feinstein, Robert E

2017-04-01

Offering a new framework for understanding and studying basic dimensions of normal and abnormal human functioning and mental disorders, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project in which a series of higher order domains, representing major systems of emotion, cognition, motivation, and social behavior, and their constituent operationally defined constructs serve as organizing templates for further research and inquiry, eg, to discover validated biomarkers and endophenotypes. Cutting across traditional DSM diagnoses, the domains are defined as Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Systems for Social Processes, and Arousal/Regulatory Systems. To inform educators, trainees, and practitioners about RDoC, alert them to potential practical applications, and encourage their broad exploration in clinical settings, this article reviews the RDoC domains and their subsystem constructs with regard to potential current clinical considerations and applications. We describe ways in which the RDoC domains and constructs offer transdiagnostic frameworks for complementing traditional practice; suggest clinical questions to help elucidate salient information; and, translating RDoC domains and constructs headings into clinically friendly language, offer a template for the psychiatric review of systems that can serve in clinical notes. © Copyright 2017 Physicians Postgraduate Press, Inc.

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

PubMed Central

Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

2016-01-01

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia. PMID:27242415

Managing and Communicating Operational Workflow

PubMed Central

Weinberg, Stuart T.; Danciu, Ioana; Unertl, Kim M.

2016-01-01

Summary Background Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. Objective To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). Methods The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. Results The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. Conclusions The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings. PMID:27081407

[Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

PubMed

Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

2011-12-27

To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

What strategy should France implement for H2020?

PubMed

Dhainaut, Jean-François; Diebolt, Vincent; Pouletty-Lefèbvre, Brigitte; Baker, Angela; Bassompierre, François; Borel, Thomas; Braunstein, David; Demotes, Jacques; François, Bruno; Huet, Stéphane; Micallef, Joëlle; Misse, Christophe; Molon, Annamaria; Rascol, Olivier; Ravoire, Sophie; Schwartz, Bertrand; Donne, Nathalie; Donne, Nathalie; Fusaï, Guillaume; Pouletty, Philippe; Vicaut, Eric

2015-01-01

The initiation of Horizon 2020--the European Union's 8th Framework Programme for Research and Innovation, allotted a budget of 79 billion euros--provides an opportunity to review France's participation in previous Framework Programmes. Indeed, French participation does not match either its scientific importance or its financial investment. While France contributed 16.5 to 17% of the EU's 7th Framework Programme research budget, its return through the funding of coordinated projects in which French teams are participating stands at around 12.5 to 13%, a shortfall of 600 million euros. Although the situation depends on the type of activity, French participation in clinical research appears to be smaller than that of its neighbours, with fewer responses to European calls for proposals. While France has many assets, which include the assured funding of clinical research, structured thematic networks and the initiation of major national programmes, it suffers from the dilution of resources due to France's regional development policy, the lack of multidisciplinarity and the ignorance of both the medical and scientific community and the institutions to which they belong as to how Horizon 2020 actually works. We propose three types of strategy to encourage proposals for coordinated clinical research projects or projects involving French teams, and to help in the drawing up of applications: Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. Recognise the value of European actions to influence the European landscape and change mentalities. Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application. • Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. • Recognise the value of European actions to influence the European landscape and change mentalities. • Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Challenges and Opportunities for Quantitative Clinical Pharmacology in Cancer Immunotherapy: Something Old, Something New, Something Borrowed, and Something Blue.

PubMed

Stroh, M; Carlile, D J; Li, C-C; Wagg, J; Ribba, B; Ramanujan, S; Jin, J; Xu, J; Charoin, J-E; Xhu, Z-X; Morcos, P N; Davis, J D; Phipps, A

2015-09-01

Cancer immunotherapy (CIT) initiates or enhances the host immune response against cancer. Following decades of development, patients with previously few therapeutic options may now benefit from CIT. Although the quantitative clinical pharmacology (qCP) of previous classes of anticancer drugs has matured during this time, application to CIT may not be straightforward since CIT acts via the immune system. Here we discuss where qCP approaches might best borrow or start anew for CIT.

International Standardization of the Clinical Dosimetry of Beta Radiation Brachytherapy Sources: Progress of an ISO Standard

NASA Astrophysics Data System (ADS)

Soares, Christopher

2006-03-01

In 2004 a new work item proposal (NWIP) was accepted by the International Organization for Standardization (ISO) Technical Committee 85 (TC85 -- Nuclear Energy), Subcommittee 2 (Radiation Protection) for the development of a standard for the clinical dosimetry of beta radiation sources used for brachytherapy. To develop this standard, a new Working Group (WG 22 - Ionizing Radiation Dosimetry and Protocols in Medical Applications) was formed. The standard is based on the work of an ad-hoc working group initiated by the Dosimetry task group of the Deutsches Insitiut für Normung (DIN). Initially the work was geared mainly towards the needs of intravascular brachytherapy, but with the decline of this application, more focus has been placed on the challenges of accurate dosimetry for the concave eye plaques used to treat ocular melanoma. Guidance is given for dosimetry formalisms, reference data to be used, calibrations, measurement methods, modeling, uncertainty determinations, treatment planning and reporting, and clinical quality control. The document is currently undergoing review by the ISO member bodies for acceptance as a Committee Draft (CD) with publication of the final standard expected by 2007. There are opportunities for other ISO standards for medical dosimetry within the framework of WG22.

Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

NASA Astrophysics Data System (ADS)

Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

2009-02-01

Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.

Viral mHealth​

PubMed Central

Fölster, Stefan

2017-01-01

ABSTRACT Thousands of mHealth applications are developed every year, but few of these spread or ‘go viral’. Even clinical applications that provide health benefits and social value often linger after an initial pilot phase. An examination of common hindrances in low-income countries suggests that more subsidies and education of health care personnel are insufficient solutions. Instead we propose better a priori screening of mHealth applications based on four criteria that may largely determine whether an mHealth application will spread. Further, we illustrate how using these criteria forms a good basis for involving ‘impact investors’ in the development of mHealth applications. This can reduce risks for public health care providers and increase the likelihood of success. PMID:28838304

Screening for important unwarranted variation in clinical practice: a triple-test of processes of care, costs and patient outcomes.

PubMed

Partington, Andrew; Chew, Derek P; Ben-Tovim, David; Horsfall, Matthew; Hakendorf, Paul; Karnon, Jonathan

2017-03-01

Objective Unwarranted variation in clinical practice is a target for quality improvement in health care, but there is no consensus on how to identify such variation or to assess the potential value of initiatives to improve quality in these areas. This study illustrates the use of a triple test, namely the comparative analysis of processes of care, costs and outcomes, to identify and assess the burden of unwarranted variation in clinical practice. Methods Routinely collected hospital and mortality data were linked for patients presenting with symptoms suggestive of acute coronary syndromes at the emergency departments of four public hospitals in South Australia. Multiple regression models analysed variation in re-admissions and mortality at 30 days and 12 months, patient costs and multiple process indicators. Results After casemix adjustment, an outlier hospital with statistically significantly poorer outcomes and higher costs was identified. Key process indicators included admission patterns, use of invasive diagnostic procedures and length of stay. Performance varied according to patients' presenting characteristics and time of presentation. Conclusions The joint analysis of processes, outcomes and costs as alternative measures of performance inform the importance of reducing variation in clinical practice, as well as identifying specific targets for quality improvement along clinical pathways. Such analyses could be undertaken across a wide range of clinical areas to inform the potential value and prioritisation of quality improvement initiatives. What is known about the topic? Variation in clinical practice is a long-standing issue that has been analysed from many different perspectives. It is neither possible nor desirable to address all forms of variation in clinical practice: the focus should be on identifying important unwarranted variation to inform actions to reduce variation and improve quality. What does this paper add? This paper proposes the comparative analysis of processes of care, costs and outcomes for patients with similar diagnoses presenting at alternative hospitals, using linked, routinely collected data. This triple test of performance indicators extracts maximum value from routine data to identify priority areas for quality improvement to reduce important and unwarranted variations in clinical practice. What are the implications for practitioners? The proposed analyses need to be applied to other clinical areas to demonstrate the general application of the methods. The outputs can then be validated through the application of quality improvement initiatives in clinical areas with identified important and unwarranted variation. Validated frameworks for the comparative analysis of clinical practice provide an efficient approach to valuing and prioritising actions to improve health service quality.

Statistical controversies in clinical research: an initial evaluation of a surrogate end point using a single randomized clinical trial and the Prentice criteria

PubMed Central

Heller, G.

2015-01-01

Surrogate end point research has grown in recent years with the increasing development and usage of biomarkers in clinical research. Surrogacy analysis is derived through randomized clinical trial data and it is carried out at the individual level and at the trial level. A common surrogate analysis at the individual level is the application of the Prentice criteria. An approach for the evaluation of the Prentice criteria is discussed, with a focus on its most difficult component, the determination of whether the treatment effect is captured by the surrogate. An interpretation of this criterion is illustrated using data from a randomized clinical trial in prostate cancer. PMID:26254442

Pragmatic Applications of RE-AIM for Health Care Initiatives in Community and Clinical Settings

PubMed Central

Estabrooks, Paul E.

2018-01-01

The RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) planning and evaluation framework has been applied broadly, but users often have difficulty in applying the model because of data collection needs across multiple domains and sources. Questions in the more common “who, what, where, how, when, and why” format may be an effective guide to ensure that individual participants, organization staff, and the perspectives of the setting are considered in planning and evaluation. Such a format can also help users in typical community and clinical settings to identify which outcomes are most valued and to focus limited measurement resources. Translations of RE-AIM that are easy to understand and apply are needed for application in real-world community and clinical settings where research and evaluation resources are limited. The purpose of this article is to provide simplified, pragmatic, user-centered and stakeholder-centered recommendations to increase the use of RE-AIM in community and clinical settings and in translational research. PMID:29300695

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

PubMed

Lansky, Alexandra J; Messé, Steven R; Brickman, Adam M; Dwyer, Michael; van der Worp, H Bart; Lazar, Ronald M; Pietras, Cody G; Abrams, Kevin J; McFadden, Eugene; Petersen, Nils H; Browndyke, Jeffrey; Prendergast, Bernard; Ng, Vivian G; Cutlip, Donald E; Kapadia, Samir; Krucoff, Mitchell W; Linke, Axel; Moy, Claudia Scala; Schofer, Joachim; van Es, Gerrit-Anne; Virmani, Renu; Popma, Jeffrey; Parides, Michael K; Kodali, Susheel; Bilello, Michel; Zivadinov, Robert; Akar, Joseph; Furie, Karen L; Gress, Daryl; Voros, Szilard; Moses, Jeffrey; Greer, David; Forrest, John K; Holmes, David; Kappetein, Arie P; Mack, Michael; Baumbach, Andreas

2017-02-14

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Deep learning applications in ophthalmology.

PubMed

Rahimy, Ehsan

2018-05-01

To describe the emerging applications of deep learning in ophthalmology. Recent studies have shown that various deep learning models are capable of detecting and diagnosing various diseases afflicting the posterior segment of the eye with high accuracy. Most of the initial studies have centered around detection of referable diabetic retinopathy, age-related macular degeneration, and glaucoma. Deep learning has shown promising results in automated image analysis of fundus photographs and optical coherence tomography images. Additional testing and research is required to clinically validate this technology.

Digital stethoscope: technology update.

PubMed

Swarup, Supreeya; Makaryus, Amgad N

2018-01-01

Cardiovascular disease (CVD) is recognized as the leading cause of mortality throughout the world. About one-third of global mortality is attributable to CVD. In addition to clinical presentation, specific clinical exam findings can assist in treating and preventing CVD. CVD may initially manifest as pulmonary pathology, and thus, accurate cardiopulmonary auscultation is paramount to establishing accurate diagnosis. One of the most powerful tools available to physicians is the stethoscope. The stethoscope first emerged in the year 1818, invented by a French physician, René Laennec. Since then, the initial modest monaural wooden tube has evolved into a sophisticated digital device. This paper provides an analysis of the evolution of the stethoscope as well as highlights the advancement made by the modern digital stethoscope including the application of this tool in advancing care for patients suffering from CVD.

Standardizing patient-reported outcomes assessment in cancer clinical trials: a patient-reported outcomes measurement information system initiative.

PubMed

Garcia, Sofia F; Cella, David; Clauser, Steven B; Flynn, Kathryn E; Lad, Thomas; Lai, Jin-Shei; Reeve, Bryce B; Smith, Ashley Wilder; Stone, Arthur A; Weinfurt, Kevin

2007-11-10

Patient-reported outcomes (PROs), such as symptom scales or more broad-based health-related quality-of-life measures, play an important role in oncology clinical trials. They frequently are used to help evaluate cancer treatments, as well as for supportive and palliative oncology care. To be most beneficial, these PROs must be relevant to patients and clinicians, valid, and easily understood and interpreted. The Patient-Reported Outcomes Measurement Information System (PROMIS) Network, part of the National Institutes of Health Roadmap Initiative, aims to improve appreciably how PROs are selected and assessed in clinical research, including clinical trials. PROMIS is establishing a publicly available resource of standardized, accurate, and efficient PRO measures of major self-reported health domains (eg, pain, fatigue, emotional distress, physical function, social function) that are relevant across chronic illnesses including cancer. PROMIS is also developing measures of self-reported health domains specifically targeted to cancer, such as sleep/wake function, sexual function, cognitive function, and the psychosocial impacts of the illness experience (ie, stress response and coping; shifts in self-concept, social interactions, and spirituality). We outline the qualitative and quantitative methods by which PROMIS measures are being developed and adapted for use in clinical oncology research. At the core of this activity is the formation and application of item banks using item response theory modeling. We also present our work in the fatigue domain, including a short-form measure, as a sample of PROMIS methodology and work to date. Plans for future validation and application of PROMIS measures are discussed.

[Vaccinations in psychiatry].

PubMed

Dols, A; van den Brink, W; Eikelenboom, P

2009-01-01

Vaccination is a well-known strategy for preventing and treating infections. The purpose of vaccinations is to render antigens harmless by the production of antibodies. In psychiatry there are also situations where antigens that have been introduced from outside or that have developed during an illness constitute a threat to the patient's health. To explore the possible applications of vaccination in psychiatry. In this article we discuss the applications of vaccination in psychiatry on the basis of two examples. In addiction research, trials are being conducted with antibodies against substances such as cocaine and nicotine in order to prevent such addictive substances from crossing the blood-brain barrier and thereby initiating their rewarding effect. The first clinical results are very promising, but vaccines have not yet been applied clinically. With regard to Alzheimer's disease it has been shown by means of animal models that specific antibodies can prevent AlphaBeta aggregation and dissolve existing aggregates. On the basis of these findings various large-scale clinical trials have begun in order to study immunotherapy for Alzheimer's disease. The first clinical results showed little neurocognitive effects. A wellknown study had to be terminated because of side-effects of the therapy, in the form of neuro-encephalitis. Our tentative conclusion is that the clinical application of immunotherapy in psychiatry still has its limitations, but is indeed promising.

Universal suprapubic approach for complete mesocolic excision and central vascular ligation using the da Vinci Xi® system: from cadaveric models to clinical cases.

PubMed

Yeo, Shen Ann; Noh, Gyoung Tae; Han, Jeong Hee; Cheong, Chinock; Stein, Hubert; Kerdok, Amy; Min, Byung Soh

2017-12-01

There has been little enthusiasm for performing robotic colectomy for colon cancer in recent years due to multiple factors, one being that the previous robotic systems such as the da Vinci Si ® (dVSi) were poorly designed for multi-quadrant surgery. The new da Vinci Xi ® (dVXi) system enables colectomy with central mesocolic excision to be performed easily in a single docking procedure. We developed a universal port placement strategy to allow right and left hemicolectomies to be performed via a suprapubic approach and a Pfannensteil extraction site. This proof of concept paper describes the development and subsequent clinical application of this setup. After extensive training on the dVXi system concepts in collaboration with clinical development engineers, we developed a port placement strategy which was tested and adapted after performing experimental surgery in three cadaveric models. Subsequently our port placement was used for two clinical cases of suprapubic right and left hemicolectomy. With some modifications of port placements after the initial cadaveric colectomies, we have developed a potentially universal suprapubic port placement strategy for robotic colectomy with complete mesocolic excision and central vascular ligation using the dVXi robotic system. This port placement strategy was applied successfully in our first two clinical cases. Based on our cadaveric laboratory as well as our initial clinical application, the suprapubic port placement strategy for the dVXi system with its improved features over the dVSi can feasibly perform right and left hemicolectomy with complete mesocolic excision and central vascular ligation. Further studies will be required to establish efficacy as well as safety profile of these procedures.

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

Systematization of Nursing Care in undergraduate training: the perspective of Complex Thinking 1

PubMed Central

da Silva, Josilaine Porfírio; Garanhani, Mara Lucia; Peres, Aida Maris

2015-01-01

AIM: to evaluate the clinical applicability of outcomes, according to the Nursing Outcomes Classification (NOC) in the evolution of orthopedic patients with Impaired Physical Mobility METHOD: longitudinal study conducted in 2012 in a university hospital, with 21 patients undergoing Total Hip Arthroplasty, evaluated daily by pairs of trained data collectors. Data were collected using an instrument containing five Nursing Outcomes, 16 clinical indicators and a five point Likert scale, and statistically analyzed. RESULTS: The outcomes Body Positioning: self-initiated, Mobility, Knowledge: prescribed activity, and Fall Prevention Behavior presented significant increases in mean scores when comparing the first and final evaluations (p<0.001) and (p=0.035). CONCLUSION: the use of the NOC outcomes makes it possible to demonstrate the clinical progression of orthopedic patients with Impaired Physical Mobility, as well as its applicability in this context. PMID:25806632

Femtosecond lasers in ophthalmology: clinical applications in anterior segment surgery

NASA Astrophysics Data System (ADS)

Juhasz, Tibor; Nagy, Zoltan; Sarayba, Melvin; Kurtz, Ronald M.

2010-02-01

The human eye is a favored target for laser surgery due to its accessibility via the optically transparent ocular tissue. Femtosecond lasers with confined tissue effects and minimized collateral tissue damage are primary candidates for high precision intraocular surgery. The advent of compact diode-pumped femtosecond lasers, coupled with computer controlled beam delivery devices, enabled the development of high precision femtosecond laser for ophthalmic surgery. In this article, anterior segment femtosecond laser applications currently in clinical practice and investigation are reviewed. Corneal procedures evolved first and remain dominant due to easy targeting referenced from a contact surface, such as applanation lenses placed on the eye. Adding a high precision imaging technique, such as optical coherence tomography (OCT), can enable accurate targeting of tissue beyond the cornea, such as the crystalline lens. Initial clinical results of femtosecond laser cataract surgery are discussed in detail in the latter portion part of the article.

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

Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.

Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is an imperative goal for the field of medicine. While mass spectrometry (MS)-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry (IMS) separations [1, 2] with liquid chromatography (LC) andmore » MS to dramatically increase measurement sensitivity and throughput, further enabling future MS-based clinical applications. An initial application of the LC-IMS-MS platform for the analysis of blood serum samples from stratified post-liver transplant patients with recurrent fibrosis progression illustrates its potential utility for disease characterization and use in personalized medicine [3, 4].« less

Fundamental principles of writing a successful grant proposal.

PubMed

Chung, Kevin C; Shauver, Melissa J

2008-04-01

It is important for the field of hand surgery to develop a new generation of surgeon-scientists who can produce high-impact studies to raise the profile of this specialty. To this end, organizations such as the American Society for Surgery of the Hand have initiated programs to promote multicenter clinical research that can be competitive for fiscal support from the National Institutes of Health and other funding agencies. Crafting a well-structured grant proposal is critical to securing adequate funding to investigate the many clinical and basic science questions in hand surgery. In this article, we present the key elements of a successful grant proposal to help potential applicants to navigate the complex pathways in the grant application process.

Fundamental Principles of Writing a Successful Grant Proposal

PubMed Central

Chung, Kevin C.; Shauver, Melissa J.

2015-01-01

It is important for the field of hand surgery to develop a new generation of surgeon-scientists who can produce high impact studies to raise the profile of this specialty. To this end, organizations such as the American Society for Surgery of the Hand have initiated programs to promote multicenter clinical research that can be competitive for fiscal support from the National Institutes of Health and other funding agencies. Crafting a well-structured grant proposal is critical to securing adequate funding to investigate the many ambitious clinical and basic science projects in hand surgery. In this paper, we present the key elements to a successful grant proposal to help potential applicants to navigate the complex pathways in the grant application process. PMID:18406962

Telehealth on advanced networks.

PubMed

Wilson, Laurence S; Stevenson, Duncan R; Cregan, Patrick

2010-01-01

We address advanced Internet for complex telehealth applications by reviewing four hospital-based broadband telehealth projects and identifying common threads. These projects were conducted in Australia under a 6-year research project on broadband Internet applications. Each project addressed specific clinical needs and its development was guided by the clinicians involved. Each project was trialed in the field and evaluated against the initial requirements. The four projects covered remote management of a resuscitation team in a district hospital, remote guidance and interpretation of echocardiography, virtual-reality-based instructor-student surgical training, and postoperative outpatient consultations following pediatric surgery. Each was characterized by a high level of interpersonal communication, a high level of clinical expertise, and multiple participants. Each made use of multiple high-quality video and audio links and shared real-time access to clinical data. Four common threads were observed. Each application provided a high level of usability and task focus because the design and use of broadband capability was aimed directly to meet the clinicians' needs. Each used the media quality available over broadband to convey words, gestures, body movements, and facial expressions to support communication and a sense of presence among the participants. Each required a complex information space shared among the participants, including real-time access to stored patient data and real-time interactive access to the patients themselves. Finally, each application supported the social and organizational aspects of their healthcare focus, creating and maintaining relationships between the various participants, and this was done by placing the telehealth application into a wider functioning clinical context. These findings provide evidence for a significantly enhanced role for appropriate telemedicine systems running on advanced networks, in a wider range of clinical applications, more deeply integrated into healthcare systems.

The James Blundell Award Lecture 2006: transfusion and the treatment of haemorrhage: past, present and future.

PubMed

Dzik, W H

2007-10-01

In the early years of the 19th century, James Blundell reported in the Lancet the first clinical application of blood transfusion for the treatment of haemorrhage. Although these initial experiments may appear to us to have burst upon the medical world, Blundell had in fact done a decade of pre clinical research using animal models to establish principles to be brought to the clinic. His pivotal pre clinical experiments and the insights he gained are described in detail. Today, blood transfusion remains the cornerstone of treatment for serious bleeding - not only to restore oxygen carrying capacity but also to improve haemostasis, arrest and prevent bleeding. However, the indications for the use of blood components to treat bleeding remain ill-defined. In particular, despite the enormous volumes of fresh frozen plasma (FFP) transfused worldwide, the evidence that commonly used coagulation tests are reliable guides to transfusion with FFP is scant. Recent laboratory and clinical studies provide insight into the weaknesses of current coagulation tests as a guide to blood management. In the future, the application of genomics to haemostasis will uncover genetic polymorphisms leading to improved diagnostics and more tailored medical therapeutics. Examples of the emerging use of clinical genomics are presented. Ultimately, the application of widescale genomics testing will refresh our understanding of human physiology and will reassert the importance of the individual in patient care.

The Effects of NBF Gingival Gel Application in the Treatment of the Erosive Lichen Planus: Case Report.

PubMed

Popovska, Mirjana; Fidovski, Jasmin; Mindova, Sonja; Dirjanska, Katerina; Ristoska, Stevica; Stefanovska, Emilija; Radojkova-Nikolovska, Vera; Mitic, Kristina; Rusevska, Biljana

2016-03-15

The therapy of erosive lichen planus (ELP) has been particular problem in the treatment of oral lesions. This case of ELP in male patient 29 years old was treated with topic application of the NBF gingival gel, three times a day after meal, previously rinsed with Clorhexidine gluconate 0.12%. After 5 days of treatment, initial improvements were recorded, and after two weeks of application of the NBF gingival gel we observed significant improvement. Clinical monitoring after the fifth day showed mild epithelialization of the eroded mucosa, yet still present erythematous base of the lesion. After the second week the erythema area was significantly reduced and the eroded surfaces of the mucosa were minimal, measured less than 0.5 mm. After the third week there were no erosions to detect on the oral mucosa, yet still present vague redness, which completely pulled after the fourth week. Treatment ended after the fifth week when the topical application of the NBF gingival gel was terminated, and therapy was done, and clinically achieved effects remained stable even after the third month of the treatment. Topic application of the NBF gingival gel with ELP patients showed positive clinical effects in relatively short time period.

The Effects of NBF Gingival Gel Application in the Treatment of the Erosive Lichen Planus: Case Report

PubMed Central

Popovska, Mirjana; Fidovski, Jasmin; Mindova, Sonja; Dirjanska, Katerina; Ristoska, Stevica; Stefanovska, Emilija; Radojkova-Nikolovska, Vera; Mitic, Kristina; Rusevska, Biljana

2016-01-01

The therapy of erosive lichen planus (ELP) has been particular problem in the treatment of oral lesions. This case of ELP in male patient 29 years old was treated with topic application of the NBF gingival gel, three times a day after meal, previously rinsed with Clorhexidine gluconate 0.12%. After 5 days of treatment, initial improvements were recorded, and after two weeks of application of the NBF gingival gel we observed significant improvement. Clinical monitoring after the fifth day showed mild epithelialization of the eroded mucosa, yet still present erythematous base of the lesion. After the second week the erythema area was significantly reduced and the eroded surfaces of the mucosa were minimal, measured less than 0.5 mm. After the third week there were no erosions to detect on the oral mucosa, yet still present vague redness, which completely pulled after the fourth week. Treatment ended after the fifth week when the topical application of the NBF gingival gel was terminated, and therapy was done, and clinically achieved effects remained stable even after the third month of the treatment. Topic application of the NBF gingival gel with ELP patients showed positive clinical effects in relatively short time period. PMID:27275352

Integrating dental screening and fluoride varnish application into a pediatric residency outpatient program: clinical and financial implications.

PubMed

Grant, Jonelle S; Roberts, Michael W; Brown, Wallace D; Quinoñez, Rocio B

2007-01-01

Delivery of preventive oral health services (POHS) has been embraced by many pediatric andfamily medical practices in North Carolina (NC). The outcome of implementing a state-wide Medicaid-supported oral health prevention initiative, "Into the Mouth of Babes Varnish and Screening Program (IMB), in an academic medical residency setting is described Retrospective chart audit of encounterforms and collection of administrative records related to POHS provided by pediatric medical residents for Medicaid recipients less than 3 years of age at the University of North Carolina pediatric continuity care clinic over 31 months were examined A total of 1,081 visits and 655 patients were documented during the study period accountingfor 36.6% of all children aged 6-36 months seen in the clinic during the period of this study. Thirty-eight percentof the patients received one or more IMB follow-up visits. Twenty-nine (4.4%) children were reported to have one or more carious teeth and 94 children (14.1%) were referred to a dentist. The IMB program provides an oral screening, parent oral health counseling and application of fluoride varnish to the teeth at the medical appointment by non-dental personnel. Following a cost/revenue analysis it was concluded that a preventive oral health initiative in an academic setting provides an additional access to oral health preventative services for underserved children and contributes to the financial viability of the clinic.

Therapeutic Application of Pluripotent Stem Cells: Challenges and Risks.

PubMed

Martin, Ulrich

2017-01-01

Stem-cell-based therapies are considered to be promising and innovative but complex approaches. Induced pluripotent stem cells (iPSCs) combine the advantages of adult stem cells with the hitherto unique characteristics of embryonic stem cells (ESCs). Major progress has already been achieved with regard to reprogramming technology, but also regarding targeted genome editing and scalable expansion and differentiation of iPSCs and ESCs, in some cases yielding highly enriched preparations of well-defined cell lineages at clinically required dimensions. It is noteworthy, however, that for many applications critical requirements such as the targeted specification into distinct cellular subpopulations and a proper cell maturation remain to be achieved. Moreover, current hurdles such as low survival rates and insufficient functional integration of cellular transplants remain to be overcome. Nevertheless, PSC technologies obviously have come of age and matured to a stage where various clinical applications of PSC-based cellular therapies have been initiated and are conducted.

Designing multifunctional quantum dots for bioimaging, detection, and drug delivery

PubMed Central

Zrazhevskiy, Pavel; Sena, Mark; Gao, Xiaohu

2011-01-01

The emerging field of bionanotechnology aims at revolutionizing biomedical research and clinical practice via introduction of nanoparticle-based tools, expanding capabilities of existing investigative, diagnostic, and therapeutic techniques as well as creating novel instruments and approaches for addressing challenges faced by medicine. Quantum dots (QDs), semiconductor nanoparticles with unique photo-physical properties, have become one of the dominant classes of imaging probes as well as universal platforms for engineering of multifunctional nanodevices. Possessing versatile surface chemistry and superior optical features, QDs have found initial use in a variety of in vitro and in vivo applications. However, careful engineering of QD probes guided by application-specific design criteria is becoming increasingly important for successful transition of this technology from proof-of-concept studies towards real-life clinical applications. This review outlines the major design principles and criteria, from general ones to application-specific, governing the engineering of novel QD probes satisfying the increasing demands and requirements of nanomedicine and discusses the future directions of QD-focused bionanotechnology research (critical review, 201 references). PMID:20697629

[Current Status and Future Perspectives of SCRUM-Japan].

PubMed

Ohtsu, Atsushi; Goto, Koichi; Yoshino, Takayuki; Okamoto, Wataru; Tsuchihara, Katsuya

2017-08-01

SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting patients to 35 sponsor-/investigator- initiated registration trials in collaboration with 15 pharmaceutical companies and 240 hospitals. During the first period between February 2015 and March 2017, a total of 4,805 patients have been enrolled. Genomic profiling of each cancer were analyzed and newdrug applications of label expansion are in preparation based on the results of several registration studies including investigator-initiated trial of vandetanib for RET fusion gene positive non-small cell lung cancer. In addition, on-time clinical-genome data sharing with industries and academic institutions and prospective cohort registry for new drug evaluation as a historical control data have already initiated, which will facilitate new agent development in Japan. In the second period started from April 2017, new studies using cutting-edge liquid biopsy and immune-genome panel for precision medi- cine will start soon. These efforts are attempted towards a leading group for innovative clinical/translations researches in the world.

SU-G-201-04: Can the Dynamic Library of Flap Applicators Replace Treatment Planning in Surface Brachytherapy?

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

Buzurovic, I; Devlin, P; Hansen, J

Purpose: Contemporary brachytherapy treatment planning systems-(TPS) include the applicator model libraries to improve digitization; however, the library of surface-flap-applicators-(SFA) is not incorporated into the commercial TPS. We propose the dynamic library-(DL) for SFA and investigate if such library can eliminate applicator reconstruction, source activation and dose normalization. Methods: DL was generated for the SFA using the C++class libraries of the Visualization Toolkit-(VTK) and Qt-application framework for complete abstraction of the graphical interface. DL was designed such that the user can initially choose the size of the applicator that corresponds to the one clinically placed to the patient. The virtual applicator-(VA)more » has an elastic property so that it can be registered to the clinical CT images with a real applicator-(RA) on it. The VA and RA matching is performed by adjusting the position and curvature of the VA. The VA does not elongate or change its size so each catheter could always be at a distance of 5mm from the skin and 10mm apart from the closest catheter maintaining the physical accuracy of the clinical setup. Upon the applicator placement, the dwell positions were automatically activated, and the dose is normalized to the prescription depth. The accuracy of source positioning was evaluated using various applicator sizes. Results: The accuracy of the applicator placement was in the sub-millimeter range. The time-study reveals that up to 50% of the planning time can be saved depending on the complexity of the clinical setup. Unlike in the classic approach, the planning time was not highly dependent on the applicator size. Conclusion: The practical benefits of the DL of the SFA were demonstrated. The time demanding planning processes can be partially automated. Consequently, the planner can dedicate effort to fine tuning, which can result in the improvement of the quality of treatment plans in surface brachytherapy.« less

Percutaneous management of postoperative bile leaks with an ethylene vinyl alcohol copolymer (Onyx).

PubMed

Uller, W; Müller-Wille, R; Loss, M; Hammer, S; Schleder, S; Goessmann, H; Wiggermann, P; Stroszczynski, C; Wohlgemuth, W A

2013-12-01

The management of postoperative bile leakage is challenging especially if the leak rises from the cut surface of the liver and endoscopic treatment fails. Percutaneous transhepatic treatment of bile leaks with biliary drainage is accepted but often requires long-term placement of the drains and is associated with treatment failures. This series evaluates selective embolization of bile ducts with an ethylene vinyl alcohol copolymer (Onyx) in patients with postoperative bile leaks as an alternative treatment option. Between January and September 2012, five consecutive patients with persistent postoperative bile leaks underwent percutaneous transhepatic Onyx application and were analyzed regarding procedural management, complications and success rates. The persistent bile leaks were situated at the cystic stump (after cholecystectomy, n = 2), at the cut surface of the liver (after extended liver resection, n = 2) and at the surface of the liver after surgical exploration and perihepatic abscess (n = 1). Bile drainage alone (endoscopic or percutaneous) failed in all patients and open redo-surgery was deemed potentially harmful. Bilomas were externally drained in all patients before Onyx application. For the closure of bile leaks, Onyx was injected through a microcatheter in a previously built coil nest to keep Onyx in place. All bile leaks were initially closed immediately. In the 2nd week after Onyx embolization, 2 patients showed recurrent small bile leaks without clinical symptoms. In the 4th week after Onyx application, all leaks were closed. No complications occurred. All leaking bile ducts were initially closed immediately after Onyx application. In the 2nd week after Onyx application, 2 patients showed small bile leaks without clinical symptoms. All leaks were closed in the 4th week after Onyx application. © Georg Thieme Verlag KG Stuttgart · New York.

Patient access and clinical efficiency improvement in a resident hospital-based women's medicine center clinic.

PubMed

Bush, Stephen H; Lao, Michael R; Simmons, Kathy L; Goode, Jeff H; Cunningham, Steve A; Calhoun, Byron C

2007-12-01

To apply the Six Sigma tools of Change Acceleration Process and Work-Out and to improve patient access in an outpatient clinic in a hospital-based residency training program. Observational study. Comparison of productivity in an obstetrics and gynecology clinic after implementation of the Six Sigma principles, with a comparable internal medicine clinic as a control group. Productivity from January 1 through December 31, 2005, was assessed in both clinics. After applying the Six Sigma tools to obstetrics and gynecology, outputs from both clinics from January 1 through December 31, 2006, were analyzed. Wait times for new obstetrical visits decreased from 38 to 8 days. The patient time spent in the clinic dropped from 3.2 to 1.5 hours. Initial gynecologic visits increased by 87% (from 453 to 850 per year), return gynecologic visits increased by 66% (from 1392 to 2311 per year), initial obstetrical visits increased by 55% (from 520 to 808 per year), repeat obstetrical visits increased by 45% (from 2239 to 3243 per year), and the mean patient satisfaction scores increased from 5.75 to 8.54 (on a 10-point scale). The gross clinic revenue increased by 73% in the first 6 months of 2006 over that of the previous year. By contrast, internal medicine patient wait times for new patients and for revisits, patient satisfaction scores, total number of clinic visits, and revenues remained unchanged. Application of the Six Sigma principles resulted in a team approach to solving the clinic's productivity issues.

Validation of elastic registration algorithms based on adaptive irregular grids for medical applications

NASA Astrophysics Data System (ADS)

Franz, Astrid; Carlsen, Ingwer C.; Renisch, Steffen; Wischmann, Hans-Aloys

2006-03-01

Elastic registration of medical images is an active field of current research. Registration algorithms have to be validated in order to show that they fulfill the requirements of a particular clinical application. Furthermore, validation strategies compare the performance of different registration algorithms and can hence judge which algorithm is best suited for a target application. In the literature, validation strategies for rigid registration algorithms have been analyzed. For a known ground truth they assess the displacement error at a few landmarks, which is not sufficient for elastic transformations described by a huge number of parameters. Hence we consider the displacement error averaged over all pixels in the whole image or in a region-of-interest of clinical relevance. Using artificially, but realistically deformed images of the application domain, we use this quality measure to analyze an elastic registration based on transformations defined on adaptive irregular grids for the following clinical applications: Magnetic Resonance (MR) images of freely moving joints for orthopedic investigations, thoracic Computed Tomography (CT) images for the detection of pulmonary embolisms, and transmission images as used for the attenuation correction and registration of independently acquired Positron Emission Tomography (PET) and CT images. The definition of a region-of-interest allows to restrict the analysis of the registration accuracy to clinically relevant image areas. The behaviour of the displacement error as a function of the number of transformation control points and their placement can be used for identifying the best strategy for the initial placement of the control points.

The evidence-based dentistry initiative at Baylor College of Dentistry.

PubMed

Jones, Daniel L; Hinton, Robert J; Dechow, Paul C; Abdellatif, Hoda; McCann, Ann L; Schneiderman, Emet D; D'Souza, Rena

2011-02-01

This report describes the impact of an R25 Oral Health Research Education Grant awarded to the Texas A&M Health Science Center-Baylor College of Dentistry (BCD) to promote the application of basic and clinical research findings to clinical training and encourage students to pursue careers in oral health research. At Baylor, the R25 grant supports a multi-pronged initiative that employs clinical research as a vehicle for acquainting both students and faculty with the tools of evidence-based dentistry (EBD). New coursework and experiences in all 4 years of the curriculum plus a variety of faculty development offerings are being used to achieve this goal. Progress on these fronts is reflected in a nascent "EBD culture" characterized by increasing participation and buy-in by students and faculty. The production of a new generation of dental graduates equipped with the EBD skill set as well as a growing nucleus of faculty who can model the importance of evidence-based practice is of paramount importance for the future of dentistry.

Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference.

PubMed

Murray, Patrick T; Mehta, Ravindra L; Shaw, Andrew; Ronco, Claudio; Endre, Zoltan; Kellum, John A; Chawla, Lakhmir S; Cruz, Dinna; Ince, Can; Okusa, Mark D

2014-03-01

Over the last decade there has been considerable progress in the discovery and development of biomarkers of kidney disease, and several have now been evaluated in different clinical settings. Although there is a growing literature on the performance of various biomarkers in clinical studies, there is limited information on how these biomarkers would be utilized by clinicians to manage patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we convened the 10th Acute Dialysis Quality Initiative meeting to review the literature on biomarkers in AKI and their application in clinical practice. We asked an international group of experts to assess four broad areas for biomarker utilization for AKI: risk assessment, diagnosis, and staging; differential diagnosis; prognosis and management; and novel physiological techniques including imaging. This article provides a summary of the key findings and recommendations of the group, to equip clinicians to effectively use biomarkers in AKI.

Documenting progress: hand therapy treatment shift from biomechanical to occupational adaptation.

PubMed

Jack, Jada; Estes, Rebecca I

2010-01-01

The investment of time and self to develop therapeutic relationships with clients appears incongruent with today's time-constrained health care system, yet bridging the gap of these incongruencies is the challenge therapists face to provide high-quality, client-centered, occupation-based treatment. This case report illustrates a shift in approach from biomechanical to occupational adaptation (OA) in an orthopedic outpatient clinic. The progress of a client with lupus-related arthritis who was 6 days postsurgery is documented. The intervention initially used a biomechanical frame of reference, but when little progress had been made at 10 weeks after surgery, a shift was made to the more client-centered OA approach. The Canadian Occupational Performance Measure was administered, and an OA approach was initiated. On reassessment, clinically important improvements were documented in all functional tasks addressed. An OA approach provides the bridge between the application of clinical expertise, client-centered, occupation-based therapy and the time constraints placed by payer sources.

Nanotechnology applications in urology: a review.

PubMed

Maddox, Michael; Liu, James; Mandava, Sree Harsha; Callaghan, Cameron; John, Vijay; Lee, Benjamin R

2014-11-01

The objectives of this review are to discuss the current literature and summarise some of the promising areas with which nanotechnology may improve urological care. A Medline literature search was performed to elucidate all relevant studies of nanotechnology with specific attention to its application in urology. Urological applications of nanotechnology include its use in medical imaging, gene therapy, drug delivery, and photothermal ablation of tumours. In vitro and animal studies have shown initial encouraging results. Further study of nanotechnology for urological applications is warranted to bridge the gap between preclinical studies and translation into clinical practice, but nanomedicine has shown significant potential to improve urological patient care. © 2014 The Authors. BJU International © 2014 BJU International.

An initial assessment of the cost and utilization of the Integrated Academic Information System (IAIMS) at Columbia Presbyterian Medical Center.

PubMed Central

Clayton, P. D.; Anderson, R. K.; Hill, C.; McCormack, M.

1991-01-01

The concept of "one stop information shopping" is becoming a reality at Columbia Presbyterian Medical Center (CPMC). The goal of our effort is to provide access to university and hospital administrative systems as well as clinical and library applications from a single workstation, which also provides utility functions such as word processing and mail. Since June 1987, CPMC has invested the equivalent of $23 million dollars to install a digital communications network that encompasses 18 buildings at seven geographically separate sites and to develop clinical and library applications that are integrated with the existing hospital and university administrative and research computing facilities. During June 1991, 2425 different individuals used the clinical information system, 425 different individuals used the library applications, and 900 different individuals used the hospital administrative applications via network access. If we were to freeze the system in its current state, amortize the development and network installation costs, and add projected maintenance costs for the clinical and library applications, our integrated information system would cost $2.8 million on an annual basis. This cost is 0.3% of the medical center's annual budget. These expenditures could be justified by very small improvements in time savings for personnel and/or decreased length of hospital stay and/or more efficient use of resources. In addition to the direct benefits which we detail, a major benefit is the ease with which additional computer-based applications can be added incrementally at an extremely modest cost. PMID:1666966

Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative.

PubMed

Kottner, J; Jacobi, L; Hahnel, E; Alam, M; Balzer, K; Beeckman, D; Busard, C; Chalmers, J; Deckert, S; Eleftheriadou, V; Furlan, K; Horbach, S E R; Kirkham, J; Nast, A; Spuls, P; Thiboutot, D; Thorlacius, L; Weller, K; Williams, H C; Schmitt, J

2018-04-01

Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers. © 2018 British Association of Dermatologists.

[ISO 9001certification of a quality management system in a clinical investigation center].

PubMed

Chesnais, Jimmy; Fougerou-Leurent, Claire; Laforest, Claire; Renault, Alain; Bellissant, Eric; Laviolle, Bruno

2018-05-03

Beyond the application of legal requirements, clinical trials must have a permanent approach of quality control. The clinical investigation centers (CICs) are academic structures of clinical research certified by the French National institute of health and medical research (Inserm) and whose functioning relies on recommendations of good practice. It is important to accompany this standardization of practices by the implementation of a quality management system. This article presents the process that enabled the CIC of Rennes to become certified ISO 9001 by French standards association (Afnor) certification in May, 2016. The application of the fundamental principles of the standard ISO 9001 in the domain of clinical research is approached. The problem of the perimeter for the certification and the related process mapping are exposed. The activities of methodology, management and analysis of clinical studies were chosen for the initial certification of the CIC of Rennes. The perspectives for the extension of the perimeter of certification are also approached at the end of article. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Translation of ERC resuscitation guidelines into clinical practice by emergency physicians

PubMed Central

2014-01-01

Purpose Austrian out-of-hospital emergency physicians (OOHEP) undergo mandatory biannual emergency physician refresher courses to maintain their licence. The purpose of this study was to compare different reported emergency skills and knowledge, recommended by the European Resuscitation Council (ERC) guidelines, between OOHEP who work regularly at an out-of-hospital emergency service and those who do not currently work as OOHEP but are licenced. Methods We obtained data from 854 participants from 19 refresher courses. Demographics, questions about their practice and multiple-choice questions about ALS-knowledge were answered and analysed. We particularly explored the application of therapeutic hypothermia, intraosseous access, pocket guide use and knowledge about the participants’ defibrillator in use. A multivariate logistic regression analysed differences between both groups of OOHEP. Age, gender, years of clinical experience, ERC-ALS provider course attendance and the self-reported number of resuscitations were control variables. Results Licenced OOHEP who are currently employed in emergency service are significantly more likely to initiate intraosseous access (OR = 4.013, p < 0.01), they initiate mild-therapeutic hypothermia after successful resuscitation (OR = 2.550, p < 0.01) more often, and knowledge about the used defibrillator was higher (OR = 2.292, p < 0.01). No difference was found for the use of pocket guides. OOHEP who have attended an ERC-ALS provider course since 2005 have initiated more mild therapeutic hypothermia after successful resuscitation (OR = 1.670, p <0.05) as well as participants who resuscitated within the last year (OR = 2.324, p < 0.01), while older OOHEP initiated mild therapeutic hypothermia less often, measured per year of age (OR = 0.913, p <0.01). Conclusion Licenced and employed OOHEP implement ERC guidelines better into clinical practice, but more training on life-saving rescue techniques needs to be done to improve knowledge and to raise these rates of application. PMID:24476488

Digital stethoscope: technology update

PubMed Central

Swarup, Supreeya; Makaryus, Amgad N

2018-01-01

Cardiovascular disease (CVD) is recognized as the leading cause of mortality throughout the world. About one-third of global mortality is attributable to CVD. In addition to clinical presentation, specific clinical exam findings can assist in treating and preventing CVD. CVD may initially manifest as pulmonary pathology, and thus, accurate cardiopulmonary auscultation is paramount to establishing accurate diagnosis. One of the most powerful tools available to physicians is the stethoscope. The stethoscope first emerged in the year 1818, invented by a French physician, René Laennec. Since then, the initial modest monaural wooden tube has evolved into a sophisticated digital device. This paper provides an analysis of the evolution of the stethoscope as well as highlights the advancement made by the modern digital stethoscope including the application of this tool in advancing care for patients suffering from CVD. PMID:29379321

Application of person-centered analytic methodology in longitudinal research: exemplars from the Women's Health Initiative Clinical Trial data.

PubMed

Zaslavsky, Oleg; Cochrane, Barbara B; Herting, Jerald R; Thompson, Hilaire J; Woods, Nancy F; Lacroix, Andrea

2014-02-01

Despite the variety of available analytic methods, longitudinal research in nursing has been dominated by use of a variable-centered analytic approach. The purpose of this article is to present the utility of person-centered methodology using a large cohort of American women 65 and older enrolled in the Women's Health Initiative Clinical Trial (N = 19,891). Four distinct trajectories of energy/fatigue scores were identified. Levels of fatigue were closely linked to age, socio-demographic factors, comorbidities, health behaviors, and poor sleep quality. These findings were consistent regardless of the methodological framework. Finally, we demonstrated that energy/fatigue levels predicted future hospitalization in non-disabled elderly. Person-centered methods provide unique opportunities to explore and statistically model the effects of longitudinal heterogeneity within a population. © 2013 Wiley Periodicals, Inc.

Agmatine: clinical applications after 100 years in translation.

PubMed

Piletz, John E; Aricioglu, Feyza; Cheng, Juei-Tang; Fairbanks, Carolyn A; Gilad, Varda H; Haenisch, Britta; Halaris, Angelos; Hong, Samin; Lee, Jong Eun; Li, Jin; Liu, Ping; Molderings, Gerhard J; Rodrigues, Ana Lúcia S; Satriano, Joseph; Seong, Gong Je; Wilcox, George; Wu, Ning; Gilad, Gad M

2013-09-01

Agmatine (decarboxylated arginine) has been known as a natural product for over 100 years, but its biosynthesis in humans was left unexplored owing to long-standing controversy. Only recently has the demonstration of agmatine biosynthesis in mammals revived research, indicating its exceptional modulatory action at multiple molecular targets, including neurotransmitter systems, nitric oxide (NO) synthesis and polyamine metabolism, thus providing bases for broad therapeutic applications. This timely review, a concerted effort by 16 independent research groups, draws attention to the substantial preclinical and initial clinical evidence, and highlights challenges and opportunities, for the use of agmatine in treating a spectrum of complex diseases with unmet therapeutic needs, including diabetes mellitus, neurotrauma and neurodegenerative diseases, opioid addiction, mood disorders, cognitive disorders and cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

3D Bioprinting of Artificial Tissues: Construction of Biomimetic Microstructures.

PubMed

Luo, Yongxiang; Lin, Xin; Huang, Peng

2018-04-24

It is promising that artificial tissues/organs for clinical application can be produced via 3D bioprinting of living cells and biomaterials. The construction of microstructures biomimicking native tissues is crucially important to create artificial tissues with biological functions. For instance, the fabrication of vessel-like networks to supply cells with initial nutrient and oxygen, and the arrangement of multiple types of cells for creating lamellar/complex tissues through 3D bioprinting are widely reported. The current advances in 3D bioprinting of artificial tissues from the view of construction of biomimetic microstructures, especially the fabrication of lamellar, vascular, and complex structures are summarized. In the end, the conclusion and perspective of 3D bioprinting for clinical applications are elaborated. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advanced Practice Nursing Committee on Process Improvement in Trauma: An Innovative Application of the Strong Model.

PubMed

West, Sarah Katherine

2016-01-01

This article aims to summarize the successes and future implications for a nurse practitioner-driven committee on process improvement in trauma. The trauma nurse practitioner is uniquely positioned to recognize the need for clinical process improvement and enact change within the clinical setting. Application of the Strong Model of Advanced Practice proves to actively engage the trauma nurse practitioner in process improvement initiatives. Through enhancing nurse practitioner professional engagement, the committee aims to improve health care delivery to the traumatically injured patient. A retrospective review of the committee's first year reveals trauma nurse practitioner success in the domains of direct comprehensive care, support of systems, education, and leadership. The need for increased trauma nurse practitioner involvement has been identified for the domains of research and publication.

Functional brain imaging in neuropsychology over the past 25 years.

PubMed

Roalf, David R; Gur, Ruben C

2017-11-01

Outline effects of functional neuroimaging on neuropsychology over the past 25 years. Functional neuroimaging methods and studies will be described that provide a historical context, offer examples of the utility of neuroimaging in specific domains, and discuss the limitations and future directions of neuroimaging in neuropsychology. Tracking the history of publications on functional neuroimaging related to neuropsychology indicates early involvement of neuropsychologists in the development of these methodologies. Initial progress in neuropsychological application of functional neuroimaging has been hampered by costs and the exposure to ionizing radiation. With rapid evolution of functional methods-in particular functional MRI (fMRI)-neuroimaging has profoundly transformed our knowledge of the brain. Its current applications span the spectrum of normative development to clinical applications. The field is moving toward applying sophisticated statistical approaches that will help elucidate distinct neural activation networks associated with specific behavioral domains. The impact of functional neuroimaging on clinical neuropsychology is more circumscribed, but the prospects remain enticing. The theoretical insights and empirical findings of functional neuroimaging have been led by many neuropsychologists and have transformed the field of behavioral neuroscience. Thus far they have had limited effects on the clinical practices of neuropsychologists. Perhaps it is time to add training in functional neuroimaging to the clinical neuropsychologist's toolkit and from there to the clinic or bedside. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Measuring verbal communication in initial physical therapy encounters.

PubMed

Roberts, Lisa C; Whittle, Christopher T; Cleland, Jennifer; Wald, Mike

2013-04-01

Communication in clinical encounters is vital in ensuring a positive experience and outcome for both patient and clinician. The purpose of this study was to measure verbal communication between physical therapists and patients with back pain during their initial consultation and trial management of the data using a novel, Web-based application. A cross-sectional study was conducted. Nine musculoskeletal physical therapists and 27 patients with back pain participated in this study. Twenty-five initial consultations were observed, audio recorded, and categorized using the Medical Communications Behavior System. Data were managed using Synote, a freely available application enabling synchronization of audio recordings with transcripts and coded notes. In this sample, physical therapists spoke for 49.5% of the encounter and patients for 33.1%. Providers and patients spent little time overtly discussing emotions (1.4% and 0.9%, respectively). More-experienced clinicians used more "history/background probes," more "advice/suggestion," and less "restatement" than less-experienced staff, although they demonstrated a greater prevalence of talking concurrently and interrupting patients (7.6% compared with 2.6%). Although studies measuring actual behavior are considered to be the gold standard, audio recordings do not enable nonverbal behaviors to be recorded. This study investigated a method for measuring the verbal content of clinical encounters in a physical therapy outpatient setting. The study has directly contributed to developing a research-friendly version of the application (i.e., Synote Researcher). Given the pivotal role of communication in ensuring a positive experience and outcome for both patient and provider, investing time in further developing communication skills should be an on-going priority for providers. Further work is needed to explore affective behaviors and the prevalence of interrupting patients, considering differences in sex and provider experience.

SU-F-T-100: Development and Implementation of a Treatment Planning Tracking System Into the Radiation Oncology Clinic

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

Kabat, C; Cline, K; Li, Y

Purpose: With increasing numbers of cancer patients being diagnosed and the complexity of radiotherapy treatments rising it’s paramount that patient plan development continues to stay fluid within the clinic. In order to maintain a high standard of care and clinical efficiency the establishment of a tracking system for patient plan development allows healthcare providers to view real time plan progression and drive clinical workflow. In addition, it provides statistical datasets which can further identify inefficiencies within the clinic. Methods: An application was developed utilizing Microsoft’s ODBC SQL database engine to track patient plan status throughout the treatment planning process whilemore » also managing key factors pertaining to the patient’s treatment. Pertinent information is accessible to staff in many locations, including tracking monitors within dosimetry, the clinic network for both computers and handheld devices, and through email notifications. Plans are initiated with a CT and continually tracked through planning stages until final approval by staff. Patient’s status is dynamically updated by the physicians, dosimetrists, and medical physicists based on the stage of the patient’s plan. Results: Our application has been running over a six month period with all patients being processed through the system. Modifications have been made to allow for new features to be implemented along with additional tracking parameters. Based on in-house feedback, the application has been supportive in streamlining patient plans through the treatment planning process and data has been accumulating to further improve procedures within the clinic. Conclusion: Over time the clinic will continue to track data with this application. As data accumulates the clinic will be able to highlight inefficiencies within the workflow and adapt accordingly. We will add in new features to help support the treatment planning process in the future.« less

Stem cell stratagems in alternative medicine.

PubMed

Sipp, Douglas

2011-05-01

Stem cell research has attracted an extraordinary amount of attention and expectation due to its potential for applications in the treatment of numerous medical conditions. These exciting clinical prospects have generated widespread support from both the public and private sectors, and numerous preclinical studies and rigorous clinical trials have already been initiated. Recent years, however, have also seen alarming growth in the number and variety of claims of clinical uses of notional 'stem cells' that have not been adequately tested for safety and/or efficacy. In this article, I will survey the contours of the stem cell industry as practiced by alternative medicine providers, and highlight points of commonality in their strategies for marketing.

Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

PubMed

Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

2018-03-01

Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

[What everybody should know about good clinical practices].

PubMed

Osorio, Lyda

2015-01-01

An increasing number of countries are adopting good clinical practices guidelines as part of the regulation of clinical studies to register pharmaceutical products and other health-related products. Consequently, all parties involved in the research and development of these products should know them, implement them and ensure their compliance. However, good clinical practices guidelines are just one of the initiatives seeking to achieve the highest ethical and scientific standards in health research and in other areas where humans are research subjects. This review defines such practices and their objectives presenting in a practical manner their legal framework in Colombia, and clarifying their application in studies where interventions use no medications or those that are not clinical trials. Finally, the work discusses the challenges to ensure that good clinical practices contribute to the protection of research participants, the education of trustworthy health professionals, and a culture of respect for human beings.

Advances in radio frequency tumor ablation therapy: technical considerations, strategies for increasing coagulation necrosis volume, and preliminary clinical results

NASA Astrophysics Data System (ADS)

Goldberg, S. Nahum; Gazelle, G. Scott

1998-04-01

Radiofrequency (RF) tumor ablation has been demonstrated as a reliable method for creating thermally induced coagulation necrosis using either a percutaneous approach with image- guidance or direct surgical application of thin electrodes into treated tissues. Early clinical trials with this technology have studied the treatment of hepatic, cerebral, and bony malignancies. The extent of coagulation necrosis induced with conventional monopolar radiofrequency electrodes is dependent on overall energy deposition, the duration of RF application, and RF electrode tip length and gauge. This article will discuss these technical considerations with the goal of defining optimal parameters for RF ablation. Strategies to further increase induced coagulation necrosis including: multiprobe and bipolar arrays, and internally-cooled RF electrodes, with or without pulsed-RF or cluster technique will be presented. The development and laboratory results for many of these radiofrequency techniques, initial clinical results, and potential biophysical limitations to RF induced coagulation, such as perfusion mediated tissue cooling (vascular flow) will likewise be discussed.

Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference.

PubMed

James, Matthew T; Hobson, Charles E; Darmon, Michael; Mohan, Sumit; Hudson, Darren; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A; Bagshaw, Sean M

2016-01-01

Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI.

Evaluation of the clinical and antimicrobial effects of the Er:YAG laser or topical gaseous ozone as adjuncts to initial periodontal therapy.

PubMed

Yılmaz, Selçuk; Algan, Serdar; Gursoy, Hare; Noyan, Ulku; Kuru, Bahar Eren; Kadir, Tanju

2013-06-01

The aim of this study was to evaluate the clinical and microbiological results of treatment with the Er:YAG laser and topical gaseous ozone application as adjuncts to initial periodontal therapy in chronic periodontitis (CP) patients. Although many studies have evaluated the effectiveness of the Er:YAG laser as an adjunct to initial periodontal therapy, few studies have focused on the use of gaseous ozone as an adjunct. Thirty patients with CP were randomly divided into three parallel groups, each composed of 10 individuals with at least four teeth having at least one approximal site with a probing depth (PD) of ≥5 mm and a sulcus bleeding index (SBI) ≥2 in each quadrant. Groups of patients received: (1) Scaling and root planing (SRP)+Er:YAG laser; (2) SRP+topical gaseous ozone; or (3) SRP alone. The microbiological and clinical parameters were monitored at day 0 and day 90. At the end of the observation period, statistically significant improvements in clinical parameters were observed within each group. Parallel to the clinical changes, all treatments reduced the number of total bacteria and the proportion of obligately anaerobic microorganisms. Although intergroup comparisons of microbiological parameters showed no significant differences, clinical findings, including attachment gain and PD reduction, were found to be statistically significant in favor of the SRP+Er:YAG laser group. Although statistically nonsignificant, the fact that the obligate anaerobic change was mostly observed in the SRP+Er:YAG laser group, and a similar decrease was noted in the SRP+topical gaseous ozone group, shows that ozone has an antimicrobial effect equivalent to that of the Er:YAG laser.

A transposon and transposase system for human application.

PubMed

Hackett, Perry B; Largaespada, David A; Cooper, Laurence J N

2010-04-01

The stable introduction of therapeutic transgenes into human cells can be accomplished using viral and nonviral approaches. Transduction with clinical-grade recombinant viruses offers the potential of efficient gene transfer into primary cells and has a record of therapeutic successes. However, widespread application for gene therapy using viruses can be limited by their initially high cost of manufacture at a limited number of production facilities as well as a propensity for nonrandom patterns of integration. The ex vivo application of transposon-mediated gene transfer now offers an alternative to the use of viral vectors. Clinical-grade DNA plasmids can be prepared at much reduced cost and with lower immunogenicity, and the integration efficiency can be improved by the transient coexpression of a hyperactive transposase. This has facilitated the design of human trials using the Sleeping Beauty (SB) transposon system to introduce a chimeric antigen receptor (CAR) to redirect the specificity of human T cells. This review examines the rationale and safety implications of application of the SB system to genetically modify T cells to be manufactured in compliance with current good manufacturing practice (cGMP) for phase I/II trials.

Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature.

PubMed

Antony, Dinu; Nampoory, Narayanan; Bacchelli, Chiara; Melhem, Motasem; Wu, Kaman; James, Chela T; Beales, Philip L; Hubank, Mike; Thomas, Daisy; Mashankar, Anant; Behbehani, Kazem; Schmidts, Miriam; Alsmadi, Osama

2017-12-01

Exome sequencing is becoming widely popular and affordable, making it one of the most desirable methods for the identification of rare genetic variants for clinical diagnosis. Here, we report the clinical application of whole exome sequencing for the ultimate diagnosis of a ciliary chondrodysplasia case presented with an initial clinical diagnosis of Asphyxiating Thoracic Dystrophy (ATD, Jeune Syndrome). We have identified a novel homozygous missense mutation in WDR35 (c.206G > A), a gene previously associated with Sensenbrenner Syndrome, Ellis-van Creveld syndrome and Short-rib polydactyly syndrome type V. The genetic findings in this family led to the re-evaluation of the initial diagnosis and a differential diagnosis of Sensenbrenner Syndrome was made after cautious re-examination of the patient. Cell culture studies revealed normal subcellular localization of the mutant WDR35 protein in comparison to wildtype protein, pointing towards impaired protein-protein interaction and/or altered cell signaling pathways as a consequence of the mutated allele. This research study highlights the importance of including pathogenic variant identification in the diagnosis pipeline of ciliary chondrodysplasias, especially for clinically not fully defined phenotypes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Development and performance of electronic acute kidney injury triggers to identify pediatric patients at risk for nephrotoxic medication-associated harm.

PubMed

Kirkendall, E S; Spires, W L; Mottes, T A; Schaffzin, J K; Barclay, C; Goldstein, S L

2014-01-01

Nephrotoxic medication-associated acute kidney injury (NTMx-AKI) is a costly clinical phenomenon and more common than previously recognized. Prior efforts to use technology to identify AKI have focused on detection after renal injury has occurred. Describe an approach and provide a technical framework for the creation of risk-stratifying AKI triggers and the development of an application to manage the AKI trigger data. Report the performance characteristics of those triggers and the refinement process and on the challenges of implementation. Initial manual trigger screening guided design of an automated electronic trigger report. A web-based application was designed to alleviate inefficiency and serve as a user interface and central workspace for the project. Performance of the NTMx exposure trigger reports from September 2011 to September 2013 were evaluated using sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). Automated reports were created to replace manual screening for NTMx-AKI. The initial performance of the NTMx exposure triggers for SN, SP, PPV, and NPV all were ≥0.78, and increased over the study, with all four measures reaching ≥0.95 consistently. A web-based application was implemented that simplifies data entry and couriering from the reports, expedites results viewing, and interfaces with an automated data visualization tool. Sociotechnical challenges were logged and reported. We have built a risk-stratifying system based on electronic triggers that detects patients at-risk for NTMx-AKI before injury occurs. The performance of the NTMx-exposed reports has neared 100% through iterative optimization. The complexity of the trigger logic and clinical workflows surrounding NTMx-AKI led to a challenging implementation, but one that has been successful from technical, clinical, and quality improvement standpoints. This report summarizes the construction of a trigger-based application, the performance of the triggers, and the challenges uncovered during the design, build, and implementation of the system.

Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

PubMed

Karpawich, Peter P

2015-01-01

Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

HPV vaccination: Population approaches for improving rates.

PubMed

Oliver, Kristin; Frawley, Alean; Garland, Elizabeth

2016-06-02

To review the literature on interventions to increase HPV vaccinations and assess whether The Community Preventive Services Task Force recommendations are supported by current evidence. We used a PubMed search to identify studies that assessed interventions that looked at provider assessment and feedback, provider reminders, client reminder and recall, and clinic based education programs. Of the 13 studies identified, 8 included client reminder and recall interventions, 4 included provider assessment and feedback and/or provider reminders and 2 included clinic based education. 11 of the 13 studies demonstrated a positive effect on HPV vaccine initiation or completion. Provider assessment and feedback studies were more likely to report a positive effect on HPV vaccine initiation than on series completion, while client reminder recall interventions more frequently produced an effect on series completion than on initiation. There is evidence to support the application of the Community Preventive Services Task Force recommendations specifically to HPV vaccination both for client reminder and recall programs and for provider assessment and feedback interventions. Multiple targeted approaches will be needed to substantially impact HPV vaccine rates.

Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

PubMed

Celià-Terrassa, Toni

2018-05-04

Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

Improving the availability of clinical history accompanying radiographic examinations in a large pediatric radiology department.

PubMed

Hawkins, C Matthew; Anton, Christopher G; Bankes, Wendy M; Leach, Alan D; Zeno, Michael J; Pryor, Rebecca M; Larson, David B

2014-04-01

The purpose of this quality improvement initiative was to improve the consistency with which radiologists are provided a complete clinical history when interpreting radiography examinations performed in the outpatient and emergency department settings. The clinical history was considered complete if it contained three elements: nature of the symptoms, description of injury, or cause for clinical concern; duration of symptoms or time of injury; and focal site of pain or abnormality, if applicable. This was reduced to three elements: "what-when-where." A goal was established that 95% of the clinical histories should contain all three elements. To achieve this goal, technologists supplemented referring clinicians' history. The project was divided into four phases: launch, support, transition to sustainability, and maintenance. During the support phase, results of automated weekly audits automatically populated group-level performance reports. During the transition to the sustainability phase, audit results populated individual-level performance reports. During the maintenance phase, quarterly audit results were incorporated into technologists' employee performance goals. Before initiation of the project, 38% (76/200) of radiography examinations were accompanied by a complete clinical history. This increased to 92% (928/1006) by the end of the 15-week improvement phase. Performance was sustained at 96% (1168/1213) 7 months later [corrected]. By clearly defining expectations for an appropriate clinical history and establishing system and organizational mechanisms to facilitate verifiable compliance, we were able to successfully and sustainably improve the consistency with which radiography examinations were accompanied by a complete clinical history.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

CISUS: an integrated 3D ultrasound system for IGT using a modular tracking API

NASA Astrophysics Data System (ADS)

Boctor, Emad M.; Viswanathan, Anand; Pieper, Steve; Choti, Michael A.; Taylor, Russell H.; Kikinis, Ron; Fichtinger, Gabor

2004-05-01

Ultrasound has become popular in clinical/surgical applications, both as the primary image guidance modality and also in conjunction with other modalities like CT or MRI. Three dimensional ultrasound (3DUS) systems have also demonstrated usefulness in image-guided therapy (IGT). At the same time, however, current lack of open-source and open-architecture multi-modal medical visualization systems prevents 3DUS from fulfilling its potential. Several stand-alone 3DUS systems, like Stradx or In-Vivo exist today. Although these systems have been found to be useful in real clinical setting, it is difficult to augment their functionality and integrate them in versatile IGT systems. To address these limitations, a robotic/freehand 3DUS open environment (CISUS) is being integrated into the 3D Slicer, an open-source research tool developed for medical image analysis and surgical planning. In addition, the system capitalizes on generic application programming interfaces (APIs) for tracking devices and robotic control. The resulting platform-independent open-source system may serve as a valuable tool to the image guided surgery community. Other researchers could straightforwardly integrate the generic CISUS system along with other functionalities (i.e. dual view visualization, registration, real-time tracking, segmentation, etc) to rapidly create their medical/surgical applications. Our current driving clinical application is robotically assisted and freehand 3DUS-guided liver ablation, which is fully being integrated under the CISUS-3D Slicer. Initial functionality and pre-clinical feasibility are demonstrated on phantom and ex-vivo animal models.

Implementation and applications of dual-modality imaging

NASA Astrophysics Data System (ADS)

Hasegawa, Bruce H.; Barber, William C.; Funk, Tobias; Hwang, Andrew B.; Taylor, Carmen; Sun, Mingshan; Seo, Youngho

2004-06-01

In medical diagnosis, functional or physiological data can be acquired using radionuclide imaging with positron emission tomography or with single-photon emission computed tomography. However, anatomical or structural data can be acquired using X-ray computed tomography. In dual-modality imaging, both radionuclide and X-ray detectors are incorporated in an imaging system to allow both functional and structural data to be acquired in a single procedure without removing the patient from the imaging system. In a clinical setting, dual-modality imaging systems commonly are used to localize radiopharmaceutical uptake with respect to the patient's anatomy. This helps the clinician to differentiate disease from regions of normal radiopharmaceutical accumulation, to improve diagnosis or cancer staging, or to facilitate planning for radiation therapy or surgery. While initial applications of dual-modality imaging were developed for clinical imaging on humans, it now is recognized that these systems have potentially important applications for imaging small animals involved in experimental studies including basic investigations of mammalian biology and development of new pharmaceuticals for diagnosis or treatment of disease.

Review of optical coherence tomography in oncology

NASA Astrophysics Data System (ADS)

Wang, Jianfeng; Xu, Yang; Boppart, Stephen A.

2017-12-01

The application of optical coherence tomography (OCT) in the field of oncology has been prospering over the past decade. OCT imaging has been used to image a broad spectrum of malignancies, including those arising in the breast, brain, bladder, the gastrointestinal, respiratory, and reproductive tracts, the skin, and oral cavity, among others. OCT imaging has initially been applied for guiding biopsies, for intraoperatively evaluating tumor margins and lymph nodes, and for the early detection of small lesions that would often not be visible on gross examination, tasks that align well with the clinical emphasis on early detection and intervention. Recently, OCT imaging has been explored for imaging tumor cells and their dynamics, and for the monitoring of tumor responses to treatments. This paper reviews the evolution of OCT technologies for the clinical application of OCT in surgical and noninvasive interventional oncology procedures and concludes with a discussion of the future directions for OCT technologies, with particular emphasis on their applications in oncology.

Barriers to Achieving Economies of Scale in Analysis of EHR Data. A Cautionary Tale.

PubMed

Sendak, Mark P; Balu, Suresh; Schulman, Kevin A

2017-08-09

Signed in 2009, the Health Information Technology for Economic and Clinical Health Act infused $28 billion of federal funds to accelerate adoption of electronic health records (EHRs). Yet, EHRs have produced mixed results and have even raised concern that the current technology ecosystem stifles innovation. We describe the development process and report initial outcomes of a chronic kidney disease analytics application that identifies high-risk patients for nephrology referral. The cost to validate and integrate the analytics application into clinical workflow was $217,138. Despite the success of the program, redundant development and validation efforts will require $38.8 million to scale the application across all multihospital systems in the nation. We address the shortcomings of current technology investments and distill insights from the technology industry. To yield a return on technology investments, we propose policy changes that address the underlying issues now being imposed on the system by an ineffective technology business model.

Muscle Injuries in Sports: A New Evidence-Informed and Expert Consensus-Based Classification with Clinical Application.

PubMed

Valle, Xavier; Alentorn-Geli, Eduard; Tol, Johannes L; Hamilton, Bruce; Garrett, William E; Pruna, Ricard; Til, Lluís; Gutierrez, Josep Antoni; Alomar, Xavier; Balius, Ramón; Malliaropoulos, Nikos; Monllau, Joan Carles; Whiteley, Rodney; Witvrouw, Erik; Samuelsson, Kristian; Rodas, Gil

2017-07-01

Muscle injuries are among the most common injuries in sport and continue to be a major concern because of training and competition time loss, challenging decision making regarding treatment and return to sport, and a relatively high recurrence rate. An adequate classification of muscle injury is essential for a full understanding of the injury and to optimize its management and return-to-play process. The ongoing failure to establish a classification system with broad acceptance has resulted from factors such as limited clinical applicability, and the inclusion of subjective findings and ambiguous terminology. The purpose of this article was to describe a classification system for muscle injuries with easy clinical application, adequate grouping of injuries with similar functional impairment, and potential prognostic value. This evidence-informed and expert consensus-based classification system for muscle injuries is based on a four-letter initialism system: MLG-R, respectively referring to the mechanism of injury (M), location of injury (L), grading of severity (G), and number of muscle re-injuries (R). The goal of the classification is to enhance communication between healthcare and sports-related professionals and facilitate rehabilitation and return-to-play decision making.

Clinical oncologic applications of PET/MRI: a new horizon

PubMed Central

Partovi, Sasan; Kohan, Andres; Rubbert, Christian; Vercher-Conejero, Jose Luis; Gaeta, Chiara; Yuh, Roger; Zipp, Lisa; Herrmann, Karin A; Robbin, Mark R; Lee, Zhenghong; Muzic, Raymond F; Faulhaber, Peter; Ros, Pablo R

2014-01-01

Positron emission tomography/magnetic resonance imaging (PET/MRI) leverages the high soft-tissue contrast and the functional sequences of MR with the molecular information of PET in one single, hybrid imaging technology. This technology, which was recently introduced into the clinical arena in a few medical centers worldwide, provides information about tumor biology and microenvironment. Studies on indirect PET/MRI (use of positron emission tomography/computed tomography (PET/CT) images software fused with MRI images) have already generated interesting preliminary data to pave the ground for potential applications of PET/MRI. These initial data convey that PET/MRI is promising in neuro-oncology and head & neck cancer applications as well as neoplasms in the abdomen and pelvis. The pediatric and young adult oncology population requiring frequent follow-up studies as well as pregnant woman might benefit from PET/MRI due to its lower ionizing radiation dose. The indication and planning of therapeutic interventions and specifically radiation therapy in individual patients could be and to a certain extent are already facilitated by performing PET/MRI. The objective of this article is to discuss potential clinical oncology indications of PET/MRI. PMID:24753986

Completed | Office of Cancer Clinical Proteomics Research

Cancer.gov

Prior to the current Clinical Proteomic Tumor Analysis Consortium (CPTAC), previously funded initiatives associated with clinical proteomics research included: Clinical Proteomic Tumor Analysis Consortium (CPTAC 2.0) Clinical Proteomic Technologies for Cancer Initiative (CPTC) Mouse Proteomic Technologies Initiative

Workshop on neutron capture therapy

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

Fairchild, R.G.; Bond, V.P.

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed tomore » be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior.« less

Telemedical technologies in urological cancer care: past, present and future applications.

PubMed

Bogen, Etai M; Aarsæther, Erling; Augestad, Knut M; Lindsetmo, Rolv-Ole; Patel, Hiten Rh

2013-07-01

Since the initial development of telegraphy by Sir Charles Wheatstone in 1837 and the telephone by Alexander Graham Bell in 1875, doctors have been able to convey medical information across great distances. The exchange and sharing of medical information has evolved and adapted to suit the vast array of today's medicine. Early adopters of telemedicine within clinical practice have gained significant health economic benefits. The arrival of wireless connections has further enhanced the possibilities for all clinical work with focus on diagnosis, treatment and management of urological cancers, as highlighted in this article.

The impact of psychopharmacology on contemporary clinical psychiatry.

PubMed

Vázquez, Gustavo H

2014-08-01

Clinical psychiatric evaluations of patients have changed dramatically in recent decades. Both initial assessments and follow-up visits have become brief and superficial, focused on searching for categorical diagnostic criteria from checklists, with limited inquiry into patient-reported symptomatic status and tolerability of treatments. The virtually exclusive therapeutic task has become selecting a plausible psychotropic, usually based on expert consensus guidelines. These guidelines and practice patterns rest mainly on published monotherapy trials that may or may not be applicable to particular patients but are having a profound impact, not only on modern psychiatric practice but also on psychiatric education, research, and theory.

Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Fuchs, Michael; Kriz, Jan; Semrau, Robert; Baues, Christian; Kobe, Carsten; Behringer, Karolin; Eichenauer, Dennis A; von Tresckow, Bastian; Klimm, Beate; Halbsguth, Teresa; Wongso, Diana; Plütschow, Annette; Haverkamp, Heinz; Dietlein, Markus; Eich, Hans T; Stein, Harald; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2015-11-01

Accurate clinical staging is crucial for adequate risk-adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first-line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte-predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk-adapted first-line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice. © 2015 John Wiley & Sons Ltd.

Process, cost, and clinical quality: the initial oral contraceptive visit.

PubMed

McMullen, Michael J; Woolford, Samuel W; Moore, Charles L; Berger, Barry M

2013-01-01

To demonstrate how the analysis of clinical process, cost, and outcomes can identify healthcare improvements that reduce cost without sacrificing quality, using the example of the initial visit associated with oral contraceptive pill use. Cross-sectional study using data collected by HealthMETRICS between 1996 and 2009. Using data collected from 106 sites in 24 states, the unintended pregnancy (UIP) rate, effectiveness of patient education, and unit visit cost were calculated. Staff type providing education and placement of education were recorded. Two-way analysis of variance models were created and tested for significance to identify differences between groups. Sites using nonclinical staff to provide education outside the exam were associated with lower cost, higher education scores, and a UIP rate no different from that of sites using clinical staff. Sites also providing patient education during the physical examination were associated with higher cost, lower education scores, and a UIP rate no lower than that of sites providing education outside of the exam. Through analyzing process, cost, and quality, lower-cost processes that did not reduce clinical quality were identified. This methodology is applicable to other clinical services for identifying low-cost processes that do not result in lower clinical quality. By using nonclinical staff educators to provide education outside of the physical examination, sites could save an average of 32% of the total cost of the visit.

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

A dynamic model for tumour growth and metastasis formation.

PubMed

Haustein, Volker; Schumacher, Udo

2012-07-05

A simple and fast computational model to describe the dynamics of tumour growth and metastasis formation is presented. The model is based on the calculation of successive generations of tumour cells and enables one to describe biologically important entities like tumour volume, time point of 1st metastatic growth or number of metastatic colonies at a given time. The model entirely relies on the chronology of these successive events of the metastatic cascade. The simulation calculations were performed for two embedded growth models to describe the Gompertzian like growth behaviour of tumours. The initial training of the models was carried out using an analytical solution for the size distribution of metastases of a hepatocellular carcinoma. We then show the applicability of our models to clinical data from the Munich Cancer Registry. Growth and dissemination characteristics of metastatic cells originating from cells in the primary breast cancer can be modelled thus showing its ability to perform systematic analyses relevant for clinical breast cancer research and treatment. In particular, our calculations show that generally metastases formation has already been initiated before the primary can be detected clinically.

A dynamic model for tumour growth and metastasis formation

PubMed Central

2012-01-01

A simple and fast computational model to describe the dynamics of tumour growth and metastasis formation is presented. The model is based on the calculation of successive generations of tumour cells and enables one to describe biologically important entities like tumour volume, time point of 1st metastatic growth or number of metastatic colonies at a given time. The model entirely relies on the chronology of these successive events of the metastatic cascade. The simulation calculations were performed for two embedded growth models to describe the Gompertzian like growth behaviour of tumours. The initial training of the models was carried out using an analytical solution for the size distribution of metastases of a hepatocellular carcinoma. We then show the applicability of our models to clinical data from the Munich Cancer Registry. Growth and dissemination characteristics of metastatic cells originating from cells in the primary breast cancer can be modelled thus showing its ability to perform systematic analyses relevant for clinical breast cancer research and treatment. In particular, our calculations show that generally metastases formation has already been initiated before the primary can be detected clinically. PMID:22548735

Initial clinical application of a robotically steerable catheter system in endovascular aneurysm repair.

PubMed

Riga, Celia; Bicknell, Colin; Cheshire, Nicholas; Hamady, Mohamad

2009-04-01

To report the initial clinical use of a robotically steerable catheter during endovascular aneurysm repair (EVAR) in order to assess this novel and innovative approach in a clinical setting. Following a series of in-vitro studies and procedure rehearsals using a pulsatile silicon aneurysm model, a 78-year-old man underwent robot-assisted EVAR of a 5.9-cm infrarenal abdominal aortic aneurysm. During the standard procedure, a 14-F remotely steerable robotic catheter was used to successfully navigate through the aneurysm sac, cannulate the contralateral limb of a bifurcated stent-graft under fluoroscopic guidance, and place stiff wires using fine and controlled movements. The procedure was completed successfully. There were no postoperative complications, and computed tomographic angiography prior to discharge and at 3 months confirmed that the stent-graft remained in good position, with no evidence of an endoleak. EVAR using robotically-steerable catheters is feasible. This technology may simplify more complex procedures by increasing the accuracy of vessel cannulation and perhaps reduce procedure times and radiation exposure to the patient and operator.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

PubMed

Fields, Jeremy D; Liu, Kenneth C; Barnwell, Stanley L; Clark, Wayne M; Lutsep, Helmi L

2010-01-01

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

The role of extended duties dental nurses in applying fluoride varnish for the prevention and control of dental caries.

PubMed

Jones, Colwyn M; Walker, Alan

2010-10-01

The role of extended duties dental nurses (EDDNs) in undertaking preventive dental care has provided an opportunity for their direct involvement in patient care, both at an individual patient level and as part of a population wide health improvement initiative. The article describes the developing role of the dental nurse in the clinical application of fluoride varnish, with associated evidence of effectiveness for the prevention and control of dental caries. The use of fluoride varnish as being central to caries preventive programmes for individual patients judged at risk of future dental caries is considered. A Scottish dental public health initiative which utilizes these extended skills and the benefits of fluoride varnish application is described. This paper illustrates how EDDNs can help to foster a greater team approach to overall patient care and preventive practice by applying fluoride varnish as part of an effective caries preventive programme.

An ontology-driven, diagnostic modeling system.

PubMed

Haug, Peter J; Ferraro, Jeffrey P; Holmen, John; Wu, Xinzi; Mynam, Kumar; Ebert, Matthew; Dean, Nathan; Jones, Jason

2013-06-01

To present a system that uses knowledge stored in a medical ontology to automate the development of diagnostic decision support systems. To illustrate its function through an example focused on the development of a tool for diagnosing pneumonia. We developed a system that automates the creation of diagnostic decision-support applications. It relies on a medical ontology to direct the acquisition of clinic data from a clinical data warehouse and uses an automated analytic system to apply a sequence of machine learning algorithms that create applications for diagnostic screening. We refer to this system as the ontology-driven diagnostic modeling system (ODMS). We tested this system using samples of patient data collected in Salt Lake City emergency rooms and stored in Intermountain Healthcare's enterprise data warehouse. The system was used in the preliminary development steps of a tool to identify patients with pneumonia in the emergency department. This tool was compared with a manually created diagnostic tool derived from a curated dataset. The manually created tool is currently in clinical use. The automatically created tool had an area under the receiver operating characteristic curve of 0.920 (95% CI 0.916 to 0.924), compared with 0.944 (95% CI 0.942 to 0.947) for the manually created tool. Initial testing of the ODMS demonstrates promising accuracy for the highly automated results and illustrates the route to model improvement. The use of medical knowledge, embedded in ontologies, to direct the initial development of diagnostic computing systems appears feasible.

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

A decade of the Clinical Trials Transformation Initiative: What have we accomplished? What have we learned?

PubMed

Tenaerts, P; Madre, L; Landray, M

2018-02-01

The Clinical Trials Transformation Initiative reflects on 10 years of working to improve the quality and efficiency of clinical trials. This article highlights many of the Clinical Trials Transformation Initiative's accomplishments and offers examples of the impact that the Clinical Trials Transformation Initiative has had on the clinical trials enterprise. After conducting more than 25 projects and issuing recommendations for specific strategies to improve the design and execution of clinical trials, some common themes and lessons learned have emerged. Lessons include the importance of engaging many stakeholders, advanced planning to address critical issues, discontinuation of non-value added practices, and new opportunities presented by technology. Through its work, the Clinical Trials Transformation Initiative has also derived some operational best practices for conducting collaborative, multi-stakeholder projects covering project selection, project team dynamics and execution, and multi-stakeholder meetings and team discussions. Through these initiatives, the Clinical Trials Transformation Initiative has helped move the needle toward needed change in the clinical trials enterprise that has directly impacted stakeholders and patients alike.

The genomic applications in practice and prevention network.

PubMed

Khoury, Muin J; Feero, W Gregory; Reyes, Michele; Citrin, Toby; Freedman, Andrew; Leonard, Debra; Burke, Wylie; Coates, Ralph; Croyle, Robert T; Edwards, Karen; Kardia, Sharon; McBride, Colleen; Manolio, Teri; Randhawa, Gurvaneet; Rasooly, Rebekah; St Pierre, Jeannette; Terry, Sharon

2009-07-01

The authors describe the rationale and initial development of a new collaborative initiative, the Genomic Applications in Practice and Prevention Network. The network convened by the Centers for Disease Control and Prevention and the National Institutes of Health includes multiple stakeholders from academia, government, health care, public health, industry and consumers. The premise of Genomic Applications in Practice and Prevention Network is that there is an unaddressed chasm between gene discoveries and demonstration of their clinical validity and utility. This chasm is due to the lack of readily accessible information about the utility of most genomic applications and the lack of necessary knowledge by consumers and providers to implement what is known. The mission of Genomic Applications in Practice and Prevention Network is to accelerate and streamline the effective integration of validated genomic knowledge into the practice of medicine and public health, by empowering and sponsoring research, evaluating research findings, and disseminating high quality information on candidate genomic applications in practice and prevention. Genomic Applications in Practice and Prevention Network will develop a process that links ongoing collection of information on candidate genomic applications to four crucial domains: (1) knowledge synthesis and dissemination for new and existing technologies, and the identification of knowledge gaps, (2) a robust evidence-based recommendation development process, (3) translation research to evaluate validity, utility and impact in the real world and how to disseminate and implement recommended genomic applications, and (4) programs to enhance practice, education, and surveillance.

Early developments and clinical applications of total parenteral nutrition.

PubMed

Dudrick, Stanley J

2003-01-01

This article recounts the conditions and status of surgical nutrition support in the 1960s and the antecedent basic and clinical investigational work leading to the development of a practical and efficacious method of adequate nourishment entirely by vein in Beagle puppies; describes the subsequent clinical application of the knowledge, techniques, and technology to the first successful long-term total parenteral nutrition (TPN) support of critically ill pediatric and adult patients; and admonishes nutritionists of all backgrounds that some need for parenteral nutrition will likely always exist and that it is incumbent upon everyone to continue endeavors to advance the germinal methodology to perfection. The relevant indications, limitations, hindrances, motivational factors, and studies regarding the development of TPN are reviewed, and the fundamental investigational work culminating in the first successful growth and development of Beagle puppies and a human infant fed entirely by vein are described firsthand. The details of the orderly and logical scientific development of the principles and components of the techniques in animals, infants, and adults are related. Knowledge, techniques, and technologic constituents of the first successful long-term TPN system were developed in the basic biochemical and animal laboratories initially in 6 puppies and subsequently adapted clinically for the efficacious long-term i.v. support of 6 critically ill surgical adult patients and a newborn infant before its widespread clinical application. Long-term TPN was inaugurated successfully as a safe and effective i.v. feeding technique nearly 4 decades ago. However, basic and clinical investigations must continue to be encouraged, supported, and carried out in the quest to perfect the current rudimentary technology, methodology, and outcomes.

Conditionally replicative adenovirus for gastrointestinal cancers.

PubMed

Yamamoto, Masato

2004-08-01

The clinical outcome of advanced gastrointestinal (GI) cancers (especially pancreatic and oesophageal cancers) is dismal, despite the advance of conventional therapeutic strategies. Cancer gene therapy is a category of new therapeutics, among which conditionally replicative adenovirus (CRAd) is one promising strategy to overcome existing obstacles of cancer gene therapy. Various CRAds have been developed for GI cancer treatment by taking advantage of the replication biology of adenovirus. Some CRAds have already been tested in clinical trials, but have fallen short of initial expectations. Concerns for clinical applicability include therapeutic potency, replication selectivity and interval end points in clinical trials. In addition, improvement of experimental animal models is needed for a deeper understanding of CRAd biology. Despite these obstacles, CRAds continue to be an exciting area of investigation with great potential for clinical utility. Further virological and oncological research will eventually lead to full realisation of the therapeutic potential of CRAds in the field of GI cancers.

A historical overview of magnetic resonance imaging, focusing on technological innovations.

PubMed

Ai, Tao; Morelli, John N; Hu, Xuemei; Hao, Dapeng; Goerner, Frank L; Ager, Bryan; Runge, Val M

2012-12-01

Magnetic resonance imaging (MRI) has now been used clinically for more than 30 years. Today, MRI serves as the primary diagnostic modality for many clinical problems. In this article, historical developments in the field of MRI will be discussed with a focus on technological innovations. Topics include the initial discoveries in nuclear magnetic resonance that allowed for the advent of MRI as well as the development of whole-body, high field strength, and open MRI systems. Dedicated imaging coils, basic pulse sequences, contrast-enhanced, and functional imaging techniques will also be discussed in a historical context. This article describes important technological innovations in the field of MRI, together with their clinical applicability today, providing critical insights into future developments.

SMARTWheel: From Concept to Clinical Practice

PubMed Central

Cooper, Rory A.

2009-01-01

Background Wheelchair prescription is complex with thousands of choices and options. Theoretically, a higher quality or innovative wheelchair that is appropriately matched to the user and their unique needs will increase participation. It is well accepted that there is an alarmingly high incidence of carpal tunnel syndrome, and rotator cuff injuries among manual wheelchair users. Development Since the initial conceptualization, the SMARTWheel was intended to better understand the physiological and physical effects of wheelchair propulsion on the body. Initially, little was known about wheelchair propulsion and the SMARTWheel transformed the nascent field of wheelchair propulsion biomechanics. Impact Although still an important area of clinical research, the SMARTWheel has been critical to the study of the relationship between the type of wheelchair, set-up, activity, technique, anatomy, and physiology and repetitive strain injury. There has been growing evidence that the wheelchair-user interaction explains a substantial portion of the risk of developing a degenerative injury and on community participation. A noteworthy contribution of this work was the release of the clinical practice guideline, entitled, Preservation of Upper Limb Function Following Spinal Cord Injury in 2005. Discussion The SMARTWheel has been used by other scientists in areas that were not originally envisioned to be applications. It has been used to support the design of tools for developing a trail mapping rating and description system. It has also supported the design of accessible pedestrian walkways standards, accessible playground surfaces, and to evaluate carpets for wheelchair accessibility. It is likely that there are more new areas of exploration to emerge. This article describes the evolution of the SMARTWheel as new technologies became available and its applications in the field of wheelchair biomechanics and clinical service delivery. PMID:19658010

Dentin Biomodification: Strategies, Renewable Resources and Clinical Applications

PubMed Central

Bedran-Russo, Ana K.; Pauli, Guido F.; Chen, Shao-Nong; McAlpine, James; Castellan, Carina S.; Phansalkar, Rasika S; Aguiar, Thaiane R.; Vidal, Cristina M.P.; Napotilano, José; Nam, Joo-Won; Leme, Ariene A.

2014-01-01

Objectives The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications. Methods The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents. Results Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic collagen cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation. Significance Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management. PMID:24309436

MedEx: a medication information extraction system for clinical narratives

PubMed Central

Stenner, Shane P; Doan, Son; Johnson, Kevin B; Waitman, Lemuel R; Denny, Joshua C

2010-01-01

Medication information is one of the most important types of clinical data in electronic medical records. It is critical for healthcare safety and quality, as well as for clinical research that uses electronic medical record data. However, medication data are often recorded in clinical notes as free-text. As such, they are not accessible to other computerized applications that rely on coded data. We describe a new natural language processing system (MedEx), which extracts medication information from clinical notes. MedEx was initially developed using discharge summaries. An evaluation using a data set of 50 discharge summaries showed it performed well on identifying not only drug names (F-measure 93.2%), but also signature information, such as strength, route, and frequency, with F-measures of 94.5%, 93.9%, and 96.0% respectively. We then applied MedEx unchanged to outpatient clinic visit notes. It performed similarly with F-measures over 90% on a set of 25 clinic visit notes. PMID:20064797

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

[SmartCare: automatizing clinical guidelines].

PubMed

Mersmann, Stefan

2009-10-01

In critical care environments, important medical and economic challenges are presented by the enhancement of therapeutic quality and the reduction of therapeutic costs. For this purpose, several clinical studies have demonstrated a positive impact of the adoption of so-called clinical guidelines. Clinical guidelines represent well documented best practices in healthcare and are fundamental aspects of evidence-based medicine. However, at the bedside, such clinical guidelines remain difficult to use by clinical staff. The knowledge-based technology SmartCare allows incorporation of arbitrary computerized clinical guidelines into various medical target systems. SmartCare constitutes a clinical guideline engine because it executes one or more clinical guidelines on a specific medical device. SmartCare was initially applied for the automated control of a mechanical ventilator to assist the process of weaning from a medical device. The methodology allows further applications to be implemented effectively with other medical devices and/or with other appropriate guidelines. In this paper, we report on the methodology and the resulting versatility of such a system, as well as the clinical evaluation of SmartCare/PS and its perspectives.

Psychoeducation in bipolar disorder with a SIMPLe smartphone application: Feasibility, acceptability and satisfaction.

PubMed

Hidalgo-Mazzei, Diego; Mateu, Ainoa; Reinares, María; Murru, Andrea; Del Mar Bonnín, Caterina; Varo, Cristina; Valentí, Marc; Undurraga, Juan; Strejilevich, Sergio; Sánchez-Moreno, José; Vieta, Eduard; Colom, Francesc

2016-08-01

During the last fifteen years, the possibility of delivering psychoeducation programs through Internet-based platforms have been explored. Studies evaluating those programs have shown good to acceptable retention rates. In this context, we developed a smartphone application (SIMPLe) collecting information about mood symptoms and offering personalized psychoeducation messages. The main aims of this study were to evaluate the feasibility, acceptability and satisfaction of the smartphone application. The study was conducted from March to August 2015. Participation in the study was proposed to a consecutive sample of adult patients attending an outpatient mental health clinic. Sociodemographic data, clinical and functional assessments alongside smartphone ownership and uses were collected at baseline and at 3 months' follow-up. A 5 item Likert-scale satisfaction questionnaire was also employed. 51 participants were initially enrolled in the study, 36 (74%) remained actively using the application after 3 months. The whole sample interacted with the application a mean of 77 days (SD=26.2). During these days they completed 88% of the daily tests. Over 86% of the participants agreed that the experience using the application was satisfactory. The diversity of smartphones operating systems led to a moderate, although representative, sample number. Additionally, the subjective data reporting, narrow time frame of use and stability of the patients could have affected the results. The results confirm that this particular intervention is feasible and represent a satisfactory and acceptable instrument for the self-management of bipolar disorder as an add-on to the usual treatment but future clinical trials must still probe its efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic Failure of Materials. Volume 1 - Experiments and Analyses

DTIC Science & Technology

1998-11-01

initial increments of voids do not lead to substantial relaxation of stress. In this case, the condition (8.1) gives Vv = Ao- aVv * ß=— (8.10) pc...enough strain steps to define the process accurately. At each strain step, a combined Newton-Raphson and regulafalsi solution technique (multiple trials ...laser surgery. Clinical studies have demonstrated that, for some applications, surgical lasers are superior to conventional surgical procedures

JPRS Report, Science & Technology, Europe Economic Competitiveness

DTIC Science & Technology

1991-11-14

budget resources, excluding industrial research, had increased from Fr35.6 billion in 1988 to Fr45 billion in 1992, i.e., an overall increase of...Research or the Biomedical Research Center, shows a disproportionately high growth of 18.8 percent. In environmental engineering, projects for...January 1992 with an initial complement of 350 employees, biomedical research and its clinical application will be carried out "as never before

Technical experiences of implementing a wireless tracking and facial biometric verification system for a clinical environment

NASA Astrophysics Data System (ADS)

Liu, Brent; Lee, Jasper; Documet, Jorge; Guo, Bing; King, Nelson; Huang, H. K.

2006-03-01

By implementing a tracking and verification system, clinical facilities can effectively monitor workflow and heighten information security in today's growing demand towards digital imaging informatics. This paper presents the technical design and implementation experiences encountered during the development of a Location Tracking and Verification System (LTVS) for a clinical environment. LTVS integrates facial biometrics with wireless tracking so that administrators can manage and monitor patient and staff through a web-based application. Implementation challenges fall into three main areas: 1) Development and Integration, 2) Calibration and Optimization of Wi-Fi Tracking System, and 3) Clinical Implementation. An initial prototype LTVS has been implemented within USC's Healthcare Consultation Center II Outpatient Facility, which currently has a fully digital imaging department environment with integrated HIS/RIS/PACS/VR (Voice Recognition).

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

PubMed

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

2016-02-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Early experiences in evolving an enterprise-wide information model for laboratory and clinical observations.

PubMed

Chen, Elizabeth S; Zhou, Li; Kashyap, Vipul; Schaeffer, Molly; Dykes, Patricia C; Goldberg, Howard S

2008-11-06

As Electronic Healthcare Records become more prevalent, there is an increasing need to ensure unambiguous data capture, interpretation, and exchange within and across heterogeneous applications. To address this need, a common, uniform, and comprehensive approach for representing clinical information is essential. At Partners HealthCare System, we are investigating the development and implementation of enterprise-wide information models to specify the representation of clinical information to support semantic interoperability. This paper summarizes our early experiences in: (1) defining a process for information model development, (2) reviewing and comparing existing healthcare information models, (3) identifying requirements for representation of laboratory and clinical observations, and (4) exploring linkages to existing terminology and data standards. These initial findings provide insight to the various challenges ahead and guidance on next steps for adoption of information models at our organization.

Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications.

PubMed

Golab, Karolina; Leveson-Gower, Dennis; Wang, Xiao-Jun; Grzanka, Jakub; Marek-Trzonkowska, Natalia; Krzystyniak, Adam; Millis, J Michael; Trzonkowski, Piotr; Witkowski, Piotr

2013-07-01

Promising results of initial studies applying ex-vivo expanded regulatory T cell (Treg) as a clinical intervention have increased interest in this type of the cellular therapy and several new clinical trials involving Tregs are currently on the way. Methods of isolation and expansion of Tregs have been studied and optimized to the extent that such therapy is feasible, and allows obtaining sufficient numbers of Tregs in the laboratory following Good Manufacturing Practice (GMP) guidelines. Nevertheless, Treg therapy could even more rapidly evolve if Tregs could be efficiently cryopreserved and stored for future infusion or expansions rather than utilization of only freshly isolated and expanded cells as it is preferred now. Currently, our knowledge regarding the impact of cryopreservation on Treg recovery, viability, and functionality is still limited. Based on experience with cryopreserved peripheral blood mononuclear cells (PBMCs), cryopreservation may have a detrimental effect on Tregs, can decrease Treg viability, cause abnormal cytokine secretion, and compromise expression of surface markers essential for proper Treg function and processing. Therefore, optimal strategies and conditions for Treg cryopreservation in conjunction with cell culture, expansion, and processing for clinical application still need to be investigated and defined. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

PubMed

Salmikangas, P; Flory, E; Reinhardt, J; Hinz, T; Maciulaitis, R

2010-01-01

The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

Antagonists of toll like receptor 4 maybe a new strategy to counteract opioid-induced hyperalgesia and opioid tolerance.

PubMed

Li, Qian

2012-12-01

Long term opioid treatment results in hyperalgesia and tolerance, which is a troublesome phenomenon in clinic application. Recent studies have revealed a critical role of toll-like receptor 4 (TLR4) in the neuropathological process of opioid-induced hyperalgesia and tolerance. TLR4 is predominantly expressed by microglial cells and is a key modulator in the activation of the innate immune system. Activation of TLR4 may initiate the activation of microglia and hence a number of neurotransmitters and neuromodulators that could enhance neuronal excitability are released. Blockade of TLR4 activation by its antagonists alleviate neuropathic pain. We hypothesized that opioid antagonists such as naloxone and naltrexone, which were also demonstrated to be TLR4 antagonist, may have clinic application value in attenuation of opioid-induced hyperalgesia and tolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alumina-zirconia machinable abutments for implant-supported single-tooth anterior crowns.

PubMed

Sadoun, M; Perelmuter, S

1997-01-01

Innovative materials and application techniques are constantly being developed in the ongoing search for improved restorations. This article describes a new material and the fabrication process of aesthetic machinable ceramic anterior implant abutments. The ceramic material utilized is a mixture of alumina (aluminum oxide) and ceria (cerium oxide) with partially stabilized zirconia (zirconium oxide). The initial core material is a cylinder with a 9-mm diameter and a 15-mm height, obtained by ceramic injection and presintering processes. The resultant alumina-zirconia core is porous and readily machinable. It is secured to the analog, and its design is customized by machining the abutment to suit the particular clinical circumstances. The machining is followed by glass infiltration, and the crown is finalized. The learning objective of this article is to gain a basic knowledge of the fabrication and clinical application of the custom machinable abutments.

Psychologist in a pocket: towards depression screening on mobile phones.

PubMed

Bitsch, Jó Ágila; Ramos, Roann; Ix, Tim; Ferrer-Cheng, Paula Glenda; Wehrle, Klaus

2015-01-01

Depression is the most prevalent clinical disorder and one of the main causes of disability. This makes early detection of depressive symptoms critical in its prevention and management. This paper presents and discusses the development of Psychologist in a Pocket (PiaP), a mental mHealth application for Android which screens and monitors for these symptoms, and-given the explicit permission of the user-alerts a trusted contact such as the mental health professional or a close friend, if it detects symptoms. All text inputted electronically-such as short message services, emails, social network posts-is analyzed based on keywords related to depression based on DSM-5 and ICD criteria as well as Beck's Cognitive Theory of Depression and the Self-Focus Model. Data evaluation and collection happen in the background, on-device, without requiring any user involvement. Currently, the application is in an early prototype phase entering initial clinical validation.

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

Neglect assessment as an application of virtual reality.

PubMed

Broeren, J; Samuelsson, H; Stibrant-Sunnerhagen, K; Blomstrand, C; Rydmark, M

2007-09-01

In this study a cancellation task in a virtual environment was applied to describe the pattern of search and the kinematics of hand movements in eight patients with right hemisphere stroke. Four of these patients had visual neglect and four had recovered clinically from initial symptoms of neglect. The performance of the patients was compared with that of a control group consisting of eight subjects with no history of neurological deficits. Patients with neglect as well as patients clinically recovered from neglect showed aberrant search performance in the virtual reality (VR) task, such as mixed search pattern, repeated target pressures and deviating hand movements. The results indicate that in patients with a right hemispheric stroke, this VR application can provide an additional tool for assessment that can identify small variations otherwise not detectable with standard paper-and-pencil tests. VR technology seems to be well suited for the assessment of visually guided manual exploration in space.

Mind-Body Therapies: Evidence and Implications in Advanced Oncology Practice

PubMed Central

Mayden,, Kelley D.

2012-01-01

The idea that thoughts and emotions influence health outcomes is an ancient concept that was initially abandoned by Western medicine researchers. Today, researchers are showing a renewed interest in the interactions of the mind and body and the role these interactions play in disease formation and recovery. Complementary and alternative interventions, such as mind-body therapies, are increasingly being used by cancer survivors for disease prevention, immune system enhancement, and symptom control. Traditional training has not been structured to provide advanced practitioners with an in-depth knowledge of the clinical applications of mind-body therapies. The aim of this article is to acquaint the reader with common mind-body modalities (meditation/mindfulness-based stress reduction, relaxation therapy, cognitive-behavioral therapy, hypnosis, biofeedback, music therapy, art therapy, support groups, and aromatherapy) and to examine important evidence in support of or against their clinical application. PMID:25031967

Diffusion-weighted imaging in cancer: Physical foundations and applications of Restriction Spectrum Imaging

PubMed Central

White, Nathan S.; McDonald, Carrie; Farid, Niky; Kuperman, Josh; Karow, David; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Rakow-Penner, Rebecca; Holland, Dominic; Shabaik, Ahmed; Bjørnerud, Atle; Hope, Tuva; Hattangadi-Gluth, Jona; Liss, Michael; Parsons, J. Kellogg; Chen, Clark C.; Raman, Steve; Margolis, Daniel; Reiter, Robert E.; Marks, Leonard; Kesari, Santosh; Mundt, Arno J.; Kane, Chris J.; Carter, Bob S.; Bradley, William G.; Dale, Anders M.

2014-01-01

Diffusion weighted imaging (DWI) has been at the forefront of cancer imaging since the early 2000’s. Prior to its application in clinical oncology, this powerful technique had already achieved widespread recognition due to its utility in the diagnosis of cerebral infarction. Following this initial success, the ability of DWI to detect inherent tissue contrast began to be exploited in the field of oncology. Although the initial oncologic applications for tumor detection and characterization, assessing treatment response, and predicting survival were primarily in the field of neuro-oncology, the scope of DWI has since broadened to include oncologic imaging of the prostate gland, breast, and liver. Despite its growing success and application, misconceptions as to the underlying physical basis of the DWI signal exist among researchers and clinicians alike. In this review, we provide a detailed explanation of the biophysical basis of diffusion contrast, emphasizing the difference between hindered and restricted diffusion, and elucidating how diffusion parameters in tissue are derived from the measurements via the diffusion model. We describe one advanced DWI modeling technique, called Restriction Spectrum Imaging (RSI). This technique offers a more direct in vivo measure of tumor cells, due to its ability to distinguish separable pools of water within tissue based on their intrinsic diffusion characteristics. Using RSI as an example, we then highlight the ability of advanced DWI techniques to address key clinical challenges in neuro-oncology, including improved tumor conspicuity, distinguishing actual response to therapy from pseudoresponse, and delineation of white matter tracts in regions of peritumoral edema. We also discuss how RSI, combined with new methods for correction of spatial distortions inherent diffusion MRI scans, may enable more precise spatial targeting of lesions, with implications for radiation oncology, and surgical planning. PMID:25183788

TRIAD: The Translational Research Informatics and Data Management Grid

PubMed Central

Payne, P.; Ervin, D.; Dhaval, R.; Borlawsky, T.; Lai, A.

2011-01-01

Objective Multi-disciplinary and multi-site biomedical research programs frequently require infrastructures capable of enabling the collection, management, analysis, and dissemination of heterogeneous, multi-dimensional, and distributed data and knowledge collections spanning organizational boundaries. We report on the design and initial deployment of an extensible biomedical informatics platform that is intended to address such requirements. Methods A common approach to distributed data, information, and knowledge management needs in the healthcare and life science settings is the deployment and use of a service-oriented architecture (SOA). Such SOA technologies provide for strongly-typed, semantically annotated, and stateful data and analytical services that can be combined into data and knowledge integration and analysis “pipelines.” Using this overall design pattern, we have implemented and evaluated an extensible SOA platform for clinical and translational science applications known as the Translational Research Informatics and Data-management grid (TRIAD). TRIAD is a derivative and extension of the caGrid middleware and has an emphasis on supporting agile “working interoperability” between data, information, and knowledge resources. Results Based upon initial verification and validation studies conducted in the context of a collection of driving clinical and translational research problems, we have been able to demonstrate that TRIAD achieves agile “working interoperability” between distributed data and knowledge sources. Conclusion Informed by our initial verification and validation studies, we believe TRIAD provides an example instance of a lightweight and readily adoptable approach to the use of SOA technologies in the clinical and translational research setting. Furthermore, our initial use cases illustrate the importance and efficacy of enabling “working interoperability” in heterogeneous biomedical environments. PMID:23616879

TRIAD: The Translational Research Informatics and Data Management Grid.

PubMed

Payne, P; Ervin, D; Dhaval, R; Borlawsky, T; Lai, A

2011-01-01

Multi-disciplinary and multi-site biomedical research programs frequently require infrastructures capable of enabling the collection, management, analysis, and dissemination of heterogeneous, multi-dimensional, and distributed data and knowledge collections spanning organizational boundaries. We report on the design and initial deployment of an extensible biomedical informatics platform that is intended to address such requirements. A common approach to distributed data, information, and knowledge management needs in the healthcare and life science settings is the deployment and use of a service-oriented architecture (SOA). Such SOA technologies provide for strongly-typed, semantically annotated, and stateful data and analytical services that can be combined into data and knowledge integration and analysis "pipelines." Using this overall design pattern, we have implemented and evaluated an extensible SOA platform for clinical and translational science applications known as the Translational Research Informatics and Data-management grid (TRIAD). TRIAD is a derivative and extension of the caGrid middleware and has an emphasis on supporting agile "working interoperability" between data, information, and knowledge resources. Based upon initial verification and validation studies conducted in the context of a collection of driving clinical and translational research problems, we have been able to demonstrate that TRIAD achieves agile "working interoperability" between distributed data and knowledge sources. Informed by our initial verification and validation studies, we believe TRIAD provides an example instance of a lightweight and readily adoptable approach to the use of SOA technologies in the clinical and translational research setting. Furthermore, our initial use cases illustrate the importance and efficacy of enabling "working interoperability" in heterogeneous biomedical environments.

Automatic initialization and quality control of large-scale cardiac MRI segmentations.

PubMed

Albà, Xènia; Lekadir, Karim; Pereañez, Marco; Medrano-Gracia, Pau; Young, Alistair A; Frangi, Alejandro F

2018-01-01

Continuous advances in imaging technologies enable ever more comprehensive phenotyping of human anatomy and physiology. Concomitant reduction of imaging costs has resulted in widespread use of imaging in large clinical trials and population imaging studies. Magnetic Resonance Imaging (MRI), in particular, offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and pathology. A wide range of analysis methods offer sophisticated cardiac image assessment and quantification for clinical and research studies. However, most methods have only been evaluated on relatively small databases often not accessible for open and fair benchmarking. Consequently, published performance indices are not directly comparable across studies and their translation and scalability to large clinical trials or population imaging cohorts is uncertain. Most existing techniques still rely on considerable manual intervention for the initialization and quality control of the segmentation process, becoming prohibitive when dealing with thousands of images. The contributions of this paper are three-fold. First, we propose a fully automatic method for initializing cardiac MRI segmentation, by using image features and random forests regression to predict an initial position of the heart and key anatomical landmarks in an MRI volume. In processing a full imaging database, the technique predicts the optimal corrective displacements and positions in relation to the initial rough intersections of the long and short axis images. Second, we introduce for the first time a quality control measure capable of identifying incorrect cardiac segmentations with no visual assessment. The method uses statistical, pattern and fractal descriptors in a random forest classifier to detect failures to be corrected or removed from subsequent statistical analysis. Finally, we validate these new techniques within a full pipeline for cardiac segmentation applicable to large-scale cardiac MRI databases. The results obtained based on over 1200 cases from the Cardiac Atlas Project show the promise of fully automatic initialization and quality control for population studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Cell and tissue engineering and clinical applications: an overview.

PubMed

Stoltz, J F; Bensoussan, D; Decot, V; Ciree, A; Netter, P; Gillet, P

2006-01-01

Most human tissues do not regenerate spontaneously; this is why cell therapies and tissue engineering are promising alternatives. The principle is simple: cells are collected in a patient and introduced in the damaged tissue or in a tridimentional porous support and harvested in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells is a field of research in turmoil given the hopes for clinical applications that it brings up. Embryonic stem cells are potentially more interesting since they are totipotent, but they can only be obtained at the very early stages of the embryo. The potential of adult stem cells is limited but isolating them induces no ethical problem and it has been known for more than 40 years that bone marrow does possess the regenerating functions of blood cells. Finally, the properties of foetal stem cells (blood cells from the umbilical cord) are forerunners of the haematopoietic system but the ability of these cells to participate to the formation of other tissues is more problematic. Another field for therapeutic research is that of dendritic cells, antigen presenting cells. Their efficiency in cell therapy relies on the initiation of specific immune responses. They represent a promising tool in the development of a protective immune response against antigens which the host is usually unable to generate an efficient response (melanomas, breast against cancer, prostate cancer, ..). Finally, gene therapy, has been nourishing high hopes but few clinical applications can be envisaged in the short term, although potential applications are multiple (haemophilia, myopathies, ..). A large number of clinical areas stand as candidates for clinical applications: leukaemia and cancers, cardiac insufficiency and vascular diseases, cartilage and bone repair, ligaments and tendons, liver diseases, ophthalmology, diabetes, neurological diseases (Parkinson, Huntington disease, ..), .. Various aspects of this new regenerative therapeutic medicine are developed in this work.

Integrating evidence-based interventions into client care plans.

PubMed

Doran, Diane; Carryer, Jennifer; Paterson, Jane; Goering, Paula; Nagle, Lynn; Kushniruk, Andre; Bajnok, Irmajean; Clark, Carrie; Srivastava, Rani

2009-01-01

Within the mental health care system, there is an opportunity to improve patient safety and the overall quality of care by integrating clinical practice guidelines with the care planning process through the use of information technology. Electronic assessment tools such as the Resident Assessment Inventory - Mental Health (RAI-MH) are widely used to identify the health care needs and outcomes of clients. In this knowledge translation initiative, an electronic care planning tool was enhanced to include evidence-based clinical interventions from schizophrenia guidelines. This paper describes the development of a mental health decision support prototype, a field test by clinicians, and user experiences with the application.

The McGill Interactive Pediatric OncoGenetic Guidelines: An approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation.

PubMed

Goudie, Catherine; Coltin, Hallie; Witkowski, Leora; Mourad, Stephanie; Malkin, David; Foulkes, William D

2017-08-01

Identifying cancer predisposition syndromes in children with tumors is crucial, yet few clinical guidelines exist to identify children at high risk of having germline mutations. The McGill Interactive Pediatric OncoGenetic Guidelines project aims to create a validated pediatric guideline in the form of a smartphone/tablet application using algorithms to process clinical data and help determine whether to refer a child for genetic assessment. This paper discusses the initial stages of the project, focusing on its overall structure, the methodology underpinning the algorithms, and the upcoming algorithm validation process. © 2017 Wiley Periodicals, Inc.

Peer coaching: the next step in staff development.

PubMed

Waddell, Donna L; Dunn, Nancy

2005-01-01

A common problem in continuing nursing education and staff development is the transfer of learning to clinical practice. Peer coaching offers a solution to this problem. Initiated by educators, peer coaching has been researched in educational settings and found to be effective in facilitating the transfer of newly acquired knowledge and skill into classroom teaching strategies. This article describes the background, components, process, characteristics, and benefits of peer coaching. A specific example of using peer coaching to teach clinical breast examination skills is used to illustrate the application of peer coaching to the staff development of healthcare professionals. Peer coaching is the next step in nursing staff development.

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

Optimizing clinical operations as part of a global emergency medicine initiative in Kumasi, Ghana: application of Lean manufacturing principals to low-resource health systems.

PubMed

Carter, Patrick M; Desmond, Jeffery S; Akanbobnaab, Christopher; Oteng, Rockefeller A; Rominski, Sarah D; Barsan, William G; Cunningham, Rebecca M

2012-03-01

Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems, but use of Lean in low to middle income countries with developing emergency medicine (EM) systems has not been well characterized. To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital (KATH) in Ghana and to identify key lessons learned to aid future global EM initiatives. A 3-week Lean improvement program focused on the hospital admissions process at KATH was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem-solving techniques worked well in a low-resource system without modification; 7) using Lean highlighted that important changes do not require an influx of resources; and 8) despite different levels of resources, root causes of system inefficiencies are often similar across health care systems, but require unique solutions appropriate to the clinical setting. Lean manufacturing techniques can be successfully adapted for use in developing health systems. Lessons learned from this Lean project will aid future introduction of advanced operations management techniques in low- to middle-income countries. © 2012 by the Society for Academic Emergency Medicine.

Optimizing Clinical Operations as part of a Global Emergency Medicine Initiative in Kumasi, Ghana: Application of Lean Manufacturing Principals to Low Resource Health Systems

PubMed Central

Carter, Patrick M.; Desmond, Jeffery S.; Akanbobnaab, Christopher; Oteng, Rockefeller A.; Rominski, Sarah; Barsan, William G.; Cunningham, Rebecca

2012-01-01

Background Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems; but use of Lean in low to middle income countries with developing emergency medicine systems has not been well characterized. Objectives To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital in Ghana and to identify key lessons learned to aid future global EM initiatives. Methods A three-week Lean improvement program focused on the hospital admissions process at Komfo Anokye Teaching Hospital was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. Results The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem solving techniques worked well in a low resource system without modification; 7) using Lean highlighted that important changes do not require an influx of resources; 8) despite different levels of resources, root causes of system inefficiencies are often similar across health care systems, but require unique solutions appropriate to the clinical setting. Conclusions Lean manufacturing techniques can be successfully adapted for use in developing health systems. Lessons learned from this Lean project will aid future introduction of advanced operations management techniques in low to middle income countries. PMID:22435868

Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens

PubMed Central

Stedtfeld, Robert D.; Williams, Maggie R.; Fakher, Umama; Johnson, Timothy A.; Stedtfeld, Tiffany M.; Wang, Fang; Khalife, Walid T.; Hughes, Mary; Etchebarne, Brett E.; Tiedje, James M.; Hashsham, Syed A.

2016-01-01

An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities. PMID:26850162

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.

Advances in gene therapy for heart failure.

PubMed

Fish, Kenneth M; Ishikawa, Kiyotake

2015-04-01

Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.

Genome editing in pluripotent stem cells: research and therapeutic applications.

PubMed

Deleidi, Michela; Yu, Cong

2016-05-06

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

siRNA Versus miRNA as Therapeutics for Gene Silencing

PubMed Central

Lam, Jenny K W; Chow, Michael Y T; Zhang, Yu; Leung, Susan W S

2015-01-01

Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently been investigated as novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. Clinical trials of siRNA- and miRNA-based drugs have already been initiated. siRNAs and miRNAs share many similarities, both are short duplex RNA molecules that exert gene silencing effects at the post-transcriptional level by targeting messenger RNA (mRNA), yet their mechanisms of action and clinical applications are distinct. The major difference between siRNAs and miRNAs is that the former are highly specific with only one mRNA target, whereas the latter have multiple targets. The therapeutic approaches of siRNAs and miRNAs are therefore very different. Hence, this review provides a comparison between therapeutic siRNAs and miRNAs in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed. PMID:26372022

Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

PubMed Central

Martini, Andrea; Gallotta, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2015-01-01

Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. PMID:26689503

Trabecular bone score (TBS): Method and applications.

PubMed

Martineau, P; Leslie, W D

2017-11-01

Trabecular bone score (TBS) is a texture index derived from standard lumbar spine dual energy X-ray absorptiometry (DXA) images and provides information about the underlying bone independent of the bone mineral density (BMD). Several salient observations have emerged. Numerous studies have examined the relationship between TBS and fracture risk and have shown that lower TBS values are associated with increased risk for major osteoporotic fracture in postmenopausal women and older men, with this result being independent of BMD values and other clinical risk factors. Therefore, despite being derived from standard DXA images, the information contained in TBS is independent and complementary to the information provided by BMD and the FRAX® tool. A procedure to generate TBS-adjusted FRAX probabilities has become available with the resultant predicted fracture risks shown to be more accurate than the standard FRAX tool. With these developments, TBS has emerged as a clinical tool for improved fracture risk prediction and guiding decisions regarding treatment initiation, particularly for patients with FRAX probabilities around an intervention threshold. In this article, we review the development, validation, clinical application, and limitations of TBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial

PubMed Central

Lalu, Manoj M; Sullivan, Katrina J; Mei, Shirley HJ; Moher, David; Straus, Alexander; Fergusson, Dean A; Stewart, Duncan J; Jazi, Mazen; MacLeod, Malcolm; Winston, Brent; Marshall, John; Hutton, Brian; Walley, Keith R; McIntyre, Lauralyn

2016-01-01

Evaluation of preclinical evidence prior to initiating early-phase clinical studies has typically been performed by selecting individual studies in a non-systematic process that may introduce bias. Thus, in preparation for a first-in-human trial of mesenchymal stromal cells (MSCs) for septic shock, we applied systematic review methodology to evaluate all published preclinical evidence. We identified 20 controlled comparison experiments (980 animals from 18 publications) of in vivo sepsis models. Meta-analysis demonstrated that MSC treatment of preclinical sepsis significantly reduced mortality over a range of experimental conditions (odds ratio 0.27, 95% confidence interval 0.18–0.40, latest timepoint reported for each study). Risk of bias was unclear as few studies described elements such as randomization and no studies included an appropriately calculated sample size. Moreover, the presence of publication bias resulted in a ~30% overestimate of effect and threats to validity limit the strength of our conclusions. This novel prospective application of systematic review methodology serves as a template to evaluate preclinical evidence prior to initiating first-in-human clinical studies. DOI: http://dx.doi.org/10.7554/eLife.17850.001 PMID:27870924

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

A national survey on the initial management of upper gastrointestinal bleeding.

PubMed

Liang, Peter S; Saltzman, John R

2014-01-01

To evaluate the initial management of upper gastrointestinal (GI) bleeding in the United States. Various guidelines have addressed the initial management of upper GI bleeding, but the extent to which these guidelines are followed in clinical practice is unknown. We conducted a national survey of emergency physicians, internists, and gastroenterologists practicing in hospitals affiliated with an ACGME-accredited gastroenterology fellowship. Participants rated their agreement and adherence to 9 preendoscopic quality indicators for the initial management of upper GI bleeding. Awareness, use, and barriers to the use of early prognostic risk scores were also assessed. A total of 1402 surveys were completed, with an estimated response rate of 11.3%. Gastroenterologists and trainees agreed with the quality indicators more than nongastroenterologists and attending physicians, respectively. There was no difference in the application of the quality indicators by specialty or clinical position. Among all physicians, 53% had ever heard of and 30% had ever used an upper GI bleeding risk score. More gastroenterologists than nongastroenterologists had heard of (82% vs. 44%, P<0.001) and used (51% vs. 23%, P<0.001) a risk score. There was no difference between attending physicians and trainees. Gastroenterologists and attending physicians more often cited lack of utility as a reason to not use risk scores, whereas nongastroenterologists and trainees more often cited lack of knowledge. Among emergency physicians, internists, and gastroenterologists in the United States, agreement with upper GI bleeding initial management guidelines was high but adherence--especially pertaining to the use of risk scores--was low.

Comprehensive Reproductive System Care Program - Clinical Breast Care Project (CRSCP-CBCP)

DTIC Science & Technology

2013-01-01

biomedical informatics group here, the ProLogic team, and the MDR Global leader. This Pathology Checklist tablet data capturing system development with...initiative in developing a prototype tablet application using the Pathology Checklist as the first example following a decision made at the last CBCP...enabling surgery within the center. The Breast Imaging Center has a designated Aurora Breast MRI machine. The merging of the Army and Navy Breast

Potent Inhalational Anesthetics for Dentistry

PubMed Central

Satuito, Mary; Tom, James

2016-01-01

Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

10 CFR 55.33 - Disposition of an initial application.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Disposition of an initial application. 55.33 Section 55.33 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES Applications § 55.33 Disposition of an initial application. (a) Requirements for the approval of an initial application. The Commission...

The potential offered by real-time, high-sensitivity monitoring of ethane in breath and some pilot studies using optical spectroscopy

NASA Astrophysics Data System (ADS)

Skeldon, Kenneth D.; Patterson, Claire; Wyse, Cathy A.; Gibson, Graham M.; Padgett, Miles J.; Longbottom, Chris; McMillan, Lesley C.

2005-06-01

Breath analysis applied to biomedical applications has gained much momentum is recent years due to the growing research demonstrating that breath gas can provide clinically useful data. Particularly exciting is the area of real-time breath analysis which, when coupled with appropriately chosen target species, can offer a novel method for non-invasive patient monitoring. Here we describe the role of ethane, a breath gas of universal appeal in assessing in vivo oxidative stress (cell damage). We first present a review of emerging applications where real-time ethane monitoring could yield original new results for healthcare. We then report on results from a portable ethane spectroscopy system (accuracy better then 100 parts per trillion (1 part in 1010) over a 1 s time response) that we have developed to exploit some of these applications. By presenting some initial results from pilot studies in the life sciences, we comment on the requirements that the next stage of optical spectroscopy technology has to meet in order to benefit clinical end-users.

Nanoinformatics: developing new computing applications for nanomedicine

PubMed Central

Maojo, V.; Fritts, M.; Martin-Sanchez, F.; De la Iglesia, D.; Cachau, R.E.; Garcia-Remesal, M.; Crespo, J.; Mitchell, J.A.; Anguita, A.; Baker, N.; Barreiro, J.M.; Benitez, S. E.; De la Calle, G.; Facelli, J. C.; Ghazal, P.; Geissbuhler, A.; Gonzalez-Nilo, F.; Graf, N.; Grangeat, P.; Hermosilla, I.; Hussein, R.; Kern, J.; Koch, S.; Legre, Y.; Lopez-Alonso, V.; Lopez-Campos, G.; Milanesi, L.; Moustakis, V.; Munteanu, C.; Otero, P.; Pazos, A.; Perez-Rey, D.; Potamias, G.; Sanz, F.; Kulikowski, C.

2012-01-01

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended “nanotype” to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other –omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others. PMID:22942787

Cardiac radiology: centenary review.

PubMed

de Roos, Albert; Higgins, Charles B

2014-11-01

During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

Psychosomatic approaches to obstetrics, gynaecology and andrology--a review.

PubMed

Lal, Mira

2009-01-01

This review aims to clarify the scope and clinical importance of psychosomatic approaches to obstetrics, gynaecology and andrology. This gradually expanding sub-specialty covers a wide domain of complex disease conditions that can be managed more effectively if the various biological, psychological and social aspects are recognised at the start and concurrent treatment initiated. The current need to practise biopsychosocial management of disease conditions is highlighted along with a description of what this would involve. The nine-field psychosomatic approach, which can be applied to everyday clinical encounters, has been illustrated. Clinical applications of the psychosomatic approach are discussed for various conditions including chronic pelvic pain, eating disorders, tokophobia, post-traumatic stress disorder, depression, menstrual disorders, infertility, bereavement and testicular cancer. Cultural considerations and the need for further research are also briefly discussed.

Government health policy and the diffusion of new medical devices.

PubMed Central

Hillman, B J

1986-01-01

The combination of absent financial incentives, aspects of physicians' clinical training, and the uncertainty surrounding the appropriate application of expensive new medical devices have been the most significant factors in promoting their wasteful diffusion and use. This presentation summarizes the forces that have resulted in regulatory and reimbursement initiatives to make more efficient the acquisition and utilization of new medical devices. The case histories of computed tomography (CT) and magnetic resonance imaging (MRI) serve as a paradigm demonstrating why such initiatives have thus far proved ineffectual. More effective would be to abandon distinctions between inpatient and outpatient reimbursement for using new medical devices and to improve the relationship between reimbursement and technology assessment. PMID:3818311

Juvenile animal studies and pediatric drug development: a European regulatory perspective.

PubMed

Carleer, Jacqueline; Karres, Janina

2011-08-01

During the workshop organized by ILSI/HESI on May 5-6, 2010 on the value of juvenile animal toxicity studies, the implementation of the European Pediatric Regulation and in particular the review process of the nonclinical part of the Pediatric Investigation Plan (PIP) were described. A PIP is intended to outline the development of a medicinal product in the pediatric population (i.e. quality, safety, efficacy of the medicine and timing of studies); it is reviewed and agreed by the Pediatric Committee (PDCO) of the European Medicines Agency (EMA).  The Nonclinical Working Group (NcWG) supports the PDCO in the review process of the nonclinical part of a PIP and is composed of members from the PDCO, the EMA Safety Working Party, additional experts from national competent authorities and the FDA.  This article summarizes the NcWG review process and outcomes of 97 approved or ongoing PIPs, from the establishment of the NcWG in November 2008 to May 2010, as presented during the workshop. Juvenile animal studies were proposed by the applicant in 33% or required by the NcWG in 26% of the PIPs. The requirements were mainly motivated by concerns regarding potential developmental toxicities, in view of the young age of the pediatric population to be investigated, the lack of knowledge concerning the maturation of the pharmacological target, the lack of sufficient (non)clinical data, observed toxicities in the adult (non)clinical studies and the long duration of the intended treatments. Most juvenile animal studies were in the therapeutic areas of oncology, infectious diseases and endocrinology. In about 14% of the PIPs submitted, the NcWG requested either justifications of, or amendments to the study designs proposed by the applicants (e.g. justification of endpoints, study duration, species selection and timing with regards to clinical pediatric studies). Generally, only one species was selected or proposed for the juvenile studies, the rat being the most prevalent. The number of juvenile studies initially proposed by the applicant plus those requested by the NcWG was higher than the number of studies included in the "key binding elements" of the PIP opinions. This apparent discrepancy was mainly due to additional information or justifications submitted by the applicant during the clock stop. It was noted that the PIPs initially submitted often lacked information relevant to the nonclinical evaluation. Therefore, during the workshop, the need to provide scientifically based justifications when no juvenile animal studies are proposed in the initial PIP submission was stressed. © 2011 Wiley-Liss, Inc.

Gas-Stabilizing Gold Nanocones for Acoustically Mediated Drug Delivery.

PubMed

Mannaris, Christophoros; Teo, Boon M; Seth, Anjali; Bau, Luca; Coussios, Constantin; Stride, Eleanor

2018-06-01

The efficient penetration of drugs into tumors is a major challenge that remains unmet. Reported herein is a strategy to promote extravasation and enhanced penetration using inertial cavitation initiated by focused ultrasound and cone-shaped gold nanoparticles that entrap gas nanobubbles. The cones are capable of initiating inertial cavitation under pressures and frequencies achievable with existing clinical ultrasound systems and of promoting extravasation and delivery of a model large therapeutic molecule in an in vitro tissue mimicking flow phantom, achieving penetration depths in excess of 2 mm. Ease of functionalization and intrinsic imaging capabilities provide gold with significant advantages as a material for biomedical applications. The cones show neither cytotoxicity in Michigan Cancer Foundation (MCF)-7 cells nor hemolytic activity in human blood at clinically relevant concentrations and are found to be colloidally stable for at least 5 d at 37 °C and several months at 4 °C. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

PubMed

Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

2014-01-01

The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

PubMed

Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

2014-01-01

The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, medical researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

Developing a clinical information system: the role of the chief information officer.

PubMed

Glaser, J

1994-11-01

Chief information officers (CIOs) must play a pivotal role in the formation and implementation of a clinical information system, the subset of an organizational information system that deals specifically with support of clinical care activities. Major elements include the applications software, technology and data architecture, databases, and analysis. The organizational structures and processes that manage the development of improvement activities, including the clinical information system itself, are just as vital to the design of an information system as the hardware and software. To develop, sustain, and advance an information infrastructure, the CIO must help establish certain organizational precursors, such as medical staff involvement, experience with quality improvement, and ability to meet data needs. The CIO must then work with the senior administrative and medical leadership in developing a vision for the information system. The CIO must also create new roles and knowledge for information system and medical staff members. Interaction between information services and medical staff is vitally important to the success of a clinical information system. Organizational committees and structures that Brigham and Women's Hospital in Boston put in place to formalize the relationship between information systems and medical staff include the Clinical Initiative Development Program and the Center for Applied Medical Information Systems Research. Improving the clinical management of care and the efficacy of care processes involves complex changes in organizational culture and processes, medical practice and information system applications, technologies, staff, and data.

[Generalization of the results of clinical studies through the analysis of subgroups].

PubMed

Costa, João; Fareleira, Filipa; Ascensão, Raquel; Vaz Carneiro, António

2012-01-01

Subgroup analysis in clinical trials are usually performed to define the potential heterogeneity of treatment effect in relation with the baseline risk, physiopathology, practical application of therapy or the under-utilization in clinical practice of effective interventions due to uncertainties of its benefit/risk ratio. When appropriately planned, subgroup analysis are a valid methodology the define benefits in subgroups of patients, thus providing good quality evidence to support clinical decision making. However, in order to be correct, subgroup analysis should be defined a priori, done in small numbers, should be fully reported and, most important, must endure statistical tests for interaction. In this paper we present an example of the treatment of post-menopausal osteoporosis, in which the benefits of an intervention (the higher the fracture risk is, the better the benefit is) with a specific agent (bazedoxifene) was only disclosed after a post-hoc analysis of the initial global trial sample.

System Architecture for Temporal Information Extraction, Representation and Reasoning in Clinical Narrative Reports

PubMed Central

Zhou, Li; Friedman, Carol; Parsons, Simon; Hripcsak, George

2005-01-01

Exploring temporal information in narrative Electronic Medical Records (EMRs) is essential and challenging. We propose an architecture for an integrated approach to process temporal information in clinical narrative reports. The goal is to initiate and build a foundation that supports applications which assist healthcare practice and research by including the ability to determine the time of clinical events (e.g., past vs. present). Key components include: (1) a temporal constraint structure for temporal expressions and the development of an associated tagger; (2) a Natural Language Processing (NLP) system for encoding and extracting medical events and associating them with formalized temporal data; (3) a post-processor, with a knowledge-based subsystem to help discover implicit information, that resolves temporal expressions and deals with issues such as granularity and vagueness; and (4) a reasoning mechanism which models clinical reports as Simple Temporal Problems (STPs). PMID:16779164

In Vivo Imaging and Monitoring of Transplanted Stem Cells: Clinical Applications

PubMed Central

Rodriguez-Porcel, Martin

2010-01-01

Regenerative medicine using stem cells has appeared as a potential therapeutic alternative for coronary artery disease, and stem cell clinical studies are currently on their way. However, initial results of these studies have provided mixed information, in part because of the inability to correlate organ functional information with the presence/absence of transplanted stem cells. Recent advances in molecular biology and imaging have allowed the successful noninvasive monitoring of transplanted stem cells in the living subject. In this article, different imaging strategies (direct labeling, indirect labeling with reporter genes) to study the viability and biology of stem cells are discussed. In addition, the limitations of each approach and imaging modality (eg, single photon emission computed tomography, positron emission tomography, and MRI) and their requirements for clinical use are addressed. Use of these strategies will be critical as the different regenerative therapies are being tested for clinical use. PMID:20425184

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer

PubMed Central

Wei, Fang; Wong, David T.; Su, Wu-Chou

2015-01-01

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer. PMID:26448936

Three Decades of Research on Computer Applications in Health Care

PubMed Central

Michael Fitzmaurice, J.; Adams, Karen; Eisenberg, John M.

2002-01-01

The Agency for Healthcare Research and Quality and its predecessor organizations—collectively referred to here as AHRQ—have a productive history of funding research and development in the field of medical informatics, with grant investments since 1968 totaling $107 million. Many computerized interventions that are commonplace today, such as drug interaction alerts, had their genesis in early AHRQ initiatives. This review provides a historical perspective on AHRQ investment in medical informatics research. It shows that grants provided by AHRQ resulted in achievements that include advancing automation in the clinical laboratory and radiology, assisting in technology development (computer languages, software, and hardware), evaluating the effectiveness of computer-based medical information systems, facilitating the evolution of computer-aided decision making, promoting computer-initiated quality assurance programs, backing the formation and application of comprehensive data banks, enhancing the management of specific conditions such as HIV infection, and supporting health data coding and standards initiatives. Other federal agencies and private organizations have also supported research in medical informatics, some earlier and to a greater degree than AHRQ. The results and relative roles of these related efforts are beyond the scope of this review. PMID:11861630

Remineralization Capacity of Three Fissure Sealants with and without Gaseous Ozone on Non-Cavitated Incipient Pit and Fissure Caries.

PubMed

Unal, M; Oztas, N

2015-01-01

The purpose of this study was to investigate the remineralization activation of the application of three fissure sealants (FSs), alone or with gaseous ozone (GO), on non-cavitated initial caries and evaluate the clinical success of FS. Sixty children who had DIAGNOdent scores between 10-30 on bilateral symmetric mandibular first permanent molars were included in study. In a split-mouth design, teeth were assigned to experimental (with GO) and control (without GO) groups. GO was applied to teeth on one side and then the same brand of randomly selected FSs was applied to the teeth on both sides. Children were divided into 3 groups based on type of FS (Group 1: Aegis {Bosworth Co, North Hamlin Avenue Skokie, Illinois, USA}, Group 2: Fuji Triage {GC, Tokyo, Japan}, Group 3: Helioseal {Ivoclar Vivadent, Liechtenstein, Germany}). All FSs were then examined for retention rates at 1, 3, 6, 9, and 12 months; at the end of 12 months, all FSs were removed with an air-abrasion device and DIAGNOdent scores noted to compare with the initial values. The application of GO with either Fuji Triage or Aegis FS was effective on remineralization (p<0.05); however, the application of Helioseal FSs was not effective (p>0.05). The 1(st) and 12(th) months' full retention rates of Fuji Triage FSs was a significant difference (p<0.05) from other FSs (Aegis and Helioseal) (p>0.05). GO+Aegis FS showed the highest remineralization; and, at the end of 12 months, its clinical success was higher than other FSs.

Applicable or non-applicable: investigations of clinical heterogeneity in systematic reviews.

PubMed

Chess, Laura E; Gagnier, Joel J

2016-02-17

Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. The most recent 100 systematic reviews from the top five journals in medicine-JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine-and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81% of Cochrane reviews and 90% of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1% of non-Cochrane reviews and 8% of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very few studies mentioned clinician training, compliance, brand, co-interventions, dose route, ethnicity, prognostic markers and psychosocial variables as covariates to investigate as potentially clinically heterogeneous. Addressing aspects of clinical heterogeneity was not different between Cochrane and non-Cochrane reviews. The ability to quantify and compare the clinical differences of trials within a meta-analysis is crucial to determining its applicability and use in clinical practice. Despite Cochrane Collaboration emphasis on methodology, the proportion of reviews that assess clinical heterogeneity is less than those of non-Cochrane reviews. Our assessment reveals that there is room for improvement in assessing clinical heterogeneity in both Cochrane and non-Cochrane reviews.

Comprehensive in-hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Parissis, John; Brunner-La Rocca, Hans-Peter; Čelutkienė, Jelena; Chioncel, Ovidiu; Collins, Sean P; De Backer, Daniel; Filippatos, Gerasimos S; Gayat, Etienne; Hill, Loreena; Lainscak, Mitja; Lassus, Johan; Masip, Josep; Mebazaa, Alexandre; Miró, Òscar; Mortara, Andrea; Mueller, Christian; Mullens, Wilfried; Nieminen, Markku S; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar M; Sionis, Alessandro; Vieillard-Baron, Antoine; Weinstein, Jean Marc; de Boer, Rudolf A; Crespo Leiro, Maria G; Piepoli, Massimo; Riley, Jillian P

2018-04-30

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future.

PubMed

Jonnal, Ravi S; Kocaoglu, Omer P; Zawadzki, Robert J; Liu, Zhuolin; Miller, Donald T; Werner, John S

2016-07-01

Optical coherence tomography (OCT) has enabled "virtual biopsy" of the living human retina, revolutionizing both basic retina research and clinical practice over the past 25 years. For most of those years, in parallel, adaptive optics (AO) has been used to improve the transverse resolution of ophthalmoscopes to foster in vivo study of the retina at the microscopic level. Here, we review work done over the last 15 years to combine the microscopic transverse resolution of AO with the microscopic axial resolution of OCT, building AO-OCT systems with the highest three-dimensional resolution of any existing retinal imaging modality. We surveyed the literature to identify the most influential antecedent work, important milestones in the development of AO-OCT technology, its applications that have yielded new knowledge, research areas into which it may productively expand, and nascent applications that have the potential to grow. Initial efforts focused on demonstrating three-dimensional resolution. Since then, many improvements have been made in resolution and speed, as well as other enhancements of acquisition and postprocessing techniques. Progress on these fronts has produced numerous discoveries about the anatomy, function, and optical properties of the retina. Adaptive optics OCT continues to evolve technically and to contribute to our basic and clinical knowledge of the retina. Due to its capacity to reveal cellular and microscopic detail invisible to clinical OCT systems, it is an ideal companion to those instruments and has the demonstrable potential to produce images that can guide the interpretation of clinical findings.

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).

What rheumatologists need to know about CRISPR/Cas9.

PubMed

Gibson, Gary J; Yang, Maozhou

2017-04-01

CRISPR/Cas9 genome editing technology has taken the research world by storm since its use in eukaryotes was first proposed in 2012. Publications describing advances in technology and new applications have continued at an unrelenting pace since that time. In this Review, we discuss the application of CRISPR/Cas9 for creating gene mutations - the application that initiated the current avalanche of interest - and new developments that have largely answered initial concerns about its specificity and ability to introduce new gene sequences. We discuss the new, diverse and rapidly growing adaptations of the CRISPR/Cas9 technique that enable activation, repression, multiplexing and gene screening. These developments have enabled researchers to create sophisticated tools for dissecting the function and inter-relatedness of genes, as well as noncoding regions of the genome, and to identify gene networks and noncoding regions that promote disease or confer disease susceptibility. These approaches are beginning to be used to interrogate complex and multilayered biological systems and to produce complex animal models of disease. CRISPR/Cas9 technology has enabled the application of new therapeutic approaches to treating disease in animal models, some of which are beginning to be seen in the first human clinical trials. We discuss the direct application of these techniques to rheumatic diseases, which are currently limited but are sure to increase rapidly in the near future.

TU-EF-210-01: HIFU, Drug Delivery, and Immunotherapy

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

Ferrara, K.

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imagingmore » Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.« less

TU-EF-210-04: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy

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

Farahani, K.

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imagingmore » Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.« less

TU-EF-210-03: Real-Time Ablation Monitoring and Lesion Quantification Using Harmonic Motion Imaging

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

Konofagou, E.

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imagingmore » Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.« less

TU-EF-210-00: Therapeutic Strategies and Image Guidance

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

NONE

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imagingmore » Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.« less

TU-EF-210-02: MRg Hyperthermia

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

Chopra, R.

2015-06-15

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imagingmore » Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.« less

Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.

PubMed

Rincon, Melvin Y; VandenDriessche, Thierry; Chuah, Marinee K

2015-10-01

Gene therapy is a promising modality for the treatment of inherited and acquired cardiovascular diseases. The identification of the molecular pathways involved in the pathophysiology of heart failure and other associated cardiac diseases led to encouraging preclinical gene therapy studies in small and large animal models. However, the initial clinical results yielded only modest or no improvement in clinical endpoints. The presence of neutralizing antibodies and cellular immune responses directed against the viral vector and/or the gene-modified cells, the insufficient gene expression levels, and the limited gene transduction efficiencies accounted for the overall limited clinical improvements. Nevertheless, further improvements of the gene delivery technology and a better understanding of the underlying biology fostered renewed interest in gene therapy for heart failure. In particular, improved vectors based on emerging cardiotropic serotypes of the adeno-associated viral vector (AAV) are particularly well suited to coax expression of therapeutic genes in the heart. This led to new clinical trials based on the delivery of the sarcoplasmic reticulum Ca(2+)-ATPase protein (SERCA2a). Though the first clinical results were encouraging, a recent Phase IIb trial did not confirm the beneficial clinical outcomes that were initially reported. New approaches based on S100A1 and adenylate cyclase 6 are also being considered for clinical applications. Emerging paradigms based on the use of miRNA regulation or CRISPR/Cas9-based genome engineering open new therapeutic perspectives for treating cardiovascular diseases by gene therapy. Nevertheless, the continuous improvement of cardiac gene delivery is needed to allow the use of safer and more effective vector doses, ultimately bringing gene therapy for heart failure one step closer to reality. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Designing for scale: optimising the health information system architecture for mobile maternal health messaging in South Africa (MomConnect)

PubMed Central

Seebregts, Christopher; Dane, Pierre; Parsons, Annie Neo; Fogwill, Thomas; Rogers, Debbie; Bekker, Marcha; Shaw, Vincent; Barron, Peter

2018-01-01

MomConnect is a national initiative coordinated by the South African National Department of Health that sends text-based mobile phone messages free of charge to pregnant women who voluntarily register at any public healthcare facility in South Africa. We describe the system design and architecture of the MomConnect technical platform, planned as a nationally scalable and extensible initiative. It uses a health information exchange that can connect any standards-compliant electronic front-end application to any standards-compliant electronic back-end database. The implementation of the MomConnect technical platform, in turn, is a national reference application for electronic interoperability in line with the South African National Health Normative Standards Framework. The use of open content and messaging standards enables the architecture to include any application adhering to the selected standards. Its national implementation at scale demonstrates both the use of this technology and a key objective of global health information systems, which is to achieve implementation scale. The system’s limited clinical information, initially, allowed the architecture to focus on the base standards and profiles for interoperability in a resource-constrained environment with limited connectivity and infrastructural capacity. Maintenance of the system requires mobilisation of national resources. Future work aims to use the standard interfaces to include data from additional applications as well as to extend and interface the framework with other public health information systems in South Africa. The development of this platform has also shown the benefits of interoperability at both an organisational and technical level in South Africa. PMID:29713506

Designing for scale: optimising the health information system architecture for mobile maternal health messaging in South Africa (MomConnect).

PubMed

Seebregts, Christopher; Dane, Pierre; Parsons, Annie Neo; Fogwill, Thomas; Rogers, Debbie; Bekker, Marcha; Shaw, Vincent; Barron, Peter

2018-01-01

MomConnect is a national initiative coordinated by the South African National Department of Health that sends text-based mobile phone messages free of charge to pregnant women who voluntarily register at any public healthcare facility in South Africa. We describe the system design and architecture of the MomConnect technical platform, planned as a nationally scalable and extensible initiative. It uses a health information exchange that can connect any standards-compliant electronic front-end application to any standards-compliant electronic back-end database. The implementation of the MomConnect technical platform, in turn, is a national reference application for electronic interoperability in line with the South African National Health Normative Standards Framework. The use of open content and messaging standards enables the architecture to include any application adhering to the selected standards. Its national implementation at scale demonstrates both the use of this technology and a key objective of global health information systems, which is to achieve implementation scale. The system's limited clinical information, initially, allowed the architecture to focus on the base standards and profiles for interoperability in a resource-constrained environment with limited connectivity and infrastructural capacity. Maintenance of the system requires mobilisation of national resources. Future work aims to use the standard interfaces to include data from additional applications as well as to extend and interface the framework with other public health information systems in South Africa. The development of this platform has also shown the benefits of interoperability at both an organisational and technical level in South Africa.

Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models

PubMed Central

Finch, Paul W; Mark Cross, Lawrence J; McAuley, Daniel F; Farrell, Catherine L

2013-01-01

Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre-clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre-clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre-clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin. PMID:24151975

Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting.

PubMed

Gibney, Geoffrey T; Gauthier, Geneviève; Ayas, Charles; Galebach, Philip; Wu, Eric Q; Abhyankar, Sarang; Reyes, Carolina; Guérin, Annie; Yim, Yeun Mi

2015-08-01

Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases (MBM). We examined the real-world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0-1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow-up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan-Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5-10 mm vs. < 5 mm) and number of brain metastases (≥ 5 vs. < 2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. < 2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥ 2 extracranial disease sites, progressive extracranial disease, and ≥ 5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Using digital photography in a clinical setting: a valid, accurate, and applicable method to assess food intake.

PubMed

Winzer, Eva; Luger, Maria; Schindler, Karin

2018-06-01

Regular monitoring of food intake is hardly integrated in clinical routine. Therefore, the aim was to examine the validity, accuracy, and applicability of an appropriate and also quick and easy-to-use tool for recording food intake in a clinical setting. Two digital photography methods, the postMeal method with a picture after the meal, the pre-postMeal method with a picture before and after the meal, and the visual estimation method (plate diagram; PD) were compared against the reference method (weighed food records; WFR). A total of 420 dishes from lunch (7 weeks) were estimated with both photography methods and the visual method. Validity, applicability, accuracy, and precision of the estimation methods, and additionally food waste, macronutrient composition, and energy content were examined. Tests of validity revealed stronger correlations for photography methods (postMeal: r = 0.971, p < 0.001; pre-postMeal: r = 0.995, p < 0.001) compared to the visual estimation method (r = 0.810; p < 0.001). The pre-postMeal method showed smaller variability (bias < 1 g) and also smaller overestimation and underestimation. This method accurately and precisely estimated portion sizes in all food items. Furthermore, the total food waste was 22% for lunch over the study period. The highest food waste was observed in salads and the lowest in desserts. The pre-postMeal digital photography method is valid, accurate, and applicable in monitoring food intake in clinical setting, which enables a quantitative and qualitative dietary assessment. Thus, nutritional care might be initiated earlier. This method might be also advantageous for quantitative and qualitative evaluation of food waste, with a resultantly reduction in costs.

Oral Anticoagulant Therapy

PubMed Central

Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

2012-01-01

Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

Innovative partnerships: the clinical nurse leader role in diverse clinical settings.

PubMed

Lammon, Carol Ann Barnett; Stanton, Marietta P; Blakney, John L

2010-01-01

The American Association of Colleges of Nursing in collaboration with leaders in the health care arena has developed a new role in nursing, the clinical nurse leader (CNL). The CNL is a master's-prepared advanced nurse generalist, accountable for providing high-quality, cost-effective care for a cohort of patients in a specific microsystem. Although initial implementation of the CNL has been predominantly in urban acute care settings, the skill set of the CNL role is equally applicable to diverse clinical settings, such as smaller rural hospitals, home-based home care providers, long-term care facilities, schools, Veteran's Administration facilities, and public health settings. This article reports the strategies used and the progress made at The University of Alabama Capstone College of Nursing in the development of innovative partnerships to develop the role of the CNL in diverse clinical settings. With academia and practice working in partnership, the goal of transforming health care and improving patient outcomes can be achieved. Copyright © 2010 Elsevier Inc. All rights reserved.

Latest developments in MUC1 immunotherapy.

PubMed

Taylor-Papadimitriou, Joyce; Burchell, Joy M; Graham, Rosalind; Beatson, Richard

2018-05-21

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. © 2018 The Author(s).

PTT Advisor: A CDC-supported initiative to develop a mobile clinical laboratory decision support application for the iOS platform

PubMed Central

Savel, Thomas G.; Lee, Brian A.; Ledbetter, Greg; Brown, Sara; LaValley, Dale; Taylor, Julie; Thompson, Pam

2013-01-01

Objectives: This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. Methods: The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. Results: As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Conclusions: Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development). PMID:23923100

PTT Advisor: A CDC-supported initiative to develop a mobile clinical laboratory decision support application for the iOS platform.

PubMed

Savel, Thomas G; Lee, Brian A; Ledbetter, Greg; Brown, Sara; Lavalley, Dale; Taylor, Julie; Thompson, Pam

2013-01-01

This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development).

Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation

PubMed Central

Gong, Inna Y.; Schwarz, Ute I.; Crown, Natalie; Dresser, George K.; Lazo-Langner, Alejandro; Zou, GuangYong; Roden, Dan M.; Stein, C. Michael; Rodger, Marc; Wells, Philip S.; Kim, Richard B.; Tirona, Rommel G.

2011-01-01

Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. PMID:22114699

CRNDE: An important oncogenic long non-coding RNA in human cancers.

PubMed

Zhang, Jiaming; Yin, Minuo; Peng, Gang; Zhao, Yingchao

2018-06-01

Aberrant overexpression of long non-coding RNA CRNDE (Colorectal Neoplasia Differentially Expressed) is confirmed in various human cancers, which is correlated with advanced clinicopathological features and poor prognosis. CRNDE promotes cancer cell proliferation, migration and invasion, and suppresses apoptosis in complicated mechanisms, which result in the initialization and development of human cancers. In this review, we provide an overview of the oncogenic role and potential clinical applications of CRNDE. © 2018 John Wiley & Sons Ltd.

A Scoping Review of Health Game Research: Past, Present, and Future

PubMed Central

Lu, Amy Shirong; Gharghabi, Fardad; Coleman, Whitney

2012-01-01

Abstract Health game research has flourished over the last decade. The number of peer-reviewed scientific publications has surged as the clinical application of health games has diversified. In response to this growth, several past literature reviews have assessed the effectiveness of health games in specific clinical subdomains. The past literature reviews, however, have not provided a general scope of health games independent of clinical context. The present systematic review identified 149 publications. All sources were published before 2011 in a peer-reviewed venue. To be included in this review, publications were required (1) to be an original research, (2) to focus on health, (3) to utilize a sound research design, (4) to report quantitative health outcomes, and (5) to target healthcare receivers. Initial findings showed certain trends in health game publications: Focus on younger male demographics, relatively low number of study participants, increased number of controlled trials, short duration of intervention periods, short duration and frequency of user–game interaction, dominance of exercise and rehab games, lack of underlying theoretical frameworks, and concentration on clinical contexts such as physical activity and nutrition. The review concludes that future research should (1) widen the demographics to include females and elderly, (2) increase the number of participants in controlled trials, (3) lengthen both the intervention period and user–game interaction duration, and (4) expand the application of health games in new clinical contexts. PMID:24416638

Building the Evidence Base for Decision-making in Cancer Genomic Medicine Using Comparative Effectiveness Research

PubMed Central

Goddard, Katrina A.B.; Knaus, William A.; Whitlock, Evelyn; Lyman, Gary H.; Feigelson, Heather Spencer; Schully, Sheri D.; Ramsey, Scott; Tunis, Sean; Freedman, Andrew N.; Khoury, Muin J.; Veenstra, David L.

2013-01-01

Background The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. Objectives To identify approaches to help stakeholders make evidence-based decisions, and to describe potential challenges and opportunities using CER to produce evidence-based guidance. Methods We identified general CER approaches for genomic applications through literature review, the authors’ experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Results Evidence generation and synthesis approaches include comparative observational and randomized trials, patient reported outcomes, decision modeling, and economic analysis. We identified significant challenges to conducting CER in cancer genomics: the rapid pace of innovation, the lack of regulation, the limited evidence for clinical utility, and the beliefs that genomic tests could have personal utility without having clinical utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. Conclusions CER offers a variety of methodological approaches to address stakeholders’ needs. Innovative approaches are needed to ensure an effective translation of genomic discoveries. PMID:22516979

Adoption of telemedicine in Scottish remote and rural general practices: a qualitative study.

PubMed

King, Gerry; Richards, Helen; Godden, David

2007-01-01

We conducted a qualitative interview study to explore the factors that have facilitated and prevented the adoption of telemedicine in general practice in remote and rural Scotland. Face-to-face interviews were carried out with general practitioners (GPs) and practice nurses in 26 of Scotland's most remote practices and five of the seven most rural health boards. The interview study found that GPs were more positive about the use of computers and telemedicine than nurses. Although electronic access to simple data, such as laboratory results, had become widely accepted, most respondents had very little experience of more sophisticated telemedicine applications, such as videoconferencing. There was widespread scepticism about the potential usefulness of clinical applications of telemedicine, although it was perceived to have potential benefit in facilitating access to educational resources. A number of barriers to the adoption of telemedicine were reported, including concerns that videoconferencing could diminish the quality of communication in educational and clinical settings, and that telemedicine would not fit easily with the organizational routines of the practices. Policy-makers should prioritize strategies to develop educational programmes, as these are more likely to succeed than clinical initiatives. It may then follow that clinicians will see opportunities for use in their clinical work.

[Comparison and review on specifications of fermented Cordyceps sinensis products].

PubMed

Yang, Ping; Zhao, Xiao-Xia; Zhang, Yong-Wen

2018-02-01

There are five kinds of fermented Cordyceps crude drug and their preparations that have been approved as medicine on the market. Since the initial strains of the crude drug were all isolated from natural Cordyceps sinensis， they have similar names， chemical components and even clinical applications. However， because of the different strain species and fermentation processes， there was significant difference in quality. As a result， they should be clearly distinguished in clinical use. Most of the products were researched and developed during the 1980s and 1990s， so there was difference in quality standards for different products， and their quality control levels of some products were not perfect. At present， some of the products are approved as Chinese medicine， others are approved as chemical drugs， with a confusion in products name， management and clinical application. In this paper， the approval numbers， quality standards and clinical applications， and current problems of these products were summarized and compared; some suggestions were put forward， such as standardizing the product name， unifying the management of approval number category， and increasing the specific quality control attributes， in order to provide reference for standard implementation， quality control and drug regulation for fermented Cordyceps crude drugs and their preparations. Copyright© by the Chinese Pharmaceutical Association.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

The NIMH Research Domain Criteria Initiative: Background, Issues, and Pragmatics.

PubMed

Kozak, Michael J; Cuthbert, Bruce N

2016-03-01

This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct "grain size," and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells.

PubMed

Hong, So Gun; Dunbar, Cynthia E; Winkler, Thomas

2013-02-01

Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced.

A systematic review of healthcare applications for smartphones.

PubMed

Mosa, Abu Saleh Mohammad; Yoo, Illhoi; Sheets, Lincoln

2012-07-10

Advanced mobile communications and portable computation are now combined in handheld devices called "smartphones", which are also capable of running third-party software. The number of smartphone users is growing rapidly, including among healthcare professionals. The purpose of this study was to classify smartphone-based healthcare technologies as discussed in academic literature according to their functionalities, and summarize articles in each category. In April 2011, MEDLINE was searched to identify articles that discussed the design, development, evaluation, or use of smartphone-based software for healthcare professionals, medical or nursing students, or patients. A total of 55 articles discussing 83 applications were selected for this study from 2,894 articles initially obtained from the MEDLINE searches. A total of 83 applications were documented: 57 applications for healthcare professionals focusing on disease diagnosis (21), drug reference (6), medical calculators (8), literature search (6), clinical communication (3), Hospital Information System (HIS) client applications (4), medical training (2) and general healthcare applications (7); 11 applications for medical or nursing students focusing on medical education; and 15 applications for patients focusing on disease management with chronic illness (6), ENT-related (4), fall-related (3), and two other conditions (2). The disease diagnosis, drug reference, and medical calculator applications were reported as most useful by healthcare professionals and medical or nursing students. Many medical applications for smartphones have been developed and widely used by health professionals and patients. The use of smartphones is getting more attention in healthcare day by day. Medical applications make smartphones useful tools in the practice of evidence-based medicine at the point of care, in addition to their use in mobile clinical communication. Also, smartphones can play a very important role in patient education, disease self-management, and remote monitoring of patients.

A Systematic Review of Healthcare Applications for Smartphones

PubMed Central

2012-01-01

Background Advanced mobile communications and portable computation are now combined in handheld devices called “smartphones”, which are also capable of running third-party software. The number of smartphone users is growing rapidly, including among healthcare professionals. The purpose of this study was to classify smartphone-based healthcare technologies as discussed in academic literature according to their functionalities, and summarize articles in each category. Methods In April 2011, MEDLINE was searched to identify articles that discussed the design, development, evaluation, or use of smartphone-based software for healthcare professionals, medical or nursing students, or patients. A total of 55 articles discussing 83 applications were selected for this study from 2,894 articles initially obtained from the MEDLINE searches. Results A total of 83 applications were documented: 57 applications for healthcare professionals focusing on disease diagnosis (21), drug reference (6), medical calculators (8), literature search (6), clinical communication (3), Hospital Information System (HIS) client applications (4), medical training (2) and general healthcare applications (7); 11 applications for medical or nursing students focusing on medical education; and 15 applications for patients focusing on disease management with chronic illness (6), ENT-related (4), fall-related (3), and two other conditions (2). The disease diagnosis, drug reference, and medical calculator applications were reported as most useful by healthcare professionals and medical or nursing students. Conclusions Many medical applications for smartphones have been developed and widely used by health professionals and patients. The use of smartphones is getting more attention in healthcare day by day. Medical applications make smartphones useful tools in the practice of evidence-based medicine at the point of care, in addition to their use in mobile clinical communication. Also, smartphones can play a very important role in patient education, disease self-management, and remote monitoring of patients. PMID:22781312

The use of renal replacement therapy in acute decompensated heart failure.

PubMed

Udani, Suneel M; Murray, Patrick T

2009-01-01

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

PubMed

Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M

2017-02-07

The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

Big data in healthcare - the promises, challenges and opportunities from a research perspective: A case study with a model database.

PubMed

Adibuzzaman, Mohammad; DeLaurentis, Poching; Hill, Jennifer; Benneyworth, Brian D

2017-01-01

Recent advances in data collection during routine health care in the form of Electronic Health Records (EHR), medical device data (e.g., infusion pump informatics, physiological monitoring data, and insurance claims data, among others, as well as biological and experimental data, have created tremendous opportunities for biological discoveries for clinical application. However, even with all the advancement in technologies and their promises for discoveries, very few research findings have been translated to clinical knowledge, or more importantly, to clinical practice. In this paper, we identify and present the initial work addressing the relevant challenges in three broad categories: data, accessibility, and translation. These issues are discussed in the context of a widely used detailed database from an intensive care unit, Medical Information Mart for Intensive Care (MIMIC III) database.

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis.

PubMed

Velupillai, S; Mowery, D; South, B R; Kvist, M; Dalianis, H

2015-08-13

We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices.

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis

PubMed Central

Mowery, D.; South, B. R.; Kvist, M.; Dalianis, H.

2015-01-01

Summary Objectives We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. Methods We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Results Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. Conclusions There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices. PMID:26293867

Success factors for telehealth--a case study.

PubMed

Moehr, J R; Schaafsma, J; Anglin, C; Pantazi, S V; Grimm, N A; Anglin, S

2006-01-01

To present the lessons learned from an evaluation of a comprehensive telehealth project regarding success factors and evaluation methodology for such projects. A recent experience with the evaluation of new telehealth services in BC, Canada, is summarized. Two domains of clinical applications, as well as educational and administrative uses, and the project environment were evaluated. In order to contribute to the success of the project, the evaluation included formative and summative approaches employing qualitative and quantitative methods with data collection from telehealth events, participants and existing databases. The evaluation had to be carried out under severe budgetary and time constraints. We therefore deliberately chose a broad ranging exploratory approach within a framework provided, and generated questions to be answered on the basis of initial observations and participant driven interviews with progressively more focused and detailed data gathering, including perusal of a variety of existing data sources. A unique feature was an economic evaluation using static simulation models. The evaluation yielded rich and detailed data, which were able to explain a number of unanticipated findings. One clinical application domain was cancelled after 6 months, the other continues. The factors contributing to success include: Focus on chronic conditions which require visual information for proper management. Involvement of established teams in regular scheduled visits or in sessions scheduled well in advance. Problems arose with: Ad hoc applications, in particular under emergency conditions. Applications that disregard established referral patterns. Applications that support only part of a unit's services. The latter leads to the service mismatch dilemma (SMMD) with the end result that even those e-health services provided are not used. The problems encountered were compounded by issues arising from the manner in which the telehealth services had been introduced, in particular the lack of time for preparation and establishment of routine use. Educational applications had significant clinical benefits. Administrative applications generated savings which exceeded the substantial capital investment and made educational and clinical applications available at variable cost. Evaluation under severe constraints can yield rich information. The identified success factors, including provision of an overarching architecture and infrastructure, strong program management, thorough needs analysis and detailing applications to match the identified needs should improve the sustainability of e-health projects. Insights gained: Existing assumptions before the study was conducted: Evaluation has to proceed from identified questions according to a rigorous experimental design. Emergency and trauma services in remote regions can and should be supported via telehealth based on video-conferencing. Educational applications of telehealth directed at providers are beneficial for recruitment and retention of providers in remote areas. Insights gained by the study: An exploratory approach to evaluation using a multiplicity of methods can yield rich and detailed information even under severe constraints. Ad hoc and emergency clinical applications of telehealth can present problems unless they are based on thorough, detailed analyses of environment and need, conform to established practice patterns and rely on established trusting collaborative relationships. Less difficult applications should be introduced before attempting to support use under emergency conditions. Educational applications are of interest beyond the provider community to patients, family and community members, and have clinical value. In large, sparsely populated areas with difficult travel conditions administrative applications by themselves generate savings that compensate for the substantial capital investment for telehealth required for clinical applications.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes.

PubMed

Serra-Guillén, Carlos; Nagore, Eduardo; Hueso, Luis; Traves, Victor; Messeguer, Francesc; Sanmartín, Onofre; Llombart, Beatriz; Requena, Celia; Botella-Estrada, Rafael; Guillén, Carlos

2012-04-01

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Only one cycle of imiquimod was administered. The follow-up period was brief. Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

A unified approach to computational drug discovery.

PubMed

Tseng, Chih-Yuan; Tuszynski, Jack

2015-11-01

It has been reported that a slowdown in the development of new medical therapies is affecting clinical outcomes. The FDA has thus initiated the Critical Path Initiative project investigating better approaches. We review the current strategies in drug discovery and focus on the advantages of the maximum entropy method being introduced in this area. The maximum entropy principle is derived from statistical thermodynamics and has been demonstrated to be an inductive inference tool. We propose a unified method to drug discovery that hinges on robust information processing using entropic inductive inference. Increasingly, applications of maximum entropy in drug discovery employ this unified approach and demonstrate the usefulness of the concept in the area of pharmaceutical sciences. Copyright © 2015. Published by Elsevier Ltd.

[Current status and clinical application prospect of Akabane's test].

PubMed

Wang, Wenjie; Du, Yanjun

2016-06-12

The Akabane's test is one of the meridian diagnostic methods. Compared with the current meridian diagnostic methods, it has the advantages of convenience and efficiency, but it also has several disadvantages such as the accuracy is difficult to control, the outcome interpretation is limited, etc. In this paper, the influence factors of Akabane's test were analyzed one by one, especially proposed personal opinion on outcome interpretation, which could ascertain the location and nature of disease, leading to disease syndrome. With accurate syndrome, the treatment plan could be established. The application prospect of Akabane's test was initially explored, and it was proposed that wearable automation equipment could be one of the development directions.

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

Wheeler, F.; Wessol, D.; Atkinson, C.

During the past few years, murine and large animal research, as well as human studies have provided data to the point where human clinical trials have been initiated at the BMRR using BPA-F for gliomas and at the Massachusetts Institute of Technology Reactor (MITR) using BPA for melanomas of the extremeties. It is expected that glioma trials using BSH will proceed soon at the Petten High Flux Reactor (HFR) in the Netherlands. The first human glioma epithermal boron neutron capture therapy application was performed at the BMRR in the fall of 1994. This was a collaborative effort by BNL, Bethmore » Israel Manhattan hospital, and INEL. The INEL planning system was chosen to perform dose predictions for this application.« less

The evolution of robotic urologic surgery.

PubMed

Nguyen, Mike Minh; Das, Sakti

2004-11-01

The incorporation of robotics into surgical technology is a relatively recent development. Robotic surgical systems can be classified as master-slave systems, precise-path systems, or intern-replacement systems. Master-slave systems, the most familiar type, were developed from initial experiments in "telepresence" surgery funded by the US Department of Defense. Urology has embraced the use of commercial robotic surgical systems in a growing number of clinical applications. Although drawbacks and limitations exist for the use of surgical robotics, the systems are developing rapidly and an expanded role for this technology in the future of urology is inevitable. This article reviews the history of the use of robotics in surgery, focusing on its specific application to urology.

Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens.

PubMed

Stedtfeld, Robert D; Williams, Maggie R; Fakher, Umama; Johnson, Timothy A; Stedtfeld, Tiffany M; Wang, Fang; Khalife, Walid T; Hughes, Mary; Etchebarne, Brett E; Tiedje, James M; Hashsham, Syed A

2016-03-01

An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interprofessional communication training: benefits to practicing pharmacists.

PubMed

Luetsch, Karen; Rowett, Debra

2015-10-01

Interprofessional communication skills are important for pharmacists to build collaborative relationships with other health professionals, integrate into healthcare teams, maximise their effectiveness in patient care in addressing complex care needs and meet the demands of health care reforms. This qualitative study explores clinical pharmacists' experiences and reflections after completing a learning and practice module which introduced them to a framework for successful interprofessional communication. The postgraduate clinical pharmacy program at The University of Queensland and the clinical pharmacy practice environments of forty-eight hospital and seven community based pharmacists. A learning and practice module outlining a framework for successful interprofessional communication was designed and integrated into a postgraduate clinical pharmacy program. Enrolled pharmacists applied newly learnt communication skills in pro-actively initiated, clinical discussions with a health professional in their practice environment. They provided written reflections on their experiences which were analysed using thematic analysis. Pharmacists' perceptions of the impact of applying the communication framework during their interaction with a health professional in their practice setting. Themes which emerged from reflections described pharmacists' confidence and capabilities to successfully conduct a clinical discussion with a health professional after initial apprehension and nervousness about the scheduled interaction. The application of the communication framework enhanced their perception of their professional identity, credibility and ability to build a collaborative working relationship with other health professionals. Pharmacists perceived that a learning and practice module for successful interprofessional practice integrated into a postgraduate clinical pharmacy program enhanced their interprofessional communication skills. The development of pro-active, interprofessional communication skills has the potential to increase interprofessional collaboration and pharmacists' personal role satisfaction. Pharmacists also observed it added value to their professional contribution in health care teams when addressing the demands of increasingly complex health care needs and reforms.

An investigation into the placement of force delivery systems and the initial forces applied by clinicians during space closure.

PubMed

Nattrass, C; Ireland, A J; Sherriff, M

1997-05-01

This in vitro investigation was designed to establish not only how clinicians apply forces for space closure when using the straight wire appliance and sliding mechanics, but also to quantify the initial force levels produced. A single typodont, with residual extraction space in each quadrant, was set up to simulate space closure using sliding mechanics. On two occasions, at least 2 months apart, 18 clinicians were asked to apply three force delivery systems to the typodont, in the manner in which they would apply it in a clinical situation. The three types of force delivery system investigated were elastomeric chain, an elastomeric module on a steel ligature, and a nickel-titanium closed coil spring. A choice of spaced or unspaced elastomeric chain produced by a single manufacturer was provided. The amount of stretch which was placed on each type of system was measured and, using an Instron Universal Testing Machine, the initial force which would be generated by each force delivery system was established. Clinicians were assessed to examine their consistency in the amount of stretch which each placed on the force delivery systems, their initial force application and their ability to apply equivalent forces with the different types of force delivery system. The clinicians were found to be consistent in their method of application of the force delivery systems and, therefore, their force application, as individuals, but there was a wide range of forces applied as a group. However, most clinicians applied very different forces when using different force delivery systems. When using the module on a ligature the greatest force was applied, whilst the nickel titanium coil springs provided the least force.

Fatherhood and depression: a review of risks, effects, and clinical application.

PubMed

Spector, Aaron Z

2006-10-01

This literature review attempted to compile a complete evaluation of the presentation, risks, and subsequent effects upon a family in relation to paternal depression. Clinical applications are reviewed as well. As with women, fathers will present with a dysphoric mood, but unlike their female counterparts, depressed men often experience a change in social behavior. Withdrawal from social situations, indecisiveness, cynicism, and an irritable mood are often found as hallmark signs of depression in the adult male. Life stress, or family stress and low social support, are risk factors associated with depression among fathers. Marital difficulties may be the most common trigger for first-time depression in husbands just as divorce amplifies depressive episodes, especially when children are involved. A variety of treatments have proven effective for depressed fathers including traditional psycho-dynamic, CBT, and group therapy. Therapy is effective when it can be initiated and continued but research repeatedly showed that men seek it out far less than women. Effective outreach programs to encourage treatment among depressed fathers are recommended.

Use of digital technologies for nasal prosthesis manufacturing.

PubMed

Palousek, David; Rosicky, Jiri; Koutny, Daniel

2014-04-01

Digital technology is becoming more accessible for common use in medical applications; however, their expansion in prosthetic and orthotic laboratories is not large because of the persistent image of difficult applicability to real patients. This article aims to offer real example in the area of human facial prostheses. This article describes the utilization of optical digitization, computational modelling, rapid prototyping, mould fabrication and manufacturing of a nasal silicone prosthesis. This technical note defines the key points of the methodology and aspires to contribute to the introduction of a certified manufacturing procedure. The results show that the used technologies reduce the manufacturing time, reflect patient's requirements and allow the manufacture of high-quality prostheses for missing facial asymmetric parts. The methodology provides a good position for further development issues and is usable for clinical practice. Clinical relevance Utilization of digital technologies in facial prosthesis manufacturing process can be a good contribution for higher patient comfort and higher production efficiency but with higher initial investment and demands for experience with software tools.

[Intraoperative augmented reality visualization. Current state of development and initial experiences with the CamC].

PubMed

Weidert, S; Wang, L; von der Heide, A; Navab, N; Euler, E

2012-03-01

The intraoperative application of augmented reality (AR) has so far mainly taken place in the field of endoscopy. Here, the camera image of the endoscope was augmented by computer graphics derived mostly from preoperative imaging. Due to the complex setup and operation of the devices, they have not yet become part of routine clinical practice. The Camera Augmented Mobile C-arm (CamC) that extends a classic C-arm by a video camera and mirror construction is characterized by its uncomplicated handling. It combines its video live stream geometrically correct with the acquired X-ray. The clinical application of the device in 43 cases showed the strengths of the device in positioning for X-ray acquisition, incision placement, K-wire placement, and instrument guidance. With its new function and the easy integration into the OR workflow of any procedure that requires X-ray imaging, the CamC has the potential to become the first widely used AR technology for orthopedic and trauma surgery.

Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

PubMed Central

Borenstein, Jeffrey T.; Megley, Katie; Wall, Kimberly; Pritchard, Eleanor M.; Truong, David; Kaplan, David L.; Tao, Sarah L.; Herman, Ira M.

2010-01-01

One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

Improvement of retinal blood vessel detection by spur removal and Gaussian matched filtering compensation

NASA Astrophysics Data System (ADS)

Xiao, Di; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi

2016-03-01

Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. In this paper, we proposed approaches for improving the quality of blood vessel detection based on our initial blood vessel detection methods. A blood vessel spur pruning method has been developed for removing the blood vessel spurs both on vessel medial lines and binary vessel masks, which are caused by artifacts and side-effect of Gaussian matched vessel enhancement. A Gaussian matched filtering compensation method has been developed for removing incorrect vessel branches in the areas of low illumination. The proposed approaches were applied and tested on the color fundus images from one publicly available database and our diabetic retinopathy screening dataset. A preliminary result has demonstrated the robustness and good performance of the proposed approaches and their potential application for improving retinal blood vessel detection.

Therapeutic Ultrasound in Navicular Stress Injuries in Elite Track and Field Athletes.

PubMed

Malliaropoulos, Nikolaos; Alaseirlis, Dimosthenis; Konstantinidis, George; Papalada, Agapi; Tsifountoudis, Ioannis; Petras, Kosmas; Maffulli, Nicola

2017-05-01

To ascertain whether therapeutic ultrasound (TUS) can be used to assess the progression of conservative management in navicular stress injuries. This is a prospective, clinical case series. Level of evidence IV. All participants were examined and followed up in a private Sports Injury Clinic. Ten elite track and field athletes with severe dorsal midfoot pain over the navicular bone participated in this study. All patients underwent both TUS and magnetic resonance imaging (MRI) evaluation. The painful threshold of TUS on initial evaluation was a mean of 0.707 ± 149 W/cm, and MRI detected a navicular stress injury in all patients. The athletes received conservative treatment and underwent sequential TUS evaluations at 4, 8, 12 and 16 weeks. Therapeutic ultrasound pain threshold values were recorded, and the patients were additionally asked to grade local tenderness on a Visual Analogue Scale. Time to return to play was also recorded. The level of pain produced by the application of TUS on a navicular stress fracture seemed to correlate well with Visual Analogue Scale scores and the grade of fracture demonstrated on MRI. The initial low TUS painful mean value increased to a normal mean value of 1.97 ± 0.067 W/cm by 16 weeks. When clinical and TUS findings had returned to normal, the patients were allowed to return to sports activities, with no recurrences experienced during the study period. The production of pain associated with the application of TUS on a navicular stress fracture is a safe and reproducible method of monitoring the resolution of these fractures. We have used it successfully in making return-to-play decisions for elite level track and field athletes.

The role of lymphoscintigraphy, sentinel mode biopsy and positron emission tomography in the staging of the neck in early oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Hyde, Nicholas Charles

This thesis explores the limitations of current imaging modalities in the evaluation of the clinically node negative (N0) neck in early oral squamous cell carcinoma and evaluates the utility of two new interventions. It will become evident that the use of clinical parameters and conventional imaging to detect clinically occult cervical lymph node metastases is an imprecise science. The presence of metastases in the neck is the single most important determinant of survival. Hitherto the lack of timely intervention in this regard may have been contributory in amplifying their effect upon survival. There is an obvious requirement for a more accurate technique to stage the neck in this patient group. Therefore the application of lymphoscintigraphy in combination with sentinel node biopsy (SNB), and positron emission tomography (PET) have been investigated. It appears that PET, whilst having a number of useful roles in the generic head and neck oncology patient, has little to contribute in the diagnosis of occult neck disease. In contra-distinction lymphoscintigraphy and SNB are not only feasible in the diagnosis of occult metastases, but also enhance our knowledge of lymphatic drainage from the oral cavity. This has, in some circumstances, led to the modification of initially prescribed treatment plans. Such is the current pace of technological advance that over the course of this research an entirely new imaging modality has emerged - PET/CT. Whilst it has not been possible to apply this retrospectively to the original patient population early experience of this novel technique in head and neck malignancy is explored and reported. The results of these initial applications are encouraging.

A fast 4D cone beam CT reconstruction method based on the OSC-TV algorithm.

PubMed

Mascolo-Fortin, Julia; Matenine, Dmitri; Archambault, Louis; Després, Philippe

2018-01-01

Four-dimensional cone beam computed tomography allows for temporally resolved imaging with useful applications in radiotherapy, but raises particular challenges in terms of image quality and computation time. The purpose of this work is to develop a fast and accurate 4D algorithm by adapting a GPU-accelerated ordered subsets convex algorithm (OSC), combined with the total variation minimization regularization technique (TV). Different initialization schemes were studied to adapt the OSC-TV algorithm to 4D reconstruction: each respiratory phase was initialized either with a 3D reconstruction or a blank image. Reconstruction algorithms were tested on a dynamic numerical phantom and on a clinical dataset. 4D iterations were implemented for a cluster of 8 GPUs. All developed methods allowed for an adequate visualization of the respiratory movement and compared favorably to the McKinnon-Bates and adaptive steepest descent projection onto convex sets algorithms, while the 4D reconstructions initialized from a prior 3D reconstruction led to better overall image quality. The most suitable adaptation of OSC-TV to 4D CBCT was found to be a combination of a prior FDK reconstruction and a 4D OSC-TV reconstruction with a reconstruction time of 4.5 minutes. This relatively short reconstruction time could facilitate a clinical use.

Gene therapy on the move

PubMed Central

Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

2013-01-01

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

Therapeutic Ultrasound Research And Development From An Industrial And Commercial Perspective

NASA Astrophysics Data System (ADS)

Seip, Ralf

2009-04-01

The objective of this paper is to share the challenges and opportunities as viewed from an industrial and commercial perspective that one encounters when performing therapeutic ultrasound research, development, manufacturing, and sales activities. Research in therapeutic ultrasound has become an active field in the last decade, spurred by technological advances in the areas of transducer materials, control electronics, treatment monitoring techniques, an ever increasing number of clinical applications, and private and governmental funding opportunities. The development of devices and methods utilizing therapeutic ultrasound to cure or manage disease is being pursued by startup companies and large established companies alike, driven by the promise of profiting at many levels from this new and disruptive technology. Widespread penetration within the clinical community remains elusive, with current approaches focusing on very specific applications and niche markets. Challenges include difficulties in securing capital to develop the technology and undertake costly clinical trials, a regulatory landscape that varies from country to country, resistance from established practitioners, and difficulties in assembling a team with the right mix of technological savvy and business expertise. Success is possible and increasing, however, as evidenced by several companies, initiatives, and products with measurable benefits to the patient, clinician, and companies alike.

MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine

PubMed Central

Smith, Bethany; Agarwal, Priyanka

2017-01-01

The high degree of conservation in microRNA from Caenorhabditis elegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microRNA to address these changes holds significant promise. However, prostate, ovarian and breast cancers are heterogeneous and face issues of evolving therapeutic resistance. The transforming growth factor-beta (TGFβ) signaling axis plays an important role in the progression of these cancers by regulating microRNAs. Reciprocally, microRNAs regulate TGFβ actions during cancer progression. One must consider the expression of miRNA in the tumor microenvironment a source of biomarkers of disease progression and a viable target for therapeutic targeting. The differential expression pattern of microRNAs in health and disease, therapeutic response and resistance has resulted in its application as robust biomarkers. With two microRNA mimetics in ongoing restorative clinical trials, the paradigm for future clinical studies rests on the current observational trials to validate microRNA markers of disease progression. Some of today’s biomarkers can be translated to the next generation of microRNA-based therapies. PMID:28289080

Collaborative Social and Medical Service System

PubMed Central

Petermann, Cynthia A.; Bobroff, Risa B.; Moore, Dwight M.; Gilson, Hillary S.; Li, Yizhen; Dargahi, Ross; Classen, David W.; Fowler, Jerry; Moreau, Dennis R.; Beck, J. Robert; Buffone, Gregory J.

1994-01-01

This paper describes the Collaborative Social and Medical Services System, a robust information infrastructure for integrated social and medical care. The Collaborative Social and Medical Services System design and architecture address the primary goals of creating a readily extensible social and ambulatory care system. Our initial step toward reaching this goal is the delivery of an application supporting the operations of the Baylor Teen Health Clinics. This paper discusses our protoype experiences, system architecture, components, and the standards we are addressing. PMID:7950001

Clinical operations management in radiology.

PubMed

Ondategui-Parra, Silvia; Gill, Ileana E; Bhagwat, Jui G; Intrieri, Lisa A; Gogate, Adheet; Zou, Kelly H; Nathanson, Eric; Seltzer, Steven E; Ros, Pablo R

2004-09-01

Providing radiology services is a complex and technically demanding enterprise in which the application of operations management (OM) tools can play a substantial role in process management and improvement. This paper considers the benefits of an OM process in a radiology setting. Available techniques and concepts of OM are addressed, along with gains and benefits that can be derived from these processes. A reference framework for the radiology processes is described, distinguishing two phases in the initial assessment of a unit: the diagnostic phase and the redesign phase.

Wound management in rodents.

PubMed

Langlois, Isabelle

2004-01-01

Successful wound management requires appropriate evaluation of the wound at the time of initial physical examination, an all throughout the healing process. Factors affecting wound healing need to be identified though a complete patient history and addressed to ensure proper healing. The clinician must have current knowledge of topical medications and bandages available and their clinical applications according to the stage of healing. It is essential to remember that wounds are painful; therefore, analgesics should be administered to render the animal pain-free during wound cleaning, debridement, bandaging, and surgical procedures.

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

PubMed

Wang, Ling-Wei; Liu, Yen-Wan Hsueh; Chou, Fong-In; Jiang, Shiang-Huei

2018-06-19

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

Research Areas - Clinical Trials

Cancer.gov

Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis.

PubMed

Buzurovic, Ivan M; O'Farrell, Desmond A; Bhagwat, Mandar S; Hansen, Jorgen L; Harris, Thomas C; Friesen, Scott; Cormack, Robert A; Devlin, Phillip M

2017-06-01

In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192 Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

Basic investigation of the laminated alginate impression technique: Setting time, permanent deformation, elastic deformation, consistency, and tensile bond strength tests.

PubMed

Kitamura, Aya; Kawai, Yasuhiko

2015-01-01

Laminated alginate impression for edentulous is simple and time efficient compared to border molding technique. The purpose of this study was to examine clinical applicability of the laminated alginate impression, by measuring the effects of different Water/Powder (W/P) and mixing methods, and different bonding methods in the secondary impression of alginate impression. Three W/P: manufacturer-designated mixing water amount (standard), 1.5-fold (1.5×) and 1.75-fold (1.75×) water amount were mixed by manual and automatic mixing methods. Initial and complete setting time, permanent and elastic deformation, and consistency of the secondary impression were investigated (n=10). Additionally, tensile bond strength between the primary and secondary impression were measured in the following surface treatment; air blow only (A), surface baking (B), and alginate impression material bonding agent (ALGI-BOND: AB) (n=12). Initial setting times significantly shortened with automatic mixing for all W/P (p<0.05). The permanent deformation decreased and elastic deformation increased as high W/P, regardless of the mixing method. Elastic deformation significantly reduced in 1.5× and 1.75× with automatic mixing (p<0.05). All of these properties resulted within JIS standards. For all W/P, AB showed a significantly high bonding strength as compared to A and B (p<0.01). The increase of mixing water, 1.5× and 1.75×, resulted within JIS standards in setting time, suggesting its applicability in clinical setting. The use of automatic mixing device decreased elastic strain and shortening of the curing time. For the secondary impression application of adhesives on the primary impression gives secure adhesion. Copyright © 2014 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

The "physician on call patient engagement trial" (POPET): measuring the impact of a mobile patient engagement application on health outcomes and quality of life in allergic rhinitis and asthma patients.

PubMed

Cingi, Cemal; Yorgancioglu, Arzu; Cingi, Can Cemal; Oguzulgen, Kıvılcım; Muluk, Nuray Bayar; Ulusoy, Seçkin; Orhon, Nezih; Yumru, Cengiz; Gokdag, Dursun; Karakaya, Gul; Çelebi, Şaban; Çobanoglu, H Bengü; Unlu, Halis; Aksoy, Mehmet Akif

2015-06-01

In this prospective, multicenter, randomized, controlled, double-blind study, we investigated the impact of a mobile patient engagement application on health outcomes and quality of life in allergic rhinitis (AR) and asthma patients. In total, 327 patients with diagnoses of persistent AR or mild-to-severe persistent asthma were randomized into 2 intervention groups and 2 control groups upon their admission at outpatient clinics. The intervention groups (POPET-AR and POPET-Asthma) received a mobile phone application ("physician on call patient engagement trial" [POPET]), enabling them to communicate with their physician, and record their health status and medication compliance. The AR groups completed the Rhinitis Quality of Life Questionnaire (RQLQ) at initiation and at the first month of the study. The asthma groups completed the Asthma Control Test (ACT) at initiation and at the third month of the study. The POPET-AR group showed better clinical improvement than the control group in terms of the overall RQLQ score as well in measures of general problems, activity, symptoms other than nose/eye, and emotion domains (p < 0.05). In the POPET-Asthma group, more patients (49%) achieved a well-controlled asthma score (ACT > 19) compared with the control group (27%); this was statistically significant (p < 0.05). Use of a mobile engagement platform, such as POPET, can have a significant impact on health outcomes and quality of life in both AR and asthma, potentially decreasing the number of hospital admissions, repeat doctor visits, and losses in productivity. Improvements were seen in domains related to activity, productivity, perception of disease, and emotion. © 2015 ARS-AAOA, LLC.

Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine

PubMed Central

Lee, Cody S.; Bishop, Elliot S.; Zhang, Ruyi; Yu, Xinyi; Farina, Evan M.; Yan, Shujuan; Zhao, Chen; Zheng, Zongyue; Shu, Yi; Wu, Xingye; Lei, Jiayan; Li, Yasha; Zhang, Wenwen; Yang, Chao; Wu, Ke; Wu, Ying; Ho, Sherwin; Athiviraham, Aravind; Lee, Michael J.; Wolf, Jennifer Moriatis; Reid, Russell R.; He, Tong-Chuan

2017-01-01

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2,000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and pre-clinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. PMID:28944281

A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future

PubMed Central

Jonnal, Ravi S.; Kocaoglu, Omer P.; Zawadzki, Robert J.; Liu, Zhuolin; Miller, Donald T.; Werner, John S.

2016-01-01

Purpose Optical coherence tomography (OCT) has enabled “virtual biopsy” of the living human retina, revolutionizing both basic retina research and clinical practice over the past 25 years. For most of those years, in parallel, adaptive optics (AO) has been used to improve the transverse resolution of ophthalmoscopes to foster in vivo study of the retina at the microscopic level. Here, we review work done over the last 15 years to combine the microscopic transverse resolution of AO with the microscopic axial resolution of OCT, building AO-OCT systems with the highest three-dimensional resolution of any existing retinal imaging modality. Methods We surveyed the literature to identify the most influential antecedent work, important milestones in the development of AO-OCT technology, its applications that have yielded new knowledge, research areas into which it may productively expand, and nascent applications that have the potential to grow. Results Initial efforts focused on demonstrating three-dimensional resolution. Since then, many improvements have been made in resolution and speed, as well as other enhancements of acquisition and postprocessing techniques. Progress on these fronts has produced numerous discoveries about the anatomy, function, and optical properties of the retina. Conclusions Adaptive optics OCT continues to evolve technically and to contribute to our basic and clinical knowledge of the retina. Due to its capacity to reveal cellular and microscopic detail invisible to clinical OCT systems, it is an ideal companion to those instruments and has the demonstrable potential to produce images that can guide the interpretation of clinical findings. PMID:27409507

Whole-exome/genome sequencing and genomics.

PubMed

Grody, Wayne W; Thompson, Barry H; Hudgins, Louanne

2013-12-01

As medical genetics has progressed from a descriptive entity to one focused on the functional relationship between genes and clinical disorders, emphasis has been placed on genomics. Genomics, a subelement of genetics, is the study of the genome, the sum total of all the genes of an organism. The human genome, which is contained in the 23 pairs of nuclear chromosomes and in the mitochondrial DNA of each cell, comprises >6 billion nucleotides of genetic code. There are some 23,000 protein-coding genes, a surprisingly small fraction of the total genetic material, with the remainder composed of noncoding DNA, regulatory sequences, and introns. The Human Genome Project, launched in 1990, produced a draft of the genome in 2001 and then a finished sequence in 2003, on the 50th anniversary of the initial publication of Watson and Crick's paper on the double-helical structure of DNA. Since then, this mass of genetic information has been translated at an ever-increasing pace into useable knowledge applicable to clinical medicine. The recent advent of massively parallel DNA sequencing (also known as shotgun, high-throughput, and next-generation sequencing) has brought whole-genome analysis into the clinic for the first time, and most of the current applications are directed at children with congenital conditions that are undiagnosable by using standard genetic tests for single-gene disorders. Thus, pediatricians must become familiar with this technology, what it can and cannot offer, and its technical and ethical challenges. Here, we address the concepts of human genomic analysis and its clinical applicability for primary care providers.

Host Defense Antimicrobial Peptides as Antibiotics: Design and Application Strategies

PubMed Central

Mishra, Biswajit; Reiling, Scott; Zarena, D.; Wang, Guangshun

2017-01-01

This review deals with the design and application strategies of new antibiotics based on naturally occurring antimicrobial peptides (AMPs). The initial candidate can be designed based on three-dimensional structure or selected from a library of peptides from natural or laboratory sources followed by optimization via structure-activity relationship studies. There are also advanced application strategies such as induction of AMP expression from host cells by various factors (e.g., metals, amino acids, vitamin D and sunlight), the use of engineered probiotic bacteria to deliver peptides, the design of prodrug and peptide conjugates to improve specific targeting. In addition, combined uses of newly developed AMPs with existing antimicrobial agents may provide a practical avenue for effective management of antibiotic-resistant bacteria (superbugs, including biofilm). Finally, we highlight AMPs already in use or under clinical trials. PMID:28399505

Bone Graft Substitute Provides Metaphyseal Fixation for a Stemless Humeral Implant.

PubMed

Kim, Myung-Sun; Kovacevic, David; Milks, Ryan A; Jun, Bong-Jae; Rodriguez, Eric; DeLozier, Katherine R; Derwin, Kathleen A; Iannotti, Joseph P

2015-07-01

Stemless humeral fixation has become an alternative to traditional total shoulder arthroplasty, but metaphyseal fixation may be compromised by the quality of the trabecular bone that diminishes with age and disease, and augmentation of the fixation may be desirable. The authors hypothesized that a bone graft substitute (BGS) could achieve initial fixation comparable to polymethylmethacrylate (PMMA) bone cement. Fifteen fresh-frozen human male humerii were randomly implanted using a stemless humeral prosthesis, and metaphyseal fixation was augmented with either high-viscosity PMMA bone cement (PMMA group) or a magnesium-based injectable BGS (OsteoCrete; Bone Solutions Inc, Dallas, Texas) (OC group). Both groups were compared with a control group with no augmentation. Initial stiffness, failure load, failure displacement, failure cycle, and total work were compared among groups. The PMMA and OC groups showed markedly higher failure loads, failure displacements, and failure cycles than the control group (P<.01). There were no statistically significant differences in initial stiffness, failure load, failure displacement, failure cycle, or total work between the PMMA and OC groups. The biomechanical properties of magnesium-based BGS fixation compared favorably with PMMA bone cement in the fixation of stemless humeral prostheses and may provide sufficient initial fixation for this clinical application. Future work will investigate the long-term remodeling characteristics and bone quality at the prosthetic-bone interface in an in vivo model to evaluate the clinical efficacy of this approach. Copyright 2015, SLACK Incorporated.

Systematic Reviews and Clinical Trials in Rehabilitation: Comprehensive Analyses of Publication Trends.

PubMed

Jesus, Tiago S

2016-11-01

To analyze publication trends of clinical trials (CTs) and systematic reviews (SRs) in rehabilitation. PubMed searches were performed with appropriate combinations of Medical Subject Headings. All entries until December 2013, and their yearly distributions since 1981 (when the first rehabilitation SR was identified), were retrieved. After the initial data visualization, data analyses were narrowed to specific periods. Linear regression techniques analyzed the growth of publications and their relative percentages over time. Not applicable. Not applicable. Not applicable. Not applicable. Although not observed for SRs, CTs have grown at a much higher rate in rehabilitation than in the broader health/medical field-more than twice the difference for both periods analyzed (1989-2001, 2001-2013). Rehabilitation journals published about 20% or less of the rehabilitation SRs and CTs, and no significant increases were observed over time (P>.05; 2001-2013). Neurologic conditions, particularly cerebrovascular, were the most addressed by rehabilitation SRs and CTs, while differences between neurologic and other groups of conditions typically widened over time (eg, more than doubled between neurologic and musculoskeletal conditions in 15y). While publications of CTs are increasing at a much higher rate within rehabilitation than within broader health care, further research is warranted to explain why this trend is not being followed by SRs, particularly those with meta-analysis. Similarly, research might determine whether the (growing) differences in the publications of rehabilitation SRs and CTs across groups of conditions are justified by clinical or population need. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Support Team for Investigator-Initiated Clinical Research].

PubMed

Fujii, Hisako

2017-07-01

Investigator-initiated clinical research is that in which investigators plan and carry out their own clinical research in academia. For large-scale clinical research, a team should be organized and implemented. This team should include investigators and supporting staff, who will promote smooth research performance by fulfilling their respective roles. The supporting staff should include project managers, administrative personnel, billing personnel, data managers, and clinical research coordinators. In this article, I will present the current status of clinical research support and introduce the research organization of the Dominantly Inherited Alzheimer Network (DIAN) study, an investigator-initiated international clinical research study, with particular emphasis on the role of the project management staff and clinical research coordinators.

The basics of preclinical drug development for neurodegenerative disease indications.

PubMed

Steinmetz, Karen L; Spack, Edward G

2009-06-12

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial.

The basics of preclinical drug development for neurodegenerative disease indications

PubMed Central

Steinmetz, Karen L; Spack, Edward G

2009-01-01

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and services to assist applicants in preparing the preclinical programs and documentation for their drugs. Increasingly, private foundations are also funding preclinical work. Close interaction with the FDA, including a meeting to prepare for submission of an Investigational New Drug application, is critical to ensure that the preclinical development package properly supports the planned phase I clinical trial. PMID:19534731

Engineering long term clinical success of advanced ceramic prostheses.

PubMed

Rekow, Dianne; Thompson, Van P

2007-01-01

Biocompatability and, in some applications, esthetics make all-ceramic prostheses compelling choices but despite significant improvements in materials properties and toughening mechanisms, these still have significant failure rates. Factors that contribute to the degradation in strength and survival include material selection and prosthesis design which set the upper limit for performance. However, fabrication operations introduce damage that can be exacerbated by environmental conditions and clinical function. Using all-ceramic dental crowns as an example, experimentally derived models provide insight into the relationships between materials properties and initial critical loads to failure. Analysis of fabrication operations suggests strategies to minimize damage. Environmental conditions can create viscoplastic flow of supporting components which can contribute additional stress within the prosthesis. Fatigue is a particularly challenging problem, not only providing the energy to propagate existing damage but, when combined with the wet environment, can create new damage modes. While much is known, the influence of these new damage modes has not been completely elucidated. The role of complex prosthesis geometry and its interaction with other factors on damage initiation and propagation has yet to be well characterized.

Managing Attribute—Value Clinical Trials Data Using the ACT/DB Client—Server Database System

PubMed Central

Nadkarni, Prakash M.; Brandt, Cynthia; Frawley, Sandra; Sayward, Frederick G.; Einbinder, Robin; Zelterman, Daniel; Schacter, Lee; Miller, Perry L.

1998-01-01

ACT/DB is a client—server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity—attribute—value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment. PMID:9524347

Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

PubMed

Bottomley, Andrew; Pe, Madeline; Sloan, Jeff; Basch, Ethan; Bonnetain, Franck; Calvert, Melanie; Campbell, Alicyn; Cleeland, Charles; Cocks, Kim; Collette, Laurence; Dueck, Amylou C; Devlin, Nancy; Flechtner, Hans-Henning; Gotay, Carolyn; Greimel, Eva; Griebsch, Ingolf; Groenvold, Mogens; Hamel, Jean-Francois; King, Madeleine; Kluetz, Paul G; Koller, Michael; Malone, Daniel C; Martinelli, Francesca; Mitchell, Sandra A; Moinpour, Carol M; Musoro, Jammbe; O'Connor, Daniel; Oliver, Kathy; Piault-Louis, Elisabeth; Piccart, Martine; Pimentel, Francisco L; Quinten, Chantal; Reijneveld, Jaap C; Schürmann, Christoph; Smith, Ashley Wilder; Soltys, Katherine M; Taphoorn, Martin J B; Velikova, Galina; Coens, Corneel

2016-11-01

Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic antitumor activity of the combination of salubrinal and rapamycin against human cholangiocarcinoma cells.

PubMed

Zhao, Xiaofang; Zhang, Chunyan; Zhou, Hong; Xiao, Bin; Cheng, Ying; Wang, Jinju; Yao, Fuli; Duan, Chunyan; Chen, Run; Liu, Youping; Feng, Chunhong; Li, Hong; Li, Jing; Dai, Rongyang

2016-12-20

Less is known about the roles of eukaryotic initiation factor alpha (eIF2α) in cholangiocarcinoma (CCA). Here, we report that eIF2α inhibitor salubrinal inhibits the proliferation of human CCA cells. Clinical application of mammalian target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy. Therefore, combination approaches may be required for effective clinical use of mTOR inhibitors. Here, we investigated the efficacy of the combination of salubrinal and rapamycin in the treatment of CCA. Our data demonstrate a synergistic antitumor effect of the combination of salubrinal and rapamycin against CCA cells. Rapamycin significantly inhibits the proliferation of CCA cells. However, rapamycin initiates a negative feedback activation of Akt. Inhibition of Akt by salubrinal potentiates the efficacy of rapamycin both in vitro and in vivo. Additionally, rapamycin treatment results in the up-regulation of Bcl-xL in a xenograft mouse model. It is notable that salubrinal inhibits rapamycin-induced Bcl-xL up-regulation in vivo. Taken together, our data suggest that salubrinal and rapamycin combination might be a new and effective strategy for the treatment of CCA.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A; Miller, Douglas R

2014-03-18

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A; Miller, Douglas R

2012-10-23

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

Administering an epoch initiated for remote memory access

DOEpatents

Blocksome, Michael A.; Miller, Douglas R.

2013-01-01

Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

[Alternative hemodialysis regimens].

PubMed

Matos, Jorge Paulo Strogoff de; Lugon, Jocemir Ronaldo

2010-03-01

The mortality rate among patients on hemodialysis (HD) is extremely high. Remaining life expectancy for a patient initiating HD is only approximately one quarter of that of the general population at the same age bracket. The conventional HD regimen based on four-hour sessions three times a week was empirically established nearly four decades ago and needs to be revisited. Since the failure of the HEMO Study to demonstrate the clinical benefits of higher urea Kt/V for patients on conventional HD, an increasing interest for alternative HD regimens has emerged aiming at providing a treatment for improving survival rates. Short daily HD and long nocturnal HD stand out as the most promising alternative regimens. Economical obstacles which could hinder the clinical application of emerging knowledge in the field should be overcome.

Automated electroencephalography system and electroencephalographic coordinates of space motion sickness, part 1

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.

1976-01-01

A self-contained and portable device which permits clinical electroencephalography (EEG) to be conducted in remote locations by minimally trained, nontechnical personnel was developed and tested. The unit accomplishes semiautomatic acquisition of EEG data from the patient, simultaneous transmission of eight data channels to a central hospital facility over conventional telephone equipment, and automatic printing (at the remote site) of the EEG report generated at the central location. Consequently, this system enables the delivery of high-quality EEG diagnostic services in a geographically remote site with the accuracy and speed formerly possible only in certain large medical centers. Beside obvious potential clinical applications, this system serves as an initial prototype of a unit which could provide inflight EEG during future space missions.

Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

PubMed

Reisler, Ronald B; Yu, Chenggang; Donofrio, Michael J; Warren, Travis K; Wells, Jay B; Stuthman, Kelly S; Garza, Nicole L; Vantongeren, Sean A; Donnelly, Ginger C; Kane, Christopher D; Kortepeter, Mark G; Bavari, Sina; Cardile, Anthony P

2017-08-01

The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

White Paper: Interventional MRI: Current Status and Potential for Development Considering Economic Perspectives, Part 1: General Application.

PubMed

Barkhausen, Jörg; Kahn, Thomas; Krombach, Gabriele A; Kuhl, Christiane K; Lotz, Joachim; Maintz, David; Ricke, Jens; Schönberg, Stefan O; Vogl, Thomas J; Wacker, Frank K

2017-07-01

Background  MRI is attractive for the guiding and monitoring of interventional procedures due to its high intrinsic soft tissue contrast and the possibility to measure physiologic parameters like flow and cardiac function. Method  The current status of interventional MRI for the clinical routine was analyzed. Results  The effort needed for the development of MR-safe monitoring systems and instruments initially resulted in the application of interventional MRI only for procedures that could not be performed by other means. Accordingly, biopsy of lesions in the breast, which are not detectable by other modalities, has been performed under MRI guidance for decades. Currently, biopsies of the prostate under MRI guidance are established in a similar fashion. At many sites blind biopsy has already been replaced by MR-guided biopsy or at least by the fusion of MR images with ultrasound. Cardiovascular interventions are performed at several centers for ablation as a treatment for atrial fibrillation. Conclusion  Interventional MRI has been established in the clinical routine for a variety of indications. Broader application can be expected in the clinical routine in the future owing to the multiple advantages compared to other techniques. Key points   · Due to the significant technical effort, MR-guided interventions are only recommended in the long term for regions in which MRI either facilitates or greatly improves the intervention.. · Breast biopsy of otherwise undetectable target lesions has long been established in the clinical routine. Prostate biopsy is currently being introduced in the clinical routine for similar reasons. Other methods such as MR-guided focused ultrasound for the treatment of uterine fibroids or tumor ablation of metastases represent alternative methods and are offered in many places.. · Endovascular MR-guided interventions offer advantages for a number of indications and have already been clinically established for the treatment of children with congenital heart defects and for atrial ablation at individual centers. Greater application can be expected in the future.. Citation format · Barkhausen J, Kahn T, Krombach GA et al. White Paper: Interventional MRI: Current Status and Potential for Development Considering Economic Perspectives, Part 1: General Application. Fortschr Röntgenstr 2017; 189: 611 - 623. © Georg Thieme Verlag KG Stuttgart · New York.

The AcCell series 2000 as a support system for training and evaluation in educational and clinical settings.

PubMed

Greening, S E; Grohs, D H; Guidos, B J

1997-01-01

Providing effective training, retraining and evaluation programs, including proficiency testing programs, for cytoprofessionals is a challenge shared by many academic and clinical educators internationally. In cytopathology the quality of training has immediately transferable and critically important impacts on satisfactory performance in the clinical setting. Well-designed interactive computer-assisted instruction and testing programs have been shown to enhance initial learning and to reinforce factual and conceptual knowledge. Computer systems designed not only to promote diagnostic accuracy but to integrate and streamline work flow in clinical service settings are candidates for educational adaptation. The AcCell 2000 system, designed as a diagnostic screening support system, offers technology that is adaptable to educational needs during basic and in-service training as well as testing of screening proficiency in both locator and identification skills. We describe the considerations, approaches and applications of the AcCell 2000 system in education programs for both training and evaluation of gynecologic diagnostic screening proficiency.

Neurofeedback and networks of depression

PubMed Central

Linden, David E. J.

2014-01-01

Recent advances in imaging technology and in the understanding of neural circuits relevant to emotion, motivation, and depression have boosted interest and experimental work in neuromodulation for affective disorders. Real-time functional magnetic resonance imaging (fMRI) can be used to train patients in the self regulation of these circuits, and thus complement existing neurofeedback technologies based on electroencephalography (EEG). EEG neurofeedback for depression has mainly been based on models of altered hemispheric asymmetry. fMRI-based neurofeedback (fMRI-NF) can utilize functional localizer scans that allow the dynamic adjustment of the target areas or networks for self-regulation training to individual patterns of emotion processing. An initial application of fMRI-NF in depression has produced promising clinical results, and further clinical trials are under way. Challenges lie in the design of appropriate control conditions for rigorous clinical trials, and in the transfer of neurofeedback protocols from the laboratory to mobile devices to enhance the sustainability of any clinical benefits. PMID:24733975

Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

PubMed Central

Lee, Jee-Wook; Han, Hyung-Seop; Han, Kyeong-Jin; Park, Jimin; Jeon, Hojeong; Ok, Myoung-Ryul; Seok, Hyun-Kwang; Ahn, Jae-Pyoung; Lee, Kyung Eun; Lee, Dong-Ho; Yang, Seok-Jo; Cho, Sung-Youn; Cha, Pil-Ryung; Kwon, Hoon; Nam, Tae-Hyun; Han, Jee Hye Lo; Rho, Hyoung-Jin; Lee, Kang-Sik; Kim, Yu-Chan; Mantovani, Diego

2016-01-01

There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study. PMID:26729859

Emerging commercial molecular tests for the diagnosis of bloodstream infection.

PubMed

Mwaigwisya, Solomon; Assiri, Rasha Assad M; O'Grady, Justin

2015-05-01

Bloodstream infection (BSI) by microorganisms can lead to sepsis. This condition has a high mortality rate, which rises significantly with delays in initiation of appropriate antimicrobial treatment. Current culture methods for diagnosing BSI have long turnaround times and poor clinical sensitivity. While clinicians wait for culture diagnosis, patients are treated empirically, which can result in inappropriate treatment, undesirable side effects and contribute to drug resistance development. Molecular diagnostics assays that target pathogen DNA can identify pathogens and resistance markers within hours. Early diagnosis improves antibiotic stewardship and is associated with favorable clinical outcomes. Nonetheless, limitations of current molecular diagnostic methods are substantial. This article reviews recent commercially available molecular methods that use pathogen DNA to diagnose BSI, either by testing positive blood cultures or directly testing patient blood. We critically assess these tests and their application in clinical microbiology. A view of future directions in BSI diagnosis is also provided.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS)

PubMed Central

Anastasiadis, Kyriakos; Murkin, John; Antonitsis, Polychronis; Bauer, Adrian; Ranucci, Marco; Gygax, Erich; Schaarschmidt, Jan; Fromes, Yves; Philipp, Alois; Eberle, Balthasar; Punjabi, Prakash; Argiriadou, Helena; Kadner, Alexander; Jenni, Hansjoerg; Albrecht, Guenter; van Boven, Wim; Liebold, Andreas; de Somer, Fillip; Hausmann, Harald; Deliopoulos, Apostolos; El-Essawi, Aschraf; Mazzei, Valerio; Biancari, Fausto; Fernandez, Adam; Weerwind, Patrick; Puehler, Thomas; Serrick, Cyril; Waanders, Frans; Gunaydin, Serdar; Ohri, Sunil; Gummert, Jan; Angelini, Gianni; Falk, Volkmar; Carrel, Thierry

2016-01-01

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists. PMID:26819269

Enabling Cross-Platform Clinical Decision Support through Web-Based Decision Support in Commercial Electronic Health Record Systems: Proposal and Evaluation of Initial Prototype Implementations

PubMed Central

Zhang, Mingyuan; Velasco, Ferdinand T.; Musser, R. Clayton; Kawamoto, Kensaku

2013-01-01

Enabling clinical decision support (CDS) across multiple electronic health record (EHR) systems has been a desired but largely unattained aim of clinical informatics, especially in commercial EHR systems. A potential opportunity for enabling such scalable CDS is to leverage vendor-supported, Web-based CDS development platforms along with vendor-supported application programming interfaces (APIs). Here, we propose a potential staged approach for enabling such scalable CDS, starting with the use of custom EHR APIs and moving towards standardized EHR APIs to facilitate interoperability. We analyzed three commercial EHR systems for their capabilities to support the proposed approach, and we implemented prototypes in all three systems. Based on these analyses and prototype implementations, we conclude that the approach proposed is feasible, already supported by several major commercial EHR vendors, and potentially capable of enabling cross-platform CDS at scale. PMID:24551426

Model based LV-reconstruction in bi-plane x-ray angiography

NASA Astrophysics Data System (ADS)

Backfrieder, Werner; Carpella, Martin; Swoboda, Roland; Steinwender, Clemens; Gabriel, Christian; Leisch, Franz

2005-04-01

Interventional x-ray angiography is state of the art in diagnosis and therapy of severe diseases of the cardiovascular system. Diagnosis is based on contrast enhanced dynamic projection images of the left ventricle. A new model based algorithm for three dimensional reconstruction of the left ventricle from bi-planar angiograms was developed. Parametric super ellipses are deformed until their projection profiles optimally fit measured ventricular projections. Deformation is controlled by a simplex optimization procedure. A resulting optimized parameter set builds the initial guess for neighboring slices. A three dimensional surface model of the ventricle is built from stacked contours. The accuracy of the algorithm has been tested with mathematical phantom data and clinical data. Results show conformance with provided projection data and high convergence speed makes the algorithm useful for clinical application. Fully three dimensional reconstruction of the left ventricle has a high potential for improvements of clinical findings in interventional cardiology.

Cell-based therapies and imaging in cardiology.

PubMed

Bengel, Frank M; Schachinger, Volker; Dimmeler, Stefanie

2005-12-01

Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application.

A review of the use of simulation in dental education.

PubMed

Perry, Suzanne; Bridges, Susan Margaret; Burrow, Michael Francis

2015-02-01

In line with the advances in technology and communication, medical simulations are being developed to support the acquisition of requisite psychomotor skills before real-life clinical applications. This review article aimed to give a general overview of simulation in a cognate field, clinical dental education. Simulations in dentistry are not a new phenomenon; however, recent developments in virtual-reality technology using computer-generated medical simulations of 3-dimensional images or environments are providing more optimal practice conditions to smooth the transition from the traditional model-based simulation laboratory to the clinic. Evidence as to the positive aspects of virtual reality include increased effectiveness in comparison with traditional simulation teaching techniques, more efficient learning, objective and reproducible feedback, unlimited training hours, and enhanced cost-effectiveness for teaching establishments. Negative aspects have been indicated as initial setup costs, faculty training, and the lack of a variety of content and current educational simulation programs.

[Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects].

PubMed

Hoffmann, H; Gutsche, W; Amlacher, R; Schulze, W; Werner, W; Lenk, H; Wohlrab, W; Haupt, E

1989-01-01

Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance. M-G seems to be effective especially in combination with other antineoplastic drugs. Its final evaluation may be reserved to further randomized trials. Recently, the psoriasis vulgaris is expected to be an additional field of the application of M-G. In this minireview data on synthesis, preclinical pharmacology, pharmacokinetics, biochemical effects and toxicology of M-G are given. Furthermore, clinical findings on M-G concerning its pharmacokinetic behaviour, antitumor and antipsoriatic activities are described.

Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models.

PubMed

Finch, Paul W; Mark Cross, Lawrence J; McAuley, Daniel F; Farrell, Catherine L

2013-09-01

Keratinocyte growth factor (KGF) is a paracrine-acting epithelial mitogen produced by cells of mesenchymal origin, that plays an important role in protecting and repairing epithelial tissues. Pre-clinical data initially demonstrated that a recombinant truncated KGF (palifermin) could reduce gastrointestinal injury and mortality resulting from a variety of toxic exposures. Furthermore, the use of palifermin in patients with hematological malignancies reduced the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. Based upon these findings, as well as the observation that KGF receptors are expressed in many, if not all, epithelial tissues, pre-clinical studies have been conducted to determine the efficacy of palifermin in protecting different epithelial tissues from toxic injury in an attempt to model various clinical situations in which it might prove to be of benefit in limiting tissue damage. In this article, we review these studies to provide the pre-clinical background for clinical trials that are described in the accompanying article and the rationale for additional clinical applications of palifermin. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Electronic health records to facilitate clinical research.

PubMed

Cowie, Martin R; Blomster, Juuso I; Curtis, Lesley H; Duclaux, Sylvie; Ford, Ian; Fritz, Fleur; Goldman, Samantha; Janmohamed, Salim; Kreuzer, Jörg; Leenay, Mark; Michel, Alexander; Ong, Seleen; Pell, Jill P; Southworth, Mary Ross; Stough, Wendy Gattis; Thoenes, Martin; Zannad, Faiez; Zalewski, Andrew

2017-01-01

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

Antenatal peer support workers and initiation of breast feeding: cluster randomised controlled trial.

PubMed

MacArthur, Christine; Jolly, Kate; Ingram, Lucy; Freemantle, Nick; Dennis, Cindy-Lee; Hamburger, Ros; Brown, Julia; Chambers, Jackie; Khan, Khalid

2009-01-30

To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. Cluster randomised controlled trial. Community antenatal clinics in one primary care trust in a multiethnic, deprived population. 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 weeks' gestation within the antenatal clinic or at home. The trained peer support workers were of similar ethnic and sociodemographic backgrounds to their clinic population. Initiation of breast feeding obtained from computerised maternity records of the hospitals where women from the primary care trust delivered. The sample was multiethnic, with only 9.4% of women being white British, and 70% were in the lowest 10th for deprivation. Most of the contacts with peer support workers took place in the antenatal clinics. Data on initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women (1083/1140 intervention and 1315/1371 controls). The groups did not differ for initiation of breast feeding: 69.0% (747/1083) in the intervention group and 68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95% confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery independently predicted initiation of breast feeding, but randomisation to the peer support worker service did not. A universal service for initiation of breast feeding using peer support workers provided within antenatal clinics serving a multiethnic, deprived population was ineffective in increasing initiation rates. Current Controlled Trials ISRCTN16126175.

High Rate of Awarding Compensation for Claims of Injuries Related to Clinical Trials by Pharmaceutical Companies in Japan: A Questionnaire Survey

PubMed Central

Kurihara, Chieko; Kusuoka, Hideo; Ono, Shunsuke; Kakee, Naoko; Saito, Kazuyuki; Takehara, Kenji; Tsujide, Kiyokazu; Nabeoka, Yuzo; Sakuhiro, Takuya; Aoki, Hiroshi; Morishita, Noriko; Suzuki, Chieko; Kachi, Shigeo; Kondo, Emiko; Komori, Yukiko; Isobe, Tetsu; Kageyama, Shigeru; Watanabe, Hiroshi

2014-01-01

Introduction International norms and ethical standards have suggested that compensation for research-related injury should be provided to injured research volunteers. However, statistical data of incidence of compensation claims and the rate of awarding them have been rarely reported. Method Questionnaire surveys were sent to pharmaceutical companies and medical institutions, focusing on industry-initiated clinical trials aiming at new drug applications (NDAs) on patient volunteers in Japan. Results With the answers from pharmaceutical companies, the incidence of compensation was 0.8%, including 0.06% of monetary compensation. Of the cases of compensation claims, 99% were awarded. In turn, with the answers from medical institutions, the incidence of compensation was 0.6%, including 0.4% of serious but not death cases, and 0.04% of death cases. Furthermore, most claims for compensation were initiated by medical institutions, rather than by the patients. On the other hand, with the answers from clinical trial volunteers, 3% of respondents received compensations. These compensated cases were 25% of the injuries which cannot be ruled out from the scope of compensation. Conclusion Our study results demonstrated that Japanese pharmaceutical companies have provided a high rate of compensation for clinical trial-related injuries despite the possibility of overestimation. In the era of global clinical development, our study indicates the importance of further surveys to find each country's compensation policy by determining how it is being implemented based on a survey of the actual status of compensation coming from statistical data. PMID:24416332

OCT for early quality evaluation of tooth-composite bond in clinical trials.

PubMed

Haak, Rainer; Schmidt, Patrick; Park, Kyung-Jin; Häfer, Matthias; Krause, Felix; Ziebolz, Dirk; Schneider, Hartmut

2018-06-19

To evaluate early quality of composite restorations with a universal adhesive in different application modes clinically and with optical coherence tomography (OCT). 22 patients with four non-carious cervical lesions each received composite restorations (Filtek Supreme TM XTE, 3 M). The universal adhesive Scotchbond Universal TM (SBU, 3 M) was applied with three etching protocols: self-etch (SE), selective-enamel-etch (SEE) and etch-and-rinse (ER). The etch-and-rinse adhesive OptiBond TM FL (OFL, Kerr) served as a control. Restorations were imaged by OCT (Thorlabs) directly after application (t 0 ). After 14 days (t 1 ) and 6 month (t 2 ) OCT imaging (interfacial adhesive defects) was repeated combined with clinical assessment (FDI criteria). Groups were compared by Friedman-/Wilcoxon- and McNemar-Test. No differences were seen clinically between groups (p i ≥ 0.500). OCT assessment revealed more adhesive defects at the enamel interface with SBU/SE at t 0- t 2 compared to all groups (p i ≤ 0.016). OFL showed more defects than SBU/ER (t 1 : p = 0.01; t 2 : p = 0.083). At dentin/cementum interface OFL exhibited more adhesive defects than SBU with all conditioning modes (t 0 , t 1 , p i ≤ 0.003) and at t 2 to SBU/SE and SBU/ER (p < 0.001). Since t 1 defects with SBU were detected more frequently in the SE and SEE modes compared to ER (p i ≤ 0.037). In contrast to SBU defects increased with OFL up to t 2 (p i ≤ 0.007). In contrast to clinical evaluation, OCT revealed subtle adhesive defects directly after application that might interfere with clinical success. It was demonstrated that ER doesn't decrease initial adhesion of SBU to dentin. Copyright © 2018. Published by Elsevier Ltd.

Practice development 'without walls' and the quandary of corporate practice.

PubMed

Graham, Iain; Fielding, Carol; Rooke, Debbie; Keen, Steven

2006-08-01

The context of this study is a group of clinical nurse specialists from across a Trust seeking accreditation as a practice development unit. The university was asked to facilitate the accreditation process via 11 2-hour learning sessions (including a one-hour focus group). During initial discussions between the university and practice development unit, the overarching research question for this study was set as: 'what are the main roles and responsibilities of clinical nurse specialists?' Although there is no known study of a practice development unit based beyond a ward or speciality, the central tenet of the practice development unit literature is that units must demonstrate their worth if they are to survive and harness senior management support in doing so. Data gleaned from the transcribed audio tape-recordings of the learning sessions were studied at least three times to ensure transcription accuracy and produce detailed charts. Ethical approval was granted by the appropriate Local Research Ethics Committee and written informed consent obtained from clinical nurse specialists. The study lasted 30 months and ended in October 2004. The four crucial statements that give meaning to specialist practice are: quality care giver; expert; information giver and initiator of change. Further analysis reveals the area of corporate and political practice as being missing from this and other lists of clinical nurse specialist attributes found in the literature. Clinical nurse specialists characterize their relationship with the Trust in terms of dichotomy--differing agendas and perceptions of value. The specialist role requires professional development in the areas of corporate and political acumen and professional business management. While the findings of this study relate to one Trust and a group of 16 clinical nurse specialists, with careful application they may be transferable to other settings and groups of senior nurses.

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.

Clinical application of micro-implant anchorage in initial orthodontic retraction.

PubMed

Wahabuddin, Shaji; Mascarenhas, Rohan; Iqbal, Mahamad; Husain, Akhter

2015-02-01

Micro-implant is a device that is temporarily fixed to bone for the purpose of enhancing orthodontic anchorage either by supporting the teeth of the reactive unit or by obviating the need for the reactive unit altogether, and which is subsequently removed after use. The purpose of this study was to evaluate the clinical efficiency of micro-implants in reinforcing anchorage during the initial retraction of anterior teeth, check the rate of initial retraction for 8 weeks, and assess the stability of micro-implants during this period. Eighteen micro-implants were placed (10 in the maxilla and 8 in the mandible) and immediately loaded with 200-250 g of force using 9-mm closed coil Nitinol springs. The amount of space closure was measured every 2 weeks until the eighth week. Cephalometric measurements were made at the end of the study to evaluate anchor loss, if any. Micro-implant stability was also assessed. The rate of initial retraction in the maxilla at the end of 8 weeks was 1.65 mm/quadrant and 1.51 mm/quadrant in the mandible. The amount of retraction on the left side of the arches was 1.66 mm/quadrant and 1.49 mm/quadrant on the right side. The average initial retraction for both arches per month was 0.78 mm. An anchor loss of 0.1 mm (0.06%) was observed in the maxilla while no mandibular anchor loss was recorded. The rate of initial retraction observed in the maxilla was more than that achieved in the mandible. Initial retraction was also more on the left side of the arches. There was no anchor loss in the mandible. The micro-implant-reinforced anchorage was helpful in minimizing anchor loss and accepted heavy traction forces but did not bring about a faster rate of retraction.

Concussion Care Practices and Utilization of Evidence-Based Guidelines in the Evaluation and Management of Concussion: A Survey of New England Emergency Departments.

PubMed

Stern, Robert A; Seichepine, Daniel; Tschoe, Christine; Fritts, Nathan G; Alosco, Michael L; Berkowitz, Oren; Burke, Peter; Howland, Jonathan; Olshaker, Jonathan; Cantu, Robert C; Baugh, Christine M; Holsapple, James W

2017-02-15

Evidence-based clinical practice guidelines can facilitate proper evaluation and management of concussions in the emergency department (ED), often the initial and primary point of contact for concussion care. There is no universally adopted set of guidelines for concussion management, and extant evidence suggests that there may be variability in concussion care practices and limited application of clinical practice guidelines in the ED. This study surveyed EDs throughout New England to examine current practices of concussion care and utilization of evidence-based clinical practice guidelines in the evaluation and management of concussions. In 2013, a 32-item online survey was e-mailed to 149/168 EDs throughout New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine). Respondents included senior administrators asked to report on their EDs use of clinical practice guidelines, neuroimaging decision-making, and discharge instructions for concussion management. Of the 72/78 respondents included, 35% reported absence of clinical practice guidelines, and 57% reported inconsistency in the type of guidelines used. Practitioner preference guided neuroimaging decision-making for 57%. Although 94% provided written discharge instructions, there was inconsistency in the recommended time frame for follow-up care (13% provided no specific time frame), the referral specialist to be seen (25% did not recommend any specialist), and return to activity instructions were inconsistent. There is much variability in concussion care practices and application of evidence-based clinical practice guidelines in the evaluation and management of concussions in New England EDs. Knowledge translational efforts will be critical to improve concussion management in the ED setting.

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review.

PubMed

Rutstein, Sarah E; Ananworanich, Jintanat; Fidler, Sarah; Johnson, Cheryl; Sanders, Eduard J; Sued, Omar; Saez-Cirion, Asier; Pilcher, Christopher D; Fraser, Christophe; Cohen, Myron S; Vitoria, Marco; Doherty, Meg; Tucker, Joseph D

2017-06-28

The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review

PubMed Central

Rutstein, Sarah E.; Ananworanich, Jintanat; Fidler, Sarah; Johnson, Cheryl; Sanders, Eduard J.; Sued, Omar; Saez-Cirion, Asier; Pilcher, Christopher D.; Fraser, Christophe; Cohen, Myron S.; Vitoria, Marco; Doherty, Meg; Tucker, Joseph D.

2017-01-01

Abstract Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. Results and Discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI – evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens. PMID:28691435

38 CFR 77.4 - Applications.

Code of Federal Regulations, 2014 CFR

2014-07-01

... grant application package, as described in the NOFA. (b) Renewal application. After receiving an initial... evaluations of renewal applications rely on performance data related to the initial grant, the application and...

[Evaluation of the German Research Foundation's (GRF) »Clinical Trials Academy for Junior Researchers« - publications and funding profiles].

PubMed

Dahmen, Levka; Krummenauer, Frank

2016-11-01

Background | The »Clinical Trials Academy for Junior Researchers« is a strategic funding instrument of the German Research Foundation (GRF). In clinical research, this program responds to an increasing lack of qualified clinician scientists. Application for participation in the workshop is based on a self-proposed academy project; participants can furthermore apply for a GRF grant to implement this academy project. This evaluation should quantify publication and third-party-funding profiles after participation in one of the previous GRF junior researchers workshops on clinical trials. Methods | Participants of all four GRF workshops were addressed by a standardized questionnaire to consider the project related number of publications and the cumulative impact factor, as well as the cumulative project-related consequential third-party-funding. Results | 64 of 92 former participants took part in the survey. From 41 implemented projects, 32 were granted with initial financial support by the GRF. 27 publications with a cumulative impact factor of 130 impact factor points (IP) were published by 13 authors. Of the 21 persons who submitted a grant application for subsequent third-party-funding a cumulative total grant volume of 5 223 000 € was reported by 13 participants. Conclusion | Although only 13 out of 64 participants reported impact publications or third-party-funding, respectively, these junior researchers' output can be considered encouraging. © Georg Thieme Verlag KG Stuttgart · New York.

Diffusion heterogeneity tensor MRI (?-Dti): mathematics and initial applications in spinal cord regeneration after trauma - biomed 2009.

PubMed

Ellington, Benjamin M; Schmit, Brian D; Gourab, Krishnaj; Sieber-Blum, Maya; Hu, Yao F; Schmainda, Kathleen M

2009-01-01

Diffusion weighted magnetic resonance imaging (DWI) is a powerful tool for evaluation of microstructural anomalies in numerous central nervous system pathologies. Diffusion tensor imaging (DTI) allows for the magnitude and direction of water self diffusion to be estimated by sampling the apparent diffusion coefficient (ADC) in various directions. Clinical DWI and DTI performed at a single level of diffusion weighting, however, does not allow for multiple diffusion compartments to be elicited. Furthermore, assumptions made regarding the precise number of diffusion compartments intrinsic to the tissue of interest have resulted in a lack of consensus between investigations. To overcome these challenges, a stretched-exponential model of diffusion was applied to examine the diffusion coefficient and "heterogeneity index" within highly compartmentalized brain tumors. The purpose of the current study is to expand on the stretched-exponential model of diffusion to include directionality of both diffusion heterogeneity and apparent diffusion coefficient. This study develops the mathematics of this new technique along with an initial application in quantifying spinal cord regeneration following acute injection of epidermal neural crest stem cell (EPI-NCSC) grafts.

Three-dimensional (3D) printed endovascular simulation models: a feasibility study.

PubMed

Mafeld, Sebastian; Nesbitt, Craig; McCaslin, James; Bagnall, Alan; Davey, Philip; Bose, Pentop; Williams, Rob

2017-02-01

Three-dimensional (3D) printing is a manufacturing process in which an object is created by specialist printers designed to print in additive layers to create a 3D object. Whilst there are initial promising medical applications of 3D printing, a lack of evidence to support its use remains a barrier for larger scale adoption into clinical practice. Endovascular virtual reality (VR) simulation plays an important role in the safe training of future endovascular practitioners, but existing VR models have disadvantages including cost and accessibility which could be addressed with 3D printing. This study sought to evaluate the feasibility of 3D printing an anatomically accurate human aorta for the purposes of endovascular training. A 3D printed model was successfully designed and printed and used for endovascular simulation. The stages of development and practical applications are described. Feedback from 96 physicians who answered a series of questions using a 5 point Likert scale is presented. Initial data supports the value of 3D printed endovascular models although further educational validation is required.

Validation of a Behavioral Approach for Measuring Saccades in Parkinson's Disease.

PubMed

Turner, Travis H; Renfroe, Jenna B; Duppstadt-Delambo, Amy; Hinson, Vanessa K

2017-01-01

Speed and control of saccades are related to disease progression and cognitive functioning in Parkinson's disease (PD). Traditional eye-tracking complexities encumber application for individual evaluations and clinical trials. The authors examined psychometric properties of standalone tasks for reflexive prosaccade latency, volitional saccade initiation, and saccade inhibition (antisaccade) in a heterogeneous sample of 65 PD patients. Demographics had minimal impact on task performance. Thirty-day test-retest reliability estimates for behavioral tasks were acceptable and similar to traditional eye tracking. Behavioral tasks demonstrated concurrent validity with traditional eye-tracking measures; discriminant validity was less clear. Saccade initiation and inhibition discriminated PD patients with cognitive impairment. The present findings support further development and use of the behavioral tasks for assessing latency and control of saccades in PD.

NASA/Drexel program. [research effort in large-scale technical programs management for application to urban problems

NASA Technical Reports Server (NTRS)

1973-01-01

The results are reported of the NASA/Drexel research effort which was conducted in two separate phases. The initial phase stressed exploration of the problem from the point of view of three primary research areas and the building of a multidisciplinary team. The final phase consisted of a clinical demonstration program in which the research associates consulted with the County Executive of New Castle County, Delaware, to aid in solving actual problems confronting the County Government. The three primary research areas of the initial phase are identified as technology, management science, and behavioral science. Five specific projects which made up the research effort are treated separately. A final section contains the conclusions drawn from total research effort as well as from the specific projects.

Automated and real-time segmentation of suspicious breast masses using convolutional neural network

PubMed Central

Gregory, Adriana; Denis, Max; Meixner, Duane D.; Bayat, Mahdi; Whaley, Dana H.; Fatemi, Mostafa; Alizad, Azra

2018-01-01

In this work, a computer-aided tool for detection was developed to segment breast masses from clinical ultrasound (US) scans. The underlying Multi U-net algorithm is based on convolutional neural networks. Under the Mayo Clinic Institutional Review Board protocol, a prospective study of the automatic segmentation of suspicious breast masses was performed. The cohort consisted of 258 female patients who were clinically identified with suspicious breast masses and underwent clinical US scan and breast biopsy. The computer-aided detection tool effectively segmented the breast masses, achieving a mean Dice coefficient of 0.82, a true positive fraction (TPF) of 0.84, and a false positive fraction (FPF) of 0.01. By avoiding positioning of an initial seed, the algorithm is able to segment images in real time (13–55 ms per image), and can have potential clinical applications. The algorithm is at par with a conventional seeded algorithm, which had a mean Dice coefficient of 0.84 and performs significantly better (P< 0.0001) than the original U-net algorithm. PMID:29768415

Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology

PubMed Central

Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

2011-01-01

Abstract Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. PMID:21251219

Designed electromagnetic pulsed therapy: clinical applications.

PubMed

Gordon, Glen A

2007-09-01

First reduced to science by Maxwell in 1865, electromagnetic technology as therapy received little interest from basic scientists or clinicians until the 1980s. It now promises applications that include mitigation of inflammation (electrochemistry) and stimulation of classes of genes following onset of illness and injury (electrogenomics). The use of electromagnetism to stop inflammation and restore tissue seems a logical phenomenology, that is, stop the inflammation, then upregulate classes of restorative gene loci to initiate healing. Studies in the fields of MRI and NMR have aided the understanding of cell response to low energy EMF inputs via electromagnetically responsive elements. Understanding protein iterations, that is, how they process information to direct energy, we can maximize technology to aid restorative intervention, a promising step forward over current paradigms of therapy.

The EUROMEDIES EDI prototype system.

PubMed

Pramataris, K; Doukidis, G; Giaglis, G; Raptakis, J

1996-01-01

EDI is expected to be the dominant form of business communication between organisations moving to the Electronic Commerce era of 2000. The healthcare sector is already using EDI in the hospital supply function as well as in the clinical area and the reimbursement process. In this paper, we examine the use of EDI in the healthcare administration sector and move specifically its application to the Medical Devices Vigilance System. At a first place, the potential of this approach is examined, after an initial brief presentation of the EDI concept and its application in healthcare. This presentation is followed by an overall description of the EDI prototype system, which was developed in the context of the EUROMEDIES Concerted Action, in order to facilitate the requirements definition phase.

[Use of the reliable change index to evaluate the effectiveness of clinical interventions: Application of an asthma training program].

PubMed

Montero, Mikel; Iraurgi, Ioseba; Matellanes, Begoña; Montero, José Manuel

2015-12-01

To compare two methods for the evaluation of outcomes to assess effectiveness of a therapeutic intervention of a professional education program on asthma control. A naturalistic, intervention study in which asthmatic patients were attended by clinicians (IG group) who Had taken part in a special education program and a control group (CG) that received medical assistance from clinicians still waiting to be trained. Five urban Primary Care Health Centres of the same region. From an initial sample of 100 patients, 76 formed the final sample for analysis. The study included 37 males and 39 females, aged between 18 and 65 years (M=41.2 years). The two study groups were found to be homogeneous except for the sex variable. Training program for clinical treatment adherence. Peak flow as spirometric index, and structured interview. The results were initially analysed using classical techniques based on robust ANOVA models, and then by calculating the Reliable Change Index (RCI). ANOVA models, conducted separately for each sex, showed no significant differences, due to sample size. RCI methodology showed significant differences in the percentage of patients improved in both groups, as well as clinically relevant changes being observed individually. The RCI method is presented as an attractive alternative as regards the classical methods of analysis that can help in the clinical decision. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

A modified varying-stage adaptive phase II/III clinical trial design.

PubMed

Dong, Gaohong; Vandemeulebroecke, Marc

2016-07-01

Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A pragmatic method for transforming clinical research data from the research electronic data capture "REDCap" to Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM): Development and evaluation of REDCap2SDTM.

PubMed

Yamamoto, Keiichi; Ota, Keiko; Akiya, Ippei; Shintani, Ayumi

2017-06-01

The Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM) can be used for new drug application studies as well as secondarily for creating a clinical research data warehouse to leverage clinical research study data across studies conducted within the same disease area. However, currently not all clinical research uses Clinical Data Acquisition Standards Harmonization (CDASH) beginning in the set-up phase of the study. Once already initiated, clinical studies that have not utilized CDASH are difficult to map in the SDTM format. In addition, most electronic data capture (EDC) systems are not equipped to export data in SDTM format; therefore, in many cases, statistical software is used to generate SDTM datasets from accumulated clinical data. In order to facilitate efficient secondary use of accumulated clinical research data using SDTM, it is necessary to develop a new tool to enable mapping of information for SDTM, even during or after the clinical research. REDCap is an EDC system developed by Vanderbilt University and is used globally by over 2100 institutions across 108 countries. In this study, we developed a simulated clinical trial to evaluate a tool called REDCap2SDTM that maps information in the Field Annotation of REDCap to SDTM and executes data conversion, including when data must be pivoted to accommodate the SDTM format, dynamically, by parsing the mapping information using R. We confirmed that generating SDTM data and the define.xml file from REDCap using REDCap2SDTM was possible. Conventionally, generation of SDTM data and the define.xml file from EDC systems requires the creation of individual programs for each clinical study. However, our proposed method can be used to generate this data and file dynamically without programming because it only involves entering the mapping information into the Field Annotation, and additional data into specific files. Our proposed method is adaptable not only to new drug application studies but also to all types of research, including observational and public health studies. Our method is also adaptable to clinical data collected with CDASH at the beginning of a study in non-standard format. We believe that this tool will reduce the workload of new drug application studies and will support data sharing and reuse of clinical research data in academia. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of WHO 2010 Guidelines on Antiretroviral Therapy Initiation among Patients with HIV-Associated Tuberculosis in Clinics with and without Onsite HIV Services in the Democratic Republic of Congo

PubMed Central

Tabala, Martine; Batumbula, Marie Louise; Wenzi, Landry; Basaki, Emmanuel; Mungoyo, Eugenie; Mangala, Richard; Behets, Frieda

2016-01-01

Background. We assessed the impact of WHO's 2010 guidelines that removed the requirement of CD4 count before ART, on timely initiation of ART among HIV/TB patients in the Democratic Republic of Congo (DRC). Methods. Data collected to monitor implementation of provider initiated HIV testing and counseling (PITC) and linkage to HIV care from 65 and 13 TB clinics in Kinshasa and Kisangani, respectively, between November 2010 and June 2013. Results. Prior to the WHO's 2010 guidelines, in Kinshasa, 79.1% (401/507) of HIV/TB patients referred for HIV services were initiated on ART in clinics with onsite ART services compared to 50.0% (63/123) in clinics without. Following the implementation of the new guidelines, 89.8% (714/795) and 93.0% (345/371) of HIV/TB patients referred for HIV services were initiated on ART, respectively, in clinics with onsite and without onsite ART services. Similarly, in Kisangani, 69.7% (53/120) and 36.4% (16/44) in clinics with and without onsite ART service, respectively, were initiated on ART prior to the 2010 guidelines and 88.8% (135/152) and 72.6% (106/146), respectively, after the new guidelines. Conclusion. Though implementation of the 2010 guidelines increased the proportion of HIV/TB patients initiated on ART substantially, it remained below the 100% target, particularly in clinics without onsite ART services. PMID:27595020

Factors affecting initial disability allowance rates for the Disability Insurance and Supplemental Security Income programs: the role of the demographic and diagnostic composition of applicants and local labor market conditions.

PubMed

Rupp, Kalman

2012-01-01

Various factors outside the control of decision makers may affect the rate at which disability applications are allowed or denied during the initial step of eligibility determination in the Social Security Disability Insurance (DI) and Supplemental Security Income (SSI) programs. In this article, using individual-level data on applications, I estimate the role of three important factors--the demographic characteristics of applicants, the diagnostic mix of applicants, and the local unemployment rate--in affecting the probability of an initial allowance and state allowance rates. I use a random sample of initial determinations from 1993 through 2008 and a fixed-effects multiple regression framework. The empirical results show that the demographic and diagnostic characteristics of applicants and the local unemployment rate substantially affect the initial allowance rate. An increase in the local unemployment rate tends to be associated with a decrease in the initial allowance rate. This negative relationship holds for adult DI and SSI applicants and for SSI childhood applicants.

Next-generation sequencing for endocrine cancers: Recent advances and challenges.

PubMed

Suresh, Padmanaban S; Venkatesh, Thejaswini; Tsutsumi, Rie; Shetty, Abhishek

2017-05-01

Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

Practice of Regulatory Science (Development of Medical Devices).

PubMed

Niimi, Shingo

2017-01-01

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained. After a prototype passes through a clinical trial process similar to that for new drugs, application for approval is made. In the approval application process, medical devices are divided into new, improved, and generic types. Reviewers judge the validity of intended use, indications, operation procedures, and precautions, and in addition evaluate the balance between risk and benefit in terms of efficacy and safety. Other characteristics of medical devices are the need for the user to attain proficiency in usage techniques to ensure efficacy and safety, and the existence of a variety of medical devices for which assessment strategies differ, including differences in impact on the body in cases in which a physical burden to the body or failure of a medical device develops. Regulatory science of medical devices involves prediction, judgment, and evaluation of efficacy, safety, and quality, from which data result which can become indices in the development stages from design to application for approval. A reduction in the number of animals used for testing, improvement in efficiency, reduction of the necessity for clinical trials, etc. are expected through rational setting of evaluation items.

Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

PubMed

Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-06-01

The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors replied that their greatest challenges include (1) lack of global harmonization in reporting rules, (2) determining causality, and (3) fear of regulatory repercussions. Interaction with the Food and Drug Administration has helped improve sponsors' adherence to the final rule, and sponsors would benefit from increased communication with the Food and Drug Administration and educational materials. The goal of the final rule is to minimize uninformative safety reports so that important safety signals can be captured and communicated early enough in a clinical program to make changes that help ensure patient safety. Investigative staff and sponsors acknowledge that the rule has not been fully implemented although they agree with the intention. Clinical Trials Transformation Initiative will use the results from the surveys and interviews to develop new recommendations and educational materials that will be available to sponsors to increase compliance with the final rule and facilitate discussion between sponsors, investigators, and Food and Drug Administration representatives.

13 CFR 124.205 - Can an applicant ask SBA to reconsider SBA's initial decision to decline its application?

Code of Federal Regulations, 2011 CFR

2011-01-01

... reconsider SBA's initial decision to decline its application? (a) An applicant may request the AA/BD to... pertinent to overcoming the reason(s) for the initial decline. (b) The AA/BD will issue a written decision within 45 days of the regional DPCE's receipt of the applicant's request. The AA/BD may either approve...

13 CFR 124.205 - Can an applicant ask SBA to reconsider SBA's initial decision to decline its application?

Code of Federal Regulations, 2010 CFR

2010-01-01

... reconsider SBA's initial decision to decline its application? (a) An applicant may request the AA/BD to... pertinent to overcoming the reason(s) for the initial decline. (b) The AA/BD will issue a written decision within 45 days of the regional DPCE's receipt of the applicant's request. The AA/BD may either approve...

Measurement of user performance and attitudes assists the initial design of a computer user display and orientation method.

PubMed

Chase, C R; Ashikaga, T; Mazuzan, J E

1994-07-01

The objective of our study was to assess the acceptability of a proposed user interface to visually interfaced computer-assisted anesthesia record (VISI-CAARE), before the application was begun. The user interface was defined as the user display and its user orientation methods. We designed methods to measure user performance and attitude toward two different anesthesia record procedures: (1) the traditional pen and paper anesthetic record procedure of our hospital, and (2) VISI-CAARE. Performance measurements included the reaction speed (identifying the type and time of an event) and completion speed (describing the event). Performance also included accuracy of the recorded time of the event and accuracy of the description. User attitude was measured by (1) the physician's rating on a scale of 0 to 9 of the potential usefulness of computers in anesthesia care; (2) willingness to use the future application in the clinical environment; and (3) user suggestions for change. These measurements were used in a randomized trial of 21 physicians, of which data from 20 were available. After exposure to VISI-CAARE, the experimental subjects' ranking of computer usefulness in anesthesia care improved significantly (4.2 +/- 1.1 to 7.6 +/- 1.5, p = 0.0001), as did controls' (5.2 +/- 2.6 to 8 +/- 1.5, p = 0.0019). All the volunteers were willing to try the proposed prototype clinically, when it was ready. VISI-CAARE exposure was associated with faster and more accurate reaction to events over the traditional pen and paper machine, and slower and more accurate description of events in an artificial mock setting. VISI-CAARE 1.1 demonstrated significant improvements in both reaction speed and completion speed over VISI-CAARE 1.0, after changes were made to the user display and orientation methods. With graphic user interface prototyping environments, one can obtain preliminary user attitude and performance data, even before application programming is begun. This may be helpful in revising initial display and orientation methods, while obtaining user interest and commitment before actual programming and clinical testing.

Care zoning in a psychiatric intensive care unit: strengthening ongoing clinical risk assessment.

PubMed

Mullen, Antony; Drinkwater, Vincent; Lewin, Terry J

2014-03-01

To implement and evaluate the care zoning model in an eight-bed psychiatric intensive care unit and, specifically, to examine the model's ability to improve the documentation and communication of clinical risk assessment and management. Care zoning guides nurses in assessing clinical risk and planning care within a mental health context. Concerns about the varying quality of clinical risk assessment prompted a trial of the care zoning model in a psychiatric intensive care unit within a regional mental health facility. The care zoning model assigns patients to one of 3 'zones' according to their clinical risk, encouraging nurses to document and implement targeted interventions required to manage those risks. An implementation trial framework was used for this research to refine, implement and evaluate the impact of the model on nurses' clinical practice within the psychiatric intensive care unit, predominantly as a quality improvement initiative. The model was trialled for three months using a pre- and postimplementation staff survey, a pretrial file audit and a weekly file audit. Informal staff feedback was also sought via surveys and regular staff meetings. This trial demonstrated improvement in the quality of mental state documentation, and clinical risk information was identified more accurately. There was limited improvement in the quality of care planning and the documentation of clinical interventions. Nurses' initial concerns over the introduction of the model shifted into overall acceptance and recognition of the benefits. The results of this trial demonstrate that the care zoning model was able to improve the consistency and quality of risk assessment information documented. Care planning and evaluation of associated outcomes showed less improvement. Care zoning remains a highly applicable model for the psychiatric intensive care unit environment and is a useful tool in guiding nurses to carry out routine patient risk assessments. © 2013 John Wiley & Sons Ltd.

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.

Natural Occurring Silks and Their Analogues as Materials for Nerve Conduits.

PubMed

Radtke, Christine

2016-10-20

Spider silk and its synthetic derivatives have a light weight in combination with good strength and elasticity. Their high cytocompatibility and low immunogenicity make them well suited for biomaterial products such as nerve conduits. Silk proteins slowly degrade enzymatically in vivo, thus allowing for an initial therapeutic effect such as in nerve scaffolding to facilitate endogenous repair processes, and then are removed. Silks are biopolymers naturally produced by many species of arthropods including spiders, caterpillars and mites. The silk fibers are secreted by the labial gland of the larvae of some orders of Holometabola (insects with pupa) or the spinnerets of spiders. The majority of studies using silks for biomedical applications use materials from silkworms or spiders, mostly of the genus Nephila clavipes . Silk is one of the most promising biomaterials with effects not only in nerve regeneration, but in a number of regenerative applications. The development of silks for human biomedical applications is of high scientific and clinical interest. Biomaterials in use for biomedical applications have to meet a number of requirements such as biocompatibility and elicitation of no more than a minor inflammatory response, biodegradability in a reasonable time and specific structural properties. Here we present the current status in the field of silk-based conduit development for nerve repair and discuss current advances with regard to potential clinical transfer of an implantable nerve conduit for enhancement of nerve regeneration.

Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

PubMed Central

Cimino, George D; Pan, Chong-xian; Henderson, Paul T

2013-01-01

The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

Can an educational application increase risk perception accuracy amongst patients attending a high-risk breast cancer clinic?

PubMed

Keohane, D; Lehane, E; Rutherford, E; Livingstone, V; Kelly, L; Kaimkhani, S; O'Connell, F; Redmond, H P; Corrigan, M A

2017-04-01

To design, develop and test the effect of an educational initiative to improve risk perception amongst patients attending a high-risk breast cancer clinic. This was achieved through three objectives - 1. identifying an optimal method of presenting risk data, 2. designing and building a risk application, and 3. testing the ability of the application to successfully modify patients perceived risk of cancer. A mobile application was developed for this project using best practice methods for displaying risk information. Patients (n = 84) were randomly allocated into two groups - 'Control' or 'Treatment'. Both groups underwent standard risk counseling while the application was employed in the 'Treatment' group. The patients were surveyed before their session, immediately after and six weeks later. Increases in accuracy were seen in both groups with larger increases demonstrated in the 'Treatment' group with 'Personal 10 Year Risk' statistically significant ('Control' group increase from 21% to 48% vs the 'Treatment' group increase from 33% to 71% - p = 0.003). This project demonstrated trends towards improved risk perception, however mixed logistic regression was unable to show a 30% difference between groups. Numerical literacy and understanding of risk were identified as issues amongst the general population. Overestimating risk remains high amongst attendees. Using mobile applications to convey risk information to patients is a new and evolving area with a corresponding paucity of data. We have demonstrated its potential and emphasised the importance of designing how this information is communicated to patients in order to make it understandable and meaningful. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using technology to enhance the quality of home health care: three case studies of health information technology initiatives at the visiting nurse service of New York.

PubMed

Russell, David; Rosenfeld, Peri; Ames, Sylvia; Rosati, Robert J

2010-01-01

There is a growing recognition among health services researchers and policy makers that Health Information Technology (HIT) has the potential to address challenging issues that face patients and providers of healthcare. The Visiting Nurse Service of New York (VNSNY), a large not-for-profit home healthcare agency, has integrated technology applications into the service delivery model of several programs. Case studies, including the development and implementation, of three informatics initiatives at VNSNY are presented on: (1) Quality Scorecards that utilize process, outcomes, cost, and satisfaction measures to assess performance among clinical staff and programs; (2) a tool to identify patients at risk of being hospitalized, and (3) a predictive model that identifies patients who are eligible for physical rehabilitation services. Following a description of these initiatives, we discuss their impact on quality and process indicators, as well as the opportunities and challenges to implementation. © 2010 National Association for Healthcare Quality.

Twin robotic x-ray system for 2D radiographic and 3D cone-beam CT imaging

NASA Astrophysics Data System (ADS)

Fieselmann, Andreas; Steinbrener, Jan; Jerebko, Anna K.; Voigt, Johannes M.; Scholz, Rosemarie; Ritschl, Ludwig; Mertelmeier, Thomas

2016-03-01

In this work, we provide an initial characterization of a novel twin robotic X-ray system. This system is equipped with two motor-driven telescopic arms carrying X-ray tube and flat-panel detector, respectively. 2D radiographs and fluoroscopic image sequences can be obtained from different viewing angles. Projection data for 3D cone-beam CT reconstruction can be acquired during simultaneous movement of the arms along dedicated scanning trajectories. We provide an initial evaluation of the 3D image quality based on phantom scans and clinical images. Furthermore, initial evaluation of patient dose is conducted. The results show that the system delivers high image quality for a range of medical applications. In particular, high spatial resolution enables adequate visualization of bone structures. This system allows 3D X-ray scanning of patients in standing and weight-bearing position. It could enable new 2D/3D imaging workflows in musculoskeletal imaging and improve diagnosis of musculoskeletal disorders.

Genome editing in pluripotent stem cells: research and therapeutic applications

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

Deleidi, Michela, E-mail: michela.deleidi@dzne.de; Hertie Institute for Clinical Brain Research, University of Tübingen; Yu, Cong

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases formore » ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. - Highlights: • Programmable nucleases have proven efficient and specific for genome editing in human pluripotent stem cells (hPSCs). • Genome edited hPSCs can be employed to study gene function in health and disease as well as drug and chemical screens. • Genome edited hPSCs hold great promise for ex vivo gene therapy approaches. • Technical and safety issues should be first addressed to advance the clinical use of gene-edited hPSCs.« less

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

PubMed Central

Aldhamen, Yasser Ali; Seregin, Sergey S.; Amalfitano, Andrea

2011-01-01

Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general. PMID:22566830

Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar.

PubMed

Harrison, Steven M; Dolinsky, Jill S; Knight Johnson, Amy E; Pesaran, Tina; Azzariti, Danielle R; Bale, Sherri; Chao, Elizabeth C; Das, Soma; Vincent, Lisa; Rehm, Heidi L

2017-10-01

Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar-thereby allowing identification of differences and motivation to resolve those differences-is critical to moving toward more consistent variant interpretations.Genet Med advance online publication 09 March 2017.

Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children.

PubMed

Visudtibhan, Anannit; Bhudhisawadi, Kasama; Vaewpanich, Jarin; Chulavatnatol, Suvatna; Kaojareon, Sming

2011-03-01

Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Big Data in Designing Clinical Trials: Opportunities and Challenges

PubMed Central

Mayo, Charles S.; Matuszak, Martha M.; Schipper, Matthew J.; Jolly, Shruti; Hayman, James A.; Ten Haken, Randall K.

2017-01-01

Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials. PMID:28913177

Big Data in Designing Clinical Trials: Opportunities and Challenges.

PubMed

Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

2017-01-01

Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

The synergy of the whole: building a global system for clinical trials to accelerate medicines development.

PubMed

Koski, Greg; Tobin, Mary F; Whalen, Matthew

2014-10-01

The pharmaceutical industry, once highly respected, productive, and profitable, is in the throes of major change driven by many forces, including economics, science, regulation, and ethics. A variety of initiatives and partnerships have been launched to improve efficiency and productivity but without significant effect because they have failed to consider the process as a system. Addressing the challenges facing this complex endeavor requires more than modifications of individual processes; it requires a fully integrated application of systems thinking and an understanding of the desired goals and complex interactions among essential components and stakeholders of the whole. A multistakeholder collaborative effort, led by the Alliance for Clinical Research Excellence and Safety (ACRES), a global nonprofit organization operating in the public interest, is now under way to build a shared global system for clinical research. Its systems approach focuses on the interconnection of stakeholders at critical points of interaction within 4 operational domains: site development and support, quality management, information technology, and safety. The ACRES initiatives, Site Accreditation and Standards, Product Safety Culture, Global Ethical Review and Regulatory Innovation, and Quality Assurance and Safety, focus on building and implementing systems solutions. Underpinning these initiatives is an open, shared, integrated technology (site and optics and quality informatics initiative). We describe the rationale, challenges, progress, and successes of this effort to date and lessons learned. The complexity and fragmentation of the intensely proprietary ecosystem of drug development, challenging regulatory climate, and magnitude of the endeavor itself pose significant challenges, but the economic, social, and scientific rewards will more than justify the effort. An effective alliance model requires a willingness of multiple stakeholders to work together to build a shared system within a noncompetitive space that will have major benefits for all, including better access to medicines, better health, and more productive lives. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Conceptual Model of Research to Reduce Stigma Related to Mental Disorders in Adolescents

PubMed Central

Pinto-Foltz, Melissa D.; Logsdon, M. Cynthia

2010-01-01

Purpose: To explicate an initial conceptual model that is amenable to testing and guiding anti-stigma interventions with adolescents. Design/Sources Used: Multidisciplinary research and theoretical articles were reviewed. . Conclusions: The conceptual model may guide anti-stigma interventions, and undergo testing and refinement in the future to reflect scientific advances in stigma reduction among adolescents. Use of a conceptual model enhances empirical evaluation of anti-stigma interventions yielding a casual explanation for the intervention effects and enhances clinical applicability of interventions across settings. PMID:19916813

Using a spreadsheet/table template for economic value added analysis.

PubMed

Cassey, Margaret

2008-01-01

Translating clinical research into practical applications that are cost effective has received significant attention as staff nurses attempt to expand new knowledge into an already complex daily workflow. spreadsheet/table template created in a word processing format can assist with setting up and carrying out the analysis of costs for comparing different approaches to routine activities. By encouraging nurses to take the initiative to examine parts of everyday nursing practice with an eye to cost analysis, significant contributions can be made to maximizing the bottom line.

The ethics of human gene transfer.

PubMed

Kimmelman, Jonathan

2008-03-01

Almost 20 years since the first gene-transfer trial was carried out in humans, the field has made significant advances towards clinical application. Nevertheless, it continues to face numerous unresolved ethical challenges--among them are the question of when to initiate human testing, the acceptability of germline modification and whether the technique should be applied to the enhancement of traits. Although such issues have precedents in other medical contexts, they take on a different character in gene transfer, in part because of the scientific uncertainty and the social context of innovation.

Heat-shock proteins in stromal joint tissues: innocent bystanders or disease-initiating proteins?

PubMed

Lambrecht, Stijn; Juchtmans, Nele; Elewaut, Dirk

2014-02-01

Heat-shock proteins (HSPs) are molecular chaperones that are highly conserved between species. In recent decades it has become clear that these proteins play an important role in the pathogenesis of inflammatory and degenerative joint diseases by (dys)regulating the immune system and by direct effects on the stromal tissues of the joint. In this review we discuss current insights into the expression pattern of HSPs in connective tissues, the direct biological role of HSPs in stromal tissues and the potential clinical applications.

Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use

PubMed Central

Nayak, Satyaprakash; Sander, Oliver; Al‐Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj

2018-01-01

Quantitative pharmacology (QP) applications in translational medicine, drug‐development, and therapeutic use were crowd‐sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial‐burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model‐informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. PMID:29330855

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

PubMed

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Application of 4G wireless network-based system for remote diagnosis and nursing of stomal complications

PubMed Central

Xu, Xiulian; Cao, Yingjuan; Luan, Xiaorong

2014-01-01

Background: This study aims to apply 4G wireless network in the remote diagnosis of stoma complications for the first time. Background: Remote diagnosis and nursing care for a variety of illnesses are urgently needed in clinical settings. Objectives: Combining with relevant clinical manifestations, an Android phone-based intelligent diagnosis system was designed to construct a universe, easy access to exploitation and human-computer interaction database and exploitation environment for applications and programs. Methods: “Production rule” and forward reasoning method were utilized to design arborescence structures and logic reasoner associated with stoma complications. Stoma physicians were responsible for delivering evaluation scores on patients’ health status using analytic hierarchy process. The emphasis of this study is to exploit an “Android phone-based system for remote diagnosis of stoma”, which is of certain universe usage. Results: Such system was tested in the Medicine Information Center of Qilu Hospital of Shandong University and initially applied in the city of De Zhou, Shandong province, China. Conclusions: These results collectively demonstrated that the system is easy to carry, of high utility and free from the limitations of wire network environment, etc. It provides clinical evidence for establishing a novel type model for the exchange between patients and physicians. PMID:25550986

Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

PubMed

Konijeti, Gauree G; Sauk, Jenny; Shrime, Mark G; Gupta, Meera; Ananthakrishnan, Ashwin N

2014-06-01

Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

Application of Appropriate Use Criteria for Initial Transthoracic Echocardiography in an Academic Outpatient Pediatric Cardiology Program.

PubMed

Safa, Raya; Aggarwal, Sanjeev; Misra, Amrit; Kobayashi, Daisuke

2017-08-01

Transthoracic echocardiography (TTE) is a non-invasive diagnostic modality for children with suspected heart disease. The American College of Cardiology published Appropriate Use Criteria (AUC) for an initial outpatient pediatric TTE in 2014 to promote effective care and improve resource utilization. The objective was to determine the appropriateness of TTE per the published AUC in a single academic pediatric cardiology clinic as a baseline performance quality measure. The echocardiography database was used to identify initial outpatient TTE in children during January-March 2014. TTE indications (appropriate [A], may be appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or abnormal) were recorded. The effect of AUC and age groups on yield of abnormal TTE findings was analyzed. Of the 2166 screened studies, our study cohort consisted of 247 TTEs. Indications rated A, M, and R were found in 129, 27, and 90, respectively, and 1 was unclassifiable. Majority of TTE (n = 183) were normal, although incidental findings were noted in 32 and abnormal findings in 32 cases. Abnormal findings were noted in 26/129 of A, 2/27 of M, and 4/90 of R. Indications rated A were significantly associated with yield of abnormal TTE findings, adjusted by age group. Infants and adolescents were more likely to have abnormal TTE findings compared to young children. Recently published AUC were validated for initial TTE in the outpatient pediatric cardiology clinic. Appropriateness rated by AUC was highly associated with yield of abnormal TTE findings and worked best in infants and adolescent.

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.

Adoptive cell therapy: genetic modification to redirect effector cell specificity.

PubMed

Morgan, Richard A; Dudley, Mark E; Rosenberg, Steven A

2010-01-01

Building on the principals that the adoptive transfer of T cells can lead to the regression of established tumors in humans, investigators are now further manipulating these cells using genetic engineering. Two decades of human gene transfer experiments have resulted in the translation of laboratory technology into robust clinical applications. The purpose of this review is to give the reader an introduction to the 2 major approaches being developed to redirect effector T-cell specificity. Primary human T cells can be engineered to express exogenous T-cell receptors or chimeric antigen receptors directed against multiple human tumor antigens. Initial clinical trial results have demonstrated that both T-cell receptor- and chimeric antigen receptor-engineered T cells can be administered to cancer patients and mediate tumor regression.

Optimizing resource allocation and patient flow: process analysis and reorganization in three chemotherapy outpatient clinics.

PubMed

Holmes, Morgan; Bodie, Kelly; Porter, Geoffrey; Sullivan, Victoria; Tarasuk, Joy; Trembley, Jodie; Trudeau, Maureen

2010-01-01

Optimizing human and physical resources is a major concern for cancer care decision-makers and practitioners. This issue is particularly acute in the context of ambulatory out patient chemotherapy clinics, especially when - as is the case almost everywhere in the industrialized world - the number of people requiring systemic therapy is increasing while budgets, staffing and physical space remain static. Recent initiatives at three hospital-based chemotherapy units - in Halifax, Toronto and Kingston - shed light on the value of process analysis and reorganization for using existing human and physical resources to their full potential, improving patient flow and enhancing patient satisfaction. The steps taken in these settings are broadly applicable to other healthcare settings and would likely result in similar benefits in those environments.

47 CFR 22.959 - Rules governing processing of applications for initial systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... initial systems. 22.959 Section 22.959 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.959 Rules governing processing of applications for initial systems. Pending applications for authority to operate the first...

Plasma medicine—current state of research and medical application

NASA Astrophysics Data System (ADS)

Weltmann, K.-D.; von Woedtke, Th

2017-01-01

Plasma medicine means the direct application of cold atmospheric plasma (CAP) on or in the human body for therapeutic purposes. Further, the field interacts strongly with results gained for biological decontamination. Experimental research as well as first practical application is realized using two basic principles of CAP sources: dielectric barrier discharges (DBD) and atmospheric pressure plasma jets (APPJ). Originating from the fundamental insights that the biological effects of CAP are most probably caused by changes of the liquid environment of cells, and are dominated by reactive oxygen and nitrogen species (ROS, RNS), basic mechanisms of biological plasma activity are identified. It was demonstrated that there is no increased risk of cold plasma application and, above all, there are no indications for genotoxic effects. The most important biological effects of cold atmospheric pressure plasma were identified: (1) inactivation of a broad spectrum of microorganisms including multidrug resistant ones; (2) stimulation of cell proliferation and tissue regeneration with lower plasma treatment intensity (treatment time); (3) inactivation of cells by initialization of programmed cell death (apoptosis) with higher plasma treatment intensity (treatment time). In recent years, the main focus of clinical applications was in the field of wound healing and treatment of infective skin diseases. First CAP sources are CE-certified as medical devices now which is the main precondition to start the introduction of plasma medicine into clinical reality. Plasma application in dentistry and, above all, CAP use for cancer treatment are becoming more and more important research fields in plasma medicine. A further in-depth knowledge of control and adaptation of plasma parameters and plasma geometries is needed to obtain suitable and reliable plasma sources for the different therapeutic indications and to open up new fields of medical application.

IMPLEMENTATION OF HEALTH TECHNOLOGY ASSESSMENT WORK IN A HOSPITAL IN KAZAKHSTAN.

PubMed

Kosherbayeva, Lyazzat; Hailey, David; Kurakbaev, Kural; Tsoy, Aleksey; Zhuzzhanov, Ormanbek; Donbay, Abilay; Kumar, Ainur; Nadyrov, Kamalzhan

2016-01-01

The aim of this study was to implement health technology assessment (HA) in the First General City Hospital in Astana, Kazakhstan. We organized trainings to familiarize hospital staff with the purpose and details of HTA. An HTA committee was established, with representation from hospital physicians and managers, and criteria for prioritization of health technologies determined. Clinical departments of the hospital were asked to prepare applications for new technologies for their services. The HTA committee reviewed five applications and selected a technology from one of these, on single incision laparoscopic surgery (SILS), for assessment. A short HTA report on SILS was prepared, covering its safety, clinical effectiveness, and cost effectiveness. The report was used to support a request to the Department of Health for additional funding to implement this technology within the hospital. This funding was approved and SILS was established in several hospital departments. This successful initial experience with HTA has paved the way for its routine use by the hospital for informing decisions on the procurement and use of new health technologies.

Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

PubMed

Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

2016-04-01

A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering.

Gold-Containing Indoles as Anti-Cancer Agents that Potentiate the Cytotoxic Effects of Ionizing Radiation

PubMed Central

Craig, Sandra; Gao, Lei; Lee, Irene; Gray, Thomas; Berdis, Anthony J.

2012-01-01

This report describes the design and application of several distinct gold-containing indoles as anti-cancer agents. When used individually, all gold-bearing compounds display cytostatic effects against leukemia and adherent cancer cell lines. However, two gold-bearing indoles show unique behavior by increasing the cytotoxic effects of clinically relevant levels of ionizing radiation. Quantifying the amount of DNA damage demonstrates that each gold-indole enhances apoptosis by inhibiting DNA repair. Both Au(I)-indoles were tested for inhibitory effects against various cellular targets including thioredoxin reductase, a known target of several gold compounds, and various ATP-dependent kinases. While neither compound significantly inhibits the activity of thioreoxin reductase, both showed inhibitory effects against several kinases associated with cancer initiation and progression. The inhibition of these kinases provides a possible mechanism for the ability of these Au(I)-indoles potentiate the cytotoxic effects of ionizing radiation. Clinical applications of combining Au(I)-indoles with ionizing radiation are discussed as a new strategy to achieve chemosensitization of cancer cells. PMID:22289037

A historical evaluation of Chinese tongue diagnosis in the treatment of septicemic plague in the pre-antibiotic era, and as a new direction for revolutionary clinical research applications.

PubMed

Solos, Ioannis; Liang, Yuan

2018-04-12

Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities, may have discouraged doctors to come in direct contact with their patients and take the pulse. However, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world's earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Clinical and economic impact of remote monitoring on the follow-up of patients with implantable electronic cardiovascular devices: an observational study.

PubMed

Costa, Paulo Dias; Reis, A Hipólito; Rodrigues, Pedro P

2013-02-01

Traditional follow-up of patients with cardiovascular devices is still an activity that, in addition to serving an increasing population, requires a considerable amount of time and specialized human and technical resources. Our aim was to evaluate the applicability of the CareLink(®) (Medtronic, Minneapolis, MN) remote monitoring system as a complementary option to the follow-up of patients with implanted devices, between in-office visits. Evaluated outcomes included both clinical (event detection and time to diagnosis) and nonclinical (patient's satisfaction and economic costs) aspects. An observational, longitudinal, prospective study was conducted with patients from a Portuguese central hospital sampled by convenience during 1 week (43 patients). Data were collected in four moments: two in-office visits and two remote evaluations, reproducing 1 year of clinical follow-up. Data sources included health records, implant reports, initial demographic data collection, follow-up printouts, and a questionnaire. After selection criteria were verified, 15 patients (11 men [73%]) were included, 63.4±10.8 years old, representing 14.0±6.3 implant months. Clinically, 15 events were detected (9 by remote monitoring and 6 by patient-initiated activation), of which only 9 were symptomatic. We verified that remote monitoring could detect both symptomatic and asymptomatic events, whereas patient-initiated activation only detected symptomatic ones (p=0.028). Moreover, the mean diagnosis anticipation in patients with events was approximately 58 days (p<0.001). In nonclinical terms, we observed high or very high satisfaction (67% and 33%, respectively) with using remote monitoring technology, but still 8 patients (53%) stated they preferred in-office visits. Finally, the introduction of remote monitoring technology has the ability to reduce total follow-up costs for patients by 25%. We conclude that the use of this system constitutes a viable complementary option to the follow-up of patients with implantable devices, between in-office visits.

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 critical narrative review of transfer of basic science knowledge in health professions education.

PubMed

Castillo, Jean-Marie; Park, Yoon Soo; Harris, Ilene; Cheung, Jeffrey J H; Sood, Lonika; Clark, Maureen D; Kulasegaram, Kulamakan; Brydges, Ryan; Norman, Geoffrey; Woods, Nicole

2018-06-01

'Transfer' is the application of a previously learned concept to solve a new problem in another context. Transfer is essential for basic science education because, to be valuable, basic science knowledge must be transferred to clinical problem solving. Therefore, better understanding of interventions that enhance the transfer of basic science knowledge to clinical reasoning is essential. This review systematically identifies interventions described in the health professions education (HPE) literature that document the transfer of basic science knowledge to clinical reasoning, and considers teaching and assessment strategies. A systematic search of the literature was conducted. Articles related to basic science teaching at the undergraduate level in HPE were analysed using a 'transfer out'/'transfer in' conceptual framework. 'Transfer out' refers to the application of knowledge developed in one learning situation to the solving of a new problem. 'Transfer in' refers to the use of previously acquired knowledge to learn from new problems or learning situations. Of 9803 articles initially identified, 627 studies were retrieved for full text evaluation; 15 were included in the literature review. A total of 93% explored 'transfer out' to clinical reasoning and 7% (one article) explored 'transfer in'. Measures of 'transfer out' fostered by basic science knowledge included diagnostic accuracy over time and in new clinical cases. Basic science knowledge supported learning - 'transfer in' - of new related content and ultimately the 'transfer out' to diagnostic reasoning. Successful teaching strategies included the making of connections between basic and clinical sciences, the use of commonsense analogies, and the study of multiple clinical problems in multiple contexts. Performance on recall tests did not reflect the transfer of basic science knowledge to clinical reasoning. Transfer of basic science knowledge to clinical reasoning is an essential component of HPE that requires further development for implementation and scholarship. © 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Nanoscale platforms for messenger RNA delivery.

PubMed

Li, Bin; Zhang, Xinfu; Dong, Yizhou

2018-05-04

Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA-based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA-based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid-derived nanoparticles, polymer-based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures. © 2018 Wiley Periodicals, Inc.

Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles After Dermal Application of Rivastigmine Patch.

PubMed

Nozaki, Sachiko; Yamaguchi, Masayuki; Lefèvre, Gilbert

2016-07-01

Rivastigmine is an inhibitor of acetylcholinesterases and butyrylcholinesterases for symptomatic treatment of Alzheimer disease and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the plasma concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks after misuse of the patch (e.g., longer application than 24 h, multiple patches applied at the same time, and so forth). The model comprised 2 compartments which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine and PK parameters after intravenous administration. The model was fitted to the clinical PK profiles after single application of rivastigmine patch to obtain model parameters. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and area under the drug plasma concentration-time curve) conformed to the observed values and then was used to simulate the PK profiles of rivastigmine. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after patch misuse. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Compressed Sensing for Body MRI

PubMed Central

Feng, Li; Benkert, Thomas; Block, Kai Tobias; Sodickson, Daniel K; Otazo, Ricardo; Chandarana, Hersh

2016-01-01

The introduction of compressed sensing for increasing imaging speed in MRI has raised significant interest among researchers and clinicians, and has initiated a large body of research across multiple clinical applications over the last decade. Compressed sensing aims to reconstruct unaliased images from fewer measurements than that are traditionally required in MRI by exploiting image compressibility or sparsity. Moreover, appropriate combinations of compressed sensing with previously introduced fast imaging approaches, such as parallel imaging, have demonstrated further improved performance. The advent of compressed sensing marks the prelude to a new era of rapid MRI, where the focus of data acquisition has changed from sampling based on the nominal number of voxels and/or frames to sampling based on the desired information content. This paper presents a brief overview of the application of compressed sensing techniques in body MRI, where imaging speed is crucial due to the presence of respiratory motion along with stringent constraints on spatial and temporal resolution. The first section provides an overview of the basic compressed sensing methodology, including the notion of sparsity, incoherence, and non-linear reconstruction. The second section reviews state-of-the-art compressed sensing techniques that have been demonstrated for various clinical body MRI applications. In the final section, the paper discusses current challenges and future opportunities. PMID:27981664

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.

Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

PubMed

Patrick-Lake, Bray

2018-02-01

Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

Needles in Hay II: Detecting Cardiac Pathology by the Pediatric Chest Pain Standardized Clinical Assessment and Management Plan.

PubMed

Kane, David A; Friedman, Kevin G; Fulton, David R; Geggel, Robert L; Saleeb, Susan F

2016-09-01

To determine if patients evaluated using the pediatric chest pain standardized clinical assessment and management plan (SCAMP) in cardiology clinic were later diagnosed with unrecognized cardiac pathology, and to determine if other patients with cardiac pathology not enrolled in the SCAMP would have been identified using the algorithm. Patients 7-21 years of age, newly diagnosed with hypertrophic or dilated cardiomyopathy, coronary anomalies, pulmonary embolus, pulmonary hypertension, pericarditis, or myocarditis were identified from the Boston Children's Hospital (BCH) cardiac database between July 1, 2010 and December 31, 2012. Patients were cross-referenced to the SCAMP database or retrospectively assessed with the SCAMP algorithm. Among 98 patients with cardiac pathology, 34 (35%) reported chest pain, of whom 10 were diagnosed as outpatients. None of these patients were enrolled in the SCAMP because of alternate chief complaints (n = 4) or referral to BCH for management of the new diagnosis (n = 6). Each of these patients would have had an echocardiogram recommended by retrospective application of the SCAMP algorithm. Two other patients with cardiac pathology were among the 1124 patients assessed by the SCAMP. One patient initially diagnosed with noncardiac chest pain presented 18 months later and was diagnosed with myocarditis as an inpatient. One patient seen initially in the emergency department was subsequently diagnosed with pericarditis as an outpatient. Patients assessed by the chest pain SCAMP at BCH were not later diagnosed with cardiac pathology that was missed at the initial encounter. Nonenrolled outpatients with cardiac pathology and chest pain would have been successfully identified with the SCAMP algorithm. © 2016 Wiley Periodicals, Inc.

Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering.

PubMed

Hamad, Islam; Al-Hanbali, Othman; Hunter, A Christy; Rutt, Kenneth J; Andresen, Thomas L; Moghimi, S Moein

2010-11-23

Nanoparticles with surface projected polyethyleneoxide (PEO) chains in "mushroom-brush" and "brush" configurations display stealth properties in systemic circulation and have numerous applications in site-specific targeting for controlled drug delivery and release as well as diagnostic imaging. We report on the "structure-activity" relationship pertaining to surface-immobilized PEO of various configurations on model nanoparticles, and the initiation of complement cascade, which is the most ancient component of innate human immunity, and its activation may induce clinically significant adverse reactions in some individuals. Conformational states of surface-projected PEO chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only switches complement activation from C1q-dependent classical to lectin pathway but also reduces the level of generated complement activation products C4d, Bb, C5a, and SC5b-9. Also, changes in adsorbed polymer configuration trigger alternative pathway activation differently and through different initiators. Notably, the role for properdin-mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom-brush configuration. Since nanoparticle-mediated complement activation is of clinical concern, our findings provide a rational basis for improved surface engineering and design of immunologically safer stealth and targetable nanosystems with polymers for use in clinical medicine.

Classifying orofacial pains: a new proposal of taxonomy based on ontology

PubMed Central

NIXDORF, D. R.; DRANGSHOLT, M. T.; ETTLIN, D. A.; GAUL, C.; DE LEEUW, R.; SVENSSON, P.; ZAKRZEWSKA, J. M.; DE LAAT, A.; CEUSTERS, W.

2012-01-01

SUMMARY Propose a new taxonomy model based on ontological principles for disorders that manifest themselves through the symptom of persistent orofacial pain and are commonly seen in clinical practice and difficult to manage. Consensus meeting of eight experts from various geographic areas representing different perspectives (orofacial pain, headache, oral medicine and ontology) as an initial step towards improving the taxonomy. Ontological principles were introduced, reviewed and applied during the consensus building process. Diagnostic criteria for persistent dento-alveolar pain disorder (PDAP) were formulated as an example to be used to model the taxonomical structure of all orofacial pain conditions. These criteria have the advantage of being (i) anatomically defined, (ii) in accordance with other classification systems for the provision of clinical care, (iii) descriptive and succinct, (iv) easy to adapt for applications in varying settings, (v) scalable and (vi) transferable for the description of pain disorders in other orofacial regions of interest. Limitations are that the criteria introduce new terminology, do not have widespread acceptance and have yet to be tested. These results were presented to the greater conference membership and were unanimously accepted. Consensus for the diagnostic criteria of PDAP was established within this working group. This is an initial first step towards developing a coherent taxonomy for orofacial pain disorders, which is needed to improve clinical research and care. PMID:21848527

The Photodynamic Bone Stabilization System: a minimally invasive, percutaneous intramedullary polymeric osteosynthesis for simple and complex long bone fractures.

PubMed

Vegt, Paul; Muir, Jeffrey M; Block, Jon E

2014-01-01

The treatment of osteoporotic long bone fractures is difficult due to diminished bone density and compromised biomechanical integrity. The majority of osteoporotic long bone fractures occur in the metaphyseal region, which poses additional problems for surgical repair due to increased intramedullary volume. Treatment with internal fixation using intramedullary nails or plating is associated with poor clinical outcomes in this patient population. Subsequent fractures and complications such as screw pull-out necessitate additional interventions, prolonging recovery and increasing health care costs. The Photodynamic Bone Stabilization System (PBSS) is a minimally invasive surgical technique that allows clinicians to repair bone fractures using a light-curable polymer contained within an inflatable balloon catheter, offering a new treatment option for osteoporotic long bone fractures. The unique polymer compound and catheter application provides a customizable solution for long bone fractures that produces internal stability while maintaining bone length, rotational alignment, and postsurgical mobility. The PBSS has been utilized in a case series of 41 fractures in 33 patients suffering osteoporotic long bone fractures. The initial results indicate that the use of the light-cured polymeric rod for this patient population provides excellent fixation and stability in compromised bone, with a superior complication profile. This paper describes the clinical uses, procedural details, indications for use, and the initial clinical findings of the PBSS.

Classifying orofacial pains: a new proposal of taxonomy based on ontology.

PubMed

Nixdorf, D R; Drangsholt, M T; Ettlin, D A; Gaul, C; De Leeuw, R; Svensson, P; Zakrzewska, J M; De Laat, A; Ceusters, W

2012-03-01

We propose a new taxonomy model based on ontological principles for disorders that manifest themselves through the symptom of persistent orofacial pain and are commonly seen in clinical practice and difficult to manage. Consensus meeting of eight experts from various geographic areas representing different perspectives (orofacial pain, headache, oral medicine and ontology) as an initial step towards improving the taxonomy. Ontological principles were introduced, reviewed and applied during the consensus building process. Diagnostic criteria for persistent dento-alveolar pain disorder (PDAP) were formulated as an example to be used to model the taxonomical structure of all orofacial pain conditions. These criteria have the advantage of being (i) anatomically defined, (ii) in accordance with other classification systems for the provision of clinical care, (iii) descriptive and succinct, (iv) easy to adapt for applications in varying settings, (v) scalable and (vi) transferable for the description of pain disorders in other orofacial regions of interest. Limitations are that the criteria introduce new terminology, do not have widespread acceptance and have yet to be tested. These results were presented to the greater conference membership and were unanimously accepted. Consensus for the diagnostic criteria of PDAP was established within this working group. This is an initial first step towards developing a coherent taxonomy for orofacial pain disorders, which is needed to improve clinical research and care. © 2011 Blackwell Publishing Ltd.

The Photodynamic Bone Stabilization System: a minimally invasive, percutaneous intramedullary polymeric osteosynthesis for simple and complex long bone fractures

PubMed Central

Vegt, Paul; Muir, Jeffrey M; Block, Jon E

2014-01-01

The treatment of osteoporotic long bone fractures is difficult due to diminished bone density and compromised biomechanical integrity. The majority of osteoporotic long bone fractures occur in the metaphyseal region, which poses additional problems for surgical repair due to increased intramedullary volume. Treatment with internal fixation using intramedullary nails or plating is associated with poor clinical outcomes in this patient population. Subsequent fractures and complications such as screw pull-out necessitate additional interventions, prolonging recovery and increasing health care costs. The Photodynamic Bone Stabilization System (PBSS) is a minimally invasive surgical technique that allows clinicians to repair bone fractures using a light-curable polymer contained within an inflatable balloon catheter, offering a new treatment option for osteoporotic long bone fractures. The unique polymer compound and catheter application provides a customizable solution for long bone fractures that produces internal stability while maintaining bone length, rotational alignment, and postsurgical mobility. The PBSS has been utilized in a case series of 41 fractures in 33 patients suffering osteoporotic long bone fractures. The initial results indicate that the use of the light-cured polymeric rod for this patient population provides excellent fixation and stability in compromised bone, with a superior complication profile. This paper describes the clinical uses, procedural details, indications for use, and the initial clinical findings of the PBSS. PMID:25540600

The Development of a Postgraduate Orthopaedic Manual Therapy Residency Program in Nairobi, Kenya.

PubMed

Cunningham, Shala; Jackson, Richard; Muli, Daniel Kangutu; McFelea, Joni

2017-01-01

There are very few opportunities for long-term, comprehensive postgraduate education in developing countries because of fiscal and human resource constraints. Therefore, physiotherapists have little opportunity following graduation to advance their skills through the improvement of clinical reasoning and treatment planning and application. To address the need for sustainable advanced instruction in physiotherapy within the country, a postgraduate Residency program was initiated in Nairobi, Kenya in 2012. The mission of the program is to graduate advanced orthopedic practitioners who can lead their communities and local profession in the advancement of clinical care and education. Since its inception, six cohorts have been initiated for a total of 90 resident participants. In addition, six program graduates are being trained to continue the Residency program and are serving as teaching assistants for the on campus modules. This training will result in a self-sustaining program by 2020. The manual therapy Residency education model allowed for advancement of the participating physiotherapists professional development utilizing evidence-based practice. This was done without altering the current education system within the country, or accessing expensive equipment. The Residency program was developed and established with the cooperation of a local education institution and a non-profit corporation in the United States. This collaboration has facilitated the advancement of orthopedic clinical standards in the country and will, hopefully, one day serve an as a template for future programs.

Physician reasons for nonpharmacologic treatment of hyperglycemia in older patients newly diagnosed with type 2 diabetes mellitus.

PubMed

Marrett, Elizabeth; Zhang, Qiaoyi; Kanitscheider, Claudia; Davies, Michael J; Radican, Larry; Feinglos, Mark N

2012-11-01

To identify reasons why primary care physicians (PCPs) do not treat older patients newly diagnosed with type 2 diabetes mellitus (T2DM) with antihyperglycemic agents following diagnosis. US PCPs were surveyed via the internet regarding their reasons for not treating patients aged >65 years diagnosed with T2DM and had not yet initiated antihyperglycemic therapy for ≥6 months after diagnosis. PCPs were requested to provide relevant clinical information for untreated older patients and select applicable reasons for not initiating treatment from a list of 35 possibilities, grouped into five categories. A total of 508 PCPs completed the online survey and provided complete clinical data for 770 patients. The reasons provided by the first-ranked physician for not initiating antihyperglycemic therapy were related to diet and exercise (57.5%); mild hyperglycemia (23.8%); patient's concerns (13.4%); concerns about antihyperglycemic agents (3.0%); and comorbidities and polypharmacy (2.3%). The "diet and exercise" category was the most common first-ranked non-treatment reason, regardless of recent hemoglobin A(1c) (HbA(1c)) stratum. Reasons within the "patient's concerns," "concerns related to antihyperglycemic agents," and "comorbidities and polypharmacy" categories tended to be selected more often as first-ranked reasons by physicians for patients with higher HbA(1c) values. Of the 158 patients whose physicians planned to initiate antihyperglycemic therapy within the next month, 54.4% already had a most recent HbA(1c) value above their physician-stated threshold for treatment initiation. In the PCPs studied, there was a tendency to select appropriate reasons for non-treatment with antihyperglycemic agents given their patients' glycemic status. However, there was inertia related to the initiation of pharmacological therapy in some older patients with newly diagnosed T2DM. Important factors included physicians' perceptions of "mild" hyperglycemia and the HbA(1c) threshold for using antihyperglycemic agents.

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

PubMed

Kim, Gyuri; Bae, Ji Cheol; Yi, Byoung Kee; Hur, Kyu Yeon; Chang, Dong Kyung; Lee, Moon-Kyu; Kim, Jae Hyeon; Jin, Sang-Man

2017-07-18

A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. This clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field. Clinicaltrials.gov NCT 03112343 . Registered on 12 April 2017.

The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.

PubMed

Heijman, Jordi; Algalarrondo, Vincent; Voigt, Niels; Melka, Jonathan; Wehrens, Xander H T; Dobrev, Dobromir; Nattel, Stanley

2016-04-01

Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The high road to success: how investing in ethics enhances corporate objectives.

PubMed

Dashefsky, Richard

2003-01-01

There is a growing gap between the tidal wave of information emerging from the Human Genome Project and other molecular biology initiatives, and the clinical research needed to transform these discoveries into new diagnostics and therapeutics. While genomics-based technologies are being rapidly integrated into pharmaceutical R&D, many steps in the experimental process are still reliant on traditional surrogate model systems whose predictive power about human disease is incomplete or inaccurate. There is a growing trend underway in the research community to introduce actual human disease understanding as early as possible into discovery, thereby improving accuracy of results throughout the R&D continuum. Such an approach (known as clinical genomics: the large scale study of genes in the context of actual human disease) requires the availability of large quantities of ethically and legally sourced, high-quality human tissues with associated clinical information.Heretofore, no source could meet all of these requirements. Ardais Corporation was the first to address this need by pioneering a systematized, standardized network for the collection, processing, dissemination and research application of human tissue and associated clinical information, all of which rest on the highest ethical standards. Based on a novel model of collaboration between industry and the academic/medical community, Ardais has created procedures, structures, technologies, and information tools that collectively compromise a new paradigm in the application of human disease to biomedical research. Ardais now serves as a clinical genomics resource to dozens of academic researchers and biopharmaceutical companies, providing products and services to accelerate and improve drug discovery and development.

Challenges in the Clinical Application of the American Society of Clinical Oncology Value Framework: A Medicare Cost-Benefit Analysis in Chronic Lymphocytic Leukemia.

PubMed

Seymour, Erlene K; Schiffer, Charles A; de Souza, Jonas A

2017-12-01

The ASCO Value Framework calculates the value of cancer therapies. Given costly novel therapeutics for chronic lymphocytic leukemia, we used the framework to compare net health benefit (NHB) and cost within Medicare of all regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines. The current NCCN guidelines for chronic lymphocytic leukemia were reviewed. All referenced studies were screened, and only randomized controlled prospective trials were included. The revised ASCO Value Framework was used to calculate NHB. Medicare drug pricing was used to calculate the cost of therapies. Forty-nine studies were screened. The following observations were made: only 10 studies (20%) could be evaluated; when comparing regimens studied against the same control arm, ranking NHB scores were comparable to their preference in guidelines; NHB scores varied depending on which variables were used, and there were no clinically validated thresholds for low or high values; treatment-related deaths were not weighted in the toxicity scores; and six of the 10 studies used less potent control arms, ranked as the least-preferred NCCN-recommended regimens. The ASCO Value Framework is an important initial step to quantify value of therapies. Essential limitations include the lack of clinically relevant validated thresholds for NHB scores and lack of incorporation of grade 5 toxicities/treatment-related mortality into its methodology. To optimize its application for clinical practice, we urge investigators/sponsors to incorporate and report the required variables to calculate the NHB of regimens and encourage trials with stronger comparator arms to properly quantify the relative value of therapies.

The influence of lidocaine topical anesthesia during transesophageal echocardiography on blood methemoglobin level and risk of methemoglobinemia.

PubMed

Filipiak-Strzecka, Dominika; Kasprzak, Jarosław D; Wiszniewska, Marta; Walusiak-Skorupa, Jolanta; Lipiec, Piotr

2015-04-01

Methemoglobinemia is a relatively rare, but potentially life-threating medical condition, which may be induced by application of topical anaesthetic agents commonly used during endoscopic procedure. The aim of our study was to assess the influence of lidocaine used prior to transesophageal echocardiography (TEE) on the blood level of methemoglobin in vivo. Additionally we attempted to establish the occurrence rate of clinically evident lidocaine-induced methemoglobinemia on the basis of data collected in our institution. We retrospectively analyzed patient records from 3,354 TEEs performed in our echocardiographic laboratory over the course of 13 years in search for clinically evident methemoglobinemia cases. Additionally, 18 consecutive patients referred for TEE were included in the prospective part of our analysis. Blood samples were tested before and 60 min after pre-TEE lidocaine anesthesia application. Information concerning concomitant conditions and pharmacotherapy were also obtained. In 3,354 patients who underwent TEE in our institution no cases of clinically evident methemoglobinemia occurred. In the prospective part of the study, none of 18 patients [16 (89 %) men, mean age 63 ± 13] was diagnosed with either clinical symptoms of methemoglobinemia or exceeded normal blood concentration of methemoglobin. Initial mean methemoglobin level was 0.5 ± 0.1 % with mild, statistically (but not clinically) significant rise to 0.6 ± 0.1 % after 60 min (p = 0.02). Among the analyzed factors only the relation between the proton pump inhibitors intake and methemoglobin blood level rise was identified as statistically relevant (p = 0.03). In adults, pre-TEE lidocaine anesthesia with recommended dosage results in significant increase in methemoglobin blood level, which however does not exceed normal values and does not result in clinically evident methemoglobinemia.

The efficacy of self-directed modules for clinical learning: advanced competencies in entry-level physical therapy education.

PubMed

Peck, Kirk; Paschal, Karen; Black, Lisa; Nelson, Kelly

2014-01-01

Prior to graduation, students often express an interest to advance clinical and professional skills in teaching, research, administration, and various niche practice areas. The acquisition of advanced education in selected areas of practice is believed to improve employment opportunities, accelerate career advancement including eligibility for professional certifications, and contribute to personal satisfaction in the profession. The purpose of this paper is to (1) describe an innovative model of education, the Directed Practice Experience (DPE) elective, that incorporates a student-initiated learning process designed to achieve student-identified professional goals, and (2) report the outcomes for graduates who have completed the DPE in an entry-level program in physical therapy education. Students who met select criteria were eligible to complete a DPE. Applicants designed a 4- to 6-week clinical education experience consisting of stated rationale for personal and professional growth, examples of leadership and service, and self-directed objectives that are beyond entry-level expectations as measured by the revised Physical Therapist Clinical Performance Instrument, version 2006. Twenty-six students have completed DPEs since 2005. Fifty percent resulted in new academic partnerships. At least 25% of graduates now serve as clinical instructors for the entry-level program. Those who participated in DPEs have also completed post-graduate residencies, attained ABPTS Board certifications, authored peer-reviewed publications, and taught in both PT and residency programs. The DPE model allows qualified students to acquire advanced personal skills and knowledge prior to graduation in areas of professional practice that exceed entry-level expectations. The model is applicable to all CAPTE accredited physical therapy education programs and is especially beneficial for academic programs desiring to form new community partnerships for student clinical education.

Improved participants' understanding of research information in real settings using the SIDCER informed consent form: a randomized-controlled informed consent study nested with eight clinical trials.

PubMed

Koonrungsesomboon, Nut; Tharavanij, Thipaporn; Phiphatpatthamaamphan, Kittichet; Vilaichone, Ratha-Korn; Manuwong, Sudsayam; Curry, Parichat; Siramolpiwat, Sith; Punchaipornpon, Thanachai; Kanitnate, Supakit; Tammachote, Nattapol; Yamprasert, Rodsarin; Chanvimalueng, Waipoj; Kaewkumpai, Ruchirat; Netanong, Soiphet; Kitipawong, Peerapong; Sritipsukho, Paskorn; Karbwang, Juntra

2017-02-01

This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. A single-center, randomized-controlled study nested with eight clinical trials was conducted at Thammasat University Hospital, Thailand. A total of 258 participants from any of the eight clinical trials were enrolled and randomly assigned to read either the SIDCER ICF (n = 130) or the conventional ICF (n = 128) of the respective trial. Their understanding of necessary information was assessed using the post-test questionnaire; they were allowed to consult a given ICF while completing the questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥80%, and the secondary endpoint was the total score of the post-test. The proportion of the participants in the SIDCER ICF group who achieved the primary endpoint was significantly higher than that of the conventional ICF group (60.8 vs. 41.4%, p = 0.002). The total score of the post-test was also significantly higher among the participants who read the SIDCER ICF than those who read the conventional ICF (83.3 vs. 76.0%, p < 0.001). The present study demonstrated that the SIDCER ICF was applicable and effective to improve Thai research participants' understanding of research information in diverse clinical trials. Using the SIDCER ICF methodology, clinical researchers can improve the quality of ICFs for their trials.

Concussion Care Practices and Utilization of Evidence-Based Guidelines in the Evaluation and Management of Concussion: A Survey of New England Emergency Departments

PubMed Central

Seichepine, Daniel; Tschoe, Christine; Fritts, Nathan G.; Alosco, Michael L.; Berkowitz, Oren; Burke, Peter; Howland, Jonathan; Olshaker, Jonathan; Cantu, Robert C.; Baugh, Christine M.; Holsapple, James W.

2017-01-01

Abstract Evidence-based clinical practice guidelines can facilitate proper evaluation and management of concussions in the emergency department (ED), often the initial and primary point of contact for concussion care. There is no universally adopted set of guidelines for concussion management, and extant evidence suggests that there may be variability in concussion care practices and limited application of clinical practice guidelines in the ED. This study surveyed EDs throughout New England to examine current practices of concussion care and utilization of evidence-based clinical practice guidelines in the evaluation and management of concussions. In 2013, a 32-item online survey was e-mailed to 149/168 EDs throughout New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine). Respondents included senior administrators asked to report on their EDs use of clinical practice guidelines, neuroimaging decision-making, and discharge instructions for concussion management. Of the 72/78 respondents included, 35% reported absence of clinical practice guidelines, and 57% reported inconsistency in the type of guidelines used. Practitioner preference guided neuroimaging decision-making for 57%. Although 94% provided written discharge instructions, there was inconsistency in the recommended time frame for follow-up care (13% provided no specific time frame), the referral specialist to be seen (25% did not recommend any specialist), and return to activity instructions were inconsistent. There is much variability in concussion care practices and application of evidence-based clinical practice guidelines in the evaluation and management of concussions in New England EDs. Knowledge translational efforts will be critical to improve concussion management in the ED setting. PMID:27112592

Outcomes of Australian rural clinical schools: a decade of success building the rural medical workforce through the education and training continuum.

PubMed

Greenhill, Jennene A; Walker, Judi; Playford, Denese

2015-01-01

The establishment of the rural clinical schools funded through the Commonwealth Department of Health and Ageing (now Department of Health) Rural Clinical Training and Support program over a decade ago has been a significant policy initiative in Australian rural health. This article explores the impacts of this policy initiative and presents the wide range of educational innovations contextualised to each rural community they serve. This article reviews the achievements of the Australian rural clinical and regional medical schools (RCS/RMS) through semi-structured interviews with the program directors or other key informants. The questions and responses were analysed according to the funding parameters to ascertain the numbers of students, types of student placements and range of activities undertaken by each university program. Sixteen university medical schools have established 18 rural programs, creating an extensive national network of RCS and RMS in every state and territory. The findings reveal extensive positive impacts on rural and regional communities, curriculum innovation in medical education programs and community engagement activities. Teaching facilities, information technology, video-conferencing and student accommodation have brought new infrastructure to small rural towns. Rural clinicians are thriving on new opportunities for education and research. Clinicians continue to deliver clinical services and some have taken on formal academic positions, reducing professional isolation, improving the quality of care and their job satisfaction. This strategy has created many new clinical academics in rural areas, which has retained and expanded the clinical workforce. A total of 1224 students are provided with high-quality learning experiences for long-term clinical placements. These placements consist of a year or more in primary care, community and hospital settings across hundreds of rural and remote areas. Many programs offer longitudinal integrated clerkships; others offer block rotations in general practice and specialist clinics. Nine universities established programs prior to 2004, and these well-established programs are finding graduates who are returning to rural practice. Universities are required to have 25% of the students from a rural background. University admission policies have changed to encourage more applications from rural students. This aspect of the policy implements the extensive research evidence that rural-origin students are more likely to become rural practitioners. Additional capacity for research in RCS has influenced the rural health agenda in fields including epidemiology, population health, Aboriginal health, aged care, mental health and suicide prevention, farming families and climate change. There are strong research partnerships with rural workforce agencies, research centres for early career researchers and PhD students. The RCS policy initiative has vastly increased opportunities for medical students to have long-term clinical placements in rural health services. Over a decade since the policy has been implemented, graduates are being attracted to rural practice because they have positive learning experiences, good infrastructure and support within rural areas. The study shows the RCS initiative sets the stage for a sustainable future Australian rural medical workforce now requiring the development of a seamless rural clinical training pipeline linking undergraduate and postgraduate medical education.

Use of an Orientation Clinic to Reduce Failed New Patient Appointments in Primary Care

PubMed Central

Jain, Sharad; Chou, Calvin L

2000-01-01

Patients who fail to attend initial appointments reduce clinic efficiency. To maximize attendance by newly referred outpatients, we introduced a mandatory group orientation clinic for all new patients and determined its effects on no-show rates. Orientation clinic also provided health care screening and opportunities for patient feedback. The new patient no-show rate for initial provider visits decreased significantly from 45% before institution of orientation clinic to 18% afterwards (P < .0001). The total no-show (patients who failed to attend orientation clinic or an initial provider visit) rate of the postintervention group was 51% (P = .28, compared with before the intervention). This intervention improved the efficiency and minimized the wasted time of our clinicians. PMID:11119184

Closure of a Recurrent Bronchopleural Fistula Using a Matrix Seeded With Patient-Derived Mesenchymal Stem Cells.

PubMed

Aho, Johnathon M; Dietz, Allan B; Radel, Darcie J; Butler, Greg W; Thomas, Mathew; Nelson, Timothy J; Carlsen, Brian T; Cassivi, Stephen D; Resch, Zachary T; Faubion, William A; Wigle, Dennis A

2016-10-01

: Management of recurrent bronchopleural fistula (BPF) after pneumonectomy remains a challenge. Although a variety of devices and techniques have been described, definitive management usually involves closure of the fistula tract through surgical intervention. Standard surgical approaches for BPF incur significant morbidity and mortality and are not reliably or uniformly successful. We describe the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to repair a multiply recurrent postpneumonectomy BPF. Adipose-derived MSCs were isolated from patient abdominal adipose tissue, expanded, and seeded onto bio-absorbable mesh, which was surgically implanted at the site of BPF. Clinical follow-up and postprocedural radiological and bronchoscopic imaging were performed to ensure BPF closure, and in vitro stemness characterization of patient-specific MSCs was performed. The patient remained clinically asymptomatic without evidence of recurrence on bronchoscopy at 3 months, computed tomographic imaging at 16 months, and clinical follow-up of 1.5 years. There is no evidence of malignant degeneration of MSC populations in situ, and the patient-derived MSCs were capable of differentiating into adipocytes, chondrocytes, and osteocytes using established protocols. Isolation and expansion of autologous MSCs derived from patients in a malnourished, deconditioned state is possible. Successful closure and safety data for this approach suggest the potential for an expanded study of the role of autologous MSCs in regenerative surgical applications for BPF. Bronchopleural fistula is a severe complication of pulmonary resection. Current management is not reliably successful. This work describes the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to the repair of a large, multiply recurrent postpneumonectomy BPF. Clinical follow-up of 1.5 years without recurrence suggests initial safety and feasibility of this approach. Further assessment of MSC grafts in these difficult clinical scenarios requires expanded study. ©AlphaMed Press.

Biomarkers for oxidative stress: clinical application in pediatric medicine.

PubMed

Tsukahara, Hirokazu

2007-01-01

Loads of reactive oxygen species (ROS), including superoxide anion and nitric oxide, that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Circumstantial evidence suggests that ROS play a crucial role in the initiation and progression of various diseases in children and adolescents. The involvement of ROS and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in young subjects and appropriate methods for its measurement remain to be defined. Recently, specific biomarkers for oxidative damage and antioxidant defense have been introduced into the field of pediatric medicine. This review is intended to provide an overview of clinical applications of oxidative stress biomarkers in the field of pediatric medicine. First, this review presents the biochemistry and pathophysiology of ROS and antioxidant defense systems. Second, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that several reliable biomarkers are easily measurable using enzyme-linked immunosorbent assay. Third, this review presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2'-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in several clinical conditions, including atopic dermatitis and diabetes mellitus. New and interesting data on oxidative stress and antioxidant defenses in neonatal biology are also presented. Fourth, this review discusses the ever-accumulating body of data linking oxidative stress to disturbances of the nitric oxide system and vascular endothelial activation/dysfunction. Finally, this review describes the reported clinical trials that have evaluated the efficacy of antioxidants for oxidative-stress related diseases. Suggestions are advanced for the direction of future trials using antioxidant therapies. Repeated measurement of appropriate parameters will enable us to discern the pathophysiological patterns of pediatric diseases and guide our therapies appropriately.

Nucleic acid-based aptamers: applications, development and clinical trials.

PubMed

Kanwar, Jagat R; Roy, Kislay; Maremanda, Nihal G; Subramanian, Krishnakumar; Veedu, Rakesh N; Bawa, Raj; Kanwar, Rupinder K

2015-01-01

Short single-stranded oligonucleotides called aptamers, often termed as chemical antibodies, have been developed as powerful alternatives to traditional antibodies with respect to their obvious advantages like high specificity and affinity, longer shelf-life, easier manufacturing protocol, freedom to introduce chemical modifications for further improvement, etc. Reiterative selection process of aptamers over 10-15 cycles starting from a large initial pool of random nucleotide sequences renders them with high binding affinity, thereby making them extremely specific for their targets. Aptamer-based detection systems are well investigated and likely to displace primitive detection systems. Aptamer chimeras (combination of aptamers with another aptamer or biomacromolecule or chemical moiety) have the potential activity of both the parent molecules, and thus hold the capability to perform diverse functions at the same time. Owing to their extremely high specificity and lack of immunogenicity or pathogenicity, a number of other aptamers have recently entered clinical trials and have garnered favorable attention from pharmaceutical companies. Promising results from the clinical trials provide new hope to change the conventional style of therapy. Aptamers have attained high therapeutic relevance in a short time as compared to synthetic drugs and/or other modes of therapy. This review follows the various trends in aptamer technology including production, selection, modifications and success in clinical fields. It focusses largely on the various applications of aptamers which mainly depend upon their selection procedures. The review also sheds light on various modifications and chimerizations that have been implemented in order to improve the stability and functioning of the aptamers, including introduction of locked nucleic acids (LNAs). The application of various aptamers in detection systems has been discussed elaborately in order to stress on their role as efficient diagnostic agents. The key aspect of this review is focused on success of aptamers on the basis of their performance in clinical trials for various diseases.

Towards application of rule learning to the meta-analysis of clinical data: an example of the metabolic syndrome.

PubMed

Wojtusiak, Janusz; Michalski, Ryszard S; Simanivanh, Thipkesone; Baranova, Ancha V

2009-12-01

Systematic reviews and meta-analysis of published clinical datasets are important part of medical research. By combining results of multiple studies, meta-analysis is able to increase confidence in its conclusions, validate particular study results, and sometimes lead to new findings. Extensive theory has been built on how to aggregate results from multiple studies and arrive to the statistically valid conclusions. Surprisingly, very little has been done to adopt advanced machine learning methods to support meta-analysis. In this paper we describe a novel machine learning methodology that is capable of inducing accurate and easy to understand attributional rules from aggregated data. Thus, the methodology can be used to support traditional meta-analysis in systematic reviews. Most machine learning applications give primary attention to predictive accuracy of the learned knowledge, and lesser attention to its understandability. Here we employed attributional rules, the special form of rules that are relatively easy to interpret for medical experts who are not necessarily trained in statistics and meta-analysis. The methodology has been implemented and initially tested on a set of publicly available clinical data describing patients with metabolic syndrome (MS). The objective of this application was to determine rules describing combinations of clinical parameters used for metabolic syndrome diagnosis, and to develop rules for predicting whether particular patients are likely to develop secondary complications of MS. The aggregated clinical data was retrieved from 20 separate hospital cohorts that included 12 groups of patients with present liver disease symptoms and 8 control groups of healthy subjects. The total of 152 attributes were used, most of which were measured, however, in different studies. Twenty most common attributes were selected for the rule learning process. By applying the developed rule learning methodology we arrived at several different possible rulesets that can be used to predict three considered complications of MS, namely nonalcoholic fatty liver disease (NAFLD), simple steatosis (SS), and nonalcoholic steatohepatitis (NASH).

40 CFR 75.20 - Initial certification and recertification procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... all applicable initial certification tests under paragraph (c) of this section are completed by the... installed, initial certification is required. (1) Notification of initial certification test dates. The...) tests. (4) Certification (or recertification) application formal approval process. The Administrator...

40 CFR 75.20 - Initial certification and recertification procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... all applicable initial certification tests under paragraph (c) of this section are completed by the... installed, initial certification is required. (1) Notification of initial certification test dates. The...) tests. (4) Certification (or recertification) application formal approval process. The Administrator...

40 CFR 75.20 - Initial certification and recertification procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... all applicable initial certification tests under paragraph (c) of this section are completed by the... installed, initial certification is required. (1) Notification of initial certification test dates. The...) tests. (4) Certification (or recertification) application formal approval process. The Administrator...

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

Soffientini, Chiara Dolores, E-mail: chiaradolores.soffientini@polimi.it; Baselli, Giuseppe; De Bernardi, Elisabetta

Purpose: Quantitative {sup 18}F-fluorodeoxyglucose positron emission tomography is limited by the uncertainty in lesion delineation due to poor SNR, low resolution, and partial volume effects, subsequently impacting oncological assessment, treatment planning, and follow-up. The present work develops and validates a segmentation algorithm based on statistical clustering. The introduction of constraints based on background features and contiguity priors is expected to improve robustness vs clinical image characteristics such as lesion dimension, noise, and contrast level. Methods: An eight-class Gaussian mixture model (GMM) clustering algorithm was modified by constraining the mean and variance parameters of four background classes according to the previousmore » analysis of a lesion-free background volume of interest (background modeling). Hence, expectation maximization operated only on the four classes dedicated to lesion detection. To favor the segmentation of connected objects, a further variant was introduced by inserting priors relevant to the classification of neighbors. The algorithm was applied to simulated datasets and acquired phantom data. Feasibility and robustness toward initialization were assessed on a clinical dataset manually contoured by two expert clinicians. Comparisons were performed with respect to a standard eight-class GMM algorithm and to four different state-of-the-art methods in terms of volume error (VE), Dice index, classification error (CE), and Hausdorff distance (HD). Results: The proposed GMM segmentation with background modeling outperformed standard GMM and all the other tested methods. Medians of accuracy indexes were VE <3%, Dice >0.88, CE <0.25, and HD <1.2 in simulations; VE <23%, Dice >0.74, CE <0.43, and HD <1.77 in phantom data. Robustness toward image statistic changes (±15%) was shown by the low index changes: <26% for VE, <17% for Dice, and <15% for CE. Finally, robustness toward the user-dependent volume initialization was demonstrated. The inclusion of the spatial prior improved segmentation accuracy only for lesions surrounded by heterogeneous background: in the relevant simulation subset, the median VE significantly decreased from 13% to 7%. Results on clinical data were found in accordance with simulations, with absolute VE <7%, Dice >0.85, CE <0.30, and HD <0.81. Conclusions: The sole introduction of constraints based on background modeling outperformed standard GMM and the other tested algorithms. Insertion of a spatial prior improved the accuracy for realistic cases of objects in heterogeneous backgrounds. Moreover, robustness against initialization supports the applicability in a clinical setting. In conclusion, application-driven constraints can generally improve the capabilities of GMM and statistical clustering algorithms.« less

49 CFR 236.502 - Automatic brake application, initiation by restrictive block conditions stopping distance in...

Code of Federal Regulations, 2010 CFR

2010-10-01

... restrictive block conditions stopping distance in advance. 236.502 Section 236.502 Transportation Other... Cab Signal Systems Standards § 236.502 Automatic brake application, initiation by restrictive block... initiate an automatic brake application at least stopping distance from the entrance to a block, wherein...

14 CFR 302.211 - Procedures in certificate cases involving initial or continuing fitness.

Code of Federal Regulations, 2012 CFR

2012-01-01

... initial or continuing fitness. 302.211 Section 302.211 Aeronautics and Space OFFICE OF THE SECRETARY... Disposition of Applications § 302.211 Procedures in certificate cases involving initial or continuing fitness... applicant's fitness to operate. Where such applications propose the operation of scheduled service in...

14 CFR 302.211 - Procedures in certificate cases involving initial or continuing fitness.

Code of Federal Regulations, 2014 CFR

2014-01-01

... initial or continuing fitness. 302.211 Section 302.211 Aeronautics and Space OFFICE OF THE SECRETARY... Disposition of Applications § 302.211 Procedures in certificate cases involving initial or continuing fitness... applicant's fitness to operate. Where such applications propose the operation of scheduled service in...

14 CFR 302.211 - Procedures in certificate cases involving initial or continuing fitness.

Code of Federal Regulations, 2013 CFR

2013-01-01

... initial or continuing fitness. 302.211 Section 302.211 Aeronautics and Space OFFICE OF THE SECRETARY... Disposition of Applications § 302.211 Procedures in certificate cases involving initial or continuing fitness... applicant's fitness to operate. Where such applications propose the operation of scheduled service in...

9 CFR 2.11 - Denial of initial license application.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Denial of initial license application. 2.11 Section 2.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.11 Denial of initial license application. (a...

9 CFR 2.11 - Denial of initial license application.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Denial of initial license application. 2.11 Section 2.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.11 Denial of initial license application. (a...

9 CFR 2.11 - Denial of initial license application.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Denial of initial license application. 2.11 Section 2.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.11 Denial of initial license application. (a...

14 CFR 302.211 - Procedures in certificate cases involving initial or continuing fitness.

Code of Federal Regulations, 2010 CFR

2010-01-01

... initial or continuing fitness. 302.211 Section 302.211 Aeronautics and Space OFFICE OF THE SECRETARY... Disposition of Applications § 302.211 Procedures in certificate cases involving initial or continuing fitness... applicant's fitness to operate. Where such applications propose the operation of scheduled service in...

14 CFR 302.211 - Procedures in certificate cases involving initial or continuing fitness.

Code of Federal Regulations, 2011 CFR

2011-01-01

... initial or continuing fitness. 302.211 Section 302.211 Aeronautics and Space OFFICE OF THE SECRETARY... Disposition of Applications § 302.211 Procedures in certificate cases involving initial or continuing fitness... applicant's fitness to operate. Where such applications propose the operation of scheduled service in...

9 CFR 2.11 - Denial of initial license application.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Denial of initial license application. 2.11 Section 2.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Licensing § 2.11 Denial of initial license application. (a...

49 CFR 236.503 - Automatic brake application; initiation when predetermined rate of speed exceeded.

Code of Federal Regulations, 2011 CFR

2011-10-01

... predetermined rate of speed exceeded. 236.503 Section 236.503 Transportation Other Regulations Relating to... § 236.503 Automatic brake application; initiation when predetermined rate of speed exceeded. An automatic train control system shall operate to initiate an automatic brake application when the speed of...

49 CFR 236.503 - Automatic brake application; initiation when predetermined rate of speed exceeded.

Code of Federal Regulations, 2010 CFR

2010-10-01

... predetermined rate of speed exceeded. 236.503 Section 236.503 Transportation Other Regulations Relating to... § 236.503 Automatic brake application; initiation when predetermined rate of speed exceeded. An automatic train control system shall operate to initiate an automatic brake application when the speed of...

Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India

PubMed Central

Hingankar, Nitin K.; Thorat, Smita R.; Deshpande, Alaka; Rajasekaran, S.; Chandrasekar, C.; Kumar, Suria; Srikantiah, Padmini; Chaturbhuj, Devidas N.; Datkar, Sharda R.; Deshmukh, Pravin S.; Kulkarni, Smita S.; Sane, Suvarna; Reddy, D. C. S.; Garg, Renu; Jordan, Michael R.; Kabra, Sandhya; Paranjape, Ramesh S.

2012-01-01

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/μL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART. PMID:22544202

Development and Preliminary Feasibility Study of a Brief Behavioral Activation Mobile Application (Behavioral Apptivation) to Be Used in Conjunction With Ongoing Therapy.

PubMed

Dahne, Jennifer; Kustanowitz, Jacob; Lejuez, C W

2018-02-01

Depressive symptoms are the most frequently treated psychiatric condition in the United States. Brief behavioral activation treatment for depression (BATD) is a popular, evidence-based psychotherapy with strong research support for the treatment of depression. In this paper, we describe the development and initial pilot feasibility testing of a BATD mobile application (Behavioral Apptivation) to be used by patients and therapists in conjunction with BATD therapy. We present information regarding the app development process as well as results from a small open-label feasibility trial of the app utilized in conjunction with individual BATD. We include a case series from the open-label trial highlighting how Behavioral Apptivation can be utilized in clinical practice.

Integrating cancer genomic data into electronic health records.

PubMed

Warner, Jeremy L; Jain, Sandeep K; Levy, Mia A

2016-10-26

The rise of genomically targeted therapies and immunotherapy has revolutionized the practice of oncology in the last 10-15 years. At the same time, new technologies and the electronic health record (EHR) in particular have permeated the oncology clinic. Initially designed as billing and clinical documentation systems, EHR systems have not anticipated the complexity and variety of genomic information that needs to be reviewed, interpreted, and acted upon on a daily basis. Improved integration of cancer genomic data with EHR systems will help guide clinician decision making, support secondary uses, and ultimately improve patient care within oncology clinics. Some of the key factors relating to the challenge of integrating cancer genomic data into EHRs include: the bioinformatics pipelines that translate raw genomic data into meaningful, actionable results; the role of human curation in the interpretation of variant calls; and the need for consistent standards with regard to genomic and clinical data. Several emerging paradigms for integration are discussed in this review, including: non-standardized efforts between individual institutions and genomic testing laboratories; "middleware" products that portray genomic information, albeit outside of the clinical workflow; and application programming interfaces that have the potential to work within clinical workflow. The critical need for clinical-genomic knowledge bases, which can be independent or integrated into the aforementioned solutions, is also discussed.

The clinician's guide to composing effective business plans.

PubMed

Ettinger, Alan B; Blondell, Catherine

2011-01-01

In today's challenging healthcare environment, clinicians need to understand the fundamentals of financial analysis, which are the underpinnings of their clinical programs, especially when seeking administrative support for new initiatives. The business plan for new clinical program initiatives is composed of diverse elements such as the mission statement, market and competitive analyses, operations plan, and financial analysis. Armed with a basic knowledge of financial analysis of clinical programs, as well as forward-looking analysis of an initiative's added value, the healthcare provider can work much more effectively with administration in developing or creating new healthcare program initiatives.

Using surface water application to reduce 1,3-dichloropropene emission from soil fumigation.

PubMed

Gao, Suduan; Trout, Thomas J

2006-01-01

High emissions from soil fumigants increase the risk of detrimental impact on workers, bystanders, and the environment, and jeopardize future availability of fumigants. Efficient and cost-effective approaches to minimize emissions are needed. This study evaluated the potential of surface water application (or water seal) to reduce 1,3-dichloropropene (1,3-D) emissions from soil (Hanford sandy loam) columns. Treatments included dry soil (control), initial water application (8 mm of water just before fumigant application), initial plus a second water application (2.6 mm) at 12 h, initial plus two water applications (2.6 mm each time) at 12 and 24 h, standard high density polyethylene (HDPE) tarp, initial water application plus HDPE tarp, and virtually impermeable film (VIF) tarp. Emissions from the soil surface and distribution of 1,3-D in the soil-gas phase were monitored for 2 wk. Each water application abruptly reduced 1,3-D emission flux, which rebounded over a few hours. Peak emission rates were substantially reduced, but total emission reduction was small. Total fumigant emission was 51% of applied for the control, 46% for initial water application only, and 41% for the three intermittent water applications with the remaining water treatment intermediate. The HDPE tarp alone resulted in 45% emission, while initial water application plus HDPE tarp resulted in 38% emission. The most effective soil surface treatment was VIF tarp (10% emission). Surface water application can be as effective, and less expensive than, standard HDPE tarp. Frequent water application is required to substantially reduce emissions.

Initial testing of an instrument to measure teacher identity in physicians.

PubMed

Starr, Susan; Haley, Heather-Lyn; Mazor, Kathleen M; Ferguson, Warren; Philbin, Mary; Quirk, Mark

2006-01-01

A previous study described 7 elements of teacher identity: intrinsic satisfaction from teaching, knowledge and skill about teaching, belonging to a community of teachers, receiving rewards for teaching, believing that being a doctor means being a teacher, feeling a responsibility to teach, and sharing clinical expertise. To conduct the initial testing of an instrument to measure the 7 elements of teacher identity in clinical educators and to consider the potential applications of such an instrument. A 37-item questionnaire was mailed to 153 preceptors of preclinical students. Categories reflected the elements of teacher identity listed here. Demographic data were collected. Means, alphas, ANOVAs, and paired t tests were calculated. Of 153 preceptors, 127 (83%) completed the questionnaire. Cronbach's alpha for the overall scale and several subscales were high. Salaried physicians and those who had completed a faculty development program scored significantly higher on several subscales than physicians who volunteered to teach or who did not have faculty development. This study provides preliminary evidence that teacher identity can be measured and that preceptors do not respond as a homogeneous group. Assessing teacher identity may be helpful to medical schools looking to identify and support physicians who teach.

Design and development of a new cryosurgical instrument utilizing the Peltier thermoelectric effect.

PubMed

Holman, M R; Rowland, S J

1997-01-01

Warts and some other dermatological conditions may be treated by the application of intense cold. This freezing has to be so severe as to form ice crystals which will rupture the cell membranes. The initial part of this project was to investigate the feasibility of using Peltier thermoelectric coolers (TECs) to cool down a suitable hand-held treatment tip to a temperature of approximately -50 degrees C. The results of these initial experiments showed how this could be accomplished and a prototype cryosurgical instrument, suitable for clinical trials, was designed and constructed. This new design is freestanding, self-contained and is operated from a standard 230 V mains supply. Unlike existing systems it does not use any disposable gases or liquids. A cryoprobe of this new design would allow reliable cryosurgery to be performed in a GP's treatment room where supplies of liquid nitrogen, nitrous oxide or carbon dioxide are not readily available. The design also has a built-in thermometer to measure the treatment tip temperature thus ensuring consistency in treatment. Clinical trials are being conducted at a number of GP practices to evaluate this new design.

Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

PubMed

Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

2010-11-01

Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

Positron emission tomography/magnetic resonance imaging (PET/MRI): An update and initial experience at HC-FMUSP.

PubMed

Queiroz, Marcelo A; Barbosa, Felipe de Galiza; Buchpiguel, Carlos Alberto; Cerri, Giovanni Guido

2018-01-01

The new technology of PET/MRI is a prototype of hybrid imaging, allowing for the combination of molecular data from PET scanning and morphofunctional information derived from MRI scanning. Recent advances regarding the technical aspects of this device, especially after the development of MRI-compatible silicon photomultipliers of PET, permitted an increase in the diagnostic performance of PET/MRI translated into dose reduction and higher imaging quality. Among several clinical applications, PET/MRI gains ground initially in oncology, where MRI per se plays an essential role in the assessment of primary tumors (which is limited in the case of PET/CT), including prostate, rectal and gynecological tumors. On the other hand, the evaluation of the lungs remains an enigma although new MRI sequences are being designed to overcome this. More clinical indications of PET/MRI are seen in the fields of neurology, cardiology and inflammatory processes, and the use of PET/MRI also opens perspectives for pediatric populations as it involves very low radiation exposure. Our review aimed to highlight the current indications of PET/MRI and discuss the challenges and perspectives of PET/MRI at HC-FMUSP.

Applying Social Network Analysis to Identify the Social Support Needs of Adolescent and Young Adult Cancer Patients and Survivors.

PubMed

Koltai, Kolina; Walsh, Casey; Jones, Barbara; Berkelaar, Brenda L

2018-04-01

This article examines how theoretical and clinical applications of social network analysis (SNA) can inform opportunities for innovation and advancement of social support programming for adolescent and young adult (AYA) cancer patients and survivors. SNA can help address potential barriers and challenges to initiating and sustaining AYA peer support by helping to identify the diverse psychosocial needs among individuals in the AYA age range; find strategic ways to support and connect AYAs at different phases of the cancer trajectory with resources and services; and increase awareness of psychosocial resources and referrals from healthcare providers. Network perspectives on homophily, proximity, and evolution provide a foundational basis to explore the utility of SNA in AYA clinical care and research initiatives. The uniqueness of the AYA oncology community can also provide insight into extending and developing current SNA theories. Using SNA in AYA psychosocial cancer research has the potential to create new ideas and pathways for supporting AYAs across the continuum of care, while also extending theories of SNA. SNA may also prove to be a useful tool for examining social support resources for AYAs with various chronic health conditions and other like groups.

Review of an initial experience with an experimental spectral photon-counting computed tomography system

NASA Astrophysics Data System (ADS)

Si-Mohamed, Salim; Bar-Ness, Daniel; Sigovan, Monica; Cormode, David P.; Coulon, Philippe; Coche, Emmanuel; Vlassenbroek, Alain; Normand, Gabrielle; Boussel, Loic; Douek, Philippe

2017-11-01

Spectral photon-counting CT (SPCCT) is an emerging X-ray imaging technology that extends the scope of available diagnostic imaging tools. The main advantage of photon-counting CT technology is better sampling of the spectral information from the transmitted spectrum in order to benefit from additional physical information being produced during matter interaction, including photo-electric and Compton effects, and the K-edge effect. The K-edge, which is specific for a given element, is the increase in X-ray absorption of the element above the binding energy between its inner electronic shell and the nucleus. Hence, the spectral information contributes to better characterization of tissues and materials of interest, explaining the excitement surrounding this area of X-ray imaging. Other improvements of SPCCT compared with conventional CT, such as higher spatial resolution, lower radiation exposure and lower noise are also expected to provide benefits for diagnostic imaging. In this review, we describe multi-energy CT imaging, from dual energy to photon counting technology, and our initial experience results using a clinical-scale spectral photon counting CT (SPCCT) prototype system in vitro and in vivo. In addition, possible clinical applications are introduced.

Laser ultrasonic techniques for assessment of tooth structure

NASA Astrophysics Data System (ADS)

Blodgett, David W.; Baldwin, Kevin C.

2000-06-01

Dental health care and research workers require a means of imaging the structures within teeth in vivo. For example, there is a need to image the margins of a restoration for the detection of poor bonding or voids between the restorative material and the dentin. With conventional x-ray techniques, it is difficult to detect cracks and to visualize interfaces between hard media. This due to the x-ray providing only a 2 dimensional projection of the internal structure (i.e. a silhouette). In addition, a high resolution imaging modality is needed to detect tooth decay in its early stages. If decay can be detected early enough, the process can be monitored and interventional procedures, such as fluoride washes and controlled diet, can be initiated which can help the tooth to re-mineralize itself. Currently employed x-ray imaging is incapable of detecting decay at a stage early enough to avoid invasive cavity preparation followed by a restoration with a synthetic material. Other clinical applications include the visualization of periodontal defects, the localization of intraosseous lesions, and determining the degree of osseointegration between a dental implant and the surrounding bone. A means of assessing the internal structure of the tooth based upon use of high frequency, highly localized ultrasound (acoustic waves) generated by a laser pulse is discussed. Optical interferometric detection of ultrasound provides a complementary technique with a very small detection footprint. Initial results using laser-based ultrasound for assessment of dental structures are presented. Discussion will center on the adaptability of this technique to clinical applications.

Developing an evaluation framework for clinical redesign programs: lessons learnt.

PubMed

Samaranayake, Premaratne; Dadich, Ann; Fitzgerald, Anneke; Zeitz, Kathryn

2016-09-19

Purpose The purpose of this paper is to present lessons learnt through the development of an evaluation framework for a clinical redesign programme - the aim of which was to improve the patient journey through improved discharge practices within an Australian public hospital. Design/methodology/approach The development of the evaluation framework involved three stages - namely, the analysis of secondary data relating to the discharge planning pathway; the analysis of primary data including field-notes and interview transcripts on hospital processes; and the triangulation of these data sets to devise the framework. The evaluation framework ensured that resource use, process management, patient satisfaction, and staff well-being and productivity were each connected with measures, targets, and the aim of clinical redesign programme. Findings The application of business process management and a balanced scorecard enabled a different way of framing the evaluation, ensuring measurable outcomes were connected to inputs and outputs. Lessons learnt include: first, the importance of mixed-methods research to devise the framework and evaluate the redesigned processes; second, the need for appropriate tools and resources to adequately capture change across the different domains of the redesign programme; and third, the value of developing and applying an evaluative framework progressively. Research limitations/implications The evaluation framework is limited by its retrospective application to a clinical process redesign programme. Originality/value This research supports benchmarking with national and international practices in relation to best practice healthcare redesign processes. Additionally, it provides a theoretical contribution on evaluating health services improvement and redesign initiatives.

Unravelling functional neurology: a scoping review of theories and clinical applications in a context of chiropractic manual therapy.

PubMed

Meyer, Anne-Laure; Meyer, Amanda; Etherington, Sarah; Leboeuf-Yde, Charlotte

2017-01-01

Functional Neurology (FN), a seemingly attractive treatment approach used by some chiropractors, proposes to have an effect on a multitude of conditions but some of its concepts are controversial. A scoping review was performed to describe, in the context of chiropractic manual therapy, 1) the FN theories, and 2) its clinical applications (i.e. its indications, examination procedures, treatment modalities, treatment plans, and clinical outcomes) using four sources: i) one key textbook, ii) the scientific peer-reviewed literature, iii) websites from chiropractors using FN, and iv) semi-structured interviews of chiropractors using FN. The scientific literature was searched in PubMed, PsycINFO, and SPORTDiscus, completed by a hand search in the journal Functional Neurology, Rehabilitation and Ergonomics (November 2016 and March 2017, respectively). The only textbook on the topic we found was included and articles were chosen if they had an element of manual therapy. There was no restriction for study design but discussion papers were excluded. Websites were found in Google using the search term "Functional Neurology". Chiropractors, known to use FN, were invited based on their geographical location. Theories were mainly uncovered in the textbook as were all aspects of the clinical applications except treatment plans. The other three sources were used for the five aspects of clinical applications. Results were summarized and reported extensively in tables. Eleven articles were included, five websites scrutinized, and four semi-structured interviews performed. FN is based on the belief that reversible lesions in the nervous system are the cause of a multitude of conditions and that specific clusters of neurons can be positively affected by manipulative therapy, but also by many other stimuli. Diagnostic procedures include both conventional and unusual tests, with an interpretation specific to FN. Initial treatment is intense and clinical outcomes reported as positive. FN gives the impression to be a complex alternative to the old variant of the chiropractic subluxation model, in which the vertebral subluxation is replaced by "physiological lesions" of the brain, and the treatment, spinal adjustments, are complemented by various neurological stimuli. Both models purport to treat not the symptoms but the cause. We conclude there is a need for more scientific documentation on the validity of FN.

Medical students' attitudes towards early clinical exposure in Iran.

PubMed

Khabaz Mafinejad, Mahboobeh; Mirzazadeh, Azim; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

2016-06-19

This study was carried out to investigate the medical students' attitudes towards early clinical exposure at Tehran University of Medical Sciences. A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students' attitudes toward early clinical exposure. Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students' responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: "integration of theory and practice", "interaction with others and professional development" and "desire and motivation for learning medicine". Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students' understanding of the role they will play in the future as a physician.

Initial strides for invent-VTE: Towards global collaboration to accelerate clinical research in venous thromboembolism.

PubMed

Rodger, Marc; Langlois, Nicole; Middeldorp, Saskia; Kahn, Susan; Sandset, Per Morten; Brighton, Timothy; Huisman, Menno V; Meyer, Guy; Konstantinides, Stavros; Ageno, Walter; Morange, Pierre; Garcia, David; Kreuziger, Lisa Baumann; Young, Laura; Key, Nigel; Monreal, Manuel; Jiménez, David

2018-03-01

Venous thromboembolism (VTE) represents a major global burden of disease and requires collaborative efforts to conduct large, high-quality investigator-initiated and academically sponsored studies addressing the most relevant clinical questions. Owing to increasing regulatory requirements, the highly competitive nature of peer-reviewed funding and costs associated with conducting large, multinational clinical trials, completing practice-changing research constitutes a growing challenge for clinical investigators. As clinical trialists interested in VTE, we founded INVENT (International Network of Venous Thromboembolism Clinical Research Networks) in an effort to promote and accelerate patient-oriented, investigator-initiated, international collaborative research, to identify, prioritize and answer key clinical research questions for patients with VTE. We report on our activities to formalize the INVENT network and our accomplishments in our first year. Copyright © 2018 Elsevier Ltd. All rights reserved.

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

PubMed Central

Ebner, Lukas; Kammerman, Jeff; Driehuys, Bastiaan; Schiebler, Mark L.; Cadman, Robert V.; Fain, Sean B.

2016-01-01

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3 He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe MRI, and (4) propose clinical applications. PMID:27707585

Technical aspects and inter-laboratory variability in native peptide profiling: the CE-MS experience.

PubMed

Mischak, Harald; Vlahou, Antonia; Ioannidis, John P A

2013-04-01

Mass spectrometry platforms have attracted a lot of interest in the last 2 decades as profiling tools for native peptides and proteins with clinical potential. However, limitations associated with reproducibility and analytical robustness, especially pronounced with the initial SELDI systems, hindered the application of such platforms in biomarker qualification and clinical implementation. The scope of this article is to give a short overview on data available on performance and on analytical robustness of the different platforms for peptide profiling. Using the CE-MS platform as a paradigm, data on analytical performance are described including reproducibility (short-term and intermediate repeatability), stability, interference, quantification capabilities (limits of detection), and inter-laboratory variability. We discuss these issues by using as an example our experience with the development of a 273-peptide marker for chronic kidney disease. Finally, we discuss pros and cons and means for improvement and emphasize the need to test in terms of comparative clinical performance and impact, different platforms that pass reasonably well analytical validation tests. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Rapid method for direct identification of bacteria in urine and blood culture samples by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: intact cell vs. extraction method.

PubMed

Ferreira, L; Sánchez-Juanes, F; Muñoz-Bellido, J L; González-Buitrago, J M

2011-07-01

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is a fast and reliable technology for the identification of microorganisms with proteomics approaches. Here, we compare an intact cell method and a protein extraction method before application on the MALDI plate for the direct identification of microorganisms in both urine and blood culture samples from clinical microbiology laboratories. The results show that the intact cell method provides excellent results for urine and is a good initial method for blood cultures. The extraction method complements the intact cell method, improving microorganism identification from blood culture. Thus, we consider that MALDI-TOF MS performed directly on urine and blood culture samples, with the protocols that we propose, is a suitable technique for microorganism identification, as compared with the routine methods used in the clinical microbiology laboratory. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

[Basic concepts for network meta-analysis].

PubMed

Catalá-López, Ferrán; Tobías, Aurelio; Roqué, Marta

2014-12-01

Systematic reviews and meta-analyses have long been fundamental tools for evidence-based clinical practice. Initially, meta-analyses were proposed as a technique that could improve the accuracy and the statistical power of previous research from individual studies with small sample size. However, one of its main limitations has been the fact of being able to compare no more than two treatments in an analysis, even when the clinical research question necessitates that we compare multiple interventions. Network meta-analysis (NMA) uses novel statistical methods that incorporate information from both direct and indirect treatment comparisons in a network of studies examining the effects of various competing treatments, estimating comparisons between many treatments in a single analysis. Despite its potential limitations, NMA applications in clinical epidemiology can be of great value in situations where there are several treatments that have been compared against a common comparator. Also, NMA can be relevant to a research or clinical question when many treatments must be considered or when there is a mix of both direct and indirect information in the body of evidence. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Collaborating across organizational boundaries to improve the quality of care.

PubMed

Plsek, P E

1997-04-01

The paradigm of modern quality management is in wide use in health care. Although much of the initial effort in health care has focused on improving service, administrative, and support processes, many organizations are also using these concepts to improve clinical care. The analysis of data on clinical outcomes has undoubtedly led to many local improvements, but such analysis is inevitably limited by three issues: small samples, lack of detailed knowledge of what others are doing, and paradigm paralysis. These issues can be partially overcome when multiple health care organizations work together on focused clinical quality improvement efforts. Through the use of multiorganizational collaborative groups, literature reviews, expert panels, best-practice conferences, multiorganizational databases, and bench-marking groups, organizations can effectively pool data and learn from the many natural experiments constantly underway in the health care community. This article outlines the key concepts behind such collaborative improvement efforts and describes pioneering work in the application of these techniques in health care. A better understanding and wider use of collaborative improvement efforts may lead to dramatic breakthroughs in clinical outcomes in the coming years.

Telepsychiatry: an overview for psychiatrists.

PubMed

Hilty, Donald M; Luo, John S; Morache, Chris; Marcelo, Divine A; Nesbitt, Thomas S

2002-01-01

Telepsychiatry, in the form of videoconferencing and other modalities, brings enormous opportunities for clinical care, education, research and administration to the field of medicine. A comprehensive review of the literature related to telepsychiatry - specifically videoconferencing - was conducted using the MEDLINE, Embase, Science Citation Index, Social Sciences Citation Index and Telemedicine Information Exchange databases (1965 to June 2001). The keywords used were telepsychiatry, telemedicine, videoconferencing, Internet, primary care, education, personal digital assistant and handheld computers. Studies were selected for review if they discussed videoconferencing for patient care, satisfaction, outcomes, education and costs, and provided models of facilitating clinical service delivery. Literature on other technologies was also assessed and compared with telepsychiatry to provide an idea of future applications of technology. Published data indicate that telepsychiatry is successfully used for a variety of clinical services and educational initiatives. Telepsychiatry is generally feasible, offers a number of models of care and consultation, in general satisfies patients and providers, and has positive and negative effects on interpersonal behaviour. More quantitative and qualitative research is warranted with regard to the use of telepsychiatry in clinical and educational programmes and interventions.

Becoming a teacher of clinical reasoning.

PubMed

Trowbridge, Robert L; Olson, Andrew P J

2018-03-28

Diagnostic reasoning is one of the most challenging and rewarding aspects of clinical practice. As a result, facility in teaching diagnostic reasoning is a core necessity for all medical educators. Clinician educators' limited understanding of the diagnostic process and how expertise is developed may result in lost opportunities in nurturing the diagnostic abilities of themselves and their learners. In this perspective, the authors describe their journeys as clinician educators searching for a coherent means of teaching diagnostic reasoning. They discuss the initial appeal and immediate applicability of dual process theory and cognitive biases to their own clinical experiences and those of their trainees, followed by the eventual and somewhat belated recognition of the importance of context specificity. They conclude that there are no quick fixes in guiding learners to expertise of diagnostic reasoning, but rather the development of these abilities is best viewed as a long, somewhat frustrating, but always interesting journey. The role of the teacher of clinical reasoning is to guide the learners on this journey, recognizing true mastery may not be attained, but should remain a goal for teacher and learner alike.

Monitoring surgical and medical outcomes: the Bernoulli cumulative SUM chart. A novel application to assess clinical interventions

PubMed Central

Leandro, G; Rolando, N; Gallus, G; Rolles, K; Burroughs, A

2005-01-01

Background: Monitoring clinical interventions is an increasing requirement in current clinical practice. The standard CUSUM (cumulative sum) charts are used for this purpose. However, they are difficult to use in terms of identifying the point at which outcomes begin to be outside recommended limits. Objective: To assess the Bernoulli CUSUM chart that permits not only a 100% inspection rate, but also the setting of average expected outcomes, maximum deviations from these, and false positive rates for the alarm signal to trigger. Methods: As a working example this study used 674 consecutive first liver transplant recipients. The expected one year mortality set at 24% from the European Liver Transplant Registry average. A standard CUSUM was compared with Bernoulli CUSUM: the control value mortality was therefore 24%, maximum accepted mortality 30%, and average number of observations to signal was 500—that is, likelihood of false positive alarm was 1:500. Results: The standard CUSUM showed an initial descending curve (nadir at patient 215) then progressively ascended indicating better performance. The Bernoulli CUSUM gave three alarm signals initially, with easily recognised breaks in the curve. There were no alarms signals after patient 143 indicating satisfactory performance within the criteria set. Conclusions: The Bernoulli CUSUM is more easily interpretable graphically and is more suitable for monitoring outcomes than the standard CUSUM chart. It only requires three parameters to be set to monitor any clinical intervention: the average expected outcome, the maximum deviation from this, and the rate of false positive alarm triggers. PMID:16210461

Rotigotine transdermal patch in combination therapy for Parkinson's disease--observations in routine clinical practice.

PubMed

Ceballos-Baumann, Andres; Häck, Hermann-Josef

2011-10-01

The dopamine agonist rotigotine has shown efficacy and safety for the treatment of early and advanced Parkinson's disease (PD) in controlled clinical trials. This observational study evaluated rotigotine administration in combination with other antiparkinsonian medication in routine clinical practice. Data were collected by 688 German practice-based neurologists, initiating rotigotine treatment in patients with idiopathic Parkinson's disease. Assessments included rotigotine maintenance dose, changes in concomitant PD medication, changes in sleep quality, and rotigotine tolerability over an observation period of 12-16 weeks. The median rotigotine maintenance dose was 6 mg/24 h (n = 969, full analysis set). The proportion of all other prescribed PD medications declined over the observation period; combination therapy decreased by 18.7%. Daily levodopa intake was markedly reduced by 87 mg (18.9%) in 47.6% of the patients with levodopa documentation; 7% no longer required levodopa after 12-16 weeks. Mean overall sleep quality (PD Sleep Scale item 1) improved by 21.4 points, the occurrence of nocturias (PDSS item 8) by 13.4 points, and 'turning in bed' (Unified Parkinson's Disease Rating Scale part II) by 0.6 points. Drug-related adverse events were reported for 7.9% of all patients (n = 1152, safety population). Application site reactions were the most common adverse events (2.2%) resulting in early discontinuation in 1.4% of patients. In routine clinical practice, treatment initiation with rotigotine transdermal patch was associated with a reduction of other prescribed PD medications and with an improvement of self-reported sleep quality.

Integrating clinical performance improvement across physician organizations: the PhyCor experience.

PubMed

Loeppke, R; Howell, J W

1999-02-01

There is a paucity of literature describing the implementation of clinical performance improvement (CPI) efforts across geographically dispersed multispecialty group practices and independent practice associations. PhyCor, a physician management company based in Nashville, Tennessee, has integrated CPI initiatives into its operating infrastructure. PhyCor CPI INITIATIVES: The strategic framework guiding PhyCor's CPI initiatives is built around a physician-driven, patient-centered model. Physician/administrator leadership teams develop and implement a clinical and financial strategic plan for performance improvement; adopt local clinical and operational performance indicators; and agree on and gain consensus with local physician champions to engage in CPI initiatives. The area/regional leadership councils integrate and coordinate regional medical management and CPI initiatives among local groups and independent practice associations. In addition to these councils and a national leadership council, condition-specific care management councils have also been established. These councils develop condition-specific protocols and outcome measures and lead the implementation of CPI initiatives at their own clinics. Key resources supporting CPI initiatives include information/knowledge management, education and training, and patient education and consumer decision support. Localized efforts in both the asthma care and diabetes management initiatives have led to some preliminary improvements in quality of care indicators. Physician leadership and strategic vision, CPI-oriented organizational infrastructure, broad-based physician involvement in CPI, providing access to performance data, parallel incentives, and creating a sense of urgency for accelerated change are all critical success factors to the implementation of CPI strategies at the local, regional, and national levels.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Novel point estimation from a semiparametric ratio estimator (SPRE): long-term health outcomes from short-term linear data, with application to weight loss in obesity.

PubMed

Weissman-Miller, Deborah

2013-11-02

Point estimation is particularly important in predicting weight loss in individuals or small groups. In this analysis, a new health response function is based on a model of human response over time to estimate long-term health outcomes from a change point in short-term linear regression. This important estimation capability is addressed for small groups and single-subject designs in pilot studies for clinical trials, medical and therapeutic clinical practice. These estimations are based on a change point given by parameters derived from short-term participant data in ordinary least squares (OLS) regression. The development of the change point in initial OLS data and the point estimations are given in a new semiparametric ratio estimator (SPRE) model. The new response function is taken as a ratio of two-parameter Weibull distributions times a prior outcome value that steps estimated outcomes forward in time, where the shape and scale parameters are estimated at the change point. The Weibull distributions used in this ratio are derived from a Kelvin model in mechanics taken here to represent human beings. A distinct feature of the SPRE model in this article is that initial treatment response for a small group or a single subject is reflected in long-term response to treatment. This model is applied to weight loss in obesity in a secondary analysis of data from a classic weight loss study, which has been selected due to the dramatic increase in obesity in the United States over the past 20 years. A very small relative error of estimated to test data is shown for obesity treatment with the weight loss medication phentermine or placebo for the test dataset. An application of SPRE in clinical medicine or occupational therapy is to estimate long-term weight loss for a single subject or a small group near the beginning of treatment.

Manuscript Architect: a Web application for scientific writing in virtual interdisciplinary groups

PubMed Central

Pietrobon, Ricardo; Nielsen, Karen C; Steele, Susan M; Menezes, Andreia P; Martins, Henrique; Jacobs, Danny O

2005-01-01

Background Although scientific writing plays a central role in the communication of clinical research findings and consumes a significant amount of time from clinical researchers, few Web applications have been designed to systematically improve the writing process. This application had as its main objective the separation of the multiple tasks associated with scientific writing into smaller components. It was also aimed at providing a mechanism where sections of the manuscript (text blocks) could be assigned to different specialists. Manuscript Architect was built using Java language in conjunction with the classic lifecycle development method. The interface was designed for simplicity and economy of movements. Manuscripts are divided into multiple text blocks that can be assigned to different co-authors by the first author. Each text block contains notes to guide co-authors regarding the central focus of each text block, previous examples, and an additional field for translation when the initial text is written in a language different from the one used by the target journal. Usability was evaluated using formal usability tests and field observations. Results The application presented excellent usability and integration with the regular writing habits of experienced researchers. Workshops were developed to train novice researchers, presenting an accelerated learning curve. The application has been used in over 20 different scientific articles and grant proposals. Conclusion The current version of Manuscript Architect has proven to be very useful in the writing of multiple scientific texts, suggesting that virtual writing by interdisciplinary groups is an effective manner of scientific writing when interdisciplinary work is required. PMID:15960855

Current Concepts in Gastrointestinal Photodynamic Therapy

PubMed Central

Webber, John; Herman, Mark; Kessel, David; Fromm, David

1999-01-01

Objective To review current concepts of photodynamic therapy (PDT) applied to the treatment of tumors of the gastrointestinal tract. Summary Background Data PDT initially involves the uptake or production of a photosensitive compound by tumor cells. Subsequent activation of the photoreactive compound by a specific wavelength of light results in cell death, either directly or as a result of vascular compromise and/or apoptosis. Methods The authors selectively review current concepts relating to photosensitization, photoactivation, time of PDT application, tissue selectivity, sites of photodynamic action, PDT effects on normal tissue, limitations of PDT, toxicity of photosensitizers, application of principles of PDT to tumor detection, and current applications of PDT to tumors of the gastrointestinal tract. Results PDT is clearly effective for small cancers, but it is not yet clear in which cases such treatment is more effective than other currently acceptable approaches. The major side effect of PDT is cutaneous photosensitization. The major limitation of PDT is depth of tumor kill. As data from current and future clinical trials become available, a clearer perspective of where PDT fits in the treatment of cancers will be gained. Many issues regarding pharmacokinetic data of photosensitizers, newer technology involved in light sources, optimal treatment regimens that take advantage of the pharmacophysiology of photoablation, and light dosimetry still require solution. One can foresee application of differing sensitizers and light sources depending on the specific clinical situation. As technologic advances occur, interstitial PDT may have significant application. Conclusions PDT has a potentially important role either as a primary or adjuvant mode of treatment of tumors of the gastrointestinal tract. PMID:10400031

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

PubMed

Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

2015-01-01

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

47 CFR 1.926 - Application processing; initial procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Application processing; initial procedures. 1.926 Section 1.926 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Wireless Radio Services Applications and Proceedings Application Requirements...

47 CFR 1.926 - Application processing; initial procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Application processing; initial procedures. 1.926 Section 1.926 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Wireless Radio Services Applications and Proceedings Application Requirements...

47 CFR 1.926 - Application processing; initial procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false Application processing; initial procedures. 1.926 Section 1.926 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Wireless Radio Services Applications and Proceedings Application Requirements...

Using PACS and wavelet-based image compression in a wide-area network to support radiation therapy imaging applications for satellite hospitals

NASA Astrophysics Data System (ADS)

Smith, Charles L.; Chu, Wei-Kom; Wobig, Randy; Chao, Hong-Yang; Enke, Charles

1999-07-01

An ongoing PACS project at our facility has been expanded to include providing and managing images used for routine clinical operation of the department of radiation oncology. The intent of our investigation has been to enable out clinical radiotherapy service to enter the tele-medicine environment through the use of a PACS system initially implemented in the department of radiology. The backbone for the imaging network includes five CT and three MR scanners located across three imaging centers. A PC workstation in the department of radiation oncology was used to transmit CT imags to a satellite facility located approximately 60 miles from the primary center. Chest CT images were used to analyze network transmission performance. Connectivity established between the primary department and satellite has fulfilled all image criteria required by the oncologist. Establishing the link tot eh oncologist at the satellite diminished bottlenecking of imaging related tasks at the primary facility due to physician absence. A 30:1 compression ratio using a wavelet-based algorithm provided clinically acceptable images treatment planning. Clinical radiotherapy images can be effectively managed in a wide- area-network to link satellite facilities to larger clinical centers.

Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology.

PubMed

Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

2011-06-01

Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Towards meaningful medication-related clinical decision support: recommendations for an initial implementation.

PubMed

Phansalkar, S; Wright, A; Kuperman, G J; Vaida, A J; Bobb, A M; Jenders, R A; Payne, T H; Halamka, J; Bloomrosen, M; Bates, D W

2011-01-01

Clinical decision support (CDS) can improve safety, quality, and cost-effectiveness of patient care, especially when implemented in computerized provider order entry (CPOE) applications. Medication-related decision support logic forms a large component of the CDS logic in any CPOE system. However, organizations wishing to implement CDS must either purchase the computable clinical content or develop it themselves. Content provided by vendors does not always meet local expectations. Most organizations lack the resources to customize the clinical content and the expertise to implement it effectively. In this paper, we describe the recommendations of a national expert panel on two basic medication-related CDS areas, specifically, drug-drug interaction (DDI) checking and duplicate therapy checking. The goals of this study were to define a starter set of medication-related alerts that healthcare organizations can implement in their clinical information systems. We also draw on the experiences of diverse institutions to highlight the realities of implementing medication decision support. These findings represent the experiences of institutions with a long history in the domain of medication decision support, and the hope is that this guidance may improve the feasibility and efficiency CDS adoption across healthcare settings.

A phase II prospective, non-comparative assessment of a new silver sodium carboxymethylcellulose (AQUACEL(®) Ag BURN) glove in the management of partial thickness hand burns.

PubMed

Duteille, Franck; Jeffery, Steven L A

2012-11-01

Nylon-reinforced silver sodium carboxymethylcellulose (AQUACEL(®) Ag BURN) dressings were developed to be pliable and conforming for the management of partial-thickness burns. This study evaluated the AQUACEL(®) Ag BURN glove for the management of hand burns. This 21-day, phase II, prospective, non-comparative study included 23 patients with partial-thickness hand burn of at least two fingers. The AQUACEL(®) Ag BURN glove was applied to one hand and could remain in place up to 21 days until clinically indicated to change the glove. Dressings were evaluated 1, 2, 4, 6, 8, 14, and 21 days after initial application. Safety was the primary study endpoint. Sixteen (70%) hand burns re-epithelialized fully over a mean of 15.6 days. Initial application was easy/very easy for 20 (87%) patients. Mean time for initial dressing application was 5.4 min. At final evaluation, most patients gave ratings of excellent/good for conformability (91%), overall glove performance (74%), and appropriateness of sizes (83%). Mean pain score from 0 (none) to 10 (worst imaginable) was 3.43 at baseline; during the study, mean scores were 1.15 at rest and 2.29 during movement. Of 61 glove removals, most (72%) were easy/very easy, and 12% had fallen off. Adverse events (wound site or elsewhere) occurred in 15 (65%) patients. Treatment-related adverse events were wound pain (17%), maceration (9%), and stiff fingers (4%). The AQUACEL(®) Ag BURN glove was well tolerated in the management of partial-thickness hand burn. Many patients used only one glove. When glove changes were required, they were usually quick and easy. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Initial psychometric evaluation of the Moral Injury Questionnaire--Military version.

PubMed

Currier, Joseph M; Holland, Jason M; Drescher, Kent; Foy, David

2015-01-01

Moral injury is an emerging construct related to negative consequences associated with war-zone stressors that transgress military veterans' deeply held values/beliefs. Given the newness of the construct, there is a need for instrumentation that might assess morally injurious experiences (MIEs) in this population. Drawing on a community sample of 131 Iraq and/or Afghanistan Veterans and clinical sample of 82 returning Veterans, we conducted an initial psychometric evaluation of the newly developed Moral Injury Questionnaire-Military version (MIQ-M)-a 20-item self-report measure for assessing MIEs. Possibly due to low rates of reporting, an item assessing sexual trauma did not yield favourable psychometric properties and was excluded from analyses. Veterans in the clinical sample endorsed significantly higher scores across MIQ-M items. Factor analytic results for the final 19 items supported a unidimensional structure, and convergent validity analyses revealed that higher scores (indicative of more MIEs) were correlated with greater general combat exposure, impairments in work/social functioning, posttraumatic stress and depression in the community sample. In addition, when controlling for demographics, deployment-related factors and exposure to life threat stressors associated with combat, tests of incremental validity indicated that MIQ-M scores were also uniquely linked with suicide risk and other mental health outcomes. These findings provide preliminary evidence for the validity of the MIQ-M and support the applicability of this measure for further research and clinical work with Veterans. Military service can confront service members with experiences that undermine their core sense of humanity and violate global values and beliefs. These types of experiences increase the risk for posttraumatic maladjustment in this population, even when accounting for rates of exposure to life threat traumas. Moral injury is an emerging construct to more fully capture the many possible psychological, ethical, and spiritual/existential challenges among persons who served in modern wars and other trauma-exposed professional groups. There is currently a need for psychometrically sound instrumentation for assessing morally injurious experiences (MIEs). The Moral Injury Questionnaire - Military Version (MIQ-M) was developed to provide a tool for assessing possible MIEs among military populations. This study provides preliminary evidence of the validity - including factorial, concurrent, and incremental - and clinical utility of the MIQ-M for further applications in clinical and research contexts. Copyright © 2013 John Wiley & Sons, Ltd.

Views of Translational Research from a Somewhat Translational Scientist

PubMed Central

Talman, William T.

2013-01-01

This review arose from a talk entitled “Identifying Targets” and given by the author at EB2011 at the invitation of the American Federation for Medical Research (AFMR). The presentation was part of the AFMR workshop entitled “Keys for Translation: Science and Strategy” and focused on identifying clinically relevant targets as a result of observations made during basic scientific studies. The review emphasizes that targets do not have to be the aim that drives basic discovery, but communication between the basic scientist and clinical investigators may aid recognition of such targets and their translation to clinical applications. Using one line of investigator-initiated research from his own laboratory as an example, the author emphasizes that basic discovery must be hypothesis driven and allowed to follow its logical sequence. Finding treatments, while always an aim of biomedical research, may arise as a result of basic studies that were not originally aimed at a target of translational research. PMID:22781556

Elevating the quality of disability and rehabilitation research: mandatory use of the reporting guidelines.

PubMed

Chan, Leighton; Heinemann, Allen W; Roberts, Jason

2014-01-01

Note from the AJOT Editor-in-Chief: Since 2010, the American Journal of Occupational Therapy (AJOT) has adopted reporting standards based on the Consolidated Standards of Reporting Trials (CONSORT) Statement and American Psychological Association (APA) guidelines in an effort to publish transparent clinical research that can be easily evaluated for methodological and analytical rigor (APA Publications and Communications Board Working Group on Journal Article Reporting Standards, 2008; Moher, Schulz, & Altman, 2001). AJOT has now joined 28 other major rehabilitation and disability journals in a collaborative initiative to enhance clinical research reporting standards through adoption of the EQUATOR Network reporting guidelines, described below. Authors will now be required to use these guidelines in the preparation of manuscripts that will be submitted to AJOT. Reviewers will also use these guidelines to evaluate the quality and rigor of all AJOT submissions. By adopting these standards we hope to further enhance the quality and clinical applicability of articles to our readers. Copyright © 2014 by the American Occupational Therapy Association, Inc.

Establishing a successful HIV counseling and testing service. A blueprint for preventing pediatric HIV infections and translating research into clinical practice.

PubMed

Rips, J

1997-12-01

The findings of ACTG 076 have already resulted in local, state, and federal legislative initiatives targeted at pregnant and post-partum women and their newborns. This article advises clinicians and administrations on setting up successful voluntary prenatal HIV counseling and testing programs for early detection of HIV infection, and complying with the burgeoning array of legislative directives. Over the past several years their have been attempts to optimize and evaluate testing programs--perinatal ZDV counseling and administration of ZDV--and to link HIV-infected women with care in academic, community, and municipal hospitals. The suggestions are, therefore, broad enough to be applicable to a full array of clinical practices, from a private single provider office to a large hospital-based prenatal clinic. It is hoped that the models presented in this article can be replicated in diverse settings, and that readers can avoid the pitfalls and barriers sometimes encountered.

Advances and challenges in biosensor-based diagnosis of infectious diseases

PubMed Central

Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

2014-01-01

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

Students' learning of clinical sonography: use of computer-assisted instruction and practical class.

PubMed

Wood, A K; Dadd, M J; Lublin, J R

1996-08-01

The application of information technology to teaching radiology will profoundly change the way learning is mediated to students. In this project, the integration of veterinary medical students' knowledge of sonography was promoted by a computer-assisted instruction program and a subsequent practical class. The computer-assisted instruction program emphasized the physical principles of clinical sonography and contained simulations and user-active experiments. In the practical class, the students used an actual sonographic machine for the first time and made images of a tissue-equivalent phantom. Students' responses to questionnaires were analyzed. On completing the overall project, 96% of the students said that they now understood sonographic concepts very or reasonably well, and 98% had become very or moderately interested in clinical sonography. The teaching and learning initiatives enhanced an integrated approach to learning, stimulated student interest and curiosity, improved understanding of sonographic principles, and contributed to an increased confidence and skill in using sonographic equipment.

Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system.

PubMed

Kuo, Nathanael; Kang, Hyun Jae; Song, Danny Y; Kang, Jin U; Boctor, Emad M

2012-06-01

Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.

Application of Smart Infrastructure Systems approach to precision medicine.

PubMed

Govindaraju, Diddahally R; Annaswamy, Anuradha M

2015-12-01

All biological variation is hierarchically organized dynamic network system of genomic components, organelles, cells, tissues, organs, individuals, families, populations and metapopulations. Individuals are axial in this hierarchy, as they represent antecedent, attendant and anticipated aspects of health, disease, evolution and medical care. Humans show individual specific genetic and clinical features such as complexity, cooperation, resilience, robustness, vulnerability, self-organization, latent and emergent behavior during their development, growth and senescence. Accurate collection, measurement, organization and analyses of individual specific data, embedded at all stratified levels of biological, demographic and cultural diversity - the big data - is necessary to make informed decisions on health, disease and longevity; which is a central theme of precision medicine initiative (PMI). This initiative also calls for the development of novel analytical approaches to handle complex multidimensional data. Here we suggest the application of Smart Infrastructure Systems (SIS) approach to accomplish some of the goals set forth by the PMI on the premise that biological systems and the SIS share many common features. The latter has been successfully employed in managing complex networks of non-linear adaptive controls, commonly encountered in smart engineering systems. We highlight their concordance and discuss the utility of the SIS approach in precision medicine programs.

New telemedicine techniques in dermatology - evaluation with reflectance confocal microscopy via cloud-based platform.

PubMed

Łudzik, Joanna; Witkowski, Alexander Michael; Roterman-Konieczna, Irena

Dermoscopically equivocal skin lesions may present a diagnostic challenge in daily clinical practice and are regularly sent for second expert opinion. We present a new approach to handling these cases in a consultation referral system that enables communication between the initial doctor at the image upload site and dermatology experts at a distance via cloud-based telemedicine. In our study we retrospectively evaluated 100 equivocal cases with complete digital dermoscopy-reflectance confocal microscopy image sets and compared suggested management of the initial doctor to a second expert confocal reader. We evaluated the effect of reader concordance on final management of these lesions resulting in a single reader overall sensitivity of 89% and specificity of 66% and double reader concordance method sensitivity of 98% and specificity of 54%. In conclusion, we found that application of double reader evaluation of these image sets with automatic referral of lesions for removal in the case of discordant diagnosis between two doctors improved the sensitivity of diagnosis in this subset of lesions and may increase the safety threshold of management choice reducing potential misdiagnosis in telemedicine settings. This paper concerns the application of telemedicine in practical medicine.

Efficient production of erythroid, megakaryocytic and myeloid cells, using single cell-derived iPSC colony differentiation.

PubMed

Hansen, Marten; Varga, Eszter; Aarts, Cathelijn; Wust, Tatjana; Kuijpers, Taco; von Lindern, Marieke; van den Akker, Emile

2018-04-28

Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we introduce an efficient way to produce three major blood cell types using a standardized differentiation protocol that starts with a single hematopoietic initiation step. This system is feeder-free, avoids EB-formation, starts with a hematopoietic initiation step based on a novel single cell-derived iPSC colony differentiation and produces multi-potential progenitors within 8-10 days. Followed by lineage-specific growth factor supplementation these cells can be matured into well characterized erythroid, megakaryocytic and myeloid cells with high-purity, without transcription factor overexpression or any kind of pre-purification step. This standardized differentiation system provides a simple platform to produce specific blood cells in a reproducible manner for hematopoietic development studies, disease modelling, drug testing and the potential for future therapeutic applications. Copyright © 2018. Published by Elsevier B.V.

SMART on FHIR: a standards-based, interoperable apps platform for electronic health records

PubMed Central

Kreda, David A; Mandl, Kenneth D; Kohane, Isaac S; Ramoni, Rachel B

2016-01-01

Objective In early 2010, Harvard Medical School and Boston Children’s Hospital began an interoperability project with the distinctive goal of developing a platform to enable medical applications to be written once and run unmodified across different healthcare IT systems. The project was called Substitutable Medical Applications and Reusable Technologies (SMART). Methods We adopted contemporary web standards for application programming interface transport, authorization, and user interface, and standard medical terminologies for coded data. In our initial design, we created our own openly licensed clinical data models to enforce consistency and simplicity. During the second half of 2013, we updated SMART to take advantage of the clinical data models and the application-programming interface described in a new, openly licensed Health Level Seven draft standard called Fast Health Interoperability Resources (FHIR). Signaling our adoption of the emerging FHIR standard, we called the new platform SMART on FHIR. Results We introduced the SMART on FHIR platform with a demonstration that included several commercial healthcare IT vendors and app developers showcasing prototypes at the Health Information Management Systems Society conference in February 2014. This established the feasibility of SMART on FHIR, while highlighting the need for commonly accepted pragmatic constraints on the base FHIR specification. Conclusion In this paper, we describe the creation of SMART on FHIR, relate the experience of the vendors and developers who built SMART on FHIR prototypes, and discuss some challenges in going from early industry prototyping to industry-wide production use. PMID:26911829