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Sample records for clinically relevant potential

  1. Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

    Science.gov (United States)

    Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

    2018-06-01

    Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Science.gov (United States)

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  3. Valerian: No Evidence for Clinically Relevant Interactions

    Directory of Open Access Journals (Sweden)

    Olaf Kelber

    2014-01-01

    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  4. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  5. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  6. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  7. Clinically relevant incidental cardiovascular findings in CT examinations

    International Nuclear Information System (INIS)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A.; Schramm, D.; Bach, A.G.

    2017-01-01

    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [de

  8. Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

    Science.gov (United States)

    Blake, Margaret Lehman

    2006-01-01

    Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

  9. Extracellular vesicles: fundamentals and clinical relevance

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    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  10. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  11. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  12. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  13. Detecting clinically relevant new information in clinical notes across specialties and settings.

    Science.gov (United States)

    Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

    2017-07-05

    Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

  14. Clinical relevance of findings in trials of CBT for depression

    NARCIS (Netherlands)

    Lepping, P.; Whittington, R.; Sambhi, R.S.; Lane, S.; Poole, R.; Leucht, S.; Cuijpers, P.; McCabe, R.; Waheed, W.

    2017-01-01

    Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We

  15. Clinical relevance of findings in trials of CBT for depression.

    Science.gov (United States)

    Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

    2017-09-01

    Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

    Science.gov (United States)

    Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K

    2016-02-01

    Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

  17. Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

    Science.gov (United States)

    Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

    2014-06-01

    All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

  18. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    NARCIS (Netherlands)

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.

    2000-01-01

    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  19. There’s an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications

    Directory of Open Access Journals (Sweden)

    Warren Wiechmann, MD, MBA

    2016-03-01

    Full Text Available Introduction: The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decisionmaking, prescription information and other medical information. The iTunes App Store (Apple, Inc. contains approximately 20,000 apps in its “Medical” category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. Methods: We found applications related to emergency medicine (EM by searching the iTunes App Store for 21 terms representing core content areas of EM, such as “emergency medicine,” “critical care,” “orthopedics,” and “procedures.” Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/ Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. Results: We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store’s “Medical” Category and 0.1% of the overall App Store. Conclusion: Clinically relevant apps represent only a small percentage (6.9% of the total App

  20. Clinical relevance of pharmacist intervention in an emergency department.

    Science.gov (United States)

    Pérez-Moreno, Maria Antonia; Rodríguez-Camacho, Juan Manuel; Calderón-Hernanz, Beatriz; Comas-Díaz, Bernardino; Tarradas-Torras, Jordi

    2017-08-01

    To evaluate the clinical relevance of pharmacist intervention on patient care in emergencies, to determine the severity of detected errors. Second, to analyse the most frequent types of interventions and type of drugs involved and to evaluate the clinical pharmacist's activity. A 6-month observational prospective study of pharmacist intervention in the Emergency Department (ED) at a 400-bed hospital in Spain was performed to record interventions carried out by the clinical pharmacists. We determined whether the intervention occurred in the process of medication reconciliation or another activity, and whether the drug involved belonged to the High-Alert Medications Institute for Safe Medication Practices (ISMP) list. To evaluate the severity of the errors detected and clinical relevance of the pharmacist intervention, a modified assessment scale of Overhage and Lukes was used. Relationship between clinical relevance of pharmacist intervention and the severity of medication errors was assessed using ORs and Spearman's correlation coefficient. During the observation period, pharmacists reviewed the pharmacotherapy history and medication orders of 2984 patients. A total of 991 interventions were recorded in 557 patients; 67.2% of the errors were detected during medication reconciliation. Medication errors were considered severe in 57.2% of cases and 64.9% of pharmacist intervention were considered relevant. About 10.9% of the drugs involved are in the High-Alert Medications ISMP list. The severity of the medication error and the clinical significance of the pharmacist intervention were correlated (Spearman's ρ=0.728/pclinical pharmacists identified and intervened on a high number of severe medication errors. This suggests that emergency services will benefit from pharmacist-provided drug therapy services. 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/.

  1. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  2. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre

    2012-11-01

    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  3. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

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    Saleem A

    2017-02-01

    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  4. Blocking Avoidance and Escape Responses: Relations With Clinically Relevant Behaviors

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    Juliana Maria Bubna Popovitz

    Full Text Available Abstract: The current study aims to evaluate the possible effects of interrupting problematic clinically relevant behaviors on the percentage of these responses and of clinical improvement-related responses. Two clients were treated with Functional Analytic Psychotherapy (FAP, alternating two conditions (ABAB. On condition A, procedures to the therapist consisted of responding to the clinical improvement responses, and to description of outside of therapeutic setting behaviors, but therapists were advised to ignore problem behaviors emitted in session. During condition B, therapists followed the same procedures, but they were oriented to block (interrupt problematic responses emitted in session. Results suggest increase in the percentage of problem behaviors during condition B. Results are discussed, highlighting the viability of planning the contingent response the therapist emits to clinically relevant behaviors.

  5. What is the clinically relevant change on the ADAS-Cog?

    Science.gov (United States)

    Schrag, Anette; Schott, Jonathan M

    2012-02-01

    To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD). Cohort study. 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative. Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative. The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6-12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM. 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41-47) had an average ADAS-Cog change of 3.1-3.8 points. Similar results were found for the 177 patients with 6-12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7. 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required. http://clinicalTrials.gov Identifier: NCT00106899.

  6. The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

    Science.gov (United States)

    Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca

    2016-01-01

    The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Streptococcus pyogenes biofilms – formation, biology,and clinical relevance

    Directory of Open Access Journals (Sweden)

    Tomas eFiedler

    2015-02-01

    Full Text Available Streptococcus pyogenes (group A streptococci, GAS is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  8. Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

    Science.gov (United States)

    Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

    2018-01-01

    Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

  9. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Subclinical Hypothyroidism in Children and Adolescents: Is It Clinically Relevant?

    Directory of Open Access Journals (Sweden)

    Aneta Gawlik

    2015-01-01

    Full Text Available Although subclinical hypothyroidism (SH is a common clinical problem, its diagnosis tends to be incidental. According to the definition, it should be asymptomatic, only detectable by screening. The presence or coincidence of any symptoms leads to L-thyroxine treatment. The clinical presentation, especially in younger patients with subclinical hypothyroidism, is still under dispute. Accordingly, the aim of this paper was to review the literature from the past seven years. The literature search identified 1,594 potentially relevant articles, of which 24 met the inclusion criteria. Few studies focus on the symptomatology of subclinical hypothyroidism, and most of them analyzed a small number of subjects. A significant correlation was found by some authors between subclinical hypothyroidism and a higher risk of hypertension, dyslipidemia, and migraine. No evidence of the impact of subclinical hypothyroidism on weight, growth velocity, and puberty was revealed. As the quality of most studies is poor and no definite conclusions can be drawn, randomized, large-scale studies in children and adolescents are warranted to determine the best care for patients with SH.

  11. Using mixed methods to identify and answer clinically relevant research questions.

    Science.gov (United States)

    Shneerson, Catherine L; Gale, Nicola K

    2015-06-01

    The need for mixed methods research in answering health care questions is becoming increasingly recognized because of the complexity of factors that affect health outcomes. In this article, we argue for the value of using a qualitatively driven mixed method approach for identifying and answering clinically relevant research questions. This argument is illustrated by findings from a study on the self-management practices of cancer survivors and the exploration of one particular clinically relevant finding about higher uptake of self-management in cancer survivors who had received chemotherapy treatment compared with those who have not. A cross-sectional study generated findings that formed the basis for the qualitative study, by informing the purposive sampling strategy and generating new qualitative research questions. Using a quantitative research component to supplement a qualitative study can enhance the generalizability and clinical relevance of the findings and produce detailed, contextualized, and rich answers to research questions that would be unachievable through quantitative or qualitative methods alone. © The Author(s) 2015.

  12. Classification of first branchial cleft anomalies: is it clinically relevant ...

    African Journals Online (AJOL)

    Background: There are three classification systems for first branchial cleft anomalies currently in use. The Arnot, Work and Olsen classifications describe these lesions on the basis of morphology, tissue of origin and clinical appearance. However, the clinical relevance of these classifications is debated, as they may not be ...

  13. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    Science.gov (United States)

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-11-01

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  14. The clinical relevance and newsworthiness of NIHR HTA-funded research: a cohort study.

    Science.gov (United States)

    Wright, D; Young, A; Iserman, E; Maeso, R; Turner, S; Haynes, R B; Milne, R

    2014-05-07

    To assess the clinical relevance and newsworthiness of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme funded reports. Retrospective cohort study. The cohort included 311 NIHR HTA Programme funded reports publishing in HTA in the period 1 January 2007-31 December 2012. The McMaster Online Rating of Evidence (MORE) system independently identified the clinical relevance and newsworthiness of NIHR HTA publications and non-NIHR HTA publications. The MORE system involves over 4000 physicians rating publications on a scale of relevance (the extent to which articles are relevant to practice) and a scale of newsworthiness (the extent to which articles contain news or something clinicians are unlikely to know). The proportion of reports published in HTA meeting MORE inclusion criteria and mean average relevance and newsworthiness ratings were calculated and compared with publications from the same studies publishing outside HTA and non-NIHR HTA funded publications. 286/311 (92.0%) of NIHR HTA reports were assessed by MORE, of which 192 (67.1%) passed MORE criteria. The average clinical relevance rating for NIHR HTA reports was 5.48, statistically higher than the 5.32 rating for non-NIHR HTA publications (mean difference=0.16, 95% CI 0.04 to 0.29, p=0.01). Average newsworthiness ratings were similar between NIHR HTA reports and non-NIHR HTA publications (4.75 and 4.70, respectively; mean difference=0.05, 95% CI -0.18 to 0.07, p=0.402). NIHR HTA-funded original research reports were statistically higher for newsworthiness than reviews (5.05 compared with 4.64) (mean difference=0.41, 95% CI 0.18 to 0.64, p=0.001). Funding research of clinical relevance is important in maximising the value of research investment. The NIHR HTA Programme is successful in funding projects that generate outputs of clinical relevance.

  15. Clinical relevance of studies on the accuracy of visual inspection for detecting caries lesions

    DEFF Research Database (Denmark)

    Gimenez, Thais; Piovesan, Chaiana; Braga, Mariana M

    2015-01-01

    Although visual inspection is the most commonly used method for caries detection, and consequently the most investigated, studies have not been concerned about the clinical relevance of this procedure. Therefore, we conducted a systematic review in order to perform a critical evaluation considering...... the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature...... to clinical relevance and the methodological quality of the studies were evaluated. 96 of the 5,578 articles initially identified met the inclusion criteria. In general, most studies failed in considering some clinically relevant aspects: only 1 included study validated activity status of lesions, no study...

  16. Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species.

    Science.gov (United States)

    Springer, Jan; Goldenberger, Daniel; Schmidt, Friderike; Weisser, Maja; Wehrle-Wieland, Elisabeth; Einsele, Hermann; Frei, Reno; Löffler, Jürgen

    2016-03-01

    PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n = 17). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n = 10). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

  17. Self-relevant beauty evaluation: Evidence from an event-related potentials study.

    Science.gov (United States)

    Kong, Fanchang; Zhang, Yan; Tian, Yuan; Fan, Cuiying; Zhou, Zongkui

    2015-03-01

    This study examines the electrophysiological correlates of beauty evaluation when participants performed the self-reference task. About 13 (7 men, 6 women) undergraduates participated in the experiment using event-related potentials. Results showed that the response to self-relevant information was faster compared to other-relevant information and no significant differences for self-relevant relative to mother-relevant information were observed. Both physical and interior beauty words for self-relevant information showed an enhanced late positive component as compared to other-relevant information. Physical beauty for self-relevant information yielded a larger late positive component in contrast to mother-relevant information but not for interior beauty. This study indicates that beauty is specific to the person who judges it though an individual and one's mother may hold similar views of interior beauty.

  18. Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

    Science.gov (United States)

    Htun, Nay Min; Peter, Karlheinz

    2014-10-01

    Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  20. Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.

    Science.gov (United States)

    Muhič, Neža; Mrhar, Ales; Brvar, Miran

    2017-07-01

    Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.

  1. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    DEFF Research Database (Denmark)

    Haahtela, T.; Burbach, G. J.; Bachert, C.

    2014-01-01

    , asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. ResultsDepending on the allergen, from 40% (blatella...... by providing quantitative decision points. MethodsThe GA(2)LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis...... SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10mm depending on the allergen. ConclusionThese reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form...

  2. Clinical relevance of narrow-band imaging in flexible cystoscopy

    DEFF Research Database (Denmark)

    Drejer, Ditte; Béji, Sami; Munk Nielsen, Anna

    2017-01-01

    urological departments. Patients had either hematuria (n = 483) or known recurrent non-muscle-invasive bladder cancer (NMIBC) (n = 472). High-definition (HD) cystoscopy was performed in white light (WL) and a preliminary clinical decision was made. Then, a second cystoscopy was performed in NBI...... in NBI compared to WL (NBI: 100.0% vs WL: 83.2%, p decision making as a supplement to WL because it yields a significantly higher...... and a conclusive clinical decision was made. A difference between the two decisions that had a clinical impact on the patient was considered clinically relevant. RESULTS: Pathology was found in 216 WL cystoscopies, and additional pathology in 15 NBI cystoscopies (6.9%). Based on NBI, pathology was suspected in 23...

  3. Using language models to identify relevant new information in inpatient clinical notes.

    Science.gov (United States)

    Zhang, Rui; Pakhomov, Serguei V; Lee, Janet T; Melton, Genevieve B

    2014-01-01

    Redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous and may negatively impact the use of these notes by clinicians, and, potentially, the efficiency of patient care delivery. Automated methods to identify redundant versus relevant new information may provide a valuable tool for clinicians to better synthesize patient information and navigate to clinically important details. In this study, we investigated the use of language models for identification of new information in inpatient notes, and evaluated our methods using expert-derived reference standards. The best method achieved precision of 0.743, recall of 0.832 and F1-measure of 0.784. The average proportion of redundant information was similar between inpatient and outpatient progress notes (76.6% (SD=17.3%) and 76.7% (SD=14.0%), respectively). Advanced practice providers tended to have higher rates of redundancy in their notes compared to physicians. Future investigation includes the addition of semantic components and visualization of new information.

  4. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G

    2009-01-01

    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was ...... the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.......BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess...

  5. Clinical empathy and narrative competence: the relevance of reading talmudic legends as literary fiction.

    Science.gov (United States)

    Davidson, John H

    2015-04-01

    The "curative potential" in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve "narrative competence" in discerning and acting in accord with their preferences and best interests. The "narrative medicine" model of shared "close reading of literature and reflective writing" among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah's death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including-especially-beneficence, non-maleficence, and autonomy.

  6. The potentials of ICT application to increased relevance and ...

    African Journals Online (AJOL)

    The potentials of ICT application to increased relevance and sustainability of University Library Services in Nigeria. ... in Kenneth Dike library, University of Ibadan and University of Lagos Libraries and library search of recent literature on ICT application and marketing of ICT based services in Nigerian University libraries.

  7. Intraductal papillary mucinous neoplasms of the pancreas: reporting clinically relevant features.

    Science.gov (United States)

    Del Chiaro, Marco; Verbeke, Caroline

    2017-05-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can exhibit a wide spectrum of macroscopic and microscopic appearances. This not only causes occasional difficulties for the reporting pathologist in distinguishing these tumours from other lesions, but is also relevant clinically. As evidence accumulates, it becomes clear that multiple macroscopic and histological features of these neoplasms are relevant to the risk for malignant transformation and, consequently, of prime importance for clinical patient management. The need for detailed reporting is therefore increasing. This review discusses the panoply of gross and microscopic features of IPMN as well as the recommendations from recent consensus meetings regarding the pathology reporting on this tumour entity. © 2016 John Wiley & Sons Ltd.

  8. Relevance of MICA and other non-HLA antibodies in clinical transplantation.

    Science.gov (United States)

    Sumitran-Holgersson, Suchitra

    2008-10-01

    The clinical importance of HLA-specific antibodies for organ allograft outcome is well established. In the past few years, there has been an increasing interest in non-HLA antigens as targets of injury in organ transplant recipients. This increased interest has been spurred by the fact that HLA-identical kidney transplants also undergo immunological rejections. Polymorphisms within non-HLA genes associated with evoking an immune response to alloantigens are currently being studied for their association with transplant outcome. Non-HLA antigens, such as the polymorphic MHC class I-related chain A (MICA), expressed on endothelial cells have been implicated in the pathogenesis of hyperacute, acute and chronic organ allograft rejections. Use of endothelial cells as targets may clarify the specificities of other clinically relevant non-HLA antibodies in graft rejections. This review summarizes past and current knowledge of the clinical importance and specificities of non-HLA antibodies, and mechanisms by which these antibodies may contribute to graft destruction in clinical transplantation. The aims of current research into the role of non-HLA antigens and their genetics in predicting outcome are to develop an improved insight into the basic science of transplantation and to develop a risk or prognostic index for use in the clinical setting. Non-HLA antibody responses are receiving increasing interest in acute and chronic rejection and specificity, affinity, and pathogenicity need to be investigated to estimate their contribution. Undoubtedly, this will continue to be an area of interest in terms of fully understanding the role of non-HLA antigens as targets of immune-mediated injury and the potential for clinical intervention.

  9. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner

    2012-03-01

    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  10. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Decaying relevance of clinical data towards future decisions in data-driven inpatient clinical order sets.

    Science.gov (United States)

    Chen, Jonathan H; Alagappan, Muthuraman; Goldstein, Mary K; Asch, Steven M; Altman, Russ B

    2017-06-01

    Determine how varying longitudinal historical training data can impact prediction of future clinical decisions. Estimate the "decay rate" of clinical data source relevance. We trained a clinical order recommender system, analogous to Netflix or Amazon's "Customers who bought A also bought B..." product recommenders, based on a tertiary academic hospital's structured electronic health record data. We used this system to predict future (2013) admission orders based on different subsets of historical training data (2009 through 2012), relative to existing human-authored order sets. Predicting future (2013) inpatient orders is more accurate with models trained on just one month of recent (2012) data than with 12 months of older (2009) data (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10 -10 ). Algorithmically learned models from even the older (2009) data was still more effective than existing human-authored order sets (ROC AUC 0.81, precision 16% recall 35%). Training with more longitudinal data (2009-2012) was no better than using only the most recent (2012) data, unless applying a decaying weighting scheme with a "half-life" of data relevance about 4 months. Clinical practice patterns (automatically) learned from electronic health record data can vary substantially across years. Gold standards for clinical decision support are elusive moving targets, reinforcing the need for automated methods that can adapt to evolving information. Prioritizing small amounts of recent data is more effective than using larger amounts of older data towards future clinical predictions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Relevance of human anatomy in daily clinical practice.

    Science.gov (United States)

    Arráez-Aybar, Luis-Alfonso; Sánchez-Montesinos, Indalecio; Mirapeix, Rosa-M; Mompeo-Corredera, Blanca; Sañudo-Tejero, Jose-Ramón

    2010-12-20

    the aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). a total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. the response rate was 42.9% (n=536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals. 2010 Elsevier GmbH. All rights reserved.

  13. Laboratory exercises to teach clinically relevant chemistry of antibiotics.

    Science.gov (United States)

    El Sayed, Khalid A; Chelette, Candace T

    2014-03-12

    To design, implement, and evaluate student performance on clinically relevant chemical and spectral laboratory exercises on antibiotics. In the first of 2 exercises, second-year pharmacy students enrolled in an integrated laboratory sequence course studied the aqueous stability of ß-lactam antibiotics using a spectral visual approach. In a second exercise, students studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form insoluble chelate complexes (turbidity) with polyvalent metals. On a survey to assess achievement of class learning objectives, students agreed the laboratory activities helped them better retain important information concerning antibiotic stability and interactions. A significant improvement was observed in performance on examination questions related to the laboratory topics for 2012 and 2013 students compared to 2011 students who did not complete the laboratory. A 1-year follow-up examination question administered in a separate course showed >75% of the students were able to identify rifamycins-food interactions compared with laboratory exercises. The use of spectral visual approaches allowed students to investigate antibiotic stability and interactions, thus reinforcing the clinical relevance of medicinal chemistry. Students' performance on questions at the 1-year follow-up suggested increased retention of the concepts learned as a result of completing the exercises.

  14. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  15. Cerebral activation studies by PET and fMRT, clinical relevance?

    International Nuclear Information System (INIS)

    Brandt, T.

    1997-01-01

    Cerebral activation studies by PET and fMRT will gain increasing clinical relevance for functional neuroanatomy (reading, speaking), localisation of largely unknown cortical functions (vestibular cortex), imaging of subjective complaints of functional impairments (pain, smell, memory), and documentation of neurological rehabilitation at neuronal level (regeneration, compensation, substitution, learning). (orig.) [de

  16. Recurrence, submicroscopic complexity, and potential clinical relevance of copy gains detected by array CGH that are shown to be unbalanced insertions by FISH.

    Science.gov (United States)

    Neill, Nicholas J; Ballif, Blake C; Lamb, Allen N; Parikh, Sumit; Ravnan, J Britt; Schultz, Roger A; Torchia, Beth S; Rosenfeld, Jill A; Shaffer, Lisa G

    2011-04-01

    Insertions occur when a segment of one chromosome is translocated and inserted into a new region of the same chromosome or a non-homologous chromosome. We report 71 cases with unbalanced insertions identified using array CGH and FISH in 4909 cases referred to our laboratory for array CGH and found to have copy-number abnormalities. Although the majority of insertions were non-recurrent, several recurrent unbalanced insertions were detected, including three der(Y)ins(Y;18)(q?11.2;p11.32p11.32)pat inherited from parents carrying an unbalanced insertion. The clinical significance of these recurrent rearrangements is unclear, although the small size, limited gene content, and inheritance pattern of each suggests that the phenotypic consequences may be benign. Cryptic, submicroscopic duplications were observed at or near the insertion sites in two patients, further confounding the clinical interpretation of these insertions. Using FISH, linear amplification, and array CGH, we identified a 126-kb duplicated region from 19p13.3 inserted into MECP2 at Xq28 in a patient with symptoms of Rett syndrome. Our results demonstrate that although the interpretation of most non-recurrent insertions is unclear without high-resolution insertion site characterization, the potential for an otherwise benign duplication to result in a clinically relevant outcome through the disruption of a gene necessitates the use of FISH to determine whether copy-number gains detected by array CGH represent tandem duplications or unbalanced insertions. Further follow-up testing using techniques such as linear amplification or sequencing should be used to determine gene involvement at the insertion site after FISH has identified the presence of an insertion.

  17. Taijin kyofusho and social anxiety and their clinical relevance in indonesia and Switzerland.

    Science.gov (United States)

    Vriends, N; Pfaltz, M C; Novianti, P; Hadiyono, J

    2013-01-01

    Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears. TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms. TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings.

  18. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    Directory of Open Access Journals (Sweden)

    Noortje eVriends

    2013-02-01

    Full Text Available Background: Taijin Kyofusho (TKS is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. Method: 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears.Results: TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms.Discussion: TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings.

  19. Properties and clinical relevance of osteoinductive biomaterials

    NARCIS (Netherlands)

    Habibovic, Pamela

    2005-01-01

    This thesis had two main goals: (¿) to investigate parameters influencing osteoinductive potential of biomaterials in order to unravel the mechanism underlying osteoinduction and (¿¿) to investigate performance of osteoinductive biomaterials orthotopically in order to get insight into their clinical

  20. FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding

    International Nuclear Information System (INIS)

    Stahl, A.; Wieder, H.; Schwaiger, M.; Weber, W.A.; Stollfuss, J.; Ott, K.; Fink, U.

    2005-01-01

    Aim: the incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. Patients, methods: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. Results: when read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of MI-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. Conclusion: about half of discordances between FDG PET and CT are clinically relevant

  1. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    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

  2. Clinically relevant incidental cardiovascular findings in CT examinations; Klinisch relevante kardiovaskulaere Zufallsbefunde bei CT-Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A. [Universitaetsklinikum Leipzig, Klinik fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Schramm, D.; Bach, A.G. [Universitaetsklinikum Halle (Saale), Klinik fuer Radiologie, Halle (Germany)

    2017-04-15

    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [German] Inzidentelle kardiovaskulaere Befunde sind ein haeufiges Phaenomen bei CT-Untersuchungen. Mit dieser Arbeit soll nach gezielter PubMed-Recherche ein systematischer Literaturueberblick ueber die wichtigsten kardiovaskulaeren Zufallsbefunde sowie deren Haeufigkeit und klinische Relevanz gegeben werden. Die Mehrzahl der inzidentellen kardiovaskulaeren Befunde sind klinisch nur von untergeordneter Bedeutung, allerdings werden immer wieder auch hochgradig relevante Zufallsbefunde wie beispielsweise Aortenaneurysmata oder - gerade bei onkologischen Patienten - Thrombosen und thrombembolische Ereignisse detektiert. Jede CT-Untersuchung sollte gezielt nach inzidentellen Befunden durchsucht werden, da diese je nach klinischer Relevanz von entscheidender Bedeutung fuer das weitere klinische Management des Patienten sein koennen. (orig.)

  3. Mirror neurons and their clinical relevance.

    Science.gov (United States)

    Rizzolatti, Giacomo; Fabbri-Destro, Maddalena; Cattaneo, Luigi

    2009-01-01

    One of the most exciting events in neurosciences over the past few years has been the discovery of a mechanism that unifies action perception and action execution. The essence of this 'mirror' mechanism is as follows: whenever individuals observe an action being done by someone else, a set of neurons that code for that action is activated in the observers' motor system. Since the observers are aware of the outcome of their motor acts, they also understand what the other individual is doing without the need for intermediate cognitive mediation. In this Review, after discussing the most pertinent data concerning the mirror mechanism, we examine the clinical relevance of this mechanism. We first discuss the relationship between mirror mechanism impairment and some core symptoms of autism. We then outline the theoretical principles of neurorehabilitation strategies based on the mirror mechanism. We conclude by examining the relationship between the mirror mechanism and some features of the environmental dependency syndromes.

  4. Automatic classification and detection of clinically relevant images for diabetic retinopathy

    Science.gov (United States)

    Xu, Xinyu; Li, Baoxin

    2008-03-01

    We proposed a novel approach to automatic classification of Diabetic Retinopathy (DR) images and retrieval of clinically-relevant DR images from a database. Given a query image, our approach first classifies the image into one of the three categories: microaneurysm (MA), neovascularization (NV) and normal, and then it retrieves DR images that are clinically-relevant to the query image from an archival image database. In the classification stage, the query DR images are classified by the Multi-class Multiple-Instance Learning (McMIL) approach, where images are viewed as bags, each of which contains a number of instances corresponding to non-overlapping blocks, and each block is characterized by low-level features including color, texture, histogram of edge directions, and shape. McMIL first learns a collection of instance prototypes for each class that maximizes the Diverse Density function using Expectation- Maximization algorithm. A nonlinear mapping is then defined using the instance prototypes and maps every bag to a point in a new multi-class bag feature space. Finally a multi-class Support Vector Machine is trained in the multi-class bag feature space. In the retrieval stage, we retrieve images from the archival database who bear the same label with the query image, and who are the top K nearest neighbors of the query image in terms of similarity in the multi-class bag feature space. The classification approach achieves high classification accuracy, and the retrieval of clinically-relevant images not only facilitates utilization of the vast amount of hidden diagnostic knowledge in the database, but also improves the efficiency and accuracy of DR lesion diagnosis and assessment.

  5. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2017-02-01

    Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) 2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

  6. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    Science.gov (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  7. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

    Science.gov (United States)

    Papale, Alessandro; Morella, Ilaria Maria; Indrigo, Marzia Tina; Bernardi, Rick Eugene; Marrone, Livia; Marchisella, Francesca; Brancale, Andrea; Spanagel, Rainer; Brambilla, Riccardo; Fasano, Stefania

    2016-01-01

    Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. DOI: http://dx.doi.org/10.7554/eLife.17111.001 PMID:27557444

  8. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

    Science.gov (United States)

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

  9. Increasing clinical relevance in oral radiology: Benefits and challenges when implementing digital assessment.

    Science.gov (United States)

    de Lange, T; Møystad, A; Torgersen, G R

    2018-02-13

    The aims of the study were to investigate benefits and challenges in implementing a digital examination and study the clinical relevance of the digital examination in relation to clinical training and practice. The study was based on semi-structured focus-group interviews from two distinct student populations (2016 and 2017) in a bachelor programme in dental hygiene. In addition, conversational data from a plenary discussion from the whole second student population (2017) were collected and analysed. The data were approached on basis of content analysis. A benefit experienced in the digital examination was the ease in typing and editing answers on the computer. This suggests an increased effectiveness in computer-based compared to analogue examinations. An additional advantage was the experienced relevance of the examination related to the clinic. This finding refers not only to the digital presentations of images, but also to the entire setting in the clinic and dental practice. The limitations reported by the students were non-optimal viewing conditions for presenting radiographic images and difficulties in obtaining an overview of the assignments compared to paper-based examinations due to the linear digital examination format. The last finding on lacking overview revealed an influence on student performances which should be taken seriously in designing digital examinations. In conclusion, the digital layout increases efficiency and clinical relevance of examinations to a certain extent. Obstacles were found in limitations related to image presentation and lack of overview of the examination. The latter challenge raises questions related to developing suitable assessment software. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Clinical relevance of and risk factors associated with medication administration time errors

    NARCIS (Netherlands)

    Teunissen, R.; Bos, J.; Pot, H.; Pluim, M.; Kramers, C.

    2013-01-01

    PURPOSE: The clinical relevance of and risk factors associated with errors related to medication administration time were studied. METHODS: In this explorative study, 66 medication administration rounds were studied on two wards (surgery and neurology) of a hospital. Data on medication errors were

  11. Reporting the results of meta-analyses: a plea for incorporating clinical relevance referring to an example.

    Science.gov (United States)

    Bartels, Ronald H M A; Donk, Roland D; Verhagen, Wim I M; Hosman, Allard J F; Verbeek, André L M

    2017-11-01

    The results of meta-analyses are frequently reported, but understanding and interpreting them is difficult for both clinicians and patients. Statistical significances are presented without referring to values that imply clinical relevance. This study aimed to use the minimal clinically important difference (MCID) to rate the clinical relevance of a meta-analysis. This study is a review of the literature. This study is a review of meta-analyses relating to a specific topic, clinical results of cervical arthroplasty. The outcome measure used in the study was the MCID. We performed an extensive literature search of a series of meta-analyses evaluating a similar subject as an example. We searched in Pubmed and Embase through August 9, 2016, and found articles concerning meta-analyses of the clinical outcome of cervical arthroplasty compared with that of anterior cervical discectomy with fusion in cases of cervical degenerative disease. We evaluated the analyses for statistical significance and their relation to MCID. MCID was defined based on results in similar patient groups and a similar disease entity reported in the literature. We identified 21 meta-analyses, only one of which referred to MCID. However, the researchers used an inappropriate measurement scale and, therefore, an incorrect MCID. The majority of the conclusions were based on statistical results without mentioning clinical relevance. The majority of the articles we reviewed drew conclusions based on statistical differences instead of clinical relevance. We recommend introducing the concept of MCID while reporting the results of a meta-analysis, as well as mentioning the explicit scale of the analyzed measurement. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

    Science.gov (United States)

    Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

    2003-09-01

    Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

  13. Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic

    Directory of Open Access Journals (Sweden)

    Adekunle T. Bademosi

    2018-01-01

    Full Text Available Summary: Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters. : Bademosi et al. use single-molecule imaging microscopy to understand how general anesthetics might affect presynaptic release mechanisms. They find that a clinically relevant concentration of propofol targets the presynaptic release machinery by specifically restricting syntaxin1A mobility on the plasma membrane. This suggests an alternate target process for these drugs. Keywords: super-resolution microscopy, sptPALM, propofol, etomidate, SNARE, Drosophila melanogaster, PC12, syntaxin1A, SNAP-25, neurotransmission

  14. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS...... therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy...

  15. Phenotypic and genotypic characterization of clinically relevant bacteria isolated from dental waste and waste workers' hands, mucosas and coats.

    Science.gov (United States)

    Tagliaferri, T L; Vieira, C D; de Carvalho, M A R; Ladeira, L C D; Magalhães, P P; de Macêdo Farias, L; Dos Santos, S G

    2017-10-01

    Infectious wastes are potential sources of pathogenic micro-organisms, which may represent a risk to the professionals who manage them. In this study, we aimed to characterize the infectious bacteria present in dental waste and waste workers. The dental waste produced over 24 h was collected and waste workers were sampled by swabbing. Isolate resistance profiles were characterized by Vitek ® and PCR and biofilm formation by Congo Red agar, string test and microtitre assay. To assess similarity between the waste and the workers' samples, a random amplified polymorphic DNA test was used. Twenty-eight bacteria were identified as clinically relevant. The most frequent gene was bla TEM present in five Gram-negative micro-organisms, and one bla SHV in Klebsiella pneumoniae. All Pseudomonas aeruginosa were positive to extracellular polymeric substances formation, except one isolated from a worker. Klebsiella pneumoniae had negative results for the string test. Pseudomonas aeruginosa showed better adherence at 25°C after 48 h of incubation and K. pneumonia had the best biofilm formation at the same temperature, after 24 h. The similarity between P. aeruginosa recovered from dental waste and from workers was low, however, it is important to note that a pathogen was found on a worker's hands and that improvements in biosafety are required. Infectious dental waste can contain clinically relevant bacteria with important resistance and biofilm profiles. These micro-organisms could be transmitted to waste workers, other professionals and patients if the principles of biosafety measures are neglected. To our knowledge, no study has ever evaluated the microbial characterization and the potential contamination risk of dental infectious waste and waste handlers. The presence of clinically relevant bacteria in the hands and nasal mucosa of waste workers highlights the need for studies in this field to clarify the risk of these pathogens in dental healthcare services, and to

  16. Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

    Science.gov (United States)

    Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

    Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Abundances of Clinically Relevant Antibiotic Resistance Genes and Bacterial Community Diversity in the Weihe River, China

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wang

    2018-04-01

    Full Text Available The spread of antibiotic resistance genes in river systems is an emerging environmental issue due to their potential threat to aquatic ecosystems and public health. In this study, we used droplet digital polymerase chain reaction (ddPCR to evaluate pollution with clinically relevant antibiotic resistance genes (ARGs at 13 monitoring sites along the main stream of the Weihe River in China. Six clinically relevant ARGs and a class I integron-integrase (intI1 gene were analyzed using ddPCR, and the bacterial community was evaluated based on the bacterial 16S rRNA V3–V4 regions using MiSeq sequencing. The results indicated Proteobacteria, Actinobacteria, Cyanobacteria, and Bacteroidetes as the dominant phyla in the water samples from the Weihe River. Higher abundances of blaTEM, strB, aadA, and intI1 genes (103 to 105 copies/mL were detected in the surface water samples compared with the relatively low abundances of strA, mecA, and vanA genes (0–1.94 copies/mL. Eight bacterial genera were identified as possible hosts of the intI1 gene and three ARGs (strA, strB, and aadA based on network analysis. The results suggested that the bacterial community structure and horizontal gene transfer were associated with the variations in ARGs.

  18. 4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

    Science.gov (United States)

    Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A

    2015-01-01

    4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. High-angle scattering events strongly affect light collection in clinically relevant measurement geometries for light transport through tissue

    International Nuclear Information System (INIS)

    Canpolat, M.; Mourant, J.R.

    2000-01-01

    Measurement of light transport in tissue has the potential to be an inexpensive and practical tool for non-invasive tissue diagnosis in medical applications because it can provide information on both morphological and biochemical properties. To capitalize on the potential of light transport as a diagnostic tool, an understanding of what information can be gleaned from light transport measurements is needed. We present data concerning the sensitivity of light transport measurements, made in clinically relevant geometries, to scattering properties. The intensity of the backscattered light at small source-detector separations is shown to be sensitive to the phase function, and furthermore the collected light intensity is found to be correlated with the amount of high-angle scattering in the medium. (author)

  20. Measuring agreement between rating interpretations and binary clinical interpretations of images: a simulation study of methods for quantifying the clinical relevance of an observer performance paradigm

    International Nuclear Information System (INIS)

    Chakraborty, Dev P

    2012-01-01

    Laboratory receiver operating characteristic (ROC) studies, that are often used to evaluate medical imaging systems, differ from ‘live’ clinical interpretations in several respects which could compromise their clinical relevance. The aim was to develop methodology for quantifying the clinical relevance of a laboratory ROC study. A simulator was developed to generate ROC ratings data and binary clinical interpretations classified as correct or incorrect for a common set of images interpreted under clinical and laboratory conditions. The area under the trapezoidal ROC curve (AUC) was used as the laboratory figure-of-merit and the fraction of correct clinical decisions as the clinical figure-of-merit. Conventional agreement measures (Pearson, Spearman, Kendall and kappa) between the bootstrap-induced fluctuations of the two figures of merit were estimated. A jackknife pseudovalue transformation applied to the figures of merit was also investigated as a way to capture agreement existing at the individual image level that could be lost at the figure-of-merit level. It is shown that the pseudovalues define a relevance-ROC curve. The area under this curve (rAUC) measures the ability of the laboratory figure-of-merit-based pseudovalues to correctly classify incorrect versus correct clinical interpretations. Therefore, rAUC is a measure of the clinical relevance of an ROC study. The conventional measures and rAUC were compared under varying simulator conditions. It was found that design details of the ROC study, namely the number of bins, the difficulty level of the images, the ratio of disease-present to disease-absent images and the unavoidable difference between laboratory and clinical performance levels, can lead to serious underestimation of the agreement as indicated by conventional agreement measures, even for perfectly correlated data, while rAUC showed high agreement and was relatively immune to these details. At the same time rAUC was sensitive to factors such

  1. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  2. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor

    2017-01-01

    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal...... and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft...... enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat...

  3. Dissociative absorption: An empirically unique, clinically relevant, dissociative factor.

    Science.gov (United States)

    Soffer-Dudek, Nirit; Lassri, Dana; Soffer-Dudek, Nir; Shahar, Golan

    2015-11-01

    Research of dissociative absorption has raised two questions: (a) Is absorption a unique dissociative factor within a three-factor structure, or a part of one general dissociative factor? Even when three factors are found, the specificity of the absorption factor is questionable. (b) Is absorption implicated in psychopathology? Although commonly viewed as "non-clinical" dissociation, absorption was recently hypothesized to be specifically associated with obsessive-compulsive symptoms. To address these questions, we conducted exploratory and confirmatory factor analyses on 679 undergraduates. Analyses supported the three-factor model, and a "purified" absorption scale was extracted from the original inclusive absorption factor. The purified scale predicted several psychopathology scales. As hypothesized, absorption was a stronger predictor of obsessive-compulsive symptoms than of general psychopathology. In addition, absorption was the only dissociative scale that longitudinally predicted obsessive-compulsive symptoms. We conclude that absorption is a unique and clinically relevant dissociative tendency that is particularly meaningful to obsessive-compulsive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Development of a new microtiter plate format for clinically relevant assays.

    Science.gov (United States)

    Piletska, Elena V; Piletsky, Stanislav S; Whitcombe, Michael J; Chianella, Iva; Piletsky, Sergey A

    2012-02-21

    A new format for the microtiter plate-based assays was proposed. The novelty involves the use of disk-shaped inserts for immobilization of biological and chemical reagents. The internal opening of the disks allows measurements of the reactions by standard microtiter plate readers without any additional steps involving liquid handling. Ideally the plate end-users just have to add the sample and take the measurement without any need of multiple reagent additions or transfer of the liquid to a different plate. The novel assay format also allows handling of reagents which are not soluble in an aqueous environment. As a proof of concept we describe here several model reactions which are compatible with microtiter plate format, such as monitoring enzymatic reactions catalyzed by glucose oxidase (GOx) and urease, measurements of proteins by BCA assay, analysis of pH, and concentration of antioxidants. The "mix and match" approach in the disk-shape format allows multiplexing and could be particularly useful for high throughput screening. One of the potential application areas for this novel assay format could be in a multianalyte system for measurement of clinically relevant analytes in primary care.

  5. Clinical relevance of routinely measured vital signs in hospitalized patients: a systematic review

    NARCIS (Netherlands)

    Storm-Versloot, Marja N.; Verweij, Lotte; Lucas, Cees; Ludikhuize, Jeroen; Goslings, J. Carel; Legemate, Dink A.; Vermeulen, Hester

    2014-01-01

    Conflicting evidence exists on the effectiveness of routinely measured vital signs on the early detection of increased probability of adverse events. To assess the clinical relevance of routinely measured vital signs in medically and surgically hospitalized patients through a systematic review.

  6. Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers.

    Science.gov (United States)

    Puchades-Carrasco, Leonor; Palomino-Schätzlein, Martina; Pérez-Rambla, Clara; Pineda-Lucena, Antonio

    2016-05-01

    Metabolomics, a systems biology approach focused on the global study of the metabolome, offers a tremendous potential in the analysis of clinical samples. Among other applications, metabolomics enables mapping of biochemical alterations involved in the pathogenesis of diseases, and offers the opportunity to noninvasively identify diagnostic, prognostic and predictive biomarkers that could translate into early therapeutic interventions. Particularly, metabolomics by Nuclear Magnetic Resonance (NMR) has the ability to simultaneously detect and structurally characterize an abundance of metabolic components, even when their identities are unknown. Analysis of the data generated using this experimental approach requires the application of statistical and bioinformatics tools for the correct interpretation of the results. This review focuses on the different steps involved in the metabolomics characterization of biofluids for clinical applications, ranging from the design of the study to the biological interpretation of the results. Particular emphasis is devoted to the specific procedures required for the processing and interpretation of NMR data with a focus on the identification of clinically relevant biomarkers. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting: A Systematic Review.

    Science.gov (United States)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor; Herly, Mikkel; Trojahn Kølle, Stig-Frederik; Fischer-Nielsen, Anne; Drzewiecki, Krzysztof Tadeusz

    2017-07-01

    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat grafting. Improvements in graft retention, the SVF to fat (SVF:fat) ratio, and the ASC concentration used for enrichment were emphasized. We proposed an increased retention rate greater than 1.5-fold relative to nonenriched grafts and a maximum SVF:fat ratio of 1:1 as the thresholds for clinical relevance and feasibility, respectively. Nine studies fulfilled these criteria, whereof 6 used ASCs for enrichment. We found no convincing evidence of a clinically relevant effect of SVF enrichment in humans. ASC enrichment has shown promising results in enhancing graft retention, but additional clinical trials are needed to substantiate this claim and also determine the optimal concentration of SVF cells/ASCs for enrichment. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  8. A clinically relevant major cross-reactive allergen from mesquite tree pollen.

    Science.gov (United States)

    Dhyani, A; Singh, B P; Arora, N; Jain, V K; Sridhara, S

    2008-10-01

    Prosopis juliflora (mesquite) is one of the major sources of pollinosis in tropical and semi-arid countries of the world. The present study was undertaken to purify and characterize a major cross-reactive allergen from this tree species. Mesquite pollen extract was purified using reverse-phase chromatography. Allergen characterization was done by electrophoresis, enzyme-linked immunosorbent assay (ELISA) and Western blotting. Clinical relevance of the purified protein was analyzed by in vivo (skin tests) and in vitro experiments such as ELISA, histamine release, peripheral blood mononuclear cells (PBMC) proliferation and cytokine assays. Cross-reactivity of purified protein with allergenic tree species and lima bean (food) was assessed by inhibition assays. A 66-kDa protein was purified from mesquite pollen extract using octadecyl silica resin. Purified protein recognized 90% of mesquite-sensitized patients in skin test and ELISA. It induced significant histamine release in allergic patients' blood and interleukin-4 secretion in the PBMC culture supernatants. Inhibition assays suggested close allergenic relationship of this protein with Ailanthus excelsa, Cassia siamea, Salvadora persica pollen and Phaseolus lunatus (lima bean - an edible legume). A 66-kDa major cross-reactive allergen was isolated from mesquite pollen using single-step purification procedure. The protein seems relevant for clinical applications in allergic disorders.

  9. Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Maughan, Benjamin L; Antonarakis, Emmanuel S

    2015-12-01

    Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

  10. Clinical relevance of cimetidine drug interactions.

    Science.gov (United States)

    Shinn, A F

    1992-01-01

    The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

  11. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  12. Cardiac Remote Conditioning and Clinical Relevance: All Together Now!

    Directory of Open Access Journals (Sweden)

    Kristin Luther

    2015-12-01

    mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective “conditioning” phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-кB, Stat3/5, protein kinase C, bradykinin, and the mitoKATP channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

  13. Assessment of relevant fungal species in clinical solid wastes.

    Science.gov (United States)

    Noman, Efaq Ali; Al-Gheethi, A A; Rahman, Nik Norulaini Nik Ab; Nagao, H; Ab Kadir, M O

    2016-10-01

    The study aimed to determine the fungal diversity in clinical waste samples from a healthcare facility in Penang Malaysia. Different fungi species were detected in 83.75 % of the 92 clinical waste samples that were screened from different sections of the healthcare facility. One hundred fifty fungal isolates comprising of 8 genera and 36 species were obtained. They were purified by using single spore isolation technique. Subsequently, the isolates were identified by phenotypic method based on morphological and culture characteristics on different culture media. Among all fungal isolates, Aspergillus spp. in section Nigri 10.2 %, Aspergillus niger 9.5 %, Aspergillus fumigatus 8.8 %, Penicillium. simplicissium 8 %, Aspergillus tubingensis 7.3 %, Aspergillus terreus var. terreus 6.6 %, Penicillium waksmanii 5.9 % and Curvularia lunata 6.5 % were the most frequent. Among five sections of the Wellness Centre, the clinical wastes collected from the diagnostic labs of haematology section had the highest numbers of fungal species (29 species). Glove wastes had the highest numbers of fungal species (19 species) among 17 types of clinical wastes screened. Among all fungal species, Aspergillus spp. exhibited higher growth at 37 °C than at 28 °C, indicating the potential of these opportunistic fungi to cause diseases in human. These results indicated the potential of hospital wastes as reservoirs for fungal species.

  14. Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures.

    Science.gov (United States)

    Pan, Xuequn; Cimino, James J

    2014-01-01

    Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

  15. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  16. [Relevance of drug use in clinical manifestations of schizophrenia].

    Science.gov (United States)

    Arias Horcajadas, F; Sánchez Romero, S; Padín Calo, J J

    2002-01-01

    To study the association between drugs use with schizophrenia clinical manifestations. The sample consists of 82 out-patients with schizophrenia, between 18 and 45 years old. They were evaluated with Addiction Severity Index (ASI) and with Positive and Negative Syndrome Scale (PANSS). A 6 months follow up was carried out. 37,8% patients had lifetime drug dependence (including alcohol and others drugs except for tobacco). The prevalence of dependence for the different drugs were: opioids 9,8%, cocaine 11%, alcohol 29,3%, cannabis 24,4%, tobacco 68,3%, caffeine 15,9%. Drug dependent had more family and legal problems. At the multiple regression analysis it was observed that cannabis and tobacco dependence was associated with a decrease in the PANSS negative symptoms subscale, and on the contrary, alcohol dependence produces a similar intensity increase at that scoring. We don't detect any clinical relevance effects over positive symptoms. Cannabis and tobacco may improve schizophrenia negative symptoms or neuroleptic secondary effects or patients with few negative symptoms may have more predisposition to the use, on the contrary alcohol use can impairment those symptoms.

  17. Clinical Relevance of Steroid Use in Neuro-Oncology.

    Science.gov (United States)

    Ly, K Ina; Wen, Patrick Y

    2017-01-01

    Corticosteroids are commonly used in the management of primary central nervous system (CNS) tumors and CNS metastases to treat cancer- and treatment-related cerebral edema and improve neurologic function. However, they are also associated with significant morbidity and mortality, given their wide range of adverse effects. To review the mechanism of action, pharmacology, and toxicity profile of corticosteroids and to critically appraise the evidence that supports their use in neuro-oncologic practice based on the latest scientific and clinical data. Recent data suggest that corticosteroids may negatively impact survival in glioma patients. In addition, corticosteroids should be incorporated as a standard criterion to assess a patient's clinical and radiographic response to treatment. Corticosteroids should be used judiciously in neuro-oncologic patients, given the potential deleterious effects on clinical outcome and patient survival. Anti-angiogenic agents, which lack these adverse effects, may be a reasonable alternative to corticosteroids.

  18. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  19. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    Science.gov (United States)

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2018-03-01

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

  20. Prevalence of clinically relevant muscle weakness and its association with vitamin D status among older adults in Ecuador.

    Science.gov (United States)

    Orces, Carlos H

    2017-10-01

    Muscle weakness and 25-hydroxyvitamin D (25(OH)D) deficiency have been associated with adverse outcomes among older adults. However, little is known about the relationship between clinically relevant muscle weakness and 25(OH)D levels in Ecuador. To examine the prevalence of muscle weakness and its association with 25(OH)D status among subjects aged 60 years and older in Ecuador. The present study was based on data from 2205 participants in the first National Survey of Health, Wellbeing, and Aging. The Foundation for the National Institute of Health Sarcopenia Project criteria was used to examine muscle weakness prevalence rates. Gender-specific general linear and logistic regression models adjusted for potential confounders were created to compare mean 25(OH)D concentrations and 25(OH)D deficiency across muscle strength categories, respectively. An estimated 32.2% of women and 33.4% of men had evidence of clinically relevant muscle weakness in Ecuador. In general, increased muscle weakness prevalence rates were present among Indigenous, residents in the rural Andes Mountains, underweight subjects, and those with a sedentary lifestyle. Muscle strength was significantly and directly correlated with mean 25(OH)D levels. After controlling for potential confounders, 25(OH)D deficiency prevalence rates were 31 and 43% higher among men and women with muscle weakness than those with normal strength, respectively. One-third of older adults nationwide had evidence of muscle weakness. While the present study found a significant correlation between muscle strength and 25(OH)D concentrations, further research is needed to examine whether optimizing 25(OH)D levels may improve muscle weakness among older adults.

  1. The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults

    DEFF Research Database (Denmark)

    Osterballe, M.; Hansen, T.K.; Mørtz, Charlotte G

    2005-01-01

    BACKGROUND: Previous studies have described cross-reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults with and without symptoms in the pollen...... season. OBJECTIVE: The aim of this study was to estimate the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults and to examine the diagnostic value of skin-prick test (SPT), histamine release and specific IgE compared with the outcome...... of oral challenge. METHODS: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross-reactivity with pollen-related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. RESULTS...

  2. [Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

    Science.gov (United States)

    Martínez-Múgica, Cristina

    2015-12-01

    Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

  3. A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

    Science.gov (United States)

    Akhloufi, H; Hulscher, M; van der Hoeven, C P; Prins, J M; van der Sijs, H; Melles, D C; Verbon, A

    2018-04-26

    To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.

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

    Science.gov (United States)

    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.

  5. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

    Directory of Open Access Journals (Sweden)

    Xinxin Peng

    2018-04-01

    Full Text Available Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism

  6. Statistical significance versus clinical relevance.

    Science.gov (United States)

    van Rijn, Marieke H C; Bech, Anneke; Bouyer, Jean; van den Brand, Jan A J G

    2017-04-01

    In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  7. Assessing Hospital Physicians' Acceptance of Clinical Information Systems: A Review of the Relevant Literature

    Directory of Open Access Journals (Sweden)

    Bram Pynoo

    2013-06-01

    Full Text Available In view of the tremendous potential benefits of clinical information systems (CIS for the quality of patient care; it is hard to understand why not every CIS is embraced by its targeted users, the physicians. The aim of this study is to propose a framework for assessing hospital physicians' CIS-acceptance that can serve as a guidance for future research into this area. Hereto, a review of the relevant literature was performed in the ISI Web-of-Science database. Eleven studies were withheld from an initial dataset of 797 articles. Results show that just as in business settings, there are four core groups of variables that influence physicians' acceptance of a CIS: its usefulness and ease of use, social norms, and factors in the working environment that facilitate use of the CIS (such as providing computers/workstations, compatibility between the new and existing system.... We also identified some additional variables as predictors of CIS-acceptance.

  8. Music's relevance for children with cancer: music therapists' qualitative clinical data-mining research.

    Science.gov (United States)

    O'Callaghan, Clare; Dun, Beth; Baron, Annette; Barry, Philippa

    2013-01-01

    Music is central in most children's lives. Understanding its relevance will advance efficacious pediatric supportive cancer care. Qualitative clinical data-mining uncovered four music therapists' perspectives about music and music therapy's relevance for pediatric oncology patients up to 14 years old. Inductive and comparative thematic analysis was performed on focus group transcripts and qualitative interrater reliability integrated. Music can offer children a safe haven for internalizing a healthy self-image alongside patient identity. Music therapy can calm, relieve distress, promote supportive relationships, enable self-care, and inspire playful creativity, associated with "normalcy" and hope. Preferred music and music therapy should be available in pediatric oncology.

  9. Mild obstructive sleep apnoea: clinical relevance and approaches to management.

    Science.gov (United States)

    McNicholas, Walter T; Bonsignore, Maria R; Lévy, Patrick; Ryan, Silke

    2016-10-01

    Obstructive sleep apnoea is highly prevalent in the general population worldwide, especially in its mild form. Clinical manifestations correlate poorly with disease severity measured by the apnoea-hypopnoea index (AHI), which complicates diagnosis. Full polysomnography might be more appropriate to assess suspected mild cases because limited ambulatory diagnostic systems are least accurate in mild disease. Treatment options in mild obstructive sleep apnoea include continuous positive airway pressure (CPAP) and oral appliance therapy, in addition to positional therapy and weight reduction when appropriate. The superior efficacy of CPAP in reducing AHI is offset by greater tolerance of oral appliances, especially in mild disease. Although severe obstructive sleep apnoea is associated with adverse health consequences, including cardiometabolic comorbidities, the association with mild disease is unclear, and reports differ regarding the clinical relevance of mild obstructive sleep apnoea. Improved diagnostic techniques and evidence-based approaches to management in mild obstructive sleep apnoea require further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Making the history of psychology clinically and philosophically relevant.

    Science.gov (United States)

    Vande Kemp, Hendrika

    2002-08-01

    The author discusses ways to make the history of psychology course relevant for a clinical psychology doctoral program within a multidenominational Protestant theological seminary. She uses a personalist orientation to emphasize the need to integrate psychology, philosophy, and theology. She differentiates among the intrapersonal, interpersonal, impersonal, and transpersonal dimensions of experience. She illustrates the rich multidisciplinary historical roots of contemporary psychology by tracing the the history of the term psychology and examining its meanings in the existential psychology of Søren Kierkegaard and in the 19th-century novel. She includes brief histories of the "new psychology" and of the unconscious. She describes how she uses the field of psychotheological integration to illustrate principles of historiography and summarizes resources used to supplement traditional textbooks.

  11. A review of potential factors relevant to coping in patients with advanced cancer

    DEFF Research Database (Denmark)

    Thomsen, Thora G.; Rydahl-Hansen, Susan; Wagner, Lis

    2010-01-01

    The aim was to identify characteristics that are considered to describe coping in patients with advanced cancer, as seen from a patient perspective. Based on the identified characteristics, the second aim was to identify potential factors that are relevant to coping in patients with advanced cancer....

  12. Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Britten, Richard A.; Evans, Andrew J.; Allalunis-Turner, M. Joan; Pearcey, Robert G.

    1996-01-01

    Purpose: To evaluate the effect of clinically relevant levels of cisplatin on the radiosensitivity of human cervical tumor cells, and to estimate what changes in local control rates might be expected to accrue from the concomitant use of cisplatin during fractionated radiotherapy. Methods and Materials: The effects of concomitant cisplatin (1 μg/ml, a typical intratumor concentration) on the clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF 2 ) values, was determined in 19 cloned human cervical tumor cell lines. These early passage cell lines had SF 2 values ranging from 0.26 to 0.87. Results: The concomitant administration of cisplatin reduced the clinically relevant radiosensitivity in the majority (11 out of 19) of the human tumor cell lines investigated. In only 4 out of 19 was any radiosensitization observed, and in 4 out of 19 cell lines there was no significant change in radiosensitivity. However, the sum of the independent cell killing by radiation and cisplatin, was approximately twofold higher than after radiation alone. There was no apparent dependence of the cisplatin-induced changes in SF 2 values upon the level of cell killing by cisplatin. However, there is a suggestion that concomitant cisplatin administration may have a differential effect in inherently radiosensitive and resistant human tumor cell lines. Conclusions: Our data suggest that concomitant cisplatin/radiotherapy regimens may result in a higher level of local tumor control, but primarily through additive toxicity and not through radiosensitization. Future improvements in local tumor control may, thus, be derived by increasing the total dose of cisplatin

  13. Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention

    DEFF Research Database (Denmark)

    Henriksen, N A; Meyhoff, C S; Wetterslev, J

    2010-01-01

    Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant (C...... a suitable standard definition for monitoring and identifying SSI, even if some cases of less clinically significant superficial SSI are included.......Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant...... hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant...

  14. Whole-Exome Sequencing Reveals Clinically Relevant Variants in Family Affected with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Jiaxiu Zhou

    2016-10-01

    Full Text Available Chromosomal microarray (CMA has been suggested as a first tier clinical diagnostic test for ASD. High-throughput sequencing (HTS has associated hundreds of genes associated with ASD. Whole Exome Sequencing (WES was used in combination with CMA to identify clinically-relevant ASD variants. In prior work, a trio-based (father, mother, and proband WGS (Whole Genome Sequencing was used to reveal clinically-relevant de novo, or inherited, rare variants in half (16 / 32 of the ASD families in which all probands had normal, or VOUS (Variant of Uncertain Clinical Significance, CMA results. In this study, after CMA screening chromosome structural abnormalities of a proband affected with ASD, a WES was performed on the patient and parents. Some rare de novo, and inherited, variants were detected using trio-based bioinformatics analysis. ASD variants were ranked by SFARI Gene score, HPO (human phenotype ontology, protein function damage, and manual searching PubMed. Sanger sequencing was used to validated some candidate variants in family members. A de novo homozygous mutation in SPG11 (p.C209F, two inherited, compound-heterozygote mutations in SCN9A (p.Q10R and p.R1893H and BEST1 (p.A135V and p.A297V were confirmed. Heterozygous mutations in TSC1 (p.S487C and SHANK2 (p.Arg569His inherited from mother were also confirmed.

  15. Online drug databases: a new method to assess and compare inclusion of clinically relevant information.

    Science.gov (United States)

    Silva, Cristina; Fresco, Paula; Monteiro, Joaquim; Rama, Ana Cristina Ribeiro

    2013-08-01

    Evidence-Based Practice requires health care decisions to be based on the best available evidence. The model "Information Mastery" proposes that clinicians should use sources of information that have previously evaluated relevance and validity, provided at the point of care. Drug databases (DB) allow easy and fast access to information and have the benefit of more frequent content updates. Relevant information, in the context of drug therapy, is that which supports safe and effective use of medicines. Accordingly, the European Guideline on the Summary of Product Characteristics (EG-SmPC) was used as a standard to evaluate the inclusion of relevant information contents in DB. To develop and test a method to evaluate relevancy of DB contents, by assessing the inclusion of information items deemed relevant for effective and safe drug use. Hierarchical organisation and selection of the principles defined in the EGSmPC; definition of criteria to assess inclusion of selected information items; creation of a categorisation and quantification system that allows score calculation; calculation of relative differences (RD) of scores for comparison with an "ideal" database, defined as the one that achieves the best quantification possible for each of the information items; pilot test on a sample of 9 drug databases, using 10 drugs frequently associated in literature with morbidity-mortality and also being widely consumed in Portugal. Main outcome measure Calculate individual and global scores for clinically relevant information items of drug monographs in databases, using the categorisation and quantification system created. A--Method development: selection of sections, subsections, relevant information items and corresponding requisites; system to categorise and quantify their inclusion; score and RD calculation procedure. B--Pilot test: calculated scores for the 9 databases; globally, all databases evaluated significantly differed from the "ideal" database; some DB performed

  16. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

    Science.gov (United States)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

    2013-02-01

    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  17. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    OpenAIRE

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

    2015-01-01

    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  18. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  19. Clinically relevant magnetic resonance imaging (MRI findings in elite swimmers’ shoulders

    Directory of Open Access Journals (Sweden)

    Arno Celliers

    2017-01-01

    Objective: To assess clinically relevant MRI findings in the shoulders of symptomatic and asymptomatic elite swimmers. Method: Twenty (aged 16–23 years elite swimmers completed questionnaires on their swimming training, pain and shoulder function. MRI of both shoulders (n = 40 were performed and all swimmers were given a standardised clinical shoulder examination. Results: Both shoulders of 11 male and 9 female elite swimmers (n = 40 were examined. Eleven of the 40 shoulders were clinically symptomatic and 29 were asymptomatic. The most common clinical finding in both the symptomatic and asymptomatic shoulders was impingement during internal rotation, with impingement in 54.5% of the symptomatic shoulders and in 31.0% of the asymptomatic shoulders. The most common MRI findings in the symptomatic and asymptomatic shoulders were supraspinatus tendinosis (45.5% vs. 20.7%, subacromial subdeltoid fluid (45.5% vs. 34.5%, increased signal in the AC Joint (45.5% vs. 37.9% and AC joint arthrosis (36.4% vs. 34.5%. Thirty-nine (97.5% of the shoulders showed abnormal MRI features. Conclusion: MRI findings in the symptomatic and asymptomatic shoulders of young elite swimmers are similar and care should be taken when reporting shoulder MRIs in these athletes. Asymptomatic shoulders demonstrate manifold MRI abnormalities that may be radiologically significant but appear not to be clinically significant.

  20. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

    International Nuclear Information System (INIS)

    Choesmel, Valérie; Pierga, Jean-Yves; Nos, Claude; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Thiery, Jean-Paul; Blin, Nathalie

    2004-01-01

    Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. These improved methods for the detection of

  1. [Enduring relevance. An introduction to the clinical contributions of K. R. Eissler].

    Science.gov (United States)

    Garcia, Emanuel E

    2007-01-01

    The author offers a personal selection and discussion of papers that epitomize the enduring relevance of Eissler's contributions to psychoanalytic therapy. The innovations of technique embodied by these works (on parameters, schizophrenia, adolescence, cure, fees, and the treatment of the dying patient) reveal a therapeutic approach that is a natural extension of psychoanalytic science: patient-centered, maximally comprehensive and appropriately flexible. Firsthand observations of Eissler's clinical manner and a selected bibliography are also presented.

  2. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Epigenetics in prostate cancer: biologic and clinical relevance.

    Science.gov (United States)

    Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

    2011-10-01

    Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

    Coldwell, Kate E; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2008-09-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  5. Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD Symptoms and PTSD Symptom Profiles in Military Personnel.

    Science.gov (United States)

    Martin, Christiana; Cho, Young-Eun; Kim, Hyungsuk; Yun, Sijung; Kanefsky, Rebekah; Lee, Hyunhwa; Mysliwiec, Vincent; Cashion, Ann; Gill, Jessica

    2018-05-01

    Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6). Symptom measures were obtained, and genome-wide DNA methylation was measured using methylated DNA immunoprecipitation (MeDIP-seq) from whole blood samples at baseline and 3 months later. A longitudinal comparison measured DNA methylation changes in military personnel with clinically relevant increases in PTSD symptoms between time points (PTSD onset) and compared methylation patterns to controls with no clinical changes in PTSD. In military personnel with elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD-onset group relate to the canonical pathways of netrin signaling, Wnt/Ca + pathway, and axonal guidance signaling. These gene pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.

  6. Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

    Science.gov (United States)

    Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

    2018-06-01

    Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

  7. Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study

    Directory of Open Access Journals (Sweden)

    Clare L. van Halsema

    2015-01-01

    Full Text Available Background. The clinical relevance of nontuberculous mycobacteria (NTM, detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Results. Of 232 individuals included (228 (98% male, median age 44 years, M. gordonae (60 individuals, M. kansasii (50, and M. avium complex (MAC: 38 were the commonest species. Of 38 MAC isolates, only 2 (5.3% were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77% among those tested. No differences were found in probability of death or medical separation by NTM species. Conclusions. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment.

  8. Two clinically relevant pressures of carbon dioxide pneumoperitoneum cause hepatic injury in a rabbit model

    OpenAIRE

    Li, Jun; Liu, Ying-Hai; Ye, Zhan-Yong; Liu, He-Nian; Ou, Shan; Tian, Fu-Zhou

    2011-01-01

    AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum (CDP) in rabbits, compare the effects of low- and high-pressure pneumoperitoneum, and to determine the degree of hepatic injury induced by these two clinically relevant CDP pressures.

  9. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  10. Clinical relevance of comorbidity in anxiety disorders: A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Klein Hofmeijer-Sevink, M.; Batelaan, N.M.; van Megen, H.J.G.M.; Penninx, B.W.J.H.; Cath, D.C.; van Hout, M.A.; van Balkom, A.J.L.M.

    2012-01-01

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  11. Chiral drug analysis using mass spectrometric detection relevant to research and practice in clinical and forensic toxicology.

    Science.gov (United States)

    Schwaninger, Andrea E; Meyer, Markus R; Maurer, Hans H

    2012-12-21

    This paper reviews analytical approaches published in 2002-2012 for chiral drug analysis and their relevance in research and practice in the field of clinical and forensic toxicology. Separation systems such as gas chromatography, high performance liquid chromatography, capillary electromigration, and supercritical fluid chromatography, all coupled to mass spectrometry, are discussed. Typical applications are reviewed for relevant chiral analytes such as amphetamines and amphetamine-derived designer drugs, methadone, tramadol, psychotropic and other CNS acting drugs, anticoagulants, cardiovascular drugs, and some other drugs. Usefulness of chiral drug analysis in the interpretation of analytical results in clinical and forensic toxicology is discussed as well. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Combining radiotherapy and ipilimumab induces clinically relevant radiation-induced abscopal effects in metastatic melanoma patients: A systematic review

    Directory of Open Access Journals (Sweden)

    Rodolfo Chicas-Sett

    2018-02-01

    Conclusion: Early clinical outcomes reports suggest that the combination of ipilimumab and RT may improve survival in metastatic melanoma patients. The abscopal responses become a clinically relevant effect of such combination and should be studied in controlled randomized trials.

  13. Paediatric case mix in a rural clinical school is relevant to future practice.

    Science.gov (United States)

    Wright, Helen M; Maley, Moira A L; Playford, Denese E; Nicol, Pam; Evans, Sharon F

    2017-11-29

    Exposure to a representative case mix is essential for clinical learning, with logbooks established as a way of demonstrating patient contacts. Few studies have reported the paediatric case mix available to geographically distributed students within the same medical school. Given international interest in expanding medical teaching locations to rural contexts, equitable case exposure in rural relative to urban settings is topical. The Rural Clinical School of Western Australia locates students up to 3500 km from the urban university for an academic year. There is particular need to examine paediatric case mix as a study reported Australian graduates felt unprepared for paediatric rotations. We asked: Does a rural clinical school provide a paediatric case mix relevant to future practice? How does the paediatric case mix as logged by rural students compare with that by urban students? The 3745 logs of 76 urban and 76 rural consenting medical students were categorised by presenting symptoms and compared to the Australian Institute of Health and Welfare (AIHW) database Major Diagnostic Categories (MDCs). Rural and urban students logged core paediatric cases, in similar order, despite the striking difference in geographic locations. The pattern of overall presenting problems closely corresponded to Australian paediatric hospital admissions. Rural students logged 91% of cases in secondary healthcare settings; urban students logged 90% of cases in tertiary settings. The top four presenting problems were ENT/respiratory, gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made up 60% of all cases. Rural and urban students logged similar proportions of infants, children and adolescents, with a variety of case morbidity. Rural clinical school students logged a mix of core paediatric cases relevant to illnesses of Australian children admitted to public hospitals, with similar order and pattern by age group to urban students, despite major differences

  14. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

    Directory of Open Access Journals (Sweden)

    Francesco Celandroni

    Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  15. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Michelle Millington

    2009-07-01

    Full Text Available Hematopoietic stem cells (HSC, in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multi-potency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34(+ HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin.Using commercially available G-CSF mobilized peripheral blood (PB CD34(+ cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, pre-stimulation time, multiplicity of infection (MOI, transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV carrying enhanced green fluorescent protein (GFP was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin.This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34(+ cells.

  16. The efficacy of chiropractic manipulation for back pain : Blinded review of relevant randomized clinical trials

    NARCIS (Netherlands)

    Assendelft, W. J J; Koes, B. W.; Van der Heijden, G. J M G; Bouter, L. M.

    1992-01-01

    Objective: To assess the efficacy of chiropractic for patients with back pain. Data Sources: Randomized clinical trials (RCTs) on spinal manipulation were identified with a Medline search (1966-1990), by citation tracking, and by manual examination of the relevant chiropractic reference systems

  17. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.

    2007-01-01

    of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

  18. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    Directory of Open Access Journals (Sweden)

    Hillebrands Jan-Luuk

    2008-10-01

    Full Text Available Abstract Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  19. A rule-based electronic phenotyping algorithm for detecting clinically relevant cardiovascular disease cases.

    Science.gov (United States)

    Esteban, Santiago; Rodríguez Tablado, Manuel; Ricci, Ricardo Ignacio; Terrasa, Sergio; Kopitowski, Karin

    2017-07-14

    The implementation of electronic medical records (EMR) is becoming increasingly common. Error and data loss reduction, patient-care efficiency increase, decision-making assistance and facilitation of event surveillance, are some of the many processes that EMRs help improve. In addition, they show a lot of promise in terms of data collection to facilitate observational epidemiological studies and their use for this purpose has increased significantly over the recent years. Even though the quantity and availability of the data are clearly improved thanks to EMRs, still, the problem of the quality of the data remains. This is especially important when attempting to determine if an event has actually occurred or not. We sought to assess the sensitivity, specificity, and agreement level of a codes-based algorithm for the detection of clinically relevant cardiovascular (CaVD) and cerebrovascular (CeVD) disease cases, using data from EMRs. Three family physicians from the research group selected clinically relevant CaVD and CeVD terms from the international classification of primary care, Second Edition (ICPC-2), the ICD 10 version 2015 and SNOMED-CT 2015 Edition. These terms included both signs, symptoms, diagnoses and procedures associated with CaVD and CeVD. Terms not related to symptoms, signs, diagnoses or procedures of CaVD or CeVD and also those describing incidental findings without clinical relevance were excluded. The algorithm yielded a positive result if the patient had at least one of the selected terms in their medical records, as long as it was not recorded as an error. Else, if no terms were found, the patient was classified as negative. This algorithm was applied to a randomly selected sample of the active patients within the hospital's HMO by 1/1/2005 that were 40-79 years old, had at least one year of seniority in the HMO and at least one clinical encounter. Thus, patients were classified into four groups: (1) Negative patients (2) Patients with Ca

  20. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?

    Science.gov (United States)

    Mouly, Stéphane; Lloret-Linares, Célia; Sellier, Pierre-Olivier; Sene, Damien; Bergmann, J-F

    2017-04-01

    An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Phospholipase A1-based cross-reactivity among venoms of clinically relevant Hymenoptera from Neotropical and temperate regions.

    Science.gov (United States)

    Perez-Riverol, Amilcar; Fernandes, Luís Gustavo Romani; Musacchio Lasa, Alexis; Dos Santos-Pinto, José Roberto Aparecido; Moitinho Abram, Débora; Izuka Moraes, Gabriel Hideki; Jabs, Frederic; Miehe, Michaela; Seismman, Henning; Palma, Mario Sergio; de Lima Zollner, Ricardo; Spillner, Edzard; Brochetto-Braga, Márcia Regina

    2018-01-01

    Molecular cross-reactivity caused by allergen homology or cross-reactive carbohydrate determinants (CCDs) is a major challenge for diagnosis and immunotherapy of insect venom allergy. Venom phospholipases A1 (PLA1s) are classical, mostly non-glycosylated wasp and ant allergens that provide diagnostic benefit for differentiation of genuine sensitizations from cross-reactivity. As CCD-free molecules, venom PLA1s are not causative for CCD-based cross-reactivity. Little is known however about the protein-based cross-reactivity of PLA1 within vespid species. Here, we address PLA1-based cross-reactivity among ten clinically relevant Hymenoptera venoms from Neotropical and temperate regions including Polybia paulista (paulistinha) venom and Vespula vulgaris (yellow jacket) venom. In order to evaluate cross-reactivity, sera of mice sensitized with recombinant PLA1 (rPoly p 1) from P. paulista wasp venom were used. Pronounced IgE and IgG based cross-reactivity was detected for wasp venoms regardless the geographical region of origin. The cross-reactivity correlated well with the identity of the primary sequence and 3-D models of PLA1 proteins. In contrast, these mice sera showed no reaction with honeybee (HBV) and fire ant venom. Furthermore, sera from patients monosensitized to HBV and fire ants did not recognize the rPoly p 1 in immunoblotting. Our findings reveal the presence of conserved epitopes in the PLA1s from several clinically relevant wasps as major cause of PLA1-based in vitro cross-reactivity. These findings emphasize the limitations but also the potential of PLA1-based HVA diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Self-esteem modulates automatic attentional responses to self-relevant stimuli: evidence from event-related brain potentials

    OpenAIRE

    Chen, Jie; Shui, Qing; Zhong, Yiping

    2015-01-01

    Previous studies have widely shown that self-esteem modulates the attention bias towards social rejection or emotion-related information. However, little is known about the influences of self-esteem on attention bias towards self-relevant stimuli. We aimed to investigate neural correlates that underlie the modulation effect of self-esteem on self-relevant processing. Event-related potentials (ERP) were recorded for subjects’ own names and close others’ names (the names of their friends) while...

  3. Clinically applied medical ethnography: relevance to cultural competence in patient care.

    Science.gov (United States)

    Engebretson, Joan

    2011-06-01

    Medical anthropology provides an excellent resource for nursing research that is relevant to clinical nursing. By expanding the understanding of ethnographic research beyond ethnicity, nurses can conduct research that explores patient's constructions and explanatory models of health and healing and how they make meaning out of chronic conditions and negotiate daily life. These findings can have applicability to culturally competent care at both the organizational or systems level, as well as in the patient/provider encounter. Individual patient care can be improved by applying ethnographic research findings to build provider expertise and then using a cultural negotiation process for individualized patient care. Copyright © 2011. Published by Elsevier Inc.

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

    Science.gov (United States)

    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.

  5. The potential relevance of cognitive neuroscience for the development and use of technology-enhanced learning

    NARCIS (Netherlands)

    Howard-Jones, Paul; Ott, Michela; van Leeuwen, Theo; De Smedt, Bert

    2015-01-01

    There is increasing interest in the application of cognitive neuroscience in educational thinking and practice, and here we review findings from neuroscience that demonstrate its potential relevance to technology-enhanced learning (TEL). First, we identify some of the issues in integrating

  6. Rotational patient setup errors in IGRT with XVI system in Elekta Synergy and their clinical relevance

    International Nuclear Information System (INIS)

    Madhusudhana Sresty, N.V.N.; Muralidhar, K.R.; Raju, A.K.; Sha, R.L.; Ramanjappa

    2008-01-01

    The goal of Image Guided Radiotherapy (IGRT) is to improve the accuracy of treatment delivery. In this technique, it is possible to get volumetric images of patient anatomy before delivery of treatment.XVI( release 3.5) system in Elekta Synergy linear accelerator (Elekta,Crawley,UK) has the potential to ensure that, the relative positions of the target volume is same as in the treatment plan. It involves acquiring planar images produced by a kilo Voltage cone beam rotating about the patient in the treatment position. After 3 dimensional match between reference and localization images, the system gives rotational errors also along with translational shifts. One can easily perform translational shifts with treatment couch. But rotational shifts cannot be performed. Most of the studies dealt with translational shifts only. Few studies reported regarding rotational errors. It is found that in the treatment of elongated targets, even small rotational errors can show difference in results. The main objectives of this study is 1) To verify the magnitude of rotational errors in different clinical sites observed and to compare with the other reports. 2) To find its clinical relevance 3) To find difference in rotational shift results with improper selection of kV collimator

  7. Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis.

    Science.gov (United States)

    Liu, Xuan; Jiang, Hui

    2017-12-04

    Biosensors for proteins have shown attractive advantages compared to traditional techniques in clinical laboratory diagnosis. In virtue of modern fabrication modes and detection techniques, various immunosensing platforms have been reported on basis of the specific recognition between antigen-antibody pairs. In addition to profit from the development of nanotechnology and molecular biology, diverse fabrication and signal amplification strategies have been designed for detection of protein antigens, which has led to great achievements in fast quantitative and simultaneous testing with extremely high sensitivity and specificity. Besides antigens, determination of antibodies also possesses great significance for clinical laboratory diagnosis. In this review, we will categorize recent immunosensors for proteins by different detection techniques. The basic conception of detection techniques, sensing mechanisms, and the relevant signal amplification strategies are introduced. Since antibodies and antigens have an equal position to each other in immunosensing, all biosensing strategies for antigens can be extended to antibodies under appropriate optimizations. Biosensors for antibodies are summarized, focusing on potential applications in clinical laboratory diagnosis, such as a series of biomarkers for infectious diseases and autoimmune diseases, and an evaluation of vaccine immunity. The excellent performances of these biosensors provide a prospective space for future antibody-detection-based disease serodiagnosis.

  8. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    OpenAIRE

    Vriends, Noortje; Pfaltz, Monique C.; Novianti, Peppy; Hadiyono, Johana

    2013-01-01

    Background: Taijin Kyofusho (TKS) is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-constr...

  9. Taijin Kyofusho and Social Anxiety and Their Clinical Relevance in Indonesia and Switzerland

    OpenAIRE

    Vriends, N.; Pfaltz, M. C.; Novianti, P.; Hadiyono, J.

    2013-01-01

    Background: Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-cons...

  10. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    OpenAIRE

    Noortje eVriends; Noortje eVriends; Monique C Pfaltz; Peppy eNovianti; Johana eHadiyono

    2013-01-01

    Background: Taijin Kyofusho (TKS) is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-const...

  11. Isolation, speciation, and antibiogram of clinically relevant non-diphtherial Corynebacteria (Diphtheroids

    Directory of Open Access Journals (Sweden)

    B S Reddy

    2012-01-01

    Full Text Available Purpose: Coryneform or the non-diphtherial Corynebacterium species largely remains a neglected group with the traditional consideration of these organisms as contaminants. This concept, however, is slowly changing in the light of recent observations. This study has been done to find out the species distribution and antibiogram of various members of the clinically relevant Coryneform group, isolated from various clinical materials. Materials and Methods: One hundred and fourteen non-duplicate isolates of diphtheroids from various clinical isolates were selected for the study. The isolates were identified to the species level by using a battery of tests; and antimicrobial susceptibility was tested by using a combination of Clinical and Laboratory Standards Institute (CLSI and the British Society for Antimicrobial Chemotherapy (BSAC guidelines, in the absence of definitive CLSI guidelines. Results: Corynebacterium amycolatum was the predominant species (35.9% in our series followed by the CDC Group G organisms (15.7%. Each of the remaining 19 species comprised of less than 10% of the isolates. More than half the total isolates were resistant to the penicillins, erythromycin, and clindamycin; while excellent activity (all the strains being susceptible was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol and tetracycline also had good activity in inhibiting more than 80% of the isolates. Multiply drug resistance was exhibited by all the species. Conclusion: This study was an attempt to establish the clinical significance of coryneform organisms. The high level of resistance shown by this group to some of the common antibacterial agents highlights the importance of processing these isolates in select conditions to guide the clinicians towards an appropriate therapy.

  12. Presence and Persistence of Viable, Clinically Relevant Legionella pneumophila Bacteria in Garden Soil in the Netherlands

    Science.gov (United States)

    van Heijnsbergen, E.; van Deursen, A.; Bouwknegt, M.; Bruin, J. P.; Schalk, J. A. C.

    2016-01-01

    ABSTRACT Garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. Legionella bacteria were detected in 22 of 177 garden soil samples (12%) by amoebal coculture. Of these 22 Legionella-positive soil samples, seven contained Legionella pneumophila. Several other species were found, including the pathogenic Legionella longbeachae (4 gardens) and Legionella sainthelensi (9 gardens). The L. pneumophila isolates comprised 15 different sequence types (STs), and eight of these STs were previously isolated from patients according to the European Working Group for Legionella Infections (EWGLI) database. Six gardens that were found to be positive for L. pneumophila were resampled after several months, and in three gardens, L. pneumophila was again isolated. One of these gardens was resampled four times throughout the year and was found to be positive for L. pneumophila on all occasions. IMPORTANCE Tracking the source of infection for sporadic cases of Legionnaires' disease (LD) has proven to be hard. L. pneumophila ST47, the sequence type that is most frequently isolated from LD patients in the Netherlands, is rarely found in potential environmental sources. As L. pneumophila ST47 was previously isolated from a garden soil sample during an outbreak investigation, garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. The detection of viable, clinically relevant Legionella strains indicates that garden soil is a potential source of Legionella bacteria, and future research should assess the public health implication of the presence of L. pneumophila in garden soil. PMID:27316958

  13. Presence and Persistence of Viable, Clinically Relevant Legionella pneumophila Bacteria in Garden Soil in the Netherlands.

    Science.gov (United States)

    van Heijnsbergen, E; van Deursen, A; Bouwknegt, M; Bruin, J P; de Roda Husman, A M; Schalk, J A C

    2016-09-01

    Garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. Legionella bacteria were detected in 22 of 177 garden soil samples (12%) by amoebal coculture. Of these 22 Legionella-positive soil samples, seven contained Legionella pneumophila Several other species were found, including the pathogenic Legionella longbeachae (4 gardens) and Legionella sainthelensi (9 gardens). The L. pneumophila isolates comprised 15 different sequence types (STs), and eight of these STs were previously isolated from patients according to the European Working Group for Legionella Infections (EWGLI) database. Six gardens that were found to be positive for L. pneumophila were resampled after several months, and in three gardens, L. pneumophila was again isolated. One of these gardens was resampled four times throughout the year and was found to be positive for L. pneumophila on all occasions. Tracking the source of infection for sporadic cases of Legionnaires' disease (LD) has proven to be hard. L. pneumophila ST47, the sequence type that is most frequently isolated from LD patients in the Netherlands, is rarely found in potential environmental sources. As L. pneumophila ST47 was previously isolated from a garden soil sample during an outbreak investigation, garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. The detection of viable, clinically relevant Legionella strains indicates that garden soil is a potential source of Legionella bacteria, and future research should assess the public health implication of the presence of L. pneumophila in garden soil. Copyright © 2016 van Heijnsbergen et al.

  14. Patient-reported symptoms during radiotherapy : Clinically relevant symptom burden in patients treated with palliative and curative intent.

    Science.gov (United States)

    Körner, Philipp; Ehrmann, Katja; Hartmannsgruber, Johann; Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael; van Oorschot, Birgitt

    2017-07-01

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom

  15. Patient-reported symptoms during radiotherapy. Clinically relevant symptom burden in patients treated with palliative and curative intent

    International Nuclear Information System (INIS)

    Koerner, Philipp; Ehrmann, Katja; Hartmannsgruber, Johann; Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael; Oorschot, Birgitt van

    2017-01-01

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom burden

  16. Evaluation of exome filtering techniques for the analysis of clinically relevant genes.

    Science.gov (United States)

    Kernohan, Kristin D; Hartley, Taila; Alirezaie, Najmeh; Robinson, Peter N; Dyment, David A; Boycott, Kym M

    2018-02-01

    A significant challenge facing clinical translation of exome sequencing is meaningful and efficient variant interpretation. Each exome contains ∼500 rare coding variants; laboratories must systematically and efficiently identify which variant(s) contribute to the patient's phenotype. In silico filtering is an approach that reduces analysis time while decreasing the chances of incidental findings. We retrospectively assessed 55 solved exomes using available datasets as in silico filters: Online Mendelian Inheritance in Man (OMIM), Orphanet, Human Phenotype Ontology (HPO), and Radboudumc University Medical Center curated panels. We found that personalized panels produced using HPO terms for each patient had the highest success rate (100%), while producing considerably less variants to assess. HPO panels also captured multiple diagnoses in the same individual. We conclude that custom HPO-derived panels are an efficient and effective way to identify clinically relevant exome variants. © 2017 Wiley Periodicals, Inc.

  17. The Intestinal Microbiome in Infectious Diseases: The Clinical Relevance of a Rapidly Emerging Field

    NARCIS (Netherlands)

    Harris, Vanessa C.; Haak, Bastiaan W.; Boele van Hensbroek, Michaël; Wiersinga, Willem J.

    2017-01-01

    The field of infectious disease is undergoing a paradigm shift as the intestinal microbiome is becoming understood. The aim of this review is to inform infectious disease physicians of the potential relevance of the intestinal microbiome to their practice. We searched Medline using both index and

  18. Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

    International Nuclear Information System (INIS)

    Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner; Feuchtner, Gudrun M.

    2010-01-01

    Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm 2 ) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm 2 ) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p 2 aortic valve orifice area. Conclusions: The interpretation of extracoronary findings on CCTA scans is mandatory given high prevalence of clinically significant findings by using a full 'thoracic' FOV.

  19. Polanyi's tacit knowing and the relevance of epistemology to clinical medicine.

    Science.gov (United States)

    Henry, Stephen G

    2010-04-01

    Most clinicians take for granted a simple, reductionist understanding of medical knowledge that is at odds with how they actually practice medicine; routine medical decisions incorporate more complicated kinds of information than most standard accounts of medical reasoning suggest. A better understanding of the structure and function of knowledge in medicine can lead to practical improvements in clinical medicine. This understanding requires some familiarity with epistemology, the study of knowledge and its structure, in medicine. Michael Polanyi's theory of tacit knowing is advanced as the basis for developing a more accurate understanding of medical knowledge. Tacit knowing, which explores the taken-for-granted background knowledge that underlies all human knowing, is explained in detail with a focus on its relevance for clinical medicine. The implications of recognizing tacit knowing in medicine and medical decisions are discussed. These include the ability to explain the importance of the clinical encounter in medical practice, mechanisms for analysing patient and doctor as persons, and the need for humility given the uncertainty that the tacit dimension injects into all medical decisions. This more robust medical epistemology allows clinicians to better articulate the nature and importance of patient-centred care, to avoid pitfalls inherent in reductionist approaches to medical knowledge, and to think more clearly about the relationships between medicine and health care at the individual and population levels.

  20. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance.

    Science.gov (United States)

    De Win, Maartje M L; Jager, Gerry; Vervaeke, Hylke K E; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C; Den Heeten, Gerard J; Ramsey, Nick F; Korf, Dirk J; Van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin axons, but most of these studies have serious methodological limitations. The current study is a combination of different approaches with three substudies: (1) a crosssectional substudy among heavy ecstasy users and controls with variation in drug use, which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs; (2) a prospective cohort substudy in ecstasy-naive subjects with high risk for future ecstasy use, which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity, and (3) a retrospective cohort substudy in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population. Neurotoxicity is studied using (a) different imaging techniques (beta-CIT SPECT, 1H-MR spectroscopy, diffusion tensor imaging, perfusion weighted imaging and functional magnetic resonance imaging), and (b) neuropsychological and psychiatric assessments of memory, depression, and personality. The combined results will lead to conclusions that can be used in prevention messages, clinical decision making, and the development of an (inter)national ecstasy policy.

  1. A Bridge between Two Cultures: Uncovering the Chemistry Concepts Relevant to the Nursing Clinical Practice

    Science.gov (United States)

    Brown, Corina E.; Henry, Melissa L. M.; Barbera, Jack; Hyslop, Richard M.

    2012-01-01

    This study focused on the undergraduate course that covers basic topics in general, organic, and biological (GOB) chemistry at a mid-sized state university in the western United States. The central objective of the research was to identify the main topics of GOB chemistry relevant to the clinical practice of nursing. The collection of data was…

  2. Vitamin E-drug interactions: molecular basis and clinical relevance.

    Science.gov (United States)

    Podszun, Maren; Frank, Jan

    2014-12-01

    Vitamin E (α-, β-, γ- and δ-tocopherol and -tocotrienol) is an essential factor in the human diet and regularly taken as a dietary supplement by many people, who act under the assumption that it may be good for their health and can do no harm. With the publication of meta-analyses reporting increased mortality in persons taking vitamin E supplements, the safety of the micronutrient was questioned and interactions with prescription drugs were suggested as one potentially underlying mechanism. Here, we review the evidence in the scientific literature for adverse vitamin E-drug interactions and discuss the potential of each of the eight vitamin E congeners to alter the activity of drugs. In summary, there is no evidence from animal models or randomised controlled human trials to suggest that the intake of tocopherols and tocotrienols at nutritionally relevant doses may cause adverse nutrient-drug interactions. Consumption of high-dose vitamin E supplements ( ≥  300 mg/d), however, may lead to interactions with the drugs aspirin, warfarin, tamoxifen and cyclosporine A that may alter their activities. For the majority of drugs, however, interactions with vitamin E, even at high doses, have not been observed and are thus unlikely.

  3. The Potential Relevance of Cognitive Neuroscience for the Development and Use of Technology-Enhanced Learning

    Science.gov (United States)

    Howard-Jones, Paul; Ott, Michela; van Leeuwen, Theo; De Smedt, Bert

    2015-01-01

    There is increasing interest in the application of cognitive neuroscience in educational thinking and practice, and here we review findings from neuroscience that demonstrate its potential relevance to technology-enhanced learning (TEL). First, we identify some of the issues in integrating neuroscientific concepts into TEL research. We caution…

  4. [The relevance of clinical risk management].

    Science.gov (United States)

    Gulino, Matteo; Vergallo, Gianluca Montanari; Frati, Paola

    2011-01-01

    Medical activity includes a risk of possible injury or complications for the patients, that should drive the Health Care Institutions to introduce and/ or improve clinical Risk management instruments. Although Italy is still lacking a National project of Clinical Risk Management, a number of efforts have been made by different Italian Regions to introduce instruments of risk management. In addition, most of National Health Care Institutions include actually a Department specifically in charge to manage the clinical risk. Despite the practical difficulties, the results obtained until now suggest that the risk management may represent a useful instrument to contribute to the reduction of errors in clinical conduct. Indeed, the introduction of adequate instruments of prevention and management of clinical risk may help to ameliorate the quality of health care Institution services.

  5. Prospective early detection of avascular necrosis of the femoral head with MR imaging in high-risk patients: Is it clinically relevant

    International Nuclear Information System (INIS)

    Von Schulthess, G.K.; Binswanger, U.

    1987-01-01

    To evaluate the clinical relevance of early detection of avascular necrosis (AVN) of the femoral head in a high-risk group, the authors performed MR imaging in 16 renal transplant patients receiving prednisone. Imaging was done at 3-month intervals over 8-24 months. Of the 15 patients remaining in the study (one underwent nephrectomy), two have shown clear MR imaging signs of early AVN persisting for 12 months without clinical symptoms. One patient had an abrupt onset of clinically relevant AVN before the second control MR imaging study was done. These results suggest that MR imaging may detect clinically irrelevant AVN, and that even short intervals between examinations may be too long to provide a warning of impending AVN

  6. Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

    Science.gov (United States)

    Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

    2017-11-01

    The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Clinical relevance of herpes simplex virus viremia in Intensive Care Unit patients.

    Science.gov (United States)

    Lepiller, Q; Sueur, C; Solis, M; Barth, H; Glady, L; Lefebvre, F; Fafi-Kremer, S; Schneider, F; Stoll-Keller, F

    2015-07-01

    To determine the clinical relevance of herpes simplex virus (HSV) viremia episodes in critically ill adult patients. 1556 blood samples obtained for HSV PCR analysis in Intensive Care Unit (ICU) patients over 4 years were retrospectively analyzed, focusing on the comprehensive analysis of 88 HSV-viremic patients. HSV DNA was detected in 11.8% of samples from the ICU. HSV viral loads remained below 5×10(2) copies/ml in 68.2% of patients and exceeded 10(4) copies/ml in 7.9%. Episodes of HSV-viremia correlated with immunosuppressed status and mechanical ventilation in 79.5% and 65.9% of patients, respectively. Only a subset of patients exhibited HSV-related organ damage, including pneumonia and hepatitis (10.2% and 2.3%, respectively). The mortality rate in HSV-viremic patients was not significantly increased compared to the overall mortality rate in the ICU (27.3% vs. 22.9%, p = 0.33). Only patients with high HSV viral loads tended to have a higher, though non-significant, death rate (57.1%, p = 0.14). Our results suggest HSV viremia is common in ICU patients, potentially favored by immunocompromised status and mechanical ventilation. The global impact of HSV-viremia on mortality in the ICU was low. Quantifying HSV DNA may help identifying patients at-risk of severe HSV-induced symptoms. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  8. Serumferritin - diagnostic relevance and clinical usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Linkesch, W [Vienna Univ. (Austria). 2. Medizinische Klinik

    1984-01-01

    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value one should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e.g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia.

  9. Serumferritin - diagnostic relevance and clinical usefulness

    International Nuclear Information System (INIS)

    Linkesch, W.

    1984-01-01

    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value on should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e. g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia. (Author)

  10. Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

    Science.gov (United States)

    Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

    2009-02-01

    With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

  11. SU-F-T-345: Quasi-Dead Beams: Clinical Relevance and Implications for Automatic Planning

    Energy Technology Data Exchange (ETDEWEB)

    Price, R; Veltchev, I; Lin, T; Gleason, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: Beam direction selection for fixed-beam IMRT planning is typically a manual process. Severe dose-volume limits on critical structures in the thorax often result in atypical selection of beam directions as compared to other body sites. This work demonstrates the potential consequences as well as clinical relevance. Methods: 21 thoracic cases treated with 5–7 beam directions, 6 cases including non-coplanar arrangements, with fractional doses of 150–411cGy were analyzed. Endpoints included per-beam modulation scaling factor (MSF), variation from equal weighting, and delivery QA passing rate. Results: During analysis of patient-specific delivery QA a sub-standard passing rate was found for a single 5-field plan (90.48% of pixels evaluated passing 3% dose, 3mm DTA). During investigation it was found that a single beam demonstrated a MSF of 34.7 and contributed only 2.7% to the mean dose of the target. In addition, the variation from equal weighting for this beam was 17.3% absolute resulting in another beam with a MSF of 4.6 contributing 41.9% to the mean dose to the target; a variation of 21.9% from equal weighting. The average MSF for the remaining 20 cases was 4.0 (SD 1.8) with an average absolute deviation of 2.8% from equal weighting (SD 3.1%). Conclusion: Optimization in commercial treatment planning systems typically results in relatively equally weighted beams. Extreme variation from this can result in excessively high MSFs (very small segments) and potential decreases in agreement between planned and delivered dose distributions. In addition, the resultant beam may contribute minimal dose to the target (quasi-dead beam); a byproduct being increased treatment time and associated localization uncertainties. Potential ramifications exist for automatic planning algorithms should they allow for user-defined beam directions. Additionally, these quasi-dead beams may be embedded in the libraries for model-based systems potentially resulting in inefficient

  12. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

    Science.gov (United States)

    2016-10-01

    aim 2: Evaluate a panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer...and sent to Genomic Health, Inc. for processing. Task 3: Analysis of scientific Aim 2: Evaluate a panel of four-kallikrein plasma-based markers to...site: FHCRC) PCA3 and the TMPRSS2:ERG fusion are prostate cancer-specific biomarkers that hold promise for stratifying risk in the setting of AS

  13. Time-driven activity-based costing in an outpatient clinic environment: development, relevance and managerial impact.

    Science.gov (United States)

    Demeere, Nathalie; Stouthuysen, Kristof; Roodhooft, Filip

    2009-10-01

    Healthcare managers are continuously urged to provide better patient services at a lower cost. To cope with these cost pressures, healthcare management needs to improve its understanding of the relevant cost drivers. Through a case study, we show how to perform a time-driven activity-based costing of five outpatient clinic's departments and provide evidence of the benefits of such an analysis.

  14. Clinically relevant pain relief with an ibuprofen-releasing foam dressing

    DEFF Research Database (Denmark)

    Fogh, Karsten; Andersen, Maibritt B; Bischoff-Mikkelsen, Morten

    2012-01-01

    The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary......) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p...... = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen...

  15. Promoting culturally competent chronic pain management using the clinically relevant continuum model.

    Science.gov (United States)

    Monsivais, Diane B

    2011-06-01

    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. What's New in the Medicine Cabinet?: A Panoramic Review of Clinically Relevant Information for the Busy Dermatologist.

    Science.gov (United States)

    Del Rosso, James Q; Zeichner, Joshua

    2014-01-01

    This article is the first in a periodic series of therapeutic topics with short reviews gleaned from major dermatology meetings, especially Scientific Poster Sessions, and is designed to provide information that may assist the readers in adapting information from the literature to their clinical practice. The topics covered in this issue are discussions of the clinical relevance of newer information about acne pathophysiology, acne in adult women, and topical corticosteroid spray formulations for chronic plaque psoriasis.

  17. Comparative transcriptional analysis of clinically relevant heat stress response in Clostridium difficile strain 630.

    Directory of Open Access Journals (Sweden)

    Nigel G Ternan

    Full Text Available Clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. In order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41 °C versus 37 °C in C. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. While the transcriptome was relatively resilient to the applied heat stress, we noted upregulation of classical heat shock genes including the groEL and dnaK operons in addition to other stress-responsive genes. Interestingly, the flagellin gene (fliC was downregulated, yet genes encoding the cell-wall associated flagellar components were upregulated suggesting that while motility may be reduced, adherence--to mucus or epithelial cells--could be enhanced during infection. We also observed that a number of phage associated genes were downregulated, as were genes associated with the conjugative transposon Tn5397 including a group II intron, thus highlighting a potential decrease in retromobility during heat stress. These data suggest that maintenance of lysogeny and genome wide stabilisation of mobile elements could be a global response to heat stress in this pathogen.

  18. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-05-01

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  19. The marine nitrogen cycle: recent discoveries, uncertainties and the potential relevance of climate change

    OpenAIRE

    Voss, Maren; Bange, Hermann W.; Dippner, Joachim W.; Middelburg, Jack J.; Montoya, Joseph P.; Ward, Bess

    2013-01-01

    The ocean's nitrogen cycle is driven by complex microbial transformations, including nitrogen fixation, assimilation, nitrification, anammox and denitrification. Dinitrogen is the most abundant form of nitrogen in sea water but only accessible by nitrogen-fixing microbes. Denitrification and nitrification are both regulated by oxygen concentrations and potentially produce nitrous oxide (N2O), a climate-relevant atmospheric trace gas. The world's oceans, including the coastal areas and upwelli...

  20. Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

    Energy Technology Data Exchange (ETDEWEB)

    Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria); Feuchtner, Gudrun M. [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria)], E-mail: Gudrun.Feuchtner@i-med.ac.at

    2010-04-15

    Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm{sup 2}) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm{sup 2}) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p < 0.001). The detection rate of clinically significant findings was higher by using full FOV compared to small FOV (25.6% versus 15.4%) (p < 0.001), out of those 2.2% versus 1.8% of findings required immediate actions (score 1), and 23.4% versus 13.6% (p = 0.0001), respectively were of clinical relevance (non-urgent, score 2). The rate of malign findings was 0.2%, and of acute pulmonary embolism 0.1%. More lung pathologies were observed by using full FOV compared to small FOV (22% versus 7%) (p < 0.0001), and the detection rate of

  1. Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms.

    Directory of Open Access Journals (Sweden)

    Ian Morrissey

    Full Text Available To date there are no clear criteria to determine whether a microbe is susceptible to biocides or not. As a starting point for distinguishing between wild-type and resistant organisms, we set out to determine the minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC distributions for four common biocides; triclosan, benzalkonium chloride, chlorhexidine and sodium hypochlorite for 3319 clinical isolates, with a particular focus on Staphylococcus aureus (N = 1635 and Salmonella spp. (N = 901 but also including Escherichia coli (N = 368, Candida albicans (N = 200, Klebsiella pneumoniae (N = 60, Enterobacter spp. (N = 54, Enterococcus faecium (N = 53, and Enterococcus faecalis (N = 56. From these data epidemiological cut-off values (ECOFFs are proposed. As would be expected, MBCs were higher than MICs for all biocides. In most cases both values followed a normal distribution. Bimodal distributions, indicating the existence of biocide resistant subpopulations were observed for Enterobacter chlorhexidine susceptibility (both MICs and MBCs and the susceptibility to triclosan of Enterobacter (MBC, E. coli (MBC and MIC and S. aureus (MBC and MIC. There is a concern on the potential selection of antibiotic resistance by biocides. Our results indicate however that resistance to biocides and, hence any potential association with antibiotic resistance, is uncommon in natural populations of clinically relevant microorganisms.

  2. Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

    Science.gov (United States)

    Sindhurakar, Anil; Mishra, Asht M; Gupta, Disha; Iaci, Jennifer F; Parry, Tom J; Carmel, Jason B

    2017-04-01

    4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

  3. Macrotrabecular-massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance.

    Science.gov (United States)

    Ziol, Marianne; Poté, Nicolas; Amaddeo, Giuliana; Laurent, Alexis; Nault, Jean-Charles; Oberti, Frédéric; Costentin, Charlotte; Michalak, Sophie; Bouattour, Mohamed; Francoz, Claire; Pageaux, Georges Philippe; Ramos, Jeanne; Decaens, Thomas; Luciani, Alain; Guiu, Boris; Vilgrain, Valérie; Aubé, Christophe; Derman, Jonathan; Charpy, Cécile; Zucman-Rossi, Jessica; Barget, Nathalie; Seror, Olivier; Ganne-Carrié, Nathalie; Paradis, Valérie; Calderaro, Julien

    2017-12-27

    We recently identified a novel histological subtype of hepatocellular carcinoma, designated as "macrotrabecular-massive" (MTM-HCC) and associated with specific molecular features. In order to assess the clinical relevance of this novel variant, we aimed to investigate its prognostic value in two large series of patients with HCC treated either by surgical resection or radiofrequency ablation (RFA). We retrospectively included 237 HCC surgical samples and 284 HCC liver biopsies from patients treated by surgical resection and RFA, respectively. Histological slides were reviewed by pathologists specialized in liver disease, and the MTM-HCC subtype was defined by the presence of a predominant (>50%) macrotrabecular architecture (more than 6 cells thick). The main clinical and biological features were recorded at baseline. Clinical endpoints were early and overall recurrence. The MTM-HCC subtype was identified in 12% of the whole cohort (16% of surgically resected samples, 8.5% of liver biopsy samples). It was associated at baseline with known poor prognostic factors (tumor size, AFP level, satellite nodules and vascular invasion). Multivariate analysis showed that MTM-HCC subtype was an independent predictor of early and overall recurrence (surgical series: OR 3.03 (1.38-6.65), p=0.006 and 2.76 (1.63-4.67), pvalue was retained even after patients stratification according to common clinical, biological and pathological features of aggressiveness. No other baseline parameter was independently associated to recurrence in the RFA series. The MTM-HCC subtype, reliably observed in 12% of patients eligible for a curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  4. A conscious mouse model of gastric ileus using clinically relevant endpoints

    Directory of Open Access Journals (Sweden)

    Shao Yuanlin

    2005-06-01

    Full Text Available Abstract Background Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. Methods Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. Results Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. Conclusion Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of

  5. Education in the clinical context: establishing a strategic framework to ensure relevance.

    Science.gov (United States)

    Henderson, Amanda; Fox, Robyn; Armit, Lyn

    2008-01-01

    Quality contemporary practice relies on nurses to provide health care within an embedded nexus of clinical, professional and organisational learning that leads them through a career trajectory that encourages lifelong development. Within complex health service environments this is fraught with difficulties. Enhancing practice is multifaceted requiring not just education for the acquisition of skills and abilities but time and space for reflection on experience within the clinical context. This ultimately leads to professional knowledge development. Queensland Health has developed a Nursing and Midwifery Staff Development Framework to assist nurses in structuring their experiences in the practice setting to enable their professional goals. Learning is guided within this framework through its collective modus operandi, that is, the development of teams that overlap to identify and progress the educational agenda; resources to develop consistent relevant learning material that incorporates evidence obtained through practices and the literature; and educator and clinician networks across health services throughout the state, and furthermore, links with the tertiary sector to assist in marketing, applicability and synergy with further education.

  6. Peripheral White Blood Cell Subsets in Metastatic Colorectal Cancer Patients Treated with Cetuximab: The Potential Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ivana Z. Matić

    2018-01-01

    percentages of CD16+, CD56+, and CD16+CD56+ lymphocytes 2 months after treatment in the non-responder group did not differ significantly in comparison with healthy individuals. Considerable alterations of immune cell percentages observed in patients with metastatic colorectal cancer with disease progression indicate that the assessment of peripheral white blood cell architecture before treatment initiation may be clinically relevant.

  7. Glutaminase-Deficient Mice Display Hippocampal Hypoactivity, Insensitivity to Pro-Psychotic Drugs and Potentiated Latent Inhibition: Relevance to Schizophrenia

    Science.gov (United States)

    Gaisler-Salomon, Inna; Miller, Gretchen M; Chuhma, Nao; Lee, Sooyeon; Zhang, Hong; Ghoddoussi, Farhad; Lewandowski, Nicole; Fairhurst, Stephen; Wang, Yvonne; Conjard-Duplany, Agnès; Masson, Justine; Balsam, Peter; Hen, René; Arancio, Ottavio; Galloway, Matthew P; Moore, Holly M; Small, Scott A; Rayport, Stephen

    2009-01-01

    Dysregulated glutamatergic neurotransmission has been strongly implicated in the pathophysiology of schizophrenia (SCZ). Recently, presynaptic modulation of glutamate transmission has been shown to have therapeutic promise. We asked whether genetic knockdown of glutaminase (gene GLS1) to reduce glutamatergic transmission presynaptically by slowing the recycling of glutamine to glutamate, would produce a phenotype relevant to SCZ and its treatment. GLS1 heterozygous (GLS1 het) mice showed about a 50% global reduction in glutaminase activity, and a modest reduction in glutamate levels in brain regions relevant to SCZ pathophysiology, but displayed neither general behavioral abnormalities nor SCZ-associated phenotypes. Functional imaging, measuring regional cerebral blood volume, showed hippocampal hypometabolism mainly in the CA1 subregion and subiculum, the inverse of recent clinical imaging findings in prodromal and SCZ patients. GLS1 het mice were less sensitive to the behavioral stimulating effects of amphetamine, showed a reduction in amphetamine-induced striatal dopamine release and in ketamine-induced frontal cortical activation, suggesting that GLS1 het mice are resistant to the effects of these pro-psychotic challenges. Moreover, GLS1 het mice showed clozapine-like potentiation of latent inhibition, suggesting that reduction in glutaminase has antipsychotic-like properties. These observations provide further support for the pivotal role of altered glutamatergic synaptic transmission in the pathophysiology of SCZ, and suggest that presynaptic modulation of the glutamine–glutamate pathway through glutaminase inhibition may provide a new direction for the pharmacotherapy of SCZ. PMID:19516252

  8. Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance.

    Science.gov (United States)

    Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali

    2017-06-01

    The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

  9. Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.

    Science.gov (United States)

    Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F

    2015-01-01

    recommendations could be categorized under the following eight objectives to be safeguarded during clinical application of artificial gametes: (i) timing the implementation of new treatments correctly, (ii) meeting 'plausible demands of patients', (iii) improving and safeguarding public health, (iv) promoting the progress of medical science in the interest of future patients, (v) providing treatments that are morally acceptable for the general public, (vi) controlling medical practice, (vii) offering treatments that allow acquisition of informed consent and (viii) funding treatments fairly. Professionals specialized in biomedical science, science journalists and professionals specialized in ethics all addressed these eight objectives on artificial gametes, whereas professionals specialized in law or political science addressed seven objectives. Although one study reported on the perspective of parents of under-aged patients on three objectives, the perspectives of patients themselves were not reported by the reviewed literature. Of course, clinical introduction of artificial gametes should only be considered on the basis of reassuring outcomes of appropriate preclinical effectiveness and safety studies. In addition, potential users' views on the desirability and acceptability of artificial gametes should be studied before clinical introduction. A societal debate including all stakeholders is needed to determine the relative importance of all arguments in favor of and against the introduction of artificial gametes into clinical practice. More broadly, establishing pre-implementation processes for new medical techniques is relevant for all fields of medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Bottom–up protein identifications from microliter quantities of individual human tear samples. Important steps towards clinical relevance.

    Directory of Open Access Journals (Sweden)

    Peter Raus

    2015-12-01

    With 375 confidently identified proteins in the healthy adult tear, the obtained results are comprehensive and in large agreement with previously published observations on pooled samples of multiple patients. We conclude that, to a limited extent, bottom–up tear protein identifications from individual patients may have clinical relevance.

  11. [Terbinafine : Relevant drug interactions and their management].

    Science.gov (United States)

    Dürrbeck, A; Nenoff, P

    2016-09-01

    The allylamine terbinafine is the probably most frequently prescribed systemic antifungal agent in Germany for the treatment of dermatomycoses and onychomycoses. According to the German drug law, terbinafine is approved for patients who are 18 years and older; however, this antifungal agent is increasingly used off-label for treatment of onychomycoses and tinea capitis in children. Terbinafine is associated with only a few interactions with other drugs, which is why terbinafine can generally be used without problems in older and multimorbid patients. Nevertheless, some potential interactions of terbinafine with certain drug substances are known, including substances of the group of antidepressants/antipsychotics and some cardiovascular drugs. Decisive for the relevance of interactions is-along with the therapeutic index of the substrate and the possible alternative degradation pathways-the genetically determined type of metabolism. When combining terbinafine with tricyclic antidepressants or selective serotonin reuptake inhibitors and serotonin/noradrenalin reuptake inhibitors, the clinical response and potential side effects must be monitored. Problematic is the use of terbinafine with simultaneous treatment with tamoxifen. The administration of potent CYP2D6 inhibitors leads to a diminished efficacy of tamoxifen because one of its most important active metabolites-endoxifen-is not sufficiently available. Therefore, combination of tamoxifen and terbinafine should be avoided. In conclusion, the number of substances which are able to cause clinically relevant interactions in case of simultaneously administration with terbinafine is clear and should be manageable in the dermatological office with adequate monitoring.

  12. Clinical relevance of the gap between pre-marketing trials and medical practice : the case of the cardiovascular drugs

    NARCIS (Netherlands)

    Wieringa, N F; Denig, P; de Graeff, P A; Vos, R

    OBJECTIVES/BACKGROUND: The external validity of trial results of new cardiovascular drugs is limited, because the short-term studies are performed with relatively small, highly selected populations. Using qualitative methods, we examined the clinical relevance of under-representation of subgroups of

  13. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

    Science.gov (United States)

    Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

    2017-04-01

    HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

  14. [Relevance of Vascular Trauma in Trauma Care - Impact on Clinical Course and Mortality].

    Science.gov (United States)

    Lech, L; Jerkku, T; Kanz, K-G; Wierer, M; Mutschler, W; Koeppel, T A; Lefering, R; Banafsche, R

    2016-10-01

    There is a lack of evidence as to the relevance of vascular trauma (VT) in patients with severe injuries. Therefore, we reviewed registry data in the present study in order to systematically objectify the effect of VT in these patients. This study aimed to provide an adequate picture of the relevance of vascular trauma and to identify adverse prognostic factors. In a retrospective analysis of records from the TraumaRegister DGU® (TR-DGU) in two subgroups with moderate and severe VT, we examined the records for differences in terms of morbidity, mortality, follow-up and prognostic parameters compared to patients without VT with the same ISS. From a total of 42,326 patients, 2,961 (7 %) had a VT, and in 2,437 cases a severe VT (AIS ≥ 3) was diagnosed (5.8 %). In addition to a higher incidence of shock and a 2 to 3-fold increase in fluid replacement and erythrocyte transfusion, patients with severe VT had a 60 % higher rate of multiple organ failure, and in-hospital mortality was twice as high (33.8 %). The massively increased early mortality (8.0 vs. 25.2 %) clearly illustrates how severely injured patients are placed at risk by the presence of a relevant VT with a comparable ISS. In our opinion, due to an unexpected poor prognosis in the TR-DGU data for vascular injuries, increased attention is required in the care of severely injured patients. Based on our comprehensive analysis of negative prognostic factors, a further adjustment to the standards of vascular medicine could be advisable. The influence of the level of care provided by the admitting hospital and the relevance of a further hospital transfer to prognosis and clinical outcome is currently being analysed. Georg Thieme Verlag KG Stuttgart · New York.

  15. The Importance of Integrating Clinical Relevance and Statistical Significance in the Assessment of Quality of Care--Illustrated Using the Swedish Stroke Register.

    Directory of Open Access Journals (Sweden)

    Anita Lindmark

    Full Text Available When profiling hospital performance, quality inicators are commonly evaluated through hospital-specific adjusted means with confidence intervals. When identifying deviations from a norm, large hospitals can have statistically significant results even for clinically irrelevant deviations while important deviations in small hospitals can remain undiscovered. We have used data from the Swedish Stroke Register (Riksstroke to illustrate the properties of a benchmarking method that integrates considerations of both clinical relevance and level of statistical significance.The performance measure used was case-mix adjusted risk of death or dependency in activities of daily living within 3 months after stroke. A hospital was labeled as having outlying performance if its case-mix adjusted risk exceeded a benchmark value with a specified statistical confidence level. The benchmark was expressed relative to the population risk and should reflect the clinically relevant deviation that is to be detected. A simulation study based on Riksstroke patient data from 2008-2009 was performed to investigate the effect of the choice of the statistical confidence level and benchmark value on the diagnostic properties of the method.Simulations were based on 18,309 patients in 76 hospitals. The widely used setting, comparing 95% confidence intervals to the national average, resulted in low sensitivity (0.252 and high specificity (0.991. There were large variations in sensitivity and specificity for different requirements of statistical confidence. Lowering statistical confidence improved sensitivity with a relatively smaller loss of specificity. Variations due to different benchmark values were smaller, especially for sensitivity. This allows the choice of a clinically relevant benchmark to be driven by clinical factors without major concerns about sufficiently reliable evidence.The study emphasizes the importance of combining clinical relevance and level of statistical

  16. The Importance of Integrating Clinical Relevance and Statistical Significance in the Assessment of Quality of Care--Illustrated Using the Swedish Stroke Register.

    Science.gov (United States)

    Lindmark, Anita; van Rompaye, Bart; Goetghebeur, Els; Glader, Eva-Lotta; Eriksson, Marie

    2016-01-01

    When profiling hospital performance, quality inicators are commonly evaluated through hospital-specific adjusted means with confidence intervals. When identifying deviations from a norm, large hospitals can have statistically significant results even for clinically irrelevant deviations while important deviations in small hospitals can remain undiscovered. We have used data from the Swedish Stroke Register (Riksstroke) to illustrate the properties of a benchmarking method that integrates considerations of both clinical relevance and level of statistical significance. The performance measure used was case-mix adjusted risk of death or dependency in activities of daily living within 3 months after stroke. A hospital was labeled as having outlying performance if its case-mix adjusted risk exceeded a benchmark value with a specified statistical confidence level. The benchmark was expressed relative to the population risk and should reflect the clinically relevant deviation that is to be detected. A simulation study based on Riksstroke patient data from 2008-2009 was performed to investigate the effect of the choice of the statistical confidence level and benchmark value on the diagnostic properties of the method. Simulations were based on 18,309 patients in 76 hospitals. The widely used setting, comparing 95% confidence intervals to the national average, resulted in low sensitivity (0.252) and high specificity (0.991). There were large variations in sensitivity and specificity for different requirements of statistical confidence. Lowering statistical confidence improved sensitivity with a relatively smaller loss of specificity. Variations due to different benchmark values were smaller, especially for sensitivity. This allows the choice of a clinically relevant benchmark to be driven by clinical factors without major concerns about sufficiently reliable evidence. The study emphasizes the importance of combining clinical relevance and level of statistical confidence when

  17. Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

    Science.gov (United States)

    Carlsson, Anders H; Rose, Lloyd F; Fletcher, John L; Wu, Jesse C; Leung, Kai P; Chan, Rodney K

    2017-02-01

    Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300μm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (pskin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  18. [Relevant public health enteropathogens].

    Science.gov (United States)

    Riveros, Maribel; Ochoa, Theresa J

    2015-01-01

    Diarrhea remains the third leading cause of death in children under five years, despite recent advances in the management and prevention of this disease. It is caused by multiple pathogens, however, the prevalence of each varies by age group, geographical area and the scenario where cases (community vs hospital) are recorded. The most relevant pathogens in public health are those associated with the highest burden of disease, severity, complications and mortality. In our country, norovirus, Campylobacter and diarrheagenic E. coli are the most prevalent pathogens at the community level in children. In this paper we review the local epidemiology and potential areas of development in five selected pathogens: rotavirus, norovirus, Shiga toxin-producing E. coli (STEC), Shigella and Salmonella. Of these, rotavirus is the most important in the pediatric population and the main agent responsible for child mortality from diarrhea. The introduction of rotavirus vaccination in Peru will have a significant impact on disease burden and mortality from diarrhea. However, surveillance studies are needed to determine the impact of vaccination and changes in the epidemiology of diarrhea in Peru following the introduction of new vaccines, as well as antibiotic resistance surveillance of clinical relevant bacteria.

  19. Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

    NARCIS (Netherlands)

    Rayman, Nazik; Lam, King H.; van der Holt, Bronno; Koss, Clara; Veldhuizen, Dennis; Budel, Leo M.; Mulder, Andries H.; Verdonck, Leo F.; Delwel, Ruud; de Jong, Daphne; van Imhoff, Gustaaf W.; Sonneveld, Pieter

    Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large

  20. Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays

    International Nuclear Information System (INIS)

    Kuwahara, Yoshikazu; Baba, Taisuke; Nakagawa, Hironobu; Shimura, Tsutomu; Yamamoto, Yoichiro; Fukumoto, Manabu; Li Li; Ohkubo, Yasuhito

    2009-01-01

    Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5-8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30 days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of γ-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S- and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line. (author)

  1. Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen; Inam, Qurrat-ul-Aen; Haleem, Muhammad Abdul

    2015-03-15

    The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Clinical Empathy and Narrative Competence: The Relevance of Reading Talmudic Legends as Literary Fiction

    Directory of Open Access Journals (Sweden)

    John H. Davidson

    2015-04-01

    Full Text Available The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM, broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy.

  3. Reflections on relevance: Psychotherapy and Psychosomatics in 2004.

    Science.gov (United States)

    Balon, Richard

    2005-01-01

    Relevance of an article is a highly desirable yet hardly predictable quality at the time of its publication. Article relevance is frequently measured by the impact factor of the journal where the article is published. Furthermore, impact factor, citation index and citation analysis are used as a measure of research progress and scientific wealth of a nation. The wisdom and significance of this approach to relevance is debatable and thus discussed here. In 2004, Psychotherapy and Psychosomatics published a variety of articles which, in the author's view, are clinically relevant. Several selected clinically relevant issues reviewed in this article include: the conceptualization of fibromyalgia as a stress disorder; the psychosocial impact and psychosocial interventions in cancer; the impact of alexithymia on patient care; the possible relationship between depression and nutrition (namely intake of folate and pyridoxal phosphate); the significance of hypercoagulability in panic-like anxiety; the questionable value of single isomer drugs, and the relevance and adequacy of clinimetrics versus psychometrics in clinical research. The reviewed issues seem to be relevant to clinical practice, research or both, but also to our critical thinking, and the critical review of the developments in psychiatry and psychology. Copyright 2005 S. Karger AG, Basel.

  4. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  5. Clinical Relevance of HLA Gene Variants in HBV Infection

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available Host gene variants may influence the natural history of hepatitis B virus (HBV infection. The human leukocyte antigen (HLA system, the major histocompatibility complex (MHC in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs have shown that single nucleotide polymorphisms (SNPs near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC in chronic hepatitis B (CHB. These variations also influence the efficacy of interferon (IFN and nucleot(side analogue (NA treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

  6. Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention

    DEFF Research Database (Denmark)

    Henriksen, N A; Meyhoff, C S; Wetterslev, J

    2010-01-01

    Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant...... diagnosed with SSI and a matched control group (N=46) without SSI according to the CDC criteria after laparotomy. Two blinded experienced surgeons evaluated the hospital records and determined whether patients had CRSSI, based on the following criteria: antibiotic treatment, surgical intervention, prolonged...... hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant...

  7. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2008-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  8. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and Its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2007-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design, all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  9. Diagnosing congenital malaria in a high-transmission setting: clinical relevance and usefulness of P.falciparum HRP2-based testing

    NARCIS (Netherlands)

    Natama, Hamtandi Magloire; Ouedraogo, Delwendé Florence; Sorgho, Hermann; Rovira-Vallbona, Eduard; Serra-Casas, Elisa; Somé, M. Athanase; Coulibaly-Traoré, Maminata; Mens, Petra F.; Kestens, Luc; Tinto, Halidou; Rosanas-Urgell, Anna

    2017-01-01

    Congenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time

  10. Comparison of two matrix-assisted laser desorption ionisation-time of flight mass spectrometry methods for the identification of clinically relevant anaerobic bacteria

    NARCIS (Netherlands)

    Veloo, A. C. M.; Knoester, M.; Degener, J. E.; Kuijper, E. J.

    2011-01-01

    Two commercially available MALDI-TOF MS systems, Bruker MS and Shimadzu MS, were compared for the identification of clinically relevant anaerobic bacteria. A selection of 79 clinical isolates, representing 19 different genera, were tested and compared with identification obtained by 16S rRNA gene

  11. Clinical relevance of the ROC and free-response paradigms for comparing imaging system efficacies

    International Nuclear Information System (INIS)

    Chakraborty, D. P.

    2010-01-01

    Observer performance studies are widely used to assess medical imaging systems. Unlike technical/engineering measurements observer performance include the entire imaging chain and the radiologist. However, the widely used receiver operating characteristic (ROC) method ignores lesion localisation information. The free-response ROC (FROC) method uses the location information to appropriately reward or penalise correct or incorrect localizations, respectively. This paper describes a method for improving the clinical relevance of FROC studies. The method consists of assigning appropriate risk values to the different lesions that may be present on a single image. A high-risk lesion is one that is critical to detect and act upon, and is assigned a higher risk value than a low-risk lesion, one that is relatively innocuous. Instead of simply counting the number of lesions that are detected, as is done in conventional FROC analysis, a risk-weighted count is used. This has the advantage of rewarding detections of high-risk lesions commensurately more than detections of lower risk lesions. Simulations were used to demonstrate that the new method, termed case-based analysis, results in a higher figure of merit for an expert who detects more high-risk lesions than a naive observer who detects more low-risk lesions, even though both detect the same total number of lesions. Conventional free-response analysis is unable to distinguish between the two types of observers. This paper also comments on the issue of clinical relevance of ROC analysis vs. FROC for tasks that involve lesion localisation. (authors)

  12. First branchial cleft anomaly: clinical insight into its relevance in otolaryngology with pediatric considerations.

    Science.gov (United States)

    Maithani, Tripti; Pandey, Apporva; Dey, Debraj; Bhardwaj, Aparna; Singh, V P

    2014-01-01

    First branchial cleft anomalies (FBCA) represent a small subset of congenital malformations in neck. Prime objective of this study is to share our experience with FBCA, emphasize its relevance in otolaryngology and deal with its pediatric perspective. Embryology, pathologic anatomy and varied spectra of clinical presentations of FBCA are discussed. Along with this we have illustrated three different cases; all of them were of pediatric age group and were misdiagnosed by their treating specialists elsewhere. In this article we have also laid special emphasis on its pediatric considerations. FBCA are mostly misdiagnosed due to their unfamiliar clinical signs and symptoms. Swellings may masquerade as other neck masses. Majority of patients give a history of previous incision and drainage. While dealing with pediatric patients the important factors to be kept in mind are the age of child, superficial course of facial nerve, any associated agenesis of parotid gland. Alteration in surgical technique may be required in children. A thorough medical examination with high index of clinical suspicion should be kept in mind while dealing with such anomalies. Owing to their complex presentation and close relation with facial nerve they are challenging lesions for surgeons.

  13. Clinical relevance of retrieval cues for attenuating context renewal of fear.

    Science.gov (United States)

    Culver, Najwa C; Stoyanova, Milena; Craske, Michelle G

    2011-03-01

    The present studies investigated if retrieval cues (reminder objects) can attenuate context renewal of fear. In Study 1, 32 participants completed exposure in one of two contexts; 1-week follow-up testing occurred in a novel or the same context. Results indicated significant renewal of fear for those tested in a novel context. In Study 2, 40 participants completed exposure in one of these contexts; half were presented with cues. One week later, all were tested in a novel context with or without cues. Results indicated weak attenuation of context renewal for participants re-presented with cues. In Study 3, 18 participants completed exposure in one of two maximally distinct contexts; all with cues. One week later, participants were tested in a novel context with or without cues. Results indicated no group differences. These findings suggest that clinical relevance of this set of cues for attenuating context renewal may be limited. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Classification of perimenstrual headache: clinical relevance.

    Science.gov (United States)

    MacGregor, E Anne

    2012-10-01

    Although more than 50% of women with migraine report an association between migraine and menstruation, menstruation has generally considered to be no more than one of a variety of different migraine triggers. In 2004, the second edition of the International Classification of Headache Disorders introduced specific diagnostic criteria for menstrual migraine. Results from research undertaken subsequently lend support to the clinical impression that menstrual migraine should be seen as a distinct clinical entity. This paper reviews the recent research and provides specific recommendations for consideration in future editions of the classification.

  15. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Jager, Gerry; Vervaeke, Hylke K. E.; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C.; den Heeten, Gerard J.; Ramsey, Nick F.; Korf, Dirk J.; van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin

  16. Dependence and caring in clinical communication: the relevance of attachment and other theories.

    Science.gov (United States)

    Salmon, Peter; Young, Bridget

    2009-03-01

    Clinical relationships are usually asymmetric, being defined by patients' dependence and practitioners' care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Attachment theory helps to understand patients' need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners' caring. Different theories that formulate practitioners' care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners' emotions, values and sense of role in understanding their clinical communication. Extending the theoretical grounding of clinical communication can accommodate patients' dependence and practitioners' caring without return to medical paternalism. A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be.

  17. Dependence and caring in clinical communication: The relevance of attachment and other theories

    Science.gov (United States)

    Salmon, Peter; Young, Bridget

    2009-01-01

    Objective Clinical relationships are usually asymmetric, being defined by patients’ dependence and practitioners’ care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Methods Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Results Attachment theory helps to understand patients’ need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners’ caring. Different theories that formulate practitioners’ care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners’ emotions, values and sense of role in understanding their clinical communication. Conclusion Extending the theoretical grounding of clinical communication can accommodate patients’ dependence and practitioners’ caring without return to medical paternalism. Practice implications A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be. PMID:19157761

  18. Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

    Science.gov (United States)

    Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

    2017-11-01

    Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

    Science.gov (United States)

    Müller, Christoph; Neugebauer, Thomas; Zill, Patrizia; Lass-Flörl, Cornelia; Bracher, Franz; Binder, Ulrike

    2018-05-19

    Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales ( Lichtheimia corymbifera , Lichtheimia ramosa , Mucor circinelloides , Rhizomucor pusillus , Rhizopus arrhizus , and Rhizopus microsporus ) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus . This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway.

  20. Psychometric properties and clinical relevance of the adolescent sleep hygiene scale in Dutch adolescents.

    Science.gov (United States)

    de Bruin, Eduard J; van Kampen, Ris K A; van Kooten, Tamar; Meijer, Anne Marie

    2014-07-01

    This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables were measured using sleep logs and questionnaires. From the insomnia group, scores were also obtained after six weeks of cognitive behavioral therapy for insomnia (n=58) or waiting list (n=22). The full scale of the ASHS had acceptable internal consistency. The results showed moderate to strong correlations of the ASHS (domains) with sleep quality, sleep duration and chronic sleep reduction. Furthermore, the Dutch ASHS was able to discriminate between normal sleepers and adolescents with insomnia, and scores of adolescents with insomnia improved after treatment. These findings confirm the importance of sleep hygiene in adolescent sleep, and contribute to the validity of the ASHS and its applicability in research and clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

    Directory of Open Access Journals (Sweden)

    Naoki Hayashi

    Full Text Available Suicidal behavior (SB is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct.To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance.By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA.Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT, Interpersonal-change (IC, Self-renunciation (SR and Self-sustenance (SS. These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively.The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part

  2. [Basic symptoms in schizophrenia, their clinical study and relevance in research].

    Science.gov (United States)

    Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes

    2016-01-01

    Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

  3. Self-esteem modulates automatic attentional responses to self-relevant stimuli: Evidence from event-related brain potentials

    Directory of Open Access Journals (Sweden)

    Jie eChen

    2015-06-01

    Full Text Available Previous studies have widely shown that self-esteem modulates the attention bias towards social rejection or emotion-related information. However, little is known about the influences of self-esteem on attention bias towards self-relevant stimuli. We aimed to investigate neural correlates that underlie the modulation effect of self-esteem on self-relevant processing. Event-related potentials were recorded for subjects’ own names and close others’ names (the names of their friends while subjects performed a three-stimulus oddball task. The results showed larger P2 amplitudes for one’s own name than for close-other’s name in the low self-esteem group, whereas this P2 effect were not observed in the high self-esteem group. In addition, one’s own name elicited equivalent N250 amplitudes and larger P3 amplitudes compared with close-other’s name in both high and low self-esteem groups. However, no interaction effects were observed between self-esteem and self-relevant processing in the N250 and P3 components. Thus, we found that the modulation effects of self-esteem on self-relevant processing occurred at the early P2 stage, but not at the later N250 and P3 stages. These findings reflect that individuals with low self-esteem demonstrate automatic attention towards their own names.

  4. [work motivation -- assessment instruments and their relevance for medical care].

    Science.gov (United States)

    Fiedler, Rolf G; Ranft, Andreas; Greitemann, Bernhard; Heuft, Gereon

    2005-11-01

    The relevance of work motivation for medical research and healthcare, in particular rehabilitation, is described. Four diagnostic instruments in the German language are introduced which can assess work motivation using a scale system: AVEM, JDS, LMI and FBTM. Their possible application and potential usage for the clinical area are discussed. Apart from the FBTM, none of these instruments can be directly used as a general instrument in a normal medical clinical setting. Finally, a current model for work motivation (compensatory model of work motivation and volition) is presented that contains basis concepts, which are judged as important for future research questions concerning the development of motivation diagnostic instruments.

  5. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  6. Nocebo phenomena in medicine: their relevance in everyday clinical practice.

    Science.gov (United States)

    Häuser, Winfried; Hansen, Ernil; Enck, Paul

    2012-06-01

    Nocebo phenomena are common in clinical practice and have recently become a popular topic of research and discussion among basic scientists, clinicians, and ethicists. We selectively searched the PubMed database for articles published up to December 2011 that contained the key words "nocebo" or "nocebo effect." By definition, a nocebo effect is the induction of a symptom perceived as negative by sham treatment and/or by the suggestion of negative expectations. A nocebo response is a negative symptom induced by the patient's own negative expectations and/or by negative suggestions from clinical staff in the absence of any treatment. The underlying mechanisms include learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Nocebo responses may come about through unintentional negative suggestion on the part of physicians and nurses. Information about possible complications and negative expectations on the patient's part increases the likelihood of adverse effects. Adverse events under treatment with medications sometimes come about by a nocebo effect. Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information. Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects. Communication training in medical school, residency training, and continuing medical education would be desirable so that physicians can better exploit the power of words to patients' benefit, rather than their detriment.

  7. Best clinical trials reported in 2010.

    Science.gov (United States)

    Garner, John B; Grayburn, Paul A; Yancy, Clyde W

    2011-07-01

    Each year, a number of clinical trials emerge with data sufficient to change clinical practice. Determining which findings will result in practice change and which will provide only incremental benefit can be a dilemma for clinicians. The authors review selected clinical trials reported in 2010 in journals, at society meetings, and at conferences, focusing on those studies that have the potential to change clinical practice. This review offers 3 separate means of analysis: an abbreviated text summary, organized by subject area; a comprehensive table of relevant clinical trials that provides a schematic review of the hypotheses, interventions, methods, primary end points, results, and implications; and a complete bibliography for further reading as warranted. It is hoped that this compilation of relevant clinical trials and their important findings released in 2010 will be of benefit in the everyday practice of cardiovascular medicine. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.

    Science.gov (United States)

    Hoogsteen, Ilse J; Marres, Henri A M; Bussink, Johan; van der Kogel, Albert J; Kaanders, Johannes H A M

    2007-06-01

    Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

  9. A scoping review of the potential for chart stimulated recall as a clinical research method.

    Science.gov (United States)

    Sinnott, Carol; Kelly, Martina A; Bradley, Colin P

    2017-08-22

    Chart-stimulated recall (CSR) is a case-based interviewing technique, which is used in the assessment of clinical decision-making in medical education and professional certification. Increasingly, clinical decision-making is a concern for clinical research in primary care. In this study, we review the prior application and utility of CSR as a technique for research interviews in primary care. Following Arksey & O'Malley's method for scoping reviews, we searched seven databases, grey literature, reference lists, and contacted experts in the field. We excluded studies on medical education or competence assessment. Retrieved citations were screened by one reviewer and full texts were ordered for all potentially relevant abstracts. Two researchers independently reviewed full texts and performed data extraction and quality appraisal if inclusion criteria were met. Data were collated and summarised using a published framework on the reporting of qualitative interview techniques, which was chosen a priori. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines informed the review report. From an initial list of 789 citations, eight studies using CSR in research interviews were included in the review: six from North America, one from the Netherlands, and one from Ireland. The most common purpose of included studies was to examine the influence of guidelines on physicians' decisions. The number of interviewees ranged from seven to twenty nine, while the number of charts discussed per interview ranged from one to twelve. CSR gave insights into physicians' reasoning for actions taken or not taken; the unrecorded social and clinical influences on decisions; and discrepancies between physicians' real and perceived practice. Ethical concerns and the training and influence of the researcher were poorly discussed in most of the studies. Potential pitfalls included the risk of recall, selection and observation biases. Despite the proven validity

  10. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    International Nuclear Information System (INIS)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A.

    2011-01-01

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa. Conclusions: There is a lack of correlation between

  11. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Armoogum, Kris S., E-mail: kris.armoogum@nhs.net [Department of Radiotherapy Physics, Royal Derby Hospital, Derby Hospitals NHS Foundation Trust, Uttoxeter Road, Derby DE22 3NE (United Kingdom); Thorp, Nicola [The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral CH63 4JY (United Kingdom)

    2015-04-28

    Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  12. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Directory of Open Access Journals (Sweden)

    Kris S. Armoogum

    2015-04-01

    Full Text Available Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  13. Fasciculation potentials in high-density surface EMG.

    NARCIS (Netherlands)

    Drost, G.; Kleine, B.U.; Stegeman, D.F.; Engelen, B.G.M. van; Zwarts, M.J.

    2007-01-01

    Fasciculation potentials (FPs) are observed in healthy individuals, but also in patients with neurogenic disorders. The exact site of origin and the clinical relevance in distinguishing, for example, amyotrophic lateral sclerosis (ALS) from other neurogenic diseases based on specific characteristics

  14. Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre.

    Science.gov (United States)

    Paterson, Ross W; Zandi, Michael S; Armstrong, Richard; Vincent, Angela; Schott, Jonathan M

    2014-06-01

    Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Only 4 of the 32 patients with low-positive (100-400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100-400 pM (0.1-0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely

  15. Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke

    NARCIS (Netherlands)

    Otterman, Nicoline; Veerbeek, Janne; Schiemanck, Sven; van der Wees, Philip; Nollet, Frans; Kwakkel, Gert

    2017-01-01

    Purpose: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. Methods: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability

  16. Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke

    NARCIS (Netherlands)

    Otterman, N.; Veerbeek, J.; Schiemanck, S.; Wees, P.J. van der; Nollet, F.; Kwakkel, G.

    2017-01-01

    PURPOSE: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. METHODS: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability

  17. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

    Science.gov (United States)

    Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

    2017-05-01

    Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

  18. High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients; results of the REACT-2 trial

    Energy Technology Data Exchange (ETDEWEB)

    Treskes, K.; Bos, S.A.; Sierink, J.C.; Luitse, J.S.K.; Goslings, J.C. [Academic Medical Center, Trauma Unit, Department of Surgery, Amsterdam (Netherlands); Beenen, L.F.M. [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Edwards, M.J.R. [Radboud University Medical Center, Department of Trauma and emergency surgery, Nijmegen (Netherlands); Beuker, B.J.A. [University Medical Center Groningen, Trauma Unit, Department of Surgery, Groningen (Netherlands); Muradin, G.S.R. [University Medical Center Rotterdam, Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Hohmann, J. [University of Basel Hospital, Department of Radiology and Nuclear Medicine, Basel (Switzerland); Hollmann, M.W. [Academic Medical Center, Department of Anaesthesiology, Amsterdam (Netherlands); Dijkgraaf, M.G.W. [Academic Medical Center, Clinical Research Unit, Amsterdam (Netherlands); Collaboration: REACT-2 study group

    2017-06-15

    To determine whether there is a difference in frequency and clinical relevance of incidental findings detected by total-body computed tomography scanning (TBCT) compared to those by the standard work-up (STWU) with selective computed tomography (CT) scanning. Trauma patients from five trauma centres were randomized between April 2011 and January 2014 to TBCT imaging or STWU consisting of conventional imaging with selective CT scanning. Incidental findings were divided into three categories: 1) major finding, may cause mortality; 2) moderate finding, may cause morbidity; and 3) minor finding, hardly relevant. Generalized estimating equations were applied to assess differences in incidental findings. In total, 1083 patients were enrolled, of which 541 patients (49.9 %) were randomized for TBCT and 542 patients (50.1 %) for STWU. Major findings were detected in 23 patients (4.3 %) in the TBCT group compared to 9 patients (1.7 %) in the STWU group (adjusted rate ratio 2.851; 95%CI 1.337-6.077; p < 0.007). Findings of moderate relevance were detected in 120 patients (22.2 %) in the TBCT group compared to 86 patients (15.9 %) in the STWU group (adjusted rate ratio 1.421; 95%CI 1.088-1.854; p < 0.010). Compared to selective CT scanning, more patients with clinically relevant incidental findings can be expected by TBCT scanning. (orig.)

  19. Clinical relevance of quantified fundus autofluorescence in diabetic macular oedema.

    Science.gov (United States)

    Yoshitake, S; Murakami, T; Uji, A; Unoki, N; Dodo, Y; Horii, T; Yoshimura, N

    2015-05-01

    To quantify the signal intensity of fundus autofluorescence (FAF) and evaluate its association with visual function and optical coherence tomography (OCT) findings in diabetic macular oedema (DMO). We reviewed 103 eyes of 78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid were measured. We evaluated the association between quantified FAF and the logMAR VA and OCT findings. One hundred and three eyes with DMO had lower FAF signal intensity levels in the parafoveal subfields compared with 30 eyes without DMO. The autofluorescence intensity in the parafoveal subfields was associated negatively with logMAR VA and the retinal thickness in the corresponding subfields. The autofluorescence levels in the parafoveal subfield, except the nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the corresponding subfield than in those without autofluorescent cystoid spaces. The autofluorescence level in the central subfield was related to foveal cystoid spaces but not logMAR VA or retinal thickness in the corresponding area. Quantified FAF in the parafovea has diagnostic significance and is clinically relevant in DMO.

  20. Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

    Science.gov (United States)

    Wagner, Amy K; Brayer, Samuel W; Hurwitz, Max; Niyonkuru, Christian; Zou, Huichao; Failla, Michelle; Arenth, Patricia; Manole, Mioara D; Skidmore, Elizabeth; Thiels, Edda

    2013-11-01

    Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit cognition. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14-18), Probe/Visible Platform (d19), and Reversal (d20-21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant

  1. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park

    2014-10-01

    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  2. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  3. Attentional bias modification based on visual probe task: methodological issues, results and clinical relevance

    Directory of Open Access Journals (Sweden)

    Fernanda Machado Lopes

    2015-12-01

    Full Text Available Introduction: Attentional bias, the tendency that a person has to drive or maintain attention to a specific class of stimuli, may play an important role in the etiology and persistence of mental disorders. Attentional bias modification has been studied as a form of additional treatment related to automatic processing. Objectives: This systematic literature review compared and discussed methods, evidence of success and potential clinical applications of studies about attentional bias modification (ABM using a visual probe task. Methods: The Web of Knowledge, PubMed and PsycInfo were searched using the keywords attentional bias modification, attentional bias manipulation and attentional bias training. We selected empirical studies about ABM training using a visual probe task written in English and published between 2002 and 2014. Results: Fifty-seven studies met inclusion criteria. Most (78% succeeded in training attention in the predicted direction, and in 71% results were generalized to other measures correlated with the symptoms. Conclusions: ABM has potential clinical utility, but to standardize methods and maximize applicability, future studies should include clinical samples and be based on findings of studies about its effectiveness.

  4. Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance.

    Science.gov (United States)

    Wolf, O T; Atsak, P; de Quervain, D J; Roozendaal, B; Wingenfeld, K

    2016-08-01

    Stress causes a neuroendocrine response cascade, leading to the release of catecholamines and glucocorticoids (GCs). GCs influence learning and memory by acting on mineralocorticoid (MR) and glucocorticoid (GR) receptors. Typically, GCs enhance the consolidation of memory processing at the same time as impairing the retrieval of memory of emotionally arousing experiences. The present selective review addresses four recent developments in this area. First, the role of the endocannabinoid system in mediating the rapid, nongenomic effects of GCs on memory is illustrated in rodents. Subsequently, studies on the impact of the selective stimulation of MRs on different memory processes in humans are summarised. Next, a series of human experiments on the impact of stress or GC treatment on fear extinction and fear reconsolidation is presented. Finally, the clinical relevance of the effects of exogenous GC administration is highlighted by the description of patients with anxiety disorders who demonstrate an enhancement of extinction-based therapies by GC treatment. The review highlights the substantial progress made in our mechanistic understanding of the memory-modulating properties of GCs, as well as their clinical potential. © 2015 British Society for Neuroendocrinology.

  5. Lack of Clinical Relevance of ANA and ASMA Positivity in Patients with Liver Transplantation without a History of Autoimmune Diseases.

    Science.gov (United States)

    Pellegrini, Lucienne; Parrilli, Gianpaolo; Santonicola, Antonella; Cinquanta, Luigi; Caputo, Cesare; Ciacci, Carolina; Zingone, Fabiana

    2017-01-01

    The relevance of isolated autoimmunity elevation in orthotopic liver transplantation (OLT) patients is unknown. Our aim was to analyse how serum autoantibodies change in time and to evaluate their clinical relevance in OLT patients. Patients were invited to provide samples to evaluate ANA, AMA, ASMA, and LKM at the time of enrolment ( T 0), after 6 months ( T 6), and after 12 months ( T 12). We included 114 patients in the study (76% males, median age 62.5 years), finding isolated elevation of at least one serum antibody in up to 80% of them. We described fluctuating positive autoantibodies in the one year of observation, with only 45.6% of patients positive for ANA and less than 2% positive for ASMA, at all three times. Isolated elevation of tissue antibodies was not related to gender, age, HCC at transplant, early rejection, cause of transplantation, immunotherapy taken, and age at the time of the study. We did not detect a higher prevalence of positive autoimmunity in patients with signs of liver injury. ANA and ASMA evaluation in patients with liver transplantation and no history of autoimmune disease has no clinical relevance, since it varies in time and is not related to any risk factors or liver injury. Routine autoimmunity evaluation should be avoided.

  6. Advances on the molecular characterization, clinical relevance, and detection methods of Gadiform parvalbumin allergens.

    Science.gov (United States)

    Fernandes, Telmo J R; Costa, Joana; Carrapatoso, Isabel; Oliveira, Maria Beatriz P P; Mafra, Isabel

    2017-10-13

    Gadiform order includes several fish families, from which Gadidae and Merlucciidae are part of, comprising the most commercially important and highly appreciated fish species, such as cod, pollock, haddock, and hake. Parvalbumins, classified as calcium-binding proteins, are considered the main components involved in the majority of fish allergies. Nine and thirteen parvalbumins were identified in different fish species from Gadidae and Merlucciidae families, respectively. This review intends to describe their molecular characterization and the clinical relevance, as well as the prevalence of fish allergy. In addition, the main protein- and DNA-based methods to detect fish allergens are fully reviewed owing to their importance in the safeguard of sensitized/allergic individuals.

  7. Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?1

    Science.gov (United States)

    Tong, Steven Y.C.; Chen, Luke F.; Fowler, Vance G.

    2011-01-01

    Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility and therapeutics. Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use. Humans and S. aureus co-exist and the dynamic interface between host, pathogen and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA. PMID:22160374

  8. Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome.

    Science.gov (United States)

    Zhang, Shulan; Wu, Ziyan; Li, Jing; Wen, Xiaoting; Li, Liubing; Zhang, Wen; Zhao, Jiuliang; Zhang, Fengchun; Li, Yongzhe

    2017-02-01

    A hallmark feature of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPLs). Few studies have addressed the clinical relevance of anti-annexin A5 antibodies (aANXA5) in Chinese patients with APS. In this study, we evaluated the clinical performance of aANXA5 in the diagnosis of APS. Sera from 313 subjects were tested, including 170 samples from patients with APS, 104 samples from patients with non-APS diseases as disease controls (DC), and 39 healthy controls (HC). Serum IgG and IgM aANXA5 were determined by ELISA. Overall, the levels of both IgG and IgM aANXA5 were significantly increased in patients with primary APS (PAPS) and APS associated to other diseases (APSAOD) compared with DC and HC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IgG and IgM aANXA5 in the diagnosis of APS were 33.5 and 15.3, 99.0 and 99.0, 98.3 and 96.3, and 47.7 and 41.7%, respectively. Significant associations between IgG aANXA5 and arterial thrombotic events (OR, 2.60; 95% CI, 1.44-4.71) and between IgG aANXA5 and venous thrombotic events (OR, 2.80; 95% CI, 1.55-5.06) were identified. No correlations were identified between IgG or IgM aANXA5 and obstetric complications. Our data suggest that aANXA5 could serve as a diagnosis biomarker for patients with APS. More importantly, our data highlighted a potential role of IgG aANXA5 in identifying APS patients with high risk of thrombosis.

  9. Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.

    Science.gov (United States)

    Humphries, Steve E; Hingorani, Aroon

    2006-02-01

    Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

  10. Clinical relevance of the proposed sexual addiction diagnostic criteria: relation to the Sexual Addiction Screening Test-Revised.

    Science.gov (United States)

    Carnes, Patrick J; Hopkins, Tiffany A; Green, Bradley A

    2014-01-01

    The present article examines and compares the various diagnostic rubrics proposed to codify symptoms of sexual addiction, and then briefly summarizes the ongoing controversy on whether sexual addiction is a valid construct. Using the diagnostic criteria proposed by , the prevalence rate of each criterion is examined in terms of scores on the Sexual Addiction Screening Test-Revised scales (). Differences in diagnostic criteria endorsement associated with sex, sexual orientation, and setting were also explored. Results from a clinical sample of men and women seeking treatment for sexual addiction demonstrated clinical relevance of the criteria, in that all but 3 criteria are endorsed at more than 50% of participants screening positive for sexual addiction on the Sexual Addiction Screening Test-Revised. Sex differences were also noted for endorsement rates of several of the criteria. Finally, several proposed criteria may pose a higher clinical threshold and thus be utilized by clinicians to identify patients with increased pathology. Results are discussed in the context of existing diagnostic frameworks across etiological perspectives.

  11. Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

    International Nuclear Information System (INIS)

    Wroe, Andrew; Clasie, Ben; Kooy, Hanne; Flanz, Jay; Schulte, Reinhard; Rosenfeld, Anatoly

    2009-01-01

    Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields

  12. Technical Note: Display window setting: An important factor for detecting subtle but clinically relevant artifacts in daily CT quality control.

    Science.gov (United States)

    Long, Zaiyang; Bruesewitz, Michael R; Sheedy, Emily N; Powell, Michele A; Kramer, Jacqualynn C; Supalla, Randall R; Colvin, Chance M; Bechel, Jessica R; Favazza, Christopher P; Kofler, James M; Leng, Shuai; McCollough, Cynthia H; Yu, Lifeng

    2016-12-01

    This study aimed to investigate the influence of display window setting on technologist performance detecting subtle but clinically relevant artifacts in daily computed tomography (CT) quality control (dQC) images. Fifty three sets of dQC images were retrospectively selected, including 30 sets without artifacts, and 23 with subtle but clinically relevant artifacts. They were randomized and shown to six CT technologists (two new and four experienced). Each technologist reviewed all images in each of two sessions, one with a display window width (WW) of 100 HU, which is currently recommended by the American College of Radiology, and the other with a narrow WW of 40 HU, both at a window level of 0 HU. For each case, technologists rated the presence of image artifacts based on a five point scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the artifact detection performance. At a WW of 100 HU, the AUC (95% confidence interval) was 0.658 (0.576, 0.740), 0.532 (0.429, 0.635), and 0.616 (0.543, 0.619) for the experienced, new, and all technologists, respectively. At a WW of 40 HU, the AUC was 0.768 (0.687, 0.850), 0.546 (0.433, 0.658), and 0.694 (0.619, 0.769), respectively. The performance significantly improved at WW of 40 HU for experienced technologists (p = 0.009) and for all technologists (p = 0.040). Use of a narrow display WW significantly improved technologists' performance in dQC for detecting subtle but clinically relevant artifacts as compared to that using a 100 HU display WW.

  13. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    Energy Technology Data Exchange (ETDEWEB)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A. [Canis Lupus LLC and Department of Human Oncology, University of Wisconsin, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Departments of Human Oncology, Medical Physics, and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2011-02-15

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa

  14. The clinical nanomedicine handbook

    CERN Document Server

    Brenner, Sara

    2013-01-01

    Designed to foster a stronger awareness and exploration of the subject by practicing clinicians, medical researchers and scientists, The Clinical Nanomedicine Handbook discusses the integration of nanotechnology, biology, and medicine from a clinical point of view. The book highlights relevant research and applications by specialty; it examines nanotechnology in depth, and the potential to solve medical problems. It also increases literacy in nanotechnology, and allows for more effective communication and collaboration between disciplines. Details worldwide developments in nanomedicine Provide

  15. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD. PMID:24467844

  16. Extracellular membrane vesicles in blood products-biology and clinical relevance

    Directory of Open Access Journals (Sweden)

    Emilija Krstova Krajnc

    2016-01-01

    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  17. Identification of clinically relevant viridans streptococci by an oligonucleotide array.

    Science.gov (United States)

    Chen, Chao Chien; Teng, Lee Jene; Kaiung, Seng; Chang, Tsung Chain

    2005-04-01

    Viridans streptococci (VS) are common etiologic agents of subacute infective endocarditis and are capable of causing a variety of pyogenic infections. Many species of VS are difficult to differentiate by phenotypic traits. An oligonucleotide array based on 16S-23S rRNA gene intergenic spacer (ITS) sequences was developed to identify 11 clinically relevant VS. These 11 species were Streptococcus anginosus, S. constellatus, S. gordonii, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, and S. uberis. The method consisted of PCR amplification of the ITS regions by using a pair of universal primers, followed by hybridization of the digoxigenin-labeled PCR products to a panel of species-specific oligonucleotides immobilized on a nylon membrane. After 120 strains of the 11 species of VG and 91 strains of other bacteria were tested, the sensitivity and specificity of the oligonucleotide array were found to be 100% (120 of 120 strains) and 95.6% (87 of 91 strains), respectively. S. pneumoniae cross-hybridized to the probes used for the identification of S. mitis, and simple biochemical tests such as optochin susceptibility or bile solubility should be used to differentiate S. pneumoniae from S. mitis. In conclusion, identification of species of VS by use of the present oligonucleotide array is accurate and could be used as an alternative reliable method for species identification of strains of VS.

  18. Clinically relevant diagnostic research in primary care : the example of B-type natriuretic peptides in the detection of heart failure

    NARCIS (Netherlands)

    Kelder, Johannes C.; Rutten, Frans H.; Hoes, Arno W.

    With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart

  19. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  20. Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.

    Science.gov (United States)

    Reginster, J-Y; Reiter-Niesert, S; Bruyère, O; Berenbaum, F; Brandi, M-L; Branco, J; Devogelaer, J-P; Herrero-Beaumont, G; Kanis, J; Maggi, S; Maheu, E; Richette, P; Rizzoli, R; Cooper, C

    2015-12-01

    The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Automation of the consensus guidelines in diabetes care: potential impact on clinical inertia.

    Science.gov (United States)

    Albisser, A Michael; Inhaber, Francine

    2010-01-01

    To propose that automation of the consensus guidelines and mandated targets (CG&MT) in glycemia, hemoglobin A1c, and body weight will facilitate optimal clinical management of patients with diabetes. (1) A simplified method for capturing diabetes outcomes at home was devised, (2) relevant portions of the CG&MT were translated into computer code and automated, and (3) algorithms were applied to transform data from self-monitoring of blood glucose into circadian profiles and hemoglobin A1c levels. (4) The resulting procedures were integrated into a USB memory drive for use by health-care providers at the point of care. For input from patients, a simple form is used to capture data on diabetes outcomes, including blood glucose measurements before and after meals and at bedtime, medication, and lifestyle events in a structured fashion. At each encounter with a health-care provider, the patient's data are transferred into the device and become available to assist in identifying deviations from mandated targets, potential risks of hypoglycemia, and necessary prescription changes. Preliminary observations during a 2 1/2-year period from a community support group dedicated to glycemic control on 20 unselected patients (10 with and 10 without use of the device) are summarized. With use of the automated information, the health professional is supported at the point of care to achieve better, safer outcomes and practice evidence-based medicine entirely in lockstep with the CG&MT. This automation helps to overcome clinical inertia.

  2. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie; Matsuoka, Nobuhiro; Rollins, Douglas; Badger, Troy; Rodesch, Christopher K.; Barry, William H.

    2009-01-01

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca 2+ ] i was measured by flow cytometry using fluo-3. Mitochondrial [Ca 2+ ] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca 2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca 2+ ] i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca 2+ ] i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca 2+ ] i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

  3. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

    Science.gov (United States)

    Siegal, Tali

    2016-01-01

    Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

  4. Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature.

    Science.gov (United States)

    Wong, Kam Cheong

    2011-03-29

    Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.

  5. Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

    Directory of Open Access Journals (Sweden)

    Wong Kam Cheong

    2011-03-01

    Full Text Available Abstract Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries. In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings. An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.

  6. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  7. New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance.

    Science.gov (United States)

    Bove, Thierry; François, Katrien; De Wolf, Daniel

    2015-01-01

    The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

  8. A framework to assess the value of application of formal criteria to check clinical relevance in RCTs as part of a benefit assessment strategy.

    Science.gov (United States)

    Vach, Werner; Gladstone, Beryl Primrose

    2016-01-01

    Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error-specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients.

    Science.gov (United States)

    Kovarik, Miroslav; Hronek, Miloslav; Zadak, Zdenek

    2014-04-01

    Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. 7T: Physics, safety, and potential clinical applications.

    Science.gov (United States)

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  11. Assessing the prevalence and clinical relevance of positive abdominal and pelvic CT findings in senior patients presenting to the emergency department.

    Science.gov (United States)

    Alabousi, Abdullah; Patlas, Michael N; Meshki, Malek; Monteiro, Sandra; Katz, Douglas S

    2016-04-01

    The purpose of our study was to retrospectively evaluate the prevalence and clinical relevance of positive abdominal and pelvic CT findings for patients 65 years of age and older, when compared with all other scanned adult Emergency Department (ED) patients, at a single tertiary care hospital. Our hypothesis was that there is an increased prevalence and clinical relevance of positive abdominal/pelvic CT findings in senior patients. A research ethics board-approved retrospective review of all adult patients who underwent an emergency CT of the abdomen and pelvis for acute nontraumatic abdominal and/or pelvic signs and symptoms was performed. Two thousand one hundred two patients between October 1, 2011, and September 30, 2013, were reviewed. Six hundred thirty-one patients were included in the 65 group (209 men and 253 women; mean age 77.6, age range 65-99). Overall, there were more positive CT findings for patients 65 group (257 positive cases, 55.6 %), which was a statistically significant difference (p 65 group, there were no statistically significant differences in the clinical/surgical relevance of the positive CT findings between the two groups. The findings of our retrospective study therefore refute our hypothesis that there is an increased prevalence of positive abdominal CT findings in patients >65. This may be related to ED physicians at our institution being more hesitant to order CT examinations for the younger population, presumably due to radiation concerns. However, older patients in our series were more likely to present with complicated appendicitis, and a lower threshold for ordering CT examinations of the abdomen and pelvis in this patient population should therefore be considered.

  12. Clinical relevance of the effects of reach-to-grasp training using trunk restraint in individuals with hemiparesis poststroke: A systematic review.

    Science.gov (United States)

    Greisberger, Andrea; Aviv, Hanna; Garbade, Sven F; Diermayr, Gudrun

    2016-04-28

    To evaluate the evidence for, and clinical relevance of, immediate and long-term effects of trunk restraint during reach-to-grasp training poststroke on movement patterns and functional abilities within the framework of the International Classification of Functioning, Disability and Health. PubMed, Web of Science, CINAHL, Embase, PEDro, Cochrane Library (publication dates January 1985 to March 2015). Randomized controlled trials comparing training using trunk restraint with any other exercise training. Data were extracted by one researcher and checked by two other researchers. The Cochrane Collaboration's tool for assessing risk of bias and the Physiotherapy Evidence Database scale were used by two researchers to assess study quality and risk of bias. Eight studies met the inclusion criteria. Five studies found better recovery of movement patterns (trunk displacement, elbow extension, and/or shoulder flexion - body function/structure) at post-test in the experimental compared with the control groups. Functional abilities (activity/participation) improved more in the experimental groups in 3 studies at post-test. Long-term effects were found in one study after 4 weeks. Trunk restraint has immediate and some long-term effects in adults with chronic stroke. However, these effects are not consistently clinically relevant when referring to minimal detectable change or minimal clinically important difference values.

  13. Exploring the information and communication technology competence and confidence of nursing students and their perception of its relevance to clinical practice.

    Science.gov (United States)

    Levett-Jones, Tracy; Kenny, Raelene; Van der Riet, Pamela; Hazelton, Michael; Kable, Ashley; Bourgeois, Sharon; Luxford, Yoni

    2009-08-01

    This paper profiles a study that explored nursing students' information and communication technology competence and confidence. It presents selected findings that focus on students' attitudes towards information and communication technology as an educational methodology and their perceptions of its relevance to clinical practice. Information and communication technology is integral to contemporary nursing practice. Development of these skills is important to ensure that graduates are 'work ready' and adequately prepared to practice in increasingly technological healthcare environments. This was a mixed methods study. Students (n=971) from three Australian universities were surveyed using an instrument designed specifically for the study, and 24 students participated in focus groups. The focus group data revealed that a number of students were resistant to the use of information and communication technology as an educational methodology and lacked the requisite skills and confidence to engage successfully with this educational approach. Survey results indicated that 26 per cent of students were unsure about the relevance of information and communication technology to clinical practice and only 50 per cent felt 'very confident' using a computer. While the importance of information and communication technology to student's learning and to their preparedness for practice has been established, it is evident that students' motivation is influenced by their level of confidence and competence, and their understanding of the relevance of information and communication technology to their future careers.

  14. Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse

    International Nuclear Information System (INIS)

    Lallemant, Benjamin; Hollande, Frédéric; Lallemant, Jean-Gabriel; Lumbroso, Serge; Brouillet, Jean-Paul; Evrard, Alexandre; Combescure, Christophe; Chapuis, Heliette; Chambon, Guillaume; Raynal, Caroline; Reynaud, Christophe; Sabra, Omar; Joubert, Dominique

    2009-01-01

    Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva

  15. Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats.

    Science.gov (United States)

    Kandasamy, Ram; Lee, Andrea T; Morgan, Michael M

    2017-12-01

    The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.

  16. Relevance of randomised controlled trials in oncology.

    Science.gov (United States)

    Tannock, Ian F; Amir, Eitan; Booth, Christopher M; Niraula, Saroj; Ocana, Alberto; Seruga, Bostjan; Templeton, Arnoud J; Vera-Badillo, Francisco

    2016-12-01

    Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Sentinel lymph node biopsy: clinical relevance

    International Nuclear Information System (INIS)

    Howman-Giles, R.

    2002-01-01

    accurate determination of sentinel nodes in all areas. There is a significant number of unusual and unexpected drainage patterns found in melanoma many of which would be undetectable if only using a gamma probe alone or delayed imaging with large particles. There is also some controversy in breast cancer on the most accurate sentinel node technique and the relevance of extra axillary drainage sites eg internal mammary chain. The sentinel lymph node mapping with lymphoscintigraphy and blue due in association with applications of the gamma probe at surgery for accurate localisation of sentinel nodes is making a significant impact on patient management. This is in particular by more accurate staging and prognostic information with better stratification of patients requiring further regional node dissection and those suitable for adjuvant therapy and specific clinical trials

  18. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.

    2011-01-01

    designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...... exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.Leukemia advance online publication, 18 March 2011; doi:10.1038/leu.2011.32....

  19. The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Schimmack, Simon; Lawrence, Ben; Svejda, Bernhard; Alaimo, Daniele; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Kidd, Mark; Modlin, Irvin

    2012-05-15

    Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker. Functional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses. In BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior. Copyright © 2011 American Cancer Society.

  20. Comparison of Two Old Phytochemicals versus Two Newly Researched Plant-Derived Compounds: Potential for Brain and Other Relevant Ailments

    Directory of Open Access Journals (Sweden)

    Chun-Mei Wang

    2014-01-01

    Full Text Available Among hundreds of formulae of Chinese herbal prescriptions and recently extracted active components from the herbs, some of which had demonstrated their functions on nervous system. For the last decade or more, Gingko biloba and Polygala tenuifolia were widely studied for their beneficial effects against damage to the brain. Two compounds extracted from Apium graveolens and Rhizoma coptidis, butylphthalide and berberine, respectively, received much attention recently as potential neuroprotective agents. In this review, the two traditionally used herbs and the two relatively new compounds will be discussed with regard to their potential advantages in alleviating brain and other relevant ailments.

  1. Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.

    Science.gov (United States)

    Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan

    2016-12-01

    Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Are research papers reporting results from nutrigenetics clinical research a potential source of biohype?

    Science.gov (United States)

    Stenne, R; Hurlimann, T; Godard, Béatrice

    2012-01-01

    Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.

  3. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations.

    Science.gov (United States)

    Tamborero, David; Rubio-Perez, Carlota; Deu-Pons, Jordi; Schroeder, Michael P; Vivancos, Ana; Rovira, Ana; Tusquets, Ignasi; Albanell, Joan; Rodon, Jordi; Tabernero, Josep; de Torres, Carmen; Dienstmann, Rodrigo; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

    2018-03-28

    While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .

  4. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

    2018-04-06

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

  5. A comparison of two tools to screen potentially inappropriate medication in internal medicine patients.

    Science.gov (United States)

    Blanc, A-L; Spasojevic, S; Leszek, A; Théodoloz, M; Bonnabry, P; Fumeaux, T; Schaad, N

    2018-04-01

    Potentially inappropriate medication (PIM) is an important issue for inpatient management; it has been associated with safety problems, such as increases in adverse drugs events, and with longer hospital stays and higher healthcare costs. To compare two PIM-screening tools-STOPP/START and PIM-Check-applied to internal medicine patients. A second objective was to compare the use of PIMs in readmitted and non-readmitted patients. A retrospective observational study, in the general internal medicine ward of a Swiss non-university hospital. We analysed a random sample of 50 patients, hospitalized in 2013, whose readmission within 30 days of discharge had been potentially preventable, and compared them to a sample of 50 sex- and age-matched patients who were not readmitted. PIMs were screened using the STOPP/START tool, developed for geriatric patients, and the PIM-Check tool, developed for internal medicine patients. The time needed to perform each patient's analysis was measured. A clinical pharmacist counted and evaluated each PIM detected, based on its clinical relevance to the individual patient's case. The rates of screened and validated PIMs involving readmitted and non-readmitted patients were compared. Across the whole population, PIM-Check and STOPP/START detected 1348 and 537 PIMs, respectively, representing 13.5 and 5.4 PIMs/patient. Screening time was substantially shorter with PIM-Check than with STOPP/START (4 vs 10 minutes, respectively). The clinical pharmacist judged that 45% and 42% of the PIMs detected using PIM-Check and STOPP/START, respectively, were clinically relevant to individual patients' cases. No significant differences in the rates of detected and clinically relevant PIM were found between readmitted and non-readmitted patients. Internal medicine patients are frequently prescribed PIMs. PIM-Check's PIM detection rate was three times higher than STOPP/START's, and its screening time was shorter thanks to its electronic interface. Nearly

  6. Contemporary cosmetic surgery: the potential risks and relevance for practice.

    Science.gov (United States)

    Gilmartin, Jo

    2011-07-01

    To examine and critique the risks of cosmetic surgery and consider implications for practice. Cosmetic surgery is a growing industry with a significant global phenomenon. Feminists have been critical of aesthetic surgery practice, offering a range of representations in regard to 'identity', 'normality', 'cultural and social pressures', 'agency' and 'self-enhancement'. Discourses around minimising risk information acknowledge deficits in not supplying patients with full risk information. The results are usually devastating and lead to serious health complications that incisively diminish well-being for patients and increase health costs. Critical review. This paper represents a critical review of risks associated with cosmetic surgery. A Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System online (Medline) and British Nursing Index (BNI) search with relevant key words were undertaken and selected exemplary articles and research describing and/or evaluating cosmetic surgery risk. Only papers in the English language from 1982-2009 were reviewed. The papers examined were mainly empirical studies; some opinion papers, policy documents, textbooks and websites were examined too. The literature revealed that several factors influence consumer risks including regulation vagaries, medicalisation processes, fear of ageing discrimination, wanting to avoid ethnic prejudice and media pressure. Government strategies in the United Kingdom (UK) have attempted to improve clinical standards; however, little attempt has been made globally to raise institutional and professional awareness of the huge impact of cultural and social pressures on consumers. Avoiding shattering complications by improving the provision of risk information for patients is a worthwhile goal. Therefore, health professionals need to consider consumer rights and autonomy more carefully, facilitate rigorous screening and develop knowledge in regard to

  7. [18F]FDG in recurrent breast cancer: diagnostic performances, clinical impact and relevance of induced changes in management

    International Nuclear Information System (INIS)

    Grahek, Dany; Montravers, Francoise; Kerrou, Khaldoun; Aide, Nicolas; Talbot, Jean-Noel; Lotz, Jean-Pierre

    2004-01-01

    Prognosis and management of patients with recurrent breast cancer depend on the spread of the disease. The aim of this study was to evaluate the performance of fluorine-18 fluorodeoxyglucose gamma camera positron emission tomography (FDG-GPET) in detecting breast cancer recurrence, its clinical impact and the relevance of induced changes in management. Patients (n=134) with suspicion of recurrence either clinically or on conventional imaging (suspected recurrence: SR) or with an isolated increase in tumour marker levels (occult recurrence: OR) underwent FDG-GPET on a coincidence gamma camera. The reference standard for evaluation of accuracy, either histology (n=26) or follow-up for 1 year (n=49), was available in 75 (56%) patients. A questionnaire was sent to the referring clinician to evaluate the impact of FDG on management. Responses were obtained for 75 patients. Information regarding both approaches was available for 46 patients (46/134=34%). At the patient level, the sensitivity of FDG-GPET was 84%, significantly higher than the 63% sensitivity for conventional modalities, and the specificity was 78% versus 61%. The values for FDG-GPET were 81% and 86% respectively in the SR group and 90% and 73% respectively in the OR group, without any significant difference between these settings. The rate of change in management was 44% overall, 43% in the SR group and 45% in the OR group. Within the two groups, intermodality (major) changes were more frequent than intramodality (minor) changes. In the 46 patients for whom both approaches were available, 93% of management modifications were relevant (validated by biopsy or clinical follow-up). The results of this retrospective study show that FDG-GPET has an important role to play in patient management by confirming and evaluating the extent of recurrence or by localising occult recurrence (orig.)

  8. Clinical relevance and prognostic value of radiographic findings in Zenker's diverticulum.

    Science.gov (United States)

    Mantsopoulos, Konstantinos; Psychogios, Georgios; Karatzanis, Alexander; Künzel, Julian; Lell, Michael; Zenk, Johannes; Koch, Michael

    2014-03-01

    The aim of this study was to evaluate the clinical relevance and prognostic value of preoperative and postoperative oesophagography in patients with Zenker's diverticulum. The medical records of 155 patients who underwent surgical treatment (with an endoscopic or transcervical approach) for Zenker's diverticulum between 1992 and 2010 in a tertiary referral centre were retrospectively evaluated. The size of the diverticula on oesophagography, recognizable muscular septum, and protection of the diverticulum were assessed relative to the surgical procedures performed. The incidence of diverticular remnants on postoperative oesophagography was also assessed relative to the surgical procedure. It was investigated whether the detection of a residual pharyngeal pouch and filling of it with contrast medium were related to the patients' immediate postoperative symptoms and the development of symptomatic recurrence. Larger diverticula (Brombart III-IV) were manageable significantly more often with endoscopic procedures (P = 0.007). Residual diverticulum and filling with contrast medium were strongly associated with prolonged dysphagia immediately postoperatively (P = 0.005 and P = 0.009, respectively). However, these parameters failed to correlate significantly with a symptomatic recurrence. Preoperative oesophagography proved to be extremely important for surgical planning, with the surgeon's personal preference seeming to be the driving indicator in many cases. Postoperative oesophagography is only useful for excluding postoperative complications in the immediate postoperative phase and did not have a prognostic value as to a recurrence of the disease.

  9. Relevant energy scale of color confinement from lattice QCD

    International Nuclear Information System (INIS)

    Yamamoto, Arata; Suganuma, Hideo

    2009-01-01

    We propose a new lattice framework to extract the relevant gluonic energy scale of QCD phenomena which is based on a 'cut' on link variables in momentum space. This framework is expected to be broadly applicable to all lattice QCD calculations. Using this framework, we quantitatively determine the relevant energy scale of color confinement, through the analyses of the quark-antiquark potential and meson masses. The relevant energy scale of color confinement is found to be below 1.5 GeV in the Landau gauge. In fact, the string tension is almost unchanged even after cutting off the high-momentum gluon component above 1.5 GeV. When the relevant low-energy region is cut, the quark-antiquark potential is approximately reduced to a Coulomb-like potential, and each meson becomes a quasifree quark pair. As an analytical model calculation, we also investigate the dependence of the Richardson potential on the cut, and find the consistent behavior with the lattice result.

  10. Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer

    International Nuclear Information System (INIS)

    Schee, Kristina; Boye, Kjetil; Abrahamsen, Torveig Weum; Fodstad, Øystein; Flatmark, Kjersti

    2012-01-01

    MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and can function as oncogenes or tumor suppressors depending on the target. In this study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed. The miRNAs were chosen based on previous studies for their biomarker potential and suggested biological relevance in colorectal cancer. The miRNA expression was examined by qRT-PCR. Associations between miRNA expression and clinicopathological variables were explored using Mann–Whitney U and Kruskal-Wallis test while survival was estimated using the Kaplan-Meier method and compared using the log-rank test. MiR-101 was hardly expressed in the tumor samples, while for the other miRNAs, variable expression levels and expression ranges were observed, with miR-21 being most abundantly expressed relative to the reference (RNU44). In our study cohort, major clinical significance was demonstrated only for miR-31, as high expression was associated with advanced tumor stage and poor differentiation. No significant associations were found between expression of the investigated miRNAs and metastasis-free or overall survival. Investigating the expression of six miRNAs previously identified as candidate biomarkers in colorectal cancer, few clinically relevant associations were detected in our patient cohort. Our results emphasize the importance of validating potential tumor markers in independent patient cohorts, and indicate that the role of miRNAs as colorectal cancer biomarkers is still undetermined

  11. Passage relevance models for genomics search

    Directory of Open Access Journals (Sweden)

    Frieder Ophir

    2009-03-01

    Full Text Available Abstract We present a passage relevance model for integrating syntactic and semantic evidence of biomedical concepts and topics using a probabilistic graphical model. Component models of topics, concepts, terms, and document are represented as potential functions within a Markov Random Field. The probability of a passage being relevant to a biologist's information need is represented as the joint distribution across all potential functions. Relevance model feedback of top ranked passages is used to improve distributional estimates of query concepts and topics in context, and a dimensional indexing strategy is used for efficient aggregation of concept and term statistics. By integrating multiple sources of evidence including dependencies between topics, concepts, and terms, we seek to improve genomics literature passage retrieval precision. Using this model, we are able to demonstrate statistically significant improvements in retrieval precision using a large genomics literature corpus.

  12. Overview on Clinical Relevance of Intra-Tumor Heterogeneity.

    Science.gov (United States)

    Stanta, Giorgio; Bonin, Serena

    2018-01-01

    Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH) is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  13. Overview on Clinical Relevance of Intra-Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Giorgio Stanta

    2018-04-01

    Full Text Available Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  14. Bicuspid aortic valve syndrome and fibrillinopathies: potential impact on clinical approach

    Directory of Open Access Journals (Sweden)

    Rosina De Cario

    2014-01-01

    Full Text Available Bicuspid aortic valve (BAV is a common heterogeneous disorder whose natural history is determined by hemodynamic valvular impairment and/or increased prevalence of aortic abnormalities ranging from dilatation to aneurysm and dissection. BAV-related aortopathy is frequently associated with relevant aortic pathologic changes leading to structural alterations, characteristic degenerative lesions and histological changes of the aorta very similar to those identified and described in patients with Marfan syndrome (MFS, an inherited connective tissue disorder associated with mutations in fibrillin 1 (FBN1 gene in more than 90% of patients. Recently, a 4-fold increase in the prevalence of BAV in MFS patients has been reported. Subsequently, pathogenetic FBN1 mutations in patients with BAV and aortic dilatation/aneurysm in whom MFS and other more severe type 1 fibrillinopathies were clinically excluded have been identified. In this review we discuss how this evidence, together with that of the wide heterogeneity in pathogenetic mechanisms of BAV-related aortopathy, may impact the clinical management of BAV.

  15. Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

    Science.gov (United States)

    Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael

    2015-03-01

    Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.

  16. Genome-wide association studies in bladder cancer: first results and potential relevance.

    Science.gov (United States)

    Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

    2009-09-01

    The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

  17. Transient ischemic attacks with and without a relevant infarct on computed tomographic scans cannot be distinguished clinically. Dutch Transient Ischemic Attack Study Group

    NARCIS (Netherlands)

    Koudstaal, P. J.; van Gijn, J.; Lodder, J.; Frenken, W. G.; Vermeulen, M.; Franke, C. L.; Hijdra, A.; Bulens, C.

    1991-01-01

    We prospectively studied clinical and computed tomographic (CT) scan findings in 79 patients with a transient ischemic attack (TIA) and a relevant cerebral infarction on CT, also known as cerebral infarction with transient signs (CITS). We compared the results with those of 527 concurrent patients

  18. Clinical relevance and cost-effectiveness of HLA genotyping in children with Type 1 diabetes mellitus in screening for coeliac disease in the Netherlands

    NARCIS (Netherlands)

    Elias, J.; Hoorweg-Nijman, J. J. G.; Balemans, W. A.

    2015-01-01

    To investigate the clinical relevance and cost-effectiveness of human leukocyte antigen (HLA)-genotyping in the Netherlands as a screening tool for the development of coeliac disease in children with Type 1 diabetes mellitus. A retrospective analysis was performed in 110 children with Type 1

  19. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Kostadinova, Radina; Boess, Franziska; Applegate, Dawn; Suter, Laura; Weiser, Thomas; Singer, Thomas; Naughton, Brian; Roth, Adrian

    2013-01-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  20. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kostadinova, Radina; Boess, Franziska [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Applegate, Dawn [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Suter, Laura; Weiser, Thomas; Singer, Thomas [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland); Naughton, Brian [RegeneMed, 9855 Towne Centre Drive Suite 200, San Diego, CA 92121 (United States); Roth, Adrian, E-mail: adrian_b.roth@roche.com [Non-Clinical Safety, Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Building 73 / Room 117b, 4070 Basel (Switzerland)

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity

  1. Transformational leadership: is this still relevant to clinical leaders?

    Science.gov (United States)

    Lo, David; McKimm, Judy; Till, Alex

    2018-06-02

    Transformational leadership theory has been at the centre of health-care leadership research for the past three decades, has had a tangible influence on the evolution of NHS leadership development strategies, and is still evident in current frameworks. This article provides an overview of the key concepts and weaknesses of transformational leadership theory and discusses its relevance within the context of the NHS working environment.

  2. A Narrative Review of Lumbar Fusion Surgery With Relevance to Chiropractic Practice.

    Science.gov (United States)

    Daniels, Clinton J; Wakefield, Pamela J; Bub, Glenn A; Toombs, James D

    2016-12-01

    The purpose of this narrative review was to describe the most common spinal fusion surgical procedures, address the clinical indications for lumbar fusion in degeneration cases, identify potential complications, and discuss their relevance to chiropractic management of patients after surgical fusion. The PubMed database was searched from the beginning of the record through March 31, 2015, for English language articles related to lumbar fusion or arthrodesis or both and their incidence, procedures, complications, and postoperative chiropractic cases. Articles were retrieved and evaluated for relevance. The bibliographies of selected articles were also reviewed. The most typical lumbar fusion procedures are posterior lumbar interbody fusion, anterior lumbar interbody fusion, transforaminal interbody fusion, and lateral lumbar interbody fusion. Fair level evidence supports lumbar fusion procedures for degenerative spondylolisthesis with instability and for intractable low back pain that has failed conservative care. Complications and development of chronic pain after surgery is common, and these patients frequently present to chiropractic physicians. Several reports describe the potential benefit of chiropractic management with spinal manipulation, flexion-distraction manipulation, and manipulation under anesthesia for postfusion low back pain. There are no published experimental studies related specifically to chiropractic care of postfusion low back pain. This article describes the indications for fusion, common surgical practice, potential complications, and relevant published chiropractic literature. This review includes 10 cases that showed positive benefits from chiropractic manipulation, flexion-distraction, and/or manipulation under anesthesia for postfusion lumbar pain. Chiropractic care may have a role in helping patients in pain who have undergone lumbar fusion surgery.

  3. [Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

    Science.gov (United States)

    Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

    2013-09-01

    To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  4. Determination of redox potentials for the Watson-Crick base pairs, DNA nucleosides, and relevant nucleoside analogues.

    Science.gov (United States)

    Crespo-Hernandez, Carlos E; Close, David M; Gorb, Leonid; Leszczynski, Jerzy

    2007-05-17

    Redox potentials for the DNA nucleobases and nucleosides, various relevant nucleoside analogues, Watson-Crick base pairs, and seven organic dyes are presented based on DFT/B3LYP/6-31++G(d,p) and B3YLP/6-311+G(2df,p)//B3LYP/6-31+G* levels of calculations. The values are determined from an experimentally calibrated set of equations that correlate the vertical ionization (electron affinity) energy of 20 organic molecules with their experimental reversible oxidation (reduction) potential. Our results are in good agreement with those estimated experimentally for the DNA nucleosides in acetonitrile solutions (Seidel et al. J. Phys. Chem. 1996, 100, 5541). We have found that nucleosides with anti conformation exhibit lower oxidation potentials than the corresponding syn conformers. The lowering in the oxidation potential is due to the formation of an intramolecular hydrogen bonding interaction between the 5'-OH group of the sugar and the N3 of the purine bases or C2=O of the pyrimidine bases in the syn conformation. Pairing of adenine or guanine with its complementary pyrimidine base decreases its oxidation potential by 0.15 or 0.28 V, respectively. The calculated energy difference between the oxidation potential for the G.C base pair and that of the guanine base is in good agreement with the experimental value estimated recently (0.34 V: Caruso, T.; et al. J. Am. Chem. Soc. 2005, 127, 15040). The complete and consistent set of reversible redox values determined in this work for the DNA constituents is expected to be of considerable value to those studying charge and electronic energy transfer in DNA.

  5. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan

    2011-01-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non...

  6. Yeast identification in routine clinical microbiology laboratory and its clinical relevance

    Directory of Open Access Journals (Sweden)

    S Agarwal

    2011-01-01

    Full Text Available Rapid identification of yeast infections is helpful in prompt appropriate antifungal therapy. In the present study, the usefulness of chromogenic medium, slide culture technique and Vitek2 Compact (V2C has been analysed. A total of 173 clinical isolates of yeast species were included in the study. An algorithm to identify such isolates in routine clinical microbiology laboratory was prepared and followed. Chromogenic medium was able to identify Candida albicans, C. tropicalis, C. krusei, C. parapsilosis and Trichosporon asahii. Chromogenic medium was also helpful in identifying "multi-species" yeast infections. The medium was unable to provide presumptive identification of C. pelliculosa, C. utilis, C. rugosa, C. glabrata and C. hemulonii. Vitek 2 compact (V2C differentiated all pseudohypae non-producing yeast species. The algorithm followed was helpful in timely presumptive identification and final diagnosis of yeast infections, including multi-species yeast infections.

  7. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  8. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

    Science.gov (United States)

    Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

    2016-09-01

    Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

  9. Looking for a relevant potential evapotranspiration model at the watershed scale

    Science.gov (United States)

    Oudin, L.; Hervieu, F.; Michel, C.; Perrin, C.; Anctil, F.; Andréassian, V.

    2003-04-01

    In this paper, we try to identify the most relevant approach to calculate Potential Evapotranspiration (PET) for use in a daily watershed model, to try to bring an answer to the following question: "how can we use commonly available atmospheric parameters to represent the evaporative demand at the catchment scale?". Hydrologists generally see the Penman model as the ideal model regarding to its good adequacy with lysimeter measurements and its physically-based formulation. However, in real-world engineering situations, where meteorological stations are scarce, hydrologists are often constrained to use other PET formulae with less data requirements or/and long-term average of PET values (the rationale being that PET is an inherently conservative variable). We chose to test 28 commonly used PET models coupled with 4 different daily watershed models. For each test, we compare both PET input options: actual data and long-term average data. The comparison is made in terms of streamflow simulation efficiency, over a large sample of 308 watersheds. The watersheds are located in France, Australia and the United States of America and represent varied climates. Strikingly, we find no systematic improvements of the watershed model efficiencies when using actual PET series instead of long-term averages. This suggests either that watershed models may not conveniently use the climatic information contained in PET values or that formulae are only awkward indicators of the real PET which watershed models need.

  10. Patient-reported symptoms during radiotherapy. Clinically relevant symptom burden in patients treated with palliative and curative intent

    Energy Technology Data Exchange (ETDEWEB)

    Koerner, Philipp [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany); Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Ehrmann, Katja [Universitaetsklinikum Wuerzburg, Medizinische Psychologie und Psychotherapie, Medizinische Soziologie und Rehabilitationswissenschaften, Wuerzburg (Germany); Hartmannsgruber, Johann [Praxis Landshut, Kinderzahnheilkunde, Landshut (Germany); Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael [Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Oorschot, Birgitt van [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany)

    2017-07-15

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom burden

  11. Disposable inkjet-printed electrochemical platform for detection of clinically relevant HER-2 breast cancer biomarker.

    Science.gov (United States)

    Carvajal, Susanita; Fera, Samantha N; Jones, Abby L; Baldo, Thaisa A; Mosa, Islam M; Rusling, James F; Krause, Colleen E

    2018-05-01

    Rapidly fabricated, disposable sensor platforms hold tremendous promise for point-of-care detection. Here, we present an inexpensive (Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified surface on the WEA and placed into a microfluidic device. A full sandwich immunoassay was constructed following a simultaneous injection of target protein, biotinylated antibody, and polymerized horseradish peroxide labels into the microfluidic device housing the WEA. With an ultra fast assay time, of only 15mins a clinically relevant limit of detection of 12pgmL -1 was achieved. Excellent reproducibility and sensitivity were observed through recovery assays preformed in human serum with recoveries ranging from 76% to 103%. These easily fabricated and scalable electrochemical sensor platforms can be readily adapted for multiplex detection following this rapid assay protocol for cancer diagnostics. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Prevention of ventilator-associated pneumonia in the intensive care unit: A review of the clinically relevant recent advancements

    Directory of Open Access Journals (Sweden)

    Holly Keyt

    2014-01-01

    Full Text Available Ventilator-associated pneumonia (VAP is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. The pathophysiology, epidemiology, treatment and prevention of VAP have been extensively studied for decades, but a clear prevention strategy has not yet emerged. In this article we will review recent literature pertaining to evidence-based VAP-prevention strategies that have resulted in clinically relevant outcomes. A multidisciplinary strategy for prevention of VAP is recommended. Those interventions that have been shown to have a clinical impact include the following: (i Non-invasive positive pressure ventilation for able patients, especially in immunocompromised patients, with acute exacerbation of chronic obstructive pulmonary disease or pulmonary oedema, (ii Sedation and weaning protocols for those patients who do require mechanical ventilation, (iii Mechanical ventilation protocols including head of bed elevation above 30 degrees and oral care, and (iv Removal of subglottic secretions. Other interventions, such as selective digestive tract decontamination, selective oropharyngeal decontamination and antimicrobial-coated endotracheal tubes, have been tested in different studies. However, the evidence for the efficacy of these measures to reduce VAP rates is not strong enough to recommend their use in clinical practice. In numerous studies, the implementation of VAP prevention bundles to clinical practice was associated with a significant reduction in VAP rates. Future research that considers clinical outcomes as primary endpoints will hopefully result in more detailed prevention strategies.

  13. System for selecting relevant information for decision support.

    Science.gov (United States)

    Kalina, Jan; Seidl, Libor; Zvára, Karel; Grünfeldová, Hana; Slovák, Dalibor; Zvárová, Jana

    2013-01-01

    We implemented a prototype of a decision support system called SIR which has a form of a web-based classification service for diagnostic decision support. The system has the ability to select the most relevant variables and to learn a classification rule, which is guaranteed to be suitable also for high-dimensional measurements. The classification system can be useful for clinicians in primary care to support their decision-making tasks with relevant information extracted from any available clinical study. The implemented prototype was tested on a sample of patients in a cardiological study and performs an information extraction from a high-dimensional set containing both clinical and gene expression data.

  14. Exploring the potential duty of care in clinical genomics under UK law.

    Science.gov (United States)

    Mitchell, Colin; Ploem, Corrette; Chico, Victoria; Ormondroyd, Elizabeth; Hall, Alison; Wallace, Susan; Fay, Michael; Goodwin, Deirdre; Bell, Jessica; Phillips, Simon; Taylor, Jenny C; Hennekam, Raoul; Kaye, Jane

    2017-09-01

    Genome-wide sequencing technologies are beginning to be used in projects that have both clinical diagnostic and research components. The clinical application of this technology, which generates a huge amount of information of varying diagnostic certainty, involves addressing a number of challenges to establish appropriate standards. In this article, we explore the way that UK law may respond to three of these key challenges and could establish new legal duties in relation to feedback of findings that are unrelated to the presenting condition (secondary, additional or incidental findings); duties towards genetic relatives as well as the patient and duties on the part of researchers and professionals who do not have direct contact with patients. When considering these issues, the courts will take account of European and international comparisons, developing guidance and relevant ethical, social and policy factors. The UK courts will also be strongly influenced by precedent set in case law.

  15. Clinical relevance of novel Otarine herpesvirus-3 in California sea lions (Zalophus californianus: lymphoma, esophageal ulcers, and strandings

    Directory of Open Access Journals (Sweden)

    Venn-Watson Stephanie

    2012-12-01

    Full Text Available Abstract Herpesviruses have been recognized in marine mammals, but their clinical relevance is not always easy to assess. A novel otarine herpesvirus-3 (OtHV3 was detected in a geriatric California sea lion (Zalophus californianus, and using a newly developed quantitative PCR assay paired with histology, OtHV3 was associated with esophageal ulcers and B cell lymphoblastic lymphoma in this animal. The prevalence and quantities of OtHV3 were then determined among buffy coats from 87 stranded and managed collection sea lions. Stranded sea lions had a higher prevalence of OtHV3 compared to managed collection sea lions (34.9% versus 12.5%; p = 0.04, and among the stranded sea lions, yearlings were most likely to be positive. Future epidemiological studies comparing the presence and viral loads of OtHV3 among a larger population of California sea lions with and without lymphoid neoplasia or esophageal ulcers would help elucidate the relevance of OtHV3-associated pathologies to these groups.

  16. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

    Science.gov (United States)

    Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

    2014-01-01

    Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

  17. Animal to human translational paradigms relevant for approach avoidance conflict decision making.

    Science.gov (United States)

    Kirlic, Namik; Young, Jared; Aupperle, Robin L

    2017-09-01

    Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

    Science.gov (United States)

    Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

    2008-12-01

    This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

  19. How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

    Science.gov (United States)

    Wong, Kam Cheong

    2016-04-06

    Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

  20. Potential role of a pharmacist to enhance medication-related aspects of clinical trials conducted in a dedicated clinical research unit

    Directory of Open Access Journals (Sweden)

    Kimberly A. Redic, PharmD

    2017-06-01

    Conclusions: This pilot study showed potential roles for pharmacy personnel involvement in medication reconciliation in the clinical research setting. Pharmacists have the opportunity to ensure that IDs are accurately included in patient medication lists and to identify the use of potential protocol prohibited concomitant medications.

  1. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

    Directory of Open Access Journals (Sweden)

    Susana ede Sola

    2015-06-01

    Full Text Available The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome(DS has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining

  2. Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema

    DEFF Research Database (Denmark)

    Vujosevic, Stela; Varano, Monica; Egan, Catherine

    2015-01-01

    PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were...... included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used....... A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield...

  3. Comparison of cell-based and non-cell-based assay platforms for the detection of clinically relevant anti-drug neutralizing antibodies for immunogenicity assessment of therapeutic proteins.

    Science.gov (United States)

    Hu, Jenny; Wala, Iwona; Han, Hong; Nagatani, Janice; Barger, Troy; Civoli, Francesca; Kaliyaperumal, Arunan; Zhuang, Yao; Gupta, Shalini

    2015-04-01

    Anti-drug neutralizing antibodies (NAbs) formed due to unwanted immunogenicity of a therapeutic protein point towards a mature immune response. NAb detection is important in interpreting the therapeutic's efficacy and safety in vivo. In vitro cell-based NAb assays provide a physiological system for NAb detection, however are complex assays. Non-cell-based competitive ligand binding (CLB) approaches are also employed for NAb detection. Instead of cells, CLB assays use soluble receptor and conjugated reagents and are easier to perform, however have reduced physiological relevance. The aim of this study was to compare the performance of CLB assays to established cell-based assays to determine the former's ability to detect clinically relevant NAbs towards therapeutics that (i) acted as an agonist or (ii) acted as antagonists by binding to a target receptor. We performed a head-to-head comparison of the performance of cell-based and CLB NAb assays for erythropoietin (EPO) and two anti-receptor monoclonal antibodies (AMG-X and AMG 317). Clinically relevant NAb-positive samples identified previously by a cell-based assay were assessed in the corresponding CLB format(s). A panel of 12 engineered fully human anti-EPO monoclonal antibodies (MAbs) was tested in both EPO NAb assay formats. Our results showed that the CLB format was (i) capable of detecting human anti-EPO MAbs of differing neutralizing capabilities and affinities and (ii) provided similar results as the cell-based assay for detecting NAbs in patient samples. The cell-based and CLB assays also behaved comparably in detecting NAbs in clinical samples for AMG-X. In the case of anti-AMG 317 NAbs, the CLB format failed to detect NAbs in more than 50% of the tested samples. We conclude that assay sensitivity, drug tolerance and the selected assay matrix played an important role in the inability of AMG 317 CLB assays to detect clinically relevant NAbs. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Development of a clinically relevant impingement test method for a mobile bearing lumbar total disc replacement.

    Science.gov (United States)

    Siskey, Ryan; Peck, Jonathan; Mehta, Hitesh; Kosydar, Allison; Kurtz, Steven; Hill, Genevieve

    2016-09-01

    Total disc arthroplasty is an alternative therapy to spinal fusion for the treatment of neck or low back pain and is hypothesized to reduce the risk of disease progression to the adjacent spinal levels. Radiographic and retrieval analyses of various total disc replacements (TDRs) have shown evidence of impingement damage. Impingement of TDRs can occur when the device reaches the limits of its functional range of motion, causing contact between peripheral regions of the device. Impingement can be associated with increased wear and mechanical damage; however, impingement conditions are not simulated in current standardized mechanical bench test methods. This study explored the test conditions necessary to apply clinically relevant impingement loading to a lumbar TDR in vitro. An experimental protocol was developed and evaluated using in vivo retrievals for qualitative and quantitative validation. Retrieval analysis was conducted on a set of 11 size 3 retrieved Charité devices using American Society for Testing and Materials F561 as a guide. The impingement range of motion was determined using a combination of modeling and experiments, and was used as an input in vitro testing. A 1-million cycle in vitro test was then conducted, and the in vitro samples were characterized using methods similar to the retreived devices. All in vitro tested samples exhibited impingement regions and damage patterns consistent with retrieved devices. Consistent with the retrievals, the impingement damage on the rim was a combination of abrasive wear and plastic deformation. Micro computed tomography (microCT) was used to quantitatively assess rim damage due to impingement. Rim penetration was statistically lower in the retrievals when compared with both in vitro groups. Rim elongation was comparable among all groups. The simulated-facet group had statistically greater angular rim deformations than the retrieval group and the no-facet group. Results demonstrate that clinically relevant

  5. The clinical relevance of advanced artificial feedback in the control of a multi-functional myoelectric prosthesis.

    Science.gov (United States)

    Markovic, Marko; Schweisfurth, Meike A; Engels, Leonard F; Bentz, Tashina; Wüstefeld, Daniela; Farina, Dario; Dosen, Strahinja

    2018-03-27

    -loop control does not improve the performance, it could be beneficial as it seems to improve the subjective experience. Therefore, in this study we demonstrate, for the first time, the relevance of an advanced, multi-variable feedback interface for dexterous, multi-functional prosthesis control in a clinically relevant setting.

  6. The potential of telehealth for 'business as usual' in outpatient clinics.

    Science.gov (United States)

    Day, Karen; Kerr, Patricia

    2012-04-01

    A six-month pilot study was conducted to ascertain the value of using high-definition videoconferencing equipment in an outpatients' setting. The videoconferencing equipment, which included digital biometric equipment, was installed in the outpatient clinics of a remote health service in New Zealand. Use of the equipment was evaluated using action research techniques. Clinicians were interviewed about their assessment of the equipment's usefulness. Patients and their carers completed questionnaires about their clinic experience. During the pilot trial, 109 patients were seen in 25 clinics of six different specialities. Questionnaire results showed that patients and their companions had a good user experience, similar to a face-to-face appointment. Clinicians found that the large screen, sense of proximity, video clarity and definition, and lack of sound/picture lag worked well for certain types of outpatients' clinics, e.g. methadone maintenance clinics. The need for process changes made it difficult to turn telehealth into business as usual in an environment built for face-to-face appointments. We conclude that videoconference equipment has potential to become integral to outpatients' clinics.

  7. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    Science.gov (United States)

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-07

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  8. A survey of anatomical items relevant to the practice of rheumatology: upper extremity, head, neck, spine, and general concepts.

    Science.gov (United States)

    Villaseñor-Ovies, Pablo; Navarro-Zarza, José Eduardo; Saavedra, Miguel Ángel; Hernández-Díaz, Cristina; Canoso, Juan J; Biundo, Joseph J; Kalish, Robert A; de Toro Santos, Francisco Javier; McGonagle, Dennis; Carette, Simon; Alvarez-Nemegyei, José

    2016-12-01

    This study aimed to identify the anatomical items of the upper extremity and spine that are potentially relevant to the practice of rheumatology. Ten rheumatologists interested in clinical anatomy who published, taught, and/or participated as active members of Clinical Anatomy Interest groups (six seniors, four juniors), participated in a one-round relevance Delphi exercise. An initial, 560-item list that included 45 (8.0 %) general concepts items; 138 (24.8 %) hand items; 100 (17.8 %) forearm and elbow items; 147 (26.2 %) shoulder items; and 130 (23.2 %) head, neck, and spine items was compiled by 5 of the participants. Each item was graded for importance with a Likert scale from 1 (not important) to 5 (very important). Thus, scores could range from 10 (1 × 10) to 50 (5 × 10). An item score of ≥40 was considered most relevant to competent practice as a rheumatologist. Mean item Likert scores ranged from 2.2 ± 0.5 to 4.6 ± 0.7. A total of 115 (20.5 %) of the 560 initial items reached relevance. Broken down by categories, this final relevant item list was composed by 7 (6.1 %) general concepts items; 32 (27.8 %) hand items; 20 (17.4 %) forearm and elbow items; 33 (28.7 %) shoulder items; and 23 (17.6 %) head, neck, and spine items. In this Delphi exercise, a group of practicing academic rheumatologists with an interest in clinical anatomy compiled a list of anatomical items that were deemed important to the practice of rheumatology. We suggest these items be considered curricular priorities when training rheumatology fellows in clinical anatomy skills and in programs of continuing rheumatology education.

  9. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    Science.gov (United States)

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  10. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz

    2014-07-01

    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  11. Echography of clinically relevant disorders in the genital tract of female dromedary camels.

    Science.gov (United States)

    Ali, Ahmed; Derar, Derar; Alsamri, Ali; Al Sobayil, Fahd

    2017-07-01

    The aim of this study was to characterize the clinically relevant genital tract disorders of dromedary camels. Reproductive tract examinations were performed via transrectal palpation, ultrasonography and vaginal exploration. The ultrasonic appearance of the reproductive pathology was described and compared with its morphology at laparotomy, after surgical removal, during postmortem examination or upon slaughter. Diagnosis was also confirmed by histopathology. The most frequently encountered follicular structures were larger than typical follicles (56/338, 16.6%) having three echo textures: 1) thin walls and clear hyperechogenic content (11.6%); 2) thick walls and few fibrous trabeculae (33.7%); and 3) thick walls and many echogenic transecting fibrinous strands (54.7%). Corpora lutea with non-echoic central cavity (5/31, 16.1%) were greater in diameter than those with no cavity (26/31, 83.9%) (P=0.03). A granulosa cell tumor (1/338, 0.3%) was multilocular and honeycombed in shape. Presence of a large, well-demarcated, hypoechogenic sac lateral to or beneath the uterine horn encasing the ovary was diagnostic for ovarian hydrobursitis (102/338, 30.2%). Hydrosalpinx and pyosalpinx (6/338, 1.8%) were beaded in appearance, with the ovary located outside these structures. Clinical endometritis/cervicitis (122, 36.1%) was characterized by changes in the homogeneity in about half of the cases. A greatly dilated uterus with clear, hypoechogenic or echogenic contents with signs of hydrometra and pyometra, respectively, was another categorization of a reproductive pathology (24/338, 7.1%). Highly reflective, linear structures were observed in cases with intrauterine fetal bone retention (1/338, 0.3%). In conclusion, reproductive pathologies in dromedary camels can be efficiently imaged by use of ultrasonic technologies, thus familiarizing the practitioner with these disorders and facilitating application of these technologies so that suitable treatment can occur is important

  12. Fructose use in clinical nutrition: metabolic effects and potential consequences.

    Science.gov (United States)

    Moulin, Sandra; Seematter, Gérald; Seyssel, Kevin

    2017-07-01

    The current article presents recent findings on the metabolic effects of fructose. Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

  13. Potential benefits and risks of clinical xenotransplantation

    Directory of Open Access Journals (Sweden)

    Cooper DKC

    2012-07-01

    Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs

  14. An ERP Study on Self-Relevant Object Recognition

    Science.gov (United States)

    Miyakoshi, Makoto; Nomura, Michio; Ohira, Hideki

    2007-01-01

    We performed an event-related potential study to investigate the self-relevance effect in object recognition. Three stimulus categories were prepared: SELF (participant's own objects), FAMILIAR (disposable and public objects, defined as objects with less-self-relevant familiarity), and UNFAMILIAR (others' objects). The participants' task was to…

  15. The role of neuropsychology in UK pediatric HIV care: Relevance to clinical practice and research.

    Science.gov (United States)

    Freeman, Anita

    2017-11-01

    There has been a dramatic improvement in the survival of children with perinatally-acquired HIV (PHIV) following the introduction of effective treatment in 1990s. The care for children living with PHIV is now focused on more accurately understanding the effects of both HIV and HIV treatment on the developing body and brain. An evaluation of current HIV neuroimaging, and neurocognitive research, when combined with clinical experience in the area of HIV, could help to inform United Kingdom (UK) PHIV service provision. This paper argues that an understanding from a neuropsychological perspective will help these young people to optimize their health, quality of life, and future functioning. The aim of the paper is to bring together research and clinical understanding of HIV and its treatment effects on the developing brain, together with an understanding of other potential neurological risk factors. It is argued here that there is a need for targeted neuropsychology assessment and preventative interventions, supported by clinical and preliminary research on the neurocognitive effects of HIV and its treatments.

  16. Potential clinical relevance of the 'little brain' on the mammalian heart.

    Science.gov (United States)

    Armour, J A

    2008-02-01

    It is hypothesized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This 'little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue.

  17. MR assessment of the repaired rotator cuff: prevalence, size, location, and clinical relevance of tendon rerupture

    International Nuclear Information System (INIS)

    Mellado, J.M.; Calmet, J.; Ballabriga, J.; Gine, J.; Olona, M.; Camins, A.; Perez del Palomar, L.

    2006-01-01

    The objectives of this study were to use magnetic resonance (MR) imaging to evaluate the prevalence, size, location, and clinical relevance of tendon rerupture following complete repair of full-thickness rotator cuff tear (RCT). A total of 78 surgically proven full-thickness rotator cuff tears in 74 patients were retrospectively included in the study. Clinical assessment was performed using the University of California at Los Angeles score. Postoperative MR imaging was evaluated to determine prevalence, size, and location of tendon rerupture. At a mean 48.4 months' follow-up, 62 shoulders (79.5%) had favorable outcomes and 45 shoulders (57.6%) showed rerupture on MR imaging studies. Reruptures were significantly more prevalent among patients with intermediate-to-bad outcomes (81.3%), with surgically demonstrated two-tendon tears (78.9%) or three-tendon tears (100%), and with preoperative fatty degeneration of the supraspinatus muscle greater than 1 (91.6%). Reruptures were also significantly larger in those subgroups. Complete repair of RCT of all sizes may have favorable outcomes in a significant proportion of patients in spite of a high prevalence of reruptures. Preoperative tear size and degree of muscle fatty degeneration influence the prevalence and rerupture size. After repair of supraspinatus tears, reruptures tend to invade the posterior aspect of the tendon. (orig.)

  18. MR assessment of the repaired rotator cuff: prevalence, size, location, and clinical relevance of tendon rerupture

    Energy Technology Data Exchange (ETDEWEB)

    Mellado, J.M. [Hospital Reina Sofia de Tudela, Servicio de Radiodiagnostico, Tudela, Navarra (Spain); Calmet, J.; Ballabriga, J.; Gine, J. [Hospital Universitari de Tarragona Joan XXIII, Servei de Cirurgia Ortopedica i Traumatologia, Tarragona (Spain); Olona, M. [Hospital Universitari de Tarragona Joan XXIII, Servei de Medicina Preventiva i Epidemiologia, Tarragona (Spain); Camins, A. [Hospital Universitari de Tarragona Joan XXIII, Institut de Diagnostic per la Imatge, Tarragona (Spain); Perez del Palomar, L. [Hospital Ernest Lluch, Servicio de Radiologia, Calatayud, Zaragoza (Spain)

    2006-10-15

    The objectives of this study were to use magnetic resonance (MR) imaging to evaluate the prevalence, size, location, and clinical relevance of tendon rerupture following complete repair of full-thickness rotator cuff tear (RCT). A total of 78 surgically proven full-thickness rotator cuff tears in 74 patients were retrospectively included in the study. Clinical assessment was performed using the University of California at Los Angeles score. Postoperative MR imaging was evaluated to determine prevalence, size, and location of tendon rerupture. At a mean 48.4 months' follow-up, 62 shoulders (79.5%) had favorable outcomes and 45 shoulders (57.6%) showed rerupture on MR imaging studies. Reruptures were significantly more prevalent among patients with intermediate-to-bad outcomes (81.3%), with surgically demonstrated two-tendon tears (78.9%) or three-tendon tears (100%), and with preoperative fatty degeneration of the supraspinatus muscle greater than 1 (91.6%). Reruptures were also significantly larger in those subgroups. Complete repair of RCT of all sizes may have favorable outcomes in a significant proportion of patients in spite of a high prevalence of reruptures. Preoperative tear size and degree of muscle fatty degeneration influence the prevalence and rerupture size. After repair of supraspinatus tears, reruptures tend to invade the posterior aspect of the tendon. (orig.)

  19. Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

    Science.gov (United States)

    Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

    2018-03-11

    Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

  20. Potential CERCLA reauthorization issues relevant to US DOE's Environmental Restoration Program

    International Nuclear Information System (INIS)

    Siegel, M.R.; McKinney, M.D.; Jaksch, J.A.; Dailey, R.L.

    1993-02-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) is currently scheduled to be reauthorized in 1994. The US Department of Energy (DOE) has a significant stake in CERCLA reauthorization. CERCLA, along with its implementing regulation, the National Contingency Plan (NCP), is the principal legal authority governing DOE's environmental restoration program. The manner in which CERCLA-related issues are identified, evaluated, and dispatched may have a substantial impact on DOE's ability to conduct its environmental restoration program. A number of issues that impact DOE's environmental restoration program could be addressed through CERCLA reauthorization. These issues include the need to (1) address how the National Environmental Policy Act (NEPA) should be integrated into DOE CERCLA actions, (2) facilitate the streamlining of the Superfund process at DOE sites, (3) address the conflicts between the requirements of CERCLA and the Resource Conservation and Recovery Act (RCRA) that are especially relevant to DOE, (4) examine the criteria for waiving applicable or relevant and appropriate requirements (ARARs) at DOE sites, and (5) delineate the appropriate use of institutional controls at DOE sites

  1. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

    Science.gov (United States)

    Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

    2018-03-01

    The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

  2. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Hořáková, Zuzana; Hošek, Jan; Šimurdová, Milena; Šimurda, Jiří

    2016-10-01

    Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption.

  3. Bioprinting towards Physiologically Relevant Tissue Models for Pharmaceutics.

    Science.gov (United States)

    Peng, Weijie; Unutmaz, Derya; Ozbolat, Ibrahim T

    2016-09-01

    Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Silica desiccant packets for storage and transport of Streptococcus pneumoniae and other clinically relevant species.

    Directory of Open Access Journals (Sweden)

    Casey L Pell

    Full Text Available Bacterial isolates are often transported between laboratories for research and diagnostic purposes. Silica desiccant packets (SDPs, which are inexpensive and do not require freezing, were evaluated for storage and recovery of bacterial isolates. Conditions such as inoculum size, swab type and temperature of storage were investigated using ten Streptococcus pneumoniae isolates. The optimized protocol was then tested using 49 additional S. pneumoniae isolates representing 40 serogroups. Overall, S. pneumoniae growth was considered satisfactory (>100 colony forming units for 98/109 (89.9% and 20/20 (100% swabs after 14 days at room temperature or 28 days at 4° C, respectively. Storage in SDPs did not impact on the ability of S. pneumoniae isolates to be subsequently serotyped. When the survival of nine other clinically relevant bacterial species was tested, seven were viable after 28 days at room temperature, the exceptions being Neisseria gonorrhoeae and Haemophilus influenzae. SDPs are suitable for transport and short-term storage of bacterial species including S. pneumoniae.

  5. Does transcutaneous electrical nerve stimulation (TENS have a clinically relevant analgesic effect on different pain conditions? A literature review

    Directory of Open Access Journals (Sweden)

    Asami Naka

    2013-07-01

    Full Text Available Transcutaneous electric nerve stimulation (TENS is a standard therapy used in different painful conditions such as low back pain, diabetic polyneuropathy or arthrosis. However, literature reviews focusing on the effects and the clinical implication of this method in various painful conditions are yet scarce. The purpose of this literature research was to determine, whether TENS provides an analgesic effect on common painful conditions in clinical practice. Literature research was performed using three data bases (Pubmed, Embase, Cochrane Database, focusing on papers published in the space of time from 2007 to 2012. Papers were evaluated from two reviewers independently concerning the clinical outcome, taking account for the level of external evidence according to the German Cochrane levels of evidence (Ia – IV. 133 papers of varying methodological quality dealing with different painful conditions were selected in total. A clinically relevant analgesic effect was described in 90 painful conditions (67%. In 30 painful states (22%, the outcome was inconclusive due to the study design. No significant analgesic effect of TENS was observed in 15 painful conditions (11%. The vast majority of the papers were classified as Cochrane evidence level Ib (n = 64; 48%, followed by level Ia (n = 23; 17%, level III (n = 18; 14%, level IV (n = 15; 11%, level IIb (n = 10; 8% and level IIa (n = 3; 2%. Most of the studies revealed an analgesic effect in various painful conditions, confirming the usefulness of TENS in clinical practice.

  6. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

  7. Cerebral activation studies by PET and fMRT, clinical relevance?; Zerebrale Aktivierungsstudien mit PET und fMRT, klinische Relevanz?

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, T. [Neurologische Klinik und Poliklinik, Klinikum Grosshadern, Muenchen Univ. (Germany)

    1997-03-01

    Cerebral activation studies by PET and fMRT will gain increasing clinical relevance for functional neuroanatomy (reading, speaking), localisation of largely unknown cortical functions (vestibular cortex), imaging of subjective complaints of functional impairments (pain, smell, memory), and documentation of neurological rehabilitation at neuronal level (regeneration, compensation, substitution, learning). (orig.) [Deutsch] Zerebrale Aktivierungsstudien mit PET und fMRT erlangen zunehmend klinische Bedeutung fuer die funktionelle Neuroanatomie einzelner und komplexer Hirnleistungen (Lesen, Sprechen), die Lokalisation bislang unzureichend erforschter Hirnfunktionen (vestibulaerer Kortex), die Objektivierung subjektiver Beschwerden und Funktionsausfaelle (Schmerz, Riechen, Gedaechtnis) und die Dokumentation neurologischer Rehabilitation auf neuronaler Ebene (Regeneration, Kompensation, Substitution, Lernen). (orig.)

  8. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. The impact of gender on asthma in the daily clinical practice.

    Science.gov (United States)

    Ciprandi, Giorgio; Gallo, Fabio

    2018-03-01

    It is up-to-date to consider the potential gender impact on a disease. There are few data about gender difference in asthma. Therefore, the present cross-sectional study tested this hypothesis in a real-life setting to investigate possible difference between genders. This study was cross-sectional, considering 554 consecutive outpatients suspected of asthma, who were referred for a first specialist visit. Clinical and functional parameters were evaluated. Females with asthma could have a worse perception of asthma control, assessed by asthma control test (ACT), and more anxiety than asthmatic males. However, there was no difference regarding asthma control grading, asthma severity, and asthma medication use between genders; the differences in lung function were without clinical relevance. In the daily clinical practice, it is relevant to consider gender in the management of asthma.

  10. Why relevance theory is relevant for lexicography

    DEFF Research Database (Denmark)

    Bothma, Theo; Tarp, Sven

    2014-01-01

    This article starts by providing a brief summary of relevance theory in information science in relation to the function theory of lexicography, explaining the different types of relevance, viz. objective system relevance and the subjective types of relevance, i.e. topical, cognitive, situational...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  11. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species.

    Science.gov (United States)

    Alanio, A; Beretti, J-L; Dauphin, B; Mellado, E; Quesne, G; Lacroix, C; Amara, A; Berche, P; Nassif, X; Bougnoux, M-E

    2011-05-01

    New Aspergillus species have recently been described with the use of multilocus sequencing in refractory cases of invasive aspergillosis. The classical phenotypic identification methods routinely used in clinical laboratories failed to identify them adequately. Some of these Aspergillus species have specific patterns of susceptibility to antifungal agents, and misidentification may lead to inappropriate therapy. We developed a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based strategy to adequately identify Aspergillus species to the species level. A database including the reference spectra of 28 clinically relevant species from seven Aspergillus sections (five common and 23 unusual species) was engineered. The profiles of young and mature colonies were analysed for each reference strain, and species-specific spectral fingerprints were identified. The performance of the database was then tested on 124 clinical and 16 environmental isolates previously characterized by partial sequencing of the β-tubulin and calmodulin genes. One hundred and thirty-eight isolates of 140 (98.6%) were correctly identified. Two atypical isolates could not be identified, but no isolate was misidentified (specificity: 100%). The database, including species-specific spectral fingerprints of young and mature colonies of the reference strains, allowed identification regardless of the maturity of the clinical isolate. These results indicate that MALDI-TOF MS is a powerful tool for rapid and accurate identification of both common and unusual species of Aspergillus. It can give better results than morphological identification in clinical laboratories. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  12. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes

    Directory of Open Access Journals (Sweden)

    Wiebe Natasha

    2011-11-01

    Full Text Available Abstract Background The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. Methods We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Results Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34 compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806. One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively. No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Conclusions Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are

  13. Reduction of cross-reactive carbohydrate determinants in plant foodstuff: elucidation of clinical relevance and implications for allergy diagnosis.

    Directory of Open Access Journals (Sweden)

    Heidi Kaulfürst-Soboll

    Full Text Available BACKGROUND: A longstanding debate in allergy is whether or not specific immunoglobulin-E antibodies (sIgE, recognizing cross-reactive carbohydrate determinants (CCD, are able to elicit clinical symptoms. In pollen and food allergy, ≥20% of patients display in-vitro CCD reactivity based on presence of α1,3-fucose and/or β1,2-xylose residues on N-glycans of plant (xylose/fucose and insect (fucose glycoproteins. Because the allergenicity of tomato glycoallergen Lyc e 2 was ascribed to N-glycan chains alone, this study aimed at evaluating clinical relevance of CCD-reduced foodstuff in patients with carbohydrate-specific IgE (CCD-sIgE. METHODOLOGY/PRINCIPAL FINDINGS: Tomato and/or potato plants with stable reduction of Lyc e 2 (tomato or CCD formation in general were obtained via RNA interference, and gene-silencing was confirmed by immunoblot analyses. Two different CCD-positive patient groups were compared: one with tomato and/or potato food allergy and another with hymenoptera-venom allergy (the latter to distinguish between CCD- and peptide-specific reactions in the food-allergic group. Non-allergic and CCD-negative food-allergic patients served as controls for immunoblot, basophil activation, and ImmunoCAP analyses. Basophil activation tests (BAT revealed that Lyc e 2 is no key player among other tomato (glycoallergens. CCD-positive patients showed decreased (reactivity with CCD-reduced foodstuff, most obvious in the hymenoptera venom-allergic but less in the food-allergic group, suggesting that in-vivo reactivity is primarily based on peptide- and not CCD-sIgE. Peptide epitopes remained unaffected in CCD-reduced plants, because CCD-negative patient sera showed reactivity similar to wild-type. In-house-made ImmunoCAPs, applied to investigate feasibility in routine diagnosis, confirmed BAT results at the sIgE level. CONCLUSIONS/SIGNIFICANCE: CCD-positive hymenoptera venom-allergic patients (control group showed basophil activation despite no

  14. Establishment of clinically relevant radioresistant cell lines and their characteristics

    International Nuclear Information System (INIS)

    Fukumoto, Manabu; Kuwahara, Yoshikazu; Suzuki, Masatoshi

    2014-01-01

    Although radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors, the existence of radioresistant cells remains one of the most critical obstacles. Standard radiotherapy consists of fractionated radiation (FR) of 2-Gy X-rays once a day, 5 days a week, over 60 Gy in total. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we have established novel radioresistant cell lines by long-term (> 5 years) exposure to moderate doses of fractionated X-rays. While all the parental human cancer cells ceased, their radioresistant derivatives continue to proliferate with daily exposure to 2-Gy FR for more than 30 days. We have coined those cells as 'clinically relevant radioresistant' (CRR) cells. Transplanted tumors into nude mice were also CRR, indicating that CRR cell lines are powerful tools to improve cancer radiotherapy. We have shown that the suppression of autophagic cell death but not apoptosis was mainly involved in cellular radioresistance. An inhibitor of the mTOR pathway which enhances autophagy was effective to overcome CRR tumors induced in nude mice. But the underlined mechanism was not through the inhibition of autophagy. Guanine nucleotide-binding protein 1 (GBP1) over expression was necessary for maintaining the CRR phenotype, but radioresistant cells were not necessarily cancer stem cells (CSCs). Targeting GBP1 positive cancer cells may be a more efficient method in conquering cancer than targeting CSCs. Slight but significant radioresistance was acquired by 0.5 Gy/12 hrs of long-term FR exposures to parental cells for more than 31 days in accordance with cyclinD1 over expression. This acquired radioresistance (ARR) was stably maintained in the tumor cells even on 31 days after the cessation of 0.5-Gy FR. Present observations give a mechanistic insight for ARR of tumor cells through long-term FR exposure, and provide novel therapeutic targets for radiosensitization

  15. Tomographic diagnosis and relevant aspects of otosclerosis

    International Nuclear Information System (INIS)

    Gaiotti, Juliana Oggioni; Gomes, Natalia Delage; Costa, Ana Maria Doffemond; Villela, Caroline Laurita Batista Couto; Moreira, Wanderval; Diniz, Renata Lopes Furletti Caldeira

    2013-01-01

    A literature review and pictorial essay were developed to discuss the importance of knowing the main findings and locations of otosclerosis at multidetector computed tomography (MDCT). The authors performed a retrospective review of cases of otosclerosis diagnosed in their institution by means of high resolution multidetector computed tomography. Otosclerosis corresponds to otic capsule dysplasia characterized by metabolic derangement of its endochondral layer. Such condition constitutes a relevant cause of sensorineural hearing loss, affecting about 7% to 10% of the general population. The diagnosis is usually clinical, but imaging methods play a significant role in the anatomical detailing, differential diagnosis, surgical planning and evaluation of postoperative complications. Among such methods, the relevance of MDCT is highlighted. Radiologists should be familiar with the MDCT findings of otosclerosis, as well as with the temporal bone anatomy to assist in the appropriate clinical management of this disease. (author)

  16. Tomographic diagnosis and relevant aspects of otosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotti, Juliana Oggioni; Gomes, Natalia Delage; Costa, Ana Maria Doffemond; Villela, Caroline Laurita Batista Couto; Moreira, Wanderval; Diniz, Renata Lopes Furletti Caldeira, E-mail: jugaiotti@gmail.com [Hospital Mater Dei-Mater Imagem, Belo Horizonte, MG (Brazil)

    2013-09-15

    A literature review and pictorial essay were developed to discuss the importance of knowing the main findings and locations of otosclerosis at multidetector computed tomography (MDCT). The authors performed a retrospective review of cases of otosclerosis diagnosed in their institution by means of high resolution multidetector computed tomography. Otosclerosis corresponds to otic capsule dysplasia characterized by metabolic derangement of its endochondral layer. Such condition constitutes a relevant cause of sensorineural hearing loss, affecting about 7% to 10% of the general population. The diagnosis is usually clinical, but imaging methods play a significant role in the anatomical detailing, differential diagnosis, surgical planning and evaluation of postoperative complications. Among such methods, the relevance of MDCT is highlighted. Radiologists should be familiar with the MDCT findings of otosclerosis, as well as with the temporal bone anatomy to assist in the appropriate clinical management of this disease. (author)

  17. [Human papillomavirus infection and its correlates with clinically relevant gynecological and obstetric conditions: A cross-sectional study].

    Science.gov (United States)

    López-Hernández, Daniel; Beltrán-Lagunes, Luis; Brito-Aranda, Leticia; López-Hernández, Maria de la Luz

    2016-08-05

    To analyze the prevalence of human papillomavirus (HPV) infection and the possible epidemiological association with conditions of clinical relevance in women. A cross-sectional study from Mexico City was conducted from January 2012 to December 2014. HPV molecular detection was performed on cervical samples. Data were analyzed with appropriated statistic tests. A total of 1,604 females (median 47, interquartile range 38-54) were analyzed. Global prevalence of infection for any HPV is 9.91% (95% CI 8.6-11.3). An association between infection with 16-HPV and number of abortions (NA) (OR=1.427; 95% CI 1.091-1.866), by univariate regression model (UVRM) was estimated. Moreover, menarche (OR=1.566; 95% CI 1.079-2.272), NA (OR=1.570; 95% CI 1.106-2.227) and number of pregnancies (NP) (OR=0.461; 95% CI 0.260-0.818) have a direct and inverse association with infection by genotype 18 of HPV, respectively. Also, infection with HR-HPV genotypes has an inverse association with NP (OR=0.791; 95% CI 0.707-0.884) by normal labor (OR=0.867; 95% CI 0.767-0.979) and NA (OR=0.715; 95% CI 0.534-0.959) (UVRM), and a direct association with number of sexual partners (OR=1.082; 95% CI 1.015-1.154). Onset of sexual activity has an inverse association with infection by genotype 16- (UVRM: OR=0.814; 95% CI 0.715-0.926; multinomial regression model (MNRM): OR=0.803; 95% CI 0.702-0.918) and HR-HPV (UVRM: OR=0.933; 95% CI 0.889-0.980, and MNRM: OR=0.912; 95% CI 0.867-0.959), all P values were lower than .03. Prevalence of HPV cervical infection is different according to age and it is associated with several medical conditions of clinical relevance in women. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Dennis Löffler

    2017-03-01

    Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

  19. Toxicology and clinical potential of nanoparticles

    Science.gov (United States)

    Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.

    2011-01-01

    Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661

  20. The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.

    Science.gov (United States)

    Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol

    2015-01-01

    The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.

  1. Is refeeding syndrome relevant for critically ill patients?

    Science.gov (United States)

    Koekkoek, Wilhelmina A C; Van Zanten, Arthur R H

    2018-03-01

    To summarize recent relevant studies regarding refeeding syndrome (RFS) in critically ill patients and provide recommendations for clinical practice. Recent knowledge regarding epidemiology of refeeding syndrome among critically ill patients, how to identify ICU patients at risk, and strategies to reduce the potential negative impact on outcome are discussed. RFS is a potentially fatal acute metabolic derangement that ultimately can result in marked morbidity and even mortality. These metabolic derangements in ICU patients differ from otherwise healthy patients with RFS, as there is lack of anabolism. This is because of external stressors inducing a hypercatabolic response among other reasons also reflected by persistent high glucagon despite initiation of feeding. Lack of a proper uniform definition complicates diagnosis and research of RFS. However, refeeding hypophosphatemia is commonly encountered during critical illness. The correlations between risk factors proposed by international guidelines and the occurrence of RFS in ICU patients remains unclear. Therefore, regular phosphate monitoring is recommended. Based on recent trials among critically ill patients, only treatment with supplementation of electrolytes and vitamins seems not sufficient. In addition, caloric restriction for several days and gradual increase of caloric intake over days is recommendable.

  2. Utilization of a novel electrochemical {sup 90}Sr/{sup 90}Y generator for the preparation of {sup 90}Y-labeled RGD peptide dimer in clinically relevant dose

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, Haladhar Dev [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of {sup 90}Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]{sub 2} [DOTA-(RGD){sub 2}] for in vivo targeted therapy utilizing {sup 90}Y obtained from a novel electrochemical {sup 90}Sr/{sup 90}Y generator. The performance of the generator was evaluated to ensure its suitability for providing {sup 90}Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. {sup 90}Y-DOTA-(RGD){sub 2} was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of {sup 90}Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing {sup 90}Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α{sub ν}β{sub 3} receptors. (orig.)

  3. [Analysis of clinical relevance applied to 3methods of reducing weight in overweight or obesity followed-up for one year].

    Science.gov (United States)

    Tárraga Marcos, M L; Panisello Royo, J M; Carbayo Herencia, J A; Rosich Domenech, N; Alins Presas, J; Castell Panisello, E; Tárraga López, P J

    To analyse the effect of the use/implementation of 3methods to reduce weight in overweight or obese patients during one year of follow up. The design corresponds to a double-blind, randomised, controlled clinical trial with 3arms, and 12 months of follow-up. Patients were randomised into 3intervention groups: obesity motivational intervention, with a nurse previously trained in motivational intervention by expert psychologists (G1; n=60); lower intensity consultation, non-motivational group, with digital platform support (G2; N=61), and a third group that received recommendations for weight loss and follow-up in Primary Care Clinic (G3; n=59). Anthropometric variables (weight, height, and abdominal-waist circumference) were measured, and the percentage of patients who managed to reduce their weight ≥5% was considered as the main measurement of treatment effectiveness. All groups significantly decreased body weight at the end of the study, with a reduction in G1 (-5.6kg) followed by G2 (-4.3kg), and G3 (-1.7kg), with an overall mean: -3.9kg. The indicators of clinical relevance were in G1/G3: relative risk (RR): 4.99 (95% CI: from 2.71 to 9.18); relative risk reduction (RRR): 399.1% (171.3 to 818.0); Absolute risk reduction (RAR): 65.3% (from 51.5 to 79.1) and NNT: 2 (from 2 to 2). In the G2/G3 groups: RR: 3.01 (from 1.57 to 5.76); RRR: 200.5% (from 57.0 to 475.5); RAR: 32.8% (from 16.9 to 48.7) and NNT: 4 (from 3 to 6). In the G1/G2 groups: RR: 1.66 (from 1.25 to 2.20); RRR: 66.1% (from 25.3 to 120.1); RAR: 32.5% (from 16.6 to 48.4) and NNT: 4 (from 3 to 7). All 3groups were able to reduce weight. Although the group with motivational intervention achieved the greatest decrease, as well as the most favourable clinical relevance indicators. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. A systematic review of the literature on self-management interventions and discussion of their potential relevance for people living with HIV in sub-Saharan Africa

    NARCIS (Netherlands)

    Aantjes, C.J.; Rameran, L; Bunders-Aelen, J.G.F.

    2014-01-01

    Objective: This study systematically reviews the literature on self-management interventions provided by health care teams, community partners, patients and families and discusses the potential relevance of these interventions for people living with HIV in sub-Saharan Africa. Methods: We searched

  5. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

    Science.gov (United States)

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials.

  6. Relevance of a molecular tumour board (MTB) for patients' enrolment in clinical trials: experience of the Institut Curie.

    Science.gov (United States)

    Basse, Clémence; Morel, Claire; Alt, Marie; Sablin, Marie Paule; Franck, Coralie; Pierron, Gaëlle; Callens, Céline; Melaabi, Samia; Masliah-Planchon, Julien; Bataillon, Guillaume; Gardrat, Sophie; Lavigne, Marion; Bonsang, Benjamin; Vaflard, Pauline; Pons Tostivint, Elvire; Dubot, Coraline; Loirat, Delphine; Marous, Miguelle; Geiss, Romain; Clément, Nathalie; Schleiermacher, Gudrun; Kamoun, Choumouss; Girard, Elodie; Ardin, Maude; Benoist, Camille; Bernard, Virginie; Mariani, Odette; Rouzier, Roman; Tresca, Patricia; Servois, Vincent; Vincent-Salomon, Anne; Bieche, Ivan; Le Tourneau, Christophe; Kamal, Maud

    2018-01-01

    High throughput molecular screening techniques allow the identification of multiple molecular alterations, some of which are actionable and can be targeted by molecularly targeted agents (MTA). We aimed at evaluating the relevance of using this approach in the frame of Institut Curie Molecular Tumor Board (MTB) to guide patients with cancer to clinical trials with MTAs. We included all patients presented at Institut Curie MTB from 4 October 2014 to 31 October 2017. The following information was extracted from the chart: decision to perform tumour profiling, types of molecular analyses, samples used, molecular alterations identified and those which are actionable, and inclusion in a clinical trial with matched MTA. 736 patients were presented at the MTB. Molecular analyses were performed in 442 patients (60%). Techniques used included next-generation sequencing, comparative genomic hybridisation array and/or other techniques including immunohistochemistry in 78%, 51% and 58% of patients, respectively. Analyses were performed on a fresh frozen biopsy in 91 patients (21%), on archival tissue (fixed or frozen) in 326 patients (74%) and on both archival and fresh frozen biopsy in 25 patients (6%). At least one molecular alteration was identified in 280 analysed patients (63%). An actionable molecular alteration was identified in 207 analysed patients (47%). Forty-five analysed patients (10%) were enrolled in a clinical trial with matched MTA and 29 additional patients were oriented and included in a clinical trial based on a molecular alteration identified prior to the MTB analysis. Median time between date of specimen reception and molecular results was 28 days (range: 5-168). The implementation of an MTB at Institut Curie enabled the inclusion of 10% of patients into a clinical trial with matched therapy.

  7. Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts.

    Science.gov (United States)

    Blank, S; Seismann, H; Michel, Y; McIntyre, M; Cifuentes, L; Braren, I; Grunwald, T; Darsow, U; Ring, J; Bredehorst, R; Ollert, M; Spillner, E

    2011-10-01

    Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed. Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated. Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component. Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy. © 2011 John Wiley & Sons A/S.

  8. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    Science.gov (United States)

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

  9. Refeeding syndrome: clinical and nutritional relevance.

    Science.gov (United States)

    Viana, Larissa de Andrade; Burgos, Maria Goretti Pessoa de Araújo; Silva, Rafaella de Andrade

    2012-01-01

    Feedback syndrome is characterized clinically by neurological alterations, respiratory symptoms, arrhythmias and heart failure few days after refeeding. It happens due to severe electrolyte changes, such as hypophosphatemia, hypomagnesemia and hypokalemia associated with metabolic abnormalities that may occur as a result of nutritional support (oral, enteral or parenteral) in severely malnourished patients. To evaluate its causes and the preventive dietary measures aiming to reduce the morbimortality. Was conducted literature review in SciELO, LILACS, Medline / PUBMED, Cochrane Library and government websites in Portuguese, English and Spanish. The survey was about the last 15 years, selecting the headings: refeeding syndrome, malnutrition, hypophosphatemia, hypokalemia, hypomagnesemia. The monitoring of metabolic parameters and electrolyte levels before starting nutritional support and periodically during feeding should be based on protocols and the duration of therapy. Patients at high risk and other metabolic complications should be followed closely, and depletion of minerals and electrolytes should be replaced before starting the diet. A multidisciplinary team of nutrition therapy can guide and educate other health professionals in prevention, diagnosis and treatment of the syndrome.

  10. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  11. Relevance of collagen piezoelectricity to "Wolff's Law": a critical review.

    Science.gov (United States)

    Ahn, Andrew C; Grodzinsky, Alan J

    2009-09-01

    According to "Wolff's Law", bone is deposited and reinforced at areas of greatest stress. From a clinical perspective, this "law" is supported by the strong association between bone density and physical activity. From a mechanistic standpoint, however, the law presents a challenge to scientists seeking to understand how osteocytes and osteoblasts sense the mechanical load. In the 1960s, collagen piezoelectricity was invoked as a potential mechanism by which osteocytes could detect areas of greater stress but piezoelectricity diminished in importance as more compelling mechanisms, such as streaming potential, were identified. In addition, accumulating evidence for the role of fluid-related shear stress in osteocyte's mechanosensory function has made piezoelectricity seemingly more obsolete in bone physiology. This review critically evaluates the role of collagen piezoelectricity (if any) in Wolff's Law--specifically, the evidence regarding its involvement in strain-generated potentials, existing alternate mechanisms, the present understanding of bone mechanosensation, and whether piezoelectricity serves an influential role within the context of this newly proposed mechanism. In addition to reviewing the literature, this review generates several hypotheses and proposes future research to fully address the relevance of piezoelectricity in bone physiology.

  12. A comparison of the clinical relevance of thallium- 201 and ...

    African Journals Online (AJOL)

    1990-09-01

    Sep 1, 1990 ... Thallium-201 is at present the radiotracer of choice for the clinical evaluation of myocardial blood flow. Although different technetium-99m-isonitrile agents have been synthesised recently, only 99mTc-melhoxyisobutyl-isonitrile (99mTc_MIBI) has proved to hold promise for clinical implementation. The myo-.

  13. A comparison of the clinical relevance of thallium201 and ...

    African Journals Online (AJOL)

    Thallium-201 is at present the radiotracer of choice for the clinical evaluation of myocardial blood flow. Although different technetium-99m-isonitrile agents have been synthesised recently, only 99mTc-melhoxyisobutyl-isonitrile (99mTc_MIBI) has proved to hold promise for clinical implementation. The myocardial distribution ...

  14. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    International Nuclear Information System (INIS)

    Schillaci, Roxana; Charreau, Eduardo H; Maronna, Esteban; Roa, Juan C; Elizalde, Patricia V; Guzmán, Pablo; Cayrol, Florencia; Beguelin, Wendy; Díaz Flaqué, María C; Proietti, Cecilia J; Pineda, Viviana; Palazzi, Jorge; Frahm, Isabel

    2012-01-01

    The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration

  15. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana

    2012-02-01

    Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

  16. Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

    Directory of Open Access Journals (Sweden)

    Pignattari Elena

    2001-09-01

    Full Text Available Abstract Background Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. Objectives To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. Methods The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. Results Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%. Hyperamylasemia was more likely (17% where a microorganism could be identified in the stools (p Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 % and 10/45 (22.2%, respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P Conclusions Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

  17. Vibrational spectroscopy: a clinical tool for cancer diagnostics.

    Science.gov (United States)

    Kendall, Catherine; Isabelle, Martin; Bazant-Hegemark, Florian; Hutchings, Joanne; Orr, Linda; Babrah, Jaspreet; Baker, Rebecca; Stone, Nicholas

    2009-06-01

    Vibrational spectroscopy techniques have demonstrated potential to provide non-destructive, rapid, clinically relevant diagnostic information. Early detection is the most important factor in the prevention of cancer. Raman and infrared spectroscopy enable the biochemical signatures from biological tissues to be extracted and analysed. In conjunction with advanced chemometrics such measurements can contribute to the diagnostic assessment of biological material. This paper also illustrates the complementary advantage of using Raman and FTIR spectroscopy technologies together. Clinical requirements are increasingly met by technological developments which show promise to become a clinical reality. This review summarises recent advances in vibrational spectroscopy and their impact on the diagnosis of cancer.

  18. Pain-relevant anxiety affects desire for pain relief, but not pain perception

    Directory of Open Access Journals (Sweden)

    Adriana Banozic

    2017-01-01

    Full Text Available Background: Pain context plays a significant role in the perception of pain. Despite recent interest in vicarious learning and anxiety in pain modulation, there have been no attempts to explore pain modulation by specific environmental cues. Aims: Therefore, the present study evaluated pain responses in the condition that was attributed as either anxiety relevant (AR or anxiety irrelevant. Materials and Methods: Participants were exposed to both conditions through social observational learning. Pain perception was assessed by means of a visual analog scale ranging from 0 = no pain to 10 = maximum imaginable pain. State anxiety, empathy, expectancy, and desire for pain relief were also measured at both neutral and emotionally inducing conditions. Results: No effect of relevancy of anxiety for the pain context on any of the pain-related constructs was found. However, participants in the AR condition reported an increased desire for pain relief. Maximizing similarities between observed and experienced pain context did not enhance observational learning effects in the emotionally inducing condition regardless of its relevance, but significant changes were found in comparison to the affectively neutral group. Conclusions: These results could have potentially significant clinical implications suggesting that even though observing painful procedures does not increase pain it could affect medication usage.

  19. A comparison of the ability of rilpivirine (TMC278 and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

    Directory of Open Access Journals (Sweden)

    Johnson Barry C

    2012-12-01

    Full Text Available Abstract Background The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant is a nonnucleoside inhibitor (NNRTI that binds to reverse transcriptase (RT and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT and drug-resistant HIV-1. Results We used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective. Conclusions Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.

  20. Expanding the scope and relevance of health interventions: Moving beyond clinical trials and behavior change models

    Directory of Open Access Journals (Sweden)

    Khary K. Rigg

    2014-07-01

    Full Text Available An overemphasis on clinical trials and behavior change models has narrowed the knowledge base that can be used to design interventions. The overarching point is that the process of overanalyzing variables is impeding the process of gaining insight into the everyday experiences that shape how people define health and seek treatment. This claim is especially important to health decision-making and behavior change because subtle interpretations often influence the decisions that people make. This manuscript provides a critique of traditional approaches to developing health interventions, and theoretically justifies what and why changes are warranted. The limited scope of these models is also discussed, and an argument is made to adopt a strategy that includes the perceptions of people as necessary for understanding health and health-related decision-making. Three practical strategies are suggested to be used with the more standard approaches to assessing the effectiveness and relevance of health interventions.

  1. Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2014-11-01

    The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

  2. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  3. Seven-day human biological rhythms: An expedition in search of their origin, synchronization, functional advantage, adaptive value and clinical relevance.

    Science.gov (United States)

    Reinberg, Alain E; Dejardin, Laurence; Smolensky, Michael H; Touitou, Yvan

    2017-01-01

    This fact-finding expedition explores the perspectives and knowledge of the origin and functional relevance of the 7 d domain of the biological time structure, with special reference to human beings. These biological rhythms are displayed at various levels of organization in diverse species - from the unicellular sea algae of Acetabularia and Goniaulax to plants, insects, fish, birds and mammals, including man - under natural as well as artificial, i.e. constant, environmental conditions. Nonetheless, very little is known about their derivation, functional advantage, adaptive value, synchronization and potential clinical relevance. About 7 d cosmic cycles are seemingly too weak, and the 6 d work/1 d rest week commanded from G-d through the Laws of Mosses to the Hebrews is too recent an event to be the origin in humans. Moreover, human and insect studies conducted under controlled constant conditions devoid of environmental, social and other time cues report the persistence of 7 d rhythms, but with a slightly different (free-running) period (τ), indicating their source is endogenous. Yet, a series of human and laboratory rodent studies reveal certain mainly non-cyclic exogenous events can trigger 7 d rhythm-like phenomena. However, it is unknown whether such triggers unmask, amplify and/or synchronize previous non-overtly expressed oscillations. Circadian (~24 h), circa-monthly (~30 d) and circannual (~1 y) rhythms are viewed as genetically based features of life forms that during evolution conferred significant functional advantage to individual organisms and survival value to species. No such advantages are apparent for endogenous 7 d rhythms, raising several questions: What is the significance of the 7 d activity/rest cycle, i.e. week, storied in the Book of Genesis and adopted by the Hebrews and thereafter the residents of nearby Mediterranean countries and ultimately the world? Why do humans require 1 d off per 7 d span? Do 7 d rhythms bestow functional

  4. Search for relevant indications for selenium supplementation in thyroid diseases.

    Science.gov (United States)

    Wojciechowska-Durczynska, Katarzyna; Lewinski, Andrzej

    2017-08-01

    Selenium plays a significant role in the thyroid function and its deficiency is considered by some authors to be a cause of thyroid disorders. The potential therapeutic influence of selenium supplementation in thyroid disease was investigated in several studies and some results were encouraging, however results were inconsistent and did not allow conclusion to be drawn. For that reason, we have performed a review study on relevance of selenium supplementation in thyroid disease. Till now, there is no strong evidence that selenium supplementation leads to clinical improvement in the course of autoimmune thyroiditis, nodular goitre or thyroid cancer. On the other hand, there is some evidence that selenium is effective in the treatment of orbitopathy; thus, the European Group on Graves' Orbitopathy (EUGOGO) recommends selenium administration in mild active orbitopathy.

  5. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  6. Autologous but not Fibrin Sealant Patches for Stump Coverage Reduce Clinically Relevant Pancreatic Fistula in Distal Pancreatectomy: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Weniger, Maximilian; D'Haese, Jan Goesta; Crispin, Alexander; Angele, Martin Kurt; Werner, Jens; Hartwig, Werner

    2016-11-01

    Postoperative pancreatic fistula (POPF) causes significant morbidity and mortality after distal pancreatectomy. Patch coverage of the pancreatic stump is often used with the intention to prevent POPF. Despite numerous investigations, the effects of patch coverage remain unclear. The present meta-analysis aims to clarify the effects of patch coverage in distal pancreatectomy on the incidence of POPF. A systematic search of MEDLINE/PubMed and the Cochrane Database according to the PRISMA Statement was performed. Subsequently a meta-analysis on rates and overall incidence of POPF and length of hospital stay was carried out. By applying the inverse variance weighting method, the combined effect size and 95 % confidence interval were calculated. Heterogeneity was assessed using I 2 statistics. Five randomized controlled trials and six observational clinical studies were included for final analysis. A cumulative incidence of 43 % of POPF grades A-C was identified. Patch coverage in distal pancreatectomy is significantly associated with a decreased rate of POPF grade C (p = 0.006). Patches of autologous vascularized tissue significantly reduce the overall incidence of POPF (p = 0.04) and clinically relevant POPF grade B and C (p = 0.002). Fibrin sealant patches do not influence rates of POPF after distal pancreatectomy. None of the outcomes evaluated showed adverse results for the patch group. Patch coverage after distal pancreatectomy can reduce the rate of POPF. Patch coverage with autologous vascularized tissue but not fibrin sealant patches may be used to reduce clinically relevant POPF and postoperative morbidity in distal pancreatectomy.

  7. Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders

    OpenAIRE

    Langley, Adrian; Dameron, Charles T.

    2013-01-01

    Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.

  8. Multi-Tasking and Choice of Training Data Influencing Parietal ERP Expression and Single-Trial Detection—Relevance for Neuroscience and Clinical Applications

    Science.gov (United States)

    Kirchner, Elsa A.; Kim, Su Kyoung

    2018-01-01

    Event-related potentials (ERPs) are often used in brain-computer interfaces (BCIs) for communication or system control for enhancing or regaining control for motor-disabled persons. Especially results from single-trial EEG classification approaches for BCIs support correlations between single-trial ERP detection performance and ERP expression. Hence, BCIs can be considered as a paradigm shift contributing to new methods with strong influence on both neuroscience and clinical applications. Here, we investigate the relevance of the choice of training data and classifier transfer for the interpretability of results from single-trial ERP detection. In our experiments, subjects performed a visual-motor oddball task with motor-task relevant infrequent (targets), motor-task irrelevant infrequent (deviants), and motor-task irrelevant frequent (standards) stimuli. Under dual-task condition, a secondary senso-motor task was performed, compared to the simple-task condition. For evaluation, average ERP analysis and single-trial detection analysis with different numbers of electrodes were performed. Further, classifier transfer was investigated between simple and dual task. Parietal positive ERPs evoked by target stimuli (but not by deviants) were expressed stronger under dual-task condition, which is discussed as an increase of task emphasis and brain processes involved in task coordination and change of task set. Highest classification performance was found for targets irrespective whether all 62, 6 or 2 parietal electrodes were used. Further, higher detection performance of targets compared to standards was achieved under dual-task compared to simple-task condition in case of training on data from 2 parietal electrodes corresponding to results of ERP average analysis. Classifier transfer between tasks improves classification performance in case that training took place on more varying examples (from dual task). In summary, we showed that P300 and overlaying parietal positive

  9. Community Pharmacists' Perception of the Relevance of Drug ...

    African Journals Online (AJOL)

    HP

    Community Pharmacists' Perception of the Relevance of. Drug Package Insert as Source of Drug Information in. Southwestern Nigeria. Kenechuckwu Diobi, Titilayo O Fakeye* and Rasaq Adisa. Department of Clinical Pharmacy & Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.

  10. SU-E-T-789: Validation of 3DVH Accuracy On Quantifying Delivery Errors Based On Clinical Relevant DVH Metrics

    International Nuclear Information System (INIS)

    Ma, T; Kumaraswamy, L

    2015-01-01

    Purpose: Detection of treatment delivery errors is important in radiation therapy. However, accurate quantification of delivery errors is also of great importance. This study aims to evaluate the 3DVH software’s ability to accurately quantify delivery errors. Methods: Three VMAT plans (prostate, H&N and brain) were randomly chosen for this study. First, we evaluated whether delivery errors could be detected by gamma evaluation. Conventional per-beam IMRT QA was performed with the ArcCHECK diode detector for the original plans and for the following modified plans: (1) induced dose difference error up to ±4.0% and (2) control point (CP) deletion (3 to 10 CPs were deleted) (3) gantry angle shift error (3 degree uniformly shift). 2D and 3D gamma evaluation were performed for all plans through SNC Patient and 3DVH, respectively. Subsequently, we investigated the accuracy of 3DVH analysis for all cases. This part evaluated, using the Eclipse TPS plans as standard, whether 3DVH accurately can model the changes in clinically relevant metrics caused by the delivery errors. Results: 2D evaluation seemed to be more sensitive to delivery errors. The average differences between ECLIPSE predicted and 3DVH results for each pair of specific DVH constraints were within 2% for all three types of error-induced treatment plans, illustrating the fact that 3DVH is fairly accurate in quantifying the delivery errors. Another interesting observation was that even though the gamma pass rates for the error plans are high, the DVHs showed significant differences between original plan and error-induced plans in both Eclipse and 3DVH analysis. Conclusion: The 3DVH software is shown to accurately quantify the error in delivered dose based on clinically relevant DVH metrics, where a conventional gamma based pre-treatment QA might not necessarily detect

  11. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

  12. Impact of a novel teaching method based on feedback, activity, individuality and relevance on students' learning.

    Science.gov (United States)

    Edafe, Ovie; Brooks, William S; Laskar, Simone N; Benjamin, Miles W; Chan, Philip

    2016-03-20

    This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students' learning on clinical placement. This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model. The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of "standard" clinical teaching. Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching.

  13. [Incidence and follow-up characteristics of neurologically relevant psychogenic symptoms].

    Science.gov (United States)

    Franz, M; Schellberg, D; Reister, G; Schepank, H

    1993-06-01

    The author reports on the prevalence and stability of the course of neurologically relevant psychogenic symptoms as well as their dependence on age and sex. Altogether 240 probands from the Mannheim Cohort Study on the epidemiology of psychogenic disorders were examined for psychogenic impairment over a 10-year period during three investigation periods. On the whole, seven neurologically relevant groups of symptoms (headache, lumbar and cervical vertebral complaints, non-systematic vertigo, functional hyperkinesia, functional paresis, sleep disturbances, concentration disturbances) differ clearly in frequency, characteristics of the course and clinical relevance.

  14. Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study

    OpenAIRE

    Keizer, D.; van Wijhe, M.; Post, W.J.; Uges, D.R.A.; Wierda, J.M.K.H.

    2007-01-01

    Background: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with p...

  15. [Evidence-based medicine. 2. Research of clinically relevant biomedical information. Gruppo Italiano per la Medicina Basata sulle Evidenze--GIMBE].

    Science.gov (United States)

    Cartabellotta, A

    1998-05-01

    Evidence-based Medicine is a product of the electronic information age and there are several databases useful for practice it--MEDLINE, EMBASE, specialized compendiums of evidence (Cochrane Library, Best Evidence), practice guidelines--most of them free available through Internet, that offers a growing number of health resources. Because searching best evidence is a basic step to practice Evidence-based Medicine, this second review (the first one has been published in the issue of March 1998) has the aim to provide physicians tools and skills for retrieving relevant biomedical information. Therefore, we discuss about strategies for managing information overload, analyze characteristics, usefulness and limits of medical databases and explain how to use MEDLINE in day-to-day clinical practice.

  16. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    Energy Technology Data Exchange (ETDEWEB)

    Das, I. [NYU Langone Medical Center, New York, NY (United States)

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  17. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    International Nuclear Information System (INIS)

    Das, I.

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  18. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young-Min; Xia Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W, E-mail: young-min.kwon@ndos.ox.ac.u [Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford OX3 7LD (United Kingdom)

    2009-04-15

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10{sup 12} particles ml{sup -1} and 1000 {mu}M, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  19. The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

    Directory of Open Access Journals (Sweden)

    Juan A Ramos

    2012-01-01

    Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

  20. Covalent immobilisation of antibodies in Teflon-FEP microfluidic devices for the sensitive quantification of clinically relevant protein biomarkers.

    Science.gov (United States)

    Pivetal, Jeremy; Pereira, Filipa M; Barbosa, Ana I; Castanheira, Ana P; Reis, Nuno M; Edwards, Alexander D

    2017-03-13

    This study reports for the first time the sensitive colorimetric and fluorescence detection of clinically relevant protein biomarkers by sandwich immunoassays using the covalent immobilisation of antibodies onto the fluoropolymer surface inside Teflon®-FEP microfluidic devices. Teflon®-FEP has outstanding optical transparency ideal for high-sensitivity colorimetric and fluorescence bioassays, however this thermoplastic is regarded as chemically inert and very hydrophobic. Covalent immobilisation can offer benefits over passive adsorption to plastic surfaces by allowing better control over antibody density, orientation and analyte binding capacity, and so we tested a range of different and novel covalent immobilisation strategies. We first functionalised the inner surface of a 10-bore, 200 μm internal diameter FEP microcapillary film with high-molecular weight polyvinyl alcohol (PVOH) without changing the outstanding optical transparency of the device delivered by the matched refractive index of FEP and water. Glutaraldehyde immobilisation was compared with the use of photoactivated linkers and NHS-ester crosslinkers for covalently immobilising capture antibodies onto PVOH. Three clinically relevant sandwich ELISAs were tested against the cytokine IL-1β, the myocardial infarct marker cardiac troponin I (cTnI), and the chronic heart failure marker brain natriuretic peptide (BNP). Overall, glutaraldehyde immobilisation was effective for BNP assays, but yielded unacceptable background for IL-1β and cTnI assays caused by direct binding of the biotinylated detection antibody to the modified PVOH surface. We found NHS-ester groups reacted with APTES-treated PVOH coated fluoropolymers. This facilitated a novel method for capture antibody immobilisation onto fluoropolymer devices using a bifunctional NHS-maleimide crosslinker. The density of covalently immobilised capture antibodies achieved using PVOH/APTES/NHS/maleimide approached levels seen with passive adsorption

  1. Classification of Clinically Relevant Microorganisms in Non-Medical Environments

    National Research Council Canada - National Science Library

    Bowers, Daniel

    2004-01-01

    .... He named them Staphylococcus aureus because of their golden color. S. aureus remains one of the most important pathogens in clinical settings largely due to the rapidity of its evolutionary response to treatment...

  2. DEFINING THE RELEVANT OUTCOME MEASURES IN MEDICAL DEVICE ASSESSMENTS: AN ANALYSIS OF THE DEFINITION PROCESS IN HEALTH TECHNOLOGY ASSESSMENT.

    Science.gov (United States)

    Jacobs, Esther; Antoine, Sunya-Lee; Prediger, Barbara; Neugebauer, Edmund; Eikermann, Michaela

    2017-01-01

    Defining relevant outcome measures for clinical trials on medical devices (MD) is complex, as there is a large variety of potentially relevant outcomes. The chosen outcomes vary widely across clinical trials making the assessment in evidence syntheses very challenging. The objective is to provide an overview on the current common procedures of health technology assessment (HTA) institutions in defining outcome measures in MD trials. In 2012-14, the Web pages of 126 institutions involved in HTA were searched for methodological manuals written in English or German that describe methods for the predefinition process of outcome measures. Additionally, the institutions were contacted by email. Relevant information was extracted. All process steps were performed independently by two reviewers. Twenty-four manuals and ten responses from the email request were included in the analysis. Overall, 88.5 percent of the institutions describe the type of outcomes that should be considered in detail and 84.6 percent agree that the main focus should be on patient relevant outcomes. Specifically related to MD, information could be obtained in 26 percent of the included manuals and email responses. Eleven percent of the institutions report a particular consideration of MD related outcomes. This detailed analysis on common procedures of HTA institutions in the context of defining relevant outcome measures for the assessment of MD shows that standardized procedures for MD from the perspective of HTA institutions are not widespread. This leads to the question if a homogenous approach should be implemented in the field of HTA on MD.

  3. Developing independent investigators for clinical research relevant for Africa

    LENUS (Irish Health Repository)

    Manabe, Yukari C

    2011-12-29

    Abstract Sustainable research capacity building requires training individuals at multiple levels within a supportive institutional infrastructure to develop a critical mass of independent researchers. At many African medical institutions, a PhD is important for academic promotion and is, therefore, an important focal area for capacity building programs. We examine the training at the Infectious Diseases Institute (IDI) as a model for in-country training based on systems capacity building and attention to the academic environment. PhD training in Africa should provide a strong research foundation for individuals to perform independent, original research and to mentor others. Training the next generation of researchers within excellent indigenous academic centers of excellence with strong institutional infrastructure will empower trainees to ask regionally relevant research questions that will benefit Africans.

  4. Potential Clinical and Economic Impact of Switching Branded Medications to Generics

    Science.gov (United States)

    Straka, Robert J.; Keohane, Denis J.; Liu, Larry Z.

    2017-01-01

    Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003–2013 using key words of “generic switching” or “substitution” was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases. PMID:26099048

  5. How Long Should Routine EEG Be Recorded to Get Relevant Information?

    Science.gov (United States)

    Doudoux, Hannah; Skaare, Kristina; Geay, Thomas; Kahane, Philippe; Bosson, Jean L; Sabourdy, Cécile; Vercueil, Laurent

    2017-03-01

    The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

  6. [EDNOS is an eating disorder of clinical relevance, on a par with anorexia and bulimia nervosa].

    Science.gov (United States)

    Dingemans, A E; van Furth, E F

    2015-01-01

    The category 'eating disorder 'not otherwise specified'' (EDNOS) in DSM-IV is restricted to eating disorders of clinical severity that do not completely fulfil the criteria for anorexia and bulimia nervosa. The EDNOS category is, by definition, often regarded as a a residual category and in principle designed to incorporate a small group of patients with atypical characteristics. Health insurance companies argue that the treatment of patients diagnosed with EDNOS should not be treated in mental health institutions and therefore should not get their treatment costs reimbursed by the insurance companies. The most important argument of the insurance companies is that patients in the EDNOS category do not display serious psychiatric symptoms. The aim of this paper is to show that EDNOS is an eating disorder category of clinical relevance. The article provides a critical overview of literature on EDNOS which studies the prevalence, severity and course of the disorder. We also discuss to what extent the fifth version of dsm solves the problems relating to this residual category. We reviewed the literature. The classification given in DSM-IV is not an accurate reflection of clinical reality. Half of the patients presenting with an eating disorder and seeking treatment do meet the criteria for EDNOS. The duration and the severity of eating disorder psychopathology, the presence of comorbidity, the mortality, and the use of the mental health care services by individuals with an eating disorder appear to be very similar in EDNOS patients and in patients with anorexia and bulimia nervosa. Eating disorder classifications can be regarded as snapshots taken throughout the course of an illness. Over of the years patients can be afflicted with various subtypes of an eating disorder. DSM-5 places fewer patients in the EDNOS category that did DSM-IV. In the latest version of dsm, namely DSM-5, the number of patients with an eating disorder classified as EDNOS has declined. There

  7. In vitro and clinical evaluation of OATP-mediated drug interaction potential of sacubitril/valsartan (LCZ696).

    Science.gov (United States)

    Ayalasomayajula, S; Han, Y; Langenickel, T; Malcolm, K; Zhou, W; Hanna, I; Alexander, N; Natrillo, A; Goswami, B; Hinder, M; Sunkara, G

    2016-08-01

    Sacubitril/valsartan (LCZ696) has been recently approved for the treatment of heart failure (HF) patients with reduced ejection fraction. Several HF patients receive statins as co-medication. Because clearance of statins is meditated via OATP1B1/1B3, the inhibition potential of these transporters by LCZ696 analytes was evaluated in vitro. Furthermore, an open-label, fixed-sequence clinical study was conducted to determine the effect of LCZ696 on the exposure of simvastatin and its active metabolite simvastatin acid. In this clinical study, 26 healthy subjects received simvastatin 40 mg alone or in combination with LCZ696 or after 1 or 2 h of LCZ696 dosing. Although no significant inhibition by LBQ657 (an active metabolite of sacubitril) and valsartan was observed, sacubitril inhibited OATP1B1 and OATP1B3 in vitro, with IC50 of 1·91 and 3·81 μm, respectively. Upon co-administration of simvastatin with LCZ696, the Cmax of simvastatin and simvastatin acid decreased by 7% and 13%, respectively. When administered 1 h after LCZ696 dosing, the corresponding Cmax of simvastatin and simvastatin acid decreased by 16% and 4%, respectively. When administered 2 h after LCZ696 dosing, the Cmax of simvastatin decreased by 33% and that of simvastatin acid increased by 16%. However, no notable changes were observed in the AUCs of simvastatin or simvastatin acid upon co-administration or time-separated administration with LCZ696. No notable impact of simvastatin co-administration was observed on the pharmacokinetics of LCZ696 analytes. LCZ696 and simvastatin were generally well tolerated when administered alone or in combination. Overall, the results of this study suggest that although sacubitril inhibited OATP1B1 and OATP1B3 in vitro, it does not translate into any clinically relevant in vivo effect. © 2016 John Wiley & Sons Ltd.

  8. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Monika Novak Babič

    2017-06-01

    Full Text Available Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  9. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Science.gov (United States)

    Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João

    2017-01-01

    Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  10. Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

    Science.gov (United States)

    Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

    2015-06-01

    Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

  11. Impact of a novel teaching method based on feedback, activity, individuality and relevance on students’ learning

    Science.gov (United States)

    Brooks, William S.; Laskar, Simone N.; Benjamin, Miles W.; Chan, Philip

    2016-01-01

    Objectives This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students’ learning on clinical placement. Methods This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Results Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model.  The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of “standard” clinical teaching. Conclusions Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching. PMID:26995588

  12. Update in clinical allergy and immunology.

    Science.gov (United States)

    von Gunten, S; Marsland, B J; von Garnier, C; Simon, D

    2012-12-01

    In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field. © 2012 John Wiley & Sons A/S.

  13. [Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

    Science.gov (United States)

    Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

    2018-01-01

    If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  14. Water displacement leg volumetry in clinical studies - A discussion of error sources

    Science.gov (United States)

    2010-01-01

    Background Water displacement leg volumetry is a highly reproducible method, allowing the confirmation of efficacy of vasoactive substances. Nevertheless errors of its execution and the selection of unsuitable patients are likely to negatively affect the outcome of clinical studies in chronic venous insufficiency (CVI). Discussion Placebo controlled double-blind drug studies in CVI were searched (Cochrane Review 2005, MedLine Search until December 2007) and assessed with regard to efficacy (volume reduction of the leg), patient characteristics, and potential methodological error sources. Almost every second study reported only small drug effects (≤ 30 mL volume reduction). As the most relevant error source the conduct of volumetry was identified. Because the practical use of available equipment varies, volume differences of more than 300 mL - which is a multifold of a potential treatment effect - have been reported between consecutive measurements. Other potential error sources were insufficient patient guidance or difficulties with the transition from the Widmer CVI classification to the CEAP (Clinical Etiological Anatomical Pathophysiological) grading. Summary Patients should be properly diagnosed with CVI and selected for stable oedema and further clinical symptoms relevant for the specific study. Centres require a thorough training on the use of the volumeter and on patient guidance. Volumetry should be performed under constant conditions. The reproducibility of short term repeat measurements has to be ensured. PMID:20070899

  15. Effect of clinical specialist physiotherapists in orthopaedic diagnostic setting - A systematic review

    DEFF Research Database (Denmark)

    Trøstrup, Jeanette; Mikkelsen, Lone Ramer; Juhl, Carsten

    Relevance: Patients with musculoskeletal complaints are commonly referred to orthopaedic surgeons (OS) with 20 % of patients in primary care being referred to OS consultation. A high proportion of these referrals is not relevant for surgery and can potentially be managed entirely by physiotherapist...... with advanced clinical competencies; Clinical Specialist Physiotherapists (CSP). The use of CSPs instead of OSs to perform diagnostic assessment of patients with musculoskeletal complaints has been implemented in several countries (1). Earlier systematic reviews have evaluated CSPs effectiveness in diagnosing...... patients with musculoskeletal complaints and concluded that CSPs have the ability to diagnose musculoskeletal conditions (2), however since then more new studies have been published. Purpose: To evaluate the effectiveness of assessment of musculoskeletal complaints performed by CSP compared to OS...

  16. Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

    Science.gov (United States)

    Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

    2016-01-01

    Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

  17. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

    Science.gov (United States)

    Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

    2014-01-01

    Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (strategies may aid cancer drug development.

  18. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

    Science.gov (United States)

    de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

    2018-02-19

    Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  19. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

    Directory of Open Access Journals (Sweden)

    Ana Caroline L. de Paula

    2018-02-01

    Full Text Available Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  20. The cerebral collateral circulation: Relevance to pathophysiology and treatment of stroke.

    Science.gov (United States)

    Ginsberg, Myron D

    2017-08-09

    The brain's collateral circulation consists of arterial anastomotic channels capable of providing nutrient perfusion to brain regions whose normal sources of flow have become compromised, as occurs in acute ischemic stroke. Modern CT-based neuroimaging is capable of providing detailed information as to collateral extent and sufficiency and is complemented by magnetic resonance-based methods. In the present era of standard-of-care IV thrombolysis for acute ischemic stroke, and following the recent therapeutic successes of randomized clinical trials of acute endovascular intervention, the sufficiency of the collateral circulation has been convincingly established as a key factor influencing the likelihood of successful reperfusion and favorable clinical outcome. This article reviews the features of the brain's collateral circulation; methods for its evaluation in the acute clinical setting; the relevance of collateral circulation to prognosis in acute ischemic stroke; the specific insights into the collateral circulation learned from recent trials of endovascular intervention; and the major influence of genetic factors. Finally, we emphasize the need to develop therapeutic approaches to augment collateral perfusion as an adjunctive strategy to be employed along with, or prior to, thrombolysis and endovascular interventions, and we highlight the possible potential of inhaled nitric oxide, albumin, and other approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

    Science.gov (United States)

    Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

    2017-10-01

    The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

  2. Assessing mental imagery in clinical psychology: A review of imagery measures and a guiding framework

    Science.gov (United States)

    Pearson, David G.; Deeprose, Catherine; Wallace-Hadrill, Sophie M.A.; Heyes, Stephanie Burnett; Holmes, Emily A.

    2013-01-01

    Mental imagery is an under-explored field in clinical psychology research but presents a topic of potential interest and relevance across many clinical disorders, including social phobia, schizophrenia, depression, and post-traumatic stress disorder. There is currently a lack of a guiding framework from which clinicians may select the domains or associated measures most likely to be of appropriate use in mental imagery research. We adopt an interdisciplinary approach and present a review of studies across experimental psychology and clinical psychology in order to highlight the key domains and measures most likely to be of relevance. This includes a consideration of methods for experimentally assessing the generation, maintenance, inspection and transformation of mental images; as well as subjective measures of characteristics such as image vividness and clarity. We present a guiding framework in which we propose that cognitive, subjective and clinical aspects of imagery should be explored in future research. The guiding framework aims to assist researchers in the selection of measures for assessing those aspects of mental imagery that are of most relevance to clinical psychology. We propose that a greater understanding of the role of mental imagery in clinical disorders will help drive forward advances in both theory and treatment. PMID:23123567

  3. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

    Science.gov (United States)

    Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

    2009-05-21

    Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

  4. Application of the MALDI Biotyper to clinical microbiology: progress and potential.

    Science.gov (United States)

    Kostrzewa, Markus

    2018-03-01

    The introduction of the MALDI Biotyper in laboratories substantially changed microbiology practice, this has been called a revolution. The system accelerated diagnostic while costs were reduced and accuracy was increased. In just a few years MALDI-TOF MS became the first-line identification tool for microorganisms. Ten years after its introduction, more than 2000 MALDI Biotyper systems are installed in laboratories which are performing routine diagnostic, and the number is still increasing. Areas covered: This article summarises changes in clinical microbiology introduced by the MALDI Biotyper and its effects, as it has been published in peer reviewed articles found in PubMed. Further, the potential of novel developments to increase the value of the system is described. Expert commentary: The MALDI Biotyper has significantly improved clinical microbiology in the area of microorganism identification. Now new developments and applications, e.g. for typing and resistance testing, might further increase its value in clinical microbiology. The systems might get the central diagnostic analyser which is getting integrated into the widely automated microbiology laboratories of the future.

  5. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  6. Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Zecevic Lamija

    2018-04-01

    Full Text Available Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells and serum cytokine concentrations (IL-17 and IFN-alpha as potential biomarkers for this disease.

  7. Clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Thomaz-Soccol

    2011-06-01

    Full Text Available The aim of the present work was to study the clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Parana, Brazil. Twenty one suspected cases of mucocutaneous leishmaniasis (MCL in patients from the endemic areas of leishmaniasis were assessed. Different methods used in diagnosing the disease and the polymerase chain reaction (PCR technique were compared in order to establish the sensitivity of each method. Out of the 21 patients analyzed, 14.3% presented other etiologies such as vasculitis, syphilis, and paracoccidioidomycosis, with all tests negative for leishmaniasis. Out of the remaining 15 patients, 6.7% cases were confirmed for leishmaniasis by direct examination; 46.67% were positive for culture, which allowed isolating and identifying the parasite and - with the PCR technique - it was possible to diagnose 100% MCL patients for all the three repetitions of exams. The PCR optimized for the present work proved to be an auxiliary method for diagnosing leishmaniasis applicable in the patients carrying MCL due to Leishmania (Viannia braziliensis and did not need culture to be performed, resulting in a faster diagnosis.

  8. Systematic reviews: guidance relevant for studies of older people.

    Science.gov (United States)

    Shenkin, Susan D; Harrison, Jennifer K; Wilkinson, Tim; Dodds, Richard M; Ioannidis, John P A

    2017-09-01

    Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written-and if possible published-before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

  9. Top studies relevant to primary care practice.

    Science.gov (United States)

    Perry, Danielle; Kolber, Michael R; Korownyk, Christina; Lindblad, Adrienne J; Ramji, Jamil; Ton, Joey; Allan, G Michael

    2018-04-01

    To summarize 10 high-quality studies from 2017 that have strong relevance to primary care practice. Study selection involved routine literature surveillance by a group of primary care health professionals. This included screening abstracts of important journals and Evidence Alerts, as well as searching the American College of Physicians Journal Club. Topics of the 2017 articles include whether treating subclinical hypothyroidism improves outcomes or symptoms; whether evolocumab reduces cardiovascular disease as well as low-density lipoprotein levels; whether lifestyle interventions reduce medication use in patients with diabetes; whether vitamin D prevents cardiovascular disease, cancer, or upper respiratory tract infections; whether canagliflozin reduces clinical events in patients with diabetes; how corticosteroid injections affect knee osteoarthritis; whether drained abscesses benefit from antibiotic treatment; whether patients with diabetes benefit from bariatric surgery; whether exenatide reduces clinical events in patients with diabetes; and whether tympanostomy tubes affect outcomes in recurrent acute otitis media or chronic otitis media. We provide brief summaries, context where needed, and final recommendations for 10 studies with potential effects on primary care. We also briefly review 5 "runner-up" studies. Research from 2017 produced several high-quality studies in diabetes management. These have demonstrated benefit for alternative therapies and offered evidence not previously available. This year's selection of studies also provided information on a variety of conditions and therapies that are, or might become, more common in primary care settings. Copyright© the College of Family Physicians of Canada.

  10. Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

    Science.gov (United States)

    Gillespie, Mary

    2010-11-01

    Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Thermophilic and alkaliphilic Actinobacteria: biology and potential applications

    Science.gov (United States)

    Shivlata, L.; Satyanarayana, Tulasi

    2015-01-01

    Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications. PMID:26441937

  12. Oxidized zirconium: a potentially longer lasting hip implant

    International Nuclear Information System (INIS)

    Good, V.; Widding, K.; Hunter, G.; Heuer, D.

    2005-01-01

    Because younger, more active patients are receiving total hip replacements, it is necessary to develop materials, which would increase the life span of the implants and challenge their wear potential under adverse conditions. Oxidized zirconium (OxZr) is a metal with the surface transformed to ceramic by oxidation that offers low fracture risk and excellent abrasion resistance. This study compared wear of polyethylene (non-irradiated and highly crosslinked) with OxZr and CoCr heads under smooth and rough (clinically relevant) conditions. Wear was up to 15-fold less and up to 4-fold fewer particles were produced when coupled with OxZr than with CoCr, demonstrating that OxZr heads should increase clinical implant longevity

  13. Aggregation of the protein TRIOBP-1 and its potential relevance to schizophrenia.

    Directory of Open Access Journals (Sweden)

    Nicholas J Bradshaw

    Full Text Available We have previously proposed that specific proteins may form insoluble aggregates as a response to an illness-specific proteostatic dysbalance in a subset of brains from individuals with mental illness, as is the case for other chronic brain conditions. So far, established risk factors DISC1 and dysbindin were seen to specifically aggregate in a subset of such patients, as was a novel schizophrenia-related protein, CRMP1, identified through a condition-specific epitope discovery approach. In this process, antibodies are raised against the pooled insoluble protein fractions (aggregomes of post mortem brain samples from schizophrenia patients, followed by epitope identification and confirmation using additional techniques. Pursuing this epitope discovery paradigm further, we reveal TRIO binding protein (TRIOBP to be a major substrate of a monoclonal antibody with a high specificity to brain aggregomes from patients with chronic mental illness. TRIOBP is a gene previously associated with deafness which encodes for several distinct protein species, each involved in actin cytoskeletal dynamics. The 3' splice variant TRIOBP-1 is found to be the antibody substrate and has a high aggregation propensity when over-expressed in neuroblastoma cells, while the major 5' splice variant, TRIOBP-4, does not. Endogenous TRIOBP-1 can also spontaneously aggregate, doing so to a greater extent in cell cultures which are post-mitotic, consistent with aggregated TRIOBP-1 being able to accumulate in the differentiated neurons of the brain. Finally, upon expression in Neuroscreen-1 cells, aggregated TRIOBP-1 affects cell morphology, indicating that TRIOBP-1 aggregates may directly affect cell development, as opposed to simply being a by-product of other processes involved in major mental illness. While further experiments in clinical samples are required to clarify their relevance to chronic mental illness in the general population, TRIOBP-1 aggregates are thus

  14. Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

    Science.gov (United States)

    Grady, Haiyan; Elder, David; Webster, Gregory K; Mao, Yun; Lin, Yiqing; Flanagan, Talia; Mann, James; Blanchard, Andy; Cohen, Michael J; Lin, Judy; Kesisoglou, Filippos; Hermans, Andre; Abend, Andreas; Zhang, Limin; Curran, David

    2018-01-01

    This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades, dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle. The definitions of commonly used dissolution approaches, how they relate to one another and how they may be applied in modern drug development, and life cycle management is described in this article. Specifically, this article discusses the purpose, advantages, and limitations of quality control, biorelevant, and clinically relevant dissolution methods. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  16. Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Felix C Ringshausen

    2009-02-01

    Full Text Available Felix C Ringshausen1, Ai-Yui M Tan1, Tobias Allander2, Irmgard Borg1, Umut Arinir1, Juliane Kronsbein1, Barbara M Hauptmeier1, Gerhard Schultze-Werninghaus1, Gernot Rohde11Clinical Research Group “Significance of viral infections in chronic respiratory diseases of children and adults,” University Hospital Bergmannsheil, Department of Internal Medicine III–Pneumology, Allergology and Sleep Medicine, Bochum, Germany; 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, SwedenObjective: Human bocavirus (HBoV is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD.Methods: We retrospectively tested 212 COPD patients, 141 (66.5% with AE-COPD and 71 (33.5% with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA. The specificity of positive polymerase chain reaction results was confirmed by sequencing.Results: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%. Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8% and stable COPD (2.9%. HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain.Conclusion: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely

  17. Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

    Directory of Open Access Journals (Sweden)

    Benedikt Frieg

    2016-02-01

    Full Text Available Glutamine synthetase (GS catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

  18. Improving the quality of nurse clinical documentation for chronic patients at primary care clinics: A multifaceted intervention.

    Science.gov (United States)

    Mahomed, Ozayr H; Naidoo, Salsohni; Asmall, Shaidah; Taylor, Myra

    2015-09-25

    Deficiencies in record keeping practices have been reported at primary care level in the public health sector in South Africa. These deficiencies have the potential to negatively impact patient health outcomes as the break in information may hinder continuity of care. This disruption in information management has particular relevance for patients with chronic diseases. The aim of this study was to establish if the implementation of a structured clinical record (SCR) as an adjunct tool to the algorithmic guidelines for chronic disease management improved the quality of clinical records at primary care level. A quasi-experimental study (before and after study with a comparison group) was conducted across 30 primary health care clinics (PHCs) located in three districts in South Africa. Twenty PHCs that received the intervention were selected as intervention clinics and 10 facilities were selected as comparison facilities. The lot quality assurance sampling (LQAS) method was used to determine the number of records required to be reviewed per diagnostic condition per facility. There was a a statistically significant increase in the percentage of clinical records achieving compliance to the minimum criteria from the baseline to six months post-intervention for both HIV patients on antiretroviral treatment and patients with non-communicable diseases (hypertension and diabetes). A multifaceted intervention using a SCR to supplement the educational outreach component (PC 101 training) has demonstrated the potential for improving the quality of clinical records for patients with chronic diseases at primary care clinics in South Africa.

  19. Comparison of biomarker based Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and conventional methods in the identification of clinically relevant bacteria and yeast.

    Science.gov (United States)

    Kassim, Ali; Pflüger, Valentin; Premji, Zul; Daubenberger, Claudia; Revathi, Gunturu

    2017-05-25

    MALDI-TOF MS is an analytical method that has recently become integral in the identification of microorganisms in clinical laboratories. It relies on databases that majorly employ pattern recognition or fingerprinting. Biomarker based databases have also been developed and there is optimism that these may be superior to pattern recognition based databases. This study compared the performance of ribosomal biomarker based MALDI-TOF MS and conventional methods in the identification of selected bacteria and yeast. The study was a cross sectional study identifying clinically relevant bacteria and yeast isolated from varied clinical specimens submitted to a clinical laboratory. The identification of bacteria using conventional Vitek 2™ automated system, serotyping and MALDI-TOF MS was performed as per standard operating procedures. Comparison of sensitivities were then carried out using Pearson Chi-Square test and p-value of bacteria and Gram positive bacteria to the species level. For the Gram positive bacteria, significant difference was observed in the identification of Coagulase negative Staphylococci (p = 0.000) and Enterococcus (p = 0.008). Significant difference was also observed between serotyping and MALDI-TOF MS (p = 0.005) and this was attributed to the lack of identification of Shigella species by MALDI-TOF MS. There was no significant difference observed in the identification of yeast however some species of Candida were unidentified by MALDI-TOF MS. Biomarker based MALDI-TOF MS had good performance in a clinical laboratory setting with high sensitivities in the identification of clinically relevant microorganisms.

  20. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    Science.gov (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  1. A novel clinically relevant segmentation method and corresponding maximal ischemia score to risk-stratify patients undergoing myocardial perfusion scintigraphy.

    Science.gov (United States)

    Nudi, Francesco; Pinto, Annamaria; Procaccini, Enrica; Neri, Giandomenico; Vetere, Maurizio; Tomai, Fabrizio; Gaspardone, Achille; Biondi-Zoccai, Giuseppe; Schillaci, Orazio

    2014-08-01

    Myocardial perfusion scintigraphy (MPS) represents a key prognostic tool, but its predictive yield is far from perfect. We developed a novel clinically relevant segmentation method and a corresponding maximal ischemia score (MIS) in order to risk-stratify patients undergoing MPS. Patients referred for MPS were identified, excluding those with evidence of myocardial necrosis or prior revascularization. A seven-region segmentation approach was adopted for left ventricular myocardium, with a corresponding MIS distinguishing five groups (no, minimal, mild, moderate, or severe ischemia). The association between MIS and clinical events was assessed at 1 year and at long-term follow-up. A total of 8,714 patients were included, with a clinical follow-up of 31 ± 20 months. Unadjusted analyses showed that subjects with a higher MIS were significantly different for several baseline and test data, being older, having lower ejection fraction, and achieving lower workloads (P < .05 for all). Adverse outcomes were also more frequent in patients with higher levels of ischemia, including cardiac death, myocardial infarction (MI), and their composites (P < .05 for all). Differences in adverse events remained significant even after extensive multivariable adjustment (hazard ratio for each MIS increment = 1.57 [1.29-1.90], P < .001 for cardiac death; 1.19 [1.04-1.36], P = .013 for MI; 1.23 [1.09-1.39], P = .001 for cardiac death/MI). Our novel segmentation method and corresponding MIS efficiently yield satisfactory prognostic information.

  2. Comparison of early treatment with low doses of nilotinib, imatinib and a clinically relevant dose of silymarin in thioacetamide-induced liver fibrosis.

    Science.gov (United States)

    Shaker, Mohamed E; Shiha, Gamal E; Ibrahim, Tarek M

    2011-11-30

    Our previous study has already confirmed a promising anti-fibrotic activity especially for nilotinib; when given at a daily dose of 10 mg/kg during the last 4 weeks of thioacetamide (TAA)-induced liver fibrosis for 12 weeks in rats. Therefore, this study was carried out to compare the prophylactic potential of low dose of nilotinib to that of its predecessor, imatinib, and a clinically relevant dose of the standard hepatoprotective treatment, silymarin, in TAA-intoxication. Male Wistar rats received intraperitoneal injections of TAA (150 mg/kg, twice weekly) for 8 weeks, as well as oral treatments with imatinib (5 mg/kg/day), nilotinib (5 mg/kg/day) and silymarin (50 mg/kg/day) from the first day of TAA-intoxication. At the end of the study, chronic hepatic injury was evaluated by analysis of liver function tests in serum. Hepatic oxidative stress was assessed by measuring malondialdehyde, 4-hydroxynonenal, total nitrate/nitrite and reduced glutathione contents, as well as myeloperoxidase and superoxide dismutase activities. Hepatic fibrosis was evaluated by histopathology and collagen content. Our results suggest that the prophylactic potential of nilotinib (5 mg/kg/day), imatinib (5mg/kg/day) and silymarin (50 mg/kg/day) in TAA-intoxication for 8 weeks is lower than the late treatments of nilotinib (10 mg/kg/day), imatinib (10mg/kg/day) and silymarin (100 mg/kg/day) during the last 4 weeks of TAA-intoxication for 12 weeks in rats. Taken together, this study suggests that nilotinib may have higher anti-fibrotic activity when administered at a significant stage of fibrosis as a result of impairment of its metabolism in the fibrotic livers. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Clinical relevance of sensitization to peanut and lupine

    NARCIS (Netherlands)

    Peeters, K.A.B.M.

    2007-01-01

    This thesis demonstrates that the use of purified allergens and techniques such as NMR spectroscopy has the potential to improve current diagnostic capabilities. It also shows that lupine allergy is fairly common in The Netherlands. Characteristics of lupine allergy such as the eliciting dose and

  4. The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

    Science.gov (United States)

    Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

    2017-12-12

    Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

  5. Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

    Science.gov (United States)

    Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

    2012-01-01

    Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

  6. FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Giuseppe Sconocchia

    2017-04-01

    Full Text Available For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient’s immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient’s immune system can recognize and reject his tumor if appropriate strategies are implemented. The success immunotherapy is due to the development of at least three therapeutic strategies. They include tumor-associated antigen (TAA-specific monoclonal antibodies (mAbs, T cell checkpoint blockade, and TAA-specific chimeric antigen receptors (CARs T cell-based immunotherapy. However, the full realization of the therapeutic potential of these approaches requires the development of strategies to counteract and overcome some limitations. They include off-target toxicity and mechanisms of cancer immune evasion, which obstacle the successful clinical application of mAbs and CAR T cell-based immunotherapies. Thus, we and others have developed the Fc gamma chimeric receptors (Fcγ-CRs-based strategy. Like CARs, Fcγ-CRs are composed of an intracellular tail resulting from the fusion of a co-stimulatory molecule with the T cell receptor ζ chain. In contrast, the extracellular CAR single-chain variable fragment (scFv, which recognizes the targeted TAA, has been replaced with the extracellular portion of the FcγRIIIA (CD16. Fcγ-CR T cells have a few intriguing features. First, given in combination with mAbs, Fcγ-CR T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple cancer types provided that TAA-specific mAbs with the appropriate specificity are available

  7. Apps and eating disorders: A systematic clinical appraisal

    OpenAIRE

    Fairburn, Christopher G.; Rothwell, Emily R.

    2015-01-01

    ABSTRACT Objective Smartphone applications (apps) are proliferating and health?related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. Method A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. Results The apps f...

  8. Retrieval of diagnostic and treatment studies for clinical use through PubMed and PubMed's Clinical Queries filters.

    Science.gov (United States)

    Lokker, Cynthia; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Walter, Stephen D

    2011-01-01

    Clinical Queries filters were developed to improve the retrieval of high-quality studies in searches on clinical matters. The study objective was to determine the yield of relevant citations and physician satisfaction while searching for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with searching PubMed without these filters. Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction. For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance. Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions. Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

  9. Gatekeepers for pragmatic clinical trials.

    Science.gov (United States)

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  10. Innovating information-delivery for potential clinical trials participants. What do patients want from multi-media resources?

    Science.gov (United States)

    Shneerson, Catherine; Windle, Richard; Cox, Karen

    2013-01-01

    To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. RELEVANCE OF COLLAGEN PIEZOELECTRICITY TO “WOLFF’S LAW”: A CRITICAL REVIEW

    Science.gov (United States)

    Ahn, Andrew C.; Grodzinsky, Alan J.

    2009-01-01

    According to “Wolff’s Law”, bone is deposited and reinforced at areas of greatest stress. From a clinical perspective, this “law” is supported by the strong association between bone density and physical activity. From a mechanistic standpoint, however, the law presents a challenge to scientists seeking to understand how osteocytes and osteoblasts sense the mechanical load. In the 1960’s, collagen piezoelectricity was invoked as a potential mechanism by which osteocytes could detect areas of greater stress but piezoelectricity diminished in importance as more compelling mechanisms, such as streaming potential, were identified. In addition, accumulating evidence for the role of fluid-related shear stress in osteocyte’s mechanosensory function has made piezoelectricity seemingly more obsolete in bone physiology. This review critically evaluates the role of collagen piezoelectricity (if any) in Wolff’s Law – specifically, the evidence regarding its involvement in strain-generated potentials, existing alternate mechanisms, the present understanding of bone mechanosensation, and whether piezoelectricity serves an influential role within the context of this newly proposed mechanism. In addition to reviewing the literature, this review generates several hypotheses and proposes future research to fully address the relevance of piezoelectricity in bone physiology. PMID:19286413

  12. PROPOSED CARDIAC STEM CELLS DERIVED FROM “CARDIOSPHERES” LACK CARDIOMYOGENIC POTENTIAL

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline

       Recent studies have reported that clinical relevant numbers of cardiac stem cells (CSCs) with cardiomyogenic potential can be obtained from small heart tissue biopsies, by an intrinsic ability of CSCs to form beating cardiospheres (CSs) during ex vivo culture. Such data have provided optimism...... that injuried heart tissue may be repaired by stem cell therapy using autologous CS derived cells, and pre-clinical studies have already been described in literature.    Herein, we established CSs from neonatal rats, and by immunofluorescence, qRT-PCR, and microscopic examination we demonstrated...... to form CSs by themselves. Phenotypically, CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential.    Our data imply that at least the murine cardiosphere model seems unsuitable for enrichment of cardiac stem cells with cardiomyogenic...

  13. Sequence variation of the feline immunodeficiency virus genome and its clinical relevance.

    Science.gov (United States)

    Stickney, A L; Dunowska, M; Cave, N J

    2013-06-08

    The ongoing evolution of feline immunodeficiency virus (FIV) has resulted in the existence of a diverse continuum of viruses. FIV isolates differ with regards to their mutation and replication rates, plasma viral loads, cell tropism and the ability to induce apoptosis. Clinical disease in FIV-infected cats is also inconsistent. Genomic sequence variation of FIV is likely to be responsible for some of the variation in viral behaviour. The specific genetic sequences that influence these key viral properties remain to be determined. With knowledge of the specific key determinants of pathogenicity, there is the potential for veterinarians in the future to apply this information for prognostic purposes. Genomic sequence variation of FIV also presents an obstacle to effective vaccine development. Most challenge studies demonstrate acceptable efficacy of a dual-subtype FIV vaccine (Fel-O-Vax FIV) against FIV infection under experimental settings; however, vaccine efficacy in the field still remains to be proven. It is important that we discover the key determinants of immunity induced by this vaccine; such data would compliment vaccine field efficacy studies and provide the basis to make informed recommendations on its use.

  14. Why ritual plant use has ethnopharmacological relevance

    NARCIS (Netherlands)

    Quiroz, Diana; Sosef, Marc; Andel, Van Tinde

    2016-01-01

    Ethnopharmacological relevance Although ritual plant use is now recognised both for its socio-cultural importance and for its contribution to nature conservation, its potential pharmacological effects remain overlooked. Aim of the study Our objective was to see whether ritual plant use could have

  15. Evidence-based integrative medicine in clinical veterinary oncology.

    Science.gov (United States)

    Raditic, Donna M; Bartges, Joseph W

    2014-09-01

    Integrative medicine is the combined use of complementary and alternative medicine with conventional or traditional Western medicine systems. The demand for integrative veterinary medicine is growing, but evidence-based research on its efficacy is limited. In veterinary clinical oncology, such research could be translated to human medicine, because veterinary patients with spontaneous tumors are valuable translational models for human cancers. An overview of specific herbs, botanics, dietary supplements, and acupuncture evaluated in dogs, in vitro canine cells, and other relevant species both in vivo and in vitro is presented for their potential use as integrative therapies in veterinary clinical oncology. Published by Elsevier Inc.

  16. Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium

    Directory of Open Access Journals (Sweden)

    Hafize Sav

    2018-01-01

    Full Text Available Clinically relevant members of the fungal genus, Fusarium, exhibit an extraordinary genetic diversity and cause a wide spectrum of infections in both healthy individuals and immunocompromised patients. Generally, Fusarium species are intrinsically resistant to all systemic antifungals. We investigated whether the presence or absence of the ability to produce biofilms across and within Fusarium species complexes is linked to higher resistance against antifungals. A collection of 41 Fusarium strains, obtained from 38 patients with superficial and systemic infections, and three infected crops, were tested, including 25 species within the Fusarium fujikuroi species complex, 14 from the Fusarium solani species complex (FSSC, one Fusarium dimerum species complex, and one Fusarium oxysporum species complex isolate. Of all isolates tested, only seven strains from two species of FSSC, five F. petroliphilum and two F. keratoplasticum strains, recovered from blood, nail scrapings, and nasal biopsy samples, could produce biofilms under the tested conditions. In the liquid culture tested, sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory concentrations (MICs for amphotericin B, voriconazole, and posaconazole, compared to their planktonic counterparts, indicating that the ability to form biofilm may significantly increase resistance. Collectively, this suggests that once a surface adherent biofilm has been established, therapies designed to kill planktonic cells of Fusarium are ineffective.

  17. Thermophilic and alkaliphilic Actinobacteria: Biology and potential applications

    Directory of Open Access Journals (Sweden)

    L eShivlata

    2015-09-01

    Full Text Available Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications.

  18. [First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans/ Anaerobic Subcommittee of the Asociación Argentina de Microbiología].

    Science.gov (United States)

    Legaria, María C; Bianchini, Hebe M; Castello, Liliana; Carloni, Graciela; Di Martino, Ana; Fernández Canigia, Liliana; Litterio, Mirta; Rollet, Raquel; Rossetti, Adelaida; Predari, Silvia C

    2011-01-01

    Through time, anaerobic bacteria have shown good susceptibility to clinically useful antianaerobic agents. Nevertheless, the antimicrobial resistance profile of most of the anaerobic species related to severe infections in humans has been modified in the last years and different kinds of resistance to the most active agents have emerged, making their effectiveness less predictable. With the aim of finding an answer and for the purpose of facilitating the detection of anaerobic antimicrobial resistance, the Anaerobic Subcommittee of the Asociación Argentina de Microbiología developed the First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans. This document resulted from the compatibilization of the Clinical and Laboratory Standards Institute recommendations, the international literature and the work and experience of the Subcommittee. The Consensus document provides a brief taxonomy review, and exposes why and when anaerobic antimicrobial susceptibility tests should be conducted, and which antimicrobial agents can be used according to the species involved. The recommendations on how to perform, read and interpret in vitro anaerobic antimicrobial susceptibility tests with each method are exposed. Finally, the antibiotic susceptibility profile, the classification of antibiotics according to their in vitro activities, the natural and acquired mechanisms of resistance, the emerging resistance and the regional antibiotic resistance profile of clinically relevant anaerobic species are shown.

  19. Research methods to change clinical practice for patients with rare cancers.

    Science.gov (United States)

    Billingham, Lucinda; Malottki, Kinga; Steven, Neil

    2016-02-01

    Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Progastrin: a potential predictive marker of liver metastasis in colorectal cancer.

    Science.gov (United States)

    Westwood, David A; Patel, Oneel; Christophi, Christopher; Shulkes, Arthur; Baldwin, Graham S

    2017-07-01

    Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer. Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining. Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P colorectal cancer and supports its clinical relevance and potential use as a biomarker.

  1. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review

    NARCIS (Netherlands)

    de Rooij, S. E.; Schuurmans, M. J.; van der Mast, R. C.; Levi, M. [=Marcel M.

    2005-01-01

    Background Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The

  2. [Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections].

    Science.gov (United States)

    Stock, Ingo

    2014-07-01

    The nitrofuran derivative nitrofurantoin has been used for more than 60 years for the antibacterial therapy of uncomplicated urinary tract infections (UTI). Despite its long application, this antibiotic retained good activity against Escherichia coli and some other pathogens of uncomplicated urinary tract infections such as Staphylococcus saprophyticus and Enterococcus species. Nitrofurantoin therapy has been shown to be accompanied by numerous adverse drug effects. Among these, there are also serious side effects such as pulmonary reactions and polyneuropathy, which mainly occur in long-term use. Recent studies, however, have shown a good efficacy and tolerability of short-term nitrofurantoin therapy comparable to previous established standard therapeutic regimens applying cotrimoxazole or quinolones. Because of these data and the alarming resistance rates of uropathogenic Escherichia coli to cotrimoxazole and quinolones that have been increased markedly in several countries, the clinical significance ofnitrofurantoin has been raised again. In many current treatment guidelines, e. g., the international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women published by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases, nitrofurantoin has been recommended as one first-line antibiotic of empiric antibacterial treatment of uncomplicated cystitis in otherwise healthy women. In Germany, however, nitrofurantoin should only be applied if more effective and less risky antibiotics cannot be used. Nitrofurantoin is contraindicated in the last three months of pregnancy and in patients suffering from renal impairment of each degree. Despite compatibility concerns, nitrofurantoin has also been recommended for the re-infection prophylaxis of recurrent uncomplicated urinary tract infections in Germany and several other countries.

  3. A Critical Investigation of the Relevance and Potential of IDPS as a Local Governance Instrument for Pursuing Social Justice in South Africa

    Directory of Open Access Journals (Sweden)

    Oliver Njuh Fuo

    2013-12-01

    Full Text Available Unlike the situation in the past, when local government’s role was limited to service delivery, local government is now constitutionally mandated to play an expanded developmental role. As a “co-responsible” sphere of government, local government is obliged to contribute towards realising the transformative constitutional mandate aimed at social justice. South African scholars and jurists share the view that social justice is primarily concerned with the eradication of poverty and extreme inequalities in access to basic services, and aims to ensure that poor people command sufficient material resources to facilitate their equal participation in socio-political life. In order to enable municipalities to fulfil their broad constitutional mandate, the system of integrated development planning (IDPs came into effect in South Africa in 2000. Each municipality is obliged to design, adopt and implement an integrated development plan in order to achieve its expanded constitutional mandate. The IDP is considered to be the chief legally prescribed governance instrument for South African municipalities. The purpose of this article is to explore and critically investigate the relevance and potential of IDPs in contributing towards the achievement of social justice in South Africa. This article argues inter alia that the multitude of sectors that converge in an IDP makes it directly relevant and gives it enormous potential to contribute towards social justice because, depending on the context, municipalities could include and implement strategies that specifically respond to diverse areas of human need. In this regard, the legal and policy frameworks for IDPs provide a structured scheme that could be used by municipalities to prioritise and meet the basic needs of especially the poor. Despite its potential, it is argued that the ability of IDPs to respond to the basic needs of the poor is largely constrained by a series of implementation challenges

  4. Relevance and feasibility of Social Life Cycle Assessment from a Company Perspective

    DEFF Research Database (Denmark)

    Jørgensen, Andreas; Hauschild, Michael Zwicky; Jørgensen, Michael Søgaard

    2009-01-01

    Methodology development should reflect demands from the intended users: what are the needs of the user group and what is feasible in terms of requirements involving data and work? Mapping these questions of relevance and feasibility is thus a way to facilitate a higher degree of relevance...... of the developed methodology. For the emerging area of social life cycle assessment (SLCA), several different potential user groups may be identified. This article addresses the issues of relevance and feasibility of SLCA from a company perspective through a series of interviews among potential company users....... The empirical basis for the survey is a series of eight semi-structured interviews with larger Danish companies, all of which potentially have the capacity and will to use comprehensive social assessment methodologies. SLCA is not yet a well-defined methodology, but still it is possible to outline several...

  5. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

    Directory of Open Access Journals (Sweden)

    Kulig Kornelia

    2009-05-01

    Full Text Available Abstract Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration http://www.clinicaltrials.gov identifier NCT00847769.

  6. Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing [CFDA, Center for Medical Device Evaluation, Beijing (China); Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong [First Affiliated Hospital with Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Bao, Mei-Ling [First Affiliated Hospital with Nanjing Medical University, Department of Pathology, Nanjing (China)

    2017-10-15

    To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. (orig.)

  7. Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

    International Nuclear Information System (INIS)

    Wang, Jing; Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong; Bao, Mei-Ling

    2017-01-01

    To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal