Infectious disease following travel to developed regions: a snapshot of presentations to an Australian travel medicine clinic.

PubMed

Drewett, George; Leder, Karin

2016-06-01

Much of the travel medicine literature focuses on travel to 'developing' regions by travellers from 'developed' regions; however literature about travel to developed regions is scarce. This article examines presentations to a travel medicine clinic over a 17-year period with illnesses resulting from travel to developed regions. From a cohort of general presentations to the clinic of 1077 patients, 85 patients acquired infections due to travel to developed regions, with a total of 99 infectious diagnoses made. This serves to highlight the risk of infectious disease even among travel to only developed regions, and the importance of travel advice in these situations. © International Society of Travel Medicine, 2016.. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Allogeneic tumor cell vaccines: the promise and limitations in clinical trials.

PubMed

Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

2014-01-01

The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.

Spinal osteomyelitis due to Aspergillus flavus in a child: a rare complication after haematopoietic stem cell transplantation.

PubMed

Beluffi, Giampiero; Bernardo, Maria Ester; Meloni, Giulia; Spinazzola, Angelo; Locatelli, Franco

2008-06-01

We report the case of a child affected by acute myeloid leukaemia who was treated with allogeneic haematopoietic stem cell transplantation and developed cervicothoracic spinal osteomyelitis due to Aspergillus flavus. The diagnosis was difficult on a clinical basis, but made possible by conventional radiography and MRI.

Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions.

PubMed

Jhaveri, Komal; Ochiana, Stefan O; Dunphy, Mark Ps; Gerecitano, John F; Corben, Adriana D; Peter, Radu I; Janjigian, Yelena Y; Gomes-DaGama, Erica M; Koren, John; Modi, Shanu; Chiosis, Gabriela

2014-05-01

Heat shock protein 90 (HSP90) serves as a critical facilitator for oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an anticancer strategy. In fact, since the initial serendipitous discovery that geldanamycin (GM) inhibits HSP90, the field has rapidly moved from proof-of-concept clinical studies with GM derivatives to novel second-generation inhibitors. The authors highlight the current status of the second-generation HSP90 inhibitors in clinical development. Herein, the authors note the lessons learned from the completed clinical trials of first- and second-generation inhibitors and describe various assays attempting to serve for a more rational implementation of these agents to cancer treatment. Finally, the authors discuss the future perspectives for this promising class of agents. The knowledge gained thus far provides perhaps only a glimpse at the potential of HSP90 for which there is still much work to be done. Lessons from the clinical trials suggest that HSP90 therapy would advance at a faster pace if patient selection and tumor pharmacokinetics of these drugs were better understood and applied to their clinical development. It is also evident that combining HSP90 inhibitors with other potent anticancer therapies holds great promise not only due to synergistic antitumor activity but also due to the potential of prolonging or preventing the development of drug resistance.

New antibiotics for healthcare-associated pneumonia.

PubMed

Neuner, Elizabeth A; Ritchie, David J; Micek, Scott T

2009-02-01

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

A Study of Clinically Related Open Source Software Projects

PubMed Central

Hogarth, Michael A.; Turner, Stuart

2005-01-01

Open source software development has recently gained significant interest due to several successful mainstream open source projects. This methodology has been proposed as being similarly viable and beneficial in the clinical application domain as well. However, the clinical software development venue differs significantly from the mainstream software venue. Existing clinical open source projects have not been well characterized nor formally studied so the ‘fit’ of open source in this domain is largely unknown. In order to better understand the open source movement in the clinical application domain, we undertook a study of existing open source clinical projects. In this study we sought to characterize and classify existing clinical open source projects and to determine metrics for their viability. This study revealed several findings which we believe could guide the healthcare community in its quest for successful open source clinical software projects. PMID:16779056

Pharmacokinetic drug-drug interaction and their implication in clinical management

PubMed Central

Palleria, Caterina; Di Paolo, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2013-01-01

Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications. PMID:24516494

Pharmacokinetic drug-drug interaction and their implication in clinical management.

PubMed

Palleria, Caterina; Di Paolo, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2013-07-01

Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.

An optical microfluidic platform for spatiotemporal biofilm treatment monitoring

NASA Astrophysics Data System (ADS)

Kim, Young Wook; Mosteller, Matthew P.; Subramanian, Sowmya; Meyer, Mariana T.; Bentley, William E.; Ghodssi, Reza

2016-01-01

Bacterial biofilms constitute in excess of 65% of clinical microbial infections, with the antibiotic treatment of biofilm infections posing a unique challenge due to their high antibiotic tolerance. Recent studies performed in our group have demonstrated that a bioelectric effect featuring low-intensity electric signals combined with antibiotics can significantly improve the efficacy of biofilm treatment. In this work, we demonstrate the bioelectric effect using sub-micron thick planar electrodes in a microfluidic device. This is critical in efforts to develop microsystems for clinical biofilm infection management, including both in vivo and in vitro applications. Adaptation of the method to the microscale, for example, can enable the development of localized biofilm infection treatment using microfabricated medical devices, while augmenting existing capabilities to perform biofilm management beyond the clinical realm. Furthermore, due to scale-down of the system, the voltage requirement for inducing the electric field is reduced further below the media electrolysis threshold. Enhanced biofilm treatment using the bioelectric effect in the developed microfluidic device elicited a 56% greater reduction in viable cell density and 26% further decrease in biomass growth compared to traditional antibiotic therapy. This biofilm treatment efficacy, demonstrated in a micro-scale device and utilizing biocompatible voltage ranges, encourages the use of this method for future clinical biofilm treatment applications.

An Update on Clinical Burden, Diagnostic Tools, and Therapeutic Options of Staphylococcus aureus

PubMed Central

Reddy, Prakash Narayana; Srirama, Krupanidhi; Dirisala, Vijaya R

2017-01-01

Staphylococcus aureus is an important pathogen responsible for a variety of diseases ranging from mild skin and soft tissue infections, food poisoning to highly serious diseases such as osteomyelitis, endocarditis, and toxic shock syndrome. Proper diagnosis of pathogen and virulence factors is important for providing timely intervention in the therapy. Owing to the invasive nature of infections and the limited treatment options due to rampant spread of antibiotic-resistant strains, the trend for development of vaccines and antibody therapy is increasing at rapid rate than development of new antibiotics. In this article, we have discussed elaborately about the host-pathogen interactions, clinical burden due to S aureus infections, status of diagnostic tools, and treatment options in terms of prophylaxis and therapy. PMID:28579798

Enhancing Research Capacity for Global Health: Evaluation of a Distance-Based Program for International Study Coordinators

ERIC Educational Resources Information Center

Wilson, Lynda Law; Rice, Marti; Jones, Carolynn T.; Joiner, Cynthia; LaBorde, Jennifer; McCall, Kimberly; Jester, Penelope M.; Carter, Sheree C.; Boone, Chrissy; Onwuzuligbo, Uzoma; Koneru, Alaya

2013-01-01

Introduction: Due to the increasing number of clinical trials conducted globally, there is a need for quality continuing education for health professionals in clinical research manager (CRM) roles. This article describes the development, implementation, and evaluation of a distance-based continuing education program for CRMs working outside the…

The Use and Abuse of Diagnostic/Classification Criteria

PubMed Central

June, Rayford R.; Aggarwal, Rohit

2015-01-01

In rheumatic diseases, classification criteria have been developed to identify well-defined homogenous cohorts for clinical research. Although, they are commonly used in clinical practice, their use may not be appropriate for routine diagnostic clinical care. Classification criteria are being revised with improved methodology and further understanding of disease pathophysiology, but still may not encompass all unique clinical situations to be applied for diagnosis of heterogeneous, rare, evolving rheumatic diseases. Diagnostic criteria development is challenging primarily due to difficulty for universal application given significant differences in prevalence of rheumatic diseases based on geographical area and clinic settings. Despite these shortcomings, the clinician can still use classification criteria for understanding the disease as well as a guide for diagnosis with a few caveats. We present the limits of current classification criteria, describe their use and abuse in clinical practice, and how they should be used with caution when applied in clinics. PMID:26096094

The epidemiology of a specialist neurorehabilitation clinic: implications for clinical practice and regional service development.

PubMed

Seeley, Helen; Pickard, John; Allanson, Judith; Hutchinson, Peter

2014-01-01

To examine the epidemiology of referrals to a specialist neurotrauma clinic and explore and highlight implications for clinical practice and service development for persons with head injury/traumatic brain injury (HI/TBI). A retrospective population-based cohort study of all referrals to a specialist neurotrauma clinic over a 9-year period. Data from a specialist head injury database (which included all persons presenting to hospital with traumatic brain injury) were analysed. In total, 1235 new patients of all ages, severities of injury, both admitted and non-admitted were referred. Referrals have increased due to successful integration with new service developments and resulting optimization of resources. Data gathered from the cohort gives increased understanding of the characteristics and numbers of patients requiring rehabilitation and adds to the evidence-base. Integration with new and complementary service developments has optimized the function/aims of the clinic and enhanced its role in terms of patient service and outcome and as a research resource. The model provides principles which may be applied to planning, organizing and providing follow-up/rehabilitation services for HI/TBI.

Allogeneic tumor cell vaccines

PubMed Central

Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

2014-01-01

The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies. PMID:24064957

Improving clinical communication of students with English as a second language (ESL) using online technology: a small scale evaluation study.

PubMed

Rogan, Fran; San Miguel, Caroline

2013-09-01

Increasingly, students with English as a second language (ESL) are enrolled in nursing degrees in English speaking countries (Wang et al., 2008). However, they may be at risk of clinical practice failure due to communication difficulties associated with unfamiliar linguistic and cultural factors (Guhde, 2003). This paper describes and evaluates an innovation to assist ESL nursing students at an Australian university develop their clinical communication skills and practice readiness by providing online learning resources, using podcast and vodcast technology, that blend with classroom activities and facilitate flexible and independent learning. The innovation builds on an intensive clinical language workshop program called 'Clinically Speaking' which has evolved through a cyclical process of ongoing research to produce resources in response to students' learning needs. Whilst uptake of the resources was modest, students of ESL as well as English speaking backgrounds (ESB) found the resources improved their clinical preparation and confidence by increasing their understanding of expectations, clinical language and communication skills. The innovation, developed with a modest budget, shows potential in developing ESL and ESB students' readiness for clinical communication, enabling them to engage in clinical practice to develop competency standards required of nursing graduates and registration authorities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recent early clinical drug development for acute kidney injury.

PubMed

Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

2017-02-01

Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

Development of an evidence-based review with recommendations using an online iterative process.

PubMed

Rudmik, Luke; Smith, Timothy L

2011-01-01

The practice of modern medicine is governed by evidence-based principles. Due to the plethora of medical literature, clinicians often rely on systematic reviews and clinical guidelines to summarize the evidence and provide best practices. Implementation of an evidence-based clinical approach can minimize variation in health care delivery and optimize the quality of patient care. This article reports a method for developing an "Evidence-based Review with Recommendations" using an online iterative process. The manuscript describes the following steps involved in this process: Clinical topic selection, Evidence-hased review assignment, Literature review and initial manuscript preparation, Iterative review process with author selection, and Manuscript finalization. The goal of this article is to improve efficiency and increase the production of evidence-based reviews while maintaining the high quality and transparency associated with the rigorous methodology utilized for clinical guideline development. With the rise of evidence-based medicine, most medical and surgical specialties have an abundance of clinical topics which would benefit from a formal evidence-based review. Although clinical guideline development is an important methodology, the associated challenges limit development to only the absolute highest priority clinical topics. As outlined in this article, the online iterative approach to the development of an Evidence-based Review with Recommendations may improve productivity without compromising the quality associated with formal guideline development methodology. Copyright © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Ventilator-associated pneumonia caused by ESKAPE organisms: cause, clinical features, and management.

PubMed

Sandiumenge, Alberto; Rello, Jordi

2012-05-01

Despite important geographical variations, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE) pathogens constitute more than 80% of ventilator-associated pneumonia (VAP) episodes. Their clinical importance relies on their virulence and ability in developing mechanisms to decrease susceptibility to antimicrobials, increasing inappropriate therapy and affecting negatively on ICU patients' outcome. This review updates information on VAP due to ESKAPE pathogens. Although methicillin-resistant Staphylococcus aureus VAP may be clinically similar to that caused by susceptible strains, it is associated with poorer outcomes despite adequate treatment. Local colonization determines treatment options. The contribution of tracheobronchitis is an important issue. Minimum inhibitory concentration should be considered for nonfermentative Gram-negative bacteria VAP to prescribe extended infusion β-lactam treatment due to an increase of resistant strains. Strategies promoting antimicrobial diversity may protect against emergence and spread of resistance by ESKAPE pathogens. VAP due to ESKAPE pathogens represents a global challenge that can be prevented using stewardship programmes promoting diversity.

Have Clinical Trials Properly Assessed c-Met Inhibitors?

PubMed

Hughes, Veronica S; Siemann, Dietmar W

2018-02-01

The c-Met/HGF pathway is implicated in cancer progression and dissemination. Many inhibitors have been developed to target this pathway. Unfortunately, most trials have failed to demonstrate efficacy. However, clinical trials have not adequately tested the concept of c-Met pathway inhibition due to the lack of appropriate patient selection criteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Value of Mercaptopurine After Failing Azathioprine Therapy in Patients With Inflammatory Bowel Disease.

PubMed

Meijer, Berrie; Seinen, Margien L; Leijte, Niek N W; Mulder, Chris J J; van Bodegraven, Adriaan A; de Boer, Nanne K H

2016-08-01

Thiopurines have been widely accepted as immunosuppressive therapy in inflammatory bowel disease. However, many patients have to discontinue thiopurines due to intolerance or ineffectiveness. A therapeutically beneficial effect of switching from azathioprine (AZA) to mercaptopurine (MP) after developing adverse events (AEs) has been reported. The authors assessed the clinical value of MP therapy after AZA discontinuation due to intolerance and, secondary, due to ineffectiveness. In this retrospective single-center study, the authors analyzed data from patients in whom AZA therapy had failed and who were subsequently treated with MP. Thirty-eight patients initiated MP therapy after intolerance to AZA. Intolerance reoccurred in 22 (58%) patients and the remaining 16 (42%) tolerated MP. In 18 out of 48 patients (38%), the AEs that led to discontinuation of MP were similar to those of AZA. A longer duration of prior AZA use was more common in patients who were subsequently tolerant for MP (5.3 versus 1.2 months; P = 0.04). Twenty-two patients discontinued AZA due to ineffectiveness. Eight (36%) patients had clinical benefit from a switch to MP. Six out of these 8 (75%) patients used allopurinol alongside MP, due to ineffectiveness based on a skewed thiopurine metabolism. Patients were more likely to have clinical benefit if the interval between both thiopurines was longer (4.4 versus 0.01 months; P < 0.05). The authors showed that a noteworthy number of patients benefitted therapeutically from a switch from AZA to MP when failing due to intolerance or ineffectiveness; however, the percentage was lower than previously reported in literature.

Application of Proteomic Approaches to Accelerate Drug Development for Psychiatric Disorders.

PubMed

Rahmoune, Hassan; Martins-de-Souza, Daniel; Guest, Paul C

2017-01-01

Proteomic-based biomarkers are now an integral part of the drug development process. This chapter covers the role of proteomic biomarker tests as useful tools for improving preclinical research and clinical development. One medical area that has been lagging behind this process is the study of psychiatric disorders, and this is most likely due to the complexity of these diseases. The potential of incorporating biomarkers in the clinical pipeline to improve decision-making, accelerate drug development, improve translation and reduce development costs is also discussed, with a focus on psychiatric diseases like schizophrenia. This chapter will also discuss the next steps that must be taken to keep moving this process forwards.

Acute cholangitis due to afferent loop syndrome after a Whipple procedure: a case report.

PubMed

Spiliotis, John; Karnabatidis, Demetrios; Vaxevanidou, Archodoula; Datsis, Anastasios C; Rogdakis, Athanasios; Zacharis, Georgios; Siamblis, Demetrios

2009-08-25

Patients with resection of stomach and especially with Billroth II reconstruction (gastro jejunal anastomosis), are more likely to develop afferent loop syndrome which is a rare complication. When the afferent part is obstructed, biliary and pancreatic secretions accumulate and cause the distention of this part. In the case of a complete obstruction (rare), there is a high risk developing necrosis and perforation. This complication has been reported once in the literature. A 54-year-old Greek male had undergone a pancreato-duodenectomy (Whipple procedure) one year earlier due to a pancreatic adenocarcinoma. Approximately 10 months after the initial operation, the patient started having episodes of cholangitis (fever, jaundice) and abdominal pain. This condition progressively worsened and the suspicion of local recurrence or stenosis of the biliary-jejunal anastomosis was discussed. A few days before his admission the patient developed signs of septic cholangitis. Our case demonstrates a rare complication with serious clinical manifestation of the afferent loop syndrome. This advanced form of afferent loop syndrome led to the development of huge enterobiliary reflux, which had a serious clinical manifestation as cholangitis and systemic sepsis, due to bacterial overgrowth, which usually present in the afferent loop. The diagnosis is difficult and the interventional radiology gives all the details to support the therapeutic decision making. A variety of factors can contribute to its development including adhesions, kinking and angulation of the loop, stenosis of gastro-jejunal anastomosis and internal herniation. In order to decompress the afferent loop dilatation due to adhesions, a lateral-lateral jejunal anastomosis was performed between the afferent loop and a small bowel loop.

Validating archetypes for the Multiple Sclerosis Functional Composite.

PubMed

Braun, Michael; Brandt, Alexander Ulrich; Schulz, Stefan; Boeker, Martin

2014-08-03

Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions.This case study provides evidence that both community- and tool-enabled review processes, structured in the Clinical Knowledge Manager, ensure archetype quality. It offers a pragmatic but feasible way to reduce variation in the representation of clinical information models towards a more unified and interoperable model.

Validating archetypes for the Multiple Sclerosis Functional Composite

PubMed Central

2014-01-01

Background Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. Methods A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Results Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. Conclusions The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions. This case study provides evidence that both community- and tool-enabled review processes, structured in the Clinical Knowledge Manager, ensure archetype quality. It offers a pragmatic but feasible way to reduce variation in the representation of clinical information models towards a more unified and interoperable model. PMID:25087081

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Fat embolism syndrome: Clinical and imaging considerations: Case report and review of literature

PubMed Central

Shaikh, Nissar; Parchani, Ashok; Bhat, Venkatraman; Kattren, Marie Anne

2008-01-01

Fat embolism syndrome (FES) is a serious clinical disorder occurring after trauma, orthopedic procedures and rarely in non-traumatic patients. Fat emboli develop in nearly all patients with bone fractures, but they are usually asymptomatic. Small number of patients develop signs and symptoms of various organ system dysfunction due to either mechanical obstruction of capillaries by fat emboli or due to hydrolysis of fat to fatty acids. A triad of lung, brain and skin involvement develop after an asymptomatic period of 24 to 72 hours. This symptom complex is called FES. The incidence reported is up to 30%, but many mild cases may recover unnoticed. Diagnosis of fat embolism is clinical with nonspecific, insensitive diagnostic test results. Treatment of fat embolism syndrome remains supportive and in most cases can be prevented by early fixation of large bone factures. Here we report two cases of traumatic fat embolism, which were diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearance on magnetic resonance imaging (MRI) of the brain in these patients. These patients were successfully treated with supportive management. In conclusion, diagnosis of FES needs high index of suspicion, exclusion of other conditions and use of clinical criteria in combination with imaging. Magnetic resonance imaging of the brain is of great importance in diagnosis and management of these patients. PMID:19826589

A mobile clinical e-portfolio for nursing and medical students, using wireless personal digital assistants (PDAs).

PubMed

Garrett, Bernard Mark; Jackson, Cathryn

2006-12-01

This paper outlines the development and evaluation of a wireless personal digital assistant (PDA) based clinical learning tool designed to promote professional reflection for health professionals. The "Clinical e-portfolio" was developed at the University of British Columbia School of Nursing to enable students immediately to access clinical expertise and resources remotely, and record their clinical experiences in a variety of media (text, audio and images). The PDA e-portfolio tool was developed to demonstrate the potential use of mobile networked technologies to support and improve clinical learning; promote reflective learning in practice; engage students in the process of knowledge translation; help contextualize and embed clinical knowledge whilst in the workplace; and to help prevent the isolation of students whilst engaged in supervised clinical practice. The mobile e-portfolio was developed to synchronise wirelessly with a user's personal Web based portfolio from any remote location where a cellular telephone signal or wireless (Wi-Fi) connection could be obtained. An evaluation of the tool was undertaken with nurse practitioner and medical students, revealing positive attitudes to the use of PDA based tools and portfolios, but limits to the use of the PDA portfolio due to the inherent interface restrictions of the PDA.

How we implemented an analytical support clinic to strengthen student research capacity in Zambia.

PubMed

Andrews, Ben; Musonda, Patrick; Simuyemba, Moses; Wilson, Craig M; Nzala, Selestine; Vermund, Sten H; Michelo, Charles

2014-12-11

Abstract Background: Research outputs in sub-Saharan Africa may be limited by a scarcity of clinical research expertise. In Zambia, clinical and biomedical postgraduate students are often delayed in graduation due to challenges in completing their research dissertations. We sought to strengthen institutional research capacity by supporting student and faculty researchers through weekly epidemiology and biostatistics clinics. Methods: We instituted a weekly Analytical Support Clinic at the University of Zambia, School of Medicine. A combination of biostatisticians, clinical researchers and epidemiologists meet weekly with clients to address questions of proposal development, data management and analysis. Clinic sign-in sheets were reviewed. Results: 109 students and faculty members accounted for 197 visits to the Clinic. Nearly all clients (107/109, 98.2%) were undergraduate or postgraduate students. Reasons for attending the Clinic were primarily for proposal development (46.7%) and data management/analysis (42.1%). The most common specific reasons for seeking help were data analysis and interpretation (36.5%), development of study design and research questions (26.9%) and sample size calculation (21.8%). Conclusions: The Analytical Support Clinic is an important vehicle for strengthening postgraduate research through one-on-one and small group demand-driven interactions. The clinic approach supplements mentorship from departmental supervisors, providing specific expertise and contextual teaching.

Pathophysiology of Portal Hypertension and Its Clinical Links

PubMed Central

Seo, Yeon Seok; Shah, Vijay H

2011-01-01

Portal hypertension is a major cause of morbidity and mortality in patients with liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic vasodilatation, and development of collateral circulation have been considered as major factors for the development of portal hypertension. Recently, sinusoidal remodeling and angiogenesis have been focused as potential etiologic factors and various researchers have tried to improve portal hypertension by modulating these new targets. This article reviews potential new treatments in the context of portal hypertension pathophysiology concepts. PMID:25755320

Bilateral Traumatic Globe Luxation with Optic Nerve Transection

PubMed Central

Tok, Levent; Tok, Ozlem Yalcin; Argun, Tugba Cakmak; Yilmaz, Omer; Gunes, Alime; Unlu, Elif Nisa; Sezer, Sezgin; Ibisoglu, Seda; Argun, Mehmet

2014-01-01

Purpose The purpose of this study was to document clinical findings and management of a patient with bilateral globe luxation and optic nerve transection. Materials and Methods A 25-year-old female patient was admitted to the emergency department with bilateral traumatic globe luxation following a motor vehicle accident. Results Visual acuity testing showed no light perception. The right pupil was dilated and bilaterally did not react to light. The globes were bilaterally intact. A computed tomography scan revealed Le Fort type II fractures, bilateral optic nerve transection and disruption of all extraocular muscles. The globes of the patient were bilaterally reduced into the orbit. However, the patient developed phthisis bulbi in the right eye at month 3. Conclusion Globe luxation presents a dramatic clinical picture, and may lead to the development of severe complications due to the concomitance of complete optic nerve dissection and multiple traumas. Even if the luxated globe is repositioned into the orbit, there is still an increased risk of the development of phthisis due to ischemia. PMID:25606034

Effusive-constrictive pericarditis as the manifestation of an unexpected diagnosis.

PubMed

Marta, Liliana; Alves, Miguel; Peres, Marisa; Ferreira, Ricardo; Ferreira, Hugo; Leal, Margarida; Nobre, Ângelo

2015-01-01

Constrictive pericarditis is a clinical condition characterized by the appearance of signs and symptoms of right heart failure due to loss of pericardial compliance. Cardiac surgery is now one of the most frequent causes in developed countries, while tuberculosis remains the most prevalent cause in developing countries. Malignancy is a rare cause but usually has a poor prognosis. The diagnosis of constrictive pericarditis remains a clinical challenge and requires a combination of noninvasive diagnostic methods (echocardiography, cardiac magnetic resonance and computed tomography); in some cases, cardiac catheterization is needed to confirm the diagnosis. The authors present the case of a 51-year-old man, hospitalized due to cardiac tamponade. Diagnostic investigation was suggestive of tuberculous etiology. Despite directed medical therapy, the patient developed effusive-constrictive physiology. He underwent pericardiectomy and anatomopathologic study suggested a neoplastic etiology. The patient died in the postoperative period from biventricular failure. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

PubMed

Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

2017-10-01

Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

[Lightning strike and lesions outside the brain: Clinical cases and a review of the literature].

PubMed

Morin, A; Lesourd, A; Cabane, J

2015-01-01

Every year, 240,000 people are struck by lightning worldwide, causing injuries leading to significant handicaps. Most of the symptoms involve brain lesions; neuromuscular sequelae and myelopathy are less common. We describe five cases of patients struck by lightning with various clinical presentations. The first patient presented painful paresthesias in both upper limbs that disappeared 18 months later; the injury was a plexopathy. The second patient developed proximal weakness in the upper-left limb due to a myopathy. Two patients presented with various motor weaknesses in the lower limbs due to motor neuron disease and myelopathy. The last patient had a transient tetraplegy, which resolved in 5minutes; the diagnosis was keraunoparalysis. Lightning injuries can have many consequences depending on the different mechanisms involved. The clinical presentation is often due to a very focal lesion without any secondary extension. Motor neuron disease probably results from post-traumatic myelopathy. We discuss the ALS-electrocution association, frequently described in the literature. Various peripheral nerve and spinal cord lesions can be seen in lightning strike victims involving myelopathy, motor neuron, muscle and plexus. Clinical syndromes are often atypical but outcome is often favorable. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with palmoplantar keratoderma: A review of literature and expansion of clinical phenotype.

PubMed

Tallapaka, Karthik; Venugopal, Vineeth; Dalal, Ashwin; Aggarwal, Shagun

2018-04-01

Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal (MIM # 610644) is a clinically distinctive form of SRY-negative 46,XX disorder of sex development. It is a rare autosomal recessive disorder caused due to biallelic loss of function mutations in RSPO1 gene. RSPO1 acts by activating the canonical β-catenin pathway and is one of the most important genes controlling female gonadal differentiation. RSPO1-associated disorders of sex development have been described only in three instances in the past. We report fourth such case with additional findings and perform a comparative review of previous phenotypic descriptions, thereby expanding the clinical phenotype of this syndrome. © 2018 Wiley Periodicals, Inc.

Technological choices for mobile clinical applications.

PubMed

Ehrler, Frederic; Issom, David; Lovis, Christian

2011-01-01

The rise of cheaper and more powerful mobile devices make them a new and attractive platform for clinical applications. The interaction paradigm and portability of the device facilitates bedside human-machine interactions. The better accessibility to information and decision-support anywhere in the hospital improves the efficiency and the safety of care processes. In this study, we attempt to find out what are the most appropriate Operating System (OS) and Software Development Kit (SDK) to support the development of clinical applications on mobile devices. The Android platform is a Linux-based, open source platform that has many advantages. Two main SDKs are available on this platform: the native Android and the Adobe Flex SDK. Both of them have interesting features, but the latter has been preferred due its portability at comparable performance and ease of development.

ADMultiImg: a novel missing modality transfer learning based CAD system for diagnosis of MCI due to AD using incomplete multi-modality imaging data

NASA Astrophysics Data System (ADS)

Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

2018-02-01

Alzheimer's Disease (AD) is the most common cause of dementia and currently has no cure. Treatments targeting early stages of AD such as Mild Cognitive Impairment (MCI) may be most effective to deaccelerate AD, thus attracting increasing attention. However, MCI has substantial heterogeneity in that it can be caused by various underlying conditions, not only AD. To detect MCI due to AD, NIA-AA published updated consensus criteria in 2011, in which the use of multi-modality images was highlighted as one of the most promising methods. It is of great interest to develop a CAD system based on automatic, quantitative analysis of multi-modality images and machine learning algorithms to help physicians more adequately diagnose MCI due to AD. The challenge, however, is that multi-modality images are not universally available for many patients due to cost, access, safety, and lack of consent. We developed a novel Missing Modality Transfer Learning (MMTL) algorithm capable of utilizing whatever imaging modalities are available for an MCI patient to diagnose the patient's likelihood of MCI due to AD. Furthermore, we integrated MMTL with radiomics steps including image processing, feature extraction, and feature screening, and a post-processing for uncertainty quantification (UQ), and developed a CAD system called "ADMultiImg" to assist clinical diagnosis of MCI due to AD using multi-modality images together with patient demographic and genetic information. Tested on ADNI date, our system can generate a diagnosis with high accuracy even for patients with only partially available image modalities (AUC=0.94), and therefore may have broad clinical utility.

New criteria for Alzheimer disease and mild cognitive impairment: implications for the practicing clinician.

PubMed

Budson, Andrew E; Solomon, Paul R

2012-11-01

In most research studies and clinical trials, Alzheimer disease (AD) has been diagnosed using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association work group in 1984. Developments over the last 27 years have lead to the need for new diagnostic criteria. Four articles in the journal Alzheimer's & Dementia in 2011 describe new criteria for AD dementia and mild cognitive impairment (MCI) due to the AD pathophysiological process (MCI due to AD) and the underlying rationale for them. These new criteria emphasize that the AD pathophysiological process starts years and perhaps decades before clinical symptoms, and that biomarkers can be used to detect amyloid β deposition and the effects of neurodegeneration in the brain. These new criteria are immediately helpful to the practicing clinician, providing more accurate and specific guidelines for the diagnosis of AD dementia and MCI due to AD. As new diagnostic tools and new treatments for AD become available, diagnosis using these criteria will enable patients with this disorder to receive the best possible care.

Development and implementation of sepsis alert systems

PubMed Central

Harrison, Andrew M.; Gajic, Ognjen; Pickering, Brian W.; Herasevich, Vitaly

2016-01-01

Synopsis/Summary Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Important barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload & alert fatigue, due to suboptimal alert performance. Outside the ICU, additional barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Currently available evidence does not support routine use of sepsis alert systems in clinical practice. However, continuous improvement in both the afferent (data availability and accuracy of detection algorithms) and efferent (evidence-based decision support and smoother integration into clinical workflow) limbs of sepsis alert systems will help translate theoretical advantages into measurable patient benefit. PMID:27229639

Past, Present, and Future Trends in Teaching Clinical Skills through Web-Based Learning Environments

ERIC Educational Resources Information Center

Coe Regan, Jo Ann R.; Youn, Eric J.

2008-01-01

Distance education in social work has grown significantly due to the use of interactive television and computer networks. Given the recent developments in delivering distance education utilizing Web-based technology, this article presents a literature review focused on identifying generational trends in the development of Web-based learning…

A research review on clinical needs, technical requirements, and normativity in the design of surgical robots.

PubMed

Díaz, Carlos Eduardo; Fernández, Roemi; Armada, Manuel; García, Felipe

2017-12-01

Nowadays robots play an important role in society, mainly due to the significant benefits they provide when utilized for assisting human beings in the execution of dangerous or repetitive tasks. Medicine is one of the fields in which robots are gaining greater use and development, especially those employed in minimally invasive surgery (MIS). However, due to the particular conditions of the human body where robots have to act, the design of these systems is complex, not only from a technical point of view, but also because the clinical needs and the normativity aspects are important considerations that have to be taken into account in order to achieve better performances and more secure systems for patients and surgeons. Thus, this paper explores the clinical needs and the technical requirements that will trace the roadmap for the next scientific and technological advances in the field of robotic surgery, the metrics that should be defined for safe technology development and the standards that are being elaborated for boosting the industry and facilitating systems integration. Copyright © 2017 John Wiley & Sons, Ltd.

Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics.

PubMed

McArthur, Monica A

2017-06-13

Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV.

Flexible substrate-based devices for point-of-care diagnostics

PubMed Central

Wang, ShuQi; Chinnasamy, Thiruppathiraja; Lifson, Mark; Inci, Fatih; Demirci, Utkan

2016-01-01

Point-of-care (POC) diagnostics play an important role in delivering healthcare, particularly for clinical management and disease surveillance in both developed and developing countries. Currently, the majority of POC diagnostics utilize paper substrates owing to their affordability, disposability, and mass production capability. Recently, flexible polymer substrates have been investigated due to their enhanced physicochemical properties, potential to be integrated into wearable devices with wireless communications for personalized health monitoring, and ability to be customized for POC diagnostics. Here, we focus on the latest advances in developing flexible substrate-based diagnostic devices, including paper and polymers, and their clinical applications at the POC. PMID:27344425

Flexible Substrate-Based Devices for Point-of-Care Diagnostics.

PubMed

Wang, ShuQi; Chinnasamy, Thiruppathiraja; Lifson, Mark A; Inci, Fatih; Demirci, Utkan

2016-11-01

Point-of-care (POC) diagnostics play an important role in delivering healthcare, particularly for clinical management and disease surveillance in both developed and developing countries. Currently, the majority of POC diagnostics utilize paper substrates owing to affordability, disposability, and mass production capability. Recently, flexible polymer substrates have been investigated due to their enhanced physicochemical properties, potential to be integrated into wearable devices with wireless communications for personalized health monitoring, and ability to be customized for POC diagnostics. Here, we focus on the latest advances in developing flexible substrate-based diagnostic devices, including paper and polymers, and their clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

The value of item response theory in clinical assessment: a review.

PubMed

Thomas, Michael L

2011-09-01

Item response theory (IRT) and related latent variable models represent modern psychometric theory, the successor to classical test theory in psychological assessment. Although IRT has become prevalent in the measurement of ability and achievement, its contributions to clinical domains have been less extensive. Applications of IRT to clinical assessment are reviewed to appraise its current and potential value. Benefits of IRT include comprehensive analyses and reduction of measurement error, creation of computer adaptive tests, meaningful scaling of latent variables, objective calibration and equating, evaluation of test and item bias, greater accuracy in the assessment of change due to therapeutic intervention, and evaluation of model and person fit. The theory may soon reinvent the manner in which tests are selected, developed, and scored. Although challenges remain to the widespread implementation of IRT, its application to clinical assessment holds great promise. Recommendations for research, test development, and clinical practice are provided.

Best Practices in Stability Indicating Method Development and Validation for Non-clinical Dose Formulations.

PubMed

Henry, Teresa R; Penn, Lara D; Conerty, Jason R; Wright, Francesca E; Gorman, Gregory; Pack, Brian W

2016-11-01

Non-clinical dose formulations (also known as pre-clinical or GLP formulations) play a key role in early drug development. These formulations are used to introduce active pharmaceutical ingredients (APIs) into test organisms for both pharmacokinetic and toxicological studies. Since these studies are ultimately used to support dose and safety ranges in human studies, it is important to understand not only the concentration and PK/PD of the active ingredient but also to generate safety data for likely process impurities and degradation products of the active ingredient. As such, many in the industry have chosen to develop and validate methods which can accurately detect and quantify the active ingredient along with impurities and degradation products. Such methods often provide trendable results which are predictive of stability, thus leading to the name; stability indicating methods. This document provides an overview of best practices for those choosing to include development and validation of such methods as part of their non-clinical drug development program. This document is intended to support teams who are either new to stability indicating method development and validation or who are less familiar with the requirements of validation due to their position within the product development life cycle.

A SOA-Based Platform to Support Clinical Data Sharing.

PubMed

Gazzarata, R; Giannini, B; Giacomini, M

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the "Interoperable" Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the "Interoperable" Tier, the current solution actually covers the "Connected" Tier, due to local hospital policy restrictions.

A SOA-Based Platform to Support Clinical Data Sharing

PubMed

Gazzarata, R; Giannini, B; Giacomini, M

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions. © 2017 R. Gazzarata et al.

A SOA-Based Platform to Support Clinical Data Sharing

PubMed Central

Gazzarata, R.; Giannini, B.

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions. PMID:29065576

Influenceable and Avoidable Risk Factors for Systemic Air Embolism due to Percutaneous CT-Guided Lung Biopsy: Patient Positioning and Coaxial Biopsy Technique—Case Report, Systematic Literature Review, and a Technical Note

PubMed Central

2014-01-01

Following the first case of a systemic air embolism due to percutaneous CT-guided lung biopsy in our clinic we analysed the literature regarding this matter in view of influenceable or avoidable risk factors. A systematic review of literature reporting cases of systemic air embolism due to CT-guided lung biopsy was performed to find out whether prone positioning might be a risk factor regarding this issue. In addition, a technical note concerning coaxial biopsy practice is presented. Prone position seems to have relevance for the development and/or clinical manifestation of air embolism due to CT-guided lung biopsy and should be considered a risk factor, at least as far as lesions in the lower parts of the lung are concerned. Biopsies of small or cavitary lesions in coaxial technique should be performed using a hemostatic valve. PMID:25431666

Comprehensive clinical care for men who have sex with men: An integrated approach

PubMed Central

Bekker, Linda-Gail; Stall, Ron; Grulich, Andrew E.; Colfax, Grant; Lama, Javier

2017-01-01

Men who have sex with men have unique health care needs, partially due to biologial factors, such as their increased susceptibility to HIV and STD acquisition and transmission because of anal intercourse, but also due to the internalization of societal stigma related to homosexuality and gender non-conformity, resulting in depression, anxiety and substance use, and other adverse health outcomes. Successful responses to the global HIV/AIDS epidemic will require the development of culturally-sensitive clinical care programs for MSM that address these health disparities concerns, as well as root causes of maladaptive behavior, such as societal homophobia. Providers need to become familiar with local outreach agencies, hotlines and media that can connect MSM with positive role models and social opportunities. Research is needed to understand how the majority of MSM lead resilient and productive lives in the face of discrimination, in order to develop assets-based interventions that build on community supports that MSM have created. MSM deserve to be treated with respect and clinical providers need to interact with them in ways that promote the disclosure of actionable health information. Optimal clinical care for sexual and gender minority persons is a fundamental human right, requiring health professionals as allies. PMID:22819653

First pathological report of a de novo CD5-positive diffuse large B-cell lymphoma patient presenting with Guillain-Barré syndrome-like neuropathy due to neurolymphomatosis.

PubMed

Kobayashi, Mikiko; Sakai, Yasuhiro; Kariya, Yuta; Sakai, Hitoshi; Hineno, Akiyo; Oyanagi, Kiyomitsu; Kanno, Hiroyuki

2018-05-02

Peripheral neuropathy occurs in approximately 5% of the patients with lymphoma. Two major causes of peripheral neuropathy associated with lymphoma are neurolymphomatosis and paraneoplastic neuropathy such as demyelinating neuropathy. The differential diagnosis between neurolymphomatosis and demyelinating neuropathy is difficult, because electrophysiological findings suggestive of demyelination are frequently observed even in patients with neurolymphomatosis. Here, we report a patient with de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) who presented with Guillain-Barré syndrome (GBS)-like neuropathy. Demyelination due to paraneoplastic neuropathy was clinically suspected. However, autopsy demonstrated that the cause of the neuropathy was neurolymphomatosis. Clinical courses of neurolymphomatosis vary and neurolymphomatosis cases presenting with GBS-like neuropathy are reported. In addition, DLBCL is the most frequent histological type of malignant lymphoma that develops neurolymphomatosis. Furthermore, "CD5-positive" DLBCL may tend to develop neurolymphomatosis. If a patient with "CD5-positive" DLBCL develops peripheral neuropathy, neurolymphomatosis should be considered and imaging studies performed and, if possible, nerve tissue biopsy, regardless of clinical symptoms of the neuropathy. To our knowledge, this is the first report of a patient with de novo CD5-positive DLBCL with neurolymphomatosis who presented with GBS-like neuropathy. © 2018 Japanese Society of Neuropathology.

Phase II drugs under clinical investigation for the treatment of chronic constipation.

PubMed

Mozaffari, Shilan; Didari, Tina; Nikfar, Shekoufeh; Abdollahi, Mohammad

2014-11-01

Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability. The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract. At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.

Development and Psychometric Evaluation of the Index of Dental Anxiety and Fear (IDAF-4C[superscript +])

ERIC Educational Resources Information Center

Armfield, Jason M.

2010-01-01

The measurement of dental fear is important due to its high prevalence and appreciable individual, clinical, and public health consequences. However, existing measures of dental anxiety and fear (DAF) have theoretical or practical limitations. This study describes the development and subsequent assessment of the reliability and validity of test…

Issues in the Development of Cross-Cultural Assessments of Speech and Language for Children

ERIC Educational Resources Information Center

Carter, Julie A.; Lees, Janet A.; Murira, Gladys M.; Gona, Joseph; Neville, Brian G. R.; Newton, Charles R. J. C.

2005-01-01

Background: There is an increasing demand for the assessment of speech and language in clinical and research situations in countries where there are few assessment resources. Due to the nature of cultural variation and the potential for cultural bias, new assessment tools need to be developed or existing tools require adaptation. However, there…

Toddler Autism Screening Questionnaire: Development and Potential Clinical Validity

ERIC Educational Resources Information Center

Tsai, Wen-Che; Soong, Wei-Tsuen; Shyu, Yea-Ing Lotus

2012-01-01

No feasible screening instrument is available for early detection of children with autism in Taiwan. The existing instruments may not be appropriate for use in Taiwan due to different health care systems and child-rearing cultures. The purpose of this study was to develop and test a screening questionnaire for generic autism. The initial 18-item…

Potential oxidative stress biomarkers of mild cognitive impairment due to Alzheimer disease.

PubMed

García-Blanco, Ana; Baquero, Miguel; Vento, Máximo; Gil, Esperanza; Bataller, Luis; Cháfer-Pericás, Consuelo

2017-02-15

The high and increasing incidence of Alzheimer Disease (AD) worldwide is a major global concern. Classical diagnosis is carried out in the dementia phase, often in the moderate stages when treatment efficacy is limited. Nowadays, early diagnosis, even in pre-dementia stages, is possible in selected cases within an appropriate clinical setting, employing cerebral spinal fluid (CSF) sample analysis and neuroimaging procedures. In spite of the accurate diagnosis achieved by novel CSF biomarkers or positron emission tomography beta-amyloid tracers, these tests are invasive and expensive. Therefore, important work is being carried out to discover reliable biomarkers in peripheral biofluids (blood, plasma, urine) to be incorporated in clinical routine for early AD diagnosis. Although the nature of AD pathogenesis is complex, it is known that oxidative stress plays a key role, for which biomarkers are easily determined in peripheral biofluids. This review summarizes recent research on oxidative stress biomarkers in mild cognitive impairment due to AD. Among them, a promising research line is the study of the relationship between lipid peroxidation biomarkers and early AD clinical features. Results show a pronounced imbalance between scientific production and clinical reality due to the lack of clinical validation. We conclude that an important field in oxidative stress biomarkers could be developed with the aim to help clinicians in early disease diagnosis, effective treatment initiation and reliable disease monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical review of 95 patients with 46,XX disorders of sex development based on the new Chicago classification.

PubMed

Öcal, Gönül; Berberoğlu, Merih; Sıklar, Zeynep; Aycan, Zehra; Hacıhamdioglu, Bülent; Savas Erdeve, Şenay; Çamtosun, Emine; Kocaay, Pınar; Ruhi, Hatice I; Kılıç, Birim G; Tukun, Ajlan

2015-02-01

The aim of our study was to determine the etiologic distribution of 46,XX disorder of sexual development (DSD) according to the new DSD classification system and to evaluate the clinical features of this DSD subgroup in our patient cohort. The evaluation criteria and clinical findings of 95 46,XX patients were described by clinical presentation, gonadal morphology, genital anatomy, associated dysmorphic features, presence during prenatal period with/without postnatal virilization, hormonal characteristics, and presence or absence of steroidogenic defects among 319 patients with DSD. Types and ratios of each presentation of our 95 patients with 46,XX DSD were as follows: 82 had androgen excess (86.3%): (74 had classical congenital adrenal hyperplasia, 2 had CAH variant possibility of P450-oxidoreductase gene defect), 6 had disorders of ovarian development (6.3%): (1 patient had gonadal dysgenesis with virilization at birth with bilateral streak gonad, 4 patients had complete gonadal dysgenesis, and 1 patient had ovotesticular DSD) and 7 had other 46,XX DSD. Two sisters, who had 46,XX complete gonadal dysgenesis,were diagnosed with Perrault Syndrome with ovarian failure due to streak gonads and associated with sensorineural deafness. 46,XX DSD are usually derived from intrauterine virilization and CAH is the most common cause of 46,XX DSD due to fetal androgen exposure. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics

PubMed Central

McArthur, Monica A.

2017-01-01

Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV. PMID:28608813

Development and Implementation of Sepsis Alert Systems.

PubMed

Harrison, Andrew M; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

2016-06-01

Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Canary: An NLP Platform for Clinicians and Researchers.

PubMed

Malmasi, Shervin; Sandor, Nicolae L; Hosomura, Naoshi; Goldberg, Matt; Skentzos, Stephen; Turchin, Alexander

2017-05-03

Information Extraction methods can help discover critical knowledge buried in the vast repositories of unstructured clinical data. However, these methods are underutilized in clinical research, potentially due to the absence of free software geared towards clinicians with little technical expertise. The skills required for developing/using such software constitute a major barrier for medical researchers wishing to employ these methods. To address this, we have developed Canary, a free and open-source solution designed for users without natural language processing (NLP) or software engineering experience. It was designed to be fast and work out of the box via a user-friendly graphical interface.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases

PubMed Central

2011-01-01

Background Over 95% of rare diseases lack treatments despite many successful treatment studies in animal models. To improve access to treatments, the Accelerated Approval (AA) regulations were implemented allowing the use of surrogate endpoints to achieve drug approval and accelerate development of life-saving therapies. Many rare diseases have not utilized AA due to the difficulty in gaining acceptance of novel surrogate endpoints in untreated rare diseases. Methods To assess the potential impact of improved AA accessibility, we devised clinical development programs using proposed clinical or surrogate endpoints for fifteen rare disease treatments. Results We demonstrate that better AA access could reduce development costs by approximately 60%, increase investment value, and foster development of three times as many rare disease drugs for the same investment. Conclusion Our research brings attention to the need for well-defined and practical qualification criteria for the use of surrogate endpoints to allow more access to the AA approval pathway in clinical trials for rare diseases. PMID:21733145

Association of myasthenia gravis and Behçet's disease: A case report.

PubMed

Kisabay, Aysin; Sari, Ummu Serpil; Boyaci, Recep; Batum, Melike; Yilmaz, Hikmet; Selcuki, Deniz

2016-01-01

Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behçet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behçet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behçet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Clinical features of multiple organ failure in the elderly.

PubMed

Wang, S W; Fan, L

1990-09-01

Multiple organ failure (MOF) in the elderly is a new syndrome evolved from multiple organ chronic diseases on the basis of multiple organ dysfunction in the aged. Its characteristics are clinically different from those of MOF due to serious trauma. 122 cases of MOF were analysed retrospectively and their clinical features discussed. MOF with a long course is the natural presentation in many of the elderly before death. Its main precipitating factors are pulmonary infection, metastatic carcinoma, cardiac attack, etc. The sequence of a failure in organs is heart, lung, kidney, liver, etc. The mortality is similar to that of MOF due to trauma. However, those suffering from 4-organ failure can still survive, and instead, the renal failure can be mostly fatal. More attention should be paid to the prevention of MOF in the elderly so as to shorten its developing course.

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.

Cardiac auscultatory recording database: delivering heart sounds through the Internet.

PubMed Central

Tuchinda, C.; Thompson, W. R.

2001-01-01

The clinical skill of cardiac auscultation, while known to be sensitive, specific, and inexpensive in screening for cardiac disease among children, has recently been shown to be deficient among residents in training. This decline in clinical skill is partly due to the difficulty in teaching auscultation. Standardization, depth, and breadth of experience has been difficult to reproduce for students due to time constraints and the impracticality of examining large numbers of patients with cardiac pathology. We have developed a web-based multimedia platform that delivers complete heart sound recordings from over 800 different patients seen at the Johns Hopkins Outpatient Pediatric Cardiology Clinic. The database represents more than twenty significant cardiac lesions as well as normal and innocent murmurs. Each patient record is complete with a gold standard echo for diagnostic confirmation and a gold standard auscultatory assessment provided by a pediatric cardiology attending. PMID:11825279

Thyrotropinoma and multinodular goiter: A diagnostic challenge for hyperthyroidism.

PubMed

Aksoy, Duygu Yazgan; Gedik, Arzu; Cinar, Nese; Soylemezoglu, Figen; Berker, Mustafa; Gurlek, Omer Alper

2013-11-01

Thyroid disorders are frequently encountered. The diagnosis is straightforward unless clinical or laboratory findings are inconclusive and/or perplexing. Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma rarely occurs and symptoms due to thyroid hormone excess are subtle. The presentation of the disease becomes unusual when co-secretion of other hormones with thyrotropin or concomitant thyroid parenchymal pathology exist. We present the case of a 63-year-old female patient with thyrotropinoma co-secreting growth hormone and multinodular goiter. She developed hyperthyroidism first due to thyrotropinoma and later due to a toxic nodule. Herein, we discuss the diagnostic and therapeutic challenges of hyperthyroidism with atypical presentation.

[Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

PubMed

Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

1999-04-01

Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

PubMed

Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

2017-01-01

Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Tinea incognito due to Trichophyton mentagrophytes.

PubMed

Sánchez-Castellanos, María Elena; Mayorga-Rodríguez, Jorge Arturo; Sandoval-Tress, Cecilia; Hernández-Torres, Mercedes

2007-01-01

Tinea incognito is a ringworm infection modified by corticosteroids. We report a case of a 2-year-old girl who developed tinea incognito due to Trichophyton mentagrophytes after applying methylprednisolone aceponate for 3 months. Diagnosis was confirmed by histopathologic and mycological examination, which led to the identification of Trichophyton mentagrophytes var. mentagrophytes, a zoophilic dermatophyte. Previous corticosteroid use in dermatophyte infections can alter their clinical appearance leading to misdiagnosis and delay in appropriate therapy.

Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine

PubMed Central

Henrotin, Yves; Sanchez, Christelle; Cornet, Anne; Van de Put, Joachim; Douette, Pierre; Gharbi, Myriam

2015-01-01

Abstract Context: Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients. Objective: To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification. Methods and results: This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials. It also presents all the available regulatory requirements. Conclusions: The path through the adoption of a specific soluble biomarker for OA is steep but is worth the challenge due to the benefit that it can provide. PMID:26954785

Multiscale mechanistic modeling in pharmaceutical research and development.

PubMed

Kuepfer, Lars; Lippert, Jörg; Eissing, Thomas

2012-01-01

Discontinuation of drug development projects due to lack of efficacy or adverse events is one of the main cost drivers in pharmaceutical research and development (R&D). Investments have to be written-off and contribute to the total costs of a successful drug candidate receiving marketing authorization and allowing return on invest. A vital risk for pharmaceutical innovator companies is late stage clinical failure since costs for individual clinical trials may exceed the one billion Euro threshold. To guide investment decisions and to safeguard maximum medical benefit and safety for patients recruited in clinical trials, it is therefore essential to understand the clinical consequences of all information and data generated. The complexity of the physiological and pathophysiological processes and the sheer amount of information available overcharge the mental capacity of any human being and prevent a prediction of the success in clinical development. A rigorous integration of knowledge, assumption, and experimental data into computational models promises a significant improvement of the rationalization of decision making in pharmaceutical industry. We here give an overview of the current status of modeling and simulation in pharmaceutical R&D and outline the perspectives of more recent developments in mechanistic modeling. Specific modeling approaches for different biological scales ranging from intracellular processes to whole organism physiology are introduced and an example for integrative multiscale modeling of therapeutic efficiency in clinical oncology trials is showcased.

Impact of protein D-containing pneumococcal conjugate vaccines on non-typeable Haemophilus influenzae acute otitis media and carriage.

PubMed

Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas

2017-07-01

Protein D-containing vaccines may decrease acute otitis media (AOM) burden and nasopharyngeal carriage of non-typeable Haemophilus influenzae (NTHi). Protein D-containing pneumococcal conjugate vaccine PHiD-CV (Synflorix, GSK Vaccines) elicits robust immune responses against protein D. However, the phase III Clinical Otitis Media and PneumoniA Study (COMPAS), assessing PHiD-CV efficacy against various pneumococcal diseases, was not powered to demonstrate efficacy against NTHi; only trends of protective efficacy against NTHi AOM in children were shown. Areas covered: This review aims to consider all evidence available to date from pre-clinical and clinical phase III studies together with further evidence emerging from post-marketing studies since PHiD-CV has been introduced into routine clinical practice worldwide, to better describe the clinical utility of protein D in preventing AOM due to NTHi and its impact on NTHi nasopharyngeal carriage. Expert commentary: Protein D is an effective carrier protein in conjugate vaccines and evidence gathered from pre-clinical, clinical and observational studies suggest that it also elicits immune response that can help to reduce the burden of AOM due to NTHi. There remains a need to develop improved vaccines for prevention of NTHi disease, which could be achieved by combining protein D with other antigens.

Frailty and sarcopenia: From theory to clinical implementation and public health relevance.

PubMed

Cesari, Matteo; Nobili, Alessandro; Vitale, Giovanni

2016-11-01

The sustainability of healthcare systems is threatened by the increasing (absolute and relative) number of older persons referring to clinical services. Such global phenomenon is questioning the traditional paradigms of medicine, pushing towards the need of new criteria at the basis of clinical decision algorithms. In this context, frailty has been advocated as a geriatric condition potentially capable of overcoming the weakness of chronological age in the identification of individuals requiring adapted care due to their increased vulnerability to stressors. Interestingly, frailty poses itself beyond the concept of nosological conditions due to the difficulties at correctly framing traditional diseases in the complex and heterogeneous scenario of elders. Thus, frailty may play a key role in public health policies for promoting integrated care towards biologically aged individuals, currently presenting multiple unmet clinical needs. At the same time, the term frailty has also been frequently used in the literature for framing a physical condition of risk for (mainly functional) negative endpoints. The combination of such physical impairment with an organ-specific phenotype (e.g., the age-related skeletal muscle decline or sarcopenia) may determine the assumptions for the development of a clinical condition to be used as potential target for ad hoc interventions against physical disability. In the present article, we present the background of frailty and sarcopenia, and discuss their potentialities for reshaping current clinical and research practice in order to promote holistic approach to older patients, solicit personalization of care, and develop new targets for innovative interventions. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Interpretation of lung cancer study outcomes.

PubMed

Cortinovis, Diego; Abbate, Marida; Bidoli, Paolo; Pelizzoni, Davide; Canova, Stefania

2015-11-01

Lung cancer is the leading cause of cancer death in developed countries. However, in the last few years we observed an important acceleration in drug development due to oncogenic driver tumors discovery. Sharing and putting together preclinical data from benchmark and data from clinical research is the scientific paradigm that allows real breakthrough in clinical practice in this field, but only a few targeted agents are worthy and practice changing. The clinical research and proper use of statistical methodology are the pillars to continue to achieve important goals like improvement of overall survival. A good medical oncologist should be able to critically read a scientific paper and move from the observed outcomes into clinical perspective. Despite clinical improvements, sometimes the union of promising targeted agents and optimistic expectations misrepresent the reality and the value of clinical research. In this article, we try to analyze the meaning of statistical assumptions from clinical trials, especially in lung cancer, through a critical review of the concept of value-based medicine. We also attempt to give the reader some practical tools to weigh scientific value of literature reports.

[LIMB LENGH SHORTENING AFTER ARTERIAL CANNULATION IN INFANCY].

PubMed

Díaz-Ben, B; Balvís-Balvís, P; Lozano-Balseiro, M; González-Herranz, P

2016-01-01

The aim of this study was to assess the relationship between arterial cannulations and the development of limb length discrepancies in childhood or impaired growth of the proximal femur. A retrospective study was conducted on 300 children who required arterial cannulation and/or cardiac catheterisation during childhood in relation to congenital heart diseases. Seven of these patients were referred from the Paediatric Cardiology clinic due to a limb length discrepancy and/or proximal femoral deformities. Seven children, with a mean age of 10 years, were referred to our clinic. The mean length discrepancy was 2.7cm, and was more frequent on the right side. Three of the patients presented with proximal femoral deformities: two cases of caput valgum and one of bilateral physeal arrest of the greater trochanter. All children were initially treated with a shoe lift in the shortest limb. One of them required a tibial lengthening and two others are awaiting a similar procedure. We recommend clinical and radiological follow-up of patients who have undergone catheterisation during their infancy due to the relationship between these techniques and the risk of developing a limb length discrepancy. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

Disconnects in pedagogy and practice in community health nursing clinical experiences: Qualitative findings of a mixed method study.

PubMed

Pijl-Zieber, Em M; Barton, Sylvia; Awosoga, Olu; Konkin, Jill

2015-10-01

Many baccalaureate schools of nursing are using non-traditional placements for undergraduate community health clinical rotations. These placements occur at agencies not organizationally affiliated with the health care system and they typically do not employ registered nurses (RNs). In this paper, we describe the qualitative findings of a mixed method study that explored these gaps as they relate to pre-registration nursing students' preparation for community health roles. While non-traditional community health placements offer unique opportunities for learning through carefully crafted service learning pedagogy, these placements also present challenges for student preparation for practice in community health roles. The theory-practice gap and the gap between the expected and actual performance of new graduates are accentuated through the use of non-traditional community clinical experiences. These gaps are not necessarily due to poor pedagogy, but rather due to the perceptions and values of the stakeholders involved: nursing students, community health nursing faculty, and community health nurses. New ways must be developed between academe and community health practice areas to provide students with opportunities to develop competence for practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

PubMed

Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

2013-01-01

The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited.

PubMed

Tedesco, Dario; Farid-Kapadia, Mufiza; Offringa, Martin; Bhutta, Zulfiqar A; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina G

2018-03-01

Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs). Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse events [AEs], discontinuations due to AEs, any AE, and mortality) that included at least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple meta-analyses. Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs (64 and 66 unique RCTs respectively). The summary ROR was 0.92 (95% confidence intervals: 0.78-1.08) for severe AEs; 1.13 (0.54-2.34) for discontinuations due to AEs; 1.10 (0.77-1.59) for any AE; and 0.99 (0.61-1.61) for mortality and for the all-harms-combined-end point 0.96 (0.83-1.10). Differences of ROR-point-estimates ≥2-fold between MDCs and LDCs were identified in 35% of meta-analyses. We found no major systematic differences in harm rates in pediatric trials between MDCs and LDCs, but data on harms in children were overall very limited. Copyright © 2017 Elsevier Inc. All rights reserved.

Retracted: Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre.

PubMed

Chauhan, V; Dada, R; Jain, V

2017-11-01

Retraction: 'Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre' by Vasundhera Chauhan, Rima Dada, Vandana Jain The above article, published online on 8 August 2016 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editors-in-Chief, Wolf-Bernhard Schill and Ralf Henkel, and Blackwell Verlag GmbH. The retraction has been agreed as the result of an unresolved dispute between the first author and a colleague research fellow due to the inclusion of data from patients who were simultaneously enrolled in two studies being conducted separately by the two parties. Reference Chauhan, V., Dada, R. and Jain, V. (2016), Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre. Andrologia. doi:10.1111/and.12663. © 2016 Blackwell Verlag GmbH.

The Influence of Big (Clinical) Data and Genomics on Precision Medicine and Drug Development.

PubMed

Denny, Joshua C; Van Driest, Sara L; Wei, Wei-Qi; Roden, Dan M

2018-03-01

Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications. New biomedical informatics and machine-learning approaches advance the ability to interpret clinical information, enabling identification of complex phenotypes and subpopulations of patients. We review the recent history of use of "big data" from EHR-based cohorts and biobanks supporting these activities. Future studies using EHR data, other information sources, and new methods will promote a foundation for discovery to more rapidly advance precision medicine. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

PubMed

Artico, Marco; Riganò, Rachele; Buttari, Brigitta; Profumo, Elisabetta; Ionta, Brunella; Bosco, Sandro; Rasile, Manuela; Bianchi, Enrica; Bruno, Moira; Fumagalli, Lorenzo

2011-04-01

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

Prevention of in-hospital falls: development of criteria for the conduct of a multi-site audit.

PubMed

Giles, Kristy; Stephenson, Matthew; McArthur, Alexa; Aromataris, Edoardo

2015-06-01

Patient falls are a significant issue for hospitals due to the high rates of morbidity and mortality associated with these events, as well as the financial costs for the healthcare system. To establish what constitutes best practice in terms of fall prevention in acute care facilities and use this to inform the development of best practice audit criteria. Criteria for clinical audit were developed from evidence derived from systematic reviews and guidelines. While these were drawn from the best available evidence, they were also developed in conjunction with clinicians undertaking a fall-prevention clinical audit and key stakeholders from the clinical settings to ensure their relevance and applicability to the acute care setting. Current literature recommends a comprehensive and multifactorial approach to fall prevention. Eight audit criteria were derived from the best available evidence including the domains of physical environment, hospital culture and care processes, use of technology and targeted interventions. Existing research evidence and consultation with stakeholders has allowed the development of applicable, evidence-based audit criteria for fall prevention in acute care settings. This model can promote engagement, impact clinical practice and lead to improved outcomes.

Development of an Ontology to Model Medical Errors, Information Needs, and the Clinical Communication Space

PubMed Central

Stetson, Peter D.; McKnight, Lawrence K.; Bakken, Suzanne; Curran, Christine; Kubose, Tate T.; Cimino, James J.

2002-01-01

Medical errors are common, costly and often preventable. Work in understanding the proximal causes of medical errors demonstrates that systems failures predispose to adverse clinical events. Most of these systems failures are due to lack of appropriate information at the appropriate time during the course of clinical care. Problems with clinical communication are common proximal causes of medical errors. We have begun a project designed to measure the impact of wireless computing on medical errors. We report here on our efforts to develop an ontology representing the intersection of medical errors, information needs and the communication space. We will use this ontology to support the collection, storage and interpretation of project data. The ontology’s formal representation of the concepts in this novel domain will help guide the rational deployment of our informatics interventions. A real-life scenario is evaluated using the ontology in order to demonstrate its utility.

Overcoming regulatory and economic challenges facing pharmacogenomics.

PubMed

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

DEEPEN: A negation detection system for clinical text incorporating dependency relation into NegEx

PubMed Central

Mehrabi, Saeed; Krishnan, Anand; Sohn, Sunghwan; Roch, Alexandra M; Schmidt, Heidi; Kesterson, Joe; Beesley, Chris; Dexter, Paul; Schmidt, C. Max; Liu, Hongfang; Palakal, Mathew

2018-01-01

In Electronic Health Records (EHRs), much of valuable information regarding patients’ conditions is embedded in free text format. Natural language processing (NLP) techniques have been developed to extract clinical information from free text. One challenge faced in clinical NLP is that the meaning of clinical entities is heavily affected by modifiers such as negation. A negation detection algorithm, NegEx, applies a simplistic approach that has been shown to be powerful in clinical NLP. However, due to the failure to consider the contextual relationship between words within a sentence, NegEx fails to correctly capture the negation status of concepts in complex sentences. Incorrect negation assignment could cause inaccurate diagnosis of patients’ condition or contaminated study cohorts. We developed a negation algorithm called DEEPEN to decrease NegEx’s false positives by taking into account the dependency relationship between negation words and concepts within a sentence using Stanford dependency parser. The system was developed and tested using EHR data from Indiana University (IU) and it was further evaluated on Mayo Clinic dataset to assess its generalizability. The evaluation results demonstrate DEEPEN, which incorporates dependency parsing into NegEx, can reduce the number of incorrect negation assignment for patients with positive findings, and therefore improve the identification of patients with the target clinical findings in EHRs. PMID:25791500

Participant selection for preventive Regenerative Medicine trials: ethical challenges of selecting individuals at risk.

PubMed

Niemansburg, Sophie L; Habets, Michelle G J L; Dhert, Wouter J A; van Delden, Johannes J M; Bredenoord, Annelien L

2015-11-01

The innovative field of Regenerative Medicine (RM) is expected to extend the possibilities of prevention or early treatment in healthcare. Increasingly, clinical trials will be developed for people at risk of disease to investigate these RM interventions. These individuals at risk are characterised by their susceptibility for developing clinically manifest disease in future due to the existence of degenerative abnormalities. So far, there has been little debate about the ethical appropriateness of including such individuals at risk in clinical trials. We discuss three main challenges of selecting this participant model for testing RM interventions: the challenge of achieving a proportional risk-benefit balance; complexities in the trial design in terms of follow-up and sample size; and the difficulty of obtaining informed consent due to the many uncertainties. We conclude that selecting the model is not ethically justifiable for first-in-man trials with RM interventions due to the high risks and uncertainties. However, the model can be ethically appropriate for testing the efficacy of RM interventions under the following conditions: interventions should be low risk; the degenerative abnormalities (and other risk factors) should be strongly related with disease within a short time frame; robust preclinical evidence of efficacy needs to be present; and the informed consent procedure should contain extra safeguards with regard to communication on uncertainties. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

MAO-inhibitors in Parkinson's Disease

PubMed Central

Laux, Gerd

2011-01-01

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD. PMID:22110357

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-01-01

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects.

PubMed

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics.

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects

PubMed Central

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

Introduction The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. Methods In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Results Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. Conclusion We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics. PMID:29692626

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects.

PubMed

Danis, Ronald P; Lavine, Jeremy A; Domalpally, Amitha

2015-01-01

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA.

Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

PubMed Central

Danis, Ronald P; Lavine, Jeremy A; Domalpally, Amitha

2015-01-01

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA. PMID:26640366

Analysis of adverse events as a contribution to safety culture in the context of practice development

PubMed

Hoffmann, Susanne; Frei, Irena Anna

2017-01-01

Background: Analysing adverse events is an effective patient safety measure. Aim: We show, how clinical nurse specialists have been enabled to analyse adverse events with the „Learning from Defects-Tool“ (LFD-Tool). Method: Our multi-component implementation strategy addressed both, the safety knowledge of clinical nurse specialists and their attitude towards patient safety. The culture of practice development was taken into account. Results: Clinical nurse specialists relate competency building on patient safety due to the application of the LFD-tool. Applying the tool, fosters the reflection of adverse events in care teams. Conclusion: Applying the „Learning from Defects-Tool“ promotes work-based learning. Analysing adverse events with the „Learning from Defects-Tool“ contributes to the safety culture in a hospital.

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report.

PubMed

Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A; Hundt, Sophia; D'Alessio, Flavia; Sirima, Sodiomon B; Luty, Adrian J F; Duffy, Patrick; Leroy, Odile; Gamain, Benoit; Viebig, Nicola K

2016-09-17

Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines.

Integrating Clinical Trial Imaging Data Resources Using Service-Oriented Architecture and Grid Computing

PubMed Central

Cladé, Thierry; Snyder, Joshua C.

2010-01-01

Clinical trials which use imaging typically require data management and workflow integration across several parties. We identify opportunities for all parties involved to realize benefits with a modular interoperability model based on service-oriented architecture and grid computing principles. We discuss middleware products for implementation of this model, and propose caGrid as an ideal candidate due to its healthcare focus; free, open source license; and mature developer tools and support. PMID:20449775

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

PubMed Central

Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature.

PubMed

Abbas, Elham; Cox, Devin M; Smith, Teri; Butler, Merlin G

2016-09-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options].

PubMed

Martos-Moreno, Gabriel A; Calzada, Joan; Couce, María L; Argente, Jesús

2018-06-01

Hypophosphatasia is a very rare bone metabolism disorder caused by a deficiency in alkaline phosphatase activity, due to mutations in the ALPL gene. Its clinical hallmark is the impairment of skeletal and teeth mineralisation, although extra-skeletal manifestations are frequent. Its phenotypic spectrum is widely variable from a subtype with exclusive odontological impairment (odontohypophosphatasia) to five subtypes with systemic involvement, classified according to the age at the onset of the first symptoms (four of them in the paediatric age range: perinatal lethal, perinatal benign, infant and childhood hypophosphatasia). Those subtypes of hypophosphatasia with an earliest onset usually involve a worse prognosis, due to the risk of developing potentially lethal complications, such as seizures or severe respiratory insufficiency, secondary to rib cage malformations. Due to the extremely low prevalence of the severe forms of hypophosphatasia, its clinical variability and overlapping phenotypic features with several more prevalent conditions, the diagnosis of hypophosphatasia in the clinical setting is challenging. However, its potential lethality and impact on the patient's quality of life, along with the recent availability of an enzyme replacement therapy, increases the relevance of the early and accurate identification of patients affected with hypophosphatasia. On the basis of published evidence and clinical experience, this article suggests an algorithm with practical recommendations for the differential diagnosis of childhood hypophosphatasia, as well as an updated review of current therapeutic options. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Freud on Brothers and Sisters: A Neglected Topic

ERIC Educational Resources Information Center

Sherwin-White, Susan

2007-01-01

This paper explores Freud's developing thought on brothers and sisters, and their importance in his psychoanalytical writings and clinical work. Freud's work on sibling psychology has been seriously undervalued. This paper aims to give due recognition to Freud's work in this area. (Contains 1 note.)

The Contextualization of Archetypes: Clinical Template Governance.

PubMed

Pedersen, Rune; Ulriksen, Gro-Hilde; Ellingsen, Gunnar

2015-01-01

This paper is a status report from a large-scale openEHR-based EPR project from the North Norway Regional Health Authority. It concerns the standardization of a regional ICT portfolio and the ongoing development of a new process oriented EPR systems encouraged by the unfolding of a national repository for openEHR archetypes. Subject of interest; the contextualization of clinical templates is governed over multiple national boundaries which is complex due to the dependency of clinical resources. From the outset of this, we are interested in how local, regional, and national organizers maneuver to standardize while applying OpenEHR technology.

Complications and total care of a child with acute leukemia.

PubMed

Vietti, T J; Ragab, A H

1975-03-01

The complications which occur in a child with acute leukemia depend on the stage of the disease and the therapeutic regiman. Most children will present with some manifestation of marrow failure. An occasional child will have marked leukocytosis and disturbance of organ function due to massive leukemic infiltrates. Metabolic disturbances such as hyperuricemia and hyperphosphatemia-hypocalcemia may develop, expecially after therapy is initiated. The myelosuppression and immunosuppression due to drug toxicity may result in opportunistic infections. Other toxicities which can occur with a chemotherapeutic regimen are numerois and varied, and the physician must be cognizant of them in order to minimize damage. Therapy to the central nervous system, either for subclinical or clinical disease, has been associated with a variety of symptoms ranging from meningismus to paraplegia and death. To prevent the development of these complications, and to manage them effectively if they occur, the physician must be knowlegeable about their etiology, clinical and laboratory manifestations, and treatment.

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

PubMed

Angel, Juana; Steele, A Duncan; Franco, Manuel A

2014-01-01

Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

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

Evaluation of the rostral projection of the sacral lamina as a component of degenerative lumbosacral stenosis in German shepherd dogs.

PubMed

Saunders, Harvey; Worth, Andrew J; Bridges, Janis P; Hartman, Angela

2018-05-20

To determine the association between a greater rostral projection of the sacral lamina and clinical signs of cauda equina syndrome (CES) in German shepherd dogs (GSD) with presumptive degenerative lumbosacral disease (DLSS). Retrospective cohort study. One hundred forty-three GSD (125 police dogs and 18 pet dogs) presenting for either CES or prebreeding evaluation. Fifty-five were classified as affected by CES and diagnosed with DLSS, and 88 were classified as unaffected on the basis of clinical and imaging findings. The position of the rostral edge of the sacral lamina was measured from radiographs and/or computed tomography (CT) scans. This position was compared between affected and unaffected dogs. In dogs that underwent both radiography and CT scanning, the agreement between sacral lamina localization using each imaging modality was determined. Owners/handlers were contacted to determine whether dogs subsequently developed clinical signs compatible with CES at a mean of 29 months (unaffected). The sacral lamina did not extend as far rostrally in affected dogs, compared to unaffected dogs (P = .04). Among the 88 dogs unaffected by CES at initial evaluation, 2 developed clinical signs consistent with CES at follow-up. Rostral projection of the sacral lamina, previously proposed as a potential risk factor in dogs with CES due to lumbosacral degeneration, was not associated with a diagnosis of DLSS in this study; the opposite was true. Rostral projection of the sacral lamina may not be a predisposing factor in the development of CES due to DLSS in GSD. © 2018 The American College of Veterinary Surgeons.

Impact of regulatory assessment on clinical studies in Brazil.

PubMed

Russo, Luis Augusto Tavares; Eliaschewitz, Freddy Goldberg; Harada, Vitor; Trefiglio, Roberta Pereira; Picciotti, Raffaella; Machado, Paula Goulart Pinheiro; Kesselring, Gustavo Luiz Ferreira

2016-01-01

Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development.

Pyroglutamic acid-induced metabolic acidosis: a case report.

PubMed

Luyasu, S; Wamelink, M M C; Galanti, L; Dive, A

2014-06-01

High anion gap metabolic acidosis due to pyroglutamic acid (5-oxoproline) is a rare complication of acetaminophen treatment (which depletes glutathione stores) and is often associated with clinically moderate to severe encephalopathy. Acquired 5-oxoprolinase deficiency (penicillins) or the presence of other risk factors of glutathione depletion such as malnutrition or sepsis seems to be necessary for symptoms development. We report the case of a 55-year-old women who developed a symptomatic overproduction of 5-oxoproline during flucloxacillin treatment for severe sepsis while receiving acetaminophen for fever control. Hemodialysis accelerated the clearance of the accumulated organic acid, and was followed by a sustained clinical improvement.

Delayed-onset and recurrent limb weakness associated with West Nile virus infection.

PubMed

Sejvar, James J; Davis, Larry E; Szabados, Erica; Jackson, Alan C

2010-02-01

Human neurologic illness following infection with West Nile virus (WNV) may include meningitis, encephalitis, and acute flaccid paralysis (AFP). Most WNV-associated AFP is due to involvement of the spinal motor neurons producing an anterior (polio)myelitis. WNV poliomyelitis is typically characterized by acute and rapidly progressing limb weakness occurring early in the course of illness, which is followed by death or clinical plateauing with subsequent improvement to varying degrees. We describe four cases of WNV poliomyelitis in which the limb weakness was characterized by an atypical temporal pattern, including one case with onset several weeks after illness onset, and three cases developing relapsing or recurrent limb weakness following a period of clinical plateauing or improvement. Delayed onset or recurrent features may be due to persistence of viral infection or delayed neuroinvasion with delayed injury by excitotoxic or other mechanisms, by immune-mediated mechanisms, or a combination thereof. Further clinical and pathogenesis studies are needed to better understand the mechanisms for these phenomena. Clinicians should be aware of these clinical patterns in patients with WNV poliomyelitis.

Development and Evaluation of Polyvinyl Alcohol-Hydrogels as an Artificial Atrticular Cartilage for Orthopedic Implants

PubMed Central

Kobayashi, Masanori; Hyu, Hyon Suong

2010-01-01

Due to its excellent biocompatibility and mechanical properties, various different applications of polyvinyl alcohol-hydrogels (PVA-H) has been attempted in many fields. In the field of orthopedic surgery, we have been engaged for long time in research on the clinical applications of PVA-H as a artificial cartilage, and have performed many basic experiments on the mechanical properties, synthesis of PVA-H, and developed orthopedic implants using PVA-H. From these studies, many applications of artificial articular cartilage, intervertbral disc and artificial meniscus etc. have been developed. This review will present the overview of the applications and recent advances of PVA-H cartilages, and discuss clinical potential of PVA-H for orthopedics implant.

A secure communication using cascade chaotic computing systems on clinical decision support.

PubMed

Koksal, Ahmet Sertol; Er, Orhan; Evirgen, Hayrettin; Yumusak, Nejat

2016-06-01

Clinical decision support systems (C-DSS) provide supportive tools to the expert for the determination of the disease. Today, many of the support systems, which have been developed for a better and more accurate diagnosis, have reached a dynamic structure due to artificial intelligence techniques. However, in cases when important diagnosis studies should be performed in secret, a secure communication system is required. In this study, secure communication of a DSS is examined through a developed double layer chaotic communication system. The developed communication system consists of four main parts: random number generator, cascade chaotic calculation layer, PCM, and logical mixer layers. Thanks to this system, important patient data created by DSS will be conveyed to the center through a secure communication line.

Prevalence and Risk Factors of Obesity among Elderly Attending Geriatric Outpatient Clinics in Mansoura City

ERIC Educational Resources Information Center

Shebl, Amany Mohamed; Hatata, El Sayed Zaki; Boughdady, Aziza Mahmoud; El-Sayed, Sally Mohammed

2015-01-01

Obesity is a major public health problem affecting all ages in both developed and developing countries. It is considered the fifth leading risk factor for deaths all over the world as about 2.8 million people die due to obesity each year directly or indirectly. Obesity in elderly is considered one of the most serious public health challenges for…

Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria

PubMed Central

Valtonen, Ville

2017-01-01

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient’s history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS. PMID:28848553

Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria.

PubMed

Valtonen, Ville

2017-01-01

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient's history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.

Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion

PubMed Central

Dang, Tam; Nguyen, Cham

2017-01-01

Despite the risk of cyanide toxicity and lack of efficacy, amygdalin is still used as alternative cancer treatment. Due to the highly lethal nature of cyanide toxicity, many patients die before getting medical care. Herein, we describe the case of a 73-year-old female with metastatic pancreatic cancer who developed cyanide toxicity from taking amygdalin. Detailed history and physical examination prompted rapid clinical recognition and treatment with hydroxocobalamin, leading to resolution of her cyanide toxicity. Rapid clinical diagnosis and treatment of cyanide toxicity can rapidly improve patients' clinical outcome and survival. Inquiries for any forms of ingestion should be attempted in patients with clinical signs and symptoms suggestive of poisoning. PMID:28912981

Hemoglobin-Based Oxygen Carrier (HBOC) Development in Trauma: Previous Regulatory Challenges, Lessons Learned, and a Path Forward.

PubMed

Keipert, Peter E

2017-01-01

Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist ® (BAXTER), Hemopure ® (BIOPURE) and PolyHeme ® (NORTHFIELD) for resuscitating hypotensive shock. These trials all failed due to safety concerns (e.g., cardiac events, mortality) and certain protocol design limitations. In 2008 the Food and Drug Administration (FDA) put all HBOC trials in the US on clinical hold due to the unfavorable benefit:risk profile demonstrated by various HBOCs in different clinical studies in a meta-analysis published by Natanson et al. (2008). During standard resuscitation in trauma, organ dysfunction and failure can occur due to ischemia in critical tissues, which can be detected by the degree of lactic acidosis. SANGART'S Phase 2 trauma program with MP4OX therefore added lactate >5 mmol/L as an inclusion criterion to enroll patients who had lost sufficient blood to cause a tissue oxygen debt. This was key to the successful conduct of their Phase 2 program (ex-US, from 2009 to 2012) to evaluate MP4OX as an adjunct to standard fluid resuscitation and transfusion of RBCs. In 2013, SANGART shared their Phase 2b results with the FDA, and succeeded in getting the FDA to agree that a planned Phase 2c higher dose comparison study of MP4OX in trauma could include clinical sites in the US. Unfortunately, SANGART failed to secure new funding and was forced to terminate development and operations in Dec 2013, even though a regulatory path forward with FDA approval to proceed in trauma had been achieved.

Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations.

PubMed

Teraki, Y; Shibuya, M; Izaki, S

2010-10-01

Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant-related DIHS (n = 6). Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV-6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS. © 2009 The Author(s). Journal compilation © 2009 British Association of Dermatologists.

Estimating the Non-Monetary Burden of Neurocysticercosis in Mexico

PubMed Central

Bhattarai, Rachana; Budke, Christine M.; Carabin, Hélène; Proaño, Jefferson V.; Flores-Rivera, Jose; Corona, Teresa; Ivanek, Renata; Snowden, Karen F.; Flisser, Ana

2012-01-01

Background Neurocysticercosis (NCC) is a major public health problem in many developing countries where health education, sanitation, and meat inspection infrastructure are insufficient. The condition occurs when humans ingest eggs of the pork tapeworm Taenia solium, which then develop into larvae in the central nervous system. Although NCC is endemic in many areas of the world and is associated with considerable socio-economic losses, the burden of NCC remains largely unknown. This study provides the first estimate of disability adjusted life years (DALYs) associated with NCC in Mexico. Methods DALYs lost for symptomatic cases of NCC in Mexico were estimated by incorporating morbidity and mortality due to NCC-associated epilepsy, and morbidity due to NCC-associated severe chronic headaches. Latin hypercube sampling methods were employed to sample the distributions of uncertain parameters and to estimate 95% credible regions (95% CRs). Findings In Mexico, 144,433 and 98,520 individuals are estimated to suffer from NCC-associated epilepsy and NCC-associated severe chronic headaches, respectively. A total of 25,341 (95% CR: 12,569–46,640) DALYs were estimated to be lost due to these clinical manifestations, with 0.25 (95% CR: 0.12–0.46) DALY lost per 1,000 person-years of which 90% was due to NCC-associated epilepsy. Conclusion This is the first estimate of DALYs associated with NCC in Mexico. However, this value is likely to be underestimated since only the clinical manifestations of epilepsy and severe chronic headaches were included. In addition, due to limited country specific data, some parameters used in the analysis were based on systematic reviews of the literature or primary research from other geographic locations. Even with these limitations, our estimates suggest that healthy years of life are being lost due to NCC in Mexico. PMID:22363827

Arden Syntax Clinical Foundation Framework for Event Monitoring in Intensive Care Units: Report on a Pilot Study.

PubMed

de Bruin, Jeroen S; Zeckl, Julia; Adlassnig, Katharina; Blacky, Alexander; Koller, Walter; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

2017-01-01

The creation of clinical decision support systems has received a strong impulse over the last years, but their integration into a clinical routine has lagged behind, partly due to a lack of interoperability and trust by physicians. We report on the implementation of a clinical foundation framework in Arden Syntax, comprising knowledge units for (a) preprocessing raw clinical data, (b) the determination of single clinical concepts, and (c) more complex medical knowledge, which can be modeled through the composition and configuration of knowledge units in this framework. Thus, it can be tailored to clinical institutions or patients' caregivers. In the present version, we integrated knowledge units for several infection-related clinical concepts into the framework and developed a clinical event monitoring system over the framework that employs three different scenarios for monitoring clinical signs of bloodstream infection. The clinical event monitoring system was tested using data from intensive care units at Vienna General Hospital, Austria.

Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.

PubMed

Mansouri, Sepideh; Farahmand, Leila; Teymourzadeh, Azin; Majidzadeh-A, Keivan

2017-08-08

Despite prolonged disease-free survival and overall survival rates in estrogen receptor (ER)-positive patients undergoing adjuvant treatment, Tamoxifen therapy tends to fail due to eventual acquisition of resistance. Although numerous studies have emphasized the role of receptor tyrosine kinases (RTKs) in the development of Tamoxifen resistance, inadequate clinical evidence is available regarding the alteration of biomarker expression during acquired resistance, thus undermining the validity of the findings. Results of two meta-analyses investigating the effect of HER2 status on the prognosis of Tamoxifen-receiving patients have demonstrated that despite HER2-negative patients having longer disease-free survival; there is no difference in overhaul survival between the two groups. Furthermore, due to the intricate molecular interactions among estrogen receptors including ERα36, ERα66, and also RTKs, it is not surprising that RTK suppression does not restore Tamoxifen sensitivity. In considering such a complex network, we speculate that by the time HER2/EGFR is suppressed via targeted therapies, activation of ERα66 and ERα36 initiate molecular signaling pathways downstream of RTKs, thereby enhancing cell proliferation even in the presence of both Tamoxifen and RTK inhibitors. Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Erectile Dysfunction in the Older Adult Male.

PubMed

Mola, Joanna R

2015-01-01

Erectile dysfunction (ED) in the older adult male is a significant problem affecting more than 75% of men over 70 years of age in the United States. Older men have an increased likelihood of developing ED due to chronic disease, comorbid conditions, and age-related changes. Research has demonstrated that while the prevalence and severity of ED increases with age, sexual desire often remains unchanged. This article discusses the clinical picture of ED, including relevant pathophysiology, clinical presentation, and evaluation and treatment options.

Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

PubMed Central

Clausen, Ingelin; Glott, Thomas

2014-01-01

This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians. Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported. PMID:25248071

Development of clinically relevant implantable pressure sensors: perspectives and challenges.

PubMed

Clausen, Ingelin; Glott, Thomas

2014-09-22

This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV

PubMed Central

Kim, Michelle B.; Giesler, Kyle E.; Tahirovic, Yesim A.; Truax, Valarie M.; Liotta, Dennis C.; Wilson, Lawrence J.

2018-01-01

Introduction The chemokine receptor CCR5 has garnered significant attention in recent years as a target to treat HIV infection largely due to the approval and success of the drug Maraviroc. The side effects and inefficiencies with other first generation agents led to failed clinical trials, prompting the development of newer CCR5 antagonists. Areas covered This review aims to survey the current status of ‘next generation’ CCR5 antagonists in the preclinical pipeline with an emphasis on emerging agents for the treatment of HIV infection. These efforts have culminated in the identification of advanced second-generation agents to reach the clinic and the dual CCR5/CCR2 antagonist Cenicriviroc as the most advanced currently in phase II clinical studies. Expert opinion The clinical success of CCR5 inhibitors for treatment of HIV infection has rested largely on studies of Maraviroc and a second-generation dual CCR5/CCR2 antagonist Cenicriviroc. Although research efforts identified several promising preclinical candidates, these were dropped during early clinical studies. Despite patient access to Maraviroc, there is insufficient enthusiasm surrounding its use as front-line therapy for treatment of HIV. The non-HIV infection related development activities for Maraviroc and Cenicriviroc may help drive future interests. PMID:27791451

Development and psychometric testing of Holistic Clinical Assessment Tool (HCAT) for undergraduate nursing students.

PubMed

Wu, Xi Vivien; Enskär, Karin; Pua, Lay Hoon; Heng, Doreen Gek Noi; Wang, Wenru

2016-09-22

A major focus in nursing education is on the judgement of clinical performance, and it is a complex process due to the diverse nature of nursing practice. A holistic approach in assessment of competency is advocated. Difficulties in the development of valid and reliable assessment measures in nursing competency have resulted in the development of assessment instruments with an increase in face and content validity, but few studies have tested these instruments psychometrically. It is essential to develop a holistic assessment tool to meet the needs of the clinical education. The study aims to develop a Holistic Clinical Assessment Tool (HCAT) and test its psychometric properties. The HCAT was developed based on the systematic literature review and the findings of qualitative studies. An expert panel was invited to evaluate the content validity of the tool. A total of 130 final-year nursing undergraduate students were recruited to evaluate the psychometric properties (i.e. factor structure, internal consistency and test-retest reliability) of the tool. The HCAT has good content validity with content validity index of .979. The exploratory factor analysis reveals a four-factor structure of the tool. The internal consistency and test-retest reliability of the HCAT are satisfactory with Cronbach alpha ranging from .789 to .965 and Intraclass Correlation Coefficient ranging from .881 to .979 for the four subscales and total scale. HCAT has the potential to be used as a valid measure to evaluate clinical competence in nursing students, and provide specific and ongoing feedback to enhance the holistic clinical learning experience. In addition, HCAT functions as a tool for self-reflection, peer-assessment and guides preceptors in clinical teaching and assessment.

Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

PubMed Central

Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

2014-01-01

The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer’s disease trial samples by using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer’s disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods. PMID:24605808

Using EHR audit trail logs to analyze clinical workflow: A case study from community-based ambulatory clinics.

PubMed

Wu, Danny T Y; Smart, Nikolas; Ciemins, Elizabeth L; Lanham, Holly J; Lindberg, Curt; Zheng, Kai

2017-01-01

To develop a workflow-supported clinical documentation system, it is a critical first step to understand clinical workflow. While Time and Motion studies has been regarded as the gold standard of workflow analysis, this method can be resource consuming and its data may be biased due to the cognitive limitation of human observers. In this study, we aimed to evaluate the feasibility and validity of using EHR audit trail logs to analyze clinical workflow. Specifically, we compared three known workflow changes from our previous study with the corresponding EHR audit trail logs of the study participants. The results showed that EHR audit trail logs can be a valid source for clinical workflow analysis, and can provide an objective view of clinicians' behaviors, multi-dimensional comparisons, and a highly extensible analysis framework.

A Domain Analysis Model for eIRB Systems: Addressing the Weak Link in Clinical Research Informatics

PubMed Central

He, Shan; Narus, Scott P.; Facelli, Julio C.; Lau, Lee Min; Botkin, Jefferey R.; Hurdle, John F.

2014-01-01

Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. PMID:24929181

Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach.

PubMed

Cokelaere, Stefan; Malda, Jos; van Weeren, René

2016-08-01

Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the established and emerging surgical techniques employed for cartilage repair in horses. Through a growing insight in surgical cartilage repair possibilities, surgeons might be more stimulated to explore novel techniques in a clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Organising an investigation site: a national training reference document].

PubMed

Cornu, Catherine; David, Frédérique; Duchossoy, Luc; Hansel-Esteller, Sylvie; Bertoye, Pierre-Henri; Giacomino, Alain; Mouly, Stéphane; Diebolt, Vincent; Blazejewski, Sylvie

2014-01-01

Several surveys have shown a declining performance of French investigators in conducting clinical trials. This is partly due to insufficient and heterogeneous investigator training and site organisation. A multidisciplinary group was set up to propose solutions. We describe the tools developed to improve study site organisation. This working group was made up of clinical research experts from academia, industry, drug regulatory authorities, general practice, and consulting. Methods and tools were developed to improve site organisation. The proposed tools mainly focus on increasing investigators' awareness of their responsibilities, their research environment, the importance of a thorough feasibility analysis, and the implementation of active patient recruitment strategies. These tools should be able to improve site organisation and performances in conducting clinical trials. © 2014 Société Française de Pharmacologie et de Thérapeutique.

DoD Alcohol and Substance Abuse Consortium Award

DTIC Science & Technology

2016-10-01

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

Targeting forkhead box transcription factors FOXM1 and FOXO in leukemia (Review).

PubMed

Zhu, Hong

2014-10-01

Deregulation of forkhead box (FOX) proteins has been found in many genetic diseases and malignancies including leukemia. Leukemia is a common neoplastic disease of the blood or bone marrow characterized by the presence of immature leukocytes and is one of the leading causes of death due to cancer. Forkhead transcription factors, FOXM1 and FOXO family members (FOXOs), are important mediators in leukemia development. Aberrant expression of FOXM1 and FOXOs results in leukemogenesis. Usually the expression of FOXM1 is upregulated, whereas the expression of FOXOs is downregulated due to phosphorylation, nuclear exclusion and degradation in leukemia. On the one hand, FOXOs are bona fide tumor suppressors, on the other hand, active FOXOs maintain leukemia stem cells and stimulate drug resistance genes, contributing to leukemogenesis. FOXM1 and FOXOs have been proven to be potential targets for the development of leukemia therapeutics. They are also valuable diagnostic and prognostic markers in leukemia for clinical applications. This review summarizes the present knowledge concerning the molecular mechanisms by which FOXM1 and FOXOs modulate leukemogenesis and leukemia development, the clinical relevance of these FOX proteins in leukemia and related areas that warrant further investigation.

[Gonioscopy - How, Why, What for?

PubMed

Unterlauft, J D

2017-08-01

Aim Gonioscopy is used to exam the anterior chamber angle and the neighbouring structures. Gonioscopy can be performed using a contact lens, with the patient sitting at the slit lamp or in a supine position. Due to the total inner reflection of the cornea, the anterior chamber angle would otherwise be invisible in a healthy eye. During normal daily clinical routine, gonioscopy is often omitted, due to lack of time, although additional information could be gained. Materials and Methods The aim is to give a summary of the diagnostic possibilities using gonioscopy and to emphasise the importance of this relatively easy clinical method. Results The development of gonioscopy, the appropriate tools, proper procedure at the slit lamp and the most popular grading systems are described. In addition, an overview of detectable pathological changes in the anterior chamber angle is given and future prospects about developments in gonioscopy. Conclusion Gonioscopy can provide additional information otherwise missed by slit lamp examination or ophthalmoscopy alone. Up to now, no (semi-)automatic devices have been developed which could completely replace gonioscopy. Therefore gonioscopy remains an important part of a complete ophthalmological examination and should be learned, mastered and performed regularly by every ophthalmologist. Georg Thieme Verlag KG Stuttgart · New York.

EUCAST breakpoints for antifungals.

PubMed

Rodríguez-Tudela, Juan L; Arendrup, Maiken C; Cuenca-Estrella, Manuel; Donnelly, J Peter; Lass-Flörl, Cornelia

2010-03-01

Susceptibility testing of fungi and development of interpretative breakpoints has become increasingly important due to the growing incidence of invasive fungal infections, the number and classes of antifungals, and the emerging reports of acquired resistance. The subcommittee on antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST) has developed standards for susceptibility testing of fermentative yeasts and molds as well as proposing breakpoints for fluconazole and voriconazole against Candida. The aim of this work is to describe the EUCAST process of setting breakpoints for antifungals. Five aspects are evaluated during the process of developing breakpoints: 1) the most common dosage used in each European country, 2) the definition of the wild-type population for each target microorganism at the species level and the determination of epidemiological cutoffs, 3) the drug's pharmacokinetics and 4) pharmacodynamics, including Monte Carlo simulations, and 5) the correlation of MICs with clinical outcome of patients treated with the compound. When insufficient data are available (e.g., due to lack of information on the clinical outcome of infections caused by isolates with an elevated MIC), epidemiological cutoff values, rather than breakpoints, are recommended until the necessary information becomes available. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Radioprotective Agents: Strategies and Translational Advances.

PubMed

Kamran, Mohammad Zahid; Ranjan, Atul; Kaur, Navrinder; Sur, Souvik; Tandon, Vibha

2016-05-01

Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed. © 2016 Wiley Periodicals, Inc.

On- and off-line monitoring of ion beam treatment

NASA Astrophysics Data System (ADS)

Parodi, Katia

2016-02-01

Ion beam therapy is an emerging modality for high precision radiation treatment of cancer. In comparison to conventional radiation sources (photons, electrons), ion beams feature major dosimetric advantages due to their finite range with a localized dose deposition maximum, the Bragg peak, which can be selectively adjusted in depth. However, due to several sources of treatment uncertainties, full exploitation of these dosimetric advantages in clinical practice would require the possibility to visualize the stopping position of the ions in vivo, ideally in real-time. To this aim, different imaging methods have been proposed and investigated, either pre-clinically or even clinically, based on the detection of prompt or delayed radiation following nuclear interaction of the beam with the irradiated tissue. However, the chosen or ad-hoc developed instrumentation has often relied on technologies originally conceived for different applications, thus compromising on the achievable performances for the sake of cost-effectiveness. This contribution will review major examples of used instrumentation and related performances, identifying the most promising detector developments for next generation devices especially dedicated to on-line monitoring of ion beam treatment. Moreover, it will propose an original combination of different techniques in a hybrid detection scheme, aiming to make the most of complementary imaging methods and open new perspectives of image guidance for improved precision of ion beam therapy.

Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials.

PubMed

Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) was the 12 th and 11 th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds.

Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials

PubMed Central

Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds. PMID:29367867

Cruciate retaining and cruciate substituting ultra-congruent insert

PubMed Central

Deledda, Davide; Rosso, Federica; Ratto, Nicola; Bruzzone, Matteo; Bonasia, Davide Edoardo; Rossi, Roberto

2016-01-01

The posterior cruciate ligament (PCL) conservation and the polyethylene insert constraint in total knee arthroplasty (TKA) are still debated. The PCL is one of the primary stabilizers of the joint, but cruciate retaining (CR) implants have the disadvantage of a difficult balancing of the PCL. Postero-stabilized (PS) implants were introduced to reduce this problem. However, also the PS implants have some disadvantages, due to the cam-mechanism, such as high risk of cam-mechanism polyethylene wear. To minimize the polyethylene wear of the cam-mechanism and the bone sacrifice due to the intercondylar box, different types of inserts were developed, trying to increase the implant conformity and to reduce stresses on the bone-implant interface. In this scenario ultra-congruent (UC) inserts were developed. Those inserts are characterized by a high anterior wall and a deep-dished plate. This conformation should guarantee a good stability without the posterior cam. Few studies on both kinematic and clinical outcomes of UC inserts are available. Clinical and radiological outcomes, as well as kinematic data are similar between UC mobile bearing (MB) and standard PS MB inserts at short to mid-term follow-up. In this manuscript biomechanics and clinical outcomes of UC inserts will be described, and they will be compared to standard PS or CR inserts. PMID:26855938

Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A.

PubMed

Kobayashi, Tetsuro; Hayakawa, Kayoko; Mawatari, Momoko; Mezaki, Kazuhisa; Takeshita, Nozomi; Kutsuna, Satoshi; Fujiya, Yoshihiro; Kanagawa, Shuzo; Ohmagari, Norio; Kato, Yasuyuki; Morita, Masatomo

2014-07-20

Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections.

Jumping into the healthcare retail market: our experience.

PubMed

Pollert, Pat; Dobberstein, Darla; Wiisanen, Ronald

2008-01-01

Who among us has not heard of the retail-based clinic concept? Retail-based clinics have been springing up across the country in Target, Walmart, grocery stores, drugstores, and shopping malls. Due to multiple marketplace issues, others who have not traditionally been providers of healthcare saw an opportunity to meet the consumer's demand. Do retail and healthcare mix, and can this model be successful? MeritCare Health System in Fargo, ND made the decision to embrace and experiment with this new emerging consumerism model. This article reviews our experience in developing the first retail-based clinic in our service area and the state of North Dakota.

Platelet-rich fibrin application in dentistry: a literature review.

PubMed

Borie, Eduardo; Oliví, Daniel García; Orsi, Iara Augusta; Garlet, Katia; Weber, Benjamín; Beltrán, Víctor; Fuentes, Ramón

2015-01-01

The development of bioactive surgical additives to regulate the inflammation and increase the speed of healing process is one of the great challenges in clinical research. In this sense, platelet rich fibrin (PRF) appears as a natural and satisfactory alternative with favorable results and low risks. The following review attempts to summarize the relevant literature regarding the technique of using PRF, focusing on its preparation, advantages, and disadvantages of using it in clinical applications. PRF alone or in combination with other biomaterials seems to have several advantages and indications both for medicine and dentistry, due it is a minimally invasive technique with low risks and satisfactory clinical results.

Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

PubMed

Hansma, Patrick; Diaz, Francisco J; Njiwaji, Chantel

2016-03-01

Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

Visual Versus Fully Automated Analyses of 18F-FDG and Amyloid PET for Prediction of Dementia Due to Alzheimer Disease in Mild Cognitive Impairment.

PubMed

Grimmer, Timo; Wutz, Carolin; Alexopoulos, Panagiotis; Drzezga, Alexander; Förster, Stefan; Förstl, Hans; Goldhardt, Oliver; Ortner, Marion; Sorg, Christian; Kurz, Alexander

2016-02-01

Biomarkers of Alzheimer disease (AD) can be imaged in vivo and can be used for diagnostic and prognostic purposes in people with cognitive decline and dementia. Indicators of amyloid deposition such as (11)C-Pittsburgh compound B ((11)C-PiB) PET are primarily used to identify or rule out brain diseases that are associated with amyloid pathology but have also been deployed to forecast the clinical course. Indicators of neuronal metabolism including (18)F-FDG PET demonstrate the localization and severity of neuronal dysfunction and are valuable for differential diagnosis and for predicting the progression from mild cognitive impairment (MCI) to dementia. It is a matter of debate whether to analyze these images visually or using automated techniques. Therefore, we compared the usefulness of both imaging methods and both analyzing strategies to predict dementia due to AD. In MCI participants, a baseline examination, including clinical and imaging assessments, and a clinical follow-up examination after a planned interval of 24 mo were performed. Of 28 MCI patients, 9 developed dementia due to AD, 2 developed frontotemporal dementia, and 1 developed moderate dementia of unknown etiology. The positive and negative predictive values and the accuracy of visual and fully automated analyses of (11)C-PiB for the prediction of progression to dementia due to AD were 0.50, 1.00, and 0.68, respectively, for the visual and 0.53, 1.00, and 0.71, respectively, for the automated analyses. Positive predictive value, negative predictive value, and accuracy of fully automated analyses of (18)F-FDG PET were 0.37, 0.78, and 0.50, respectively. Results of visual analyses were highly variable between raters but were superior to automated analyses. Both (18)F-FDG and (11)C-PiB imaging appear to be of limited use for predicting the progression from MCI to dementia due to AD in short-term follow-up, irrespective of the strategy of analysis. On the other hand, amyloid PET is extremely useful to rule out underlying AD. The findings of the present study favor a fully automated method of analysis for (11)C-PiB assessments and a visual analysis by experts for (18)F-FDG assessments. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Digital holographic otoscope for measurements of the human tympanic membrane in vivo

NASA Astrophysics Data System (ADS)

Dobrev, I.; Harrington, E. J.; Cheng, T.; Furlong, C.; Rosowski, J. J.

We are developing an advanced computer-controlled digital optoelectronic holographic system (DOEHS) for diagnosing middle-ear conductive disorders and investigating the causes of failure of middle-ear surgical procedures. Our current DOEHS system can provide near real-time quantitative measurements of the sound-induced nano-meter scale motion of the eardrum. The DOEHS have been deployed and is currently being tested in clinical conditions, where it is being optimized for in-vivo measurements of patients. The stability of the measurement system during examination is crucial as the non-ideal clinical environment presents disturbances larger than the measured quantities from several domains - thermal, optical, electrical and mechanical. Examples include disturbances are due to heartbeat breathing, patients head's motion as well as environment induced mechanical disturbances (0.1-60Hz, 0.01-100 μm). In this paper we focus on our current progress in the analysis and implementation of various acquisition strategies and algorithms for minimization of the measurement error due to mechanical disturbances in a clinic. We have also developed and implemented a versatile and modular otoscope head (OH) design providing a variety of capabilities for acoustic and displacement measurements of both post-mortem samples of varying sizes (1-12mm) as well as in-vivo examination of patients. The OH offers hybrid on-axis and off axis digital Furrier holographic setup for high resolution (λ/35) 4 phase step measurements as well as fast (<0.1ms) single frame measurements for improved performance in the clinical environment. We also focus on the development of a mechatronic positioning system (MOP) for aiding in the localization of the TM in patients.

Development of a public health reporting data warehouse: lessons learned.

PubMed

Rizi, Seyed Ali Mussavi; Roudsari, Abdul

2013-01-01

Data warehouse projects are perceived to be risky and prone to failure due to many organizational and technical challenges. However, often iterative and lengthy processes of implementation of data warehouses at an enterprise level provide an opportunity for formative evaluation of these solutions. This paper describes lessons learned from successful development and implementation of the first phase of an enterprise data warehouse to support public health surveillance at British Columbia Centre for Disease Control. Iterative and prototyping approach to development, overcoming technical challenges of extraction and integration of data from large scale clinical and ancillary systems, a novel approach to record linkage, flexible and reusable modeling of clinical data, and securing senior management support at the right time were the main factors that contributed to the success of the data warehousing project.

Novel therapeutic approaches in chondrosarcoma.

PubMed

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

2017-03-01

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

Defining quality health care with outcomes assessment while achieving economic value.

PubMed

Shaw, L J; Miller, D D

2000-02-01

The effectiveness of a procedure is increasingly guided by the evaluation of patient outcomes. Outcomes data is used to develop clinical pathways of care and to define appropriate resource-use levels without sacrificing quality of care. Integration of the economic implications of medical services into an outcome-based guideline allows for the development of disease-management strategies. In cardiovascular medicine, risk reduction is associated with high cost due to the "pay-back" of new technologies and therapies. A major challenge is to define a balance between "high tech" care and cost. This paper devises an outpatient evidence-based guideline using clinical and economic outcomes data for the diagnosis of coronary disease.

[Molecular techniques in mycology].

PubMed

Rodríguez-Tudela, Juan Luis; Cuesta, Isabel; Gómez-López, Alicia; Alastruey-Izquierdo, Ana; Bernal-Martínez, Leticia; Cuenca-Estrella, Manuel

2008-11-01

An increasing number of molecular techniques for the diagnosis of fungal infections have been developed in the last few years, due to the growing prevalence of mycoses and the length of time required for diagnosis when classical microbiological methods are used. These methods are designed to resolve the following aspects of mycological diagnosis: a) Identification of fungi to species level by means of sequencing relevant taxonomic targets; b) early clinical diagnosis of invasive fungal infections; c) detection of molecular mechanisms of resistance to antifungal agents; and d) molecular typing of fungi. Currently, these methods are restricted to highly developed laboratories. However, some of these techniques will probably be available in daily clinical practice in the near future.

Aspiration in children and adolescents with neurogenic dysphagia: comparison of clinical judgment and fiberoptic endoscopic evaluation of swallowing.

PubMed

Beer, Sabrina; Hartlieb, Till; Müller, Arnd; Granel, Michael; Staudt, Martin

2014-12-01

A total of 30 children and adolescents with dysphagia due to various chronic neurological disorders were assessed for their risk of aspiration. This assessment was performed clinically by experienced speech and swallowing therapists, and verified thereafter by fiberoptic endoscopy. We found the clinical judgment to be correct in only 70% (for aspiration of saliva), 55% (of puree), and 67% (of thin liquids). We conclude that, because of this unacceptably high error rate of clinical assessment, a fiberoptic evaluation of swallowing is a necessary diagnostic step both for the planning of therapy and for the development of feeding strategies in children and adolescents with neurogenic dysphagia. Georg Thieme Verlag KG Stuttgart · New York.

Development and testing of indicators to measure coordination of clinical information and management across levels of care.

PubMed

Aller, Marta-Beatriz; Vargas, Ingrid; Coderch, Jordi; Calero, Sebastià; Cots, Francesc; Abizanda, Mercè; Farré, Joan; Llopart, Josep Ramon; Colomés, Lluís; Vázquez, María Luisa

2015-08-13

Coordination across levels of care is becoming increasingly important due to rapid advances in technology, high specialisation and changes in the organization of healthcare services; to date, however, the development of indicators to evaluate coordination has been limited. The aim of this study is to develop and test a set of indicators to comprehensively evaluate clinical coordination across levels of care. A systematic review of literature was conducted to identify indicators of clinical coordination across levels of care. These indicators were analysed to identify attributes of coordination and classified accordingly. They were then discussed within an expert team and adapted or newly developed, and their relevance, scientific soundness and feasibility were examined. The indicators were tested in three healthcare areas of the Catalan health system. 52 indicators were identified addressing 11 attributes of clinical coordination across levels of care. The final set consisted of 21 output indicators. Clinical information transfer is evaluated based on information flow (4) and the adequacy of shared information (3). Clinical management coordination indicators evaluate care coherence through diagnostic testing (2) and medication (1), provision of care at the most appropriate level (2), completion of diagnostic process (1), follow-up after hospital discharge (4) and accessibility across levels of care (4). The application of indicators showed differences in the degree of clinical coordination depending on the attribute and area. A set of rigorous and scientifically sound measures of clinical coordination across levels of care were developed based on a literature review and discussion with experts. This set of indicators comprehensively address the different attributes of clinical coordination in main transitions across levels of care. It could be employed to identify areas in which health services can be improved, as well as to measure the effect of efforts to improve clinical coordination in healthcare organizations.

Design principles for simulation games for learning clinical reasoning: A design-based research approach.

PubMed

Koivisto, J-M; Haavisto, E; Niemi, H; Haho, P; Nylund, S; Multisilta, J

2018-01-01

Nurses sometimes lack the competence needed for recognising deterioration in patient conditions and this is often due to poor clinical reasoning. There is a need to develop new possibilities for learning this crucial competence area. In addition, educators need to be future oriented; they need to be able to design and adopt new pedagogical innovations. The purpose of the study is to describe the development process and to generate principles for the design of nursing simulation games. A design-based research methodology is applied in this study. Iterative cycles of analysis, design, development, testing and refinement were conducted via collaboration among researchers, educators, students, and game designers. The study facilitated the generation of reusable design principles for simulation games to guide future designers when designing and developing simulation games for learning clinical reasoning. This study makes a major contribution to research on simulation game development in the field of nursing education. The results of this study provide important insights into the significance of involving nurse educators in the design and development process of educational simulation games for the purpose of nursing education. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel drugs in clinical development for hepatocellular carcinoma.

PubMed

Waidmann, Oliver; Trojan, Jörg

2015-01-01

Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit. This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC. In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

White Paper: Interventional MRI: Current Status and Potential for Development Considering Economic Perspectives, Part 2: Liver and Other Applications in Oncology.

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

2017-11-01

Background  MRI is attractive for guiding and monitoring interventional procedures due to its high intrinsic soft tissue contrast and the possibility to measure flow and cardiac function. Methods  Technical solutions have been developed for all procedural steps including imaging guidance, MR-safe catheters and instruments and patient monitoring. This has led to widening of the clinical applications. Interventional MRI is becoming increasingly important for the treatment of patients suffering from malignant diseases. The detectability of masses and consequently their accessibility for biopsy is higher, compared to other modalities, due to the high intrinsic soft tissue contrast of MRI. Temperature-dependent sequences allow for minimally invasive and tissue-sparing ablation (A-0 ablation). Conclusion  Interventional MRI has become established in the clinical routine for a variety of indications, including biopsies and tumor ablation. Since the economic requirement of covering costs by reimbursement is met and interventional MRI decreases the mortality and morbidity of interventional procedures, broader application of interventional MRI can be expected in the clinical routine in the future. Key points   · Particularly for the treatment of oncological patients, interventional MRI is superior to other methods with respect to minimal invasiveness and tissue protection due to the ability to exactly determine tumor borders and to visualize and control the size of the ablation area on the basis of MR temperature measurement.. · Due to the better visualization of targets and the effects of ablation in tissue, interventional MRI can lower the mortality and morbidity associated with these interventions for many indications.. · The complex comparison of costs and reimbursement shows that this application can be performed in a cost-covering manner and broader 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 2: Liver and Other Applications in Oncology. Fortschr Röntgenstr 2017; 189: 1047 - 1054. © Georg Thieme Verlag KG Stuttgart · New York.

Parastomal hernias after radical cystectomy and ileal conduit diversion

PubMed Central

Donahue, Timothy F.

2016-01-01

Parastomal hernia, defined as an "incisional hernia related to an abdominal wall stoma", is a frequent complication after conduit urinary diversion that can negatively impact quality of life and present a clinically significant problem for many patients. Parastomal hernia (PH) rates may be as high as 65% and while many patients are asymptomatic, in some series up to 30% of patients require surgical intervention due to pain, leakage, ostomy appliance problems, urinary obstruction, and rarely bowel obstruction or strangulation. Local tissue repair, stoma relocation, and mesh repairs have been performed to correct PH, however, long-term results have been disappointing with recurrence rates of 30%–76% reported after these techniques. Due to high recurrence rates and the potential morbidity of PH repair, efforts have been made to prevent PH development at the time of the initial surgery. Randomized trials of circumstomal prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have shown significant reductions in PH rates with acceptably low complication profiles. We have placed prophylactic mesh at the time of ileal conduit creation in patients at high risk for PH development and found it to be safe and effective in reducing the PH rates over the short-term. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors associated with its development, and the use of prophylactic mesh placement for patients undergoing ileal conduit urinary diversion with the intent of reducing PH rates. PMID:27437533

[Clinical and neurologic characteristic and principles of therapy of late-onset Myasthenia gravis].

PubMed

Kosachev, V D; Alekseeva, T M; Khalmurzina, A N

2016-01-01

In the present work the results of the clinic-epidemiological analysis of 223 patients with the onset of the myasthenia at 60 y. o. and later, admitted and treated in the clinic of neurology for the passed 25years are represented. A dynamic growth of incidence of the late-onset myasthenia through the passed 10 years was administered. We administered a prevalence of the generalized form of the myasthenia gravis (61,5 %). The whole clinical table of the myasthenia was developed during an year in 76,7 % of the cases. A wide range of the concomitant somatic pathology in this group of the patients (especially, with a cardio-vascular pathology - 93,3 %) was found to worsen the course of the myasthenia itself. We found that the set of the therapeutic measures in myasthenia in the elderly is determined by the course of the myasthenia and the multiple organ failure due to the concomitant diseases. The scheme of complex corrective therapy of myasthenia gravis in elderly was developed.

[Update on congenital and neonatal herpes infections: infection due to cytomegalovirus and herpes simplex].

PubMed

Baquero-Artigao, F

2017-05-17

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.

Diagnostic criteria, severity classification and guidelines of systemic sclerosis.

PubMed

Asano, Yoshihide; Jinnin, Masatoshi; Kawaguchi, Yasushi; Kuwana, Masataka; Goto, Daisuke; Sato, Shinichi; Takehara, Kazuhiko; Hatano, Masaru; Fujimoto, Manabu; Mugii, Naoki; Ihn, Hironobu

2018-06-01

Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. © 2018 Japanese Dermatological Association.

Parasitic infections in sickle cell crisis: Nigerian experience.

PubMed Central

Sodipo, J. O.; Padgett, D.; Warrie, E.; Olopoenia, L.

1997-01-01

Data collected on 150 sickle cell patients in Nigeria were analyzed to determine the frequency of parasitic infections in clinical and hematologic crisis. Fifty-three adult and 97 pediatric patients (mean age: 27.6 years and 9.7 years, respectively) were studied. Of these patients, 82 were males and 68 females. One hundred thirty-nine had the SS and 11 the SC genotype. Blood samples collected from patients on admission for sickle cell-related illnesses were examined microscopically for evidence of Plasmodium sp, and stool samples were analyzed for presence of any helminth. A total of 102 parasitic infections associated with clinical cases of sickle cell crisis were recorded (malaria, 36[35.3%]; helminths, 49 ([48%]; and malaria and helminths together, 17 [16.7%]). Of the 49 helminthic infections, 26 (53.1%) were due to Ascaris lumbricoides, 15 (30.6%) were due to hookworms, 7 (14.3%) were due to Trichuris trichiura, and 1 (2%) was due to Strongyloides stercoralis. The mean hemoglobin levels during clinical crisis were 7.1 g/dL for helminths, 6.4 g/dL for malaria, and 6.1 g/dL for malaria and helminths together. Reticulocyte counts were 1.4% for helminths, 1.5% for malaria, and 1.2% for both malaria and helminths together. Severity and duration of the clinical crisis were longer for events associated with a single parasitic organism infection than for those with multiple organisms. Routine blood smear examination for malaria and stool analysis should be included in the laboratory evaluation of individuals with sickle cell anemia in developing countries as these infestations could play an important role in precipitating a crisis. PMID:9145635

Medicinal plants and phytochemicals with anti-obesogenic potentials: A review.

PubMed

Mopuri, Ramgopal; Islam, Md Shahidul

2017-05-01

Human mortality has been significantly increased in last few decades due to the increased prevalence of obesity and associated chronic disorders such as type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease and atherosclerosis. Apart from genetic and medicine or drug related side effects, nearly 90-95% people became obese due to the imbalanced calorie intake and lack of nutritional knowledge. The anti-obesogenic drugs, Orlistat and Sibutramine, which have been duly approved by Food and Drug Administration (FDA), USA, work very well on diet-induced obesity however they are not getting popular to the people with overweight/obesity due to the higher cost and severe side effects. In contrast, plant based drugs have been considered as a better alternative due to their lower cost and negligible side effects. A number of medicinal plants and their bioactive constituents have received attention from scientists not only for their anti-obesity activity in vitro and in vivo but also in clinical trials. However, there is no systematic review of data available in the scientific domain in order to guide researchers to conduct further in depth research. In our present review, we differentiated the anti-obesogenic effects of various medicinal plant extracts, fractions and their bioactive compounds at in vitro, in vivo and clinical conditions. During our review, we could also identify the most effective plants with strong anti-obesogenic effects at in vitro or in vivo studies with lack of clinical trials when no one tried to isolate pure bioactive compounds from these plants. Hence, scientific community, government agencies/pharmaceutical industries should work together not only to isolate pure bioactive compounds but also to conduct clinical trials including toxicity to develop better alternative anti-obesity drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases.

PubMed

Bo, Ryosuke; Yamada, Kenji; Kobayashi, Hironori; Jamiyan, Purevsuren; Hasegawa, Yuki; Taketani, Takeshi; Fukuda, Seiji; Hata, Ikue; Niida, Yo; Shigematsu, Yosuke; Iijima, Kazumoto; Yamaguchi, Seiji

2017-09-01

Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is often reported in Caucasian countries due to a common mutation. However, the molecular and clinical basis of complete TFP deficiency has not been extensively reported. In this study, 14 Japanese cases (13 families) with complete TFP deficiency, including 9 previously reported cases, were analyzed to clarify the clinical and molecular characteristics of TFP deficiency. The clinical types of the 14 patients were as follows: 12 cases of neonatal (n=7) or myopathic (n=5) types and 2 cases of intermediate type. Peripheral neuropathy was found in four cases and hypocalcemia due to hypoparathyroidism, which is rarely reported in Caucasian patients, had developed in four cases. Maternal hemolysis, elevated liver enzymes and low platelet count syndrome and acute fatty liver of pregnancy were noted in two and one mothers, respectively. Fourteen mutations were identified in 26 alleles in Japanese patients, including two novel mutations (HADHA: c.361C>T, and HADHA-HADHB: g.26233880_ 26248855del), although no common mutations were found. This study suggests that the molecular and clinical aspects of Japanese patients with TFP deficiencies differ from those of Caucasian patients.

Development and implementation of a psychotherapy tracking database in primary care.

PubMed

Craner, Julia R; Sawchuk, Craig N; Mack, John D; LeRoy, Michelle A

2017-06-01

Although there is a rapid increase in the integration of behavioral health services in primary care, few studies have evaluated the effectiveness of these services in real-world clinical settings, in part due to the difficulty of translating traditional mental health research designs to this setting. Accordingly, innovative approaches are needed to fit the unique challenges of conducting research in primary care. The development and implementation of one such approach is described in this article. A continuously populating database for psychotherapy services was implemented across 5 primary care clinics in a large health system to assess several levels of patient care, including service utilization, symptomatic outcomes, and session-by-session use of psychotherapy principles by providers. Each phase of implementation revealed challenges, including clinician time, dissemination to clinics with different resources, and fidelity of data collection strategy across providers, as well as benefits, including the generation of useful data to inform clinical care, program development, and empirical research. The feasible and sustainable implementation of data collection for routine clinical practice in primary care has the potential to fuel the evidence base around integrated care. The current project describes the development of an innovative approach that, with further empirical study and refinement, could enable health care professionals and systems to understand their population and clinical process in a way that addresses essential gaps in the integrated care literature. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Application of an oligonucleotide microarray-based nano-amplification technique for the detection of fungal pathogens.

PubMed

Lu, Weiping; Gu, Dayong; Chen, Xingyun; Xiong, Renping; Liu, Ping; Yang, Nan; Zhou, Yuanguo

2010-10-01

The traditional techniques for diagnosis of invasive fungal infections in the clinical microbiology laboratory need improvement. These techniques are prone to delay results due to their time-consuming process, or result in misidentification of the fungus due to low sensitivity or low specificity. The aim of this study was to develop a method for the rapid detection and identification of fungal pathogens. The internal transcribed spacer two fragments of fungal ribosomal DNA were amplified using a polymerase chain reaction for all samples. Next, the products were hybridized with the probes immobilized on the surface of a microarray. These species-specific probes were designed to detect nine different clinical pathogenic fungi including Candida albicans, Candida tropocalis, Candida glabrata, Candida parapsilosis, Candida krusei, Candida lusitaniae, Candida guilliermondii, Candida keyfr, and Cryptococcus neoformans. The hybridizing signals were enhanced with gold nanoparticles and silver deposition, and detected using a flatbed scanner or visually. Fifty-nine strains of fungal pathogens, including standard and clinically isolated strains, were correctly identified by this method. The sensitivity of the assay for Candida albicans was 10 cells/mL. Ten cultures from clinical specimens and 12 clinical samples spiked with fungi were also identified correctly. This technique offers a reliable alternative to conventional methods for the detection and identification of fungal pathogens. It has higher efficiency, specificity and sensitivity compared with other methods commonly used in the clinical laboratory.

Clinical aspects of ECL-cell abnormalities.

PubMed Central

Hirschowitz, B. I.

1998-01-01

ECL cell hyperplasia results from hypergastrinemia, and in man this occurs due to achlorhydria in atrophic gastritis (pernicious anemia [PA]) and gastrinoma (Zollinger-Ellison syndrome [ZES]). Progression to neoplasia, i.e., ECL cell carcinoids (usually small, multicentric and non-functional), occurs in some five to 10 percent of patients with PA where they remain gastrin-dependent and reversible by normalization of serum gastrin by antrectomy. Even if untreated, the carcinoids are almost invariably benign and do not cause death. In ZES, ECL cell hyperplasia is progressive due to hypergastrinemia. However, carcinoids develop only in the MEN-I subtype but pose no additional threat of malignancy. A conservative approach is recommended for small multicentric carcinoids, and the tumors do not need removal. By contrast, single, large, non-gastrin-dependent carcinoids represent a different biological and clinical problem and are frequently malignant. PMID:10461361

[Sporadic Cerebral Amyloid Angiopathy: An Overview with Clinical Cases].

PubMed

Schöberl, F; Eren, O E; Wollenweber, F A; Kraus, T; Kellert, L

2016-09-01

Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in the elderly. Neuropathologically, it is characterized by deposition of amyloid-ß (Aß) in the wall of small to medium-sized arteries, capillaries and venules of the cerebral cortex and leptomeninges. Over the last years it was recognized as an important cause of spontaneous intracerebral hemorrhage and cognitive deficits in the elderly. The clinical and radiological manifestations are diverse ranging from acute onset focal neurological deficits due to intracerebral lobar hemorrhage to subacute progressive cognitive impairment due to Aß-mediated inflammation confluent subcortical edema. The wide clinico-radiological spectrum of CAA is a major challenge for the neurologist and stroke physician. This review provides a structured and detailed look at recent developments in CAA, and is illustrated with case studies. © Georg Thieme Verlag KG Stuttgart · New York.

[Consequences of the 12th AMG amendment on the conduct of non-commercial clinical trials].

PubMed

Rossion, I

2005-12-01

In 2004, the German Drug Law was reformed substantially putting into effect the European directive 2001/20/EG on Good Clinical Practice (GCP). Investigator initiated trials have to comply with the same requirements as clinical trials for drug development. When registered drugs are used in non-commercial clinical trials some simplifications are possible.Currently, all essential elements of GCP, such as financing of the trial, laying-down of sponsor responsibilities, establishing an extensive quality assurance system as well as immediate reporting of unexpected serious drug reactions, are stipulated by law. Since regulatory authorities and ethics committees have to approve every clinical trial, surveillance is reinforced. The new requirements cannot be met without sufficient financing, qualified personnel and professional structures for clinical trials. Compared to European partners, the research location Germany is at a disadvantage due to high administrative workload and costs.

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers

PubMed Central

Schott, Anne F.; Welch, John J.; Verschraegen, Claire F.; Kurzrock, Razelle

2015-01-01

Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible. PMID:26433554

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions.

PubMed

Ishikawa, Masayori; Yamamoto, Tetsuya; Matsumura, Akira; Hiratsuka, Junichi; Miyatake, Shin-Ichi; Kato, Itsuro; Sakurai, Yoshinori; Kumada, Hiroaki; Shrestha, Shubhechha J; Ono, Koji

2016-08-09

Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

PubMed Central

Jannin, J.; Moulia-Pelat, J. P.; Chanfreau, B.; Penchenier, L.; Louis, J. P.; Nzaba, P.; de La Baume, F. E.; Eozenou, P.; Cattand, P.

1993-01-01

A case-control study was carried out in the Congo to define a scoring system based on a number of clinical and epidemiological criteria of African trypanosomiasis due to Trypanosoma brucei gambiense which could be used by peripheral health services to establish a diagnosis. The survey comprised 163 cases and 326 controls. Clinical signs and symptoms were fever, headache, pruritus and skin lesions due to scratching, diarrhoea, oedema, cervical adenopathies, sleep rhythm disturbances, changes in appetite, amenorrhoea or impotence, mental confusion, neurological signs, and other minor clinical disturbances. Other criteria were a history of previous trypanosomiasis and the presence of domestic animals in the home environment. Analysis of the results showed that neither a single criterion nor a group of criteria is pathognomonic for the disease. The selected criteria do not allow discrimination of sleeping sickness patients among suspected individuals who present themselves. A scoring system is therefore of little use at the peripheral level of health services, particularly when considering the additional workload involved. The low diagnostic value of these clinical signs and symptoms and other indicators in African trypanosomiasis stresses the difficulty in developing an early warning tool for an integrated control strategy in primary health care. PMID:8490985

Medical Imaging Field of Magnetic Resonance Imaging: Identification of Specialties within the Field

ERIC Educational Resources Information Center

Grey, Michael L.

2009-01-01

This study was conducted to determine if specialty areas are emerging in the magnetic resonance imaging (MRI) profession due to advancements made in the medical sciences, imaging technology, and clinical applications used in MRI that would require new developments in education/training programs and national registry examinations. In this…

Evolving Science in Adolescence: Comment on Ellis et al. (2012)

ERIC Educational Resources Information Center

Dodge, Kenneth A.; Albert, Dustin

2012-01-01

Ellis et al. (2012) bring an evolutionary perspective to bear on adolescent risky behavioral development, clinical practice, and public policy. The authors offer important insights that (a) some risky behaviors may be adaptive for the individual and the species by being hard-wired due to fitness benefits and (b) interventions might be more…

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review

PubMed Central

Ogawa, Kohei; Mizuno, Ken-ichi; Shinagawa, Yoko; Kobayashi, Yuji; Abe, Hiroyuki; Watanabe, Yukari; Takahashi, Shunsaku; Hayashi, Kazunao; Yokoyama, Junji; Takeuchi, Manabu; Yamagiwa, Satoshi; Sato, Yuichi; Terai, Shuji

2016-01-01

Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently. PMID:27642293

Development of Nanoscale Approaches for Ovarian Cancer Therapeutics and Diagnostics

PubMed Central

Engelberth, Sarah A.; Hempel, Nadine; Bergkvist, Magnus

2014-01-01

Ovarian cancer is the deadliest of all gynecological cancers and the fifth leading cause of death due to cancer in women. This is largely due to late-stage diagnosis, poor prognosis related to advanced-stage disease, and the high recurrence rate associated with development of chemoresistance. Survival statistics have not improved significantly over the last three decades, highlighting the fact that improved therapeutic strategies and early detection require substantial improvements. Here, we review and highlight nanotechnology-based approaches that seek to address this need. The success of Doxil, a PEGylated liposomal nanoencapsulation of doxorubicin, which was approved by the FDA for use on recurrent ovarian cancer, has paved the way for the current wave of nanoparticle formulations in drug discovery and clinical trials. We discuss and summarize new nanoformulations that are currently moving into clinical trials and highlight novel nanotherapeutic strategies that have shown promising results in preclinical in vivo studies. Further, the potential for nanomaterials in diagnostic imaging techniques and the ability to leverage nanotechnology for early detection of ovarian cancer are also discussed. PMID:25271436

Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy.

PubMed

Fang, Ronnie H; Kroll, Ashley V; Zhang, Liangfang

2015-11-04

Immunotherapeutic approaches for treating cancer overall have been receiving a considerable amount of interest due to the recent approval of several clinical formulations. Among the different modalities, anticancer vaccination acts by training the body to endogenously generate a response against tumor cells. However, despite the large amount of work that has gone into the development of such vaccines, the near absence of clinically approved formulations highlights the many challenges facing those working in the field. The generation of potent endogenous anticancer responses poses unique challenges due to the similarity between cancer cells and normal, healthy cells. As researchers continue to tackle the limited efficacy of vaccine formulations, fresh and novel approaches are being sought after to address many of the underlying problems. Here the application of nanoparticle technology towards the development of anticancer vaccines is discussed. Specifically, there is a focus on the benefits of using such strategies to manipulate antigen presenting cells (APCs), which are essential to the vaccination process, and how nanoparticle-based platforms can be rationally engineered to elicit appropriate downstream immune responses. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Education and training for medicines development, regulation, and clinical research in emerging countries

PubMed Central

Kerpel-Fronius, Sandor; Rosenkranz, Bernd; Allen, Elizabeth; Bass, Rolf; Mainard, Jacques D.; Dodoo, Alex; Dubois, Dominique J.; Hela, Mandisa; Kern, Steven; Massud, Joao; Silva, Honorio; Whitty, Jeremy

2015-01-01

The aim of this satellite workshop held at the 17th World Congress of Basic and Clinical Pharmacology (WCP2014) was to discuss the needs, optimal methods and practical approaches for extending education and teaching of medicines development, regulation, and clinical research to Low and Middle Income Countries (LMICs). It was generally agreed that, for efficiently treating the rapidly growing number of patients suffering from non-communicable diseases, modern drug therapy has to become available more widely and with a shorter time lag in these countries. To achieve this goal many additional experts working in medicines development, regulation, and clinical research have to be trained in parallel. The competence-oriented educational programs designed within the framework of the European Innovative Medicine Initiative-PharmaTrain (IMI-PhT) project were developed with the purpose to cover these interconnected fields. In addition, the programs can be easily adapted to the various local needs, primarily due to their modular architecture and well defined learning outcomes. Furthermore, the program is accompanied by stringent quality assurance standards which are essential for providing internationally accepted certificates. Effective cooperation between international and local experts and organizations, the involvement of the industry, health care centers and governments is essential for successful education. The initiative should also support the development of professional networks able to manage complex health care strategies. In addition it should help establish cooperation between neighboring countries for jointly managing clinical trials, as well as complex regulatory and ethical issues. PMID:25926798

Cryopreservation and Revival of Human Mesenchymal Stromal Cells.

PubMed

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

2016-01-01

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

A business planning model to identify new safety net clinic locations.

PubMed

Langabeer, James; Helton, Jeffrey; DelliFraine, Jami; Dotson, Ebbin; Watts, Carolyn; Love, Karen

2014-01-01

Community health clinics serving the poor and underserved are geographically expanding due to changes in U.S. health care policy. This paper describes the experience of a collaborative alliance of health care providers in a large metropolitan area who develop a conceptual and mathematical decision model to guide decisions on expanding its network of community health clinics. Community stakeholders participated in a collaborative process that defined constructs they deemed important in guiding decisions on the location of community health clinics. This collaboration also defined key variables within each construct. Scores for variables within each construct were then totaled and weighted into a community-specific optimal space planning equation. This analysis relied entirely on secondary data available from published sources. The model built from this collaboration revolved around the constructs of demand, sustainability, and competition. It used publicly available data defining variables within each construct to arrive at an optimal location that maximized demand and sustainability and minimized competition. This is a model that safety net clinic planners and community stakeholders can use to analyze demographic and utilization data to optimize capacity expansion to serve uninsured and Medicaid populations. Communities can use this innovative model to develop a locally relevant clinic location-planning framework.

Antifungal resistance: current trends and future strategies to combat

PubMed Central

Wiederhold, Nathan P

2017-01-01

Antifungal resistance represents a major clinical challenge to clinicians responsible for treating invasive fungal infections due to the limited arsenal of systemically available antifungal agents. In addition current drugs may be limited by drug–drug interactions and serious adverse effects/toxicities that prevent their prolonged use or dosage escalation. Fluconazole resistance is of particular concern in non-Candida albicans species due to the increased incidence of infections caused by these species in different geographic locations worldwide and the elevated prevalence of resistance to this commonly used azole in many institutions. C. glabrata resistance to the echinocandins has also been documented to be rising in several US institutions, and a higher percentage of these isolates may also be azole resistant. Azole resistance in Aspergillus fumigatus due to clinical and environmental exposure to this class of agents has also been found worldwide, and these isolates can cause invasive infections with high mortality rates. In addition, several species of Aspergillus, and other molds, including Scedosporium and Fusarium species, have reduced susceptibility or pan-resistance to clinically available antifungals. Various investigational antifungals are currently in preclinical or clinical development, including several of them that have the potential to overcome resistance observed against the azoles and the echinocandins. These include agents that also target ergosterol and b-glucan biosynthesis, as well as compounds with novel mechanisms of action that may also overcome the limitations of currently available antifungal classes, including both resistance and adverse effects/toxicity. PMID:28919789

[Typhoid fever in school children: by what measures is the modification of the clinical course due to oral vaccination?].

PubMed

Contreras, R; Ferreccio, C; Sotomayor, V; Astroza, L; Berríos, G; Ortiz, E; Palomino, C; Prenzel, I; Pinto, M E; Levine, M

1992-02-01

The clinical course of infection by Salmonellae was compared between patients who had been vaccinated against typhoid fever using the Ty21a vaccine and those who had not. Of 2566 bacteriological confirmed cases 84% were infected with S typhi, 14% with S paratyphi B and 2% with S paratyphi A. Among patients with typhoid fever, 34% were treated in hospital, 3.5% had relapses, 5.4% developed complications and 1 patient died (0.05%). Among patients with paratyphoid fever, 18% were treated in hospital, 0.6% had relapses, 1.4% developed complications and there were no deaths. These figures were similar among vaccinated and non-vaccinated cases. A slightly greater proportion of vaccinated cases were treated in hospital (38 vs 30%). Thus, use of oral vaccination against typhoid fever does not alter the clinical course of infection with Salmonellae.

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation and Retrieval.

PubMed

Lee, Chia-Ju; Devine, Beth; Tarczy-Hornoch, Peter

2017-01-01

Pharmacogenomics holds promise as a critical component of precision medicine. Yet, the use of pharmacogenomics in routine clinical care is minimal, partly due to the lack of efficient and effective use of existing evidence. This paper describes the design, development, implementation and evaluation of a knowledge-based system that fulfills three critical features: a) providing clinically relevant evidence, b) applying an evidence-based approach, and c) using semantically computable formalism, to facilitate efficient evidence assessment to support timely decisions on adoption of pharmacogenomics in clinical care. To illustrate functionality, the system was piloted in the context of clopidogrel and warfarin pharmacogenomics. In contrast to existing pharmacogenomics knowledge bases, the developed system is the first to exploit the expressivity and reasoning power of logic-based representation formalism to enable unambiguous expression and automatic retrieval of pharmacogenomics evidence to support systematic review with meta-analysis.

The presentation of rickets to orthopaedic clinics: return of the English disease.

PubMed

Naseem, Haris; Wall, Alun P; Sangster, Marshall; Paton, Robin W

2011-04-01

Rickets is a potentially treatable disease of the bone that is most commonly due to deficiency of vitamin D and is increasing in incidence in developed countries. Risk factors include dietary factors, the practice of covering up and darker skin pigmentation. This small retrospective case study set out to examine all cases of rickets presenting to the Paediatric Orthopaedic clinic over a 15-month period. Rickets presented in a bimodal fashion in the 6 cases identified: in males and females aged 3 or less and female adolescents aged 10 and above. This is in keeping with what is known regarding the rapid phases of growth during development. Five cases were from ethnic minority groups. Both female adolescents presented with genu valgum. Rickets can present primarily to Orthopaedic clinics with vague musculoskeletal symptoms. We recommend that biochemical screening be performed on patients from ethnic minorities who may be 'at risk'.

Creating and sustaining an academic-practice Partnership Engagement Model.

PubMed

Schaffer, Marjorie A; Schoon, Patricia M; Brueshoff, Bonnie L

2017-11-01

Public health clinical educators and practicing public health nurses (PHNs) are experiencing challenges in creating meaningful clinical learning experiences for nursing students due to an increase in nursing programs and greater workload responsibilities for both nursing faculty and PHNs. The Henry Street Consortium (HSC), a collaborative group of PHNs and nursing faculty, conducted a project to identify best practices for public health nursing student clinical learning experiences. Project leaders surveyed HSC members about preferences for teaching-learning strategies, facilitated development of resources and tools to guide learning, organized faculty/PHN pilot teams to test resources and tools with students, and evaluated the pilot team experiences through two focus groups. The analysis of the outcomes of the partnership engagement project led to the development of the Partnership Engagement Model (PEM), which may be used by nursing faculty and their public health practice partners to guide building relationships and sustainable partnerships for educating nursing students. © 2017 Wiley Periodicals, Inc.

Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

PubMed Central

Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

2016-01-01

Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

Evolving therapies for liver fibrosis

PubMed Central

Schuppan, Detlef; Kim, Yong Ook

2013-01-01

Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifibrotic activity in early clinical trials. We also touch upon relevant clinical study endpoints, optimal study design, and developments in fibrosis imaging and biomarkers. PMID:23635787

Classification of patients with low back-related leg pain: a systematic review.

PubMed

Stynes, Siobhán; Konstantinou, Kika; Dunn, Kate M

2016-05-23

The identification of clinically relevant subgroups of low back pain (LBP) is considered the number one LBP research priority in primary care. One subgroup of LBP patients are those with back related leg pain. Leg pain frequently accompanies LBP and is associated with increased levels of disability and higher health costs than simple low back pain. Distinguishing between different types of low back-related leg pain (LBLP) is important for clinical management and research applications, but there is currently no clear agreement on how to define and identify LBLP due to nerve root involvement. The aim of this systematic review was to identify, describe and appraise papers that classify or subgroup populations with LBLP, and summarise how leg pain due to nerve root involvement is described and diagnosed in the various systems. The search strategy involved nine electronic databases including Medline and Embase, reference lists of eligible studies and relevant reviews. Selected papers were appraised independently by two reviewers using a standardised scoring tool. Of 13,358 initial potential eligible citations, 50 relevant papers were identified that reported on 22 classification systems. Papers were grouped according to purpose and criteria of the classification systems. Five themes emerged: (i) clinical features (ii) pathoanatomy (iii) treatment-based approach (iv) screening tools and prediction rules and (v) pain mechanisms. Three of the twenty two systems focused specifically on LBLP populations. Systems that scored highest following quality appraisal were ones where authors generally included statistical methods to develop their classifications, and supporting work had been published on the systems' validity, reliability and generalisability. There was lack of consistency in how LBLP due to nerve root involvement was described and diagnosed within the systems. Numerous classification systems exist that include patients with leg pain, a minority of them focus specifically on distinguishing between different presentations of leg pain. Further work is needed to identify clinically meaningful subgroups of LBLP patients, ideally based on large primary care cohort populations and using recommended methods for classification system development.

Ethical challenges in integrating patient-care with clinical research in a resource-limited setting: perspectives from Papua New Guinea

PubMed Central

2013-01-01

Background In resource-limited settings where healthcare services are limited and poverty is common, it is difficult to ethically conduct clinical research without providing patient-care. Therefore, integration of patient-care with clinical research appears as an attractive way of conducting research while providing patient-care. In this article, we discuss the ethical implications of such approach with perspectives from Papua New Guinea. Discussion Considering the difficulties of providing basic healthcare services in developing countries, it may be argued that integration of clinical research with patient-care is an effective, rational and ethical way of conducting research. However, blending patient-care with clinical research may increase the risk of subordinating patient-care in favour of scientific gains; therapeutic misconception and inappropriate inducement; and the risk of causing health system failures due to limited capacity in developing countries to sustain the level of healthcare services sponsored by the research. Nevertheless, these ethical and administrative implications can be minimised if patient-care takes precedence over research; the input of local ethics committees and institutions are considered; and funding agencies acknowledge their ethical obligation when sponsoring research in resource-limited settings. Summary Although integration of patient-care with clinical research in developing countries appears as an attractive way of conducting research when resources are limited, careful planning and consideration on the ethical implications of such approach must be considered. PMID:23885908

Ethical challenges in integrating patient-care with clinical research in a resource-limited setting: perspectives from Papua New Guinea.

PubMed

Laman, Moses; Pomat, William; Siba, Peter; Betuela, Inoni

2013-07-26

In resource-limited settings where healthcare services are limited and poverty is common, it is difficult to ethically conduct clinical research without providing patient-care. Therefore, integration of patient-care with clinical research appears as an attractive way of conducting research while providing patient-care. In this article, we discuss the ethical implications of such approach with perspectives from Papua New Guinea. Considering the difficulties of providing basic healthcare services in developing countries, it may be argued that integration of clinical research with patient-care is an effective, rational and ethical way of conducting research. However, blending patient-care with clinical research may increase the risk of subordinating patient-care in favour of scientific gains; therapeutic misconception and inappropriate inducement; and the risk of causing health system failures due to limited capacity in developing countries to sustain the level of healthcare services sponsored by the research. Nevertheless, these ethical and administrative implications can be minimised if patient-care takes precedence over research; the input of local ethics committees and institutions are considered; and funding agencies acknowledge their ethical obligation when sponsoring research in resource-limited settings. Although integration of patient-care with clinical research in developing countries appears as an attractive way of conducting research when resources are limited, careful planning and consideration on the ethical implications of such approach must be considered.

[Research & development and evaluation of oral films].

PubMed

Ren, Lian-Jie; Liu, Juan; Ma, Jun-Wei; Yan, Jia-Chen; Yin, Li-Fang

2017-10-01

Oral film is a new type of oral preparation. Due to portability, simple preparation process and good clinical compliance, oral films have become the focus of novel drug delivery system in recent years. Meanwhile, oral films have been gradually used in the development of Chinese medicine preparations. According to the application and approval situation of different types of oral films both at home and abroad in recent years, their research and development status was analyzed, including the basic concept, formulation, manufacturing process and quality control, as well as related progress and development prospects of oral films applied in traditional Chinese medicine. Some suggestions on the technical evaluation of oral films were put forward by considering specific requirements from regulatory agencies. This paper could provide some references for the development and evaluation of oral films. Due to the complexity of the drug substances and the particularity of the drug product, the development and application of oral films in traditional Chinese medicine are still faced with opportunity and challenges. Copyright© by the Chinese Pharmaceutical Association.

[Gelatin allergy].

PubMed

Hassoun, S; Sabbah, A

1998-03-01

Allergy to the gelatin used as a plasma filler product has not been recognised until now. Methods used have not been validated but are composed of specific serum IgE, skin tests and histamine release by leucotrienes. The clinical observation that we report has the merit of showing the reality of an allergy that is dependent on plasma filler products due to development of a protocol which includes firstly, during anaphylactic shock, measurement of the mediators of immediate hypersensitivity and secondly, after the clinical accident, test of the activation of basophils by flow cytometry (TAB) and measurement of leucotrienes.

[Personalization in the medicine of the future : Opportunities and risks].

PubMed

Malek, N P

2017-07-01

Personalized medicine is not a new concept. The renaissance of the term is due to the enormous progress in gene sequencing technology and functional imaging, as well as the development of targeted therapies. Application of these technologies in clinical medicine will necessitate infrastructural as well as organizational and educational changes in the healthcare system. An important change required already in the short-term is the introduction of centralized structures, preferably in university clinics, which adopt these innovations and incorporate them into clinical care. Simultaneously, the collation and use of large quantities of relevant data from highly variable sources must be successfully mastered, in order to pave the way for disruptive technologies such as artificial intelligence.

[Myeloid sarcoma of the small bowel with inversion of chromosome 16: a description of 3 clinical cases].

PubMed

Gavrilina, O A; Bariakh, E A; Parovichnikova, E N; Troitskaia, V V; Zvonkov, E E; Kravchenko, S K; Sinitsyna, M N; Obukhova, T N; Gitis, M K; Savchenko, V G

2014-01-01

Myeloid sarcoma (MS) is a rare malignant solid tumor presented with myeloid blast cells showing varying degrees of maturation. MS may have an extramedullary site, precede, or develop simultaneously with the clinical manifestations of acute myeloid leukemia (AML); it may also occur as an AML relapse. Besides AML, MS may be a manifestation of chronic myeloid leukemia or other chronic myeloproliferative diseases. Due to the fact that this disease is rare, the bulk of the literature on MS is presented with single descriptions of retrospective studies and clinical cases. The paper describes 3 cases of MS with inversion of chromosome 16 and small bowel lesion.

[Clinical ethics committees in Mexico: their development in the Mexican Institute of Social Security].

PubMed

Valdez-Martínez, Edith; Bedolla, Miguel

2007-01-01

The Mexican Institute of Social Security (IMSS) considers the relevance of ethics in a similar context than other countries have developed. According to these considerations, IMSS implemented formally of system of local committees on clinical ethics (CLEC), not only to provide support when ethical dilemmas emerge, but to facilitate the development of an ethics culture among health professionals. The implementation of the CLEC network started in 2004, and since then, its number has increased across the country. Currently IMSS has 78 CLECs. Their number continues to grow due to the level of awareness about the importance of ethics for making medical decisions. In November 2006 the first CLEC national meeting was held and the need to redefine strategies to improve performance of CLECS emerged. This article reports the current situation of the CLECs in Mexico.

The Development of Combined Raman Spectroscopy-Optical Coherence Tomography and Application for Skin Cancer Diagnosis

NASA Astrophysics Data System (ADS)

Patil, Chetan

2009-11-01

Optical spectroscopy and imaging have shown promise for performing rapid, non-invasive disease detection and diagnosis in vivo. Independently, Raman Spectroscopy (RS) has demonstrated the ability to perform diagnosis of epithelial cancers such the cervix with excellent overall classification accuracy due to the inherent biochemical specificity of the technique, however relating features of tissue morphology with techniques such as Raman mapping is clinically impractical due to the weak nature of the scattering phenomena resulting in prohibitively long acquisition times. Optical Coherence Tomography (OCT), on the other hand, has demonstrated the ability to perform real-time, high-resolution, cross-sectional imaging of the microstructural characteristics of disease, but typically lacks molecularly specific information that can assist in classifying pathological lesions. We present the development of a combined Raman Spectroscopy-OCT (RS-OCT) instrument capable of compensating for the limitations of each technique individually and performing both biochemical and microstructural evaluation of tissues. We will include the design and development of benchtop RS-OCT implementations based on independent 785 nm Raman and 1310 nm time-domain OCT system backbones, as well as with a 785nm Raman / 850nm spectral-domain OCT setup employing an integrated detection arm. These systems motivated the ultimate design of a clinical RS-OCT system for application in dermatology. In order to aid in the development of our Raman spectral processing and classification methods, we conducted a simultaneous pilot study in which RS alone was used to measure basal and squamous cell carcinomas. We will present the initial results from our clinical experiences with the combined RS-OCT device, and include a discussion of spectral classification and the ultimate potential of combined RS-OCT for skin cancer diagnosis.

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

Recurring ventriculitis due to Citrobacter diversus: clinical and bacteriologic analysis.

PubMed

Eppes, S C; Woods, C R; Mayer, A S; Klein, J D

1993-09-01

Neonatal meningitis due to Citrobacter diversus is usually accompanied by the development of brain abscesses and tends to have high rates of morbidity and mortality. We report a case of a newborn with C. diversus meningitis and brain abscesses who relapsed after initial antibiotic therapy and from whom C. diversus was recovered from cerebrospinal fluid 4 years later during a neurosurgical procedure. Genetic differences in the early and late isolates were discovered, and explanations for this phenomenon are suggested. Possible mechanisms for prolonged persistence in the central nervous system are explored. This unusual case and the analysis of the organisms illustrate the unique features of C. diversus as a pathogen and underscore the need for developing optimal therapeutic strategies.

[Clinical thinking and decision making in practice. A 7-year old boy with rapid growth and pubic hair].

PubMed

Berents-Oosterhof, M Y; Noordam, C; Otten, B J

2000-12-16

A 7-year-old boy was tall, with a developing penis and initial growth of pubic hair. Due to the accelerated growth there was no premature adrenarche and due to the increased testicular volume there must have been a central cause for the production of androgens. Further specific investigations revealed an astrocytoma of the hypothalamus. After radiotherapy, the tumour exhibited no growth. The pubertal development was inhibited and the growth later stimulated by means of medication. In the case of pubertas praecox the growth chart and pubertal stages including testicular volume can help to differentiate between central and peripheral precocious puberty, narrow the diagnostic evaluation and reduce the time of the initial therapy.

Traditional chinese medicine: an update on clinical evidence.

PubMed

Xue, Charlie C L; Zhang, Anthony L; Greenwood, Kenneth M; Lin, Vivian; Story, David F

2010-03-01

As an alternative medical system, Traditional Chinese Medicine (TCM) has been increasingly used over the last several decades. Such a consumer-driven development has resulted in introduction of education programs for practitioner training, development of product and practitioner regulation systems, and generation of an increasing interest in research. Significant efforts have been made in validating the quality, effectiveness, and safety of TCM interventions evidenced by a growing number of published trials and systematic reviews. Commonly, the results of these studies were inconclusive due to the lack of quality and quantity of the trials to answer specific and answerable clinical questions. The methodology of a randomized clinical trial (RCT) is not free from bias, and the unique features of TCM (such as individualization and holism) further complicate effective execution of RCTs in TCM therapies. Thus, data from limited RCTs and systematic reviews need to be interpreted with great caution. Nevertheless, until new and specific methodology is developed that can adequately address these methodology challenges for RCTs in TCM, evidence from quality RCTs and systematic reviews still holds the credibility of TCM in the scientific community. This article summarizes studies on TCM utilization, and regulatory and educational development with a focus on updating the TCM clinical evidence from RCTs and systematic reviews over the last decade. The key issues and challenges associated with evidence-based TCM developments are also explored.

Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

PubMed Central

Dyall, Julie; Coleman, Christopher M.; Hart, Brit J.; Venkataraman, Thiagarajan; Holbrook, Michael R.; Kindrachuk, Jason; Johnson, Reed F.; Olinger, Gene G.; Jahrling, Peter B.; Laidlaw, Monique; Johansen, Lisa M.; Lear-Rooney, Calli M.; Glass, Pamela J.; Hensley, Lisa E.

2014-01-01

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies. PMID:24841273

Research-active clinical nurses: against all odds.

PubMed

Siedlecki, Sandra L; Albert, Nancy M

2017-03-01

To develop a theoretical understanding of factors that impact decisions of clinical nurses to conduct a research study. Only a small percentage of all nurses are research-active and even fewer clinical nurses are research-active. Several researchers have explored barriers to research activity by clinical nurses, but few have examined why, in spite of all odds, some clinical nurses are research-active. As the purpose of this study was to develop a theoretical understanding of the research-active nurse, a grounded theory approach was used. The sample interviewed for this study consisted of registered nurses (n = 26) who worked in a hospital or ambulatory setting, had daily direct patient contact and had participated as principal investigator on at least one completed clinical nursing research study that was not in fulfilment of an educational requirement. The interviews were digitally recorded and analysed by two researchers using the constant comparative method. The findings from this study suggest that the conduct of research by clinical nurses was the direct result of a clinical trigger, characteristics and beliefs of the nurse about research and their role in generating knowledge, and the presence of support conditions, such as a research mentor. Clinical nurses can and do conduct research, in spite of constraints due to a lack of time, money and/or knowledge, if they have access to research mentors and are practising in a research-supportive environment. Nurses at the bedside are in a unique position to identify problems most in need of solutions. Findings from this study provide a foundation upon which to develop and test various programmes that seek to increase the number of clinical nurses who are research-active. © 2016 John Wiley & Sons Ltd.

[Four infants with upper urinary tract infection due to extended-spectrum bata lactamase (ESBL)-producing Escherichia coli].

PubMed

Hibino, Satoshi; Fukuchi, Kunihiko; Abe, Yoshifusa; Hoshino, Akihiro; Sakurai, Shunsuke; Mikawa, Takeshi; Fuke, Toshiya; Yoshida, Koichiro; Itabashi, Kazuo

2011-09-01

Bacteria producing extended-spectrum beta lactamase (ESBL) are detected mainly in adult urinary specimens, and are believed to cause hospital-acquired infection due to their resistance to many drugs. The incidence of community-acquired infection due to such bacteria is increasing, but few cases of infant upper urinary tract infection (UUTI) have been reported in Japan. We treated four infants with UUTI caused by ESBL-producing Escherichia coli, as determined by genotyping. Using medical records, we retrospectively evaluated the clinical course, antibiotic use and efficacy, antimicrobial susceptibility results, and the presence of underlying disease. One of the four had been previously hospitalized for occult bacteremia. Two developed UUTI after antibiotic treatment, indicating that previous antibiotic use may have been a risk factor in these cases. We could not identify the infection route in all cases. Two of the four had bilateral vesicoureteral reflux (VUR). Renal scintigraphy was done in three. Although an initial dimercaptosuccinic acid (DMSA) defect was detected in all four, only one had renal scarring. E. coli isolates from all four showed PCR signals for blaCTX-M-; one isolate positive for the blaCTX-M3 group and three positive for blaCTX-M14. Antimicrobial susceptibility test results showed all isolates to be resistant to cephalosporins, but discrepancies existed between antimicrobial susceptibility results and actual clinical efficacy. Clinically, cefazolin (CEZ) was effective in two subjects and ceftazidime (CAZ) effective in one. Panipenem/betamipron (PAPM/BP) was effective in one. None of the four developed sepsis or meningitis. Post hospitalization antibiotic prophylaxis showed that none of the four has had UUTI recur. Japan's ESBL-producing bacterial infection incidence is increasing, so medical professionals should watch for such UUTI even in first-case occurrence in infants.

The Virtual Maternity Clinic: a teaching and learning innovation for midwifery education.

PubMed

Phillips, Diane; Duke, Maxine; Nagle, Cate; Macfarlane, Susie; Karantzas, Gery; Patterson, Denise

2013-10-01

There are challenges for midwifery students in developing skill and competency due to limited placements in antenatal clinics. The Virtual Maternity Clinic, an online resource, was developed to support student learning in professional midwifery practice. Identifying students' perceptions of the Virtual Maternity Clinic; learning about the impact of the Virtual Maternity Clinic on the students' experience of its use and access; and learning about the level of student satisfaction of the Virtual Maternity Clinic. Two interventions were used including pre and post evaluations of the online learning resource with data obtained from questionnaires using open ended and dichotomous responses and rating scales. The pre-Virtual Maternity Clinic intervention used a qualitative design and the post-Virtual Maternity Clinic intervention applied both qualitative and quantitative approaches. Three campuses of Deakin University, located in Victoria, Australia. Midwifery students enrolled in the Bachelor of Nursing/Bachelor of Midwifery and Graduate Diploma of Midwifery were recruited across three campuses of Deakin University (n=140). Thematic analysis of the pre-Virtual Maternity Clinic intervention (return rate n=119) related to students' expectations of this resource. The data for the post-Virtual Maternity Clinic intervention (return rate n=42) including open-ended responses were thematically analysed; dichotomous data examined in the form of frequencies and percentages of agreement and disagreement; and 5-rating scales were analysed using Pearson's correlations (α=.05, two-tailed). Results showed from the pre-Virtual Maternity Clinic intervention that students previously had placements in antenatal clinics were optimistic about the online learning resource. The post-Virtual Maternity Clinic intervention results indicated that students were satisfied with the Virtual Maternity Clinic as a learning resource despite some technological issues. The Virtual Maternity Clinic provides benefits for students in repeated observation of the practice of the midwife to support their professional learning and practice development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Veterinary clinical pathologists in the biopharmaceutical industry.

PubMed

Schultze, A Eric; Bounous, Denise I; Bolliger, Anne Provencher

2008-06-01

There is an international shortage of veterinary clinical pathologists in the workplace. Current trainees in veterinary clinical pathology may choose to pursue careers in academe, diagnostic laboratories, government health services, biopharmaceutical companies, or private practice. Academic training programs attempt to provide trainees with an exposure to several career choices. However, due to the proprietary nature of much of the work in the biopharmaceutical industry, trainees may not be fully informed regarding the nature of work for veterinary clinical pathologists and the myriad opportunities that await employment in the biopharmaceutical industry. The goals of this report are to provide trainees in veterinary clinical pathology and other laboratory personnel with an overview of the work-life of veterinary clinical pathologists employed in the biopharmaceutical industry, and to raise the profile of this career choice for those seeking to enter the workforce. Biographical sketches, job descriptions, and motivation for 3 successful veterinary clinical pathologists employed in the biopharmaceutical industry are provided. Current and past statistics for veterinary clinical pathologists employed in the biopharmaceutical industry are reviewed. An overview of the drug development process and involvement of veterinary clinical pathologists in the areas of discovery, lead optimization, and candidate evaluation are discussed. Additional duties for veterinary clinical pathologists employed in the biopharmaceutical industry include development of biomarkers and new technologies, service as scientific resources, diagnostic support services, and laboratory management responsibilities. There are numerous opportunities available for trainees in veterinary clinical pathology to pursue employment in the biopharmaceutical industry and enjoy challenging and rewarding careers.

International collaboration for pediatric oncology nursing leadership: Nicaragua and Canada.

PubMed

Orozco, A; Marin, V; Reyes, S; Challinor, J; Carpio, B

2009-01-01

In 2005, with financial support from the Pediatric Oncology Group of Ontario, a pilot nursing leadership project linked pediatric oncology nurses from Canada with nurses at the La Mascota Hospital in Managua, Nicaragua. Following consultation with the pediatric oncology team in Nicaragua, a program was developed to strengthen clinical nursing leadership in a clinical setting through continuing education. The nurses believed that care of the patient and family improved due to the increased leadership skills of nurses in the unit and as the profile and credibility of nurses as peers in the health care team became evident. Providing nurses with the autonomy and financing for a project related directly to nursing care represented an important development for leadership in the profession.

A facile fluorescent "turn-off" method for sensing paraquat based on pyranine-paraquat interaction

NASA Astrophysics Data System (ADS)

Zhao, Zuzhi; Zhang, Fengwei; Zhang, Zipin

2018-06-01

Development of a technically simple yet effective method for paraquat (PQ) detection is of great importance due to its high clinical and environmental relevance. In this study, we developed a pyranine-based fluorescent "turn-off" method for PQ sensing based on pyranine-PQ interaction. We investigated the dependence of analytical performance of this method on the experimental conditions, such as the ion strength, medium pH, and so on. Under the optimized conditions, the method is sensitive and selective, and could be used for PQ detection in real-world sample. This study essentially provides a readily accessible fluorescent system for PQ sensing which is cheap, robust, and technically simple, and it is envisaged to find more interesting clinical and environmental applications.

Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis.

PubMed

Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S

2016-12-01

Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.

Rectus sheath hematoma due to cough in an elderly patient under antiplatelet therapy.

PubMed

Çoşğun, I Güven; Ünal, Yılmaz; Çetin, Mustafa

2015-04-01

Abdominal rectus sheath hematoma (ARSH) is a rare clinical condition that can be confused with other causes of acute abdomen. We report an 83-year-old woman receiving antiplatelet medication who presented with ARSH following a cough episode. The patient was hospitalized with a diagnosis of acute chronic obstructive pulmonary disease exacerbations. During hospital stay, sudden onset abdominal pain was developed following a severe cough episode. Computed tomography of the abdomen revealed ARSH. Rectus sheath hematoma is a rare and often misdiagnosed clinical condition. It is important to be considered for the diagnosis. ARSH should be considered in case of development of acute abdominal pain following cough in receiving anticoagulant or antiplatelet therapy. © 2014 John Wiley & Sons Ltd.

An information extraction framework for cohort identification using electronic health records.

PubMed

Liu, Hongfang; Bielinski, Suzette J; Sohn, Sunghwan; Murphy, Sean; Wagholikar, Kavishwar B; Jonnalagadda, Siddhartha R; Ravikumar, K E; Wu, Stephen T; Kullo, Iftikhar J; Chute, Christopher G

2013-01-01

Information extraction (IE), a natural language processing (NLP) task that automatically extracts structured or semi-structured information from free text, has become popular in the clinical domain for supporting automated systems at point-of-care and enabling secondary use of electronic health records (EHRs) for clinical and translational research. However, a high performance IE system can be very challenging to construct due to the complexity and dynamic nature of human language. In this paper, we report an IE framework for cohort identification using EHRs that is a knowledge-driven framework developed under the Unstructured Information Management Architecture (UIMA). A system to extract specific information can be developed by subject matter experts through expert knowledge engineering of the externalized knowledge resources used in the framework.

CRISPR-mediated Ophthalmic Genome Surgery.

PubMed

Cho, Galaxy Y; Abdulla, Yazeed; Sengillo, Jesse D; Justus, Sally; Schaefer, Kellie A; Bassuk, Alexander G; Tsang, Stephen H; Mahajan, Vinit B

2017-09-01

Clustered regularly interspaced short palindromic repeats (CRISPR) is a genome engineering system with great potential for clinical applications due to its versatility and programmability. This review highlights the development and use of CRISPR-mediated ophthalmic genome surgery in recent years. Diverse CRISPR techniques are in development to target a wide array of ophthalmic conditions, including inherited and acquired conditions. Preclinical disease modeling and recent successes in gene editing suggest potential efficacy of CRISPR as a therapeutic for inherited conditions. In particular, the treatment of Leber congenital amaurosis with CRISPR-mediated genome surgery is expected to reach clinical trials in the near future. Treatment options for inherited retinal dystrophies are currently limited. CRISPR-mediated genome surgery methods may be able to address this unmet need in the future.

A case of ulcerative colitis complicated with bronchiolitis obliterans organizing pneumonia (BOOP) and air leak syndrome.

PubMed

Aydoğdu, Müge; Gürsel, Gül; Özyilmaz, Ezgi; Akyürek, Nalan; Memış, Leyla

2012-01-01

Extraintestinal manifestations of inflammatory bowel diseases are well recognized and mainly affect the joints, skin, liver, and eyes; however, clinically significant pulmonary involvement is very rare. Early identification of pulmonary involvement is important and will be life-saving. We report herein a case of an ulcerative colitis patient, presenting with acute respiratory distress syndrome and bilateral recurring pneumothorax, pneumomediastinum and subcutaneous emphysema, i.e., air leak syndrome. He was diagnosed with open lung biopsy as bronchiolitis obliterans organizing pneumonia most probably due to viral etiology and responded well to steroid therapy, with almost complete resolution of radiographic and clinical findings. In inflammatory bowel disease patients, bronchiolitis obliterans organizing pneumonia developing due to viral or fungal infectious etiology or due to the inflammatory bowel disease itself may progress to acute respiratory distress syndrome and may present with air leak syndrome. Early detection is important and life-saving, since bronchiolitis obliterans organizing pneumonia often responds well to steroid treatment provided an infectious etiology has been excluded or adequate antimicrobial therapy has already been initiated.

A case of refractary epilepsy and related pain due to dysmenorrhea solved with loading dose of lacosamide: clinical and neurophysiological correlates.

PubMed

Marchitto, Nicolino; Ceratti, Umberto; Dalmaso, Serenella; Raimondi, Gianfranco

2017-10-23

 In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer. She was treated with lamotrigine, clonazepam and levomepromazina maleato. At admission the patient shew seizures due to pain related to dysmenorrhea. In emergency we treated with verapamil hydrochloride 10 mg ev, subsequently verapamil hydrochloride 20 mg in 250 ml of saline solution as maintenance dose. Then we decided to administer a loading dose of 100 mg cpr of Lacosamide to stop the treatment with verapamil hydrochloride. With Lacosamide we solved the seizures in 24 hours.

T wave abnormalities, high body mass index, current smoking and high lipoprotein (a) levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

PubMed Central

Moller, Christina Strom; Byberg, Liisa; Sundstrom, Johan; Lind, Lars

2006-01-01

Background Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI. PMID:16519804

Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

PubMed

Huard, J; Mu, X; Lu, A

2016-08-01

Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

[Role of MRI for detection and characterization of pulmonary nodules].

PubMed

Sommer, G; Koenigkam-Santos, M; Biederer, J; Puderbach, M

2014-05-01

Due to physical and technical limitations, magnetic resonance imaging (MRI) has hitherto played only a minor role in image-based diagnostics of the lungs. However, as a consequence of important methodological developments during recent years, MRI has developed into a technically mature and clinically well-proven method for specific pulmonary questions. The purpose of this article is to provide an overview on the currently available sequences and techniques for assessment of pulmonary nodules and analyzes the clinical significance according to the current literature. The main focus is on the detection of lung metastases, the detection of primary pulmonary malignancies in high-risk individuals and the differentiation between pulmonary nodules of benign and malignant character. The MRI technique has a sensitivity of approximately 80 % for detection of malignant pulmonary nodules compared to the reference standard low-dose computed tomography (CT) and is thus somewhat inferior to CT. Advantages of MRI on the other hand are a higher specificity in differentiating malignant and benign pulmonary nodules and the absence of ionizing radiation exposure. A systematic use of MRI as a primary tool for detection and characterization of pulmonary nodules is currently not recommended due to insufficient data. The diagnostic potential of MRI for early detection and staging of malignant pulmonary diseases, however, seems promising. Therefore, further evaluation of MRI as a secondary imaging modality in clinical trials is highly warranted.

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping.

PubMed

Wu, Shih-Ying; Aurup, Christian; Sanchez, Carlos Sierra; Grondin, Julien; Zheng, Wenlan; Kamimura, Hermes; Ferrera, Vincent P; Konofagou, Elisa E

2018-05-22

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Aeromonas sobria necrotizing fasciitis and sepsis in an immunocompromised patient: a case report and review of the literature

PubMed Central

2014-01-01

Introduction Aeromonas veronii biovar sobria is a rare cause of bacteremia, with several studies indicating that this isolate may be of particular clinical significance since it is enterotoxin producing. A wide spectrum of infections has been associated with Aeromonas species in developing countries that include gastroenteritis, wound infections, septicemia and lung infections. This infection, caused by Aeromonas species, is usually more severe in immunocompromised than immunocompetent individuals. We here describe a case of soft tissue infection and severe sepsis due to Aeromonas sobria in an immunocompromised patient. Case presentation A 74-year-old Caucasian man with a clinical history of chronic lymphocytic leukemia and immune thrombocytopenia, periodically treated with steroids, was admitted to our Intensive Care Unit because of necrotizing fasciitis and multiorgan failure due to Aeromonas sobria, which resulted in his death. The unfortunate coexistence of a Candida albicans infection played a key role in the clinical course. Conclusion Our experience suggests that early recognition and aggressive medical and surgical therapy are determinants in the treatment of severe septicemia caused by an Aeromonas sobria in an immunocompromised patient. PMID:25245365

Engineering stem cells for future medicine.

PubMed

Ricotti, Leonardo; Menciassi, Arianna

2013-03-01

Despite their great potential in regenerative medicine applications, stem cells (especially pluripotent ones) currently show a limited clinical success, partly due to a lack of biological knowledge, but also due to a lack of specific and advanced technological instruments able to overcome the current boundaries of stem cell functional maturation and safe/effective therapeutic delivery. This paper aims at describing recent insights, current limitations, and future horizons related to therapeutic stem cells, by analyzing the potential of different bioengineering disciplines in bringing stem cells toward a safe clinical use. First, we clarify how and why stem cells should be properly engineered and which could be in a near future the challenges and the benefits connected with this process. Second, we identify different routes toward stem cell differentiation and functional maturation, relying on chemical, mechanical, topographical, and direct/indirect physical stimulation. Third, we highlight how multiscale modeling could strongly support and optimize stem cell engineering. Finally, we focus on future robotic tools that could provide an added value to the extent of translating basic biological knowledge into clinical applications, by developing ad hoc enabling technologies for stem cell delivery and control.

Honey in wound care: effects, clinical application and patient benefit.

PubMed

Lay-flurrie, Karen

The use of honey in wound management has enjoyed a resurgence. This is largely due to the growing clinical problem of antibiotic-resistant bacteria and the combined difficulties for the practitioner in managing chronic wound types, such as burns, leg ulcers or surgical wounds, that may become infected, for example, with methicillin-resistant Staphylococcus aureus or Pseudomonas. The associated costs of treating such wounds are escalating as a result. While the use of honey as a wound dressing has been recognized, at least since Egyptian times circa 2000 BC, it is only more recently, due to the development and licensing of modern honey wound dressings, that such dressings have become more widely available and used in wound management. This article focuses on the use of honey in the treatment of infected wounds and burns. It will examine the effects of honey at the wound bed and its clinical applications, along with the current dressings available. Also discussed are the practical considerations, if, like any wound dressing, honey is to be used safely, appropriately and for the benefit of the patient.

Global Distribution, Public Health and Clinical Impact of the Protozoan Pathogen Cryptosporidium

PubMed Central

Putignani, Lorenza; Menichella, Donato

2010-01-01

Cryptosporidium spp. are coccidians, oocysts-forming apicomplexan protozoa, which complete their life cycle both in humans and animals, through zoonotic and anthroponotic transmission, causing cryptosporidiosis. The global burden of this disease is still underascertained, due to a conundrum transmission modality, only partially unveiled, and on a plethora of detection systems still inadequate or only partially applied for worldwide surveillance. In children, cryptosporidiosis encumber is even less recorded and often misidentified due to physiological reasons such as early-age unpaired immunological response. Furthermore, malnutrition in underdeveloped countries or clinical underestimation of protozoan etiology in developed countries contribute to the underestimation of the worldwide burden. Principal key indicators of the parasite distribution were associated to environmental (e.g., geographic and temporal clusters, etc.) and host determinants of the infection (e.g., age, immunological status, travels, community behaviours). The distribution was geographically mapped to provide an updated picture of the global parasite ecosystems. The present paper aims to provide, by a critical analysis of existing literature, a link between observational epidemiological records and new insights on public health, and diagnostic and clinical impact of cryptosporidiosis. PMID:20706669

Development and implementation of clinical trial protocol templates at the National Institute of Allergy and Infectious Diseases.

PubMed

Bridge, Heather; Smolskis, Mary; Bianchine, Peter; Dixon, Dennis O; Kelly, Grace; Herpin, Betsey; Tavel, Jorge

2009-08-01

A clinical research protocol document must reflect both sound scientific rationale as well as local, national and, when applicable, international regulatory and human subject protections requirements. These requirements originate from a variety of sources, undergo frequent revision and are subject to interpretation. Tools to assist clinical investigators in the production of clinical protocols could facilitate navigating these requirements and ultimately increase the efficiency of clinical research. The National Institute of Allergy and Infectious Diseases (NIAID) developed templates for investigators to serve as the foundation for protocol development. These protocol templates are designed as tools to support investigators in developing clinical protocols. NIAID established a series of working groups to determine how to improve its capacity to conduct clinical research more efficiently and effectively. The Protocol Template Working Group was convened to determine what protocol templates currently existed within NIAID and whether standard NIAID protocol templates should be produced. After review and assessment of existing protocol documents and requirements, the group reached consensus about required and optional content, determined the format and identified methods for distribution as well as education of investigators in the use of these templates. The templates were approved by the NIAID Executive Committee in 2006 and posted as part of the NIAID Clinical Research Toolkit [1] website for broad access. These documents require scheduled revisions to stay current with regulatory and policy changes. The structure of any clinical protocol template, whether comprehensive or specific to a particular study phase, setting or design, affects how it is used by investigators. Each structure presents its own set of advantages and disadvantages. While useful, protocol templates are not stand-alone tools for creating an optimal protocol document, but must be complemented by institutional resources and support. Education and guidance of investigators in the appropriate use of templates is necessary to ensure a complete yet concise protocol document. Due to changing regulatory requirements, clinical protocol templates cannot become static, but require frequent revisions.

Developing professional attributes in critical care nurses using Team-Based Learning.

PubMed

Currey, Judy; Eustace, Paula; Oldland, Elizabeth; Glanville, David; Story, Ian

2015-05-01

Australian nurses prepare for specialty practice by undertaking postgraduate theoretical and clinical education in partnership models between universities and hospitals. In our global healthcare system, nurses require advanced critical thinking and strong communication skills to provide safe, high quality patient care. Yet, few education programs focus on developing these skills. Team-Based Learning (TBL) is a specific educational strategy that encourages and rewards students to think critically and solve clinical problems individually and in teams. The aim of this study was to investigate critical care nursing students' perceptions and experiences of TBL after it was introduced into the second half of their postgraduate specialty course. Following Ethics Committee approval, thirty-two students were invited to participate in an extended response questionnaire on their perceptions of TBL as part of a larger study. Data were analyzed thematically. Postgraduate students perceived their professional growth was accelerated due to the skills and knowledge acquired through TBL. Four themes underpinned the development and accelerated acquisition of specialty nurse attributes due to TBL: Engagement, Learning Effectiveness, Critical Thinking, and Motivation to Participate. Team-Based Learning offered deep and satisfying learning experiences for students. The early acquisition of advanced critical thinking, teamwork and communication skills, and specialty practice knowledge empowered nurses to provide safe patient care with confidence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developing the Clinical Psychomotor Skills of Musculoskeletal Sonography Using a Multimedia DVD: A Pilot Study

ERIC Educational Resources Information Center

Thoirs, Kerry; Coffee, Jane

2012-01-01

Sonographers are medical or non-medical health professionals in the radiology field who skilfully manipulate ultrasound equipment to produce images that are used to diagnose medical conditions and abnormalities. This technique is also becoming popular amongst the wider community in other medical specialities and allied health professionals, due to…

Identification, Characterization, and Clinical Development of the New Generation of Breast Cancer Susceptibility Alleles

DTIC Science & Technology

2006-03-01

CHEK2 * 1100delC families to determine whether they modify or interact with these genes in breast cancer. This task has not been started as yet...Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson K, Weber B, Rahman N, Stratton MR. Low-penetrance susceptibility to breast cancer due to CHEK2

Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project.

PubMed

Moreno, Lucas; Caron, Hubert; Geoerger, Birgit; Eggert, Angelika; Schleiermacher, Gudrun; Brock, Penelope; Valteau-Couanet, Dominique; Chesler, Louis; Schulte, Johannes H; De Preter, Katleen; Molenaar, Jan; Schramm, Alexander; Eilers, Martin; Van Maerken, Tom; Johnsen, John Inge; Garrett, Michelle; George, Sally L; Tweddle, Deborah A; Kogner, Per; Berthold, Frank; Koster, Jan; Barone, Giuseppe; Tucker, Elizabeth R; Marshall, Lynley; Herold, Ralf; Sterba, Jaroslav; Norga, Koen; Vassal, Gilles; Pearson, Andrew Dj

2017-08-01

Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

In vivo two-dimensional NMR correlation spectroscopy

NASA Astrophysics Data System (ADS)

Kraft, Robert A.

1999-10-01

The poor resolution of in-vivo one- dimensional nuclear magnetic resonance spectroscopy (NMR) has limited its clinical potential. Currently, only the large singlet methyl resonances arising from N-acetyl aspartate (NAA), choline, and creatine are quantitated in a clinical setting. Other metabolites such as myo- inositol, glutamine, glutamate, lactate, and γ- amino butyric acid (GABA) are of clinical interest but quantitation is difficult due to the overlapping resonances and limited spectral resolution. To improve the spectral resolution and distinguish between overlapping resonances, a series of two- dimensional chemical shift correlation spectroscopy experiments were developed for a 1.5 Tesla clinical imaging magnet. Two-dimensional methods are attractive for in vivo spectroscopy due to their ability to unravel overlapping resonances with the second dimension, simplifying the interpretation and quantitation of low field NMR spectra. Two-dimensional experiments acquired with mix-mode line shape negate the advantages of the second dimension. For this reason, a new experiment, REVOLT, was developed to achieve absorptive mode line shape in both dimensions. Absorptive mode experiments were compared to mixed mode experiments with respect to sensitivity, resolution, and water suppression. Detailed theoretical and experimental calculations of the optimum spin lock and radio frequency power deposition were performed. Two-dimensional spectra were acquired from human bone marrow and human brain tissue. The human brain tissue spectra clearly reveal correlations among the coupled spins of NAA, glutamine, glutamate, lactate, GABA, aspartate and myo-inositol obtained from a single experiment of 23 minutes from a volume of 59 mL. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

Ten years of dengue drug discovery: progress and prospects.

PubMed

Lim, Siew Pheng; Wang, Qing-Yin; Noble, Christian G; Chen, Yen-Liang; Dong, Hongping; Zou, Bin; Yokokawa, Fumiaki; Nilar, Shahul; Smith, Paul; Beer, David; Lescar, Julien; Shi, Pei-Yong

2013-11-01

To combat neglected diseases, the Novartis Institute of Tropical Diseases (NITD) was founded in 2002 through private-public funding from Novartis and the Singapore Economic Development Board. One of NITD's missions is to develop antivirals for dengue virus (DENV), the most prevalent mosquito-borne viral pathogen. Neither vaccine nor antiviral is currently available for DENV. Here we review the progress in dengue drug discovery made at NITD as well as the major discoveries made by academia and other companies. Four strategies have been pursued to identify inhibitors of DENV through targeting both viral and host proteins: (i) HTS (high-throughput screening) using virus replication assays; (ii) HTS using viral enzyme assays; (iii) structure-based in silico docking and rational design; (iv) repurposing hepatitis C virus inhibitors for DENV. Along the developmental process from hit finding to clinical candidate, many inhibitors did not advance beyond the stage of hit-to-lead optimization, due to their poor selectivity, physiochemical or pharmacokinetic properties. Only a few compounds showed efficacy in the AG129 DENV mouse model. Two nucleoside analogs, NITD-008 and Balapiravir, entered preclinical animal safety study and clinic trial, but both were terminated due to toxicity and lack of potency, respectively. Celgosivir, a host alpha-glucosidase inhibitor, is currently under clinical trial; its clinical efficacy remains to be determined. The knowledge accumulated during the past decade has provided a better rationale for ongoing dengue drug discovery. Though challenging, we are optimistic that this continuous, concerted effort will lead to an effective dengue therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

[Report of a case of poisoning by double snake bite with neurotrope venom at the National Donka Hospital, Conakry (Guinea)].

PubMed

Sako, F B; Sow, M S; Bangoura, E F; Guilavogui, F

2011-12-01

Poisoning by snake bites remains an important cause of death in developing countries and in Africa in particular. Positive diagnosis is mostly easy because of the interrogation of the family and the local reactions that occur in the bite area. However, it is easy to know the type of the snake because the description by the victim is often unclear. We report a case of poisoning due to double bite by an unidentified snake that led to a clinical picture dominated by neurological and respiratory signs, suggestive of a neurotoxin poisoning in a young man living in rural area. Despite the delay in the management due to the ritual traditional treatment, the symptoms improved after the administration of polyvalent anti-venom. This observation raises the delicate problem of identification of snakes from the clinical symptomatology observed, considering their variety

The relational database model and multiple multicenter clinical trials.

PubMed

Blumenstein, B A

1989-12-01

The Southwest Oncology Group (SWOG) chose to use a relational database management system (RDBMS) for the management of data from multiple clinical trials because of the underlying relational model's inherent flexibility and the natural way multiple entity types (patients, studies, and participants) can be accommodated. The tradeoffs to using the relational model as compared to using the hierarchical model include added computing cycles due to deferred data linkages and added procedural complexity due to the necessity of implementing protections against referential integrity violations. The SWOG uses its RDBMS as a platform on which to build data operations software. This data operations software, which is written in a compiled computer language, allows multiple users to simultaneously update the database and is interactive with respect to the detection of conditions requiring action and the presentation of options for dealing with those conditions. The relational model facilitates the development and maintenance of data operations software.

Development and preliminary evaluation of an ultrasonic motor actuated needle guide for 3T MRI-guided transperineal prostate interventions

NASA Astrophysics Data System (ADS)

Song, Sang-Eun; Tokuda, Junichi; Tuncali, Kemal; Tempany, Clare; Hata, Nobuhiko

2012-02-01

Image guided prostate interventions have been accelerated by Magnetic Resonance Imaging (MRI) and robotic technologies in the past few years. However, transrectal ultrasound (TRUS) guided procedure still remains as vast majority in clinical practice due to engineering and clinical complexity of the MRI-guided robotic interventions. Subsequently, great advantages and increasing availability of MRI have not been utilized at its maximum capacity in clinic. To benefit patients from the advantages of MRI, we developed an MRI-compatible motorized needle guide device "Smart Template" that resembles a conventional prostate template to perform MRI-guided prostate interventions with minimal changes in the clinical procedure. The requirements and specifications of the Smart Template were identified from our latest MRI-guided intervention system that has been clinically used in manual mode for prostate biopsy. Smart Template consists of vertical and horizontal crossbars that are driven by two ultrasonic motors via timing-belt and mitergear transmissions. Navigation software that controls the crossbar position to provide needle insertion positions was also developed. The software can be operated independently or interactively with an open-source navigation software, 3D Slicer, that has been developed for prostate intervention. As preliminary evaluation, MRI distortion and SNR test were conducted. Significant MRI distortion was found close to the threaded brass alloy components of the template. However, the affected volume was limited outside the clinical region of interest. SNR values over routine MRI scan sequences for prostate biopsy indicated insignificant image degradation during the presence of the robotic system and actuation of the ultrasonic motors.

Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

PubMed

Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

2015-12-01

Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

Translational neuropathic pain research: A clinical perspective.

PubMed

Bouhassira, D; Attal, N

2016-12-03

Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. Copyright © 2016. Published by Elsevier Ltd.

RCR audit of compliance with UK guidelines for the prevention and detection of acute kidney injury in adult patients undergoing iodinated contrast media injections for CT.

PubMed

Cope, L H; Drinkwater, K J; Howlett, D C

2017-12-01

To determine radiology departmental compliance with current UK guidance on contrast-induced acute kidney injury (CI-AKI) and to provide data on the incidence of clinically significant post-contrast AKI (PC-AKI) in computed tomography (CT) practice. A questionnaire was sent to all UK acute National Health Service (NHS) providers (NHS boards in Scotland, local health boards in Wales, NHS trusts in England and health and social care trusts in Northern Ireland) to assess compliance of provider protocols with current UK guidelines for the prevention, recognition, and management of CI-AKI. Audit data were collected for 40 consecutive fit outpatients and 40 consecutive acutely unwell patients/inpatients from hospitals within each participating provider to assess clinical compliance. Eighty-nine of 172 (52%) health service providers responded, and data on 7,159 contrast-enhanced CT examinations were provided. Compliance with guidelines was poor with wide variation in clinical practice. The observed incidence of clinically significant (requiring treatment or resulting in death) PC-AKI was zero in 3,590 outpatients, although two patients developed AKI due to other causes (sepsis and progressive malignancy). Fourteen out of 3,569 (0.4%) patients in the inpatient group developed clinically significant PC-AKI, and a further 17 patients were identified who met the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI (Electronic Supplementary Material Appendix S1), but did not require active treatment, giving an overall incidence of AKI of 0.9%. In patients at high risk due to impaired renal function prior to the scan, there was no difference in the median serum creatinine (SCr) before and after contrast medium administration in either group. Health service provider protocols and clinical practice demonstrate poor compliance with current UK guidance on CI-AKI. A very low incidence of PC- AKI was demonstrated. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Clinical magnification and residual refraction after implantation of a double intraocular lens system in patients with macular degeneration.

PubMed

Amselem, Luis; Diaz-Llopis, Manuel; Felipe, Adelina; Artigas, Jose M; Navea, Amparo; García-Delpech, Salvador

2008-09-01

To evaluate the efficacy of a standard double intraocular lens (IOL) system (IOL-Vip) in patients with low vision and central scotoma due to macular degeneration and assess the predictability of the residual refraction and magnification. Ophthalmology Department, Hospital General Universitario, Valencia, Spain. This interventional prospective noncomparative case series comprised 13 consecutive surgical procedures in 10 patients with central scotoma. Follow-up was 12 months. Evaluation included the difference between preoperative and postoperative best corrected visual acuity (BCVA), refraction, position of the IOLs, endothelial cell density, and occurrence of postoperative complications. Residual refraction and eye magnification were calculated using a theory developed in a previous study, and the values were compared with the clinical results. The mean BCVA was 1.37 logMAR preoperatively and 0.68 logMAR 1 year postoperatively. The mean best corrected clinical gain was 44%. There was no statistically significant difference between the clinically evaluated and theoretically calculated residual refractions (P = .17). No intraoperative or postoperative complications occurred. Implantation of the double IOL system improved BCVA in patients with low vision due to advanced maculopathy. The results were best in myopic patients (long eyes); patients with hyperopia (short eyes) had high residual refraction. The postoperative clinical gain and residual refraction were predictable, showing the feasibility of implanting a customized double IOL.

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Fleseriu, Maria; Hashim, Ibrahim A; Karavitaki, Niki; Melmed, Shlomo; Murad, M Hassan; Salvatori, Roberto; Samuels, Mary H

2016-11-01

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

Nepali, Kunal; Ojha, Ritu; Lee, Hsueh-Yun; Liou, Jing-Ping

2016-08-01

Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.

A digital peer-to-peer learning platform for clinical skills development.

PubMed

Basnak, Jesse; Ortynski, Jennifer; Chow, Meghan; Nzekwu, Emeka

2017-02-01

Due to constraints in time and resources, medical curricula may not provide adequate opportunities for pre-clerkship students to practice clinical skills. To address this, medical students at the University of Alberta developed a digital peer-to-peer learning initiative. The initiative assessed if students can learn clinical skills from their peers in co-curricular practice objective structured clinical exams (OSCEs). A total of 144 first-year medical students participated. Students wrote case scenarios that were reviewed by physicians. Students enacted the cases in practice OSCEs, acting as the patient, physician, and evaluator. Verbal and electronic evaluations were completed. A digital platform was used to automate the process. Surveys were disseminated to assess student perceptions of their experience. Seventy-five percent of participants said they needed opportunities to practice patient histories and physical exams in addition to those provided in the medical school curriculum. All participants agreed that the co-curricular practice OSCEs met this need. The majority of participants also agreed that the digital platform was efficient and easy to use. Students found the practice OSCEs and digital platform effective for learning clinical skills. Thus, peer-to-peer learning and computer automation can be useful adjuncts to traditional medical curricula.

Pharmacological intervention of HIV-1 maturation.

PubMed

Wang, Dan; Lu, Wuxun; Li, Feng

2015-11-01

Despite significant advances in antiretroviral therapy, increasing drug resistance and toxicities observed among many of the current approved human immunodeficiency virus (HIV) drugs indicate a need for discovery and development of potent and safe antivirals with a novel mechanism of action. Maturation inhibitors (MIs) represent one such new class of HIV therapies. MIs inhibit a late step in the HIV-1 Gag processing cascade, causing defective core condensation and the release of non-infectious virus particles from infected cells, thus blocking the spread of the infection to new cells. Clinical proof-of-concept for the MIs was established with betulinic acid derived bevirimat, the prototype HIV-1 MI. Despite the discontinuation of its further clinical development in 2010 due to a lack of uniform patient response caused by naturally occurring drug resistance Gag polymorphisms, several second-generation MIs with improved activity against viruses exhibiting Gag polymorphism mediated resistance have been recently discovered and are under clinical evaluation in HIV/AID patients. In this review, current understanding of HIV-1 MIs is described and recent progress made toward elucidating the mechanism of action, target identification and development of second-generation MIs is reviewed.

Combining Non-Pharmacological Treatments with Pharmacotherapies for Neurological Disorders: A Unique Interface of the Brain, Drug–Device, and Intellectual Property

PubMed Central

Bulaj, Grzegorz

2014-01-01

Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug–device therapies may be offset by a value proposition of the exclusivity due to the patent–independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries. PMID:25071711

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

PubMed Central

Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

2014-01-01

Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

Photoacoustic tomography: applications for atherosclerosis imaging

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Goergen, Craig J.

2016-08-01

Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

Directions for new developments on statistical design and analysis of small population group trials.

PubMed

Hilgers, Ralf-Dieter; Roes, Kit; Stallard, Nigel

2016-06-14

Most statistical design and analysis methods for clinical trials have been developed and evaluated where at least several hundreds of patients could be recruited. These methods may not be suitable to evaluate therapies if the sample size is unavoidably small, which is usually termed by small populations. The specific sample size cut off, where the standard methods fail, needs to be investigated. In this paper, the authors present their view on new developments for design and analysis of clinical trials in small population groups, where conventional statistical methods may be inappropriate, e.g., because of lack of power or poor adherence to asymptotic approximations due to sample size restrictions. Following the EMA/CHMP guideline on clinical trials in small populations, we consider directions for new developments in the area of statistical methodology for design and analysis of small population clinical trials. We relate the findings to the research activities of three projects, Asterix, IDeAl, and InSPiRe, which have received funding since 2013 within the FP7-HEALTH-2013-INNOVATION-1 framework of the EU. As not all aspects of the wide research area of small population clinical trials can be addressed, we focus on areas where we feel advances are needed and feasible. The general framework of the EMA/CHMP guideline on small population clinical trials stimulates a number of research areas. These serve as the basis for the three projects, Asterix, IDeAl, and InSPiRe, which use various approaches to develop new statistical methodology for design and analysis of small population clinical trials. Small population clinical trials refer to trials with a limited number of patients. Small populations may result form rare diseases or specific subtypes of more common diseases. New statistical methodology needs to be tailored to these specific situations. The main results from the three projects will constitute a useful toolbox for improved design and analysis of small population clinical trials. They address various challenges presented by the EMA/CHMP guideline as well as recent discussions about extrapolation. There is a need for involvement of the patients' perspective in the planning and conduct of small population clinical trials for a successful therapy evaluation.

Establishing an Australian nurse practitioner-led colorectal cancer screening clinic.

PubMed

Morcom, Joylene; Dunn, Sandra V; Luxford, Yoni

2005-01-01

In Australia, colorectal cancer is the most commonly occurring internal cancer affecting both men and women, and the second most common cause of cancer-related death. Flexible sigmoidoscopy has not been commonly used as a screening tool in Australia due primarily to lack of resources. Until now, people at average risk of developing bowel cancer frequently undergo colonoscopy after referral to a specialist. To fill an identified need, a nurse practitioner-led colorectal screening service providing fecal occult blood testing and flexible sigmoidoscopy, health education and promotion, patient counseling, information and a referral point for general practitioners, and a referral service for above average-risk patients was established in a South Australian metropolitan teaching hospital. Establishment of this clinic required advanced and extended theoretical and clinical preparation for the nurse practitioner, as well as development of interdisciplinary relationships, referral processes, clinical infrastructure, and a marketing strategy. An audit of the first 100 flexible sigmoidoscopy patients revealed service and procedural outcomes that compared favorably with other colorectal screening services as well as a high level of patient satisfaction.

Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

PubMed

Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

2016-01-01

Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

The preclinical testing strategy for the development of novel chemical entities for the treatment of asthma.

PubMed

Hahn, Christian; Erb, Klaus Joseph

2008-06-01

Identifying and developing novel chemical entities (NCE) for the treatment of asthma is a time-consuming process and liabilities that endanger the successful progression of a compound from research into the patient are found throughout all phases of drug discovery. In particular the failure of advanced compounds in clinical studies due to lack of efficacy and/or safety concerns is tremendously costly. Therefore, in order to try and reduce the failure rate in clinical trials various in vitro and in vivo tests are performed during preclinical development, to rapidly identify liabilities, eliminate high risk compounds and promote promising potential drug candidates. To achieve this objective, numerous prerequisites have to be met regarding the physico-chemical properties of the compound, and bioactivity or model systems are needed to rate the therapeutic potential of new compounds. Drug liabilities such as target and species specificity, formulation issues, pharmacokinetics as well as pharmacodynamics and the toxic potential of the compound have to be analyzed in great detail before a compound can enter a clinical trial. A particularly challenging aspect of developing novel NCEs for the treatment of asthma is choosing and setting up in vivo models believed to be predictive for human disease. Numerous companies have in the past and are currently developing NCEs targeting many different pathways and cells with the aim to treat asthma. However, currently the only NCE having a significant market share are long-acting beta-agonists (LABA), inhaled and orally active steroids and leukotriene receptor antagonists. In the past many novel NCE for the treatment of asthma were effective in animal models but failed in the clinic. In this review we outline the prerequisites of novel NCE needed for clinical development.

Participatory design methods for the development of a clinical telehealth service for neonatal homecare.

PubMed

Garne Holm, Kristina; Brødsgaard, Anne; Zachariassen, Gitte; Smith, Anthony C; Clemensen, Jane

2017-01-01

Neonatal homecare delivered during home visits by neonatal nurses is a common method for supporting families of preterm infants following discharge. Telehealth has been introduced for the provision of neonatal homecare, resulting in positive feedback from parents of preterm infants. While the benefits are beginning to be realised, widespread uptake of telehealth has been limited due to a range of logistical challenges. Understanding user requirements is important when planning and developing a clinical telehealth service. We therefore used participatory design to develop a clinical telehealth service for neonatal homecare. The study adopted a participatory design approach to engage users in the development and design of a new telehealth service. Participatory design embraces qualitative research methods. Creative and technical workshops were conducted as part of the study. Tests of the telehealth service were conducted in the neonatal unit. Participants in this study were former and current parents of preterm infants eligible for neonatal homecare, and clinical staff (medical and nursing) from the neonatal unit. Preterm infants accompanied their parents. Based on the results obtained during the workshops and subsequent testing, we developed an application (app), which was integrated into the medical record at the neonatal unit. The app was used to initiate videoconferences and chat messages between the family at home and the neonatal unit, and to share information regarding infant growth and well-being. Results obtained from the workshops and testing demonstrated the importance of involving users when developing new telehealth applications. The workshops helped identify the challenges associated with delivery of the service, and helped instruct the design of a new telehealth service for neonatal homecare based on the needs of parents and clinical staff.

The Southeast Asian Influenza Clinical Research Network: development and challenges for a new multilateral research endeavor.

PubMed

Higgs, Elizabeth S; Hayden, Frederick G; Chotpitayasunondh, Tawee; Whitworth, Jimmy; Farrar, Jeremy

2008-04-01

The Southeast Asia Influenza Clinical Research Network (SEA ICRN) (www.seaclinicalresearch.org) is a recently developed multilateral, collaborative partnership that aims to advance scientific knowledge and management of human influenza through integrated clinical investigation. The partnership of hospitals and institutions in Indonesia, Thailand, United Kingdom, United States, and Viet Nam was established in late 2005 after agreement on the general principles and mission of the initiative and after securing initial financial support. The establishment of the SEA ICRN was both a response to the re-emergence of the highly pathogenic avian influenza A(H5N1) virus in Southeast Asia in late 2003 and an acknowledgment that clinical trials on emerging infectious diseases require prepared and coordinated research capacity. The objectives of the Network also include building sustainable research capacity in the region, compliance with international standards, and prompt dissemination of information and sharing of samples. The scope of research includes diagnosis, pathogenesis, treatment and prevention of human influenza due to seasonal or novel viruses. The Network has overcome numerous logistical and scientific challenges but has now successfully initiated several clinical trials. The establishment of a clinical research network is a vital part of preparedness and an important element during an initial response phase to a pandemic.

[The development of a distribution system for medical lasers and its clinical application].

PubMed

Okae, S; Ishiguchi, T; Ishigaki, T; Sakuma, S

1991-02-25

We developed a new laser beam generator system which can deliver laser beam to multiple terminals in distant clinical therapy rooms. The system possesses the distribution equipment by which Nd-YAG laser power is distributed to 8 output terminals under the computer control. Distributed laser beam is delivered to each distant terminal with clinical informations through the optical fiber. In the fundamental studies, possibility of distant transportation of laser beam (30 m) only with 10% loss of energy and without dangerous heating at the connection parts was shown. There seems to be no disadvantage associated with distribution laser beam. In the clinical study, the system was applied to five patients with the symptoms including hemosputum, esophageal stenosis, hemorrhage, lip ulcer and pain. Clinical usefulness of the system was proved. The advantages of the system are as follows: 1. Benefit of cost reduction due to multiple use of single laser source. 2. No necessity of transport of the equipment. 3. No requirement of a wide space to install the equipment in the distant room. 4. Efficient management and maintenance of the system by centralization. Further improvements, e.g., simultaneous use at multiple terminals and elongation of transportation up to 340 m, make the system more useful for clinical application.

Basic pharmacology of NMDA receptors.

PubMed

Gonda, Xenia

2012-01-01

NMDA receptors are ionotropic receptors mediating glutamatergic neurotransmission and play a role in several basic functions in the central nervous system, from regulating neurodevelopment and synaptic plasticity, learning and memory formation, cognitive processes, rhythm generation necessary for locomotor activity and breathing, and excitotoxicity. Due to their complex involvement in the above processes, NMDA receptors have been established to play a role in the etiopathology of several neuropsychiatric disorders such as ischaemia and traumatic brain injury, neurodegenerative disorders, pain syndromes, addiction, affective disorders and such neurodevelopmental disorders as autism or schizophrenia. NMDA receptors contain multiple types of subunits with distinct functional and pharmacological properties making the picture more complex. These receptors also offer multiple binding sites to be targeted with pharmacons, however, early broad-spectrum NMDA receptor antagonists had limited clinical use due to their intolerable adverse effect profile. The discovery of several types of subunit selective NMDA receptor antagonists may offer valuable therapeutic possibilities for several disorders, with improved clinical efficacy and decreased side effects. However, in spite of our increasing knowledge concerning the involvement of NMDA receptors in pathological processes, molecules with a selective action, tolerable side effect profile and good clinical efficacy are still only in clinical development in the majority of cases. Nevertheless, NMDA receptors offer a novel opportunity in the treatment of various neuropsychiatric conditions.

[A Case of Clinically Mild Encephalitis/encephalopathy with a Reversible Splenial Lesion due to Dengue Fever].

PubMed

Saito, Nobuo; Kitashouji, Emi; Kojiro, Maiko; Furumoto, Akitugu; Morimoto, Konosuke; Morita, Kouichi; Ariyoshi, Koya

2015-07-01

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48-year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS.

Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome.

PubMed

Tumiene, Birute; Čiuladaitė, Ž; Preikšaitienė, E; Mameniškienė, R; Utkus, A; Kučinskas, V

2017-11-01

Proper epigenetic regulation processes are crucial in the normal development of the human brain. An ever-increasing group of neurodevelopmental disorders due to derangements of epigenetic regulation involve both microdeletion and monogenic syndromes. Some of these syndromes have overlapping clinical phenotypes due to haploinsufficiency-sensitive genes involved in microdeletions. It was shown recently that the ZMYND11 gene has important functions in epigenetic regulation as an unconventional transcription co-repressor of highly expressed genes, possibly acting in the repression of cryptic transcription from gene bodies. The aim of our study was to compare the clinical phenotypes of patients with 10p15.3 deletions with the phenotypes of patients with loss-of-function ZMYND11 mutations. The results of our study further confirm that the ZMYND11 gene is the critical gene for the clinical phenotype of 10p15.3 microdeletion involving the terminal ~4 Mb of chromosome 10p. In addition, accumulating clinical data allow for further characterisation of this syndrome, including neurodevelopmental disorder, characteristic dysmorphic features and some other more frequent symptoms, such as behavioural disturbances, hypotonia, seizures, low birth weight, short stature in those older than 10 years of age, genitourinary malformations and recurrent infections.

A patient with 22q11.2 deletion syndrome: case report.

PubMed

Eryılmaz, Sema Kabataş; Baş, Firdevs; Satan, Ali; Darendeliler, Feyza; Bundak, Rüveyde; Günöz, Hülya; Saka, Nurçin

2009-01-01

22q11 deletion is one of the most frequently encountered genetic syndromes. The phenotypic spectrum shows a wide variability. We report a boy who presented at age 11.9 years with seizures due to hypocalcemia as a result of hypoparathyroidism. FISH analysis revealed a heterozygote deletion at 22q11.2. Positive findings for the syndrome were delayed speech development due to velofacial dysfunction, recurrent croup attacks in early childhood due to latent hypocalcemia and mild dysmorphic features. The findings of this patient indicate that 22q11 deletion syndrome may present with a wide spectrum of clinical findings and that this diagnosis needs to be considered even in patients of older ages presenting with hypocalcemia.

A Patient with 22q11.2 Deletion Syndrome: Case Report

PubMed Central

Baş, Firdevs; Satan, Ali; Darendeliler, Feyza; Bundak, Rüveyde; Günöz, Hülya; Saka, Nurçin

2009-01-01

22q11 deletion is one of the most frequently encountered genetic syndromes. The phenotypic spectrum shows a wide variability. We report a boy who presented at age 11.9 years with seizures due to hypocalcemia as a result of hypoparathyroidism. FISH analysis revealed a heterozygote deletion at 22q11.2. Positive findings for the syndrome were delayed speech development due to velofacial dysfunction, recurrent croup attacks in early childhood due to latent hypocalcemia and mild dysmorphic features. The findings of this patient indicate that 22q11 deletion syndrome may present with a wide spectrum of clinical findings and that this diagnosis needs to be considered even in patients of older ages presenting with hypocalcemia. Conflict of interest:None declared. PMID:21274400

Retinopathy of prematurity in Indonesia: Incidence and risk factors.

PubMed

Edy Siswanto, J; Sauer, Pieter Jj

2017-01-01

Retinopathy of prematurity (ROP) is a vaso-proliferative disease of the eye, which mainly affects preterm newborn infants with an incompletely vascularized retina. The incidence of ROP has increased in industrialized countries due to the increased survival of extremely low birth weight (ELBW) infants. ROP is also increasing in developing countries like Indonesia, where it is most likely due to the improved survival of ELBW infants. To ascertain the incidence of ROP and possible risk factors associated with the development of ROP in preterm infants in Indonesia. We reviewed the literature on the incidence and potential risk factors for the development of ROP in Indonesia, obtained data from three referral eye clinics and added data from our institution. The reported incidence of all stages of ROP in infants with a gestational age of <32 weeks ranged from 18-30%. One study showed that ROP also occurred at older gestational ages. Blindness due to ROP was seen in infants up to 35 weeks and with a birth weight of 2000 g. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in Indonesia. The overall incidence of ROP in infants born below 32 weeks in Indonesia is higher than in developed countries, and it is seen in infants with older gestational ages. This might be due to a less strict monitoring during the use of oxygen in Indonesia compared to industrialized countries.

Turning Access into a web-enabled secure information system for clinical trials.

PubMed

Dongquan Chen; Chen, Wei-Bang; Soong, Mayhue; Soong, Seng-Jaw; Orthner, Helmuth F

2009-08-01

Organizations that have limited resources need to conduct clinical studies in a cost-effective, but secure way. Clinical data residing in various individual databases need to be easily accessed and secured. Although widely available, digital certification, encryption, and secure web server, have not been implemented as widely, partly due to a lack of understanding of needs and concerns over issues such as cost and difficulty in implementation. The objective of this study was to test the possibility of centralizing various databases and to demonstrate ways of offering an alternative to a large-scale comprehensive and costly commercial product, especially for simple phase I and II trials, with reasonable convenience and security. We report a working procedure to transform and develop a standalone Access database into a secure Web-based secure information system. For data collection and reporting purposes, we centralized several individual databases; developed, and tested a web-based secure server using self-issued digital certificates. The system lacks audit trails. The cost of development and maintenance may hinder its wide application. The clinical trial databases scattered in various departments of an institution could be centralized into a web-enabled secure information system. The limitations such as the lack of a calendar and audit trail can be partially addressed with additional programming. The centralized Web system may provide an alternative to a comprehensive clinical trial management system.

Obstructive sleep apnea syndrome: An important piece in the puzzle of cardiovascular risk factors.

PubMed

Costa, Cátia; Santos, Beatriz; Severino, Davide; Cabanelas, Nuno; Peres, Marisa; Monteiro, Isabel; Leal, Margarida

2015-01-01

The obstructive sleep apnea syndrome (OSA) is a clinical entity characterized by recurring episodes of apnea and/or hypopnea during sleep, due to a total or partial collapse, respectively, of the upper airway. This collapse originates a set of pathophysiological changes that determine the appearance of several cardiovascular complications. OSA contributes for the development of hypertension, heart failure, arrhythmias and coronary heart disease. Nowadays it is recognized to be an important public health problem, taking into account not just its repercussions but also its prevalence, since the main risk factor for the disease is obesity, a growing problem worldwide, both in developed and developing countries. The present review summarizes the current knowledge about OSA, as regards its definition, pathophysiology, clinical manifestations, diagnosis, cardiovascular effects and treatment. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2016-01-01

Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed. © 2016 S. Karger AG, Basel.

Evaluation of a non-adherent, povidone-iodine dressing in a case series of chronic wounds.

PubMed

Campbell, N; Campbell, D

2013-08-01

Here we report a product evaluation for a non-adherent, povidone-iodine (PVP-I) dressing, determining the clinical need for the product, performing a literature review, clinical evaluation and cost-analysis, and developing a recommendation. This evaluation included 20 patients who experienced dressing pain with the previous antimicrobial dressing. Two patients discontinued the evaluation and four ulcers were non-healing; the remaining wounds closed with the PVP-I dressing. Patients indicated a preference for the PVP-I dressing, primarily due to lack of dressing pain. The PVP-I dressing was also the most cost-efficient.

Clinical relevance and biology of circulating tumor cells

PubMed Central

2011-01-01

Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

Bayesian hierarchical modeling for detecting safety signals in clinical trials.

PubMed

Xia, H Amy; Ma, Haijun; Carlin, Bradley P

2011-09-01

Detection of safety signals from clinical trial adverse event data is critical in drug development, but carries a challenging statistical multiplicity problem. Bayesian hierarchical mixture modeling is appealing for its ability to borrow strength across subgroups in the data, as well as moderate extreme findings most likely due merely to chance. We implement such a model for subject incidence (Berry and Berry, 2004 ) using a binomial likelihood, and extend it to subject-year adjusted incidence rate estimation under a Poisson likelihood. We use simulation to choose a signal detection threshold, and illustrate some effective graphics for displaying the flagged signals.

Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

PubMed

Razonable, Raymund R

2016-09-01

Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Papilloedema due to Chiari I malformation

PubMed Central

Zhang, Jason Chao; Bakir, Belal; Lee, Andrew; Yalamanchili, Sushma S

2011-01-01

The Chiari I malformation is a congenital abnormality characterised by downward displacement of the cerebellar tonsils through the foramen magnum into the cervical spine. It presents clinically most often in young adult women. Known ocular manifestations linked to Chiari I consist primarily of oculomotor paresis with cranial nerve VI palsy and convergence/divergence abnormalities. Papilloedema is a rare manifestation of Chiari I with a clinical presentation often similar to that of idiopathic intracranial hypertension. To highlight this unusual complication, the authors report a 64-year-old female who developed papilloedema as the only presenting neurological symptom resulting from a Chiari I malformation. PMID:22675036

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

Psychometric properties of the Geriatric Anxiety Inventory (GAI) and its short-form (GAI-SF) in a clinical and non-clinical sample of older adults.

PubMed

Johnco, Carly; Knight, Ashleigh; Tadic, Dusanka; Wuthrich, Viviana M

2015-07-01

The Geriatric Anxiety Inventory is a 20-item geriatric-specific measure of anxiety severity. While studies suggest good internal consistency and convergent validity, divergent validity from measures of depression are weak. Clinical cutoffs have been developed that vary across studies due to the small clinical samples used. A six-item short form (GAI-SF) has been developed, and while this scale is promising, the research assessing the psychometrics of this scale is limited. This study examined the psychometric properties of GAI and GAI-SF in a large sample of 197 clinical geriatric participants with a comorbid anxiety and unipolar mood disorder, and a non-clinical control sample (N = 59). The internal consistency and convergent validity with other measures of anxiety was adequate for GAI and GAI-SF. Divergent validity from depressive symptoms was good in the clinical sample but weak in the total and non-clinical samples. Divergent validity from cognitive functioning was good in all samples. The one-factor structure was replicated for both measures. Receiver Operating Characteristic analyses indicated that the GAI is more accurate at identifying clinical status than the GAI-SF, although the sensitivity and specificity for the recommended cutoffs was adequate for both measures. Both GAI and GAI-SF show good psychometric properties for identifying geriatric anxiety. The GAI-SF may be a useful alternative screening measure for identifying anxiety in older adults.

[Quality use of commercial laboratory for clinical testing services - considering laboratory's role].

PubMed

Ogawa, Shinji

2014-12-01

The number of commercial laboratories for clinical testing in Japan run privately has decreased to about 30 companies, and their business is getting tougher. Branch Lab. and FMS businesses have not expanded recently due to the new reimbursement system which adds an additional sample management fee, becoming effective in 2010. This presentation gives an outline of each role for hospital and commercial laboratories, and their pros & cons considering the current medical situation. Commercial laboratories have investigated how to utilize ICT systems for sharing test information between hospitals and our facilities. It would be very helpful to clarify issues for each hospital. We will develop and create new values for clinical laboratory testing services and forge mutually beneficial relationships with medical institutions. (Review).

NMOSD triggered by yellow fever vaccination - An unusual clinical presentation with segmental painful erythema.

PubMed

Schöberl, F; Csanadi, E; Eren, O; Dieterich, M; Kümpfel, T

2017-01-01

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

New approaches to the Doppler echocardiographic assessment of diastolic function: from research laboratory to clinical practice

NASA Technical Reports Server (NTRS)

Pasquet, A.; Garcia, M. J.; Thomas, J. D.

1999-01-01

Over the past decade, Doppler echocardiography has become a well-established tool for the diagnosis of left ventricular diastolic dysfunction. Unfortunately, in many clinical situations traditional Doppler indices of transmittal and pulmonary venous flow are inconclusive, primarily due to their dependence on left atrial pressure. Recently, new Doppler indices that are much less dependent on preload have been developed, based on intraventricular flow propagation and intrinsic myocardial velocity. These methodologies provide direct assessment of ventricular relaxation and the small intraventricular pressure gradients essential to efficient filling of the ventricle. We review in this article the theoretical and experiment background of these new echo techniques as well as how they can be implemented in routine clinical practice.

Conclusions and future directions for the REiNS International Collaboration

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, Clemens O.; Walsh, Karin S.; Wolters, Pamela L.; Plotkin, Scott R.

2013-01-01

The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development. The REiNS recommendations are made based on current knowledge. Experience with the use of the recommended endpoints in clinical trials, development of new tools and technologies, new knowledge of the natural history of NF, and advances in the methods used to analyze endpoints will likely lead to modifications of the currently proposed guidelines, which will be shared with the NF research community through the REiNS Web site www.reinscollaboration.org. Due to the clinical complexity of NF, there is a need to seek expertise from multiple medical disciplines, regulatory agencies, and industry to develop trial endpoints and designs, which will lead to the identification and approval of effective treatments for NF tumor and nontumor manifestations. The REiNS Collaboration welcomes anyone interested in providing his or her expertise toward this effort. PMID:24249805

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

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

Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov; Via, Laura E.; Kumar, Mia R.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT),more » with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.« less

Morbidity of mansoni schistosomiasis in Pernambuco-Brazil: Analysis on the temporal evolution of deaths, hospital admissions and severe clinical forms (1999-2014).

PubMed

Barbosa, Constança Simões; de Souza Gomes, Elainne Christine; Campos, Julyana Viegas; de Oliveira, Fernando José Moreira; da Silva Mesquita, Millena Carla; de Oliveira, Emilia Carolle Azevedo; Domingues, Ana Lucia Coutinho

2016-12-01

Current scientific information reported that due to successive treatments of schistosomiasis cases in endemic areas of Brazil in the last 30 years, there has been a decrease in severe clinical form (hepatosplenic) and mortality from upper gastrointestinal bleeding due to this disease. Against this information, literature data show that the state of Pernambuco presents significant percentage of deaths and hospitalizations due to schistosomiasis, and occurrence of severe clinical forms as schistosomiasis myeloradiculopathy and persistence of localities with high parasite loads. This scenario justified this research which seeking to update the morbidity and mortality of schistosomiasis in Pernambuco. To conduct a temporal analysis on the evolution of deaths, hospital admissions and severe forms of Manson's schistosomiasis over the last 16 years in Pernambuco, Brazil. It was performed a gathering secondary data on schistosomiasis, from healthcare information systems and from the records of Hospital das Clínicas, Federal University of Pernambuco (HC-UFPE), covering the period from 1999 to 2014. From 1999 to 2013 were registred 2578 deaths due to schistosomiasis and between 2008 and 2014 were recorded 473 hospitalizations for this disease. Among 1999-2014 were identified 1943 cases of schistosomiasis treated at the Hospital das Clínicas of Pernambuco. Among these cases, 72.6% (n. 1411) of the individuals presented the hepatosplenic clinical form (HE), 60.8% (n. 858) were at the age group 30-59 years (adults) and 58% were female. Among the HE cases, 4.6% (n. 58) had ascites, 43.2% (n. 556) had upper gastrointestinal bleeding and 39.1% (n. 489) had collateral circulation. The pattern of fibrosis in the liver E/EC (advanced fibrosis) and F/FC (very advanced fibrosis) occurred in 65.5% (n. 793) of cases. Between 1999-2014 the evolution curve of severe clinical forms of schistosomiasis remained stable, showing a tendency to decline from 2012. When compared to other states of Brazil, Pernambuco shows high numbers of deaths and hospital admissions due to schistosomiasis. The actions of the Schistosomiasis Control Program (PCE) have been developed in a disintegrated, disjointed and discontinuous way, which may explain the magnitude of deaths, hospitalizations and severe forms of the disease in Pernambuco, showing a lack of control and the maintenance of severe frame morbidity of schistosomiasis in this state. Copyright © 2016 Elsevier B.V. All rights reserved.

[Prostatic abscess. Contribution of the x-ray computed tomography. Apropos of a case].

PubMed

Husain, A; Touzard, D

1988-01-01

We reported a case of prostatic abscess due to staphylococeus aureus developed in a chronic alcoholic patient. The clinical symptoms and signs were largely masked by prior antibiotic therapy. Computed axial tomographic scanning of the pelvis made the diagnosis and demonstrated the resolution of the prostatic abscess following antibiotic therapy and spontaneous rupture to the urethra.

Brain Development in Autism: Early Overgrowth Followed by Premature Arrest of Growth

ERIC Educational Resources Information Center

Courchesne, Eric

2004-01-01

Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies…

Alzheimer’s Disease Drug Development in 2008 and Beyond: Problems and Opportunities

PubMed Central

Becker, Robert E.; Greig, Nigel H.

2008-01-01

Recently, a number of Alzheimer’s disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers’ abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development. PMID:18690832

Augmented Reality Image Guidance in Minimally Invasive Prostatectomy

NASA Astrophysics Data System (ADS)

Cohen, Daniel; Mayer, Erik; Chen, Dongbin; Anstee, Ann; Vale, Justin; Yang, Guang-Zhong; Darzi, Ara; Edwards, Philip'eddie'

This paper presents our work aimed at providing augmented reality (AR) guidance of robot-assisted laparoscopic surgery (RALP) using the da Vinci system. There is a good clinical case for guidance due to the significant rate of complications and steep learning curve for this procedure. Patients who were due to undergo robotic prostatectomy for organ-confined prostate cancer underwent preoperative 3T MRI scans of the pelvis. These were segmented and reconstructed to form 3D images of pelvic anatomy. The reconstructed image was successfully overlaid onto screenshots of the recorded surgery post-procedure. Surgeons who perform minimally-invasive prostatectomy took part in a user-needs analysis to determine the potential benefits of an image guidance system after viewing the overlaid images. All surgeons stated that the development would be useful at key stages of the surgery and could help to improve the learning curve of the procedure and improve functional and oncological outcomes. Establishing the clinical need in this way is a vital early step in development of an AR guidance system. We have also identified relevant anatomy from preoperative MRI. Further work will be aimed at automated registration to account for tissue deformation during the procedure, using a combination of transrectal ultrasound and stereoendoscopic video.

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

What is new in 2017? Update on fertility preservation in cancer patients.

PubMed

Winkler-Crepaz, Katharina; Böttcher, Bettina; Toth, Bettina; Wildt, Ludwig; Hofer-Tollinger, Susanne

2017-12-01

The prevention of fertility loss due to cancer treatment as well as non-malignant causes has been gaining importance over the last few decades. Clinically applied modalities for fertility preservation in cancer patients include cryopreservation of oocytes and embryos, the application of GnRH agonists, ovarian tissue banking, and cryopreservation of ejaculated or surgically extracted sperm. In addition, several new possibilities to restore fertility are currently being investigated, such as the establishment of in-vitro culture systems for gonadal tissue, the development of artificial gonads, and the application of germline stem cells. This review aims to provide an update on the methods currently applied in clinical practice for fertility preservation, as well as to summarize the progress made in the development of novel strategies for fertility preservation.

Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

PubMed

Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

2015-12-01

Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

[Occlusion: current situation and prospect in view of holistic integrative medicine].

PubMed

Wang, M Q; Liu, X D

2017-08-09

The rise of holistic integrative medicine (HIM) is an inevitable consequence of modern medical development which emphasizes the change from specialization to integration of the most advanced medical knowledge. It does not mean a simple collection of the medical theories, but means the digestion of those theories for the clinical practical application. Because occlusal therapy is characterized as not only a high level of individualization, but also a relation to many stomatology and other disciplines, such as plastic surgery, orthopedics, neurosciences and psychology. It needs the HIM to guide the clinical practice. With undertaking occlusal therapy, to avoid the limitation due to the excessive specialized disciplines, and to provide effective treatment plans for abnormal occlusion induced diseases, it is necessary to develop the discipline of the holistic integrative stomatology.

Defibrotide: a review on clinical use and future development.

PubMed

Larocca, A; Cavallo, F; Magarotto, V; Rossi, D; Patriarca, F; Boccadoro, M; Palumbo, A

2008-08-01

Defibrotide is a deoxyribonucleic acid derivative that has been developed for the treatment of different vascular disorders. The authors reviewed the literature to give due representation to the spectrum of pharmacological properties and clinical application of this drug, evaluating consolidate and innovative application. The authors used PubMed from November 1982 to December 2007 and meeting abstracts (form American Society of Hematology Annual Meeting) with updated data as the sources for this review and selecting the most relevant papers when two or more articles covered the same point of interest. Defibrotide has been used effectively in the treatment of endothelial complications of allogeneic stem cell transplantation and recent preclinical evidences suggest an antiangiogenic effect and an anticancer activity. Further in vivo and in vitro investigations are needed.

Post-obstructive pulmonary edema from aspirated nuts.

PubMed

Bashir, Ahsan; Ahmad, Sabina Qureshi; Silverman, Joshua; Concepcion, Emily; Lee, Haesoon

2017-01-01

Post-obstructive pulmonary edema is thought to occur from hemodynamic changes secondary to forced inspiration against the closed airway due to acute or chronic airway obstruction. We report a case of a 13 month-old boy who developed pulmonary edema from aspirated foreign body, nuts. He underwent emergency bronchoscopy to confirm the clinical diagnosis of aspirated nuts in the trachea and nuts were removed endoscopically. His trachea was then intubated and he was mechanically ventilated with oxygen. He developed florid pulmonary edema early in the course with tracheal obstruction and during endoscopic removal of nuts. After removal of obstruction he was ventilated mechanically and pulmonary edema cleared rapidly. Aspirated nuts obstructing trachea can induce obstructive pulmonary edema. Early recognition of foreign body obstruction based on clinical history and its removal resolved pulmonary edema.

Medical application and clinical validation for reliable and trustworthy physiological monitoring using functional textiles: experience from the HeartCycle and MyHeart project.

PubMed

Reiter, Harald; Muehlsteff, Jens; Sipilä, Auli

2011-01-01

Functional textiles are seen as promising technology to enable healthcare services and medical care outside hospitals due to their ability to integrate textile-based sensing and monitoring technologies into the daily life. In the past much effort has been spent onto basic functional textile research already showing that reliable monitoring solutions can be realized. The challenge remains to find and develop suited medical application and to fulfil the boundary conditions for medical endorsement and exploitation. The HeartCycle vest described in this abstract will serve as an example for a functional textile carefully developed according to the requirements of a specific medical application, its clinical validation, the related certification aspects and the next improvement steps towards exploitation.

An Information Extraction Framework for Cohort Identification Using Electronic Health Records

PubMed Central

Liu, Hongfang; Bielinski, Suzette J.; Sohn, Sunghwan; Murphy, Sean; Wagholikar, Kavishwar B.; Jonnalagadda, Siddhartha R.; Ravikumar, K.E.; Wu, Stephen T.; Kullo, Iftikhar J.; Chute, Christopher G

Information extraction (IE), a natural language processing (NLP) task that automatically extracts structured or semi-structured information from free text, has become popular in the clinical domain for supporting automated systems at point-of-care and enabling secondary use of electronic health records (EHRs) for clinical and translational research. However, a high performance IE system can be very challenging to construct due to the complexity and dynamic nature of human language. In this paper, we report an IE framework for cohort identification using EHRs that is a knowledge-driven framework developed under the Unstructured Information Management Architecture (UIMA). A system to extract specific information can be developed by subject matter experts through expert knowledge engineering of the externalized knowledge resources used in the framework. PMID:24303255

Quantitative Medical Image Analysis for Clinical Development of Therapeutics

NASA Astrophysics Data System (ADS)

Analoui, Mostafa

There has been significant progress in development of therapeutics for prevention and management of several disease areas in recent years, leading to increased average life expectancy, as well as of quality of life, globally. However, due to complexity of addressing a number of medical needs and financial burden of development of new class of therapeutics, there is a need for better tools for decision making and validation of efficacy and safety of new compounds. Numerous biological markers (biomarkers) have been proposed either as adjunct to current clinical endpoints or as surrogates. Imaging biomarkers are among rapidly increasing biomarkers, being examined to expedite effective and rational drug development. Clinical imaging often involves a complex set of multi-modality data sets that require rapid and objective analysis, independent of reviewer's bias and training. In this chapter, an overview of imaging biomarkers for drug development is offered, along with challenges that necessitate quantitative and objective image analysis. Examples of automated and semi-automated analysis approaches are provided, along with technical review of such methods. These examples include the use of 3D MRI for osteoarthritis, ultrasound vascular imaging, and dynamic contrast enhanced MRI for oncology. Additionally, a brief overview of regulatory requirements is discussed. In conclusion, this chapter highlights key challenges and future directions in this area.

Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.

PubMed

Wang, Yuchen; Newman, Maureen R; Benoit, Danielle S W

2018-06-01

Impaired fracture healing is a major clinical problem that can lead to patient disability, prolonged hospitalization, and significant financial burden. Although the majority of fractures heal using standard clinical practices, approximately 10% suffer from delayed unions or non-unions. A wide range of factors contribute to the risk for nonunions including internal factors, such as patient age, gender, and comorbidities, and external factors, such as the location and extent of injury. Current clinical approaches to treat nonunions include bone grafts and low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to select patients due to limitations including donor morbidities (grafts) and necessity of fracture reduction (LIPUS), respectively. To date, therapeutic approaches for bone regeneration rely heavily on protein-based growth factors such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under development to circumvent challenges associated with traditional growth factors. While preclinical studies has shown promise, drug delivery has become a major hurdle stalling clinical translation. Therefore, this review overviews current therapies employed to stimulate fracture healing pre-clinically and clinically, including a focus on drug delivery systems for growth factors, parathyroid hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances and future promise of fracture-targeted drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Interprofessional Obstetric Ultrasound Education: Successful Development of Online Learning Modules; Case-Based Seminars; and Skills Labs for Registered and Advanced Practice Nurses, Midwives, Physicians, and Trainees.

PubMed

Shaw-Battista, Jenna; Young-Lin, Nichole; Bearman, Sage; Dau, Kim; Vargas, Juan

2015-01-01

Ultrasound is an important aid in the clinical diagnosis and management of normal and complicated pregnancy and childbirth. The technology is widely applied to maternity care in the United States, where comprehensive standard ultrasound examinations are routine. Targeted scans are common and used for an increasing number of clinical indications due to emerging research and a greater availability of equipment with better image resolution at lower cost. These factors contribute to an increased demand for obstetric ultrasound education among students and providers of maternity care, despite a paucity of data to inform education program design and evaluation. To meet this demand, from 2012 to 2015 the University of California, San Francisco nurse-midwifery education program developed and implemented an interprofessional obstetric ultrasound course focused on clinical applications commonly managed by maternity care providers from different professions and disciplines. The course included matriculating students in nursing and medicine, as well as licensed practitioners such as registered and advanced practice nurses, midwives, and physicians and residents in obstetrics and gynecology and family medicine. After completing 10 online modules with a pre- and posttest of knowledge and interprofessional competencies related to teamwork and communication, trainees attended a case-based seminar and hands-on skills practicum with pregnant volunteers. The course aimed to establish a foundation for further supervised clinical training prior to independent practice of obstetric ultrasound. Course development was informed by professional guidelines and clinical and education research literature. This article describes the foundations, with a review of the challenges and solutions encountered in obstetric ultrasound education development and implementation. Our experience will inform educators who wish to facilitate obstetric ultrasound competency development among new and experienced maternity care providers in academic and clinical settings. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health. © 2015 by the American College of Nurse-Midwives.

Epidemiology of Mental Health Attendances at Emergency Departments: Systematic Review and Meta-Analysis

PubMed Central

Rojas-García, Antonio; Clarke, Katherine; Moore, Anna; Whittington, Craig; Stockton, Sarah; Thomas, James; Pilling, Stephen; Raine, Rosalind

2016-01-01

Background The characteristics of Emergency Department (ED) attendances due to mental or behavioural health disorders need to be described to enable appropriate development of services. We aimed to describe the epidemiology of mental health-related ED attendances within health care systems free at the point of access, including clinical reason for presentation, previous service use, and patient sociodemographic characteristics. Method Systematic review and meta-analysis of observational studies describing ED attendances by patients with common mental health conditions. Findings 18 studies from seven countries met eligibility criteria. Patients attending due to mental or behavioural health disorders accounted for 4% of ED attendances; a third were due to self-harm or suicidal ideation. 58.1% of attendees had a history of psychiatric illness and up to 58% were admitted. The majority of studies were single site and of low quality so results must be interpreted cautiously. Conclusions Prevalence studies of mental health-related ED attendances are required to enable the development of services to meet specific needs. PMID:27120350

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho

2018-01-01

Background Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. Objective The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. Methods This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. Results In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. Conclusions The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. PMID:29691212

Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.

PubMed

Castiello, Luciano; Sabatino, Marianna; Zhao, Yingdong; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Wang, Ena; Wood, Lauren V; Marincola, Francesco M; Puri, Raj K; Stroncek, David F

2013-02-01

Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers.

History, ethics, advantages and limitations of experimental models for hepatic ablation.

PubMed

Ong, Seok Ling; Gravante, Gianpiero; Metcalfe, Matthew S; Dennison, Ashley R

2013-01-14

Numerous techniques developed in medicine require careful evaluation to determine their indications, limitations and potential side effects prior to their clinical use. At present this generally involves the use of animal models which is undesirable from an ethical standpoint, requires complex and time-consuming authorization, and is very expensive. This process is exemplified in the development of hepatic ablation techniques, starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies. The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models. Ex vivo non perfused models are less expensive, easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours. In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines. Isolated perfused ex vivo liver models have been used to study drug toxicity, liver failure, organ transplantation and hepatic ablation and combine advantages of both previous models.

Repair and tissue engineering techniques for articular cartilage.

PubMed

Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

Protease-activated receptor-1 antagonists in long-term antiplatelet therapy. Current state of evidence and future perspectives.

PubMed

Moschonas, I C; Goudevenos, J A; Tselepis, A D

2015-04-15

Atherothrombosis and its clinical manifestations are among the leading causes of death in the developed world. The current standard-of-care antiplatelet therapy for the treatment of such events comprises aspirin and a thienopyridine or ticagrelor. However, recurrent ischemic events due to residual cardiovascular risk are a common phenomenon in these patients. It is believed that this residual risk is caused, at least in part, by thrombin, which signals through protease-activated receptors (PARs) and especially PAR-1. Thus, PAR-1 antagonism could represent an effective approach in the treatment of atherothrombotic disease. In this context, two potent and selective agents have been developed, vorapaxar and atopaxar. However, only vorapaxar has completed phase 3 clinical trials. In the present review, the main pharmacodynamic and pharmacokinetic properties of the PAR-1 antagonists are briefly described and the latest clinical data on vorapaxar are presented. Copyright © 2015. Published by Elsevier Ireland Ltd.

Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.

PubMed

Beavis, Paul A; Slaney, Clare Y; Kershaw, Michael H; Gyorki, David; Neeson, Paul J; Darcy, Phillip K

2016-02-01

The frontiers of cancer immunotherapy are extending in terms of both the range of cancer types that can potentially be targeted and the types of therapeutics that are in clinical development. The use of adoptive cellular therapy (ACT) and its derivative, chimeric antigen receptor (CAR) T cells, is currently limited to hematological malignancies and immunogenic cancers such as melanoma and renal cell carcinoma. Although ACT utilizing ex vivo expanded tumor-infiltrating lymphocytes (TIL) or engineered CAR/TCR T cells have undergone clinical trials for other solid cancers, their efficacy to date has been limited. This may be due, in part, to the immunosuppressive nature of the tumor microenvironment. The development of novel combination approaches which target the immunosuppressive network engineered by tumors has raised the possibility of using ACT for a broader range of cancers. This review summarizes the potential of such strategies and outlines the clinical relevance of these observations. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Clinical guidelines for the prevention of infective endocarditis].

PubMed

Pérez-Lescure Picarzo, J; Crespo Marcos, D; Centeno Malfaz, F

2014-03-01

This article sets out the recommendations for the prevention of infective endocarditis (IE), contained in the guidelines developed by the American Heart Association (AHA) and the European Society of Cardiology (ESC), from which the recommendations of the Spanish Society of Paediatric Cardiology and Congenital Heart Disease have been agreed. In recent years, there has been a considerable change in the recommendations for the prevention of IE, mainly due to the lack of evidence on the effectiveness of antibiotic prophylaxis in prevention, and the risk of the development of antibiotic resistance. The main change is a reduction of the indications for antibiotic prophylaxis, both in terms of patients and procedures considered at risk. Clinical practice guidelines and recommendations should assist health professionals in making clinical decisions in their daily practice. However, the ultimate judgment regarding the care of a particular patient must be taken by the physician responsible. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Fast interactive real-time volume rendering of real-time three-dimensional echocardiography: an implementation for low-end computers

NASA Technical Reports Server (NTRS)

Saracino, G.; Greenberg, N. L.; Shiota, T.; Corsi, C.; Lamberti, C.; Thomas, J. D.

2002-01-01

Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac imaging modality. However, partly due to lack of user-friendly software, RT3DE has not been widely accepted as a clinical tool. The object of this study was to develop and implement a fast and interactive volume renderer of RT3DE datasets designed for a clinical environment where speed and simplicity are not secondary to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy) were imaged using RT3DE. Using our newly developed software, all 3D data sets were rendered in real-time throughout the cardiac cycle and assessment of cardiac function and pathology was performed for each case. The real-time interactive volume visualization system is user friendly and instantly provides consistent and reliable 3D images without expensive workstations or dedicated hardware. We believe that this novel tool can be used clinically for dynamic visualization of cardiac anatomy.

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.

PubMed

Relling, M V; McDonagh, E M; Chang, T; Caudle, K E; McLeod, H L; Haidar, C E; Klein, T; Luzzatto, L

2014-08-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.

Why calpain inhibitors are interesting leading compounds to search for new therapeutic options to treat leishmaniasis?

PubMed

Ennes-Vidal, Vitor; Menna-Barreto, Rubem Figueiredo Sadock; Branquinha, Marta Helena; Dos Santos, André Luis Souza; D'Avila-Levy, Claudia Masini

2017-02-01

Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.

Drugs currently under investigation for the treatment of invasive candidiasis.

PubMed

McCarthy, Matthew W; Walsh, Thomas J

2017-07-01

The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

Development of the clinic of pulmonology and allergy.

PubMed

Dokic, D

2013-01-01

University Pulmology and Allergy Clinic was founded in 1975 when the Depertment of Internal Medicine, directed by Prof. Dr. Dimitar Arsov, later member of the Macedonian Academy of Sciencies and Arts, was divided into eight separate and independent clinics. The first head of the Pulmonology and Allergy Clinic was Prof. Dr. Ljubomir Kotevski. He had a very difficult goal: to establish and further develop the newly formed clinic. The Clinic flourished and became one of the leading Clinics in the Clinical Centre during the directorship of Prof. dr. Dejan Dokic.. He completely rebuilt and refurbished the Clinic, which became a modern Clinic providing excellent working conditions for the employees and, most importantly, provided a first class service to the patients. During his mandate he obtained a grant from the Japanese Government worth $1,000,000 which was used to obtain a new, modern and sophisticated medical equipment. Since the establishment of the clinic, many national and international scientific projects were carried out and many scientific papers were published as well as many monographs, and chapters in scientific books. As a result of continuous education, of the total number of 24 doctors there are 16 subspecialists in respiratory medicine and 4 specialists in internal medicine. There are 9 professors in internal medicine at the University of Pulmonology and Allergy Clinic lecturing at the Medical Faculty in Skopje. The University Pulmonology and Allergy Clinic has an international reputation due to many contacts with famous European Institutions. All these international interrelations have resulted in honouring 3 professors: Prof. Dr. Gert Kunkel from Berlin, Germany, Prof. Dr. Robert Loddenkemper from Berlin, Germany and Prof. Dr. Peter Howard from Southampton, UK.

Clinical data miner: an electronic case report form system with integrated data preprocessing and machine-learning libraries supporting clinical diagnostic model research.

PubMed

Installé, Arnaud Jf; Van den Bosch, Thierry; De Moor, Bart; Timmerman, Dirk

2014-10-20

Using machine-learning techniques, clinical diagnostic model research extracts diagnostic models from patient data. Traditionally, patient data are often collected using electronic Case Report Form (eCRF) systems, while mathematical software is used for analyzing these data using machine-learning techniques. Due to the lack of integration between eCRF systems and mathematical software, extracting diagnostic models is a complex, error-prone process. Moreover, due to the complexity of this process, it is usually only performed once, after a predetermined number of data points have been collected, without insight into the predictive performance of the resulting models. The objective of the study of Clinical Data Miner (CDM) software framework is to offer an eCRF system with integrated data preprocessing and machine-learning libraries, improving efficiency of the clinical diagnostic model research workflow, and to enable optimization of patient inclusion numbers through study performance monitoring. The CDM software framework was developed using a test-driven development (TDD) approach, to ensure high software quality. Architecturally, CDM's design is split over a number of modules, to ensure future extendability. The TDD approach has enabled us to deliver high software quality. CDM's eCRF Web interface is in active use by the studies of the International Endometrial Tumor Analysis consortium, with over 4000 enrolled patients, and more studies planned. Additionally, a derived user interface has been used in six separate interrater agreement studies. CDM's integrated data preprocessing and machine-learning libraries simplify some otherwise manual and error-prone steps in the clinical diagnostic model research workflow. Furthermore, CDM's libraries provide study coordinators with a method to monitor a study's predictive performance as patient inclusions increase. To our knowledge, CDM is the only eCRF system integrating data preprocessing and machine-learning libraries. This integration improves the efficiency of the clinical diagnostic model research workflow. Moreover, by simplifying the generation of learning curves, CDM enables study coordinators to assess more accurately when data collection can be terminated, resulting in better models or lower patient recruitment costs.

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria.

PubMed

Burden-Teh, E; Phillips, R C; Thomas, K S; Ratib, S; Grindlay, D; Murphy, R

2017-11-06

The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardize patient recruitment into clinical trials and case definitions in observational studies. The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis. A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was to record the sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool. Twenty-three studies met the inclusion criteria. None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, and questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (> 90%) were reported in many studies. However, the study authors often did not specify how the criteria would be used clinically or in research. This review identified studies with varying risk of bias, and due to each study developing separate criteria meta-analysis was not possible. Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ study designs allowing high-quality diagnostic accuracy testing. Existing and newly developed criteria require validation. © 2017 British Association of Dermatologists.

Current status of anti-picornavirus therapies.

PubMed

Barnard, Dale L

2006-01-01

Picornaviruses are important human pathogens causing severe morbidity and some mortality with the potential to cause worldwide crippling disease. Currently, there are few treatments for many of the viruses in the Picornaviridae, For rhinoviruses, there are no approved treatments, although ruprintrivir looks promising in clinical trials and pyridazinyl oxime ethers may prove useful. Poliovirus treatments are needed to supplement the World Health Organization's polio eradication plan in order to treat infections caused by reversion of the attenuated vaccine virus and to supplement vaccine coverage control in polio endemic areas. However, no promising compounds for treatment of poliovirus have been developed due to the efficacy of the vaccines in use. Broad-spectrum inhibitors developed for other picornavirus may be useful for poliovirus infections. Coxsackievirus infections in children and in infants are being treated with pleconaril with some efficacy in reducing mortality and improving recovery, albeit the treatment is often on a compassionate use basis. There are no therapies for echovirus infections. Very little drug discovery research is being done to develop inhibitors for echovirus infections, probably due to the broad-spectrum inhibition exhibited by capsid binding agents and protease inhibitors discovered for treatment of other picornaviruses. For example, pyridazinyl oxime ethers are inhibitory to most echoviruses. Treatments for enterovirus infections are also limited, although in a small clinical trial, milrinone seemed to reduce mortality and improve recovery from EV71-induced pulmonary edema. Thus, these results strongly emphasize the need for the development of potent and nontoxic compounds for the treatment of picornavirus infections.

[Kounis syndrome: a paradoxal non-ST elevation myocardial infarction case after triamcinolone treatment for dermatitis].

PubMed

Yılmaz, Mücahid; Korkmaz, Hasan

2018-04-01

Kounis syndrome is defined as the clinical development of acute coronary syndrome caused by the activation of inflammatory cells due to an allergy, hypersensitivity, anaphylaxis, or anaphylactic reaction. Corticosteroids that are used in the treatment of many inflammatory conditions may paradoxically cause allergic reactions and even anaphylaxis. This article is a description of the case of a 52-yearold female patient who had a non-ST elevation myocardial infarction after the administration of triamcinolone that was relieved with antihistaminic treatment. The patient had been diagnosed with dermatitis at another medical center and injected with 40 mg/mL (intramuscular [IM]) of triamcinolone acetonide and developed chest pain 15 minutes after the first dose. Despite a normal physical examination and echocardiogram, laboratory tests revealed troponin positivity and an inferolateral ST depression was present on an electrocardiogram (ECG). The ECG findings and clinical symptoms resolved completely after conservative anti-ischemic treatment and antihistaminic therapy (pheniramine maleate 45.5 mg/2 mL, Avil ampoule, IV; Sanofi-Aventis, Paris, France) and coronary angiography evaluation of the arteries was normal. The heart, and in particular the coronary arteries, are among the organs that are most damaged during hypersensitivity reactions and anaphylaxis. Although Kounis syndrome is not a rare condition, few cases have been reported in clinical practice. The failure to recognize Kounis syndrome due to inadequately defined cases may lead to unwanted medical results. Kounis syndrome should be kept in mind in order to make a rapid and accurate diagnosis.

3D Proximal Tubule Tissues Recapitulate Key Aspects of Renal Physiology to Enable Nephrotoxicity Testing

PubMed Central

King, Shelby M.; Higgins, J. William; Nino, Celina R.; Smith, Timothy R.; Paffenroth, Elizabeth H.; Fairbairn, Casey E.; Docuyanan, Abigail; Shah, Vishal D.; Chen, Alice E.; Presnell, Sharon C.; Nguyen, Deborah G.

2017-01-01

Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes. Histological characterization demonstrated formation of extensive microvascular networks supported by endogenous extracellular matrix deposition. The epithelial cells of the 3D proximal tubule tissues demonstrated tight junction formation and expression of renal uptake and efflux transporters; the polarized localization and function of P-gp and SGLT2 were confirmed. Treatment of 3D proximal tubule tissues with the nephrotoxin cisplatin induced loss of tissue viability and epithelial cells in a dose-dependent fashion, and cimetidine rescued these effects, confirming the role of the OCT2 transporter in cisplatin-induced nephrotoxicity. The tissues also demonstrated a fibrotic response to TGFβ as assessed by an increase in gene expression associated with human fibrosis and histological verification of excess extracellular matrix deposition. Together, these results suggest that the bioprinted 3D proximal tubule model can serve as a test bed for the mechanistic assessment of human nephrotoxicity and the development of pathogenic states involving epithelial-interstitial interactions, making them an important adjunct to animal studies. PMID:28337147

Stem cells: The Next Therapeutic Frontier

PubMed Central

Humes, H. David

2005-01-01

Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine, and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics; but recent advances in cellular and molecular biology have expanded the potential applications of this approach. Although recombinant genetic engineering to produce a variety of therapeutics such as human erythropoietin and insulin has proven successful, these treatments are unable to completely correct or reverse disease states, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering (1,2). The translation of this discipline to medical practice has tremendous potential, but in many applications technological issues need to be overcome. Since many cell-based indications are already being evaluated in the clinic, the field appears to be on the threshold of a number of successes. This review will focus on our group's use of human stem/progenitor cells in the treatment of acute and chronic renal failure as extensions to the current successful renal substitution processes of hemodialysis and hemofiltration. PMID:16555613

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations*

PubMed Central

Lynagh, Timothy; Lynch, Joseph W.

2010-01-01

The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light-activated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human α1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G α1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID:20308070

Priorities for CMV vaccine development

PubMed Central

Krause, Philip R.; Bialek, Stephanie R.; Boppana, Suresh B.; Griffiths, Paul D.; Laughlin, Catherine A.; Ljungman, Per; Mocarski, Edward S.; Pass, Robert F.; Read, Jennifer S.; Schleiss, Mark R.; Plotkin, Stanley A.

2015-01-01

A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering preemptive antiviral therapy as an endpoint, because widespread use of preemptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection. PMID:24129123

Research, evidence, and ethics: new technology or grey medicine.

PubMed

Zhai, Haoran; Zhong, Wenzhao; Wu, Yilong

2015-02-01

Major pioneering advances of medicine in history tend to manifest in two directions that seem divergent but actually unified with dialectics: one is the important biological principle revealed by in-depth studies from the clinic to the laboratory based on individual cases; the other is the colonial generality displayed by epidemiologic data from large-scale samples. Although advances predominated, we human beings were paying dearly for it due to serious incidents of endangering ourselves and defects of restrictions of laws and ethics. Subsequently, the Nuremberg Code, Declaration of Helsinki and Belmont Report came into light and constrained human experiments and clinical trials. However, the development of such laws and regulations in China is lagging behind and renders China as a breeding ground for gray medicine. There are three lessons we can learn from painful histories and apply to individualized treatment of lung cancer. Firstly, the abuse of Avastin beyond its indications reflected the similar situation of tyrosine kinase inhibitors in lung cancer due to different molecular types and stages of tumors; secondly, the black market of stem cell therapy in China reminds us how to identify the boundaries of clinical trials and clinical treatment, in similar to the cellular immunotherapy of tumors; thirdly, the theory of Xiao's Reflex Arc emerged us to rethink the level of the validity of clinical evidences, which can provide hints related to video-assisted thoracoscopic surgeries (VATSs). In conclusion, clinical applications of new techniques and treatment regimens should follow three points: identify indications and contraindications clearly, obtain informed consent and permission of patients and supervise effectively according to laws and ethics.

HIS-Based Support of Follow-Up Documentation – Concept and Implementation for Clinical Studies

PubMed Central

Herzberg, S.; Fritz, F.; Rahbar, K.; Stegger, L.; Schäfers, M.; Dugas, M.

2011-01-01

Objective Follow-up data must be collected according to the protocol of each clinical study, i.e. at certain time points. Missing follow-up information is a critical problem and may impede or bias the analysis of study data and result in delays. Moreover, additional patient recruitment may be necessary due to incomplete follow-up data. Current electronic data capture (EDC) systems in clinical studies are usually separated from hospital information systems (HIS) and therefore can provide limited functionality to support clinical workflow. In two case studies, we assessed the feasibility of HIS-based support of follow-up documentation. Methods We have developed a data model and a HIS-based workflow to provide follow-up forms according to clinical study protocols. If a follow-up form was due, a database procedure created a follow-up event which was translated by a communication server into an HL7 message and transferred to the import interface of the clinical information system (CIS). This procedure generated the required follow-up form and enqueued a link to it in a work list of the relating study nurses and study physicians, respectively. Results A HIS-based follow-up system automatically generated follow-up forms as defined by a clinical study protocol. These forms were scheduled into work lists of study nurses and study physicians. This system was integrated into the clinical workflow of two clinical studies. In a study from nuclear medicine, each scenario from the test concept according to the protocol of the single photon emission computer tomography/computer tomography (SPECT/CT) study was simulated and each scenario passed the test. For a study in psychiatry, 128 follow-up forms were automatically generated within 27 weeks, on average five forms per week (maximum 12, minimum 1 form per week). Conclusion HIS-based support of follow-up documentation in clinical studies is technically feasible and can support compliance with study protocols. PMID:23616857

Osteomyelitis due to Salmonella enterica subsp. arizonae: the price of exotic pets.

PubMed

Kolker, S; Itsekzon, T; Yinnon, A M; Lachish, T

2012-02-01

We describe a 31-year-old immunocompromised patient who developed sepsis and osteomyelitis due to Salmonella enterica subsp. arizonae secondary to exposure to iguana and snakes kept as pets at her home, and review all 23 previously published cases of bone and joint infections due to this organism, for a total of nine children and 15 adults. Eleven of the adults were female (73%), compared with three (33%) of the children (p <0.01). Significant underlying illnesses were present in all 15 adults and in five children (55%, p <0.05); 10 (77%) of the adults were immunosuppressed, compared with one child only (17%) (p <0.05). In ten of the adults the knee was infected (67%), compared with one child only (11%, p <0.01). Antibiotic therapy was prolonged in both adults and children, and in most cases consisted of 4-6 weeks of parenteral treatment. Complete cure and survival was attained in 11 of 15 adults (73%) and all nine children (NS). Optimal antibiotic treatment probably consists of ceftriaxone or a fluoroquinolone, if the organism is susceptible. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Engineered BDNF producing cells as a potential treatment for neurologic disease

PubMed Central

Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.

2018-01-01

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050

A NEW APPROACH TO THE STUDY OF MUCOADHESIVENESS OF POLYMERIC MEMBRANES USING SILICONE DISCS.

PubMed

Nowak, Karolina Maria; Szterk, Arkadiusz; Fiedor, Piotr; Bodek, Kazimiera Henryka

2016-01-01

The introduction of new test methods and the modification of existing ones are crucial for obtaining reliable results, which contributes to the development of innovative materials that may have clinical applications. Today, silicone is commonly used in medicine and the diversity of its applications are continually growing. The aim of this study is to evaluate the mucoadhesiveness of polymeric membranes by a method that modifies the existing test methods through the introduction of silicone discs. The matrices were designed for clinical application in the management of diseases within the oral cavity. The use of silicone discs allows reliable and reproducible results to be obtained, which allows us to make various tensometric measurements. In this study, different types of polymeric matrices were examined, as well as their crosslinking and the presence for the active pharmaceutical ingredient were compared to the pure dosage form. The lidocaine hydrochloride (Lid(HCl)) was used as a model active substance, due to its use in dentistry and clinical safety. The results were characterized by a high repeatability (RSD < 10.6%). The advantage of silicone material due to its mechanical strength, chemical and physical resistance, allowed a new test method using a texture analyzer to be proposed.

Usefulness of BFB/EMG in facial palsy rehabilitation.

PubMed

Dalla Toffola, Elena; Bossi, Daniela; Buonocore, Michelangelo; Montomoli, Cristina; Petrucci, Lucia; Alfonsi, Enrico

2005-07-22

To analyze and to compare the recovery and the development of synkinesis in patients with idiopathic facial palsy (Bell's palsy) following treatment with two methods of rehabilitation, kinesitherapy (KT) and biofeedback/EMG (BFB/EMG). Retrospective cases--series review. Seventy-four patients with Bell' palsy were clinically evaluated within 1 month from onset of palsy and at 12 months after palsy (House scale and synkinesis evaluation). Electromyography (EMG) and Electroneurography (ENG) were performed about 4 weeks after palsy to better evaluate functional abnormalities due to facial nerve lesion. The patients followed two different protocols for rehabilitation: the first 32 patients were treated with therapeutic exercises performed by therapists (KT group), the latter 42 patients were treated using BFB/EMG methods (BFB group) with inhibition of synkinetic movement as the primary goal. KT and BFB patients were evaluated for clinical and neurophysiological characteristics before rehabilitative treatment. BFB patients showed better clinical recovery and minor synkinesis than KT patients. BFB/EMG seems to be more useful than KT in Bell's palsy treatment. This could be due to the fact that BFB/EMG gives more accurate information than KT on muscle activation with better modulation in voluntary recruitment of motor unit.

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.

Development of quality measures for monitoring and improving care in gastroenterology.

PubMed

Germansky, Katharine A; Leffler, Daniel A

2011-06-01

Over the past decade, most quality assurance (QA) efforts in gastroenterology have been aimed at endoscopy. Endoscopic quality improvement was the rational area to begin QA work in gastroenterology due to the relatively acute nature of complications and the high volume of procedures performed. While endoscopy is currently the focus of most quality assurance (QA) measures in gastroenterology, more recent efforts have begun to address clinical gastroenterology practices both in the outpatient and inpatient settings. Clinical outpatient and inpatient gastroenterology is laden with areas where standardization could benefit patient care. While data and experience in clinical gastroenterology QA is relatively limited, it is clear that inconsistent use of guidelines and practice variations in gastroenterology can lead to lower quality care. In this review, we review a variety of areas in clinical gastroenterology where existing guidelines and published data suggest both the need and practicality of active QA measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Development and Clinical Evaluation of Second-Generation Leishmaniasis Vaccines

PubMed Central

Duthie, Malcolm S.; Raman, Vanitha S.; Piazza, Franco M.; Reed, Steven G.

2011-01-01

Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1 + MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. PMID:22085553

Carbon Nanomaterial Based Biosensors for Non-Invasive Detection of Cancer and Disease Biomarkers for Clinical Diagnosis

PubMed Central

Tung, Thanh Tran

2017-01-01

The early diagnosis of diseases, e.g., Parkinson’s and Alzheimer’s disease, diabetes, and various types of cancer, and monitoring the response of patients to the therapy plays a critical role in clinical treatment; therefore, there is an intensive research for the determination of many clinical analytes. In order to achieve point-of-care sensing in clinical practice, sensitive, selective, cost-effective, simple, reliable, and rapid analytical methods are required. Biosensors have become essential tools in biomarker sensing, in which electrode material and architecture play critical roles in achieving sensitive and stable detection. Carbon nanomaterials in the form of particle/dots, tube/wires, and sheets have recently become indispensable elements of biosensor platforms due to their excellent mechanical, electronic, and optical properties. This review summarizes developments in this lucrative field by presenting major biosensor types and variability of sensor platforms in biomedical applications. PMID:28825646

Unmet needs in obesity management: From guidelines to clinic.

PubMed

Ritten, Angela; LaManna, Jacqueline

2017-10-01

Despite the rather slow acceptance of obesity as a disease state, several obesity staging systems and weight-management guidelines have been developed and are in use, along with an ever-growing number of treatment options. Many primary care clinicians, including nurse practitioners (NPs), are at the forefront of clinical efforts to assist individuals with obesity, but face challenges due to lack of alignment and consensus among the various staging systems and guidelines. This is further complicated by shortfalls in clinical training related to obesity management and increasing complexities in reimbursement for obesity-related services. Unmet needs in the management of obesity thus stretch from guidelines to clinic. This article examines the principal barriers to effective management of individuals with obesity and considers how concerns might be overcome, with particular emphasis on the role of the NP. ©2017 American Association of Nurse Practitioners.

Bladder perforations in children.

PubMed

Bakal, U; Sarac, M; Tartar, T; Ersoz, F; Kazez, A

2015-01-01

Bladder perforations in children occur due to several different reasons. In this clinical series study, we focused on bladder perforations due to the pelvic injury, and our aim also was to create awareness for a rare type of bladder injuries. This was a retrospective study of the patients who were treated in our clinic for bladder perforation between 2006 and 2011. We reviewed the documents of childhood bladder perforations, and demographic and clinical characteristics of the patients were obtained. No statistical analyses were used because of the limited number of cases. There were ten patients who suffered from bladder perforation in 5-year period; 5 were male, and 5 were female. The mean age of the patients was 4.35 years. Four patients (40%) experienced iatrogenic perforation and six patients (60%) experienced perforation due to the accident. Common symptoms were hematuria, abdominal tenderness, and inability to urinate. Three patients were diagnosed via emergency laparotomy, without any radiological examinations performed before surgery. Four patients suffered from the intraperitoneal perforation, three patients suffered from extraperitoneal injury and three of them both of intraperitoneal and extraperitoneal injuries. Mean recovery time for patients was 15 days. One patient developed a urinary tract infection and one newborn died due to accompanying morbidities. Nine patients were discharged from the hospital. If the patients had a pelvic injury, surgeons must pay attention for the bladder perforation. Isolated bladder perforations are rare, and they are generally associated with iatrogenic injuries. Clinicians should pay attention to findings such as anuria, inability to insert a urinary catheter, and free fluid in the abdomen in order to diagnose the bladder perforation in newborns. Novice surgeons should pay more attention to avoid causing iatrogenic bladder perforation during inguinal hernia repair.

Video-mosaicking of in vivo reflectance confocal microscopy images for noninvasive examination of skin lesion (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kose, Kivanc; Gou, Mengran; Yelamos, Oriol; Cordova, Miguel A.; Rossi, Anthony; Nehal, Kishwer S.; Camps, Octavia I.; Dy, Jennifer G.; Brooks, Dana H.; Rajadhyaksha, Milind

2017-02-01

In this report we describe a computer vision based pipeline to convert in-vivo reflectance confocal microscopy (RCM) videos collected with a handheld system into large field of view (FOV) mosaics. For many applications such as imaging of hard to access lesions, intraoperative assessment of MOHS margins, or delineation of lesion margins beyond clinical borders, raster scan based mosaicing techniques have clinically significant limitations. In such cases, clinicians often capture RCM videos by freely moving a handheld microscope over the area of interest, but the resulting videos lose large-scale spatial relationships. Videomosaicking is a standard computational imaging technique to register, and stitch together consecutive frames of videos into large FOV high resolution mosaics. However, mosaicing RCM videos collected in-vivo has unique challenges: (i) tissue may deform or warp due to physical contact with the microscope objective lens, (ii) discontinuities or "jumps" between consecutive images and motion blur artifacts may occur, due to manual operation of the microscope, and (iii) optical sectioning and resolution may vary between consecutive images due to scattering and aberrations induced by changes in imaging depth and tissue morphology. We addressed these challenges by adapting or developing new algorithmic methods for videomosaicking, specifically by modeling non-rigid deformations, followed by automatically detecting discontinuities (cut locations) and, finally, applying a data-driven image stitching approach that fully preserves resolution and tissue morphologic detail without imposing arbitrary pre-defined boundaries. We will present example mosaics obtained by clinical imaging of both melanoma and non-melanoma skin cancers. The ability to combine freehand mosaicing for handheld microscopes with preserved cellular resolution will have high impact application in diverse clinical settings, including low-resource healthcare systems.

Incremental validity of estimated cannabis grams as a predictor of problems and cannabinoid biomarkers: Evidence from a clinical trial.

PubMed

Tomko, Rachel L; Baker, Nathaniel L; McClure, Erin A; Sonne, Susan C; McRae-Clark, Aimee L; Sherman, Brian J; Gray, Kevin M

2018-01-01

Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams. This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N=300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder. Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X 2 =98.3; p<0.05) and in the model predicting problems due to cannabis use (X 2 =6.4; p<0.05), relative to a model that contained only simpler measures of quantity and frequency. This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial). Copyright © 2017 Elsevier B.V. All rights reserved.

Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

PubMed

Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

2016-05-01

This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Biomarkers for the development of new medications for cocaine dependence.

PubMed

Bough, Kristopher J; Amur, Shashi; Lao, Guifang; Hemby, Scott E; Tannu, Nilesh S; Kampman, Kyle M; Schmitz, Joy M; Martinez, Diana; Merchant, Kalpana M; Green, Charles; Sharma, Jyoti; Dougherty, Anne H; Moeller, F Gerard

2014-01-01

There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.

Clinical management of a child with Prader-Willi Syndrome from maternal uniparental disomy (UPD) genetic inheritance.

PubMed

Bellon-Harn, Monica L

2005-01-01

Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals. Unfortunately, many cases are missed due to clinicians' lack of familiarity with the syndrome as well as clinical and laboratory diagnostic criteria. Although common clinical characteristics are reported, variety exists in the nature and severity of dysfunction associated with PWS. Case studies can provide information to understand relationships between phenotypic characteristics and genetic inheritance, which can in turn lead to effective clinical management. The purpose of this case study was to describe the characteristics of a child with PWS due to maternal uniparental disomy inheritance pattern and to describe clinical management and treatment outcomes. The reader will obtain information about: (1) the genetic inheritance patterns and clinical characteristics of Prader-Willi Syndrome, (2) genotypic/phenotypic relationships specific to Prader-Willi Syndrome, and (3) clinical implications, management, and outcomes in a case description of a child with PWS due to maternal uniparental disomy inheritance pattern.

[Therapy options for blind microphthalmos and clinical anophthalmos].

PubMed

Schittkowski, M P

2012-11-01

Children suffering from congenital anophthalmos (absence of eyes) or blind microphthalmos (eyes too small without light perception) show significant smaller eyelids, conjunctival sacs and orbital volume due to the lack of intrauterine growth stimulus. Highly hydrophilic osmotic expanders allow prostheses to be fitted in the first year of life to compensate for the volume deficit and the substantial aesthetic disadvantages and to stimulate lid development.

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed

Ng, S C; Lee, M K; Teh, A

1989-11-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome.

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed Central

Ng, S. C.; Lee, M. K.; Teh, A.

1989-01-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome. PMID:2616421

A case of methylene chloride poisoning due to ingestion of home-distilled alcohol and potential new treatment with ethanol infusion.

PubMed

Vetro, Joseph; Koutsogiannis, Zeff; Jones, Daryl A; Canestra, Jane

2012-03-01

We describe a case of a 51-year-old man who ingested methylene chloride and presented with the classical clinical features. He developed an acute abdomen that required repeated laparotomy. The effect of an ethanol infusion on carboxyhaemoglobin concentrations in this case was also of interest and could potentially be a new treatment modality.

Veno-venous extracorporeal membrane oxygenation using an innovative dual-lumen cannula following implantation of a total artificial heart.

PubMed

Youdle, Jemma; Penn, Sarah; Maunz, Olaf; Simon, Andre

2017-01-01

We report our first clinical use of the new Protek Duo TM cannula for peripheral veno-venous extra-corporeal life support (ECLS). A 53-year-old male patient underwent implantation of a total artificial heart (TAH) for biventricular failure. However, due to the development of post-operative respiratory dysfunction, the patient required ECLS for six days.

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design

PubMed Central

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D’Arcy, Ryan C N; Song, Xiaowei

2018-01-01

Introduction Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors’ quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Methods and analysis Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. Ethics and dissemination The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging scientists, computing scientists and clinical professionals in neurology and neuroradiology and includes patient representatives. Research outputs will be disseminated following knowledge translation plans towards improving stroke patient care. Significant findings will be published in scientific journals. Anticipated deliverables include computer solutions for improved clinical assessment of haematoma using NCCT. PMID:29674371

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure

PubMed Central

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

Purpose: To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. Methods: The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. Results: The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Conclusion: Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals. PMID:28299009

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure.

PubMed

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals.

Creating an optical spectroscopy system for use in a primary care clinical setting (Conference Presentation)

NASA Astrophysics Data System (ADS)

Eshein, Adam; Nguyen, The-Quyen; Radosevich, Andrew J.; Gould, Bradley; Wu, Wenli; Konda, Vani; Yang, Leslie W.; Koons, Ann; Feder, Seth; Valuckaite, Vesta; Roy, Hemant K.; Backman, Vadim

2016-03-01

While there are a plethora of in-vivo spectroscopic techniques that have demonstrated the ability to detect a number of diseases in research trials, very few techniques have successfully become a fully realized clinical technology. This is primarily due to the stringent demands on a clinical device for widespread implementation. Some of these demands include: simple operation requiring minimal or no training, safe for in-vivo patient use, no disruption to normal clinic workflow, tracking of system performance, warning for measurement abnormality, and meeting all FDA guidelines for medical use. Previously, our group developed a fiber optic probe-based optical sensing technique known as low-coherence enhanced backscattering spectroscopy (LEBS) to quantify tissue ultrastructure in-vivo. Now we have developed this technique for the application of prescreening patients for colonoscopy in a primary care (PC) clinical setting. To meet the stringent requirements for a viable medical device used in a PC clinical setting, we developed several novel components including an automated calibration tool, optical contact sensor for signal acquisition, and a contamination sensor to identify measurements which have been affected by debris. The end result is a state-of-the-art medical device that can be realistically used by a PC physician to assess a person's risk for harboring colorectal precancerous lesions. The pilot study of this system shows great promise with excellent stability and accuracy in identifying high-risk patients. While this system has been designed and optimized for our specific application, the system and design concepts are universal to most in-vivo fiber optic based spectroscopic techniques.

[Celiac crisis with quadriplegia due to potassium depletion as presenting feature of celiac disease].

PubMed

Atikou, A; Rabhi, M; Hidani, H; El Alaoui Faris, M; Toloune, F

2009-06-01

Adult coeliac disease revealed by coeliac crisis and quadriplegia due to potassium depletion is an extremely rare situation. A 26-year-old woman presented with a suddenly developed weakness of all four limbs and a severe diarrhea. Authors emphasize coeliac crisis, which is a presenting feature of coeliac disease, characterized by acute diarrhea with life-threatening acid base and electrolyte abnormalities. The patient improved with correction of hypokalemia and gluten-free diet. A severe acute diarrhea with metabolic and systemic complications, the so-called coeliac crisis, is a possible presenting clinical feature of a previously undiagnosed adult celiac disease.

A case of thyroid storm with multiple organ failure effectively treated with plasma exchange.

PubMed

Sasaki, Kazuki; Yoshida, Akira; Nakata, Yukiko; Mizote, Isamu; Sakata, Yasushi; Komuro, Issei

2011-01-01

We describe a 48-year-old man with thyroid storm presenting with heart failure. He presented severely impaired left ventricular wall motion and a marked increase in the liver enzymes. He developed disseminated intravascular coagulation on day 2. Due to elevated serum thyroid hormone level, anti-thyroid hormone receptor antibody positivity, and his clinical symptoms, he was diagnosed as thyroid storm due to untreated Graves' disease. His condition did not improve even after 6 days of conventional therapy including steroids. After therapeutic plasma exchange was carried out, his thyroid hormone level decreased markedly. Consequently, his condition recovered gradually, and he was discharged at day 43.

[The para-clinic investigation of temporo-mandibular joint changes in patients with acromegaly].

PubMed

Morăraşu, C; Burlui, V; Olaru, C; Boza, C; Bortă, C; Morăraşu, G; Brînză, M

2001-01-01

The Acromegaly is an endocrinological disease determined by the hypersecretion of STH in a certain period of the body evolution and it causes the hypertrophy of bones in general and of mandible and cranio-facial bones, determining a disorder due to this development of bones, associated with troubles in the activity of muscles and of the phospho-calcium metabolism. This study was made on a group of 33 acromegaly patients. Their temporo-mandibular joint was investigated by ortopantomography, tomography, computer tomography and scintigraphy. All of these exams shows the changes in temporo-mandibular joint due to the cells hyperactivity determined by the hypersecretion of STH.

A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections

PubMed Central

Gupta, Aditya K; Daigle, Deanne

2016-01-01

Luliconazole is a novel imidazole derivative, which has demonstrated in vitro efficacy against dermatophytes and Candida. The results from Phase III trials show that luliconazole 1% cream applied once daily for 2 weeks successfully resolved the clinical signs and symptoms as well as eradicated the pathologic fungi, which cause tinea pedis. A 1-week treatment with luliconazole 1% cream also produced favorable clinical and mycological results in clinical trials for tinea corporis and tinea cruris. Across trials, adverse events consisted mainly of localized reactions following application. The development of a new antifungal agent is timely due to mounting resistance among existing treatments. Because luliconazole requires a short duration of treatment, it may assist in reducing disease recurrence as a result of patient nonadherence. PMID:26848272

Spectrometric determination of clinically relevant fatty acids in the blood serum

NASA Astrophysics Data System (ADS)

Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

2017-01-01

The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

Pediatric reference intervals for alkaline phosphatase.

PubMed

Zierk, Jakob; Arzideh, Farhad; Haeckel, Rainer; Cario, Holger; Frühwald, Michael C; Groß, Hans-Jürgen; Gscheidmeier, Thomas; Hoffmann, Reinhard; Krebs, Alexander; Lichtinghagen, Ralf; Neumann, Michael; Ruf, Hans-Georg; Steigerwald, Udo; Streichert, Thomas; Rascher, Wolfgang; Metzler, Markus; Rauh, Manfred

2017-01-01

Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyte as closely linked to growth as alkaline phosphatase. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, resulting in limitations when clinical decisions are based on alkaline phosphatase activity. We applied an indirect method to generate percentile charts for alkaline phosphatase activity using clinical laboratory data collected during the clinical care of patients. A total of 361,405 samples from 124,440 patients from six German tertiary care centers and one German laboratory service provider measured between January 2004 and June 2015 were analyzed. Measurement of alkaline phosphatase activity was performed on Roche Cobas analyzers using the IFCC's photometric method. We created percentile charts for alkaline phosphatase activity in girls and boys from birth to 18 years which can be used as reference intervals. Additionally, data tables of age- and sex-specific percentile values allow the incorporation of these results into laboratory information systems. The percentile charts provided enable the appropriate differential diagnosis of changes in alkaline phosphatase activity due to disease and changes due to physiological development. After local validation, integration of the provided percentile charts into result reporting facilitates precise assessment of alkaline phosphatase dynamics in pediatrics.

Development of criteria for evaluating clinical response in thyroid eye disease (CRI-TED) using a modified Delphi technique

PubMed Central

Douglas, Raymond S.; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A.; Cahill, Kenneth; Dolman, Peter J.; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J.; Khanna, Dinesh

2014-01-01

To identify components of a provisional clinical response index for thyroid eye disease (CRI-TED) using a modified Delphi technique. The International Thyroid Eye Disease Society (ITEDS) conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in TED. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty four respondents participated in the Delphi-1 survey, providing 220 unique items. Ninety- two members (100% of the respondents from Delphi 1 plus eight new participants) responded in Delphi-2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi-3 (67 criteria were excluded due to redundancy). Criteria with a mean greater than 6 (1 least appropriate to 9 most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for TED. These measures will be iteratively refined for use in multicenter clinical trials. PMID:19752424

Developmental Origins of Health and Disease: A Paradigm for Understanding Disease Etiology and Prevention

PubMed Central

Heindel, Jerrold J.; Vandenberg, Laura N.

2015-01-01

Purpose of Review While diseases may appear clinically throughout the lifespan, it is clear that many diseases have origins during development. Altered nutrition, as well as exposure to environmental chemicals, drugs, infections, or stress during specific times of development can lead to functional changes in tissues, predisposing those tissues to diseases that manifest later in life. This review will focus on the role of altered nutrition and exposures to environmental chemicals during development in the role of disease/dysfunctions. Recent Findings Effects of altered nutrition or exposure to environmental chemicals during development are likely due to altered programming of epigenetic marks which persist across the lifespan. Indeed some changes can be transmitted to future generations. Summary Evidence in support of the DOHaD paradigm is sufficiently robust and repeatable across species including humans, suggesting a need for greater emphasis in the clinical area. Because of these data, obesity, diabetes, cardiovascular morbidity, and neuropsychiatric diseases can all be considered pediatric diseases. Disease prevention must start with improved nutrition and reduced exposures to environmental chemicals during development. PMID:25635586

Development of the small-molecule antiviral ST-246® as a smallpox therapeutic

PubMed Central

Grosenbach, Douglas W; Jordan, Robert; Hruby, Dennis E

2011-01-01

Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246® (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the ‘animal rule’). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency. PMID:21837250

Regulatory science based approach in development of novel medical devices.

PubMed

Sakuma, Ichiro

2015-08-01

For development rational evaluation method for medical devices' safety and efficacy, regulatory science studies are important. Studies on regulatory affairs related to a medical device under development should be conducted as well as its technological development. Clinical performance of a medical device is influenced by performance of the device, medical doctors' skill, pathological condition of a patient, and so on. Thus it is sometimes difficult to demonstrate superiority of the device in terms of clinical outcome although its efficacy as a medical device is accepted. Setting of appropriate end points is required to evaluate a medical device appropriately. Risk assessment and risk management are the basis of medical device safety assurance. In case of medical device software, there are difficulties in identifying the risk due to its complexity of user environment and different design and manufacturing procedure compared with conventional hardware based medical devices. Recent technological advancement such as information and communication technologies (ICT) for medical devices and wireless network has raised new issue on risk management: cybersecurity. We have to watch closely the progress of safety standard development.

The development of low-molecular weight hydrogels for applications in cancer therapy

NASA Astrophysics Data System (ADS)

Tian, Ran; Chen, Jin; Niu, Runfang

2014-03-01

To improve the anti-cancer efficacy and to counteract the side effects of chemotherapy, a variety of drug delivery systems have been invented in past decades, but few of these systems have succeeded in clinical trials due to their respective inherent shortcomings. Recently, low-molecular weight hydrogels of peptides that self-assemble via non-covalent interactions have attracted considerable attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Low-molecular weight hydrogels have already shown promise in biomedical applications as diverse as 3D-cell culture, enzyme immobilization, controllable MSC differentiation, wound healing, drug delivery etc. Here we review the recent development in the use of low-molecular weight hydrogels for cancer therapy, which may be helpful in the design of soft materials for drug delivery.

The Development of a Minority Recruitment Plan for Cancer Clinical Trials

PubMed Central

Trevino, Monica; Padalecki, Susan; Karnad, Anand; Parra, Alberto; Weitman, Steve; Nashawati, Melissa; Pollock, Brad H.; Ramirez, Amelie; Thompson, Ian M.

2014-01-01

Background Cancer does not occur in all ethnic and racial groups at similar rates. In addition, responses to treatment also vary in certain ethnic and racial groups. For Hispanics, the overall cancer incidence is generally lower yet for some specific tumor types, the incidence rates are higher compared to other populations. Objectives Although disparities are recognized for treatment outcomes and prevention methodologies for Hispanics and other minority populations, specific recruiting and reporting of minorities remains a challenge. In order to circumvent this problem, the Cancer Therapy and Research Center (CTRC) has developed a new minority recruitment plan for all cancer related clinical trials at this Institute. The overall goal of this initiative is to increase the accrual of minorities in cancer clinical trials by implementing several key interventions. Method The Cancer Therapy & Research Center (CTRC) at the University of Texas Health Science Center at San Antonio established the Clinical Trials Accrual Task Force to develop and monitor interventions designed to increase accrual to cancer clinical trials, specifically the accrual of minorities with a focus on the Hispanic population that makes up 68% of the CTRC's catchment area. Results A Minority Accrual Plan (MAP) was implemented in March 2013 as part of the process for initiating and conducting cancer-related clinical trials at the CTRC. The Minority Accrual Plan focuses on Hispanic enrollment due to the characteristics of the South Texas population served by the CTRC but could be easily adapted to other populations. Conclusions The CTRC has designed a process to prospectively address the challenge of deliberately enrolling minority subjects and accurately accounting for the results by implementing a Minority Accrual Plan for every cancer-related clinical trial at CTRC. PMID:25152846

The Development of a Minority Recruitment Plan for Cancer Clinical Trials.

PubMed

Trevino, Monica; Padalecki, Susan; Karnad, Anand; Parra, Alberto; Weitman, Steve; Nashawati, Melissa; Pollock, Brad H; Ramirez, Amelie; Thompson, Ian M

2013-09-01

Cancer does not occur in all ethnic and racial groups at similar rates. In addition, responses to treatment also vary in certain ethnic and racial groups. For Hispanics, the overall cancer incidence is generally lower yet for some specific tumor types, the incidence rates are higher compared to other populations. Although disparities are recognized for treatment outcomes and prevention methodologies for Hispanics and other minority populations, specific recruiting and reporting of minorities remains a challenge. In order to circumvent this problem, the Cancer Therapy and Research Center (CTRC) has developed a new minority recruitment plan for all cancer related clinical trials at this Institute. The overall goal of this initiative is to increase the accrual of minorities in cancer clinical trials by implementing several key interventions. The Cancer Therapy & Research Center (CTRC) at the University of Texas Health Science Center at San Antonio established the Clinical Trials Accrual Task Force to develop and monitor interventions designed to increase accrual to cancer clinical trials, specifically the accrual of minorities with a focus on the Hispanic population that makes up 68% of the CTRC's catchment area. A Minority Accrual Plan (MAP) was implemented in March 2013 as part of the process for initiating and conducting cancer-related clinical trials at the CTRC. The Minority Accrual Plan focuses on Hispanic enrollment due to the characteristics of the South Texas population served by the CTRC but could be easily adapted to other populations. The CTRC has designed a process to prospectively address the challenge of deliberately enrolling minority subjects and accurately accounting for the results by implementing a Minority Accrual Plan for every cancer-related clinical trial at CTRC.

Impact of postgraduate training on communication skills teaching: a controlled study.

PubMed

Junod Perron, Noelle; Nendaz, Mathieu; Louis-Simonet, Martine; Sommer, Johanna; Gut, Anne; Cerutti, Bernard; van der Vleuten, Cees P; Dolmans, Diana

2014-04-14

Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors' perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors' ability to identify residents' good and poor communication skills and to discuss them interactively during feedback. We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents' communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice.

Impact of postgraduate training on communication skills teaching: a controlled study

PubMed Central

2014-01-01

Background Observation of performance followed by feedback is the key to good teaching of communication skills in clinical practice. The fact that it occurs rarely is probably due to clinical supervisors’ perceived lack of competence to identify communication skills and give effective feedback. We evaluated the impact of a faculty development programme on communication skills teaching on clinical supervisors’ ability to identify residents’ good and poor communication skills and to discuss them interactively during feedback. Methods We conducted a pre-post controlled study in which clinical supervisors took part to a faculty development program on teaching communication skills in clinical practice. Outcome measures were the number and type of residents’ communication skills identified by supervisors in three videotaped simulated resident-patient encounters and the number and type of communication skills discussed interactively with residents during three feedback sessions. Results 48 clinical supervisors (28 intervention group; 20 control group) participated. After the intervention, the number and type of communication skills identified did not differ between both groups. There was substantial heterogeneity in the number and type of communication skills identified. However, trained participants engaged in interactive discussions with residents on a significantly higher number of communication items (effect sizes 0.53 to 1.77); communication skills items discussed interactively included both structural and patient-centered elements that were considered important to be observed by expert teachers. Conclusions The faculty development programme did not increase the number of communication skills recognised by supervisors but was effective in increasing the number of communication issues discussed interactively in feedback sessions. Further research should explore the respective impact of accurate identification of communication skills and effective teaching skills on achieving more effective communication skills teaching in clinical practice. PMID:24731477

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

PubMed

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

PubMed

Tinto, Halidou; Valea, Innocent; Sorgho, Hermann; Tahita, Marc Christian; Traore, Maminata; Bihoun, Biébo; Guiraud, Issa; Kpoda, Hervé; Rouamba, Jérémi; Ouédraogo, Sayouba; Lompo, Palpouguini; Yara, Sandrine; Kabore, William; Ouédraogo, Jean-Bosco; Guiguemdé, Robert Tinga; Binka, Fred N; Ogutu, Bernhards

2014-03-22

The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in resource-poor settings, well beyond the task of generating expected study data.

Implementation of a scalable, web-based, automated clinical decision support risk-prediction tool for chronic kidney disease using C-CDA and application programming interfaces.

PubMed

Samal, Lipika; D'Amore, John D; Bates, David W; Wright, Adam

2017-11-01

Clinical decision support tools for risk prediction are readily available, but typically require workflow interruptions and manual data entry so are rarely used. Due to new data interoperability standards for electronic health records (EHRs), other options are available. As a clinical case study, we sought to build a scalable, web-based system that would automate calculation of kidney failure risk and display clinical decision support to users in primary care practices. We developed a single-page application, web server, database, and application programming interface to calculate and display kidney failure risk. Data were extracted from the EHR using the Consolidated Clinical Document Architecture interoperability standard for Continuity of Care Documents (CCDs). EHR users were presented with a noninterruptive alert on the patient's summary screen and a hyperlink to details and recommendations provided through a web application. Clinic schedules and CCDs were retrieved using existing application programming interfaces to the EHR, and we provided a clinical decision support hyperlink to the EHR as a service. We debugged a series of terminology and technical issues. The application was validated with data from 255 patients and subsequently deployed to 10 primary care clinics where, over the course of 1 year, 569 533 CCD documents were processed. We validated the use of interoperable documents and open-source components to develop a low-cost tool for automated clinical decision support. Since Consolidated Clinical Document Architecture-based data extraction extends to any certified EHR, this demonstrates a successful modular approach to clinical decision support. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Long-term evaluation of TiO2-based 68Ge/68Ga generators and optimized automation of [68Ga]DOTATOC radiosynthesis.

PubMed

Lin, Mai; Ranganathan, David; Mori, Tetsuya; Hagooly, Aviv; Rossin, Raffaella; Welch, Michael J; Lapi, Suzanne E

2012-10-01

Interest in using (68)Ga is rapidly increasing for clinical PET applications due to its favorable imaging characteristics and increased accessibility. The focus of this study was to provide our long-term evaluations of the two TiO(2)-based (68)Ge/(68)Ga generators and develop an optimized automation strategy to synthesize [(68)Ga]DOTATOC by using HEPES as a buffer system. This data will be useful in standardizing the evaluation of (68)Ge/(68)Ga generators and automation strategies to comply with regulatory issues for clinical use. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening

NASA Astrophysics Data System (ADS)

Mazurenka, M.; Behrendt, L.; Meinhardt-Wollweber, M.; Morgner, U.; Roth, B.

2017-10-01

A combined optical coherence tomography (OCT)-Raman probe was designed and built into a spectral domain OCT head, and its performance was evaluated and compared to the most common Raman probe setups, based on a fiber bundle and confocal free space optics. Due to the use of the full field of view of an OCT scanning lens, the combined probe has a superior performance within maximum permissible exposure limits, compared to the other two probes. Skin Raman spectra, recorded in vivo, further prove the feasibility of the OCT-Raman probe for the future in vivo clinical applications in skin cancer screening.

Novel fiber optic immunosensor instrument

NASA Astrophysics Data System (ADS)

Wang, Zhiyu; Huang, Wenling; Tang, Lei; Zhou, Bo; Li, Yugi; He, Jun

1996-09-01

It has developed and performed a novel fiberoptic immunosensor instrument with operating wavelength 400 - 760 nm and repeatability cv equals 0.27%. The instrument has many excellent features such as simplified operation, faster testing time, higher sensitivity and economic cost. It has completely eliminated recovery period which traditional immunosensor owned due to use separative sensor structure. It can widely apply to test for bacteria, virus, hormone, parasite and cancer protein in clinical examination. The instrument has operated in laboratory and relevant medicine units and successfully tested monoclonal rat-anti-human of 413 cases in clinic and prepared with existing ELISA method, the coincidence probability reached 94 to 100%.

Regulatory considerations in application of encapsulated cell therapies.

PubMed

van Zanten, J; de Vos, Paul

2010-01-01

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

GLUT1 deficiency syndrome in clinical practice.

PubMed

Klepper, Joerg

2012-07-01

GLUT1 deficiency syndrome (GLUT1DS) is caused by impaired glucose transport into brain and is effectively treated by means of a ketogenic diet. In clinical practice the diagnosis of GLUT1DS often is challenging due to the increasing complexity of symptoms, diagnostic cut-offs for hypoglycorrhachia and genetic heterogeneity. In terms of treatment alternative ketogenic diets and their long-term side effects as well as novel compounds such as alpha-lipoic acid and triheptanoin have raised a variety of issues. The current diagnostic and therapeutic approach to GLUT1DS is discussed in this review in view of these recent developments. Copyright © 2011. Published by Elsevier B.V.

A Hormonally Active Malignant Struma Ovarii

PubMed Central

Lara, Carolina; Salame, Latife; Padilla-Longoria, Rafael

2016-01-01

Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. PMID:27882257

Multidrug resistant Fusarium keratitis.

PubMed

Antequera, P; Garcia-Conca, V; Martín-González, C; Ortiz-de-la-Tabla, V

2015-08-01

We report a case of keratitis in a female contact lens wearer, who developed a deep corneal abscess. The culture of a corneal biopsy scraping was positive for multiresistant Fusarium solani. The patient has a complicated clinical course and failed to respond to local and systemic antifungal treatment, requiring eye enucleation. Fusarium keratitis may progress to severe endophthalmitis. Clinical suspicion is paramount in order to start antifungal therapy without delay. Therapy is complex due to the high resistance of this organism to usual antifungal drugs. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Update on the Medical Management of Crohn's Disease.

PubMed

Deepak, Parakkal; Bruining, David H

2015-11-01

The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.

Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

PubMed

Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

2016-05-01

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.

Long-term outcome of acute prosthetic joint infections due to gram-negative bacilli treated with retention of prosthesis.

PubMed

Jaén, N; Martínez-Pastor, J C; Muñoz-Mahamud, E; García-Ramiro, S; Bosch, J; Mensa, J; Soriano, A

2012-09-01

To update the clinical information of the 47 patients with a prosthetic joint infection due to Gram-negative bacilli included in a previous study and to reassess the predictors of failure after a longer follow-up. Using the electronic files of our hospital, all the information regarding readmissions to the hospital, new surgical procedures and the reason for the new surgery (infection, aseptic loosening), and the last visit in the hospital were registered. The medical chart of the 35 patients that were considered in remission in the previous publication was reviewed. In 30 patients no clinical evidence of failure was detected and no additional surgery on the previously infected prosthesis was necessary and they were considered in long-term remission. In 5 cases a late complication was identified. One case had a reinfection due to coagulase-negative staphylococci after 22 months from the open debridement and required a 2-stage revision surgery. The other 4 cases developed an aseptic loosening and it was necessary to perform a 1-stage exchange. Receiving a fluoroquinolone when all the Gram-negatives involved in the infection were susceptible to fluoroquinolones was the only factor associated with remission in the univariate analysis (p=0.002). After a long-term follow-up, our results support the importance of using fluoroquinolones in acute PJI due to Gram-negative bacilli.

New developments in the use of prostatic stents

PubMed Central

Papatsoris, Athanasios G; Junaid, Islam; Zachou, Alexandra; Kachrilas, Stefanos; Zaman, Faruquz; Masood, Junaid; Buchholz, Noor

2011-01-01

Bladder outflow obstruction is a very common age-related clinical entity due to a variety of benign and malignant diseases of the prostate. Surgical treatment under general or regional anesthesia is not suitable for high-risk elderly patients who seek minimally invasive management. Unfortunately, for patients who are not fit for transurethral and/or laser prostatectomy, few treatment options remain, other than long-term catheterization and insertion (under local anesthesia) of a prostatic stent. In this review, we present developments in the use of prostatic stents. PMID:24198637

Dire need of changes in the methods for assessing university faculty productivity in developing countries.

PubMed

Sheikh, Ali Sibtain Farooq; Mohamed, Mona Adel

2015-01-01

Publishing has become a necessity for promotion of faculty in academia. The faculties in developing countries face considerable difficulties publishing due to their prime focus on clinical approaches and resources for proper research. This often leaves no room for the pressured clinicians but to pursue poor quality publications just for the sake of promotion when the time for their promotion comes. The authors suggest establishing separate promotion tracks besides research in these underprivileged areas in order to avoid infestation of original research with poor ones.

The development of non-coding RNA ontology.

PubMed

Huang, Jingshan; Eilbeck, Karen; Smith, Barry; Blake, Judith A; Dou, Dejing; Huang, Weili; Natale, Darren A; Ruttenberg, Alan; Huan, Jun; Zimmermann, Michael T; Jiang, Guoqian; Lin, Yu; Wu, Bin; Strachan, Harrison J; de Silva, Nisansa; Kasukurthi, Mohan Vamsi; Jha, Vikash Kumar; He, Yongqun; Zhang, Shaojie; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming

2016-01-01

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic annotation of large amounts of ncRNA biological and clinical data.

Development of biosensors based on the one-dimensional semiconductor nanomaterials.

PubMed

Yan, Shancheng; Shi, Yi; Xiao, Zhongdang; Zhou, Minmin; Yan, Wenfu; Shen, Haoliang; Hu, Dong

2012-09-01

Biosensors are becoming increasingly important due to their applications in biological and chemical analyses, food safety industry, biomedical diagnostics, clinical detection, and environmental monitoring. Recent years, nanostructured semiconductor materials have been used to fabricate biosensors owing to their biocompatibility, low toxicity, high electron mobility, and easy fabrication. In the present study, we focus on recent various biosensors based on the one-dimensional semiconductor nanomaterials such as electrochemical biosensor, field-effect transistors biosensor, and label-free optical biosensor. In particular, the development of the electrochemical biosensor is discussed detailedly.

Investigational drugs to treat methicillin-resistant Staphylococcus aureus

PubMed Central

Vuong, Cuong; Yeh, Anthony J; Cheung, Gordon YC; Otto, Michael

2016-01-01

Introduction Staphylococcus aureus remains one of the leading causes of morbidity and mortality worldwide. This is to a large extent due to antibiotic-resistant strains, in particular methicillin-resistant S. aureus (MRSA). While the toll of invasive MRSA infections appears to decrease in U.S. hospitals, the rate of community-associated MRSA infections remains constant and there is a surge of MRSA in many other countries. This situation calls for continuing if not increased efforts to find novel strategies to combat MRSA infections. Areas covered This review will provide an overview of current investigational antibiotics in clinical development (up to phase II), and of therapeutic antibodies and alternative drugs against S. aureus in preclinical and clinical development, including a short description of the mechanism of action and a presentation of microbiological and clinical data. Expert opinion Increased recent antibiotic development efforts and results from pathogenesis research have led to several new antibiotics and alternative drugs, as well as a more informed selection of targets for vaccination efforts against MRSA. This developing portfolio of novel anti-staphylococcal drugs will hopefully provide us with additional and more efficient ways to combat MRSA infections in the near future and prevent us from running out of treatment options, even if new resistances arise. PMID:26536498

Development of a QDots 800 based fluorescent solid phantom for validation of NIRF imaging platforms

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Sevick-Muraca, Eva M.

2013-02-01

Over the past decade, we developed near-infrared fluorescence (NIRF) devices for non-invasive lymphatic imaging using microdosages of ICG in humans and for detection of lymph node metastasis in animal models mimicking metastatic human prostate cancer. To validate imaging, a NIST traceable phantom is needed so that developed "first-inhumans" drugs may be used with different luorescent imaging platforms. In this work, we developed a QDots 800 based fluorescent solid phantom for installation and operational qualification of clinical and preclinical, NIRF imaging devices. Due to its optical clearance, polyurethane was chosen as the base material. Titanium dioxide was used as the scattering agent because of its miscibility in polyurethane. QDots 800 was chosen owing to its stability and NIR emission spectra. A first phantom was constructed for evaluation of the noise floor arising from excitation light leakage, a phenomenon that can be minimized during engineering and design of fluorescent imaging systems. A second set of phantoms were constructed to enable quantification of device sensitivity associated with our preclinical and clinical devices. The phantoms have been successfully applied for installation and operational qualification of our preclinical and clinical devices. Assessment of excitation light leakage provides a figure of merit for "noise floor" and imaging sensitivity can be used to benchmark devices for specific imaging agents.

Benefits of object-oriented models and ModeliChart: modern tools and methods for the interdisciplinary research on smart biomedical technology.

PubMed

Gesenhues, Jonas; Hein, Marc; Ketelhut, Maike; Habigt, Moriz; Rüschen, Daniel; Mechelinck, Mare; Albin, Thivaharan; Leonhardt, Steffen; Schmitz-Rode, Thomas; Rossaint, Rolf; Autschbach, Rüdiger; Abel, Dirk

2017-04-01

Computational models of biophysical systems generally constitute an essential component in the realization of smart biomedical technological applications. Typically, the development process of such models is characterized by a great extent of collaboration between different interdisciplinary parties. Furthermore, due to the fact that many underlying mechanisms and the necessary degree of abstraction of biophysical system models are unknown beforehand, the steps of the development process of the application are iteratively repeated when the model is refined. This paper presents some methods and tools to facilitate the development process. First, the principle of object-oriented (OO) modeling is presented and the advantages over classical signal-oriented modeling are emphasized. Second, our self-developed simulation tool ModeliChart is presented. ModeliChart was designed specifically for clinical users and allows independently performing in silico studies in real time including intuitive interaction with the model. Furthermore, ModeliChart is capable of interacting with hardware such as sensors and actuators. Finally, it is presented how optimal control methods in combination with OO models can be used to realize clinically motivated control applications. All methods presented are illustrated on an exemplary clinically oriented use case of the artificial perfusion of the systemic circulation.

METHOD FOR MICRORNA ISOLATION FROM CLINICAL SERUM SAMPLES

PubMed Central

Li, Yu; Kowdley, Kris V.

2012-01-01

MicroRNAs are a group of intracellular non-coding RNA molecules that have been implicated in a variety of human diseases. Due to their high stability in blood, microRNAs released into circulation could be potentially utilized as non-invasive biomarkers for diagnosis or prognosis. Current microRNA isolation protocols are specifically designed for solid tissues and are impractical for biomarker development utilizing small-volume serum samples on a large scale. Thus, a protocol for microRNA isolation from serum is needed to accommodate these conditions in biomarker development. To establish such a protocol, we developed a simplified approach to normalize sample input by using single synthetic spike-in microRNA. We evaluated three commonly used commercial microRNA isolation kits for the best performance by comparing RNA quality and yield. The manufacturer’s protocol was further modified to improve the microRNA yield from 200 μL of human serum. MicroRNAs isolated from a large set of clinical serum samples were tested on the miRCURY LNA real-time PCR panel and confirmed to be suitable for high-throughput microRNA profiling. In conclusion, we have established a proven method for microRNA isolation from clinical serum samples suitable for microRNA biomarker development. PMID:22982505

Clinical practice guidelines in complementary and alternative medicine. An analysis of opportunities and obstacles. Practice and Policy Guidelines Panel, National Institutes of Health Office of Alternative Medicine.

PubMed

1997-01-01

An estimated 1 of 3 Americans uses some form of complementary and alternative medicine (CAM), such as acupuncture, homeopathy, or herbal medicine. In 1995, the National Institutes of Health Office of Alternative Medicine convened an expert panel to examine the role of clinical practice guidelines in CAM. The panel concluded that CAM practices currently are unsuitable for the development of evidence-based practice guidelines, in part because of the lack of relevant outcomes data from well-designed clinical trials. Moreover, the notions of standardization and appropriateness, inherent in guideline development, face challenging methodologic problems when applied to CAM, which considers many different treatment practices appropriate and encourages highly individualized care. Due to different belief systems and divergent theories about the nature of health and illness, CAM disciplines have fundamental differences in how they define target conditions, causes of disease, interventions, and outcome measures of effectiveness. These differences are even more striking when compared with those used by Western medicine. The panel made a series of recommendations on strategies to strengthen the evidence base for future guideline development in CAM and to meet better the current information needs of clinicians, patients, and guideline developers who seek information about CAM treatments.

Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics.

PubMed

Elzagallaai, A A; Greff, Mje; Rieder, M J

2017-06-01

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Anal Canal Gas Gangrene in Aplastic Anaemia: Rare yet Lethal Entity - A Caveat.

PubMed

Sudharsanan, Sundaramurthi; Vijayakumar, Chellappa; Manish, Kumar; Elamurugan, T P; Manwar, Ali S

2017-07-13

Gas gangrene is one of the most serious infections of traumatic and surgical wounds. The importance lies in the fact that, if not managed at the right time, the condition is fatal. Though perianal cellulitis and gangrene are commonly reported in immunocompromised patients, we report the case of a patient with gas gangrene involving only the anal canal extending to the rectum, a rare presentation to be reported in literature.  An 18-year-old lady, a patient of aplastic anaemia - immunodeficiency, developed gas gangrene of the anal canal possibly due to faecal contamination of anal fissures. The patient was managed with surgical debridement and intravenous antibiotics.  The clinical manifestations of gas gangrene are due to the liberation of toxins by Clostridium perfringens. The infection spreads rapidly and results in necrosis and devitalisation of tissues, unless intervened surgically. The clinical manifestations are more rapid and a high index of suspicion is needed for the diagnosis.

Anal Canal Gas Gangrene in Aplastic Anaemia: Rare yet Lethal Entity - A Caveat

PubMed Central

Sudharsanan, Sundaramurthi; Vijayakumar, Chellappa; Manish, Kumar; Elamurugan, TP

2017-01-01

Gas gangrene is one of the most serious infections of traumatic and surgical wounds. The importance lies in the fact that, if not managed at the right time, the condition is fatal. Though perianal cellulitis and gangrene are commonly reported in immunocompromised patients, we report the case of a patient with gas gangrene involving only the anal canal extending to the rectum, a rare presentation to be reported in literature.  An 18-year-old lady, a patient of aplastic anaemia - immunodeficiency, developed gas gangrene of the anal canal possibly due to faecal contamination of anal fissures. The patient was managed with surgical debridement and intravenous antibiotics.  The clinical manifestations of gas gangrene are due to the liberation of toxins by Clostridium perfringens. The infection spreads rapidly and results in necrosis and devitalisation of tissues, unless intervened surgically. The clinical manifestations are more rapid and a high index of suspicion is needed for the diagnosis. PMID:28936381

Imaging biomarkers in liver fibrosis.

PubMed

Berzigotti, A; França, M; Martí-Aguado, D; Martí-Bonmatí, L

There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies

PubMed Central

Mattoo, Seema; Cherry, James D.

2005-01-01

Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines. PMID:15831828

[Consensus document for the treatment of bacteremia and endocarditis caused by methicillin-resistent Staphylococcus aureus. Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica].

PubMed

Gudiol, Francisco; Aguado, José María; Pascual, Alvaro; Pujol, Miquel; Almirante, Benito; Miró, José María; Cercenado, Emilia; Domínguez, María de Los Angeles; Soriano, Alex; Rodríguez-Baño, Jesús; Vallés, Jordi; Palomar, Mercedes; Tornos, Pilar; Bouza, Emilio

2009-02-01

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.

Tuberculosis-associated Fibrosing Mediastinitis: Case Report and Literature Review.

PubMed

Tan, Ronald; Martires, Joanne; Kamangar, Nader

2016-01-01

Fibrosing mediastinitis is a rare condition defined by the presence of fibrotic mediastinal infiltrates that obliterate normal fat planes. It is a late complication of a previous granulomatous infection, such as histoplasmosis or tuberculosis (TB). Due to its rarity, fibrosing mediastinitis is often under-recognized, and the clinical presentation is variable and dependent on the extent of infiltration or encasement of structures within the mediastinum. We present a case of fibrosing mediastinitis in a man with a prior history of TB, who presented with progressive dyspnea and was found to have chronic mediastinal soft tissue opacities and pulmonary hypertension. His diagnosis was delayed due to the lack of recognition of this clinical/radiographic entity. Fibrosing mediastinitis is a rare entity usually caused by granulomatous disease. Most cases develop as a late complication of histoplasmosis or TB. The presence of calcified mediastinal soft tissue infiltrates on advanced chest imaging can be diagnostic of fibrosing mediastinitis in patients with a prior history of a granulomatous infection once active processes such as malignancy are excluded.

Hypohidrotic ectodermal dysplasia: a clinical case with a longitudinal approach.

PubMed

Fraiz, Fabian Calixto; Gugisch, Renato Cordeiro; Cavalcante-Leão, Bianca Lopes; Macedo, Liliane Moreira

2014-11-01

This paper describes a clinical case of a male with hypohidrotic ectodermal dysplasia submitted to rehabilitation and occlusal dental interventions with follow-up from 3 to 14 years of age. Due to the severe effects on function and esthetics, the clinical manifestations of ectodermal dysplasia exert a negative impact on quality of life. However, oral rehabilitation in childhood poses a challenge due to growth and development. A male with hypohidrotic ectodermal dysplasia began dental intervention at the age of 3 years. The clinical and radiographic exams revealed the absence of several primary and permanent teeth and abnormal shape of the primary maxillary incisors. The facial characteristics were compatible with hypohidrotic ectodermal dysplasia, such as a prominent brow, everted lips, fattened bridge of the nose and small vertical facial height. The treatment proposed involved rehabilitation through successive temporary partial dentures, functional orthopedics of the jaws, esthetic reconstruction of the anterior teeth, timely occlusal intervention and preventive actions for the control of dental caries and plaque. The present case demonstrates that early care plays a fundamental role in minimizing the biopsychosocial consequences of hypohidrotic ectodermal dysplasia and preparing the patient for future oral rehabilitation. Although, the literature offers a number of papers describing dental treatment for ectodermal dysplasia, few cases include long-term follow-up and the use of a functional orthopedic appliance in combination with removable dentures in such patients.

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Strategies to enhance patient recruitment and retention in research involving patients with a first episode of mental illness.

PubMed

Furimsky, Ivana; Cheung, Amy H; Dewa, Carolyn S; Zipursky, Robert B

2008-11-01

Recruitment and retention of research participants is often the most labor-intensive and difficult component of clinical trials. Poor recruitment and retention frequently pose as a major barrier in the successful completion of clinical trials. In fact, many studies are prematurely terminated, or their findings questioned due to low recruitment and retention rates. The conduct of clinical trials involving youth with a first episode of mental illness comes with additional challenges in recruitment and retention including barriers associated with engagement and family involvement. To develop effective early interventions for first episode mental illness, it is necessary to develop strategies to enhance recruitment and retention in this patient population. This article presents the recruitment and retention challenges experienced in two clinical trials: one involving participants experiencing a first episode of depression and one involving participants experiencing a first episode psychosis. Challenges with recruitment and retention are identified and reviewed at both the patient level and clinician level. Strategies that were implemented to enhance recruitment and retention in these two studies are also discussed. Finally, ethical issues to consider when implementing these strategies are also highlighted.

Cell based advanced therapeutic medicinal products for bone repair: Keep it simple?

PubMed

Leijten, J; Chai, Y C; Papantoniou, I; Geris, L; Schrooten, J; Luyten, F P

2015-04-01

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite this great promise, the clinical outcomes of the few cell based ATMPs that have been translated into clinical treatments have been far from impressive. In part, the clinical outcomes have been hampered because of the simplicity of the first wave of products. In response the field has set-out and amassed a plethora of complexities to alleviate the simplicity induced limitations. Many of these potential second wave products have remained "stuck" in the development pipeline. This is due to a number of reasons including the lack of a regulatory framework that has been evolving in the last years and the shortage of enabling technologies for industrial manufacturing to deal with these novel complexities. In this review, we reflect on the current ATMPs and give special attention to novel approaches that are able to provide complexity to ATMPs in a straightforward manner. Moreover, we discuss the potential tools able to produce or predict 'goldilocks' ATMPs, which are neither too simple nor too complex. Copyright © 2014 Elsevier B.V. All rights reserved.

Statin intolerance - a question of definition.

PubMed

Algharably, Engi Abdel-Hady; Filler, Iris; Rosenfeld, Stephanie; Grabowski, Katja; Kreutz, Reinhold

2017-01-01

Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed. Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested. Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.

Targeted Therapies for Brain Metastases from Breast Cancer.

PubMed

Venur, Vyshak Alva; Leone, José Pablo

2016-09-13

The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

PubMed Central

Masuda, Koichi

2010-01-01

The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086

Development of a Pediatric Adverse Events Terminology

PubMed Central

Gipson, Debbie S.; Kirkendall, Eric S.; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A.; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M.; Haber, Margaret; Hirschfeld, Steven

2017-01-01

In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute’s Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute’s Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization. PMID:28028203

Development of a Pediatric Adverse Events Terminology.

PubMed

Gipson, Debbie S; Kirkendall, Eric S; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M; Haber, Margaret; Hirschfeld, Steven

2017-01-01

In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization. Copyright © 2017 by the American Academy of Pediatrics.

The development of biomarkers to reduce attrition rate in drug discovery focused on oncology and central nervous system.

PubMed

Safavi, Maliheh; Sabourian, Reyhaneh; Abdollahi, Mohammad

2016-10-01

The task of discovery and development of novel therapeutic agents remains an expensive, uncertain, time-consuming, competitive, and inefficient enterprise. Due to a steady increase in the cost and time of drug development and the considerable amount of resources required, a predictive tool is needed for assessing the safety and efficacy of a new chemical entity. This study is focused on the high attrition rate in discovery and development of oncology and central nervous system (CNS) medicines, because the failure rate of these medicines is higher than others. Some approaches valuable in reducing attrition rates are proposed and the judicious use of biomarkers is discussed. Unlike the significant progress made in identifying and characterizing novel mechanisms of disease processes and targeted therapies, the process of novel drug development is associated with an unacceptably high attrition rate. The application of clinically qualified predictive biomarkers holds great promise for further development of therapeutic targets, improved survival, and ultimately personalized medicine sets for patients. Decisions such as candidate selection, development risks, dose ranging, early proof of concept/principle, and patient stratification are based on the measurements of biologically and/or clinically validated biomarkers.

Information technology in pharmacovigilance: Benefits, challenges, and future directions from industry perspectives.

PubMed

Lu, Zhengwu

2009-01-01

Risk assessment during clinical product development needs to be conducted in a thorough and rigorous manner. However, it is impossible to identify all safety concerns during controlled clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with comorbid conditions and those being treated with concomitant medications. Therefore, postmarketing safety data collection and clinical risk assessment based on observational data are critical for evaluating and characterizing a product's risk profile and for making informed decisions on risk minimization. Information science promises to deliver effective e-clinical or e-health solutions to realize several core benefits: time savings, high quality, cost reductions, and increased efficiencies with safer and more efficacious medicines. The development and use of standard-based pharmacovigilance system with integration connection to electronic medical records, electronic health records, and clinical data management system holds promise as a tool for enabling early drug safety detections, data mining, results interpretation, assisting in safety decision making, and clinical collaborations among clinical partners or different functional groups. The availability of a publicly accessible global safety database updated on a frequent basis would further enhance detection and communication about safety issues. Due to recent high-profile drug safety problems, the pharmaceutical industry is faced with greater regulatory enforcement and increased accountability demands for the protection and welfare of patients. This changing climate requires biopharmaceutical companies to take a more proactive approach in dealing with drug safety and pharmacovigilance.

Development and psychometric properties rating scale of “clinical competency evaluation in mental health nurses”: Exploratory factor analysis

PubMed Central

Moskoei, Sara; Mohtashami, Jamileh; Ghalenoeei, Mahdie; Nasiri, Maliheh; Tafreshi, Mansoreh Zaghari

2017-01-01

Introduction Evaluation of clinical competency in nurses has a distinct importance in healthcare due to its significant impact on improving the quality of patient care and creation of opportunities for professional promotion. This is a psychometric study for development of the “Clinical Competency of Mental Health Nursing”(CCMHN) rating scale. Methods In this methodological research that was conducted in 2015, in Tehran, Iran, the main items were developed after literature review and the validity and reliability of the tool were identified. The face, content (content validity ratio and content validity index) and construct validities were calculated. For face and content validity, experts’ comments were used. Exploratory factor analysis was used to determine the construct validity. The reliability of scale was determined by the internal consistency and inter-rater correlation. The collected data were analyzed by SPSS version 16, using descriptive statistical analysis. Results A scale with 45 items in two parts including Emotional/Moral and Specific Care competencies was developed. Content validity ratio and content validity index were 0.88, 0.97 respectively. Exploratory factor analysis indicated two factors: The first factor with 23.93 eigenvalue and second factor with eigenvalue 2.58. Cronbach’s alpha coefficient for determination of internal consistency was 0.98 and the ICC for confirmation inter-rater correlation was 0.98. Conclusion A scale with 45 items and two areas was developed with appropriate validity and reliability. This scale can be used to assess the clinical competency in nursing students and mental health nurses. PMID:28607650

DNA decontamination methods for internal quality management in clinical PCR laboratories.

PubMed

Wu, Yingping; Wu, Jianyong; Zhang, Zhihui; Cheng, Chen

2018-03-01

The polymerase chain reaction (PCR) technique, one of the most commonly applied methods in diagnostic and molecular biology, has a frustrating downside: the occurrence of false-positive signals due to contamination. In previous research, various DNA decontamination methods have been developed to overcome this limitation. Unfortunately, the use of random or poorly focused sampling methods for monitoring air and/or object surfaces leads to the incomplete elimination during decontamination procedures. We herein attempted to develop a novel DNA decontamination method (environmental surveillance, including surface and air sampling) and quality management program for clinical molecular diagnostic laboratories (or clinical PCR laboratories). Here, we performed a step-by-step evaluation of current DNA decontamination methods and developed an effective procedure for assessing the presence of decontaminating DNA via PCR analysis. Performing targeted environmental surveillance by sampling, which reached optimal performance over 2 weeks, and the decontamination process had been verified as reliable. Additionally, the process was validated to not affect PCR amplification efficiency based on a comparative study. In this study, effective guidelines for DNA decontamination were developed. The method employed ensured that surface DNA contamination could be effectively identified and eliminated. Furthermore, our study highlighted the importance of overall quality assurance and good clinical laboratory practices for preventing contamination, which are key factors for compliance with regulatory or accreditation requirements. Taken together, we provided the evidence that the presented scheme ranged from troubleshooting to the elimination of surface contamination, could serve as critical foundation for developing regular environmental surveillance guidelines for PCR laboratories. © 2017 Wiley Periodicals, Inc.

Doctoral programs to train future leaders in clinical and translational science.

PubMed

Switzer, Galen E; Robinson, Georgeanna F W B; Rubio, Doris M; Fowler, Nicole R; Kapoor, Wishwa N

2013-09-01

Although the National Institutes of Health (NIH) has made extensive investments in educational programs related to clinical and translational science (CTS), there has been no systematic investigation of the number and characteristics of PhD programs providing training to future leaders in CTS. The authors undertook to determine the number of institutions that, having had received NIH-funded Clinical and Translational Science Awards (CTSAs), currently had or were developing PhD programs in CTS; to examine differences between programs developed before and after CTSA funding; and to provide detailed characteristics of new programs. In 2012, CTS program leaders at the 60 CTSA-funded institutions completed a cross-sectional survey focusing on four key domains related to PhD programs in CTS: program development and oversight; students; curriculum and research; and milestones. Twenty-two institutions had fully developed PhD programs in CTS, and 268 students were earning PhDs in this new field; 13 institutions were planning PhD programs. New programs were more likely to have fully developed PhD competencies and more likely to include students in medical school, students working only on their PhD, students working on a first doctoral degree, and students working in T1 translational research. They were less likely to include physicians and students working in clinical or T2 research. Although CTS PhD programs have similarities, they also vary in their characteristics and management of students. This may be due to diversity in translational science itself or to the relative infancy of CTS as a discipline.

Doctoral Programs to Train Future Leaders in Clinical and Translational Science

PubMed Central

Switzer, Galen E.; Robinson, Georgeanna F.W.B.; Rubio, Doris M.; Fowler, Nicole R.; Kapoor, Wishwa N.

2013-01-01

Purpose Although the National Institutes of Health (NIH) has made extensive investments in educational programs related to clinical and translational science (CTS), there has been no systematic investigation of the number and characteristics of PhD programs providing training to future leaders in CTS. The authors undertook to determine the number of institutions that, having had received NIH-funded Clinical and Translational Science Awards (CTSAs), currently had or were developing PhD programs in CTS; to examine differences between programs developed before and after CTSA funding; and to provide detailed characteristics of new programs. Method In 2012, CTS program leaders at the 60 CTSA-funded institutions completed a cross-sectional survey focusing on four key domains related to PhD programs in CTS: program development and oversight; students; curriculum and research; and milestones. Results Twenty-two institutions had fully developed PhD programs in CTS, and 268 students were earning a PhD in this new field; 13 institutions were planning a PhD program. New programs were more likely to have fully developed PhD competencies and more likely to include students in medical school, students working only on their PhD, students working on a first doctoral degree, and students working in T1 translational research. They were less likely to include physicians and students working in clinical or T2 research. Conclusions Although CTS PhD programs have similarities, they also vary in their characteristics and management of students. This may be due to diversity in translational science itself or to the relative infancy of CTS as a discipline. PMID:23899901

Development of a case definition for clinical feline herpesvirus infection in cheetahs (Acinonyx jubatus) housed in zoos.

PubMed

Witte, Carmel L; Lamberski, Nadine; Rideout, Bruce A; Fields, Victoria; Teare, Cyd Shields; Barrie, Michael; Haefele, Holly; Junge, Randall; Murray, Suzan; Hungerford, Laura L

2013-09-01

The identification of feline herpesvirus (FHV) infected cheetahs (Acinonyx jubatus) and characterization of shedding episodes is difficult due to nonspecific clinical signs and limitations of diagnostic tests. The goals of this study were to develop a case definition for clinical FHV and describe the distribution of signs. Medical records from six different zoologic institutions were reviewed to identify cheetahs with diagnostic test results confirming FHV. Published literature, expert opinion, and results of a multiple correspondence analysis (MCA) were used to develop a clinical case definition based on 69 episodes in FHV laboratory confirmed (LC) cheetahs. Four groups of signs were identified in the MCA: general ocular signs, serious ocular lesions, respiratory disease, and cutaneous lesions. Ocular disease occurred with respiratory signs alone, with skin lesions alone, and with both respiratory signs and skin lesions. Groups that did not occur together were respiratory signs and skin lesions. The resulting case definition included 1) LC cheetahs; and 2) clinically compatible (CC) cheetahs that exhibited a minimum of 7 day's duration of the clinical sign groupings identified in the MCA or the presence of corneal ulcers or keratitis that occurred alone or in concert with other ocular signs and skin lesions. Exclusion criteria were applied. Application of the case definition to the study population identified an additional 78 clinical episodes, which represented 58 CC cheetahs. In total, 28.8% (93/322) of the population was identified as LC or CC. The distribution of identified clinical signs was similar across LC and CC cheetahs. Corneal ulcers and/or keratitis, and skin lesions were more frequently reported in severe episodes; in mild episodes, there were significantly more cheetahs with ocular-only or respiratory-only disease. Our results provide a better understanding of the clinical presentation of FHV, while presenting a standardized case definition that can both contribute to earlier diagnoses and be used for population-level studies.

‘Toning’ up hypotonia assessment: A proposal and critique

PubMed Central

Joubert, Robin W.E.

2016-01-01

Background Clinical assessment of hypotonia is challenging due to the subjective nature of the initial clinical evaluation. This poses dilemmas for practitioners in gaining accuracy, given that the presentation of hypotonia can be either a non-threatening or malevolent sign. The research question posed was how clinical assessment can be improved, given the current contentions expressed in the scientific literature. Objectives This paper describes the development and critique of a clinical algorithm to aid the assessment of hypotonia. Methods An initial exploratory sequential phase, consisting of a systematic review, a survey amongst clinicians and a Delphi process, assisted in the development of the algorithm, which is presented within the framework of the International Classification of Functioning, Disability and Health. The ensuing critique followed a qualitative emergent–systematic focus group design with a purposive sample of 59 clinicians. Data were analysed using semantical content analysis and are presented thematically with analytical considerations. Results This study culminated in the development of an evidence-based clinical algorithm for practice. The qualitative critique of the algorithm considered aspects such as inadequacies, misconceptions and omissions; strengths; clinical use; resource implications; and recommendations. Conclusions The first prototype and critique of a clinical algorithm to assist the clinical assessment of hypotonia in children has been described. Barriers highlighted include aspects related to knowledge gaps of clinicians, issues around user-friendliness and formatting concerns. Strengths identified by the critique included aspects related to the evidence-based nature of the criteria within the algorithm, the suitability of the algorithm in being merged or extending current practice, the potential of the algorithm in aiding more accurate decision-making, the suitability of the algorithm across age groups and the logical flow. These findings provide a starting point towards ascertaining the clinical utility of the algorithm as an essential step towards evidence-based praxis. PMID:28730054

Case Report: Myiasis due to Cochliomyia hominivorax and Dermatobia hominis: Clinical and Pathological Differences between Two Species in Northern Peru.

PubMed

Failoc-Rojas, Virgilio E; Molina-Ayasta, Carolina; Salazar-Zuloeta, Jaime; Samamé, Abel; Silva-Díaz, Heber

2018-01-01

Infestations caused by fly larvae (Myiasis) have been observed in patients with risk factors and in tropical zones. The aim of our study was to describe the clinical and epidemiological aspects and the risk factors associated with the occurrence of obligatory myiasis, as well as the therapeutic approach to patients. We identified the cases of myiasis diagnosed in two referral hospitals in northern Peru from January 2012 to December 2015 and included patients in whom larval development and a compatible clinical profile were observed. Epidemiological, clinical, analytical, diagnostic, therapeutic, and follow-up data were collected from clinical files. Nine clinical cases were compatible with a diagnosis of myiasis; of these, two were pediatric patients, one was a middle-aged adult, and six were elderly patients. Four of the nine patients were male. The identified species were Dermatobia hominis and Cochliomyia hominivorax. The therapeutic approach included antiparasitic therapy with ivermectin, antibacterial, and in some cases, anti-inflammatory drugs. Dermatobia hominis and C. hominivorax are the predominant species causing myiasis in northern Peru.

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

PubMed

Leone, Stefania; Di Cianni, Simone; Casati, Andrea; Fanelli, Guido

2008-08-01

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: the case for conditioned overgeneralization.

PubMed

Lissek, Shmuel

2012-04-01

The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of overgeneralization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety. © 2012 Wiley Periodicals, Inc.

Childhood Ataxia: Clinical Features, Pathogenesis, Key Unanswered Questions, and Future Directions

PubMed Central

Ashley, Claire N.; Hoang, Kelly D.; Lynch, David R.; Perlman, Susan L.; Maria, Bernard L.

2013-01-01

Childhood ataxia is characterized by impaired balance and coordination primarily due to cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. PMID:22859693

Robot-aided assessment of lower extremity functions: a review.

PubMed

Maggioni, Serena; Melendez-Calderon, Alejandro; van Asseldonk, Edwin; Klamroth-Marganska, Verena; Lünenburger, Lars; Riener, Robert; van der Kooij, Herman

2016-08-02

The assessment of sensorimotor functions is extremely important to understand the health status of a patient and its change over time. Assessments are necessary to plan and adjust the therapy in order to maximize the chances of individual recovery. Nowadays, however, assessments are seldom used in clinical practice due to administrative constraints or to inadequate validity, reliability and responsiveness. In clinical trials, more sensitive and reliable measurement scales could unmask changes in physiological variables that would not be visible with existing clinical scores.In the last decades robotic devices have become available for neurorehabilitation training in clinical centers. Besides training, robotic devices can overcome some of the limitations in traditional clinical assessments by providing more objective, sensitive, reliable and time-efficient measurements. However, it is necessary to understand the clinical needs to be able to develop novel robot-aided assessment methods that can be integrated in clinical practice.This paper aims at providing researchers and developers in the field of robotic neurorehabilitation with a comprehensive review of assessment methods for the lower extremities. Among the ICF domains, we included those related to lower extremities sensorimotor functions and walking; for each chapter we present and discuss existing assessments used in routine clinical practice and contrast those to state-of-the-art instrumented and robot-aided technologies. Based on the shortcomings of current assessments, on the identified clinical needs and on the opportunities offered by robotic devices, we propose future directions for research in rehabilitation robotics. The review and recommendations provided in this paper aim to guide the design of the next generation of robot-aided functional assessments, their validation and their translation to clinical practice.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

PubMed

Sugawara, Norio; Ishioka, Masamichi; Tsuchimine, Shoko; Tsuruga, Koji; Sato, Yasushi; Tarakita, Natsumi; Furukori, Hanako; Kudo, Shuhei; Tomita, Tetsu; Nakagami, Taku; Yasui-Furukori, Norio

2018-01-01

Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. Patients were asked about possible participation in placebo-controlled clinical trials. Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial. Copyright © 2017. Published by Elsevier B.V.

What helps or hinders the transformation from a major tertiary center to a major trauma center? Identifying barriers and enablers using the Theoretical Domains Framework.

PubMed

Roberts, Neil; Lorencatto, Fabiana; Manson, Joanna; Brundage, Susan I; Jansen, Jan O

2016-03-12

Major Trauma Centers (MTCs), as part of a trauma system, improve survival and functional outcomes from injury. Developing such centers from current teaching hospitals is likely to generate diverse beliefs amongst staff. These may act as barriers or enablers. Prior identification of these may make the service development process more efficient. The importance of applying theory to systematically identify barriers and enablers to changing clinical practice in emergency medicine has been emphasized. This study systematically explored theory-based barriers and enablers towards implementing the transformation of a tertiary hospital into a MTC. Our goal was to demonstrate the use of a replicable method to identify targets that could be addressed to achieve a successful transformation from an organization evolved to provide a particular type of clinical care into a clinical system with different demands, requirements and expectations. The Theoretical Domains Framework (TDF) is a tool designed to elicit and analyze beliefs affecting behavior. Semi-structured interviews based around the TDF were conducted in a major tertiary hospital in Scotland due to become a MTC with a purposive sample of major stakeholders including clinicians and nurses from specialties involved in trauma care, clinical managers and administration. Belief statements were identified through qualitative analysis, and assessed for importance according to prevalence, discordance and evidence base. 1728 utterances were recorded and coded into 91 belief statements. 58 were classified as important barriers/enablers. There were major concerns about resource demands, with optimism conditional on these being met. Distracting priorities abound within the Emergency Department. Better communication is needed. Staff motivation is high and they should be engaged in skills development and developing performance improvement processes. This study presents a systematic and replicable method of identifying theory-based barriers and enablers towards complex service development. It identifies multiple barriers/enablers that may serve as a basis for developing an implementation intervention to enhance the development of MTCs. This method can be used to address similar challenges in developing specialist centers or implementing clinical practice change in emergency care across both developing and developed countries.

Effect of antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever: protective effects of doxycycline.

PubMed

Rikihisa, Y; Jiang, B M

1989-03-01

Effects of three antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever caused by Ehrlichia risticii infection were examined. When antibiotics were given after the development of clinical signs, antibiotics ranked in the order of reducing clinical signs and in preventing body weight loss and an intestinal enlargement were doxycycline, demeclocycline and rifampin. Infected mice treated with doxycycline and demeclocycline developed greater splenomegaly than rifampin-treated or untreated infected mice. All antibiotics used prevented thymic atrophy due to E. risticii infection. Indirect fluorescent antibody titers were highest with doxycycline treatment. Mice treated with demeclocycline and rifampin produced higher antibody titer than those without treatment. Ehrlichia risticii was reisolated from the spleens of both untreated and rifampin-treated infected mice. The effects of administering single doses of doxycycline at different times after infection were examined. Body weight loss was prevented by the drug given at every treatment day examined, i.e. Days 3, 5 and 7 post-infection (PI). Thymic atrophy was minimum in mice treated at Day 5 PI, while splenomegaly was found on every treatment day. Splenocyte proliferative response to concanavalin A and lipopolysaccharide, and specific antibody development against E. risticii was best in mice treated at Day 5 PI followed by those treated at Day 3 and Day 7 PI.

Development and comparative evaluation of SYBR Green I-based one-step real-time RT-PCR assay for detection and quantification of West Nile virus in human patients.

PubMed

Kumar, Jyoti S; Saxena, Divyasha; Parida, Manmohan

2014-01-01

The recent outbreaks of West Nile Virus (WNV) in the Northeastern American continents and other regions of the world have made it essential to develop an efficient protocol for surveillance of WN virus. Nucleic acid based techniques like, RT-PCR have the advantage of sensitivity, specificity and rapidity. A one step single tube Env gene specific real-time RT-PCR was developed for early and reliable clinical diagnosis of WNV infection in clinical samples. The applicability of this assay for clinical diagnosis was validated with 105 suspected acute-phase serum and plasma samples from the recent epidemic of mysterious fever in Tamil Nadu, India in 2009-10. The comparative evaluation revealed the higher sensitivity of real-time RT-PCR assay by picking up 4 additional samples with low copy number of template in comparison to conventional RT-PCR. All the real-time positive samples further confirmed by CDC reported TaqMan real-time RT-PCR and quantitative real-time RT-PCR assays for the simultaneous detection of WNV lineage 1 and 2 strains. The quantitation of the viral load samples was done using a standard curve. These findings demonstrated that the assay has the potential usefulness for clinical diagnosis due to detection and quantification of WNV in acute-phase patient serum samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

NEW DEVELOPMENTS IN RADIATION THERAPY FOR HEAD AND NECK CANCER: INTENSITY MODULATED RADIATION THERAPY AND HYPOXIA TARGETING

PubMed Central

Lee, Nancy Y.; Le, Quynh-Thu

2008-01-01

Intensity modulated radiation therapy (IMRT) has revolutionized radiation treatment for head and neck cancers (HNC). When compared to the traditional techniques, IMRT has the unique ability to minimize the dose delivered to normal tissues without compromising tumor coverage. As a result, side effects from high dose radiation have decreased and patient quality of life has improved. In addition to toxicity reduction, excellent clinical outcomes have been reported for IMRT. The first part of this review will focus on clinical results of IMRT for HNC. Tumor hypoxia or the condition of low oxygen is a key factor for tumor progression and treatment resistance. Hypoxia develops in solid tumors due to aberrant blood vessel formation, fluctuation in blood flow and increasing oxygen demands for tumor growth. Because hypoxic tumor cells are more resistant to ionizing radiation, hypoxia has been a focus of clinical research in radiation therapy for half a decade. Interest for targeting tumor hypoxia have waxed and waned as promising treatments emerged from the laboratory, only to fail in the clinics. However, with the development of new technologies, the prospect of targeting tumor hypoxia is more tangible. The second half of the review will focus on approaches for assessing tumor hypoxia and on the strategies for targeting this important microenvironmental factor in HNC. PMID:18544439

Liver Histology During Mipomersen Therapy for Severe Hypercholesterolemia

PubMed Central

Hashemi, Nikroo; Odze, Robert D.; McGowan, Mary P.; Santos, Raul D.; Stroes, Erik S.G.; Cohen, David E.

2014-01-01

Background Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein (apo) B synthesis and lowers plasma low density lipoprotein (LDL) cholesterol even in the absence of LDL receptor function, presumably due to the inhibition of hepatic production of triglyceride-rich very low density lipoprotein (VLDL) particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase (ALT) elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. Objective The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. Methods We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. Results The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. Conclusion These findings suggest that hepatic steatosis due to mipomersen is distinct from non-alcoholic steatohepatitis. PMID:25499943

Use of FEV1 in Cystic Fibrosis Epidemiologic Studies and Clinical Trials: A Statistical Perspective for the Clinical Researcher

PubMed Central

Szczesniak, Rhonda; Heltshe, Sonya L.; Stanojevic, Sanja; Mayer-Hamblett, Nicole

2017-01-01

Background Forced expiratory volume in 1 second (FEV1) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV1 surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV1. Results In this review, we summarize from a statistical perspective the clinical relevance of FEV1 based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations. Conclusions Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV1. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV1 analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care. PMID:28117136

Ketonuria and HELLP syndrome

PubMed Central

Gubbala, Phanendra Kumar; Karoshi, Mahantesh; Zakaria, Faris

2009-01-01

We recently managed a patient with the HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelet count) where there was a delay in diagnosis due to gastroenteritis. This case also reiterates the varied or lack of symptomatology in patients developing HELLP and obscuring the initial diagnosis. Patients with HELLP syndrome have significant maternal morbidity and mortality, hence clinical vigilance and high suspicion play a key role in the diagnosis and subsequent management. PMID:21686464

Ketonuria and HELLP syndrome.

PubMed

Gubbala, Phanendra Kumar; Karoshi, Mahantesh; Zakaria, Faris

2009-01-01

We recently managed a patient with the HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelet count) where there was a delay in diagnosis due to gastroenteritis. This case also reiterates the varied or lack of symptomatology in patients developing HELLP and obscuring the initial diagnosis. Patients with HELLP syndrome have significant maternal morbidity and mortality, hence clinical vigilance and high suspicion play a key role in the diagnosis and subsequent management.

CPTAC Develops Fit-for-Purpose Multiplex Immuno-MRM Assay for Profiling the DNA Damage Response Pathway | Office of Cancer Clinical Proteomics Research

Cancer.gov

Ionizing radiation (IR) is a commonly employed cancer treatment that kills cancer cells by damaging their DNA. While the DNA damage response (DDR) pathway may be key to determining tumor responses, radiochemical damage due to IR can target the patients’ healthy dividing cells, leading to the formation of secondary hematologic and solid tumors after DNA-damaging therapy.

Nonprofit foundations spur translational research.

PubMed

Zaratin, Paola; Battaglia, Mario Alberto; Abbracchio, Maria P

2014-11-01

Every year, hundreds of promising basic discoveries in the pharmacological field are lost and will never have a chance to be exploited for patients due to difficulties in clinical translation. This is especially true for most neurodegenerative disorders lacking disease-modifying therapies. Here we present the current scenario and our vision of a 'collective-impact' multistakeholder approach to expedite the development of new drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recent progress in the development of polysaccharide conjugates of docetaxel and paclitaxel

PubMed Central

Roy, Aniruddha; Bhattacharyya, Mousumi; Ernsting, Mark J.; May, Jonathan P; Li, Shyh-Dar

2014-01-01

Taxanes are one of the most potent and broadest spectrum chemotherapeutics used clinically, but also induce significant side effects. Different strategies have been developed to produce a safer taxane formulation. Development of polysaccharide drug conjugates has increased in the recent years due to the demonstrated biocompatibility, biodegradability, safety and low cost of the biopolymers. This review focuses on polysaccharide taxane conjugates and provides an overview on various conjugation strategies and their effect on the efficacy. Detailed analyses on the designing factors of an effective polysaccharide drug conjugate are provided with a discussion on the future direction of this field. PMID:24652678

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development.

PubMed

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho; Kim, Tae Won

2018-04-24

Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. ©Yu Rang Park, Young Jo Yoon, HaYeong Koo, Soyoung Yoo, Chang-Min Choi, Sung-Ho Beck, Tae Won Kim. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2018.

Use of interleukin-2 for management of natalizumab-associated progressive multifocal leukoencephalopathy: case report and review of literature

PubMed Central

Dubey, Divyanshu; Zhang, Yinan; Graves, Donna; DeSena, Allen D.; Frohman, Elliot; Greenberg, Benjamin

2015-01-01

A 51-year-old woman with relapsing–remitting multiple sclerosis (RRMS) and 3-year history of natalizumab use developed expressive aphasia. A brain magnetic resonance image (MRI) showed left frontotemporal and right parietal lesion with mild contrast enhancement and cerebrospinal fluid (CSF) was positive for John Cunningham virus (JCV) by polymerase chain reaction (PCR). The patient received five cycles of plasmapheresis followed by intravenous immunoglobulin. Despite this intervention, her speech deteriorated and she developed right hemiparesis. Upon referral to our institution, CSF quantitative JCV PCR was notable for 834 copies/ml. The patient was given an initial dose of 50,000 units of interleukin-2 (IL-2) subcutaneously (SQ) followed by 1 million units IL-2 SQ daily. Due to concern for immune reconstitution inflammatory syndrome (IRIS), the patient also received intravenous methylprednisone weekly. The regimen was tolerated well by the patient with no severe adverse effects. Clinically, the patient showed some improvement, and became more responsive and regained right lower extremity antigravity strength. After 12 weeks of IL-2 therapy, JCV quantitative PCR was notable for 31 copies/ml and the patient was more responsive. Due to persistence of JCV, IL-2 therapy was changed to mefloquine. At follow up after 6 months, the patient showed no clinical deterioration. PMID:27134676

Strategies to design clinical studies to identify predictive biomarkers in cancer research.

PubMed

Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

2017-02-01

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Task shifting and integration of HIV care into primary care in South Africa: The development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention

PubMed Central

2011-01-01

Background Task shifting and the integration of human immunodeficiency virus (HIV) care into primary care services have been identified as possible strategies for improving access to antiretroviral treatment (ART). This paper describes the development and content of an intervention involving these two strategies, as part of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) pragmatic randomised controlled trial. Methods: Developing the intervention The intervention was developed following discussions with senior management, clinicians, and clinic staff. These discussions revealed that the establishment of separate antiretroviral treatment services for HIV had resulted in problems in accessing care due to the large number of patients at ART clinics. The intervention developed therefore combined the shifting from doctors to nurses of prescriptions of antiretrovirals (ARVs) for uncomplicated patients and the stepwise integration of HIV care into primary care services. Results: Components of the intervention The intervention consisted of regulatory changes, training, and guidelines to support nurse ART prescription, local management teams, an implementation toolkit, and a flexible, phased introduction. Nurse supervisors were equipped to train intervention clinic nurses in ART prescription using outreach education and an integrated primary care guideline. Management teams were set up and a STRETCH coordinator was appointed to oversee the implementation process. Discussion Three important processes were used in developing and implementing this intervention: active participation of clinic staff and local and provincial management, educational outreach to train nurses in intervention sites, and an external facilitator to support all stages of the intervention rollout. The STRETCH trial is registered with Current Control Trials ISRCTN46836853. PMID:21810242

Development of a diabetes care management curriculum in a family practice residency program.

PubMed

Nuovo, Jim; Balsbaugh, Thomas; Barton, Sue; Davidson, Ellen; Fox-Garcia, Jane; Gandolfo, Angela; Levich, Bridget; Seibles, Joann

2004-01-01

Improving the quality of care for patients with chronic illness has become a high priority. Implementing training programs in disease management (DM) so the next generation of physicians can manage chronic illness more effectively is challenging. Residency training programs have no specific mandate to implement DM training. Additional barriers at the training facility include: 1) lack of a population-based perspective for service delivery; 2) weak support for self-management of illness; 3) incomplete implementation due to physician resistance or inertia; and 4) few incentives to change practices and behaviors. In order to overcome these barriers, training programs must take the initiative to implement DM training that addresses each of these issues. We report the implementation of a chronic illness management curriculum based on the Improving Chronic Illness Care (ICIC) Model. Features of this process included both patient care and learner objectives. These were: development of a multidisciplinary diabetes DM team; development of a patient registry; development of diabetes teaching clinics in the family practice center (nutrition, general management classes, and one-on-one teaching); development of a group visit model; and training the residents in the elements of the ICIC Model, ie, the community, the health system, self-management support, delivery system design, decision support, and clinical information systems. Barriers to implementing these curricular changes were: the development of a patient registry; buy-in from faculty, residents, clinic leadership, staff, and patients for the chronic care model; the ability to bill for services and maintain clinical productivity; and support from the health system key stakeholders for sustainability. Unique features of each training site will dictate differences in emphasis and structure; however, the core principles of the ICIC Model in enhancing self-management may be generalized to all sites.

Respiratory infections due to nontuberculous mycobacterias.

PubMed

Máiz Carro, Luis; Barbero Herranz, Esther; Nieto Royo, Rosa

2018-03-09

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

A systematic review evaluating the impact of online or blended learning vs. face-to-face learning of clinical skills in undergraduate nurse education.

PubMed

McCutcheon, Karen; Lohan, Maria; Traynor, Marian; Martin, Daphne

2015-02-01

To determine whether the use of an online or blended learning paradigm has the potential to enhance the teaching of clinical skills in undergraduate nursing. The need to adequately support and develop students in clinical skills is now arguably more important than previously considered due to reductions in practice opportunities. Online and blended teaching methods are being developed to try and meet this requirement, but knowledge about their effectiveness in teaching clinical skills is limited. Mixed methods systematic review, which follows the Joanna Briggs Institute User guide version 5. Computerized searches of five databases were undertaken for the period 1995-August 2013. Critical appraisal and data extraction were undertaken using Joanna Briggs Institute tools for experimental/observational studies and interpretative and critical research. A narrative synthesis was used to report results. Nineteen published papers were identified. Seventeen papers reported on online approaches and only two papers reported on a blended approach. The synthesis of findings focused on the following four areas: performance/clinical skill, knowledge, self-efficacy/clinical confidence and user experience/satisfaction. The e-learning interventions used varied throughout all the studies. The available evidence suggests that online learning for teaching clinical skills is no less effective than traditional means. Highlighted by this review is the lack of available evidence on the implementation of a blended learning approach to teaching clinical skills in undergraduate nurse education. Further research is required to assess the effectiveness of this teaching methodology. © 2014 John Wiley & Sons Ltd.

The rise and fall of the CD28 superagonist TGN1412 and its return as TAB08: a personal account.

PubMed

Hünig, Thomas

2016-09-01

Two decades ago, we discovered 'superagonistic' monoclonal antibodies specific for the CD28 molecule which are able to polyclonally activate T cells, in particular regulatory T cells, and are therapeutically active in many rodent models of autoimmunity, inflammation, transplantation, and tissue repair. A phase I trial of the human CD28 superagonist TGN1412 failed in 2006 due to an unexpected cytokine release syndrome, but after it became clear that dose-reduction allows to preferentially address regulatory T cells also in humans, clinical development was resumed under the name TAB08. Here, I recount the story of CD28 superagonist development from a personal perspective with an emphasis on the dramatic events during and after the 2006 phase I trial, the reasons for the failure of preclinical research to warn of the impending cytokine storm, and on the research which allowed resumption of clinical development. © 2016 Federation of European Biochemical Societies.

Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

PubMed

Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

2017-12-05

The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Unified Approach to the Biomechanics of Dental Implantology

NASA Technical Reports Server (NTRS)

Grenoble, D. E.; Knoell, A. C.

1973-01-01

The human need for safe and effective dental implants is well-recognized. Although many implant designs have been tested and are in use today, a large number have resulted in clinical failure. These failures appear to be due to biomechanical effects, as well as biocompatibility and surgical factors. A unified approach is proposed using multidisciplinary systems technology, for the study of the biomechanical interactions between dental implants and host tissues. The approach progresses from biomechanical modeling and analysis, supported by experimental investigations, through implant design development, clinical verification, and education of the dental practitioner. The result of the biomechanical modeling, analysis, and experimental phases would be the development of scientific design criteria for implants. Implant designs meeting these criteria would be generated, fabricated, and tested in animals. After design acceptance, these implants would be tested in humans, using efficient and safe surgical and restorative procedures. Finally, educational media and instructional courses would be developed for training dental practitioners in the use of the resulting implants.

Development of nonhuman adenoviruses as vaccine vectors

PubMed Central

Bangari, Dinesh S.; Mittal, Suresh K.

2006-01-01

Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclinical and clinical studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clinical use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addition to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination. PMID:16297508

Independent data monitoring committees: Preparing a path for the future

PubMed Central

Hess, Connie N.; Roe, Matthew T.; Gibson, C. Michael; Temple, Robert J.; Pencina, Michael J.; Zarin, Deborah A.; Anstrom, Kevin J.; Alexander, John H.; Sherman, Rachel E.; Fiedorek, Fred T.; Mahaffey, Kenneth W.; Lee, Kerry L.; Chow, Shein-Chung; Armstrong, Paul W.; Califf, Robert M.

2014-01-01

Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representatives from government, industry, and academia assembled at the Duke Clinical Research Institute to address these challenges and to develop recommendations for the future utilization of IDMCs in RCTs. PMID:25066551

Development of molecularly imprinted polymers to block quorum sensing and inhibit bacterial biofilm formation.

PubMed

Ma, Luyao; Feng, Shaolong; de la Fuente-Nunez, Cesar; Hancock, Robert E W; Lu, Xiaonan

2018-05-16

Bacterial biofilms are responsible for most clinical infections and show increased antimicrobial resistance. In this study, molecularly imprinted polymers (MIPs) were developed to specifically capture prototypical quorum sensing autoinducers [i.e., N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12AHL)], interrupt quorum sensing, and subsequently inhibit biofilm formation of Pseudomonas aeruginosa, an important human nosocomial pathogen. The synthesis of MIPs was optimized by considering the amount and type of the functional monomers itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA). IA-based MIPs showed high adsorption affinity towards 3-oxo-C12AHL with an imprinting factor of 1.68. Compared to IA-based MIPs, the adsorption capacity of HEMA-based MIPs was improved 5-fold. HEMA-based MIPs significantly reduced biofilm formation (by ~65%), while biofilm suppression by IA-based MIPs was neutralized due to increased bacterial attachment. The developed MIPs represent promising alternative biofilm intervention agents that can be applied to surfaces relevant to clinical settings and food processing equipment.

The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations

PubMed Central

Rust, Aleksander; Partridge, Lynda J.; Davletov, Bazbek

2017-01-01

Ribosome inactivating proteins (RIPs) form a class of toxins that was identified over a century ago. They continue to fascinate scientists and the public due to their very high activity and long-term stability which might find useful applications in the therapeutic killing of unwanted cells but can also be used in acts of terror. We will focus our review on the canonical plant-derived RIPs which display ribosomal RNA N-glycosidase activity and irreversibly inhibit protein synthesis by cleaving the 28S ribosomal RNA of the large 60S subunit of eukaryotic ribosomes. We will place particular emphasis on therapeutic applications and the generation of immunotoxins by coupling antibodies to RIPs in an attempt to target specific cells. Several generations of immunotoxins have been developed and we will review their optimisation as well as their use and limitations in pre-clinical and clinical trials. Finally, we endeavour to provide a perspective on potential future developments for the therapeutic use of immunotoxins. PMID:29076988

Demographic characteristics and clinical predictors of patients discharged from university hospital-affiliated pain clinic due to breach in narcotic use contract.

PubMed

Chakrabortty, Shushovan; Gupta, Deepak; Rustom, David; Berry, Hussein; Rai, Ajit

2014-01-01

The current retrospective study was completed with the aim to identify demographic characteristics and clinical predictors (if any) of the patients discharged from our pain clinic due to breach in narcotic use contract (BNUC). Retrospective patient charts' review and data audit. University hospital-affiliated pain clinic in the United States. All patient charts in our pain clinic for a 2-year period (2011-2012). The patients with BNUC were delineated from the patients who had not been discharged from our pain clinic. Pain characteristics, pain management, and substance abuse status were compared in each patient with BNUC between the time of admission and the time of discharge. The patients with BNUC discharges showed significant variability for the discharging factors among the pain physicians within a single pain clinic model with this variability being dependent on their years of experience and their proactive interventional pain management. The patients with BNUC in our pain clinic setting were primarily middle-aged, obese, unmarried males with nondocumented stable occupational history who were receiving only noninterventional pain management. Substance abuse, doctor shopping, and potential diversion were the top three documented reasons for BNUC discharges. In 2011-2012, our pain clinic discharged 1-in-16 patients due to breach in narcotic use contract.

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. Discussion To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. Trial registration Eudra CT. Identifier: 2009-016643-18. PMID:23237631

Herb-Induced Liver Injuries in Developing Nations: An Update.

PubMed

Amadi, Cecilia Nwadiuto; Orisakwe, Orish Ebere

2018-04-17

The last few decades have seen a rise in the use of herbal supplements, natural products, and traditional medicines. However, there are growing concerns related to the safety and toxicities of these medicines. These herbal medicines are associated with complications such as liver damage with a high incidence of mortalities and morbidities. Clinical manifestations range from asymptomatic cases with abnormal liver functions tests to sudden and severe liver failure necessitating liver transplantation. This work aimed to review the etiology, risk factors, diagnosis, clinical manifestations and selected clinical case reports of herbal hepatotoxicity in developing nations. PubMed and Google Scholar searches were undertaken to identify relevant literature. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. Little data exists on clinical cases of herb-induced liver injury in some developing countries such as Nigeria, as most incidences are either not reported to health care providers or reports from hospitals go unpublished. Studies in Nigeria have highlighted a possible correlation between use of herbs and liver disease. In Uganda, and association between the use of traditional herbal medicine with liver fibrosis in HIV-infected and non-HIV patients was demonstrated. Reports from China have revealed incidences of acute liver failure as a result of herbal medicine use. The actual incidence and prevalence of HILI in developing nations remain largely unknown due to both poor pharmacovigilance programs and non-application of emerging technologies. Improving education and public awareness of the potential risks of herbals and herbal products is desirable to ensure that suspected adverse effects are formally reported. There is need for stricter regulations and pre-clinical studies necessary for efficacy and safety.

The detection of oral cancer using differential pathlength spectroscopy

NASA Astrophysics Data System (ADS)

Sterenborg, H. J. C. M.; Kanick, S.; de Visscher, S.; Witjes, M.; Amelink, A.

2010-02-01

The development of optical techniques for non-invasive diagnosis of cancer is an ongoing challenge to biomedical optics. For head and neck cancer we see two main fields of potential application 1) Screening for second primaries in patients with a history of oral cancer. This requires imaging techniques or an approach where a larger area can be scanned quickly. 2) Distinguishing potentially malignant visible primary lesions from benign ones. Here fiberoptic point measurements can be used as the location of the lesion is known. This presentation will focus on point measurement techniques. Various techniques for point measurements have been developed and investigated clinically for different applications. Differential Pathlength Spectroscopy is a recently developed fiberoptic point measurement technique that measures scattered light in a broad spectrum. Due to the specific fiberoptic geometry we measure only scattered photons that have travelled a predetermined pathlength. This allows us to analyse the spectrum mathematically and translate the measured curve into a set of parameters that are related to the microvasculature and to the intracellular morphology. DPS has been extensively evaluated on optical phantoms and tested clinically in various clinical applications. The first measurements in biopsy proven squamous cell carcinoma showed significant changes in both vascular and morphological parameters. Measurements on thick keratinized lesions however failed to generate any vascular signatures. This is related to the sampling depth of the standard optical fibers used. Recently we developed a fiberoptic probe with a ~1 mm sampling depth. Measurements on several leukoplakias showed that with this new probe we sample just below the keratin layer and can obtain vascular signatures. The results of a first set of clinical measurements will be presented and the significance for clinical diagnostics will be discussed.

Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases.

PubMed

Rello, J; Solé-Lleonart, C; Rouby, J-J; Chastre, J; Blot, S; Poulakou, G; Luyt, C-E; Riera, J; Palmer, L B; Pereira, J M; Felton, T; Dhanani, J; Bassetti, M; Welte, T; Roberts, J A

2017-09-01

With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Clinical score to rule out pneumonia due to Mycoplasma pneumoniae].

PubMed

Rodríguez de Ita, J; Torres-Quintanilla, A; Paláu-Dávila, L; Silva-Gburek, J C; Ortiz de Elguea-Lizarraga, J; Chávez Caraza, K L; Santos-Guzman, J

2014-10-01

The gold standard for the diagnosis of pneumonia secondary to Mycoplasma pneumoniae is the serial measurement of IgM, since an isolated test for IgM has a poor sensitivity of 31.8%. A pneumonia due to Mycoplasma pneumoniae could be of clinically different origins, thus it is possible to perform a clinical score for its early diagnosis. To develop a clinical score in order to rule out a pneumoniae secondary to Mycoplasma pneumoniae. A total of 302 patients from 0 to 18 years-old, with a diagnosis of pneumonia were evaluated and divided into two groups: Mycoplasma positive and Mycoplasma negative. Using different variables in the medical records a clinical score was calculated. Of the 302 cases studied, 34 were classified as Mycoplasma positive and 268 as Mycoplasma negative. The variables relevant to the calculation of the score were age, days with fever, and days with cough, thus providing the CAF (Cough, Age, Fever) score. Ranges were assigned for each variable and points were given for each range. A value greater than or equal to 5 meant a positive score. The CAF score was applied to the 302 cases, resulting in 164 cases of Mycoplasma positive and 138 cases of Mycoplasma negative. The CAF score had a sensitivity of 85% and specificity of 49%. The CAF score had better sensitivity than other clinical diagnostic tools. With a negative predictive value of 96% it is possible to rule out a pneumonia secondary to M. pneumoniae. The study requires a prospective study to verify the usefulness of our score. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Effective visualization of integrated knowledge and data to enable informed decisions in drug development and translational medicine

PubMed Central

2013-01-01

Integrative understanding of preclinical and clinical data is imperative to enable informed decisions and reduce the attrition rate during drug development. The volume and variety of data generated during drug development have increased tremendously. A new information model and visualization tool was developed to effectively utilize all available data and current knowledge. The Knowledge Plot integrates preclinical, clinical, efficacy and safety data by adding two concepts: knowledge from the different disciplines and protein binding. Internal and public available data were gathered and processed to allow flexible and interactive visualizations. The exposure was expressed as the unbound concentration of the compound and the treatment effect was normalized and scaled by including expert opinion on what a biologically meaningful treatment effect would be. The Knowledge Plot has been applied both retrospectively and prospectively in project teams in a number of different therapeutic areas, resulting in closer collaboration between multiple disciplines discussing both preclinical and clinical data. The Plot allows head to head comparisons of compounds and was used to support Candidate Drug selections and differentiation from comparators and competitors, back translation of clinical data, understanding the predictability of preclinical models and assays, reviewing drift in primary endpoints over the years, and evaluate or benchmark compounds in due diligence comparing multiple attributes. The Knowledge Plot concept allows flexible integration and visualization of relevant data for interpretation in order to enable scientific and informed decision-making in various stages of drug development. The concept can be used for communication, decision-making, knowledge management, and as a forward and back translational tool, that will result in an improved understanding of the competitive edge for a particular project or disease area portfolio. In addition, it also builds up a knowledge and translational continuum, which in turn will reduce the attrition rate and costs of clinical development by identifying poor candidates early. PMID:24098919

Access to Mobile Communication Technology and Willingness to Participate in Automated Telemedicine Calls Among Chronically Ill Patients in Honduras

PubMed Central

Mendoza-Avelares, Milton O.; Milton, Evan C.; Lange, Ilta; Fajardo, Roosevelt

2010-01-01

Abstract Objectives: Patients in underdeveloped countries may be left behind by advances in telehealthcare. We surveyed chronically ill patients with low incomes in Honduras to measure their use of mobile technologies and willingness to participate in mobile disease management support. Materials and Methods: 624 chronically ill primary care patients in Honduras were surveyed. We examined variation in telephone access across groups defined by patients' sociodemographic characteristics, diagnoses, and access to care. Logistic regression was used to identify independent correlates of patients' interest in automated telephonic support for disease management. Results: Participants had limited education (mean 4.8 years), and 65% were unemployed. Eighty-four percent had telephone access, and 78% had cell phones. Most respondents had voicemail (61%) and text messaging (58%). Mobile technologies were particularly common among patients who had to forego clinic visits and medications due to cost concerns (each p < 0.05). Most patients (>80%) reported that they would be willing to receive automated calls focused on appointment reminders, medication adherence, health status monitoring, and self-care education. Patients were more likely to be willing to participate in automated telemedicine services if they had to cancel a clinic appointment due to transportation problems or forego medication due to cost pressures. Conclusions: Even in this poor region of Honduras, most chronically ill patients have access to mobile technology, and most are willing to participate in automated telephone disease management support. Given barriers to in-person care, new models of mobile healthcare should be developed for chronically ill patients in developing countries. PMID:21062234

Digging a hole under Hedgehog: downstream inhibition as an emerging anticancer strategy.

PubMed

Di Magno, Laura; Coni, Sonia; Di Marcotullio, Lucia; Canettieri, Gianluca

2015-08-01

Hedgehog signaling is a key regulator of development and stem cell fate and its aberrant activation is a leading cause of a number of tumors. Activating germline or somatic mutations of genes encoding Hh pathway components are found in Basal Cell Carcinoma (BCC) and Medulloblastoma (MB). Ligand-dependent Hedgehog hyperactivation, due to autocrine or paracrine mechanisms, is also observed in a large number of malignancies of the breast, colon, skin, bladder, pancreas and other tissues. The key tumorigenic role of Hedgehog has prompted effort aimed at identifying inhibitors of this signaling. To date, only the antagonists of the membrane transducer Smo have been approved for therapy or are under clinical trials in patients with BCC and MB linked to Ptch or Smo mutations. Despite the good initial response, patients treated with Smo antagonists have eventually developed resistance due to the occurrence of compensating mechanisms. Furthermore, Smo antagonists are not effective in tumors where the Hedgehog hyperactivation is due to mutations of pathway components downstream of Smo, or in case of non-canonical, Smo-independent activation of the Gli transcription factors. For all these reasons, the research of Hh inhibitors acting downstream of Smo is becoming an area of intensive investigation. In this review we illustrate the progresses made in the identification of effective Hedgehog inhibitors and their application in cancer, with a special emphasis on the newly identified downstream inhibitors. We describe in detail the Gli inhibitors and illustrate their mode of action and applications in experimental and/or clinical settings. Copyright © 2015 Elsevier B.V. All rights reserved.

Progress on core outcome sets for critical care research.

PubMed

Blackwood, Bronagh; Marshall, John; Rose, Louise

2015-10-01

Appropriate selection and definition of outcome measures are essential for clinical trials to be maximally informative. Core outcome sets (an agreed, standardized collection of outcomes measured and reported in all trials for a specific clinical area) were developed due to established inconsistencies in trial outcome selection. This review discusses the rationale for, and methods of, core outcome set development, as well as current initiatives in critical care. Recent systematic reviews of reported outcomes and measurement instruments relevant to the critically ill highlight inconsistencies in outcome selection, definition, and measurement, thus establishing the need for core outcome sets. Current critical care initiatives include development of core outcome sets for trials aimed at reducing mechanical ventilation duration; rehabilitation following critical illness; long-term outcomes in acute respiratory failure; and epidemic and pandemic studies of severe acute respiratory infection. Development and utilization of core outcome sets for studies relevant to the critically ill is in its infancy compared to other specialties. Notwithstanding, core outcome set development frameworks and guidelines are available, several sets are in various stages of development, and there is strong support from international investigator-led collaborations including the International Forum for Acute Care Trialists.

MRI-guided prostate focal laser ablation therapy using a mechatronic needle guidance system

NASA Astrophysics Data System (ADS)

Cepek, Jeremy; Lindner, Uri; Ghai, Sangeet; Davidson, Sean R. H.; Trachtenberg, John; Fenster, Aaron

2014-03-01

Focal therapy of localized prostate cancer is receiving increased attention due to its potential for providing effective cancer control in select patients with minimal treatment-related side effects. Magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) therapy is an attractive modality for such an approach. In FLA therapy, accurate placement of laser fibers is critical to ensuring that the full target volume is ablated. In practice, error in needle placement is invariably present due to pre- to intra-procedure image registration error, needle deflection, prostate motion, and variability in interventionalist skill. In addition, some of these sources of error are difficult to control, since the available workspace and patient positions are restricted within a clinical MRI bore. In an attempt to take full advantage of the utility of intraprocedure MRI, while minimizing error in needle placement, we developed an MRI-compatible mechatronic system for guiding needles to the prostate for FLA therapy. The system has been used to place interstitial catheters for MRI-guided FLA therapy in eight subjects in an ongoing Phase I/II clinical trial. Data from these cases has provided quantification of the level of uncertainty in needle placement error. To relate needle placement error to clinical outcome, we developed a model for predicting the probability of achieving complete focal target ablation for a family of parameterized treatment plans. Results from this work have enabled the specification of evidence-based selection criteria for the maximum target size that can be confidently ablated using this technique, and quantify the benefit that may be gained with improvements in needle placement accuracy.

Cadaveric dissection as an educational tool for anatomical sciences in the 21st century.

PubMed

Ghosh, Sanjib Kumar

2017-06-01

Anatomical education has been undergoing reforms in line with the demands of medical profession. The aim of the present study is to assess the impact of a traditional method like cadaveric dissection in teaching/learning anatomy at present times when medical schools are inclining towards student-centered, integrated, clinical application models. The article undertakes a review of literature and analyzes the observations made therein reflecting on the relevance of cadaveric dissection in anatomical education of 21st century. Despite the advent of modern technology and evolved teaching methods, dissection continues to remain a cornerstone of anatomy curriculum. Medical professionals of all levels believe that dissection enables learning anatomy with relevant clinical correlates. Moreover dissection helps to build discipline independent skills which are essential requirements of modern health care setup. It has been supplemented by other teaching/learning methods due to limited availability of cadavers in some countries. However, in the developing world due to good access to cadavers, dissection based teaching is central to anatomy education till date. Its utility is also reflected in the perception of students who are of the opinion that dissection provides them with a foundation critical to development of clinical skills. Researchers have even suggested that time has come to reinstate dissection as the core method of teaching gross anatomy to ensure safe medical practice. Nevertheless, as dissection alone cannot provide uniform learning experience hence needs to be complemented with other innovative learning methods in the future education model of anatomy. Anat Sci Educ 10: 286-299. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability.

PubMed

Parikh, Ankit; Kathawala, Krishna; Song, Yunmei; Zhou, Xin-Fu; Garg, Sanjay

2018-05-29

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

Role of micronutrients for physical growth and mental development.

PubMed

Singh, Meharban

2004-01-01

Due to control of florid and severe cases of protein-energy malnutrition, deficiencies of micronutrients in children have assumed public health importance. According to National Nutrition Monitoring Bureau of India, over 50% of apparently healthy looking children have subclinical or biochemical deficiencies of vitamin A, vitamins B2, B6, folate and vitamin C. Over two-third of children have clinical evidences of iron deficiency while deficiency of trace minerals like iodine and zinc is quite common in certain populations. Children have food preferences and they are quite fussy to take green leafy vegetables and fruits thus compromising their intake of micronutrients from dietary sources. The full genetic potential of the child for physical growth and mental development may be compromised due to subclinical deficiencies of micronutrients which are commonly referred to as "hidden hunger". Micronutrients are required for the integrity and optimal functioning of immune system. Children with subclinical deficiency of micronutrients are more vulnerable to develop frequent and more severe common day-to-day infections thus triggering a vicious cycle of undernutrition and recurrent infections. A number of micronutrients are required for optimal physical growth and neuromotor development. Isolated deficiencies of micronutrients are rare in clinical practice and usually deficiencies of multiple micronutrients co-exist. The first 3 years of life are most crucial and vulnerable to the hazards of undernutrition. All efforts should be made so that preschool children are given a balanced and nutritious home-based diet. However, it has been shown that it is not possible to meet 100% requirements of recommended dietary allowances (RDA's) of micronutrients from dietary sources alone and most preschool children need administration of nutritional supplements to optimize their genetic potential for physical growth and mental development.

Operational Transition from the First-Generation Heidelberg Spectralis Optical Coherence Tomography [OCT("OCT1")] to the Second-Generation Heidelberg Spectralis OCT("OCT2")

NASA Technical Reports Server (NTRS)

Mason, S.; Brunstetter, T.; Young, M.; Van Baalen, M.; Tarver, W.; Derrick, R.; Wells, J.; Dey, B.; Todd, K.; Smith, B.;

Development and Implementation of Clinical Trial Protocol Templates at the National Institute of Allergy and Infectious Diseases

PubMed Central

Bridge, Heather; Smolskis, Mary; Bianchine, Peter; Dixon, Dennis O.; Kelly, Grace; Herpin, Betsey; Tavel, Jorge

2009-01-01

Background: A clinical research protocol document must reflect both sound scientific rationale as well as local, national and, when applicable, international regulatory and human subject protections requirements. These requirements originate from a variety of sources, undergo frequent revision and are subject to interpretation. Tools to assist clinical investigators in the production of clinical protocols could facilitate navigating these requirements and ultimately increase the efficiency of clinical research. Purpose: The National Institute of Allergy and Infectious Diseases (NIAID) developed templates for investigators to serve as the foundation for protocol development. These protocol templates are designed as tools to support investigators in developing clinical protocols. Methods: NIAID established a series of working groups to determine how to improve its capacity to conduct clinical research more efficiently and effectively. The Protocol Template Working Group was convened to determine what protocol templates currently existed within NIAID and whether standard NIAID protocol templates should be produced. After review and assessment of existing protocol documents and requirements, the group reached consensus about required and optional content, determined the format and identified methods for distribution as well as education of investigators in the use of these templates. Results: The templates were approved by the NIAID Executive Committee in 2006 and posted as part of the NIAID Clinical Research Toolkit[1]website for broad access. These documents require scheduled revisions to stay current with regulatory and policy changes. Limitations: The structure of any clinical protocol template, whether comprehensive or specific to a particular study phase, setting or design, affects how it is used by investigators. Each structure presents its own set of advantages and disadvantages. While useful, protocol templates are not stand-alone tools for creating an optimal protocol document but must be complemented by institutional resources and support. Education and guidance of investigators in the appropriate use of templates is necessary to ensure a complete yet concise protocol document. Due to changing regulatory requirements, clinical protocol templates cannot become static but require frequent revisions. Conclusions: Standard protocol templates that meet applicable regulations can be important tools to assist investigators in the effective conduct of clinical research, but they require dedicated resources and ongoing input from key stakeholders. PMID:19625326

Stock market returns and clinical trial results of investigational compounds: an event study analysis of large biopharmaceutical companies.

PubMed

Hwang, Thomas J

2013-01-01

For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: -2.3, 13.4%; P = 0.02) for positive events and -2.0% (95% CI: -9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: -3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were -1.7% (95% CI: -9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return underperformance due to negative events is greater in magnitude and persists longer than abnormal returns due to positive events, suggesting asymmetric market reactions.

PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing and Use in Patients.

PubMed

Abuchowski, A

2016-01-01

Oxygen transfer agents have long been sought as a means to treat hypoxia caused by congenital or acquired conditions. Hemoglobin-based oxygen carriers were in clinical development as blood substitutes, but development was halted due to the finding of significant vasoactivity. Rather than develop a blood substitute, a product for indications characterized by hypoxia is in development. PEGylated bovine carboxyhemoglobin (SANGUINATE™) is both a carbon monoxide releasing molecule and an oxygen transfer agent. It is comprised of three functional components that act to inhibit vasoconstriction, reduce inflammation and optimize the delivery of oxygen. SANGUINATE has the potential to reduce or prevent the effects of ischemia by inhibiting vasoconstriction and re-oxygenating tissue. Phase 1 safety trials in healthy volunteers were completed in 2013. SANGUINATE was shown to be safe and well tolerated with no serious adverse effects. Phase Ib studies have been completed in stable patients with Sickle Cell Disease. SANGUINATE has also been administered to two patients under emergency use protocols. Both patients exhibited improved status following treatment with SANGUINATE.

i3b3: Infobuttons for i2b2 as a Mechanism for Investigating the Information Needs of Clinical Researchers.

PubMed

Kennell, Timothy; Dempsey, Donald M; Cimino, James J

2016-01-01

The information needs of clinicians, as they interact with the EHR, are well-studied. Clinical researchers also interact with the EHR and, while they might be expected to have some similar needs, the unique needs that arise due to nature of their work remain largely unstudied. For clinicians, infobuttons (context-aware hyperlinks) provide a mechanism of studying these information needs. Here we describe the integration of infobuttons into i2b2, a popular data warehouse commonly used by clinical researchers, using a plugin. A preliminary survey of i2b2 developers suggests a general interest in infobuttons for i2b2 and indicates good likelihood for their deployment, where they may be used as a tool for further studying these needs in greater detail.

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

PubMed

Huang, Wei-Lun; Chen, Yi-Lin; Yang, Szu-Chun; Ho, Chung-Liang; Wei, Fang; Wong, David T; Su, Wu-Chou; Lin, Chien-Chung

2017-03-14

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy.

Encephalopathy and Neuropathy due to Glue, Paint Thinner, and Gasoline Sniffing in Trinidad and Tobago-MRI Findings.

PubMed

Ramcharan, Kanterpersad; Ramesar, Amrit; Ramdath, Moshanti; Teelucksingh, Joel; Gosein, Maria

2014-01-01

A 29-year-old male petrol station pump attendant was admitted with ataxia and clinical evidence of a sensorimotor polyneuropathy which developed over the preceding 3 months. He had cognitive dysfunction, hearing loss, and cerebellar clinical abnormalities that came on slowly over the three years. He had a fifteen-year history of sniffing mostly glue, occasionally paint thinners, and, in the recent two years, gasoline. Magnetic resonance brain imaging showed abnormalities of the cerebral cortex, cerebral white matter, corpus callosum, hippocampus, brainstem and cerebellar atrophy, hypointensities of basal ganglia, red nuclei, and substantia nigra as previously described in toluene sniffing. Abstinence for six months led to partial clinical improvement. Clinicians need to be aware of this preventable entity which has peculiar radiological findings which are being increasingly accepted as typical.

[Clinical drug trials in Germany--an assessment of current status from the viewpoint of industry].

PubMed

Baumbauer, E

1996-01-01

Drug development today is a highly professional and costly affair, whereby quality and speed are decisive competitive factors in a global setting. Germany is in the process of losing its attractiveness for clinical drug research as evidenced by a significant decrease in funding of clinical drug research which at the moment amounts to about 1.5 billion DM/year. This decrease is due to an adverse environment created by a certain anxiety in public opinion regarding technological advances, an overburden of regulations, lack of an infrastructure in hospitals to work according to GCP and a regulatory agency which has to compete with momentarily more effective agencies in Europe (UK, France). A joint effort between industry and the medical profession is called for to change this situation for the better.

Encephalopathy and Neuropathy due to Glue, Paint Thinner, and Gasoline Sniffing in Trinidad and Tobago-MRI Findings

PubMed Central

Ramcharan, Kanterpersad; Ramesar, Amrit; Ramdath, Moshanti; Teelucksingh, Joel; Gosein, Maria

2014-01-01

A 29-year-old male petrol station pump attendant was admitted with ataxia and clinical evidence of a sensorimotor polyneuropathy which developed over the preceding 3 months. He had cognitive dysfunction, hearing loss, and cerebellar clinical abnormalities that came on slowly over the three years. He had a fifteen-year history of sniffing mostly glue, occasionally paint thinners, and, in the recent two years, gasoline. Magnetic resonance brain imaging showed abnormalities of the cerebral cortex, cerebral white matter, corpus callosum, hippocampus, brainstem and cerebellar atrophy, hypointensities of basal ganglia, red nuclei, and substantia nigra as previously described in toluene sniffing. Abstinence for six months led to partial clinical improvement. Clinicians need to be aware of this preventable entity which has peculiar radiological findings which are being increasingly accepted as typical. PMID:25045557

[Significance of PSMA imaging in prostate cancer].

PubMed

Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

PubMed

Bujalska-Zadrożny, Magdalena; Tatarkiewicz, Jan; Kulik, Kamila; Filip, Małgorzata; Naruszewicz, Marek

2017-03-01

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg 2+ ), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience.

PubMed

Abdelaziz, Ashraf Omar; Elbaz, Tamer Mahmoud; Shousha, Hend Ibrahim; Ibrahim, Mostafa Mohamed; Rahman El-Shazli, Mostafa Abdel; Abdelmaksoud, Ahmed Hosni; Aziz, Omar Abdel; Zaki, Hisham Atef; Elattar, Inas Anwar; Nabeel, Mohamed Mahmoud

2014-01-01

Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was 56.5 ± 7.7 years. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

Biosimilar safety considerations in clinical practice.

PubMed

Choy, Edwin; Jacobs, Ira Allen

2014-02-01

Biologics are important treatments for a number of cancers. Patents for several biologics will expire over the next decade, removing a barrier to the development and commercialization of biosimilars. As biologics differ from small-molecule drugs due to their size and complexity, multifaceted manufacturing process, and their potential for immunogenicity, biosimilars cannot be considered "generic versions" of currently approved biologics. In highly regulated markets, biosimilars can be authorized only if they are demonstrated to be highly similar to the original drug from an analytical and clinical perspective. Any differences must be justified and shown to have no clinically meaningful effect on the safety and efficacy of the biosimilar. The European Medicines Agency has approved a number of biosimilars and the recent approval of the biosimilar infliximab monoclonal antibody is another regulatory milestone. This article will provide context regarding key safety issues addressed in biosimilar development, approval, and delivery, as well as inform oncologists on matters of safety to consider when prescribing biosimilars. Pertinent issues about safety from countries or regions where biosimilars are currently in use also will be reviewed. © 2014 Elsevier Inc. All rights reserved.

Branchial cleft anomalies: a pictorial review of embryological development and spectrum of imaging findings.

PubMed

Adams, Ashok; Mankad, Kshitij; Offiah, Curtis; Childs, Lucy

2016-02-01

The branchial arches are the embryological precursors of the face, neck and pharynx. Anomalies of the branchial arches are the second most common congenital lesions of the head and neck in children, with second branchial arch anomalies by far the most common. Clinically, these congenital anomalies may present as cysts, sinus tracts, fistulae or cartilaginous remnants with typical clinical and radiological findings. We review the normal embryological development of the branchial arches and the anatomical structures of the head and neck that derive from each arch. The typical clinical and radiological appearances of both common and uncommon branchial arch abnormalities are discussed with an emphasis on branchial cleft anomalies. • Anomalies of the branchial arches usually present as cysts, sinuses or fistulae. • Second branchial arch anomalies account for approximately 95 % of cases. • There are no pathognomonic imaging features so diagnosis depends on a high index of suspicion and knowledge of typical locations. • Persistent cysts, fistulae or recurrent localised infection may be due to branchial arch anomalies. • Surgical excision of the cyst or tract is the most common curative option.

FGFR-targeted therapeutics for the treatment of breast cancer.

PubMed

De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

2017-03-01

Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

A Collaborative Step-Wise Process to Implementing an Innovative Clinic for Adult Survivors of Childhood Cancer.

PubMed

McClellan, Wendy; Fulbright, Joy M; Doolittle, Gary C; Alsman, Kyla; Klemp, Jennifer R; Ryan, Robin; Nelson, Eve-Lynn; Stegenga, Kristin; Krebill, Hope; Al-hihi, Eyad M; Schuetz, Nik; Heiman, Ashley; Lowry, Becky

2015-01-01

With a 5 year survival rate of approximately 80%, there is an increasing number of childhood cancer survivors in the United States. Childhood cancer survivors are at an increased risk for physical and psychosocial health problems many years after treatment. Long-term follow-up care should include education, development of individualized follow up plans and screening for health problems in accordance with the Children's Oncology Group survivor guidelines. Due to survivor, provider and healthcare system related barriers, adult survivors of childhood cancer (ASCC) infrequently are receiving care in accordance to these guidelines. In this paper we describe the stepwise process and collaboration between a children's hospital and an adult academic medical center that was implemented to develop the Survivorship Transition Clinic and address the needs of ASCC in our region. In the clinic model that we designed ASCC follow-up with a primary care physician in the adult setting who is knowledgeable about late effects of childhood cancer treatment and are provided transition support and education by a transition nurse navigator. Copyright © 2015 Elsevier Inc. All rights reserved.

Ulcerative colitis followed by the development of typical intestinal Behçet disease: A case report.

PubMed

Zhu, Zhenhua; Shu, Xu; Long, Shunhua; Jiang, Xiaozhen; Lu, Nonghua; Zhu, Xuan; Liao, Wangdi

2018-02-01

Intestinal Behçet disease (intestinal BD) and inflammatory bowel disease (IBD) share a lot of characteristics, including genetic background, clinical manifestations, and therapeutic strategies, especially the extraintestinal manifestations, such as oral ulcers, arthralgia, eye lesions, skin lesions, etc, but the coexistence of these 2 diseases are uncommon. Behçet disease with gastrointestinal involvement in ulcerative colitis (UC) patient has been reported in just 1 previous case report, but, which can not be diagnosed as definite intestinal BD based on Korean novel diagnositic criteria due to lacking the typical ileocecal ulcer. We present a 23-year-old woman with ulcerative disease who developed typical intestinal BD, which is the first case report of patient with coexisting UC and typical intestinal BD. This patient was diagnosed as coexistence of intestinal BD and UC base on the clinical manifestations, extra intestinal manifestations and typical colonoscopic findings. Steroid and methotrexate were administered. This patient achieved clinical remission and mucosal healing. Coexistence of intestinal BD and UC is uncommon, and the combination with steroid, methotrexate, and 5-aminosalicylic acids is an effective therapy.

Motion tracking to enable pre-surgical margin mapping in basal cell carcinoma using optical imaging modalities: initial feasibility study using optical coherence tomography

NASA Astrophysics Data System (ADS)

Duffy, M.; Richardson, T. J.; Craythorne, E.; Mallipeddi, R.; Coleman, A. J.

2014-02-01

A system has been developed to assess the feasibility of using motion tracking to enable pre-surgical margin mapping of basal cell carcinoma (BCC) in the clinic using optical coherence tomography (OCT). This system consists of a commercial OCT imaging system (the VivoSight 1500, MDL Ltd., Orpington, UK), which has been adapted to incorporate a webcam and a single-sensor electromagnetic positional tracking module (the Flock of Birds, Ascension Technology Corp, Vermont, USA). A supporting software interface has also been developed which allows positional data to be captured and projected onto a 2D dermoscopic image in real-time. Initial results using a stationary test phantom are encouraging, with maximum errors in the projected map in the order of 1-2mm. Initial clinical results were poor due to motion artefact, despite attempts to stabilise the patient. However, the authors present several suggested modifications that are expected to reduce the effects of motion artefact and improve the overall accuracy and clinical usability of the system.

The Dorello canal: historical development, controversies in microsurgical anatomy, and clinical implications.

PubMed

Kshettry, Varun R; Lee, Joung H; Ammirati, Mario

2013-03-01

Interest in studying the anatomy of the abducent nerve arose from early clinical experience with abducent palsy seen in middle ear infection. Primo Dorello, an Italian anatomist working in Rome in the early 1900s, studied the anatomy of the petroclival region to formulate his own explanation of this pathological entity. His work led to his being credited with the discovery of the canal that bears his name, although this structure had been described 50 years previously by Wenzel Leopold Gruber. Renewed interest in the anatomy of this region arose due to advances in surgical approaches to tumors of the petroclival region and the need to explain the abducent palsies seen in trauma, intracranial hypotension, and aneurysms. The advent of the surgical microscope has allowed more detailed anatomical studies, and numerous articles have been published in the last 2 decades. The current article highlights the historical development of the study of the Dorello canal. A review of the anatomical studies of this structure is provided, followed by a brief overview of clinical considerations.

[An Autopsy Case of Globular Glial Tauopathy Presenting with Amyotrophic Lateral Sclerosis with Dementia].

PubMed

Sasaki, Ryogen; Mimuro, Maya; Kokubo, Yasumasa; Imai, Hiroshi; Yoshida, Mari; Tomimoto, Hidekazu

2016-08-01

We report an autopsy case of globular glial tauopathy (GGT) presenting clinically with amyotrophic lateral sclerosis (ALS) with dementia. A 79-year-old female developed weakness in the right upper limb, which progressed gradually. She developed apathy and speech disorder at 80 years of age. On neurological examination, she showed signs of upper and lower motor neuron disorder and dementia, but no extrapyramidal signs. The clinical diagnosis was ALS with dementia. The autopsy revealed left predominant marked atrophy of the frontal lobe due to severe neuronal loss and Gliosis. Immunohistochemistry using anti-4-repeat tau antibody revealed numerous globular glial inclusions. Severe neurodegeneration in the primary motor cortex and corticospinal tract was observed. There were distinctive tau-positive inclusions in both Betz and anterior horn cells. TDP-43-positive inclusions in motor neurons were not detected. Sequence analysis of the tau gene revealed no mutations in exons 1-5, 7, 9-13, or the adjacent intronic sequences. GGT can cause a clinical phenotype of ALS with dementia. (Received December 28, 2015; Accepted February 23, 2016; Published August 1, 2016).

Ultrasound Elastography: Review of Techniques and Clinical Applications

PubMed Central

Sigrist, Rosa M.S.; Liau, Joy; Kaffas, Ahmed El; Chammas, Maria Cristina; Willmann, Juergen K.

2017-01-01

Elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. These techniques take advantage of changed soft tissue elasticity in various pathologies to yield qualitative and quantitative information that can be used for diagnostic purposes. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave). Ultrasound-based methods are of particular interest due to its many inherent advantages, such as wide availability including at the bedside and relatively low cost. Several ultrasound elastography techniques using different excitation methods have been developed. In general, these can be classified into strain imaging methods that use internal or external compression stimuli, and shear wave imaging that use ultrasound-generated traveling shear wave stimuli. While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging. Here, we review the basic principles, foundation physics, and limitations of ultrasound elastography and summarize its current clinical use and ongoing developments in various clinical applications. PMID:28435467

Identifying and characterising cerebral visual impairment in children: a review.

PubMed

Philip, Swetha Sara; Dutton, Gordon N

2014-05-01

Cerebral visual impairment (CVI) comprises visual malfunction due to retro-chiasmal visual and visual association pathway pathology. This can be isolated or accompany anterior visual pathway dysfunction. It is a major cause of low vision in children in the developed and developing world due to increasing survival in paediatric and neonatal care. CVI can present in many combinations and degrees. There are multiple causes and it is common in children with cerebral palsy. CVI can be identified easily, if a structured approach to history-taking is employed. This review describes the features of CVI and describes practical management strategies aimed at helping affected children. A literature review was undertaken using 'Medline' and 'Pubmed'. Search terms included cerebral visual impairment, cortical visual impairment, dorsal stream dysfunction and visual function in cerebral palsy. © 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.

Biodegradable Magnesium Alloys Developed as Bone Repair Materials: A Review

PubMed Central

Liu, Chen; Ren, Zheng; Xu, Yongdong; Pang, Song; Zhao, Xinbing

2018-01-01

Bone repair materials are rapidly becoming a hot topic in the field of biomedical materials due to being an important means of repairing human bony deficiencies and replacing hard tissue. Magnesium (Mg) alloys are potentially biocompatible, osteoconductive, and biodegradable metallic materials that can be used in bone repair due to their in situ degradation in the body, mechanical properties similar to those of bones, and ability to positively stimulate the formation of new bones. However, rapid degradation of these materials in physiological environments may lead to gas cavities, hemolysis, and osteolysis and thus, hinder their clinical orthopedic applications. This paper reviews recent work on the use of Mg alloy implants in bone repair. Research to date on alloy design, surface modification, and biological performance of Mg alloys is comprehensively summarized. Future challenges for and developments in biomedical Mg alloys for use in bone repair are also discussed. PMID:29725492

Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens.

PubMed

Cornaglia, G; Rossolini, G M

2009-03-01

Multidrug resistance in Gram-positive pathogens emerged as a major therapeutic challenge over two decades ago. The worldwide spread of methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci and other resistant Gram-positive pathogens had a major impact on antibiotic policies, and prompted the discovery and development of new antibiotics to combat difficult-to-treat infections caused by such pathogens. Several new antibiotics active against multidrug-resistant Gram-positive pathogens have recently been introduced into clinical practice, and the antibiotic pipeline contains additional anti-Gram-positive drugs at an advanced stage of development, including new glycopeptides (dalbavancin, oritavancin, and telavancin), new anti-MRSA beta-lactams (ceftobiprole), and new diaminopyrimidines (iclaprim). This article provides a brief overview of these upcoming agents, partially based on the material presented at the ESCMID Conference entitled 'Fighting infections due to multidrug-resistant Gram-positives' (Venice, Italy, 29-31 May 2008) and on the most recent literature.

[How to prevent hazards and to reduce risk in clinical trials?].

PubMed

Czarkowski, Marek

2008-12-01

Different stakeholders involved in clinical trials are exposed to hazards related with this biomedical research. Beside clinical trials participants other important stakeholders are: investigators, sponsors, centers and clinical research organizations. Hazard prevention needs effective methods of hazard disclosure and analysis. A reduction of risks related with clinical trials is possible due to education, training, inspections, research discipline and penalties. Effective ways of hazard elimination or hazard reduction should be developed as well. Education and training should be offered to all stakeholders but their forms and contents should be adapted to different types of stakeholders. Direct control of the clinical trials should be held by stakeholders conducting clinical trials and outside inspections should be done by other institutions like clinical research organizations, research ethics committees and The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. Serious oversight is an absence of any independent inspection during a phase of publication of clinical trial results. We should not accept any exception from the golden rule that results of all clinical trials must be published. Indemnity for damages is a popular way of compensation for clinical trials participants. Investigators, sponsors and centers should have valid liability insurance. Drastic measures for reduction of risks in clinical trials are different kinds of penalties. They should prevent participation of unreliable stakeholders and promote those who respect regulations and high ethical standards.

Program evaluation of a model to integrate internationally educated health professionals into clinical practice

PubMed Central

2013-01-01

Background The demand for health professionals continues to increase, partially due to the aging population and the high proportion of practitioners nearing retirement. The University of British Columbia (UBC) has developed a program to address this demand, by providing support for internationally trained Physiotherapists in their preparation for taking the National Physiotherapy competency examinations. The aim was to create a program comprised of the educational tools and infrastructure to support internationally educated physiotherapists (IEPs) in their preparation for entry to practice in Canada and, to improve their pass rate on the national competency examination. Methods The program was developed using a logic model and evaluated using program evaluation methodology. Program tools and resources included educational modules and curricular packages which were developed and refined based on feedback from clinical experts, IEPs and clinical physical therapy mentors. An examination bank was created and used to include test-enhanced education. Clinical mentors were recruited and trained to provide clinical and cultural support for participants. Results The IEP program has recruited 124 IEPs, with 69 now integrated into the Canadian physiotherapy workforce, and more IEPs continuing to apply to the program. International graduates who participated in the program had an improved pass rate on the national Physiotherapy Competency Examination (PCE); participation in the program resulted in them having a 28% (95% CI, 2% to 59%) greater possibility of passing the written section than their counterparts who did not take the program. In 2010, 81% of all IEP candidates who completed the UBC program passed the written component, and 82% passed the clinical component. Conclusion The program has proven to be successful and sustainable. This program model could be replicated to support the successful integration of other international health professionals into the workforce. PMID:24119470

The making of indigenous vascular prosthesis

PubMed Central

Unnikrishnan, Madathipat; Viswanathan, Sidharth; Balasubramaniam, K.; Muraleedharan, C.V.; Lal, Arthur Vijayan; Mohanan, P.V.; Mohanty, Meera; Kapilamoorthy, Tirur Raman

2016-01-01

Background & objectives: Vascular illnesses are on the rise in India, due to increase in lifestyle diseases and demographic transition, requiring intervention to save life, organ or limbs using vascular prosthesis. The aim of this study was to develop indigenous large diameter vascular graft for treatment of patients with vascular pathologies. Methods: The South India Textile Research Association, at Coimbatore, Tamil Nadu, India, developed seamless woven polyester (Polyethylene terephthalate) graft at its research wing. Further characterization and testing followed by clinical trials were conducted at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fifteen in vivo experiments were carried out in 1992-1994 in pigs as animal model. Controlled (phase I) clinical trial in ten patients was performed along with control graft. Thereafter, phase II trial involved 22 patients who underwent multi-centre clinical trial in four centres across India. Results: Laboratory testing showed that polyester graft was non-toxic, non-leeching and non-haemolytic with preserved long-term quality, further confirming in pigs by implanting in thoracic aorta, comparable to control Dacron grafts. Perigraft incorporation and smooth neointima formation which are prime features of excellent healing characteristics, were noted at explantation at planned intervals. Subsequently in the phase I and II clinical trials, all patients had excellent recovery without mortality or device-related adverse events. Patients receiving the test graft were followed up for 10 and 5 years, respectively. Serial clinical, duplex scans and CT angiograms performed periodically confirmed excellent graft performance. Interpretation & conclusions: Indigenously developed Chitra vascular graft was comparable to commercially available Dacron graft, ready for clinical use at affordable cost to patients as against costly imported grafts. PMID:27748302

Clinical Trial Data as Public Goods: Fair Trade and the Virtual Knowledge Bank as a Solution to the Free Rider Problem - A Framework for the Promotion of Innovation by Facilitation of Clinical Trial Data Sharing among Biopharmaceutical Companies in the Era of Omics and Big Data.

PubMed

Evangelatos, Nikolaos; Reumann, Matthias; Lehrach, Hans; Brand, Angela

2016-01-01

Knowledge in the era of Omics and Big Data has been increasingly conceptualized as a public good. Sharing of de-identified patient data has been advocated as a means to increase confidence and public trust in the results of clinical trials. On the other hand, research has shown that the current research and development model of the biopharmaceutical industry has reached its innovation capacity. In response to that, the biopharmaceutical industry has adopted open innovation practices, with sharing of clinical trial data being among the most interesting ones. However, due to the free rider problem, clinical trial data sharing among biopharmaceutical companies could undermine their innovativeness. Based on the theory of public goods, we have developed a commons arrangement and devised a model, which enables secure and fair clinical trial data sharing over a Virtual Knowledge Bank based on a web platform. Our model uses data as a virtual currency and treats knowledge as a club good. Fair sharing of clinical trial data over the Virtual Knowledge Bank has positive effects on the innovation capacity of the biopharmaceutical industry without compromising the intellectual rights, proprietary interests and competitiveness of the latter. The Virtual Knowledge Bank is a sustainable and self-expanding model for secure and fair clinical trial data sharing that allows for sharing of clinical trial data, while at the same time it increases the innovation capacity of the biopharmaceutical industry. © 2016 S. Karger AG, Basel.

A novel clinical decision support algorithm for constructing complete medication histories.

PubMed

Long, Ju; Yuan, Michael Juntao

2017-07-01

A patient's complete medication history is a crucial element for physicians to develop a full understanding of the patient's medical conditions and treatment options. However, due to the fragmented nature of medical data, this process can be very time-consuming and often impossible for physicians to construct a complete medication history for complex patients. In this paper, we describe an accurate, computationally efficient and scalable algorithm to construct a medication history timeline. The algorithm is developed and validated based on 1 million random prescription records from a large national prescription data aggregator. Our evaluation shows that the algorithm can be scaled horizontally on-demand, making it suitable for future delivery in a cloud-computing environment. We also propose that this cloud-based medication history computation algorithm could be integrated into Electronic Medical Records, enabling informed clinical decision-making at the point of care. Copyright © 2017 Elsevier B.V. All rights reserved.

The Length of Child Anxiety Treatment in a Regional Health System.

PubMed

Whiteside, Stephen P H; Ale, Chelsea M; Young, Brennan; Olsen, Mark W; Biggs, Bridget K; Gregg, Melissa S; Geske, Jennifer R; Homan, Kendra

2016-12-01

Anxiety disorders are often undertreated due to unsuccessful dissemination of evidence-based treatments (EBTs). Lack of empirical data regarding the typical length of treatment in clinical settings may hamper the development of clinically relevant protocols. The current study examined billing records for 335 children ages 7-17 years to quantify the treatment received for newly diagnosed anxiety disorders within a regional health system. The vast majority of patients did not receive a sufficient number of appointments to complete the typical cognitive behavioral therapy protocol or reach the sessions introducing exposure. Although half of the sample received pharmacotherapy, the vast majority received fewer follow-up appointments than participants in pharmacotherapy research studies. Further, the type of treatment (i.e., number of sessions and medication) differed depending on utilization of specialty care. These results underscore the need to develop brief and flexible EBT protocols that can be standardized and implemented in community practice.

Tendinopathy: injury, repair, and current exploration

PubMed Central

Lipman, Kelsey; Wang, Chenchao; Ting, Kang; Soo, Chia; Zheng, Zhong

2018-01-01

Both acute and chronic tendinopathy result in high morbidity, requiring management that is often lengthy and expensive. However, limited and conflicting scientific evidence surrounding current management options has presented a challenge when trying to identify the best treatment for tendinopathy. As a result of shortcomings of current treatments, response to available therapies is often poor, resulting in frustration in both patients and physicians. Due to a lack of understanding of basic tendon-cell biology, further scientific investigation is needed in the field for the development of biological solutions. Optimization of new delivery systems and therapies that spatially and temporally mimic normal tendon physiology hold promise for clinical application. This review focuses on the clinical importance of tendinopathy, the structure of healthy tendons, tendon injury, and healing, and a discussion of current approaches for treatment that highlight the need for the development of new nonsurgical interventions. PMID:29593382

Development of a twice daily dosing regimen of amoxicillin/clavulanate.

PubMed

Bax, Richard

2007-12-01

Amoxicillin/clavulanate was first launched as a three times daily dosage for the treatment of a range of community-acquired infections. A decade later, it became necessary to introduce a twice daily dosage for reasons of convenience, compliance and to remain competitive with other recently launched antibacterials. Twice daily formulations of amoxicillin/clavulanate were developed in which the amount of amoxicillin was increased relative to clavulanate to provide equivalent bacteriological and clinical efficacy with no change in the safety profile. Equivalence of the two dosing regimens was confirmed by randomised clinical trials in adults (in skin and soft tissue, urinary tract and lower respiratory tract infections, sinusitis and recurrent tonsillitis) and paediatrics (in lower respiratory tract infections, otitis media and recurrent tonsillitis). An improvement in the safety profile, specifically gastrointestinal effects, due to the reduced daily dose of clavulanate, was noted for all patients, but particularly in children.

Novel Development of Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome due to Insulin Therapy.

PubMed

Mainali, Naba Raj; Schmidt, Torrey R; Alweis, Richard; George, David L

2014-01-01

Male, 67 FINAL DIAGNOSIS: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome Symptoms: Bilateral wrist swelling Medication: - Clinical Procedure: - Specialty: Rheumatology. Unusual or unexpected effect of treatment. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare clinical entity characterized by the sudden onset of inflammatory arthritis and marked pitting edema on upper and lower extremities. RS3PE is considered a rheumatic process distinct from rheumatoid arthritis, which may occasionally represent a paraneoplastic syndrome. Herein, we describe a rare case of RS3PE associated with insulin therapy in a patient with no evidence of underlying malignancy. To the best of our knowledge, this is the first case report of RS3PE associated with insulin therapy. Physicians should look at the introduction of drugs as possible triggers for the development of RS3PE.

A Knowledge-Based System for the Computer Assisted Diagnosis of Endoscopic Images

NASA Astrophysics Data System (ADS)

Kage, Andreas; Münzenmayer, Christian; Wittenberg, Thomas

Due to the actual demographic development the use of Computer-Assisted Diagnosis (CAD) systems becomes a more important part of clinical workflows and clinical decision making. Because changes on the mucosa of the esophagus can indicate the first stage of cancerous developments, there is a large interest to detect and correctly diagnose any such lesion. We present a knowledge-based system which is able to support a physician with the interpretation and diagnosis of endoscopic images of the esophagus. Our system is designed to support the physician directly during the examination of the patient, thus prodving diagnostic assistence at the point of care (POC). Based on an interactively marked region in an endoscopic image of interest, the system provides a diagnostic suggestion, based on an annotated reference image database. Furthermore, using relevant feedback mechanisms, the results can be enhanced interactively.

Developing anti-inflammatory therapeutics for patients with osteoarthritis.

PubMed

Philp, Ashleigh M; Davis, Edward T; Jones, Simon W

2017-06-01

OA is the most common joint disorder in the world, but there are no approved therapeutics to prevent disease progression. Historically, OA has been considered a wear-and-tear joint disease, and efforts to identify and develop disease-modifying therapeutics have predominantly focused on direct inhibition of cartilage degeneration. However, there is now increasing evidence that inflammation is a key mediator of OA joint pathology, and also that the link between obesity and OA is not solely due to excessive load-bearing, suggesting therefore that targeting inflammation in OA could be a rewarding therapeutic strategy. In this review we therefore re-evaluate historical clinical trial data on anti-inflammatory therapeutics in OA patients, highlight some of the more promising emerging therapeutic targets and discuss the implications for future clinical trial design. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thyrotoxic crisis presenting with jaundice.

PubMed

Wickramasinghe, R D S S; Luke, W A N V; Sebastiampillai, B S; Gunathilake, M P M L; Premaratna, R

2016-06-23

Thyrotoxic crisis is a medical emergency requiring early diagnosis and urgent management, which can be challenging due to its diverse clinical presentations. While common presentations include fever, sweating, palpitations, tremors and confusion, presence of jaundice is rare. We report a 35-year-old male who presented with jaundice due to cholestasis along with other features of thyrotoxic crisis due to Graves' disease. He had a good clinical recovery with resolution of cholestasis following treatment for thyrotoxic crisis. Jaundice can be a rare manifestation of thyrotoxic crisis, and should be considered in the differential diagnosis when other clinical features of thyrotoxic crisis are present. However secondary causes of jaundice should be looked into and excluded.

Detection of foreign body using fast thermoacoustic tomography with a multielement linear transducer array

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

Nie Liming; Xing Da; Yang Diwu

2007-04-23

Current imaging modalities face challenges in clinical applications due to limitations in resolution or contrast. Microwave-induced thermoacoustic imaging may provide a complementary modality for medical imaging, particularly for detecting foreign objects due to their different absorption of electromagnetic radiation at specific frequencies. A thermoacoustic tomography system with a multielement linear transducer array was developed and used to detect foreign objects in tissue. Radiography and thermoacoustic images of objects with different electromagnetic properties, including glass, sand, and iron, were compared. The authors' results demonstrate that thermoacoustic imaging has the potential to become a fast method for surgical localization of occult foreignmore » objects.« less

Functional peptides for cartilage repair and regeneration

PubMed Central

Liu, Qisong; Jia, Zhaofeng; Duan, Li; Xiong, Jianyi; Wang, Daping; Ding, Yue

2018-01-01

Cartilage repair after degeneration or trauma continues to be a challenge both in the clinic and for scientific research due to the limited regenerative capacity of this tissue. Cartilage tissue engineering, involving a combination of cells, scaffolds, and growth factors, is increasingly used in cartilage regeneration. Due to their ease of synthesis, robustness, tunable size, availability of functional groups, and activity, peptides have emerged as the molecules with the most potential in drug development. A number of peptides have been engineered to regenerate cartilage by acting as scaffolds, functional molecules, or both. In this paper, we will summarize the application of peptides in cartilage tissue engineering and discuss additional possibilities for peptides in this field. PMID:29511444

Genetic and clinic predictors of new onset diabetes mellitus after transplantation.

PubMed

Saigi-Morgui, Núria; Quteineh, Lina; Bochud, Pierre-Yves; Crettol, Severine; Kutalik, Zoltán; Mueller, Nicolas J; Binet, Isabelle; Van Delden, Christian; Steiger, Jürg; Mohacsi, Paul; Dufour, Jean-Francois; Soccal, Paola M; Pascual, Manuel; Eap, Chin B

2017-12-27

New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main (n = 725) and replication (n = 156) samples the clinical risk score was significantly associated with NODAT (OR main : 1.60 [1.36-1.90], p = 3.72*10 -8 and OR replication : 2.14 [1.39-3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (OR w-GRS 2 :1.09 [1.04-1.15], p = 0.001 and OR w-GRS 3 :1.14 [1.01-1.29], p = 0.03) and a similar OR w-GRS 2 was found in the replication sample, although it did not reach significance probably due to a power issue. Despite the low OR of w-GRS on NODAT compared to clinical covariates, when integrating w-GRS 2 and w-GRS 3 in the clinical model, the Area under the Receiver Operating Characteristics curve (AUROC), specificity, sensitivity and accuracy were 0.69, 0.71, 0.58 and 0.68, respectively, with significant Likelihood Ratio test discrimination index (p-value 0.0004), performing better in NODAT discrimination than the clinical model alone. Twenty-five patients needed to be genotyped in order to detect one misclassified case that would have developed NODAT 1 year after transplantation if using only clinical covariates. To our knowledge, this is the first study extensively examining genetic risk scores contributing to NODAT development.

TNF-alpha antagonist induced lupus on three different agents.

PubMed

Mudduluru, Bindu Madhavi; Shah, Shalin; Shamah, Steven; Swaminath, Arun

2017-03-01

Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis. We present a case of a 28-year-old female with Crohn's disease, who developed disabling arthritis as a clinical manifestation of ATIL following treatment with three anti-TNF agents, namely infliximab, adalimumab and certolizumab.

Mobile Clinical Decision Support Systems in Our Hands - Great Potential but also a Concern.

PubMed

Masic, Izet; Begic, Edin

2016-01-01

Due to the powerful computer resources as well as the availability of today's mobile devices, a special field of mobile systems for clinical decision support in medicine has been developed. The benefits of these applications (systems) are: availability of necessary hardware (mobile phones, tablets and phablets are widespread, and can be purchased at a relatively affordable price), availability of mobile applications (free or for a "small" amount of money) and also mobile applications are tailored for easy use and save time of clinicians in their daily work. In these systems lies a huge potential, and certainly a great economic benefit, so this issue must be approached multidisciplinary.