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Sample records for providing relevant clinical

  1. Clinically Relevant Injury Patterns After an Anterior Cruciate Ligament Injury Provide Insight Into Injury Mechanisms

    Science.gov (United States)

    Levine, Jason W.; Kiapour, Ata M.; Quatman, Carmen E.; Wordeman, Samuel C.; Goel, Vijay K.; Hewett, Timothy E.; Demetropoulos, Constantine K.

    2014-01-01

    Background The functional disability and high costs of treating anterior cruciate ligament (ACL) injuries have generated a great deal of interest in understanding the mechanism of noncontact ACL injuries. Secondary bone bruises have been reported in over 80% of partial and complete ACL ruptures. Purpose The objectives of this study were (1) to quantify ACL strain under a range of physiologically relevant loading conditions and (2) to evaluate soft tissue and bony injury patterns associated with applied loading conditions thought to be responsible for many noncontact ACL injuries. Study Design Controlled laboratory study. Methods Seventeen cadaveric legs (age, 45 ± 7 years; 9 female and 8 male) were tested utilizing a custom-designed drop stand to simulate landing. Specimens were randomly assigned between 2 loading groups that evaluated ACL strain under either knee abduction or internal tibial rotation moments. In each group, combinations of anterior tibial shear force, and knee abduction and internal tibial rotation moments under axial impact loading were applied sequentially until failure. Specimens were tested at 25° of flexion under simulated 1200-N quadriceps and 800-N hamstring loads. A differential variable reluctance transducer was used to calculate ACL strain across the anteromedial bundle. A general linear model was used to compare peak ACL strain at failure. Correlations between simulated knee injury patterns and loading conditions were evaluated by the χ2 test for independence. Results Anterior cruciate ligament failure was generated in 15 of 17 specimens (88%). A clinically relevant distribution of failure patterns was observed including medial collateral ligament tears and damage to the menisci, cartilage, and subchondral bone. Only abduction significantly contributed to calculated peak ACL strain at failure (P = .002). While ACL disruption patterns were independent of the loading mechanism, tibial plateau injury patterns (locations) were

  2. Preclinical Models Provide Scientific Justification and Translational Relevance for Moving Novel Therapeutics into Clinical Trials for Pediatric Cancer.

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    Langenau, David M; Sweet-Cordero, Alejandro; Wechsler-Reya, Robert; Dyer, Michael A

    2015-12-15

    Despite improvements in survival rates for children with cancer since the 1960s, progress for many pediatric malignancies has slowed over the past two decades. With the recent advances in our understanding of the genomic landscape of pediatric cancer, there is now enthusiasm for individualized cancer therapy based on genomic profiling of patients' tumors. However, several obstacles to effective personalized cancer therapy remain. For example, relatively little data from prospective clinical trials demonstrate the selective efficacy of molecular-targeted therapeutics based on somatic mutations in the patient's tumor. In this commentary, we discuss recent advances in preclinical testing for pediatric cancer and provide recommendations for providing scientific justification and translational relevance for novel therapeutic combinations for childhood cancer. Establishing rigorous criteria for defining and validating druggable mutations will be essential for the success of ongoing and future clinical genomic trials for pediatric malignancies. ©2015 American Association for Cancer Research.

  3. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

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    Melissa Paoloni

    Full Text Available BACKGROUND: 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. METHODOLOGY: 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. CONCLUSIONS: 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 (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of

  4. Feasibility of Providing Culturally Relevant, Brief Interpersonal Psychotherapy for Antenatal Depression in an Obstetrics Clinic: A Pilot Study

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    Grote, Nancy K.; Bledsoe, Sarah E.; Swartz, Holly A.; Frank, Ellen

    2004-01-01

    Objective: To minimize barriers to care, ameliorate antenatal depression, and prevent postpartum depression, we conducted a pilot study to assess the feasibility of providing brief interpersonal psychotherapy (IPT-B) to depressed, pregnant patients on low incomes in an obstetrics and gynecological (OB/GYN) clinic. Method: Twelve pregnant,…

  5. Clinical Relevance of Adipokines

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    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.

  6. Google Scholar Retrieves Twice as Many Relevant Citations as PubMed and Provides Greater Full-Text Access for Quick, Clinical Nephrology Searches

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    Diana K. Wakimoto

    2014-03-01

    Full Text Available Objective – To compare recall and precision of results retrieved by searches in PubMed and Google Scholar for clinical nephrology literature. Design – Survey questionnaire, comparative. Setting – Canada. Subjects – Practicing nephrologists with average age of 48 years and who have practiced nephrology for an average of 15 years. Methods – The researchers identified 100 systematic reviews in renal therapy published between 2001 and 2009. The primary studies cited in the systematic reviews served as the reference standard for relevant articles; 1,574 unique citations were identified and used to measure recall and precision. The researchers created a unique clinical question from each of the objective statements of systematic reviews and sent one question to a random sample of practicing nephrologists to determine the search strings they would use to search for clinical literature; the researchers collected 100 usable responses. Using the search string in both Google Scholar and PubMed, the researchers analyzed the first 40 retrieved results in each for recall of relevant literature and precision. The researchers also analyzed the availability of full-text articles in each database. A pilot study to test the methodology preceded the main study. Results – Google Scholar’s recall for the first 40 records was 21.9% and PubMed was 10.9%. Each database contained 78% of the relevant literature/reference standard set from the systematic reviews. However, 15% of the articles were in neither database. Precision results were similar (7.6% for Google Scholar and 5.6% for PubMed. Google Scholar had more full-text available at 15% of articles versus 5% for PubMed. Google Scholar and PubMed had similar numbers of relevant articles when all retrieved records were analyzed, but Google Scholar still provided more access to free full-text articles. Conclusion – Google Scholar provides better recall and provides more access to full-text than Pub

  7. 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....

  8. 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....

  9. Providing Relevance in Chemistry for Nursing Students

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    Jones, Theodore H. D.

    1976-01-01

    Describes an introductory chemistry course for nurses in which students learn basic chemical principles by performing 12 chemical analyses that are routinely conducted on body fluids and listed on a patient's clinical laboratory chart. (MLH)

  10. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

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    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. Providing Educationally Relevant Occupational and Physical Therapy Services

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    Laverdure, Patricia A.; Rose, Deborah S.

    2012-01-01

    As defined in the Individuals with Disabilities Education Improvement Act, occupational and physical therapists provide services to support students to access, participate, and progress in their educational program within the least restrictive educational environment. Educationally relevant occupational and physical therapy services in school…

  12. Women with epilepsy: clinically relevant issues

    OpenAIRE

    Bangar, Santosh; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E.

    2016-01-01

    Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (includi...

  13. 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.

  14. Clinical embryology teaching: is it relevant anymore?

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    Scott, Karen M; Charles, Antony Robert; Holland, Andrew J A

    2013-10-01

    Embryology finds itself jostling for precious space in the crowded medical curriculum, yet remains important for helping students understand birth defects. It has been suggested that teaching embryology through clinical scenarios can increase its relevance and interest. The aim of this research was to determine the attitudes of final-year medical students to learning embryology and whether clinical scenarios aid understanding. Final-year medical students undertaking their paediatric rotation in 2009 and 2010 were invited to attend an optional lecture on clinical embryology and participate in the research. In the lecture, three clinical scenarios were presented, in which the lecturer traced the normal development of a foetus and the abnormal development that resulted in a birth defect. Outcomes were assessed quantitatively using a paper-based survey. The vast majority of students who valued embryology teaching in their medical programme thought it would assist them with clinical management, and believed learning through case scenarios helped their understanding. Students were divided in their beliefs about when embryology should be taught in the medical programme and whether it would increase their workload. Embryology teaching appears to be a valuable part of the medical curriculum. Embryology teaching was valued when taught in the clinical environment in later years of the medical programme. Students, clinicians and medical educators should be proactive in finding clinical learning opportunities for embryology teaching. © 2013 Royal Australasian College of Surgeons.

  15. Do quantitative decadal forecasts from GCMs provide decision relevant skill?

    Science.gov (United States)

    Suckling, E. B.; Smith, L. A.

    2012-04-01

    It is widely held that only physics-based simulation models can capture the dynamics required to provide decision-relevant probabilistic climate predictions. This fact in itself provides no evidence that predictions from today's GCMs are fit for purpose. Empirical (data-based) models are employed to make probability forecasts on decadal timescales, where it is argued that these 'physics free' forecasts provide a quantitative 'zero skill' target for the evaluation of forecasts based on more complicated models. It is demonstrated that these zero skill models are competitive with GCMs on decadal scales for probability forecasts evaluated over the last 50 years. Complications of statistical interpretation due to the 'hindcast' nature of this experiment, and the likely relevance of arguments that the lack of hindcast skill is irrelevant as the signal will soon 'come out of the noise' are discussed. A lack of decision relevant quantiative skill does not bring the science-based insights of anthropogenic warming into doubt, but it does call for a clear quantification of limits, as a function of lead time, for spatial and temporal scales on which decisions based on such model output are expected to prove maladaptive. Failing to do so may risk the credibility of science in support of policy in the long term. The performance amongst a collection of simulation models is evaluated, having transformed ensembles of point forecasts into probability distributions through the kernel dressing procedure [1], according to a selection of proper skill scores [2] and contrasted with purely data-based empirical models. Data-based models are unlikely to yield realistic forecasts for future climate change if the Earth system moves away from the conditions observed in the past, upon which the models are constructed; in this sense the empirical model defines zero skill. When should a decision relevant simulation model be expected to significantly outperform such empirical models? Probability

  16. [Clinical relevance of cardiopulmonary reflexes in anesthesiology].

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    Guerri-Guttenberg, R A; Siaba-Serrate, F; Cacheiro, F J

    2013-10-01

    The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge reflexes and their interaction with local mechanisms, are a demonstration of the richness of cardiovascular responses that occur in human beings. As well as these, the anesthesiologist must contend with other variables that interact by attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs, surgical manipulation, and patient positioning. In the present article we review these reflexes and their clinical relevance in anesthesiology. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  17. The clinical relevance of Tarlov cysts.

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    Langdown, Andrew John; Grundy, Julian R B; Birch, Nicholas C

    2005-02-01

    The sacral perineural cyst was first described by Tarlov in 1938 as an incidental finding at autopsy. There are very few data in the literature regarding the role of Tarlov cysts in causing symptoms, however. Most studies report low numbers, and consequently, the recommendations for treatment are vague. Our aim, therefore, is to present further detail regarding the clinical relevance of Tarlov cysts and to identify whether or not they are a cause of lumbosacral spinal canal stenosis symptoms. Over a 5-year period, 3535 patients underwent magnetic resonance imaging (MRI) scan for lumbosacral symptoms. Fifty-four patients were identified as having Tarlov cysts, and their clinical picture was correlated with the findings on MRI. The majority of Tarlov cysts (n = 38) cannot be held responsible for patients' symptoms and are clinically unimportant. However, we encountered several patients in whom Tarlov cysts (n = 9) occurred at the same level as another pathology. In these cases, the cyst itself did not require any specific therapy; treatment was directed at the other pathology, and uneventful symptom resolution occurred. A smaller subgroup of cysts (n = 7) are the main cause of patients' symptoms and may require specific treatment to facilitate local decompression. The majority of Tarlov cysts are incidental findings on MRI. Where confusion exists as to the clinical relevance of a Tarlov cyst, treatment of the primary pathology (ie, non-Tarlov lesion) is usually sufficient. Tarlov cysts may, however, be responsible for a patient's symptoms; possible mechanisms by which this may occur and treatment strategies are discussed.

  18. 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.

  19. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

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    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.

  20. Clinical relevance of Mycobacterium simiae in pulmonary samples.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Dekhuijzen, P.N.R.; Soolingen, D van

    2008-01-01

    The aim of the present study was to determine the clinical relevance of Mycobacterium simiae isolation from clinical samples. The medical files of patients in the Netherlands from whom M. simiae was isolated between 1999 and 2006 were reviewed in order to assess frequency and clinical relevance.

  1. 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

  2. Clinically Relevant Imaging in Tuberous Sclerosis

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    Rupa Radhakrishnan

    2011-01-01

    Full Text Available Tuberous sclerosis (TS, also known as Bourneville disease or Bourneville-Pringle disease, is an autosomal dominant genetic disorder classically characterized by the presence of hamartomatous growths in multiple organs. TS and tuberous sclerosis complex (TSC are different terms for the same genetic condition. Both terms describe clinical changes due to mutations involving either of the two genes named TSC1 and TSC2, which regulate cell growth. The diagnosis of TSC is established using diagnostic criteria based on clinical and imaging findings. Routine screening and surveillance of patients with TSC is needed to determine the presence and extent of organ involvement, especially the brain, kidneys, and lungs, and identify the development of associated complications. As the treatment is organ specific, imaging plays a crucial role in the management of patients with TSC.

  3. DNA barcoding of clinically relevant Cunninghamella species

    NARCIS (Netherlands)

    Yu, Jin; Walther, G; Van Diepeningen, A D; Gerrits Van Den Ende, A H G; Li, Ruo-Yu; Moussa, T A A; Almaghrabi, O A; De Hoog, G S

    2015-01-01

    Mucormycosis caused, in part, by representatives of the genus Cunninghamella is a severe infection with high mortality in patients with impaired immunity. Several species have been described in the literature as etiologic agents. A DNA barcoding study using ITS rDNA and tef-1α provided concordance

  4. Clinical relevance of drug-drug interactions : a structured assessment procedure.

    NARCIS (Netherlands)

    Roon, E.N. van; Flikweert, S.; Comte, M. le; Langendijk, P.N.; Kwee-Zuiderwijk, W.J.; Smits, P.; Brouwers, J.R.B.J.

    2005-01-01

    INTRODUCTION: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for the

  5. Clinical relevance of drug-drug interactions - A structured assessment procedure

    NARCIS (Netherlands)

    van Roon, EN; Flikweert, S; le Comte, M; Langendijk, PNJ; Kwee-Zuiderwijk, WJM; Smits, P; Brouwers, JRBJ

    2005-01-01

    Introduction: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS C, reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for

  6. Hepatocellular adenoma: Classification, variants and clinical relevance.

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    Bioulac-Sage, Paulette; Sempoux, Christine; Balabaud, Charles

    2017-03-01

    Hepatocellular adenomas are benign tumors with two major complications, bleeding and malignant transformation. The overall narrative of hepatocellular adenoma has evolved over time. Solitary or multiple hepatocellular developing in the normal liver of women of child bearing age exposed to oral contraceptives still represents the most frequent clinical context, however, new associations are being recognized. Hepatocellular adenoma is discovered on a background of liver diseases such as non-alcoholic steatohepatitis, vascular diseases, and alcoholic cirrhosis. Hepatocellular adenoma is also reported in men, young or older adults, and even in infants. On the morpho-molecular side, the great leap forward was the discovery that hepatocellular adenoma was not a single entity and that at least 3 different subtypes exist, with specific underlying gene mutations. These mutations affect the HNF1A gene, several genes leading to JAK/STAT3 pathway activation and the CTNNB1 gene. All of them are associated with more or less specific histopathological characteristics and can be recognized using immunohistochemistry either with specific antibodies or with surrogate markers. Liver pathologists and radiologists are the key actors in the identification of the different subtypes of hepatocellular adenoma by the recognition of their specific morphological features. The major impact of the classification of hepatocellular adenoma is to identify subjects who are at higher risk of malignant transformation. With the development of new molecular technologies, there is hope for a better understanding of the natural history of the different subtypes, and, particularly for their mechanisms of malignant transformation. Copyright © 2017. Published by Elsevier Inc.

  7. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy.

    Science.gov (United States)

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A

    2015-01-01

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).

  8. DNA barcoding of clinically relevant Cunninghamella species.

    Science.gov (United States)

    Yu, Jin; Walther, G; Van Diepeningen, A D; Gerrits Van Den Ende, A H G; Li, Ruo-Yu; Moussa, T A A; Almaghrabi, O A; De Hoog, G S

    2015-02-01

    Mucormycosis caused, in part, by representatives of the genus Cunninghamella is a severe infection with high mortality in patients with impaired immunity. Several species have been described in the literature as etiologic agents. A DNA barcoding study using ITS rDNA and tef-1α provided concordance of molecular data with conventional characters. The currently accepted Cunninghamella species were well supported in phylogenetic trees of both markers except for C. septata with ITS that clustered in the C. echinulata clade. Sequence variability was distinctly higher for the ITS than for tef-1α. Intraspecific ITS variability of some of the species exceeded that between some closely related species, but the marker remained applicable for species identification. The most variable species for both markers was C. echinulata. Cunninghamella bertholletiae is the main pathogenic species; infections by C. blakesleeana, C. echinulata, and C. elegans are highly exceptional. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Bed Bugs: Clinical Relevance and Control Options

    Science.gov (United States)

    Dwyer, Dominic E.; Peñas, Pablo F.; Russell, Richard C.

    2012-01-01

    Summary: Since the late 1990s, bed bugs of the species Cimex lectularius and Cimex hemipterus have undergone a worldwide resurgence. These bed bugs are blood-sucking insects that readily bite humans. Cutaneous reactions may occur and can start out as small macular lesions that can develop into distinctive wheals of around 5 cm in diameter, which are accompanied by intense itching. Occasionally, bullous eruptions may result. If bed bugs are numerous, the patient can present with widespread urticaria or eythematous rashes. Often, bites occur in lines along the limbs. Over 40 pathogens have been detected in bed bugs, but there is no definitive evidence that they transmit any disease-causing organisms to humans. Anemia may result when bed bugs are numerous, and their allergens can trigger asthmatic reactions. The misuse of chemicals and other technologies for controlling bed bugs has the potential to have a deleterious impact on human health, while the insect itself can be the cause of significant psychological trauma. The control of bed bugs is challenging and should encompass a multidisciplinary approach utilizing nonchemical means of control and the judicious use of insecticides. For accommodation providers, risk management procedures should be implemented to reduce the potential of bed bug infestations. PMID:22232375

  10. Clinically relevant issues related to preheating composites.

    Science.gov (United States)

    Daronch, Márcia; Rueggeberg, Frederick A; Moss, Linda; de Goes, Mario Fernando

    2006-01-01

    Issues regarding the use of composite preheating need to be investigated so that the clinician will better understand the variables associated with this method. To examine the multiple aspects of use of a commercial composite preheating device (Calset, AdDent Inc., Danbury, CT, USA). Temperature values of three heating units and composite compules were obtained using a K-type thermocouple and were recorded digitally in real time. The following parameters were measured: maximum heater and composite temperature and its stability upon storage, composite temperature change when removed from the heater and injected, the effect of delivery system on ejected composite temperature, and the effect of repeated and extended preheating on composite monomer conversion (using infrared spectroscopy). Monomer conversion was measured after repeated composite cycling (from room temperature [RT] to 60 degrees C, 10x) or extended preheating (24 hours at 60 degrees C), and values were compared with composite maintained at RT (control group). Among test parameters, data (N=5 for each parameter) were analyzed using Student's t-test, analysis of variance, and the Tukey-Kramer post-hoc test where appropriate (alpha=0.05). Two of the three tested units achieved the stated preset temperatures. Composite attained temperature values close to the heating unit. Composite temperature drop upon removal from the heater was dramatic: within 2 minutes a 50% temperature drop was noted. Heating the compule while preloaded in the syringe provided higher delivery temperatures than heating the compule separately (p preheated composite was dispensed and used as quickly as possible. Neither repeated nor extended preheating of composite significantly affected monomer conversion. Preheating composite has potential benefits, but should be used with knowledge of its limitations. Reheating of unused composite does not affect its degree of conversion, thus decreasing material waste. Heating of the composite

  11. Clinically Relevant Drug Interactions with Anti-Alzheimer's Drugs.

    Science.gov (United States)

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo

    2017-01-01

    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. The concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Providing effective supervision in clinical neuropsychology.

    Science.gov (United States)

    Stucky, Kirk J; Bush, Shane; Donders, Jacobus

    2010-01-01

    A specialty like clinical neuropsychology is shaped by its selection of trainees, educational standards, expected competencies, and the structure of its training programs. The development of individual competency in this specialty is dependent to a considerable degree on the provision of competent supervision to its trainees. In clinical neuropsychology, as in other areas of professional health-service psychology, supervision is the most frequently used method for teaching a variety of skills, including assessment, report writing, differential diagnosis, and treatment. Although much has been written about the provision of quality supervision in clinical and counseling psychology, very little published guidance is available regarding the teaching and provision of supervision in clinical neuropsychology. The primary focus of this article is to provide a framework and guidance for the development of suggested competency standards for training of neuropsychological supervisors, particularly at the residency level. In this paper we outline important components of supervision for neuropsychology trainees and suggest ways in which clinicians can prepare for supervisory roles. Similar to Falender and Shafranske (2004), we propose a competency-based approach to supervision that advocates for a science-informed, formalized, and objective process that clearly delineates the competencies required for good supervisory practice. As much as possible, supervisory competencies are related to foundational and functional competencies in professional psychology, as well as recent legislative initiatives mandating training in supervision. It is our hope that this article will foster further discussion regarding this complex topic, and eventually enhance training in clinical neuropsychology.

  13. Quantifying the clinical relevance of a laboratory observer performance paradigm.

    Science.gov (United States)

    Chakraborty, D P; Haygood, T M; Ryan, J; Marom, E M; Evanoff, M; McEntee, M F; Brennan, P C

    2012-09-01

    Laboratory observer performance measurements, receiver operating characteristic (ROC) and free-response ROC (FROC) differ from actual clinical interpretations in several respects, which could compromise their clinical relevance. The objective of this study was to develop a method for quantifying the clinical relevance of a laboratory paradigm and apply it to compare the ROC and FROC paradigms in a nodule detection task. The original prospective interpretations of 80 digital chest radiographs were classified by the truth panel as correct (C=1) or incorrect (C=0), depending on correlation with additional imaging, and the average of C was interpreted as the clinical figure of merit. FROC data were acquired for 21 radiologists and ROC data were inferred using the highest ratings. The areas under the ROC and alternative FROC curves were used as laboratory figures of merit. Bootstrap analysis was conducted to estimate conventional agreement measures between laboratory and clinical figures of merit. Also computed was a pseudovalue-based image-level correctness measure of the laboratory interpretations, whose association with C as measured by the area (rAUC) under an appropriately defined relevance ROC curve, is as a measure of the clinical relevance of a laboratory paradigm. Low correlations (e.g. κ=0.244) and near chance level rAUC values (e.g. 0.598), attributable to differences between the clinical and laboratory paradigms, were observed. The absolute width of the confidence interval was 0.38 for the interparadigm differences of the conventional measures and 0.14 for the difference of the rAUCs. The rAUC measure was consistent with the traditional measures but was more sensitive to the differences in clinical relevance. A new relevance ROC method for quantifying the clinical relevance of a laboratory paradigm is proposed.

  14. A review of clinically relevant human anatomy in emergency medicine.

    Science.gov (United States)

    Campanella, Lisa Marie; Bloch, Helen; Gang, Maureen; Rennie, William; Ort, Victoria

    2005-10-01

    The objectives of this project were to establish a practical model for the review of clinical anatomy relevant to the assessment and care of the ill and injured patient, and to design practice models for invasive procedures using human cadaver, porcine cadaver, and plastic model material. A practical course based on the human gross anatomy of the face, neck, thorax, airway, arm, and leg was designed. Regional anesthesia techniques, arthrocentesis, saphenous vein cutdown, central venous and arterial cannulation, surgical airway, thoracostomy tube placement and thoracotomy were integrated into the appropriate practice stations. A syllabus was developed. A clinically relevant, online anatomy atlas demonstrating all of the above was developed. In conclusion, an anatomy review course combining clinically relevant, human, gross anatomy and procedure practice stations was established.

  15. Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy

    Science.gov (United States)

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...

  16. Proprioceptive deficits after ACL injury : are they clinically relevant?

    NARCIS (Netherlands)

    Gokeler, Alli; Benjaminse, Anne; Hewett, Timothy E.; Lephart, Scott M.; Engebretsen, Lars; Ageberg, Eva; Engelhardt, Martin; Arnold, Markus P.; Postema, Klaas; Otten, Egbert; Dijkstra, Pieter U.

    Objective To establish the clinical relevance of proprioceptive deficits reported after anterior cruciate ligament (ACL) injury. Material and methods A literature search was done in electronic databases from January 1990 to June 2009. Inclusion criteria for studies were ACL deficient (ACL-D) and ACL

  17. Meaning in life : Clinical relevance and predictive power

    NARCIS (Netherlands)

    Debats, DL

    1996-01-01

    The clinical relevance of the meaning in life construct is examined by evaluating its ability to predict patients' general and psychological well-being and their posttreatment functioning. Evidence is obtained for the notion that meaning in Life (a) would affect both positive and negative aspects of

  18. 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…

  19. 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...... patients (3.1%) in whom a WL cystoscopy revealed no tumor. In total, NBI changed the clinical decision relevantly in 1.9% of the patients. In hematuria patients, the calculated sensitivities of both NBI and WL were identically high, whereas sensitivity in patients with known NMIBC was significantly higher...

  20. [Microscopic colitis--new insights relevant to clinical practice].

    Science.gov (United States)

    Miehlke, S; Aust, D; Madisch, A

    2013-12-01

    Microscopic colitis is an increasingly recognised chronic inflammatory bowel disease associated with watery, non-bloody diarrhoea. In addition, many patients suffer from abdominal pain, nocturnal diarrhoea, urgency and incontinence. The two traditional histological subtypes are collagenous colitis and lymphocytic colitis. A novel third subgroup is the so-called incomplete microscopic colitis which is clinically indistinguishable. At present, budesonide is the only evidenced-based effective therapy, however many problems in the long-term treatment strategy are still unsolved. The present paper reviews new developments in microscopic colitis which are relevant for clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Self-Esteem and Dimensions of Clinically Relevant Behavior Among Ten Year Olds.

    Science.gov (United States)

    Starr, Philip; Pearman, William A.

    Although self-concept has been linked with many behavioral variables, most studies do not deal with dependent variables which would provide an understanding of such clinically relevant behaviors as sociability, aggression, activity level, somatization, inhibition, and sleep disturbance. The relationship between self-esteem and clinically relevant…

  2. Current Views on the Clinical Relevance of Blastocystis spp.

    Science.gov (United States)

    Tan, Kevin S W; Mirza, Haris; Teo, Joshua D W; Wu, Binhui; Macary, Paul A

    2010-01-01

    Blastocystis is an enteric protistan parasite of uncertain clinical relevance. Recent studies indicate that the parasite is a species complex and humans are potentially hosts to nine Blastocystis subtypes, most of which are zoonotic. Subtype 3 is the most common in prevalence studies, followed by subtype 1. Laboratory diagnosis is challenging; the currently recommended diagnostic approach is trichrome staining of direct smears coupled with stool culture. Polymerase chain reaction testing from stools or culture is useful for determining Blastocystis subtype information. The controversial pathogenesis of Blastocystis is attributed to subtype variations in virulence; although current studies seem to support this idea, evidence suggests other factors also contribute to the clinical outcome of the infection. Clinical signs and symptoms of blastocystosis include abdominal pain, diarrhea, bloating, and flatulence. Extraintestinal manifestations, predominantly cutaneous, also were reported. In vitro and animal studies shed new light on the pathobiology of Blastocystis.

  3. 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.

  4. Selected Food/Herb-Drug Interactions: Mechanisms and Clinical Relevance.

    Science.gov (United States)

    Amadi, Cecilia N; Mgbahurike, Amaka A

    2017-11-22

    Food/Herb-drug interactions have become a major problem in health care. These interactions can lead to loss of therapeutic efficacy or toxic effects of drugs. To probe the clinical relevance of such interactions, the impact of food/herb intake on the clinical effects of drug administration has to be evaluated. Failure to identify and efficiently manage food-drug interactions can lead to serious consequences. A comprehensive knowledge of the mechanisms that underpin variability in disposition will help optimize therapy. Electronic search of literatures from relevant databases were conducted. A total of 58 original scientific reports/review articles were obtained with the search strategy; of which 25 were found eligible to be included in the present review. Required data were extracted from these studies, and their methodologies were assessed. This review updates our knowledge on clinical food-drug interactions with emphasis on mechanism and clinical implications. Results obtained from literature search identified interactions with selected foods/herbs generated from in vivo and in vitro studies. For example, interaction studies in humans revealed a reduction in the bioavailability of mercaptopurine when taken concurrently with substances containing xanthine oxidase (eg, cow milk); a reduction in the bioavailability of quinine with Garcinia kola; increased bioavailability/toxicity of felodipine, nifedipine, saquinavir, sildenafil with grape juice; increased bioavailability of felodipine, cisapride with red wine and diminished bioavailability of fexofenadine with apple. Pharmacokinetic and/or pharmacodynamic mechanisms are implicated in many of these interactions. By evaluating the dietary patterns of patients and use of prescribed medications, health professionals will be well informed of potential interactions and associated adverse effects.

  5. 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.

  6. Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Ingelin Clausen

    2014-09-01

    Full Text Available 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.

  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. Risks and clinical relevance of medication discrepancies at outpatient departments for mood and anxiety disorders

    NARCIS (Netherlands)

    Simoons, Mirjam; Mulder, Hans; Risselada, Arne J.; Wilmink, Frederik W.; Schoevers, Robert A.; Ruhé, Henricus G.; Van Roon, Eric N.

    2017-01-01

    OBJECTIVE: To identify discrepancies between actual drug use by outpatients with mood and anxiety disorders and medication overviews from health care providers as well as to investigate the clinical relevance of those discrepancies. DESIGN: Cross-sectional cohort study. METHODS: We included adults

  9. Clinical relevance of sonographically estimated amniotic fluid volume: polyhydramnios.

    Science.gov (United States)

    Sandlin, Adam T; Chauhan, Suneet P; Magann, Everett F

    2013-05-01

    Polyhydramnios is an excessive amount of amniotic fluid within the amniotic cavity. The etiology of polyhydramnios may be idiopathic, the consequence of fetal structural anomalies, or the consequence of various fetal and maternal conditions. The clinical importance of polyhydramnios is found in its association with adverse pregnancy outcomes and the risk of perinatal mortality. The antenatal management of polyhydramnios can be challenging as there are no formalized guidelines on the topic. The purpose of this review is to provide a literature-based overview on the subject of polyhydramnios in singleton pregnancies, demonstrate its clinical implications, and describe a practical approach to its management.

  10. New Clinically Relevant Findings about Violence by People with Schizophrenia.

    Science.gov (United States)

    Hodgins, Sheilagh; Klein, Sanja

    2017-02-01

    To review findings with clinical relevance that add to knowledge about antisocial and aggressive behaviour among persons with schizophrenia. Nonsystematic literature review. Recent evidence shows that individuals who develop schizophrenia present cognitive deficits, psychotic-like experiences, and internalizing and externalizing problems from childhood onwards. Many of their relatives present not only schizophrenia-related disorders but also antisocial behaviour. While the increased risk of aggressive behaviour among persons with schizophrenia has been robustly established, recent findings show that by first contact with clinical services for psychosis, most people with schizophrenia who will engage in aggressive behaviour may be identified. At first episode, 2 distinct types are distinguishable: those who present a history of antisocial and aggressive behaviour since childhood and those who began engaging in aggressive behaviour as illness onsets. Antipsychotic medications and other treatments shown to be effective for schizophrenia are needed by both types of patients. Additionally, those with a history of antisocial and aggressive behaviour since childhood require cognitive-behavioural programs aimed at reducing these behaviours and promoting prosocial behaviour. Reducing physical victimisation and cannabis use will likely reduce aggressive behaviour. Evidence suggests that threats to hurt others often precede assaults. At first contact with services, patients with schizophrenia who have engaged in aggressive behaviour should be identified and treated for schizophrenia and for aggression. Research is needed to identify interactions between genotypes and environmental factors, from conception onwards, that promote and that protect against the development of aggressive behaviour among persons with schizophrenia.

  11. 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.

  12. Holding health providers in developing countries accountable to consumers: a synthesis of relevant scholarship.

    Science.gov (United States)

    Berlan, David; Shiffman, Jeremy

    2012-07-01

    Health care providers in low-income countries often treat consumers poorly. Many providers do not consider it their responsibility to listen carefully to consumer preferences, to facilitate access to care, to offer detailed information, or to treat patients with respect. A lack of provider accountability to health consumers may have adverse effects on the quality of health care they provide, and ultimately on health outcomes. This paper synthesizes relevant research on health provision in low-, middle- and high-income countries with the aim of identifying factors that shape health provider accountability to consumers, and discerning promising interventions to enhance responsiveness. Drawing on this scholarship, we develop a framework that classifies factors into two categories: those concerning the health system and those that pertain to social influences. Among the health systems factors that may shape provider accountability are oversight mechanisms, revenue sources, and the nature of competition in the health sector-all influences that may lead providers to be accountable to entities other than consumers, such as governments and donors. Among the social factors we explore are consumer power, especially information levels, and provider beliefs surrounding accountability. Evidence on factors and interventions shaping health provider accountability is thin. For this reason, it is not possible to draw firm conclusions on what works to enhance accountability. This being said, research does suggest four mechanisms that may improve provider responsiveness: 1. Creating official community participation mechanisms in the context of health service decentralization; 2. Enhancing the quality of health information that consumers receive; 3. Establishing community groups that empower consumers to take action; 4. Including non-governmental organizations in efforts to expand access to care. This synthesis reviews evidence on these and other interventions, and points to future

  13. The doctrine of providence in the Institutes of Calvin – still relevant?

    Directory of Open Access Journals (Sweden)

    C.F.C. Coetzee

    2010-07-01

    Full Text Available In the reformed tradition and theology, the doctrine of provi- dence has always been important and relevant, so much so that it forms an integral part of the reformed confessions. At the same time some of the most difficult theological questions are raised regarding this doctrine, questions like the following: Is God in control of everything? What is the relationship between the providence of God and sin, suffering, man’s responsibility, et cetera? In our times the doctrine as such is questioned or even rejected. What makes this topic even more important is the commemoration of the publication of Darwin’s book, “The origin of species”, coupled with the renewed emphasis on Darwinism, evolutionism and atheism.1 From the perspective of the Calvinistic-reformed theology and in the light of the com- memoration of Calvin’s birth 500 years ago, it is important to determine the relevance of Calvin’s thoughts on a number of important issues in the current debate, e.g. the doctrine on God, providence and creation, sin, suffering, et cetera. It is also determined that Calvin’s thoughts are reflected in the reformed confessions, which is still the living faith of reformed churches all over the world.

  14. 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.

  15. The clinical relevance of orthostatic hypotension in elderly patients.

    Science.gov (United States)

    Hartog, Laura; Kleefstra, Nanne; Luigies, Rene; de Rooij, Sophia; Bilo, Henk; van Hateren, Kornelis

    2017-02-22

    Orthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints. We aimed to explore the relation between different definitions of OH, including relative decrease of blood pressure, and orthostatic complaints and falling. A cross-sectional study was performed with 1415 participants aged ≥65 years visiting a mobile fall-prevention team. The CAREFALL Triage Instrument and data on blood pressure, orthostatic complaints and previous fall incidents were collected. Multivariate binary logistic regression analyses were performed to assess the association of different definitions of OH and orthostatic complaints or falling. Ten different definitions of OH based on different relative declines of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were defined. The 2011 consensus definition of OH was not related to orthostatic complaints (Odds Ratio (OR) 1.07 (95 % Confidence Interval (CI) 0.68-1.69)) or previous fall incidents (OR 1.08 (95%CI 0.83-1.41)). A ≥ 25 % SBP decrease was significantly related to orthostatic complaints (OR 2.81 (95%CI 1.31-6.05)) and a ≥ 25 % DBP decrease was related to previous fall incidents (OR 2.56 (95%CI 1.08-6.09)). With the exception of a decrease of ≥25 % SBP or DBP, the clinical relevance of incidental OH blood pressure measurements seems very limited with respect to orthostatic complaints or fall incidents in elderly patients. Using relative decreases may be more appropriate in clinical practice. Geriatr Gerontol Int 2016; ••: ••-••. © 2017 Japan Geriatrics Society.

  16. [Clinical relevance of tooth brushing in relation to dental caries].

    Science.gov (United States)

    Pita-Fernández, Salvador; Pombo-Sánchez, Antonio; Suárez-Quintanilla, Juan; Novio-Mallón, Silvia; Rivas-Mundiña, Berta; Pértega-Díaz, Sonia

    2010-07-01

    To determine the impact and clinical relevance of tooth brushing on oral health. Prevalence study. Fontiñas Health Centre. (Santiago de Compostela, Spain). Prevalence study (n=281 children aged 5-14 years. Odontological examination according to WHO methodology, to determine the frequency of tooth brushing, frequency of sweet consumption and their impact on the prevalence of caries. Logistic regression and estimation of the relative prevalence difference (RPD) and the Number Needed to Treat in order to prevent one additional bad outcome (NNT). The children who never brush their teeth have a 40% (95% CI: 24.3%-57.8%) of early caries, while those who brush their teeth several times a day have 15.3% (95% CI: 9.4%-23.7%). An association between not brushing the teeth and caries in primary teeth (OR=2.3; 95% CI:1.05-5.3) was observed after adjusting for age, sweet consumption and visits to the dentist. The same occurred with final teeth (OR=3.9; 95% CI:1.4-10.3). The RPD was 62%(95% CI: 30%-79%), meaning that prevalence of caries is 62% lower in children who brush their teeth several times a day as compared to those who never brush their teeth. The NNT is 4 (95% CI: 2.4-14), so for every 4 children who brush their teeth several times a day, there is one less case of caries, compared to those who never brush their teeth. There is a dose-response relationship between prevalence of caries and brushing frequency. The same effect was observed with definitive caries: RPD=55% (95% CI:16%-76%), NNT=5 (95% CI:2.8-53.3). Tooth brushing is related to oral health, with a major clinical impact. The positive effect of tooth brushing was superior to that of a correct diet. 2009 Elsevier España, S.L. All rights reserved.

  17. Predicting clinical relevance of grapefruit-drug interactions: a complicated process.

    Science.gov (United States)

    Bailey, D G

    2017-04-01

    Grapefruit juice interacts with a number of drugs. This commentary provides feedback on a previously proposed approach for predicting clinically relevant interactions with grapefruit juice based on the average inherent oral bioavailability (F) and magnitude of increase in bioavailability with other CYP3A inhibitors of the drug. Additional factors such as variability of the magnitude of the pharmacokinetic interaction among individuals, product monograph cautionary statements and vulnerability of the patient population should be considered. A flow diagram is provided that should improve prediction of the pharmacokinetic interaction and clinical relevance for affected drugs and that recommends different courses of action for patient management. Forecasting the clinical importance of a particular drug interaction with grapefruit can be improved through consideration of additional readily available drug regulatory information. © 2016 John Wiley & Sons Ltd.

  18. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    Directory of Open Access Journals (Sweden)

    Lilla Mihályi

    2012-01-01

    Full Text Available The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus, diamino diphenyl sulfone (dapsone therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

  19. 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.

  20. Epileptic neuronal networks: methods of identification and clinical relevance.

    Science.gov (United States)

    Stefan, Hermann; Lopes da Silva, Fernando H

    2013-01-01

    The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and "generalized" epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called "generalized epilepsies," such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed.

  1. Can in vitro assessment provide relevant end points for cognitive drug programs?

    Science.gov (United States)

    Albensi, Benedict C

    2008-12-01

    Several start-up biotechnology companies have been created with the primary intent of developing cognitive enhancers. In addition, established pharmaceutical companies also frequently focus their efforts on cognitive drug discovery. In many instances, the rationale and evidence for these endeavors are based largely on in vitro assessments. In particular, the experimental paradigm, know as long-term potentiation (LTP), a cellular model of synaptic plasticity and memory encoding, is being increasing used preclinically for assessing potential nootropic drugs in vitro. Central to this thinking is the idea that the modulation of LTP and/or glutamate receptors are the key criteria that must be met for the development of cognitive enhancers. However, programs targeting the NMDA receptor, a glutamate receptor subtype, over the years have been less than fruitful. In addition, skeptics criticize the relevance of some in vitro tests such as LTP for simulating human cognitive function. Given these considerations, one may wonder if in vitro assessments in general, and the LTP paradigm in particular, provide relevant end points for cognitive drug discovery and development programs. The focus of this article is to address this question and to present evidence as to why in vitro assessment is still critical to the success of any cognitive drug program.

  2. Attitudes and Perceptions of Healthcare Providers towards Clinical ...

    African Journals Online (AJOL)

    In addition clinical pharmacist are to monitor patient adherence to therapy, provide drug information, monitor patient responses and laboratory values, and provide patient and provider education. Other responsibilities carried out by clinical pharmacists may include but are not limited to: prevention of medication errors, ...

  3. Effectiveness of a Clinically Relevant Educational Program for Improving Medical Communication and Clinical Skills of International Medical Graduates

    Directory of Open Access Journals (Sweden)

    David Watt

    2010-07-01

    Conclusions:  IMGs who participated in a clinically relevant educational program improved their English language proficiency, clinical skills and professionalism for medical practice in a host country.

  4. 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

    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......, 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......) to 87-89% (grass, mites) of the positive SPT reactions (wheal size3mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive...

  5. 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.

  6. 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.

  7. What is the clinical relevance of different lung compartments?

    Science.gov (United States)

    2009-01-01

    The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense. All these compartments are connected but the functional network is not yet fully understood. A better knowledge of the complex interactions could improve diagnosis and therapy, or enable preventive approaches of local immunization. PMID

  8. What is the clinical relevance of different lung compartments?

    Directory of Open Access Journals (Sweden)

    Pabst Reinhard

    2009-08-01

    Full Text Available Abstract The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 – the bronchoalveolar lavage (BAL, which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 – bronchus-associated lymphoid tissue (BALT: In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 – conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL. This again is also accessible via bronchoscopy. Compartment 4 – draining lymph nodes/Compartment 5 – lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments – lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 – the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 – periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense. All these compartments are connected but the functional network is not yet fully understood. A better knowledge of the complex interactions could improve diagnosis and therapy, or enable preventive approaches

  9. 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.

  10. Transcultural psychiatry made simple--asynchronous telepsychiatry as an approach to providing culturally relevant care.

    Science.gov (United States)

    Yellowlees, Peter M; Odor, Alberto; Iosif, Ana-Maria; Parish, Michelle Burke; Nafiz, Najia; Patrice, Kesha; Xiong, Glen; McCaron, Robert; Sanchez, Richard; Ochoa, Enrique; Hilty, Donald

    2013-04-01

    To examine the feasibility and diagnostic reliability of asynchronous telepsychiatry (ATP) consultations in Spanish and ATP consultation with Spanish-to-English translation. Twenty-four interviews of Spanish-speaking patients were videorecorded by a bilingual clinician who also collected patient history data and gave the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to each patient. The ATP data (video of the interview and patient history) were forwarded for psychiatric consultation and a diagnostic assessment by the investigators. The ATP data were then examined separately by two Spanish-speaking psychiatrists, before being translated into English and then re-examined by two English-speaking psychiatrists. Agreement between the expert diagnoses of the investigators and the diagnoses from the Spanish consultations, the Spanish-to-English translated consultations, and the SCID-I results was assessed using kappa statistics. We found acceptable levels of agreement for major diagnostic groupings among the Spanish- and English-speaking psychiatrists. Kappa values for diagnostic agreement between the expert and the translated consultations, the original language consultations, and the SCID-I were at least 0.52 (percentage agreement, 79%) and higher. ATP consultations in Spanish, and those translated from Spanish to English, are feasible, and broad diagnostic reliability was achieved. The ATP process allows for rapid language translation. This approach could be useful across national boundaries and in numerous ethnic groups. Cross-language ATP may also offer significant benefits over the use of real-time interpreting services and has the potential to improve the quality of care by allowing for the addition of culturally relevant information.

  11. 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

  12. Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation.

    Science.gov (United States)

    Ravichandran, Akhilandeshwari; Liu, Yuchun; Teoh, Swee-Hin

    2017-04-03

    In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non-invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non-invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the 'push' of bioreactor systems into the commercial market as well as 'pull' factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

    Science.gov (United States)

    Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

    2011-12-01

    Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. 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.

  15. [Clinical studies in oncology. Relevance, design, ethical considerations].

    Science.gov (United States)

    Wörmann, B; Wulf, G; Hiddemann, W

    1998-03-15

    Clinical research in oncology includes the evaluation of diagnostic, prognostic and therapeutic parameters in order to establish standards for the different tumor entities. Prerequisite is the retrospective and prospective analysis of large patient groups with established statistical methods. New potentially better strategies have to be compared in randomised studies with the respective "gold standard". The central role of clinical studies for evaluation and optimisation of therapy can be considered as moral obligation to included the maximal possible number of patients in clinical studies. However, only a small number of tumor patients in Germany is treated in controlled clinical studies. Reasons are lack of organisational structures, but also ethical considerations. In this article several models for clinical studies are discussed with respect to their statistical significance, indication, and potential ethical objections. Aim of the discussion is to increase the acceptance of the necessity of clinical studies for evaluation and optimisation of therapeutic options in oncology.

  16. Potential of polarization lidar to provide profiles of CCN- and INP-relevant aerosol parameters

    Directory of Open Access Journals (Sweden)

    R.-E. Mamouri

    2016-05-01

    Full Text Available We investigate the potential of polarization lidar to provide vertical profiles of aerosol parameters from which cloud condensation nucleus (CCN and ice nucleating particle (INP number concentrations can be estimated. We show that height profiles of particle number concentrations n50, dry considering dry aerosol particles with radius  > 50 nm (reservoir of CCN in the case of marine and continental non-desert aerosols, n100, dry (particles with dry radius  >  100 nm, reservoir of desert dust CCN, and of n250, dry (particles with dry radius  >  250 nm, reservoir of favorable INP, as well as profiles of the particle surface area concentration sdry (used in INP parameterizations can be retrieved from lidar-derived aerosol extinction coefficients σ with relative uncertainties of a factor of 1.5–2 in the case of n50, dry and n100, dry and of about 25–50 % in the case of n250, dry and sdry. Of key importance is the potential of polarization lidar to distinguish and separate the optical properties of desert aerosols from non-desert aerosol such as continental and marine particles. We investigate the relationship between σ, measured at ambient atmospheric conditions, and n50, dry for marine and continental aerosols, n100, dry for desert dust particles, and n250, dry and sdry for three aerosol types (desert, non-desert continental, marine and for the main lidar wavelengths of 355, 532, and 1064 nm. Our study is based on multiyear Aerosol Robotic Network (AERONET photometer observations of aerosol optical thickness and column-integrated particle size distribution at Leipzig, Germany, and Limassol, Cyprus, which cover all realistic aerosol mixtures. We further include AERONET data from field campaigns in Morocco, Cabo Verde, and Barbados, which provide pure dust and pure marine aerosol scenarios. By means of a simple CCN parameterization (with n50, dry or n100, dry as input and available INP

  17. 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 ...

  18. Evidence-Based Clinical Significance in Health Care: Toward an Inferential Analysis of Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Mahsa Dousti

    2011-09-01

    Full Text Available Evidence-based dental practice requires the developmment and evaluation of protocols that en-sure translational effectiveness: that is, the efficient incorporation of the best available efficacy and effec-tiveness findings in specific clinical dentistry settings and environments. Evidence-based dentistry predi-cates the synthesis of research for obtaining the best available evidence in a validated, stringent, systematic and unbiased fashion. Research synthesis is now established as a science in its own right, precisely because it adheres to the scientific process that is driven by a research question and a hypothesis, follows through clearly defined methodology and design, yielding quantifiable data that are analyzed statistically, and from which stringent statistical inferences are drawn. The conclusions from the protocol of research synthesis define the best available evidence, which is used in the process of evidence-based revision of clinical practice guidelines. One important hurdle of the process of applying research synthesis in evidence-based dentistry lies in the fact that the statistical inferences produced by research must be translated into clinical relevance. Here, we present a model to circumvent this limitation by means of text analysis/mining protocols, which could lead the path toward a novel, valid and reliable ap-proach for the inferential analysis of clinical relevance.

  19. Perceived barriers, resources, and training needs of rural primary care providers relevant to the management of childhood obesity.

    Science.gov (United States)

    Findholt, Nancy E; Davis, Melinda M; Michael, Yvonne L

    2013-08-01

    To explore the perceived barriers, resources, and training needs of rural primary care providers in relation to implementing the American Medical Association Expert Committee recommendations for assessment, treatment, and prevention of childhood obesity. In-depth interviews were conducted with 13 rural primary care providers in Oregon. Transcribed interviews were thematically coded. Barriers to addressing childhood obesity fell into 5 categories: barriers related to the practice (time constraints, lack of reimbursement, few opportunities to detect obesity), the clinician (limited knowledge), the family/patient (family lifestyle and lack of parent motivation to change, low family income and lack of health insurance, sensitivity of the issue), the community (lack of pediatric subspecialists and multidisciplinary/tertiary care services, few community resources), and the broader sociocultural environment (sociocultural influences, high prevalence of childhood obesity). There were very few clinic and community resources to assist clinicians in addressing weight issues. Clinicians had received little previous training relevant to childhood obesity, and they expressed an interest in several topics. Rural primary care providers face extensive barriers in relation to implementing recommended practices for assessment, treatment, and prevention of childhood obesity. Particularly problematic is the lack of local and regional resources. Employing nurses to provide case management and behavior counseling, group visits, and telehealth and other technological communications are strategies that could improve the management of childhood obesity in rural primary care settings. © 2013 National Rural Health Association.

  20. Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands.

    NARCIS (Netherlands)

    Ingen, J. van; Bendien, S.A.; Lange, W.C.M. de; Hoefsloot, W.; Dekhuijzen, P.N.R.; Boeree, M.J.; Soolingen, D. van

    2009-01-01

    BACKGROUND: The frequency of clinical isolation of non-tuberculous mycobacteria (NTM) in the Netherlands is increasing, but its clinical relevance is often uncertain. OBJECTIVE: To assess the frequency and clinical relevance of isolation of NTM in four associated hospitals in a single region in the

  1. Challenges in providing services in methadone maintenance therapy clinics in China: service providers' perceptions.

    Science.gov (United States)

    Lin, Chunqing; Wu, Zunyou; Rou, Keming; Pang, Lin; Cao, Xiaobin; Shoptaw, Steven; Detels, Roger

    2010-05-01

    The Methadone Maintenance Therapy (MMT) program has been initiated in China since 2004. As of the end of November, 2008, 558 MMT clinics had been established countrywide. The objective of this study was to elucidate the difficulties and challenges as perceived by service providers working in MMT clinics. One service provider from each of the 28 MMT study clinics in Zhejiang and Jiangxi Provinces of China participated in a face-to-face in-depth interview for about 1-2h to describe their perceptions of working in MMT clinics. Qualitative data were analysed using ATLAS.ti. The grounded theory was used to guide the data analysis. Participants identified major problems in providing services in MMT clinics including lack of resources, professional training, and institutional support. Difficulties in pursuit of career, concern for personal safety, low income, heavy working load, and poor opinion of MMT by Chinese society often contributed to greater stress and burnout among the service providers. The MMT programs in China desperately need additional resource allocation and institutional support for the current and perhaps future expansion of the programs. The service providers are in urgent need of professional training to improve the quality of care they can offer MMT clients. Copyright 2009 Elsevier B.V. All rights reserved.

  2. 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.

  3. Providing Decision-Relevant Information for a State Climate Change Action Plan

    Science.gov (United States)

    Wake, C.; Frades, M.; Hurtt, G. C.; Magnusson, M.; Gittell, R.; Skoglund, C.; Morin, J.

    2008-12-01

    Carbon Solutions New England (CSNE), a public-private partnership formed to promote collective action to achieve a low carbon society, has been working with the Governor appointed New Hampshire Climate Change Policy Task Force (NHCCTF) to support the development of a state Climate Change Action Plan. CSNE's role has been to quantify the potential carbon emissions reduction, implementation costs, and cost savings at three distinct time periods (2012, 2025, 2050) for a range of strategies identified by the Task Force. These strategies were developed for several sectors (transportation and land use, electricity generation and use, building energy use, and agriculture, forestry, and waste).New Hampshire's existing and projected economic and population growth are well above the regional average, creating additional challenges for the state to meet regional emission reduction targets. However, by pursuing an ambitious suite of renewable energy and energy efficiency strategies, New Hampshire may be able to continue growing while reducing emissions at a rate close to 3% per year up to 2025. This suite includes efficiency improvements in new and existing buildings, a renewable portfolio standard for electricity generation, avoiding forested land conversion, fuel economy gains in new vehicles, and a reduction in vehicle miles traveled. Most (over 80%) of these emission reduction strategies are projected to provide net economic savings in 2025.A collaborative and iterative process was developed among the key partners in the project. The foundation for the project's success included: a diverse analysis team with leadership that was committed to the project, an open source analysis approach, weekly meetings and frequent communication among the partners, interim reporting of analysis, and an established and trusting relationship among the partners, in part due to collaboration on previous projects.To develop decision-relevant information for the Task Force, CSNE addressed

  4. 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.

  5. Attitudes and Perceptions of Healthcare Providers towards Clinical ...

    African Journals Online (AJOL)

    Purpose: To evaluate the attitudes and perceptions of health care providers towards clinical pharmacy services at King Khalid University Hospital Riyadh Saudi Arabia Method: A cross-sectional survey of healthcare providers was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from September to ...

  6. Patient satisfaction with health care services provided at HIV clinics ...

    African Journals Online (AJOL)

    Background: Since the establishment of free HIV/AIDS care and treatment services in Tanzania a lot of research has been done to assess how health care providers discharge their duties in these clinics. Little research however has been done regarding satisfaction of HIV patients with free health care services provided.

  7. 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

  8. Pharmacogenetics in Cardiovascular Disease is there clinical relevance?

    NARCIS (Netherlands)

    Maitland-Van Der Zee, A.

    2014-01-01

    • Objectives: To give an up-to-date overview of the research in pharmacogenetics of cardiovascular disease, and the clinical implications of this research. • Methods: In this lecture I will focus on these groups cardiovascular drugs where many pharmacogenetics studies have been performed (including

  9. The placebo response: neurobiological and clinical issues of neurological relevance.

    Science.gov (United States)

    Pollo, Antonella; Benedetti, Fabrizio

    2009-01-01

    The recent upsurge in placebo research has demonstrated the sound neurobiological substrate of a phenomenon once believed to be only patient mystification, or at best a variable to control in clinical trials, bringing about a new awareness of its potential exploitation to the patient's benefit and framing it as a positive context effect, with the power to influence the therapy outcome. Placebo effects have been described both in the experimental setting and in different clinical conditions, many of which are of neurological interest. Multiple mechanisms have been described, namely conditioning and cognitive factors like expectation, desire, and reward. A body of evidence from neurochemical, pharmacological, and neuroimaging studies points to the involvement of neural pathways specific to single conditions, such as the activation of the endogenous antinociceptive system during placebo analgesia or the release of dopamine in the striatum of parkinsonian patients experiencing placebo reduction of motor impairment. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient, in order to maximize the placebo component present in any treatment.

  10. Otolaryngology Needs in a Free Clinic Providing Indigent Care.

    Science.gov (United States)

    Hu, Amanda; Sibert, Thomas; Zhao, Wei; Zarro, Vincent

    2016-06-01

    To determine the otolaryngology needs in a free clinic providing care to medically indigent patients, as perceived by the patients and health care providers. Cross-sectional survey. A survey was administered to patients and health care providers of a free clinic from September 2014 through January 2015 in an urban, inner-city location. One hundred and thirty-seven patients (35.8% male, age 50.8 ± 13.0 years) completed the survey. Mean household income was $29,838 ± $10,425; 32.1% spoke English; 54.7% were employed; 10.2% had health insurance; and 37.2% had seen a primary care provider outside of the free clinic. The top three otolaryngology symptoms among patients were sleep apnea/snoring (39.4%), heartburn/reflux (30.7%), and dizziness (29.9%). Eleven health care providers (45% male, age 50.5 ± 15.3 years, 63.6% physician, 36% nurse) completed the survey. Providers perceived the following otolaryngology complaints as the most prevalent, in descending order: cough, nasal congestion, reflux/heartburn, sore throat, and ear infection/otalgia. Providers felt that sleep apnea and hearing loss were the less common otolaryngology complaints, whereas surveyed patients indicated these symptoms with high frequency. The most requested diagnostic tool among patients and providers was chest X-rays. There are unmet otolaryngology needs in a free clinic. Medically indigent patients have significant barriers to accessing health care. Patient and provider perceptions of top otolaryngology complaints differed, but both identified access to chest X-rays as a major unmet need. Knowledge of patient perceptions may help providers elicit the breadth of otolaryngology complaints. 4. Laryngoscope, 126:1321-1326, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Clinical relevance of rehospitalizations for unstable angina and unplanned revascularization following acute myocardial infarction

    NARCIS (Netherlands)

    Shore, Supriya; Smolderen, K.G.E.; Spertus, John A.; Kennedy, Kevin F.; Jones, Philip G.; Zhao, Zhenxiang; Wang, Tracy Y.; Arnold, Suzanne V.

    2016-01-01

    Background Rehospitalizations following acute myocardial infarction for unplanned coronary revascularization and unstable angina (UA) are often included as parts of composite end points in clinical trials. Although clearly costly, the clinical relevance of these individual components has not been

  12. Current strategies and findings in clinically relevant post-translational modification-specific proteomics.

    Science.gov (United States)

    Pagel, Oliver; Loroch, Stefan; Sickmann, Albert; Zahedi, René P

    2015-06-01

    Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

  13. Hepatitis E Virus Mutations: Functional and Clinical Relevance

    OpenAIRE

    Tong, Hoang Van; Hoan, Nghiem Xuan; Wang, Bo; Wedemeyer, Heiner; Bock, C.-Thomas; Thirumalaisamy P. Velavan

    2016-01-01

    Highlights ? HEV causes acute hepatitis and recently comes into focus because of persistent infection in immunocompromised patients. ? HEV variability can be associated with clinical pathogenesis and transmission dynamics. ? Mutations in the HEV genome can influence HEV physiology and virus-host interaction. ? HEV mutations and variability are likely associated with fulminant hepatic failure and chronic hepatitis E. ? The Y1320H and G1634R/K mutations in the RdRp domain contribute to antivira...

  14. Corona mortis: an anatomical variation with clinical relevance. Case report.

    Directory of Open Access Journals (Sweden)

    Guillermo Adrián Rivera-Cardona

    2010-12-01

    Full Text Available The obturator artery is one of the parietal branches arising from the internal iliac artery, the anatomical variation from which this artery originates is called “The corona mortis”, generally from the external iliac artery or the inferior epigastric artery. This finding was observed bilaterally in a male cadaver during a pelvis dissection. Clinical consideration of the anatomical variation in the obturator artery, during surgical procedures, is of great importance due to the risk of pelvic hemorrhage.

  15. Relevance of guideline-based ICD indications to clinical practice

    Directory of Open Access Journals (Sweden)

    Nora Al-Jefairi

    2014-01-01

    Guidelines on ICD indications have been proposed by American and European scientific societies since a number of years, based upon trials and expert opinion. In the context of variable economic and political constraints, it is questionable whether these guidelines may be applied to all settings. This review discusses the guideline-based indications, critically examines their applicability to clinical practice, and discusses alternatives to ICD therapy.

  16. Clinical relevance of small copy-number variants in chromosomal microarray clinical testing.

    Science.gov (United States)

    Hollenbeck, Dana; Williams, Crescenda L; Drazba, Kathryn; Descartes, Maria; Korf, Bruce R; Rutledge, S Lane; Lose, Edward J; Robin, Nathaniel H; Carroll, Andrew J; Mikhail, Fady M

    2017-04-01

    The 2010 consensus statement on diagnostic chromosomal microarray (CMA) testing recommended an array resolution ≥400 kb throughout the genome as a balance of analytical and clinical sensitivity. In spite of the clear evidence for pathogenicity of large copy-number variants (CNVs) in neurodevelopmental disorders and/or congenital anomalies, the significance of small, nonrecurrent CNVs (<500 kb) has not been well established in a clinical setting. We investigated the clinical significance of all nonpolymorphic small, nonrecurrent CNVs (<500 kb) in patients referred for CMA clinical testing over a period of 6 years, from 2009 to 2014 (a total of 4,417 patients). We excluded from our study patients with benign or likely benign CNVs and patients with only recurrent microdeletions/microduplications <500 kb. In total, 383 patients (8.67%) were found to carry at least one small, nonrecurrent CNV, of whom 176 patients (3.98%) had one small CNV classified as a variant of uncertain significance (VUS), 45 (1.02%) had two or more small VUS CNVs, 20 (0.45%) had one small VUS CNV and a recurrent CNV, 113 (2.56%) had one small pathogenic or likely pathogenic CNV, 17 (0.38%) had two or more small pathogenic or likely pathogenic CNVs, and 12 (0.27%) had one small pathogenic or likely pathogenic CNV and a recurrent CNV. Within the pathogenic group, 80 of 142 patients (56% of all small pathogenic CNV cases) were found to have a single whole-gene or exonic deletion. The themes that emerged from our study are presented in the Discussion section. Our study demonstrates the diagnostic clinical relevance of small, nonrecurrent CNVs <500 kb during CMA clinical testing and underscores the need for careful clinical interpretation of these CNVs.Genet Med 19 4, 377-385.

  17. 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.

  18. 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......-fasting TGs as a risk factor for CVD and provide a suggested classification of non-fasting TG concentration. Secondly, we sought to describe methodologies to evaluate postprandial TG using a fat tolerance test (FTT) in the clinic. Thirdly, we discuss the role of non-fasting lipids in the treatment...... of postprandial hyperlipemia. Finally, we provide a series of clinical recommendations relating to non-fasting TGs based on the consensus of the Expert Panel: 1). Elevated non-fasting TGs are a risk factor for CVD. 2). The desirable non-fasting TG concentration is...

  19. Cashew Nut Allergy: Clinical Relevance and Allergen Characterisation.

    Science.gov (United States)

    Mendes, Cíntia; Costa, Joana; Vicente, António A; Oliveira, Maria Beatriz P P; Mafra, Isabel

    2016-09-01

    Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.

  20. 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.

  1. Clinical nurse specialist leadership in computerized provider order entry design.

    Science.gov (United States)

    Roggow, Darla J; Solie, Carol J; Tracy, Mary Fran; Gjere, Niki

    2005-01-01

    The purpose of this clinical project was to design and implement a computerized provider order entry system. Well-designed clinical computer systems can advance best practice and quality decision making, leading to improvements in patient and organizational outcomes. An Orders Design Group composed of clinical nurse specialists (CNSs), staff nurses, and information management personnel was formed. CNSs used competencies in the system sphere to lead the integration of the needs of patients, nurses, and organizations into new technologies. CNSs facilitated implementation of a collaboratively designed interdisciplinary computerized order entry process. Evaluation of the design and implementation process demonstrated greater success with the order entry system under the leadership of CNSs than past initiatives where CNSs were not in leadership roles. CNS competencies in designing and implementing innovative system-level solutions are key to clinical information systems design.

  2. Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance

    Science.gov (United States)

    Balucan, Francis S.; Morshed, Syed A.; Davies, Terry F.

    2013-01-01

    Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum. PMID:23691429

  3. Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance

    Science.gov (United States)

    Graeff-Teixeira, Carlos; da Silva, Ana Cristina Arámburu; Yoshimura, Kentaro

    2009-01-01

    Summary: Eosinophilic meningoencephalitis is caused by a variety of helminthic infections. These worm-specific infections are named after the causative worm genera, the most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Worm parasites enter an organism through ingestion of contaminated water or an intermediate host and can eventually affect the central nervous system (CNS). These infections are potentially serious events leading to sequelae or death, and diagnosis depends on currently limited molecular methods. Identification of parasites in fluids and tissues is rarely possible, while images and clinical examinations do not lead to a definitive diagnosis. Treatment usually requires the concomitant administration of corticoids and anthelminthic drugs, yet new compounds and their extensive and detailed clinical evaluation are much needed. Eosinophilia in fluids may be detected in other infectious and noninfectious conditions, such as neoplastic disease, drug use, and prosthesis reactions. Thus, distinctive identification of eosinophils in fluids is a necessary component in the etiologic diagnosis of CNS infections. PMID:19366917

  4. Osteoprotegerin and Vascular Calcification: Clinical and Prognostic Relevance.

    Science.gov (United States)

    Makarović, Sandra; Makarović, Zorin; Steiner, Robert; Mihaljević, Ivan; Milas-Ahić, Jasminka

    2015-06-01

    Osteoprotegerin (OPG) is a key regulator in bone metabolism, that also has effect in vascular system. Studies suggest that osteoprotegerin is a critical arterial calcification inhibitor, and is released by endothelial cells as a protective mechanism for their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders. That has been shown in studies in vitro and in animal models. The discovery that OPG deficient mice (OPG -/- mice) develop severe osteoporosis and arterial calcification, has led to conclusion that osteoprotegerin might be mulecule linking vascular and bone system. Paradoxically however, clinical trials have shown recently that OPG serum levels is increased in coronary artery disease and correlates with its severity, ischemic cardial decompensation, and future cardiovascular events. Therefore it is possible that osteoprotegerin could have a new function as a potential biomarker in early identification and monitoring patients with cardiovascular disease. Amongst that osteoprotegerin is in association with well known atherosclerosis risc factors: undoubtedly it is proven its relationship with age, smoking and diabetes mellitus. There is evidence regarding presence of hyperlipoproteinemia and increased serum levels of osteoprotegerin. Also the researches have been directed in genetic level, linking certain single nucleotid genetic polymorphisms of osteoprotegerin and vascular calcification appearance. This review emphasises multifactorial role of OPG, presenting numerous clinical and experimental studies regarding its role in vascular pathology, suggesting a novel biomarker in cardiovascular diseases, showing latest conclusions about this interesting topic that needs to be further explored.

  5. 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.

  6. Myocardial ischaemia in systemic lupus erythematosus: detection and clinical relevance.

    Science.gov (United States)

    Płazak, Wojciech; Gryga, Krzysztof; Sznajd, Jan; Pasowicz, Mieczysław; Musiał, Jacek; Podolec, Piotr

    2011-01-01

    Severe cardiovascular complications are among the most important causes of mortality in systemic lupus erythematosus (SLE) patients. To assess the usefulness of echocardiography, ECG, and coronary artery calcium scoring (CACS) in the detection of myocardial ischaemia in SLE patients compared to single photon emission computerised tomography (SPECT) and to assess their five-year follow-up. In 50 consecutive SLE patients (mean age 39.2 ± 12.9 years, 90% female), clinical assessment, resting and exercise ECG and echocardiography, multidetector computed tomography - based CACS and SPECT studies (Tc-99m sestamibi) were performed. Patients were then followed for five years. SPECT revealed perfusion defects in 25 (50%) patients; persistent defects in 18 (36%) and exercise-induced defects in seven (14%) subjects. No typical ischaemic heart disease clinical symptoms, signs of ischaemia in resting ECG, or left ventricular contractility impairment in echocardiography were observed. Signs of ischaemia in exercise ECG were found in 17 (34%) patients. The CACS ranged from 1 to 843.2 (median 23.15), and coronary calcifications were observed in 12 (24%) patients. Compared to the SPECT study, exercise ECG had 68% sensitivity and 100% specificity in detecting myocardial ischaemia, while CACS had only 28% sensitivity and 58% specificity. During follow-up, one patient who showed myocardial perfusion defects and the highest calcium score (843.2) at baseline, developed CCS II class symptoms of myocardial ischaemia. Coronary angiography was not performed because of severe anaemia; the patient died three months later. In two other patients with perfusion defects and calcium deposits at baseline, CCS I class symptoms were observed; coronary angiography showed only thin calcified coronary plaques that were haemodynamically insignificant. In about half of relatively young, mostly female, SLE patients, SPECT shows myocardial perfusion defects, with coronary calcifications present in one

  7. Hepatitis E Virus Mutations: Functional and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hoang van Tong

    2016-09-01

    Full Text Available Hepatitis E virus (HEV infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance.

  8. 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 and proceed......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...... in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may...

  9. Clinical relevance of the STOPP/START criteria in hip fracture patients.

    Science.gov (United States)

    Lönnbro, Johan; Wallerstedt, Susanna M

    2017-04-01

    The aim of this study was to investigate the clinical relevance of potentially inappropriate medications (PIMs), identified by the STOPP criteria, and potential prescribing omissions (PPOs), identified by the START criteria, and to identify predictors for clinically relevant PIMs and PPOs. The STOPP and START criteria were applied on the medication lists of 200 older hip fracture patients, consecutively recruited to a randomized controlled study in 2009. For each identified PIM and/or PPO, the clinical relevance was assessed at the individual level, using medical records from both hospital and primary care as well as data collected in the original study. A total of 555 PIMs/PPOs were identified in 170 (85%) patients (median age: 85 years, 67% female), 298 (54%) of which, in 141 (71%) patients, were assessed as clinically relevant. A greater proportion of PIMs than PPOs were clinically relevant: 71% (95% CI: 66%; 76%) vs. 32% (27%; 38%). A greater proportion of PPOs than PIMs could not be assessed with available information: 38% (32%; 44%) vs. 22% (17%; 27%). Number of drugs and multidose drug dispensing, but not age, sex, cognition, or nursing home residence, were associated with ≥1 clinically relevant PIMs/PPOs. The present study illustrates that one in two PIMs/PPOs identified by the STOPP/START criteria is clearly clinically relevant, PIMs being clinically relevant to a greater extent than PPOs. Based on available information, the clinical relevance could not be determined in a non-negligible proportion of PIMs/PPOs. Number of drugs and multidose drug dispensing were associated with ≥1 clinically relevant PIMs/PPOs.

  10. The inter-examiner reliability of standardized manual palpation for the identification of clinically relevant myofascial triggerpoints

    DEFF Research Database (Denmark)

    Myburgh, Corrie; Lauridsen, Henrik Hein; Larsen, Anders Holsgaard

    A clinical diagnosis of Myofascial Pain Syndrome (MPS) requires manual palpation for the identification of at least one clinically relevant trigger point (TP). However, few comparable, high quality studies exist regarding the robustness of TP examination. Our aim was to determine the inter....../absence of clinically relevant TP(s) using clinician global assessment (GA). A random case mix of 81 female participants was examined, 14 being asymptomatic and the remainder suffering from neck/shoulder pain. Examiners received psychomotor training and video analysis feedback provided prior to and during the study...

  11. Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes.

    Science.gov (United States)

    King, Paula; Pham, Long K; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca; Forsyth, R Allyn

    2016-01-01

    We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile.

  12. Uterine fibroid vascularization and clinical relevance to uterine fibroid embolization.

    Science.gov (United States)

    Pelage, Jean-Pierre; Cazejust, Julien; Pluot, Etienne; Le Dref, Olivier; Laurent, Alexandre; Spies, James B; Chagnon, Sophie; Lacombe, Pascal

    2005-10-01

    Embolization has become a first-line treatment for symptomatic uterine fibroid tumors. Selective catheterization and embolization of both uterine arteries, which are the predominant source of blood flow to fibroid tumors in most cases, is the cornerstone of treatment. Although embolization for treatment of uterine fibroid tumors is widely accepted, great familiarity with the normal and variant pelvic arterial anatomy is needed to ensure the safety and success of the procedure. The uterine artery classically arises as a first or second branch of the anterior division of the internal iliac artery and is usually dilated in the presence of a uterine fibroid tumor. Angiography is used for comprehensive pretreatment assessment of the pelvic arterial anatomy; for noninvasive evaluation, Doppler ultrasonography, contrast material-enhanced magnetic resonance (MR) imaging, and MR angiography also may be used. After the uterine artery is identified, selective catheterization should be performed distal to its cervicovaginal branch. For targeted embolization of the perifibroid arterial plexus, injection of particles with diameters larger than 500 mum is generally recommended. Excessive embolization may injure normal myometrium, ovaries, or fallopian tubes and lead to uterine necrosis or infection or to ovarian failure. Incomplete treatment or additional blood supply to the tumor (eg, via an ovarian artery) may result in clinical failure. The common postembolization angiographic end point is occlusion of the uterine arterial branches to the fibroid tumor while antegrade flow is maintained in the main uterine artery. Copyright RSNA, 2005.

  13. Metrics and clinical relevance of percutaneous penetration and lateral spreading.

    Science.gov (United States)

    Vieille-Petit, Aline; Blickenstaff, Nicholas; Coman, Garrett; Maibach, Howard

    2015-01-01

    Percutaneous penetration of urea in vivo in man has been documented. If urea can penetrate the skin, it may also move laterally. Lateral spreading of topical substances leads to unpredictable penetration dynamics and increased skin surface area exposure. The ability of urea, a low molecular-weight hydrophilic model, to penetrate the stratum corneum (SC) and spread outside the application site was investigated in vitro using tape stripping with spectroscopy. The parameters investigated were the following: time between urea application and tape stripping, formulations containing urea and use of a petrolatum-covered ring barrier around the marked application area. The percentage of urea was determined in and around the application site. The spreading of topically applied urea to neighboring areas occurred and was time but not formulation dependent. A significant difference between protocols with and without the petrolatum ring was observed. These results suggest the clinical importance of lateral spreading, occurring predominately on the skin surface. SC thickness varies between anatomical sites, predisposing areas such as the face and scalp margins to increased percutaneous penetration of topical products. The use of a protective petrolatum ring can inhibit lateral spreading of hair dye in individuals allergic to hair dye, limit systemic absorption and increase accuracy when assessing penetration dynamics. © 2014 S. Karger AG, Basel.

  14. Review of Post Ischemic Stroke Imaging and Its Clinical Relevance.

    Science.gov (United States)

    Yeo, Leonard L L; Tan, Benjamin Y Q; Andersson, Tommy

    2017-02-14

    In this day and age, multiple imaging modalities are available to the stroke physician in the post-treatment phase.The practical challenge for physicians who treat stroke is to evaluate the pros and cons of each technique and select the best choice for the situation. The choice of imaging modality remains contentious at best and varies among different institutions and centres. This is no simple task an there are many factors to consider, including the differential diagnosis which need to be evaluated, the availability and reliability of the imaging technique and time and expertise required to perform and interpret the scanning. Other ancillary competing interest also come into play such as the financial cost of the modality, the requirement for patient monitoring during the imaging procedure and patient comfort. In an effort to clear some of the ambiguity surrounding this topic we present some of the current techniques in use and others, which are still in the realm of research and have not yet transitioned into clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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.

  16. Reconsolidation of human memory: brain mechanisms and clinical relevance.

    Science.gov (United States)

    Schwabe, Lars; Nader, Karim; Pruessner, Jens C

    2014-08-15

    The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Clinical Relevance of Intraperitoneal Pressure in Peritoneal Dialysis Patients.

    Science.gov (United States)

    Castellanos, Loreley Betancourt; Clemente, Esther Ponz; Cabañas, Conchita Blasco; Parra, Dolors Marquina; Contador, Mabel Bolós; Morera, Juan Carlos Oliva; Daly, Jaume Almirall

    2017-01-01

    Intraperitoneal pressure (IPP) in peritoneal dialysis (PD) increases in sitting and upright positions and is related to some individual characteristics. Adverse effects can appear with IPP > 20 cm H2O. Few studies about peritoneal transport or abdominal wall problems have directly measured IPP. We measured IPP in our prevalent PD patients to identify the clinical factors related to its variability and its possible association with peritoneal transport and abdominal wall complications. We performed a retrospective, observational study of our stable PD patients. Intraperitoneal pressure was measured using the Durand's method in supine, sitting, and upright position. Forty-nine patients were included, 70% males, mean age 61.1 ± 15 years, body mass index (BMI) 27.9 ± 5.2 kg/m(2). The mean of supine IPP was 18.0 ± 4.4 cm H2O. Intraperitoneal pressure in sitting and upright positions were similar and higher than in supine. Supine IPP showed a positive correlation with BMI (p < 0.0005) and comorbidity (p < 0.05). A multivariate linear regression analysis showed that BMI and comorbidity (p < 0.005) had a positive correlation with IPP; time on PD and daily total ultrafiltration (UF) (p < 0.005) showed a negative correlation. Patients with an IPP ≥ 20 cm H2O had more hernias (35% vs 17%) and leakages (21% vs 8%) without statistical significance. Our supine IPPs were higher than others published in adults. Intraperitoneal pressure has an individual value associated with body size. Greater IPP was correlated with lower daily total UF and more hernias and leakages. The measurement of IPP is a simple technique and can help with PD prescription, especially in obese patients. Copyright © 2017 International Society for Peritoneal Dialysis.

  18. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Science.gov (United States)

    Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio

    2017-01-01

    Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal

  19. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ines Bucci

    2017-06-01

    Full Text Available Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH receptor (TSHR antibodies (TRAbs are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs, blocking (TBAbs, or neutral (N-TRAbs depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and

  20. [Ibogaine - structure, influence on human body, clinical relevance].

    Science.gov (United States)

    Zdrojewicz, Zygmunt; Kuszczak, Bartłomiej; Olszak, Natalia

    2016-07-29

    Ibogaine is a natural chemical compound, which belongs to the indole alkaloid family. It can be naturally found within the root bark of african plant Tabernanthe iboga. Ibogaine plays a significant role among tribal cultures. Ibogaine, in small amount, causes reduction of hunger, thirst and exhaustion. In bigger amount, however, it can cause intensive visions. Other effects include reduction or complete disappearance of absitnence symptoms visible in people addicted to the nicotine, alcohol, methamphetamine, cocaine or opioids, what has been scientifically proven after the tests on animals and small groups of people. After oral application, 80% of ibogaine is subjected to the Odemethylation into noribogaine; main catalyzing enzyme is cytochrome CYP2D6. Research suggests, that ibogaine acts in many places within central nervous system. NMDA receptors seem to play main role in its anti-addiction properties. It is important to mention the side effects of the compound, which are cardiotoxicity and neurotoxicity, what makes it harder to use its beneficial properties. Because of this, Ibogaine is included among the dangerous substance. However, there are a few clinics in the world which specializes in the use of the compound in order to interrupt the sypmtoms acute opioid withdrawal syndrome as well as a substance benficial in curing other addictions. There is more hope with synthetic derivatives of ibogaine, which although are less toxic still keep their anti-addiction properties. The aim is to collect the available knowledge related to the structure and effects on human body of alkaloid Tabernanthe iboga and consider the possibility of commercial medical use. © 2016 MEDPRESS.

  1. Upper extremity compartmental anatomy: clinical relevance to radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Toomayan, Glen A.; Robertson, Fabienne; Major, Nancy M. [Duke University Medical Center, Department of Radiology, P.O. Box 3808, Durham, NC (United States); Duke University Medical Center, Division of Orthopaedic Surgery, Department of Surgery, P.O. Box 3808, Durham, NC (United States); Brigman, Brian E. [Duke University Medical Center, Division of Orthopaedic Surgery, Department of Surgery, P.O. Box 3808, Durham, NC (United States)

    2006-04-15

    Malignant tumors of the upper extremity are uncommon, and their care should be referred to specialized facilities with experience treating these lesions. The Musculoskeletal Tumor Society (MSTS) staging system is used by the surgeon to determine appropriate surgical management, assess prognosis, and communicate with other healthcare providers. Magnetic resonance imaging (MRI) is employed pre-operatively to identify a lesion's compartment of origin, determine extent of spread, and plan biopsy and resection approaches. Involvement of neurovascular structures may result in devastating loss of upper extremity function, requiring amputation. Violation of high-resistance compartmental barriers necessitates more extensive surgical resection. Biopsy may be performed by the radiologist using imaging guidance. Knowledge of compartmental anatomy allows the radiologist or surgeon to use an easily excisable biopsy approach and prevent iatrogenic spread to unaffected compartments. Case examples are presented to illustrate the importance of compartmental anatomy in the management of benign and malignant upper extremity tumors. (orig.)

  2. Fear of cancer recurrence: a theoretical review and its relevance for clinical presentation and management.

    Science.gov (United States)

    Simonelli, Laura E; Siegel, Scott D; Duffy, Nicole M

    2017-10-01

    There is increasing recognition of the unique physical and psychosocial concerns of the growing population of cancer survivors. An emerging literature demonstrates that fear of cancer recurrence (FCR) is a problematic long-term and late effect for cancer survivors. In fact, FCR is a top concern, and this article provides a necessary synthesis of the extant research evidence and theory. Literature searches were conducted using databases including MEDLINE and PsychINFO using specified search terms including 'fear of recurrence' and 'worry about recurrence'. A comprehensive narrative review summarizes early empirical findings on FCR including current definitions, assessment tools, clinical presentations, quality of life impact, prevalence, trajectory and risk factors. This paper also critically reviews the relevant theoretical frameworks to best understand these findings and considers multiple psychosocial treatment models that may have relevance for addressing FCR in the clinical setting. There is evidence of substantial prevalence and quality of life impact of FCR. Several theories (e.g. self-regulation model of illness, a family-based model, uncertainty in illness theory, social-cognitive processing theory, terror management theory) directly or indirectly help conceptualize FCR and inform potential treatment options for those with clinically significant distress or impairment resulting from FCR. Further investigation into FCR is warranted to promote evidence-based care for this significant cancer survivorship concern. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Does the new conceptual framework provide adequate concepts for reporting relevant information about performance?

    NARCIS (Netherlands)

    Brouwer, A.; Faramarzi, A; Hoogendoorn, M.

    2014-01-01

    The basic question we raise in this paper is whether the 2013 Discussion Paper (DP 2013) on the Conceptual Framework provides adequate principles for reporting an entity’s performance and what improvements could be made in light of both user needs and evidence from academic literature. DP 2013

  4. Providing policy-relevant information for greenhouse gas management: Perspectives from science and technology policy research

    Science.gov (United States)

    Dilling, L.

    2009-12-01

    In the 12 years since the Kyoto Protocol was signed setting forth targets for greenhouse gas emissions from several nations, the number of policies, voluntary programs and commercial enterprises that have developed to manage carbon has grown exponentially. Many of these programs have occurred in a voluntary context, such as carbon trading, carbon offset programs, and climate registries . To date, no single, common system for accrediting, verifying and recording carbon credits has developed. Moreover, as the international community continues to negotiate the dimensions of an international agreement for the post-Kyoto time period, discussions still center on targets for fossil fuel emissions, biospheric carbon protection, and appropriate distribution of the burden of compliance globally. If carbon still remains the currency for discussion in a climate agreement, some type of effective measurement and verification system will be needed to ensure that commitments are being met. While entire volumes over the past decade have been written on what it is possible to observe about the carbon cycle and how to do so-- these tend to describe observations from the perspective of studying the carbon cycle to discover fundamental new knowledge. I will argue, however, that for the application under consideration in this session, i.e. a global greenhouse gas information system, it is essential to bring in the perspective of the policy and regulatory community. The needs of the scientific community for measuring the uncertainties in the global carbon cycle are not necessarily the same as those for the policy community. To ensure that such a system can serve a policy-relevant function, the scientific community must engage with policy makers, entrepreneurs, those who must comply, and others involved in constructing the policy framework. This paper will examine some of the key fundamentals that the policy community may be considering in designing a greenhouse gas monitoring system. I

  5. Providers' Response to Clinical Decision Support for QT Prolonging Drugs.

    Science.gov (United States)

    Sharma, Sunita; Martijn Bos, J; Tarrell, Robert F; Simon, Gyorgy J; Morlan, Bruce W; Ackerman, Michael J; Caraballo, Pedro J

    2017-09-02

    Commonly used drugs in hospital setting can cause QT prolongation and trigger life-threatening arrhythmias. We evaluate changes in prescribing behavior after the implementation of a clinical decision support system to prevent the use of QT prolonging medications in the hospital setting. We conducted a quasi-experimental study, before and after the implementation of a clinical decision support system integrated in the electronic medical record (QT-alert system). This system detects patients at risk of significant QT prolongation (QTc>500ms) and alerts providers ordering QT prolonging drugs. We reviewed the electronic health record to assess the provider's responses which were classified as "action taken" (QT drug avoided, QT drug changed, other QT drug(s) avoided, ECG monitoring, electrolytes monitoring, QT issue acknowledged, other actions) or "no action taken". Approximately, 15.5% (95/612) of the alerts were followed by a provider's action in the pre-intervention phase compared with 21% (228/1085) in the post-intervention phase (p=0.006). The most common type of actions taken during pre-intervention phase compared to post-intervention phase were ECG monitoring (8% vs. 13%, p=0.002) and QT issue acknowledgment (2.1% vs. 4.1%, p=0.03). Notably, there was no significant difference for other actions including QT drug avoided (p=0.8), QT drug changed (p=0.06) and other QT drug(s) avoided (p=0.3). Our study demonstrated that the QT alert system prompted a higher proportion of providers to take action on patients at risk of complications. However, the overall impact was modest underscoring the need for educating providers and optimizing clinical decision support to further reduce drug-induced QT prolongation.

  6. Continuous urethral pressure measurements; measurement techniques; pressure variations; clinical interpretations; and clinical relevance. A Systematic Literature Analysis.

    Science.gov (United States)

    Kummeling, Maxime T M; Rosier, Peter F W M; Elzevier, Henk W; Groenendijk, Pieter M

    2017-01-01

    The clinical relevance of urethral pressure variations (UPV) in the pathophysiology of over active bladder syndrome (OAB) has remained controversial to date. Some studies report an association with OAB and/or detrusor over activity (DO). Recently the International Consultation on Incontinence-Research Society recommended new clinical research to be performed on this subject. We provide a systematic review of the literature to specify this recommendation. Literature search was performed in PubMed, Embase, Web of Science, Cochrane, Central, Cinahl, Academic Science Premier, Science Direct, and Wiley Online using a sensitive search string combination. All authors independently reviewed and scored full text papers and consensus about methodological quality was obtained according to Oxford Level of Evidence (LoE). Four hundred eighty seven abstracts were screened, 25 papers met all predefined inclusion selection criteria. Incidence figures of UPV varied between 2% and 95%. Studies are of poor methodological quality with Oxford LoE scores of 3B and 4. Measurement methods and techniques show a large variety. The above mentioned association of DO/OAB with UPV is however frequently reported. There exists a phenomenon of UPV, apart from DO, which may be a separate entity within OAB syndrome. Large variation in measurement techniques and patient populations hinders fundamental research as well as clinical progress. Clinical relevance of UPV and consequences for treatment therefore are yet to be established. Future prospective research with well-defined patient population and standardised urodynamic measurement techniques is needed. Results of standardized and objective evaluations should be compared to clinical signs and symptoms by validated questionnaires. Neurourol. Urodynam. 36:51-56, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  7. Providing Cardiology Care in Rural Areas Through Visiting Consultant Clinics.

    Science.gov (United States)

    Gruca, Thomas S; Pyo, Tae-Hyung; Nelson, Gregory C

    2016-06-30

    Workforce experts predict a future shortage of cardiologists that is expected to impact rural areas more severely than urban areas. However, there is little research on how rural patients are currently served through clinical outreach. This study examines the impact of cardiology outreach in Iowa, a state with a large rural population, on participating cardiologists and on patient access. Outreach clinics are tracked annually in the Office of Statewide Clinical Education Programs Visiting Medical Consultant Database (University of Iowa Carver College of Medicine). Data from 2014 were analyzed. In 2014, an estimated 5460 visiting consultant clinic days were provided in 96 predominantly rural cities by 167 cardiologists from Iowa and adjoining states. Forty-five percent of Iowa cardiologists participated in rural outreach. Visiting cardiologists from Iowa and adjoining states drive an estimated 45 000 miles per month. Because of monthly outreach clinics, the average driving time to the nearest cardiologist falls from 42.2±20.0 to 14.7±11.0 minutes for rural Iowans. Cardiology outreach improves geographic access to office-based cardiology care for more than 1 million Iowans out of a total population of 3 million. Direct travel costs and opportunity costs associated with physician travel are estimated to be more than $2.1 million per year. Cardiologists in Iowa and adjoining states have expanded access to office-based cardiology care from 18 to 89 of the 99 counties in Iowa. In these 71 counties without a full-time cardiologist, visiting consultant clinics can accommodate more than 50% of office visits in the patients' home county. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

    Science.gov (United States)

    Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring

    2017-12-16

    Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

  9. [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.

  10. Clinical decision support systems differ in their ability to identify clinically relevant drug interactions of immunosuppressants in kidney transplant patients.

    Science.gov (United States)

    Amkreutz, J; Koch, A; Buendgens, L; Trautwein, C; Eisert, A

    2017-06-01

    In kidney transplant patients, clinically relevant drug-drug interactions (DDIs) with immunosuppressants potentially lead to serious adverse drug events (ADEs). The aim of this study was (i) to show that five clinical decision support systems (CDSSs) differ in their ability to identify clinically relevant potential DDIs (pDDIs) of immunosuppressants in kidney transplant patients and (ii) to compare CDSSs in terms of their ability to identify clinically relevant pDDIs in this context. All pDDIs being possible between nine immunosuppressants and 234 comedication drugs were identified for 264 intensive care unit (ICU) kidney transplant patients from 1999 to 2010. For pDDI identification, five CDSSs were used: DRUG-REAX® , ID PHARMA CHECK® , Lexi-Interact, mediQ and Meona. PDDIs from high severity categories were defined as clinically relevant. Classification of pDDIs as clinically relevant/non-clinically relevant by a clinical pharmacist using Stockley's Drug Interactions was employed as benchmark. We analysed inter-rater agreement, sensitivity, specificity, positive predictive value and negative predictive value. Clinical decision support systems generated a total of 759 pDDI alerts. A total of 240 pDDI alerts were in high severity categories. A total of 391 different pDDIs were identified. Only 5% (n = 35) of different pDDIs were identified by all CDSSs. A total of 49 pDDIs were classified as clinically relevant by clinical pharmacists' rating using Stockley's Drug Interactions. Meona (0·72) has the highest inter-rater agreement with the benchmark for clinically relevant pDDIs. ID PHARMA CHECK® and mediQ show highest sensitivities (0·74, respectively). Meona has the highest specificity (0·99) and positive predictive value (0·89). Five CDSSs differ in their ability to identify clinically relevant pDDIs of immunosuppressants in kidney transplant patients. Data may assist in selecting CDSSs for kidney transplant patients in the ICU. Using CDSSs to identify

  11. Reproducibility and clinical relevance of quantitative EEG parameters in cerebral ischemia: A basic approach.

    NARCIS (Netherlands)

    Sheorajpanday, Rishi V.A.; Nagels, Guy; Weeren, Arie J.T.M.; van Putten, Michel Johannes Antonius Maria; de Deyn, Peter P.

    2009-01-01

    Objective To investigate reproducibility and clinical relevance of quantitative EEG parameters in ischemic cerebrovascular disease. Methods EEG was recorded in 31 patients suffering from subacute ischemic cerebrovascular disease. Ten age-matched control subjects were included as a reference group.

  12. Patient, provider, and clinic characteristics associated with public STD clinic patient satisfaction

    OpenAIRE

    Mehta, S.; Zenilman, J; Erbelding, E

    2005-01-01

    Objectives: There is a lack of information describing levels of patient satisfaction among patients seeking sexually transmitted diseases (STD) care in a public clinic setting. We sought to identify patient, provider, and clinic characteristics associated with patient satisfaction within public STD clinics.

  13. Nurses in the clinical area: relevance of a PhD.

    Science.gov (United States)

    Wilkes, Lesley M; Mohan, Shantala

    2008-01-01

    This project aimed to explore the application and relevance of a PhD to nurses working in the clinical area. The complexity of nursing practice requires clinical nurses to be competent as investigators and professional leaders who could help structure nursing practice in more efficient ways. Research proposes that a PhD offers Limited employment opportunities, is mainly research oriented and tends to direct a nurse away from the clinical field. A mixed method study design utilising surveys and interviews was chosen to collect data for this study. Participants were nurses with a doctoral degree working/having worked in a clinical area after obtaining their PhD Nurses were recruited through student databases from Australian universities that offer doctoral degrees in nursing and also by using a snowball sampling technique. The majority of the 19 nurses who participated in the study had: varied expectation of doing a PhD; maintained their clinical positions after obtaining their doctoral degree, considered that the degree helped them to obtain better jobs/promotions and acknowledged the value of the PhD in patient care, in improving research and informing health policy. This study has exposed the positive aspects of completing a PhD and identifies its constructive application in the clinical area. It is essential to provide support and opportunities for nurses working in the clinical area to pursue doctoral degrees in order to enable them to enhance knowledge and build confidence and leadership skills and contribute to the improvement of nursing practice and the continued development of the profession.

  14. Clinical relevance of the STOPP/START criteria in hip fracture patients

    OpenAIRE

    L?nnbro, Johan; Wallerstedt, Susanna M

    2017-01-01

    Purpose The aim of this study was to investigate the clinical relevance of potentially inappropriate medications (PIMs), identified by the STOPP criteria, and potential prescribing omissions (PPOs), identified by the START criteria, and to identify predictors for clinically relevant PIMs and PPOs. Methods The STOPP and START criteria were applied on the medication lists of 200 older hip fracture patients, consecutively recruited to a randomized controlled study in 2009. For each identified PI...

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

    OpenAIRE

    van Halsema, CL; Chihota, VN; Gey van Pittius, NC; Fielding, KL; Lewis, JJ; van Helden, PD; Churchyard, GJ; Grant, AD

    2015-01-01

    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 ...

  16. Responding to the challenge of clinically relevant osteopathic research: efficacy and beyond

    Science.gov (United States)

    Licciardone, John C.

    2007-01-01

    The osteopathic profession has been challenged over the past decade to provide clinically relevant research. The conduct of evidence-based osteopathic research is imperative not only for scientific, economic, and professional reasons, but also to drive health care policy and clinical practice guidelines. This paper summarizes recent studies in response to the osteopathic research challenge, including clinical trials registered with ClinicalTrials.gov and a systematic review and meta-analysis of osteopathic manipulative treatment (OMT) for low back pain. The concept of the OMT responder is introduced and supported with preliminary data. Within the context of a pain processing model, consideration is given to genomic (e.g., the catechol-O-methyltransferase gene) and psychological (e.g., depression and somatization) factors that are associated with pain sensitivity and pain progression, and to the role that such factors may play in screening for OMT responders. While substantial progress has been made in osteopathic research, much more needs to be done. PMID:18311324

  17. 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.

  18. Innovative models for providing clinical pharmacy services to remote locations using clinical video telehealth.

    Science.gov (United States)

    Perdew, Cassie; Erickson, Katie; Litke, Jessica

    2017-07-15

    The use of videoconferencing and other telehealth technologies to expand access to clinical pharmacy services at multiple Veterans Affairs (VA) clinics in rural areas of Alaska and the northwestern United States is described. Beginning in 2014, clinical pharmacy specialists at a regional VA Telehealth Hub based at Boise VA Medical Center in Idaho have provided telehealth services for 16 clinics. In one telehealth model, a pharmacist and other remotely located primary care team members (a medical provider, a medical support assistant, a social worker, and a psychologist) conduct telehealth visits with veterans located at VA clinics, with support provided by clinic-based nursing staff; this model has been used to improve medication management services for veterans in sparsely populated areas. In the second VA telehealth model, a remotely located pharmacist uses telehealth technology to participate in clinical encounters along with primary care team members located at the patient site; this model allows on-demand remote coverage in the event of planned or unplanned absences of clinic-based pharmacists. Since the Telehealth Hub was established, pharmacists have engaged in video encounters and provided other telehealth-based clinical services to more than 1,200 veterans with diabetes, hyperlipidemia, hypertension, and other chronic conditions. Within the VA healthcare system, telehealth technology has been demonstrated to be a cost-effective and well-received means of providing clinical pharmacy services in rural areas. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  19. Update on cardiovascular safety of PPARgamma agonists and relevance to medicinal chemistry and clinical pharmacology.

    Science.gov (United States)

    Ciudin, Andreea; Hernandez, Cristina; Simó, Rafael

    2012-01-01

    Peroxisome proliferator-activator receptors (PPARs) are now known as members of the nuclear hormonereceptor superfamily of ligand-activated transcription factors that regulate gene expression in response to nutritional and physiological stimuli. PPARγ plays a crucial role in glucose homeostasis and it is involved in the regulation of lipid metabolism and adipocyte differentiation and function. From all the PAARγ ligands, the thiazolidindiones (TZDs) are of most clinical importance. Rosiglitazone and pioglitazone have been largely used so far in the clinical practice. They provide similar effects on glycemic control, as well as a range of similar adverse effects, such as weight gain, fluid retention, and increased risk of hearth failure, which seem to be PPARγ mediated. Interestingly, they differ on their effect on lipid and cardiovascular safety profile, indicating a PPARγ-independent mechanism. Indeed, rosiglitazone was recently withdrawn in Europe and its use has been restricted in USA as a consequence of increased risk of cardiovascular events in type 2 diabetic patients. This review is focused on the cardiovascular effects of rosiglitazone and pioglitazone as representative members of PPARγ ligands, because they were widely evaluated in many clinical trials and experimental studies and data obtained from these studies are relevant from medicinal chemistry and clinical pharmacology point of view. Finally, an overview on the development of selective PPARγ modulators and/or dual PPARα/γ agonists will be given. These new approaches might provide anti-hyperglycemic efficacy without the associated undesirable side-effects. However, further experimental and clinical studies evaluating the theoretical benefit and safety of this therapeutic strategy are needed.

  20. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model.

    Science.gov (United States)

    Lisowski, Leszek; Dane, Allison P; Chu, Kirk; Zhang, Yue; Cunningham, Sharon C; Wilson, Elizabeth M; Nygaard, Sean; Grompe, Markus; Alexander, Ian E; Kay, Mark A

    2014-02-20

    Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.

  1. Establishing a clinically relevant cutoff to the Dependency Scale from the dimensional clinical personality inventory.

    Science.gov (United States)

    Carvalho, Lucas de F; Pianowski, Giselle; Filho, Nelson H

    2017-05-01

    The Clinical Dimensional Personality Inventory (IDCP) is a 163-item self-report tool developed for the assessment of 12 dimensions of personality pathology. One of the scales comprising the instrument-the Dependency scale-is intended to provide psychometric information on traits closely related to the Dependent Personality Disorder (DPD). In the present study, we used both Item Response Theory modeling and Receiver Operating Characteristic curve analysis to establishing a clinically meaningful cutoff for the IDCP Dependency Scale. Participants were 2.481 adults, comprised by outpatients diagnosed with DPD, outpatients diagnosed with other PDs, and adults from the general population. The Wright's item map graphing technique revealed that outpatients were located at the very high levels in the latent scale continuum of the Dependency Scale, with a very large effect size for the mean difference between patients and non-patients. The ROC curve analysis supported a cutoff at 2.3 points in the Dependency Scale, which yielded 0.86 of sensitivity and 0.79 of specificity. Findings from the present investigation suggest the IDCP Dependency Scale is useful as a screening tool of the core features of the DPD. We address potential clinical applications for the instrument, and discuss limitations from the present study. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  2. Patient, provider, and clinic characteristics associated with public STD clinic patient satisfaction

    Science.gov (United States)

    Mehta, S; Zenilman, J; Erbelding, E

    2005-01-01

    Objectives: There is a lack of information describing levels of patient satisfaction among patients seeking sexually transmitted diseases (STD) care in a public clinic setting. We sought to identify patient, provider, and clinic characteristics associated with patient satisfaction within public STD clinics. Methods: A cross sectional survey with random sampling was conducted among patients attending two public STD clinics. Satisfaction was assessed using questions from validated national surveys. Outcomes for multivariate logistic regression analysis were ratings of overall health care and clinician. Results: 499/605 (82%) patients were enrolled. Patients were mean age 29 years, 51% male, 94% black. Lower rating of clinician technical skills (OR = 15.6 clinic A, OR = 7.9 clinic B) and clinic environment (OR = 3.9 clinic A, OR = 9.6 clinic B) were associated with lower healthcare rating, as was lower rating of television/video in waiting room (OR = 10.2, clinic A) and dysuria (OR = 4.2, clinic B). Higher clinician rating (OR = 0.58, clinic A) and receiving written materials (OR = 0.44, clinic B) were protective of lower healthcare rating. Risks for lower clinician rating at clinic A were greater pain, problems getting care, lower rating of clinician technical skill, and overall health care, while receiving written materials was protective. At clinic B, lower rating of clinician technical skill and clinic environment were risks for lower clinician rating. Conclusions: Patient satisfaction was associated with modifiable provider and clinic characteristics. Results from our study indicate a need to examine whether health outcomes of STD management vary by patient satisfaction. PMID:15800094

  3. 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.

  4. 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.

  5. 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...

  6. Administrative and clinical denials by a large dental insurance provider

    Directory of Open Access Journals (Sweden)

    Geraldo Elias MIRANDA

    2015-01-01

    Full Text Available The objective of this study was to assess the prevalence and the type of claim denials (administrative, clinical or both made by a large dental insurance plan. This was a cross-sectional, observational study, which retrospectively collected data from the claims and denial reports of a dental insurance company. The sample consisted of the payment claims submitted by network dentists, based on their procedure reports, reviewed in the third trimester of 2012. The denials were classified and grouped into ‘administrative’, ‘clinical’ or ‘both’. The data were tabulated and submitted to uni- and bivariate analyses. The confidence intervals were 95% and the level of significance was set at 5%. The overall frequency of denials was 8.2% of the total number of procedures performed. The frequency of administrative denials was 72.88%, whereas that of technical denials was 25.95% and that of both, 1.17% (p < 0.05. It was concluded that the overall prevalence of denials in the studied sample was low. Administrative denials were the most prevalent. This type of denial could be reduced if all dental insurance providers had unified clinical and administrative protocols, and if dentists submitted all of the required documentation in accordance with these protocols.

  7. Clinical management apps: creating partnerships between providers and patients.

    Science.gov (United States)

    Silow-Carroll, Sharon; Smith, Barbara

    2013-11-01

    The market for health applications, or apps, on mobile devices is growing rap­idly, with over 40,000 currently in use. One type of app technology--clinical manage­ment apps--enable patients and providers to work together to manage chronic conditions, particularly diabetes and asthma. These apps are mostly used by health plans and large health care organizations with an interest in improving outcomes and controlling costs. Challenges to broader adoption of apps include the lack of objective research to evalu­ate outcomes, uncertainty about how to pay for and encourage the use of cost-effective apps, and the absence of a regulatory framework that standardizes development to ensure performance. If this infrastructure is developed, apps may serve as a catalyst to stimulate the transformation of health care generally and target low-income populations to expand access to care and help reduce health disparities.

  8. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar

    2011-01-01

    Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...... regulatory demands. The influence on the cost effectiveness, the clinical relevance and the future perspectives of the present clinical approach are discussed....

  9. 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 ...

  10. Clinical relevance of Mycobacterium chelonae-abscessus group isolation in 95 patients.

    NARCIS (Netherlands)

    Ingen, J. van; Zwaan, R. de; Dekhuijzen, P.N.R.; Boeree, M.J.; Soolingen, D. van

    2009-01-01

    OBJECTIVES: To determine the clinical relevance of Mycobacterium chelonae-abscessus group isolation from clinical samples. METHODS: We retrospectively reviewed medical files of all patients from whom these mycobacteria were isolated between January 1999 and January 2005 and re-identified the

  11. Contact allergy to colophony. Clinical and experimental studies with emphasis on clinical relevance.

    Science.gov (United States)

    Färm, G

    1998-01-01

    Colophony--also called rosin--is a material obtained from coniferous trees. It is used widely in many products, particularly because of its good tackifying properties. Colophony is also used in paper sizing to increase water resistance. Colophony may cause contact allergy, and around 5% of Swedish dermatitis patients show allergic reactions to colophony at patch testing. There are many case reports of colophony in different products causing contact dermatitis. Often, however, the clinical relevance of a positive patch-test reaction to colophony is difficult to evaluate. The principal aims of the present thesis were to study the prevalence of contact allergy to colophony and of skin disease in individuals with an occupational exposure to colophony; to study the prognosis of dermatitis in colophony-sensitive subjects, and to investigate the outcome of repeated open applications of colophony, thereby trying to elucidate the clinical relevance of contact allergy to colophony. Employees of a tall-oil rosin (colophony) factory (n = 180), and of an opera company where colophony was used in dancers' rosin, mascara and wig glues (n = 132), were interviewed, examined and patch tested. 3.9% and 2% of these two groups respectively had a positive patch test to colophony. More than every fourth participant showed some kind of skin disease, but only few cases were related to work. Eighty-three patients with previously diagnosed contact allergy to colophony were followed-up 72% showed a positive patch-test reaction to colophony at re-testing. Around one third had hand eczema. There was no significant correlation between colophony exposure and current hand eczema. Adhesive bandages containing colophony and zinc oxide (ZnO), colophony and mixes of colophony and ZnO, were tested in 7 colophony-sensitive subjects to see whether addition of zinc oxide inhibited elicitation of allergic dermatitis to colophony, which has been proposed. No difference in reactivity between colophony and

  12. 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

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

    Science.gov (United States)

    Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji

    2017-01-01

    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 of the

  14. Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms.

    Science.gov (United States)

    Manzardo, Ann M; McGuire, Austen; Butler, Merlin G

    2015-04-15

    Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence. We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form. We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG). High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism

  15. 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.

  16. Feedback in Clinical Education, Part I: Characteristics of Feedback Provided by Approved Clinical Instructors

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Context Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). Objective To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Design Qualitative study. Setting One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants A total of 4 ACIs with various experience levels and 4 second-year ATSs. Data Collection and Analysis Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Conclusions Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form. PMID:24143902

  17. [Changes in clinically relevant goals and therapy outcome: a study with inpatients undergoing cognitive behavioral therapy].

    Science.gov (United States)

    Berking, Matthias; Grosse Holtforth, Martin; Jacobi, Claus

    2003-01-01

    According to the consistency theory clinically relevant goals, as explicated by Grosse Holtforth and Grawe, play a prominent role in the development, maintenance and therapy of psychological disorders. Thus effective psychotherapies should "normalize" the subjective importance of these goals. These changes should be positively associated with the success of psychotherapy. To test these assumptions, clinically relevant goals of 64 inpatients undergoing cognitive behavioral therapy were assessed by the Inventory of Approach and Avoidance Goals (German: Fragebogen zur Analyse motivationaler Schemata, FAMOS) before and after therapy. Results show effects of normalization, as expected, especially on scales associated with psychopathology in former studies.

  18. 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...

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

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0595 TITLE: Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi- Institutional Validation... Institutional Validation Trial 5b. GRANT NUMBER W81XWH-14-1-0595 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Daniel Lin, MD 5d. PROJECT NUMBER 5e. TASK...to report. Other Products As part of this project we continue to maintain a large biospecimen repository with associated clinical and demographic

  20. [Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas].

    Science.gov (United States)

    Brittinger, G; Bartels, H; Common, H; Dühmke, E; Engelhard, M; Fülle, H H; Gunzer, U; Gyenes, T; Heinz, R; König, E

    1986-04-01

    The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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.

  2. Clinically Relevant Changes in Emotional Expression in Children with ADHD Treated with Lisdexamfetamine Dimesylate

    Science.gov (United States)

    Katic, Alain; Ginsberg, Lawrence; Jain, Rakesh; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Scheckner, Brian; Richards, Cynthia; Lasser, Robert; Turgay, Atilla; Findling, Robert L.

    2012-01-01

    Objective: To describe clinically relevant effects of lisdexamfetamine dimesylate (LDX) on emotional expression (EE) in children with ADHD. Method: Children with ADHD participated in a 7-week, open-label, LDX dose-optimization study. Expression and Emotion Scale for Children (EESC) change scores were analyzed post hoc using two methods to…

  3. Preterm piglets are a clinically relevant model of pediatric GI disease

    Science.gov (United States)

    The goal of our research is to establish how nutritional support, enteral versus parenteral, affects gut function and susceptibility to disease in early development. We and others have used the neonatal pig to establish unique models of clinically relevant problems in pediatric gastroenterology, esp...

  4. 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…

  5. Diagnosing pubovisceral avulsions: a systematic review of the clinical relevance of a prevalent anatomical defect

    NARCIS (Netherlands)

    Lammers, K.; Futterer, J.J.; Prokop, M.; Vierhout, M.E.; Kluivers, K.B.

    2012-01-01

    The aims of this systematic literature review were to assess whether the detection of pubovisceral avulsions using magnetic resonance (MR) imaging or perineal ultrasonography was clinically relevant in women with pelvic floor dysfunction and to evaluate the relation with anatomy, symptoms, and

  6. Psychometric properties and clinical relevance of the Adolescent Sleep Hygiene Scale in Dutch adolescents

    NARCIS (Netherlands)

    de Bruin, E.J.; van Kampen, R.K.A.; van Kooten, T.; Meijer, A.M.

    2014-01-01

    Objective: This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. Methods: The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables

  7. Clinical relevancy of nonurinary nitrogen excretion in newborns and infants after digestive tract surgery

    NARCIS (Netherlands)

    Albers, MJIJ; Steyerberg, EW; Tibboel, D

    2003-01-01

    Background: Whether the contribution of nonurinary nitrogen excretion (N(2)nu) to total nitrogen excretion (N(2)tot) is clinically relevant has not been tested in children in an intensive care unit. Particularly after digestive tract surgery, fecal nitrogen losses, and losses via nasogastric tubes,

  8. Geographical distribution and clinical relevance of non-tuberculous mycobacteria in Croatia

    NARCIS (Netherlands)

    Jankovic, M.; Samarzija, M.; Sabol, I.; Jakopovic, M.; Katalinic Jankovic, V.; Zmak, L.; Ticac, B.; Marusic, A.; Obrovac, M.; Ingen, J. van

    2013-01-01

    SETTING: The clinical relevance of non-tuberculous mycobacteria (NTM) in Croatia is unknown. OBJECTIVE: To estimate the isolation rate of NTM, record geographical differences and assess the burden of pulmonary NTM disease in Croatia. DESIGN: Nationwide retrospective cohort study of all Croatian

  9. 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.)

  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. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy

    NARCIS (Netherlands)

    Heetla, Herre W; Staal, Michael; Proost, Johannes H; van Laar, Teus

    2014-01-01

    Objective: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. Data Sources: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. Study

  12. A software system to collect expert relevance ratings of medical record items for specific clinical tasks.

    Science.gov (United States)

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K

    2014-02-28

    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts' ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners.

  13. Polymicrobial infections involving clinically relevant Gram-negative bacteria and fungi.

    Science.gov (United States)

    Dhamgaye, Sanjiveeni; Qu, Yue; Peleg, Anton Y

    2016-12-01

    Interactions between fungi and bacteria and their relevance to human health and disease have recently attracted increased attention in biomedical fields. Emerging evidence shows that bacteria and fungi can have synergistic or antagonistic interactions, each with important implications for human colonization and disease. It is now appreciated that some of these interactions may be strategic and helps promote the survival of one or both microorganisms within the host. This review will shed light on clinically relevant interactions between fungi and Gram-negative bacteria. Mechanism of interaction, host immune responses, and preventive measures will also be reviewed. © 2016 John Wiley & Sons Ltd.

  14. 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.

  15. 3D Culture as a Clinically Relevant Model for Personalized Medicine.

    Science.gov (United States)

    Fong, Eliza Li Shan; Toh, Tan Boon; Yu, Hanry; Chow, Edward Kai-Hua

    2017-06-01

    Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.

  16. Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.

    Science.gov (United States)

    Leopold, Stije J; van Leth, Frank; Tarekegn, Hayalnesh; Schultsz, Constance

    2014-09-01

    Little is known about the prevalence of antimicrobial resistance (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for continent-wide surveillance to inform empirical treatment guidelines. We searched PubMed and additional databases for susceptibility data of key pathogens for surveillance, published between 1990 and 2013. Extracted data were standardized to a prevalence of resistance in populations of isolates and reported by clinical syndrome, microorganism, relevant antimicrobial drugs and region. We identified 2005 publications, of which 190 were analysed. Studies predominantly originated from east sSA (61%), were hospital based (60%), were from an urban setting (73%) and reported on isolates from patients with a febrile illness (42%). Quality procedures for susceptibility testing were described in resistance to chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third-generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The limited number of studies providing prevalence data on AMR in Gram-positive pathogens or in pathogens isolated from patients with a respiratory tract infection, meningitis, urinary tract infection or hospital-acquired infection suggested high prevalence of resistance to chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third-generation cephalosporins and fluoroquinolones. Our results indicate high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs commonly used in sSA. Enhanced approaches for AMR surveillance are needed to support empirical therapy in sSA. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. [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

  18. Interference of cationic polymeric nanoparticles with clinical chemistry tests--clinical relevance.

    Science.gov (United States)

    Shcharbin, Dzmitry; Shcharbina, Natallia; Milowska, Katarzyna; de la Mata, Francisco Javier; Muñoz-Fernandez, Maria Angeles; Mignani, Serge; Gomez-Ramirez, Rafael; Majoral, Jean-Pierre; Bryszewska, Maria

    2014-10-01

    The development of medical nanosystems requires knowledge of their behavior in vivo. Clinical chemistry tests are widely used to estimate the systemic toxicity of nanoparticles. In this paper we have explored the impact of small positively charged nanoparticles-poly(amidoamine), phosphorous and carbosilane dendrimers - on biochemical parameters of standardized serum in vitro. All the dendrimers could shift the main biochemical parameters. Thus, in the case of patients having the normal, but 'boundary', values of biochemical parameters, nanoparticle-induced changes can be wrongly interpreted as evidence of some dysfunctions (hepatic, renal, etc.). Moreover, the effects of nanoparticles of metals, carbon nanotubes, quantum dots, fullerenes, dendrimers having been sized up to 4000 nm and the hundreds of reactive groups, can be significantly higher. Thus, preliminary evaluation of any nanomaterial in vitro is required in clinical chemistry tests before its application in vivo to draw the correct conclusions and benefit animals. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. European Good Laboratory and Clinical Practices: their relevance to clinical pathology laboratories.

    Science.gov (United States)

    Dent, N J

    1991-10-01

    The requirements for Good Laboratory (GLP) and Good Clinical Practices (CGP) were established as a matter of urgency by the United States in the early 1970s. These were in response to gross misconduct and, in many instances, fraud. Over the next 15 years, a plethora of regulatory principles, guidelines, and regulations was produced by many countries of the world, culminating in single standards for European, Japanese, and United States authorities. Although with regard to GLP this has basically become a worldwide recognized standard within the preclinical (toxicology) studies, in the veterinary, chemical, agrochemical, and pharmaceutical industries, the GCPs are now seeing a rebirth. Within a clinical trials environment, there is most certainly a requirement for compliance with GCP, especially with regard to the harmonization of data within the European Community. The goal of this article is to cover the following aspects: Why should we have good practices? Why should laboratory data be audited? Why is there a need for a QA unit or function? What is the QA operational approach? How does a laboratory audit take place within laboratories? In discussing the laboratories and their subsequent data audits, the pitfalls and benefits are addressed and an examination of the data from the sponsor's viewpoint is compared with that produced by the laboratory. The types of laboratories present in a clinical environment are examined. They obviously comprise clinical pathology, microbiology, and analytical as well as ancillary hospital areas such as X-ray and cardiology. These laboratories may also be in the private sector, the National Health Service, contract laboratories, universities, or the general practitioner population.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. A head and neck lymph node classification using an anatomical grid system while maintaining clinical relevance.

    Science.gov (United States)

    Benninger, Brion; Barrett, Richard

    2011-10-01

    The current classification of head and neck lymph nodes lacks a standardized system that integrates basic anatomy and clinical relevance. Currently, anatomy texts, atlases, and journals used to educate future health care professionals use a classification system that differs from the commonly used clinical nomenclature. As a result, student trainees entering the professional world are confused by lymph node terminology. The purpose of this study was to suggest a lymph node classification system that accurately reflected anatomy and clinical applications. A literature search was conducted on anatomic and clinical texts, atlases, journals, and Web sites. Two recurring classification themes were found from anatomic texts and atlases: superficial and deep chains, and local anatomic structures. Since 1988 the clinical specialties have used a Roman numeral "level" system. The differences between anatomic and clinical classification systems have led to academic frustration. After analysis, a functional classification system was developed that integrated anatomic and clinical terminology from the current classification systems. This suggested system revised the clinically accepted level system approved in 1988 and replaced the terminology with an anatomically derived naming system. This system satisfies the need for a classification that unifies anatomic and clinical applications. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Clinical relevance of disturbances of sleep and vigilance in major depressive disorder: a review.

    Science.gov (United States)

    Thase, Michael E; Murck, Harald; Post, Anke

    2010-01-01

    The primary objective of this article is to provide a concise review of the clinical relevance of sleep and vigilance in major depressive disorder. PubMed was reviewed (1990-2009) and English-language articles were identified using the key words sleep and depression and sleep and antidepressants. Secondary searches included articles cited in sources identified by the primary search. The narrative review provides brief descriptions of the normal physiology of sleep and changes associated with depression, as well as the impact of various treatments on these processes. Although it has long been known that sleep disturbances are an important characteristic of depression, relatively few studies have been conducted with the newer-generation antidepressants. Neither of the most widely used classes of antidepressants, the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, have particularly beneficial effects on sleep and, among the medications that reliably improve sleep efficiency, including mirtazapine and the tricyclic antidepressants, problems with daytime sedation can offset therapeutic benefit. Despite relatively widespread use, trazodone has not been demonstrated to be an effective and safe hypnotic in patients taking other antidepressants. For many patients, ongoing concomitant treatment with benzodiazepines and related drugs is the preferred option, again without convincing empirical support of longer-term efficacy. Among newer and investigational antidepressants, agomelatine shows promise with respect to both overall safety and effects on insomnia, although possible negative effects on liver function warrant further study. Sleep disturbances are a significant aspect of depressive syndromes, and relief of insomnia remains an important unmet need in antidepressant therapeutics. Development of a well-tolerated antidepressant medication that rapidly improves sleep maintenance without daytime sedation is a priority for drug

  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. Clinical Relevance of Cement Leakage after Radiofrequency Kyphoplasty vs. Balloon Kyphoplasty: A Prospective Randomised Study.

    Science.gov (United States)

    Riesner, H-J; Kiupel, K; Lang, P; Stuby, F; Friemert, B; Palm, H-G

    2016-08-01

    Cement leakage is regarded as a typical complication of cement-based augmentation of vertebral fractures. The gold standard is balloon kyphoplasty (BK). Recent methods, such as radiofrequency kyphoplasty (RFK), must be compared with BK in terms of therapeutic success and complication rates. It is unclear whether the cement leakage rate in RFK is lower than with BK and whether this has any clinical relevance. Therefore, the aim of our prospective clinical study was to compare RFK with BK with respect to cement leakage rates and associated clinical complications. After prospective randomisation, 100 patients (76 women and 24 men with an average age of 78.5 years) or 162 vertebral bodies were treated by BK (n = 79) or RFK (n = 83). We evaluated the parameters "localisation of cement leakage" (epidural, intradiscal, extracorporal, intravascular) and "clinical relevance". More cement is used in BK (5.2 ml) than in RFK (4.0 ml, p = 0.001). Cement leakage was found in 48/79 patients (60.8 %) with BK and 53/83 patients (63.9 %) with RFK (p = 0.420). Even subanalysis by location showed no significant difference between the two methods. Despite the high leakage rates, we experienced only two cases (1× BK, 1× RFK) with intravascular leakage in the inferior vena cava, with interventional endovascular salvage. The two examined kyphoplasty methods (BK vs. RFK) have the same high rates of cement leakage, but are rarely associated with clinically manifest complications. Clinically relevant differences between the two compared kyphoplasty methods could not be found. Georg Thieme Verlag KG Stuttgart · New York.

  4. 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

    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-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. PMID:23382720

  5. Targeted testing with diethylthiourea often reveals clinically relevant allergic contact dermatitis caused by neoprene rubber

    DEFF Research Database (Denmark)

    Dall, Anne B-H; Andersen, Klaus Ejner; Mortz, Charlotte G

    2012-01-01

    Background. Diethylthiourea is widely used in the rubber industry, particularly in neoprene rubber, and may cause allergic contact dermatitis. However, as thiourea allergens are not part of the European baseline series, the diagnosis of allergic contact dermatitis caused by thiourea compounds......, and positive reactions were found in 15% (13/88). Thus, 15% (37/239) had positive patch test reactions to diethylthiourea, all with current clinical relevance and all strong. Conclusion. Clinical suspicion of neoprene rubber allergy and subsequent aimed patch testing with diethylthiourea give a high yield...

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Banys, Malgorzata, E-mail: maggybanys@yahoo.de [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany); Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg D-22087 (Germany); Krawczyk, Natalia; Fehm, Tanja [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany)

    2014-01-15

    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.

  8. 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.

  9. 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.

  10. Developing students' clinical reasoning skills: correlates of perceived relevance of two teaching and learning approaches.

    Science.gov (United States)

    Postma, T C; White, J G

    2017-02-01

    'Relevance' is a key concept in adult learning. Hence, this study sought to examine students' perceptions of relevance of the teaching and learning in relation to different instructional designs employed in a Comprehensive Patient Care (CPC) course that aims to develop integrated clinical reasoning skills. Third to fifth year students (2009-2011) were asked to anonymously rate the relevance of the instructional design (RELID) they participated in by means of visual analogue scales at the School of Dentistry, University of Pretoria. They were also asked to rate their perceptions of the alignment between teaching and learning and outcomes (ATLO), assessments' contribution to learning (ACL), course organisation (CO) and teacher competence (TC). RELID served as the outcome measure in stepwise linear regression analyses. ATLO, ACL, CO, TC and the instructional design (case-based learning (CBL = 1) and the combination of discipline-based and lecture-based teaching in CPC (DB-LBT = 0)) served as the co-variables for each of the years of study. The analyses showed positive correlations between RELID and ATLO and between RELID and ACL for all the years of study. RELID was associated with TC in year three and four and CO was associated with RELID in year four and five. CBL outperformed DB-LBT in terms of perceived relevance of the teaching and learning. The results suggest that students' perceptions of the relevance of the instructional design may be enhanced when outcomes, teaching, learning and assessment are constructively aligned during the development of clinical reasoning skills. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Approaches to biofilm-associated infections: the need for standardized and relevant biofilm methods for clinical applications.

    Science.gov (United States)

    Malone, Matthew; Goeres, Darla M; Gosbell, Iain; Vickery, Karen; Jensen, Slade; Stoodley, Paul

    2017-02-01

    The concept of biofilms in human health and disease is now widely accepted as cause of chronic infection. Typically, biofilms show remarkable tolerance to many forms of treatments and the host immune response. This has led to vast increase in research to identify new (and sometimes old) anti-biofilm strategies that demonstrate effectiveness against these tolerant phenotypes. Areas covered: Unfortunately, a standardized methodological approach of biofilm models has not been adopted leading to a large disparity between testing conditions. This has made it almost impossible to compare data across multiple laboratories, leaving large gaps in the evidence. Furthermore, many biofilm models testing anti-biofilm strategies aimed at the medical arena have not considered the matter of relevance to an intended application. This may explain why some in vitro models based on methodological designs that do not consider relevance to an intended application fail when applied in vivo at the clinical level. Expert commentary: This review will explore the issues that need to be considered in developing performance standards for anti-biofilm therapeutics and provide a rationale for the need to standardize models/methods that are clinically relevant. We also provide some rational as to why no standards currently exist.

  12. Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Rachinger Andrea

    2008-10-01

    Full Text Available Abstract Background In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas. Methods We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750 in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1 were quantified in 62 cancer tissues by real-time RT-PCR. Results Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy. Conclusion In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.

  13. 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

  14. 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

  15. 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.

  16. Monitoring consumer satisfaction with the clinical services provided to 'exceptional' children.

    Science.gov (United States)

    Sommers, P A; Nycz, G R

    1978-09-01

    Given recent federal and state legislation mandating all necessary services for children with handicapping conditions, it is incumbent upon the providers of health care services to demonstrate accountability for their services to children with special needs. A procedure to assess the satisfaction of parents and community-based case coordinators with clinical services provided to such children has been demonstrated. By focusing on specific service elements, it is possible to align optimum versus actual consumer satisfaction. Through an analysis of observed variance, the modification of documented weaknesses can decrease the difference between optimum and actual consumer satisfaction levels. This procedure will be continued on a bi-annual, longitudinal follow-up basis to monitor progress. The concept of consumer input into the provision of clinical services is relevant to other developments in the field of health care which place importance on administration accountability. Those health care providers who recognize the value of consumer input and allow for its incorporation into their service programs will be better able to adapt their systems to the emerging trend towards medical accountability. Self-ordered accountability is more meaningful, is easier to understand than government imposed regulations, and can be smoothly blended into an organization's goals and objectives.

  17. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

    Science.gov (United States)

    Butler, Merlin G; McGuire, Austen; Manzardo, Ann M

    2015-04-01

    Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

  18. Balancing Clinical and Pathologic Relevence in the Machine Learning Diagnosis of Epilepsy.

    Science.gov (United States)

    Kerr, Wesley T; Cho, Andrew Y; Anderson, Ariana; Douglas, Pamela K; Lau, Edward P; Hwang, Eric S; Raman, Kaavya R; Trefler, Aaron; Cohen, Mark S; Nguyen, Stefan T; Reddy, Navya M; Silverman, Daniel H

    2013-06-01

    The application of machine learning to epilepsy can be used both to develop clinically useful computer-aided diagnostic tools, and to reveal pathologically relevant insights into the disease. Such studies most frequently use neurologically normal patients as the control group to maximize the pathologic insight yielded from the model. This practice yields potentially inflated accuracy because the groups are quite dissimilar. A few manuscripts, however, opt to mimic the clinical comparison of epilepsy to non-epileptic seizures, an approach we believe to be more clinically realistic. In this manuscript, we describe the relative merits of each control group. We demonstrate that in our clinical quality FDG-PET database the performance achieved was similar using each control group. Based on these results, we find that the choice of control group likely does not hinder the reported performance. We argue that clinically applicable computer-aided diagnostic tools for epilepsy must directly address the clinical challenge of distinguishing patients with epilepsy from those with non-epileptic seizures.

  19. Bridging the financial gap through providing contract services: a model for publicly funded clinical biobanks.

    Science.gov (United States)

    Kozlakidis, Zisis; Mant, Christine; Cason, John

    2012-08-01

    Biobanks offer translational researchers a novel method of obtaining clinical research materials, patient data, and relevant ethical and legal permissions. However, such tissue collections are expensive to establish and maintain. Current opinion is that such initiatives can only survive with core funding from Government or major funding bodies. Given the present climate of financial austerity, funding agencies may be tempted to invest in fast-return research projects rather than in maintaining tissue collections, whose benefits will only become apparent in much longer timescales. Thus, securing additional funding for biobanks could provide a valuable boost enabling an extension of core services. Here we suggest that using biobank expertise to offer contract services to clinicians and industry may be an alternative approach to obtaining such extra funding.

  20. Impulsivity is relevant for trauma exposure and PTSD symptoms in a non-clinical population.

    Science.gov (United States)

    Netto, Liana R; Pereira, Juliana L; Nogueira, José F; Cavalcanti-Ribeiro, Patrícia; Santana, Rejane Conceição; Teles, Carlos A; Koenen, Karestan C; Quarantini, Lucas C

    2016-05-30

    Impulsivity is a relevant construct for explaining both normal individual differences in personality and more extreme personality disorder, and is often investigated within clinical populations. This study aims to explore the college students' impulsivity patterns and to investigate the association across levels of impulsivity with trauma exposure and PTSD development in a non-clinical population. A one-phase census survey of seven college institutions assessed 2213 students in three metropolitan regions of Northeastern Brazil. All subjects anonymously completed a self-applied protocol consisting of: a socio-demographic questionnaire, Trauma History Questionnaire (THQ), PTSD Checklist (PCL-C), and Barratt Impulsiveness Scale (BIS-11). The median for frequency of trauma exposure was 4 events for people with low and normal impulsivity, and 6 for highly impulsive ones. Individuals with higher impulsivity presented earlier exposition than non-impulsive ones, and worst outcome: 12.4% with PTSD, against 8.4% and 2.3% (normal and low impulsivity). Of the three factors of impulsivity, the Attentional factor conferred the strongest association with PTSD development. Results suggest that impulsivity is also a relevant trait in a non-clinical population and is associated with trauma exposure and PTSD. Strategies to promote mental health in adolescents may be pertinent, especially with the aim of managing impulsivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. 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.

  2. Found in Translation: Maximizing the Clinical Relevance of Nonclinical Oncology Studies.

    Science.gov (United States)

    Spilker, Mary E; Chen, Xiaoying; Visswanathan, Ravi; Vage, Chandra; Yamazaki, Shinji; Li, Gang; Lucas, Judy; Bradshaw-Pierce, Erica L; Vicini, Paolo

    2017-02-15

    Purpose: The translation of nonclinical oncology studies is a subject of continuous debate. We propose that translational oncology studies need to optimize both pharmacokinetic (drug exposure) and pharmacodynamic (xenograft model) aspects. While improvements in pharmacodynamic translatability can be obtained by choosing cell lines or patient-derived xenograft models closer to the clinical indication, significant ambiguity and variability exists when optimizing the pharmacokinetic translation of small molecule and biotherapeutic agents. Experimental Design and Results: In this work, we propose a pharmacokinetic-based strategy to select nonclinical doses for approved drug molecules. We define a clinically relevant dose (CRD) as the dosing regimen in mice that most closely approximates the relevant pharmacokinetic metric in humans. Such metrics include area under the time-concentration curve and maximal or minimal concentrations within the dosing interval. The methodology is applied to six drugs, including targeted agents and chemotherapeutics, small and large molecules (erlotinib, dasatinib, vismodegib, trastuzumab, irinotecan, and capecitabine). The resulting efficacy response at the CRD is compared with clinical responses. Conclusions: We conclude that nonclinical studies designed with the appropriate CRDs of approved drug molecules will maximize the translatability of efficacy results, which is critical when testing approved and investigational agents in combination. Clin Cancer Res; 23(4); 1080-90. ©2016 AACR . ©2016 American Association for Cancer Research.

  3. Rapid, accurate, and comparative differentiation of clinically and industrially relevant microorganisms via multiple vibrational spectroscopic fingerprinting.

    Science.gov (United States)

    Muhamadali, Howbeer; Subaihi, Abdu; Mohammadtaheri, Mahsa; Xu, Yun; Ellis, David I; Ramanathan, Rajesh; Bansal, Vipul; Goodacre, Royston

    2016-08-15

    Despite the fact that various microorganisms (e.g., bacteria, fungi, viruses, etc.) have been linked with infectious diseases, their crucial role towards sustaining life on Earth is undeniable. The huge biodiversity, combined with the wide range of biochemical capabilities of these organisms, have always been the driving force behind their large number of current, and, as of yet, undiscovered future applications. The presence of such diversity could be said to expedite the need for the development of rapid, accurate and sensitive techniques which allow for the detection, differentiation, identification and classification of such organisms. In this study, we employed Fourier transform infrared (FT-IR), Raman, and surface enhanced Raman scattering (SERS) spectroscopies, as molecular whole-organism fingerprinting techniques, combined with multivariate statistical analysis approaches for the classification of a range of industrial, environmental or clinically relevant bacteria (P. aeruginosa, P. putida, E. coli, E. faecium, S. lividans, B. subtilis, B. cereus) and yeast (S. cerevisiae). Principal components-discriminant function analysis (PC-DFA) scores plots of the spectral data collected from all three techniques allowed for the clear differentiation of all the samples down to sub-species level. The partial least squares-discriminant analysis (PLS-DA) models generated using the SERS spectral data displayed lower accuracy (74.9%) when compared to those obtained from conventional Raman (97.8%) and FT-IR (96.2%) analyses. In addition, whilst background fluorescence was detected in Raman spectra for S. cerevisiae, this fluorescence was quenched when applying SERS to the same species, and conversely SERS appeared to introduce strong fluorescence when analysing P. putida. It is also worth noting that FT-IR analysis provided spectral data of high quality and reproducibility for the whole sample set, suggesting its applicability to a wider range of samples, and perhaps the

  4. 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

    2017-09-05

    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 the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.

  5. Nonmotor Symptoms in Parkinson’s Disease in 2012: Relevant Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Anne Marie Bonnet

    2012-01-01

    Full Text Available Nonmotor symptoms (NMSs of Parkinson’s disease (PD are common, but they are often underrecognized in clinical practice, because of the lack of spontaneous complaints by the patients, and partly because of the absence of systematic questioning by the consulting physician. However, valid specific instruments for identification and assessment of these symptoms are available in 2012. The administration of the self-completed screening tool, NMSQuest, associated with questioning during the consultation, improves the diagnosis of NMSs. NMSs play a large role in degradation of quality of life. More relevant NMSs are described in this review, mood disorders, impulse control disorders, cognitive deficits, hallucinations, pain, sleep disorders, and dysautonomia.

  6. Blood lactate concentration after exposure to conducted energy weapons (including TASER® devices): is it clinically relevant?

    Science.gov (United States)

    Jauchem, James R

    2013-09-01

    In previous studies, blood lactate concentration (BLac) consistently increased in anesthetized animals and in human subjects after exposures to TASER(®) conducted energy weapons (CEWs). Some have suggested the increased BLac would have detrimental consequences. In the current review, the following are evaluated: (a) the nature of muscle contractions due to CEWs, (b) general aspects of increased BLac, (c) previous studies of conventional neuromuscular electrical stimulation and CEW exposures, and (d) BLac in disease states. On the basis of these analyses, one can conclude that BLac, per se (independent of acidemia), would not be clinically relevant immediately after short-duration CEW applications, due to the short time course of any increase.

  7. In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Claudio L. Donnici

    2014-04-01

    Full Text Available The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs, such as Candida spp. [C. albicans (two clinical isolates, C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates], Paracoccidioides brasiliensis (seven clinical isolates, Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration values were very low (from 10−6 mol mL−1 to 10−8 mol mL−1 against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50 showed that the complexes are not as toxic (IC50 values are much higher—30 to 200 fold—than MIC values. These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs.

  8. Impact of glucose measurement processing delays on clinical accuracy and relevance.

    Science.gov (United States)

    Jangam, Sujit R; Hayter, Gary; Dunn, Timothy C

    2013-05-01

    In a hospital setting, glucose is often measured from venous blood in the clinical laboratory. However, laboratory glucose measurements are typically not available in real time. In practice, turn-around times for laboratory measurements can be minutes to hours. This analysis assesses the impact of turn-around time on the effective clinical accuracy of laboratory measurements. Data obtained from an earlier study with 58 subjects with type 1 diabetes mellitus (T1DM) were used for this analysis. In the study, glucose measurements using a YSI glucose analyzer were obtained from venous blood samples every 15 min while the subjects were at the health care facility. To simulate delayed laboratory results, each YSI glucose value from a subject was paired with one from a later time point (from the same subject) separated by 15, 30, 45, and 60 min. To assess the clinical accuracy of a delayed YSI result relative to a real-time result, the percentage of YSI pairs that meet the International Organization for Standardization (ISO) 15197:2003(E) standard for glucose measurement accuracy (±15 mg/dl for blood glucose ISO 15197:2003(E) recommendation of 95%. The accuracy was less than 65% for delays of 60 min. This analysis suggests that processing delays in glucose measurements reduce the clinical relevance of results in patients with T1DM and may similarly degrade the clinical value of measurements in other patient populations. © 2013 Diabetes Technology Society.

  9. Refining Prognosis in Lung Cancer: A Report on the Quality and Relevance of Clinical Prognostic Tools.

    Science.gov (United States)

    Mahar, Alyson L; Compton, Carolyn; McShane, Lisa M; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A

    2015-11-01

    Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biological, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. A systematic search of the scientific literature for clinical prognostic tools in lung cancer published from January 1, 1996 to January 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small-cell lung cancer. All tools for small-cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only 11 were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision points and prioritized inclusion of established prognostic factors over emerging factors. Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation.

  10. Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery.

    Directory of Open Access Journals (Sweden)

    Jessica Kao

    2009-07-01

    genes.Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, cancer stem cell biology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes.

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

    Science.gov (United States)

    Davidson, John H.

    2015-01-01

    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. PMID:25973266

  12. 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

    Research into articular cartilage is a surprisingly recent endeavour and much remains to be learned about the normal development of the synovial joint and its components that interplay in osteoarthritis and focal cartilage defects. Stem cell research is likely to contribute to the understanding...... of the developmental biology of synovial joints and their pathologies. Before human clinical trials are undertaken, stem cell-based therapies for non-life-threatening disorders should be evaluated for their safety and efficacy using animal models of spontaneous disease and not solely by the existing laboratory models...... 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...

  13. 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.

  14. Prevalence and clinical relevance of autoimmune neutropenia in patients with primary Sjögren's syndrome.

    Science.gov (United States)

    Brito-Zerón, Pilar; Soria, Natalia; Muñoz, Sandra; Bové, Albert; Akasbi, Miriam; Belenguer, Rafael; Sisó, Antoni; Ramos-Casals, Manuel

    2009-04-01

    To analyze the prevalence of neutropenia in a large cohort of patients with primary Sjögren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes. The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (manifestations, neoplasia, and death. Ninety-nine (33%) patients had neutropenia during the follow-up, which was related to neoplasia or drugs in 9 (3%) patients and was considered idiopathic in the remaining 90 (30%). Patients with neutropenia had a lower mean age at diagnosis of SS (51.9 versus 59.4 years, P leukemia. Neutropenia should be considered a relevant hematologic finding of primary SS, due both to its elevated prevalence and to its clinical significance (close association with anti-Ro/La antibodies, coexistence with other cytopenias, and development of severe infections).

  15. 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.

  16. 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.

  17. Providing Culturally Relevant Services for International Black African Collegians in the United States: A Guide for Student Affairs Professionals

    Science.gov (United States)

    Onyenekwu, Ifeyinwa Uchechi

    2017-01-01

    The experience of international Black African collegians (IBAC) in U.S. higher education has not been adequately investigated, particularly as it relates to understanding the diversity within Black and international student populations. In this manuscript, I offer seven culturally relevant suggestions for student affairs professionals, all of…

  18. Gene mutations versus clinically relevant phenotypes: lyso-Gb3 defines Fabry disease.

    Science.gov (United States)

    Niemann, Markus; Rolfs, Arndt; Störk, Stefan; Bijnens, Bart; Breunig, Frank; Beer, Meinrad; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2014-02-01

    Currently, no method is available to identify α-galactosidase A (agalA) mutations determining clinically relevant Fabry disease. In our largest European Fabry cohort, we investigated whether a biomarker, specific for the defect, could stratify persons at risk. A total of 124 individuals with agalA mutations were investigated with a comprehensive clinical workup, genetic analysis, and laboratory testing, including measurements of agalA activity and lyso-Gb3 (degradation product of the accumulating Gb3). Additionally, an extensive family screening with a clinical workup of relatives was performed. The patient population was divided into 2 samples: previously described mutations (n=72) and novel mutations (n=52). The patients with previously described mutations were subdivided into 2 groups: classical mutations, which were known to cause the classic type of Fabry disease with specific symptoms and a high risk for major events in all 3 main organs (heart, kidney, and central nervous system), and atypical mutations without the typical presentation. All patients with atypical mutations (n=17) had lower lyso-Gb3 levels than any of the patients with classical Fabry disease (n=55). A cutoff value of 2.7 ng/mL separated the 2 groups. Six out of 52 patients with novel mutations showed a lyso-Gb3 level characterization of patients with lyso-Gb3≥2.7 ng/mL suggested classical Fabry mutations in most of the patients (93%). Our data show that the biomarker lyso-Gb3 may identify the clinically relevant agalA mutations leading to Fabry disease.

  19. Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures.

    Science.gov (United States)

    Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping

    2017-04-01

    Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Estimating clinically relevant mental disorders in a rural and an urban setting in postconflict Timor Leste.

    Science.gov (United States)

    Silove, Derrick; Bateman, Catherine Robina; Brooks, Robert T; Fonseca, C Amaral Zulmira; Steel, Zachary; Rodger, James; Soosay, Ian; Fox, Greg; Patel, Vikram; Bauman, Adrian

    2008-10-01

    Epidemiologic studies undertaken in postconflict countries have focused primarily on trauma-related disorders. There is a need to include disabling psychotic disorders in order to plan clinical services in these settings. To estimate the prevalence of key clinical disorders in Timor Leste (East Timor), and to assess cultural factors that may influence help-seeking patterns. A 2-phase total population survey of 1544 adults in an urban and a rural area of Timor Leste. Phase 1 involved a household informant survey using indigenous terms to detect psychosis and a screen of all adults for posttraumatic stress disorder (PTSD) and symptoms of psychologic distress, including depression and anxiety. In phase 2, clinicians interviewed all those identified by household informants and half of those who screened positive in order to assign DSM-IV diagnoses. Disability, explanatory models, and perceived needs were also assessed. Phase 1: Demographic characteristics; trauma events and PTSD (Harvard Trauma Questionnaire); psychologic distress (Kessler-10 scale). Phase 2: Structured Clinical Interview for relevant DSM-IV diagnoses; the Global Assessment of Functioning Scale and the World Health Organization Disability Assessment Scales; and the modified Short Explanatory Model Interview. The household informant method in phase 1 detected mainly psychotic disorders, and the screen method detected PTSD and depression. Phase 2 yielded a DSM-IV point prevalence estimate of 5.1% (including psychosis, 1.35%; and PTSD, 1.47%). Psychotic disorders were most disabling, primarily attributed to supernatural causes and treated mainly by traditional healers. Those with depression and PTSD experienced substantial disability but had received little treatment. They attributed their mental problems to social and traumatic causes. Our 2-phase method proved effective for identifying the range of disorders relevant to planning clinical services in postconflict developing countries. The unmet needs of

  1. Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD Association study.

    Science.gov (United States)

    Hofmeijer-Sevink, Mieke Klein; van Oppen, Patricia; van Megen, Harold J; Batelaan, Neeltje M; Cath, Danielle C; van der Wee, Nic J A; van den Hout, Marcel A; van Balkom, Anton J

    2013-09-25

    This study describes lifetime and current rates of comorbidity, its onset and its consequences in a large clinical sample of patients with obsessive compulsive disorder (OCD). A wide range of risk factors and clinical characteristics were also examined to determine whether pure OCD is different from OCD with current comorbidity. Finally, the temporal sequencing of the disorders was examined. Data were obtained from the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. A sample of 382 participants with current OCD (during the past month) was evaluated. Current comorbidity occurred in 55% of patients with OCD, while 78% suffered from lifetime comorbidity. Comorbidity is associated with more severe OCD, anxiety and depressive symptoms and more negative consequences on daily life. Multiple comorbid disorders often precede OCD and influence both its course and severity. Childhood trauma and neuroticism are vulnerability factors for the development of multiple comorbid disorders in OCD. It should be noted that causal inferences about the association between risk factors and OCD are precluded since our results were based on cross-sectional data. (Multiple) comorbidity in OCD is clinically relevant since it is associated with a specific pattern of vulnerability, with greater chronicity, with more severe OCD and more negative consequences on daily life. This indicates that the diagnosis and treatment of all comorbid disorders is clinically relevant, and clinicians should be especially aware of multiple disorders in cases of childhood trauma and high levels of neuroticism. Primary OCD has a different developmental and comorbidity pattern compared to secondary OCD. © 2013 Elsevier B.V. All rights reserved.

  2. A Pan-cancer Analysis of the Expression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer

    Directory of Open Access Journals (Sweden)

    Jing Gong

    2017-11-01

    Full Text Available Increasing evidence has demonstrated that small nucleolar RNAs (snoRNAs play important roles in tumorigenesis. We systematically investigated the expression landscape and clinical relevance of snoRNAs in >10,000 samples across 31 cancer types from The Cancer Genome Atlas. We observed overall elevated expression of snoRNAs and their ribonucleoproteins in multiple cancer types. We showed complex regulation of snoRNA expression by their host genes, copy number variation, and DNA methylation. Unsupervised clustering revealed that the snoRNA expression subtype is highly concordant with other molecular/clinical subtypes. We further identified 46 clinically relevant snoRNAs and experimentally demonstrated functional roles of SNORD46 in promoting cell proliferation, migration, and invasion. We developed a user-friendly data portal, SNORic, to benefit the research community. Our study highlights the significant roles of snoRNAs in the development and implementation of biomarkers or therapeutic targets for cancer and provides a valuable resource for cancer research.

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

    Science.gov (United States)

    Teunissen, Rick; Bos, Jacqueline; Pot, Hans; Pluim, Marien; Kramers, Cornelis

    2013-06-15

    The clinical relevance of and risk factors associated with errors related to medication administration time were studied. In this explorative study, 66 medication administration rounds were studied on two wards (surgery and neurology) of a hospital. Data on medication errors were collected using the blister collection method. The emptied packaging material of medication was collected after each round and compared with each patient's medication orders. Administration time errors were defined as medication administration (actual intake) occurring more than one hour before or after the prescribed time. Generalized estimating equations analysis was performed to study the correlation between medication administration errors and risk factors. Data from 129 patients were included in the study. Among these 129 patients, 2874 opportunities for error were recorded. The majority of opportunities for error occurred during the 7 a.m. round. Within the 2874 opportunities for errors, 10 administration time errors occurred for medications that might interact with food or another medication. Time of administration (noon and 3 p.m.), route of administration (injection or infusion), and frequency of administration (if necessary) had significant protective effects against the occurrence of administration time errors. The rectal route of administration was associated with a significant increase in the frequency of administration time errors compared with the oral route. A clinically relevant administration time error occurred in 2 cases (0.07%). Analysis of medication administration rounds found time errors to be the most common medication error.

  4. 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.

  5. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes.

    Science.gov (United States)

    Wiebe, Natasha; Padwal, Raj; Field, Catherine; Marks, Seth; Jacobs, Rene; Tonelli, Marcello

    2011-11-17

    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. 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. 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. 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 needed to determine the role of hypocaloric sweeteners in a wider

  6. 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

  7. Can analysis of Platichthys flesus otoliths provide relevant data on historical metal pollution in estuaries? Experimental and in situ approaches

    Energy Technology Data Exchange (ETDEWEB)

    Selleslagh, Jonathan, E-mail: Jonathan.Selleslagh@u-bordeaux.fr [Université de Bordeaux, CNRS, UMR EPOC 5805, Station Marine d' Arcachon, place du docteur Peyneau, 33120 Arcachon (France); Echard, Aurélie [IRSTEA Centre de Bordeaux, unité EABX, 50 avenue de Verdun, 33612 Cestas (France); Pécheyran, Christophe [Université de Pau et des pays de l' Adour, CNRS, LCABIE-IPREM UMR 5254, 64053 Pau (France); Baudrimont, Magalie [Université de Bordeaux, CNRS, UMR EPOC 5805, Station Marine d' Arcachon, place du docteur Peyneau, 33120 Arcachon (France); Lobry, Jérémy; Daverat, Françoise [IRSTEA Centre de Bordeaux, unité EABX, 50 avenue de Verdun, 33612 Cestas (France)

    2016-07-01

    Despite recent efforts to manage them more efficiently, estuaries are natural sinks for a wide range of metal contaminants, many of which accumulate at potentially toxic concentrations for fish populations, posing a threat to recruitment and stocks. While analysis of metal concentrations in soft tissue and water samples calls for continuous and long-term sampling operations, the use of otoliths to study metal pollution may be one way of providing a historical record of pollutant exposure. In this study, we examine the potential use of otoliths as natural tracers of metal contamination. A “cocktail” of different metals (Cd, Pb and Ni) was used to test bio-accumulation in otoliths and tissue (liver, kidney, muscle and gills) extracted from juvenile flounder (Platichthys flesus). Assessment took place under controlled conditions over a three month period, with water exposure concentrations increasing every 3 weeks. The concentrations used were natural (T1), X5 (T2), X10 (T3), and null (T4). Chemical analyses were carried out using an inductively coupled plasma optical emission spectrometer ICP-OES and atomic absorption spectrometer AAS for water and tissue, while otolith microchemistry analyses were performed using a femtosecond laser ablation-high resolution inductively coupled plasma mass spectrometer (fsLA-ICP-MS-HR). Significant differences between control and exposed individuals, as well as an increase in metal concentrations according to exposure level, were observed in all tissues except in muscle tissue. Significant increases in Pb were also detected in contaminated fish otoliths compared with control specimens, with the highest concentrations occurring in T3. Cartographies of Pb distribution in otoliths of both control and contaminated fish only showed high concentrations of Pb at the edge of contaminated fish otoliths, indicating an accumulation of metal during the experiment. Although the relationships between exposure level and Pb concentration in

  8. Psychiatric disorders in children and adolescents presenting with unexplained chronic pain: what is the prevalence and clinical relevancy?

    NARCIS (Netherlands)

    Knook, L.M.; Konijnenberg, A.Y.; Hoeven, J. van der; Kimpen, J.L.L.; Buitelaar, J.K.; Engeland, H. van; Graeff-Meeder, E.R. de

    2011-01-01

    The prevalence of psychiatric disorders among children with unexplained chronic pain (UCP) is high in unselected populations and pain clinics, yet the clinical relevance of these disorders in children referred for unexplained pain is not known. This study assessed the prevalence of clinically

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

    Directory of Open Access Journals (Sweden)

    Arno Celliers

    2017-01-01

    Full Text Available Background: Shoulder pain is the most common and well-documented site of musculoskeletal pain in elite swimmers. Structural abnormalities on magnetic resonance imaging (MRI of elite swimmers’ symptomatic shoulders are common. Little has been documented about the association between MRI findings in the asymptomatic shoulder versus the symptomatic shoulder.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.

  10. 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.

  11. Relevance of Plasma Cholinesterase to Clinical Findings in Acute Organophosphorous Poisoning

    Directory of Open Access Journals (Sweden)

    Devanur R.M.M. Prasad

    2013-03-01

    Full Text Available Background: Organophosphorus (OP poisoning is a major public health problem in developing world. OP pesticides inhibit carboxylic esterase enzymes including plasma cholinesterase (PChE. Clinical manifestations following OP poisoning can be associated with the extent of decrease of PChE. This study was designed to investigate the relevance of PChE level to clinical manifestations in OP poisoning and to evaluate usefulness of PChE in predicting clinical outcomes. Methods: This was a cross-sectional study which was conducted at Jawaharlal Nehru Medical College, Karnataka from 1st October 2009 to 30th September 2010. Seventy-six OP poisoned patients were enrolled and their clinical manifestations were recorded. 5-ml samples of intravenous blood were collected from each patient (on first day and fifth day of treatment under strict aseptic precaution and the PChE level was measured. Results: In total, mean age of patients were 25.5 (range: 21-30 years. Majority of patients were males (65.7 %, from rural areas (86.84 % and agricultural workers (25%. Main clinical findings at the time of admission were congested conjunctiva (87%, pin point pupil (83%, lacrimation (80%, vomiting (78%, non-reactive pupil (75%, respiratory distress (60% and abdominal pain (37%. Mean (SD PChE at 6 hours post-exposure was 3672.4 (4200.1 IU/L. At presentation, cyanosis, muscle weakness, convulsion, respiratory distress and fasciculation were related to cases with >75%reduction of PChE, while,  constricted and non-reactive pupil, lacrimation and congested conjunctivae were related to cases with 50-75% reduction and abdominal pain, dryness of conjunctiva, vomiting and diarrhea were related to

  12. [Monitoring of pain, nociception, and analgesia under general anesthesia: Relevance, current scientific status, and clinical practice].

    Science.gov (United States)

    von Dincklage, F

    2015-10-01

    To avoid negative effects of painful stimuli under general anesthesia, an adequate analgesia is needed. Since both overdosing and underdosing of analgesics may lead to negative consequences, an optimal dosing is crucial, requiring a continuous monitoring of the balance between the ongoing nociception and the level of analgesia. This review describes current methods for the monitoring of nociception and analgesia as well as their inherent differences. Monitors of nociception register organic responses that are triggered through painful stimuli and therefore allow the detection of phases of excessive nociception during inadequate analgesia. In contrast, monitors of analgesia register nociception-specific organic responses that are triggered through test stimuli and allow a preemptive adaption of the level of analgesia, before a painful clinical stimulus is applied, but require the application of test stimuli. Preliminary proof-of-concept studies were able to demonstrate the potential of the here described methods; however, an effect on the clinical outcome of patients has not yet been shown for either of the two types of monitoring. For the routine application of monitors of nociception and analgesia in daily clinical practice, large clinical studies are necessary, proving a positive outcome effect. Without reliable parameters for nociception and analgesia it was hitherto impossible to perform such studies. The progress made in recent years generates optimism that in the not too distant future the currently available methods to monitor nociception and analgesia might improve to a level of reliability to allow them to be used to investigate the clinical outcome relevance of nociception and analgesia.

  13. 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.

  14. Improved Prevention Counseling by HIV Care Providers in a Multisite, Clinic-Based Intervention: Positive STEPs

    Science.gov (United States)

    Thrun, Mark; Cook, Paul F.; Bradley-Springer, Lucy A.; Gardner, Lytt; Marks, Gary; Wright, Julie; Wilson, Tracey E.; Quinlivan, E. Byrd; O'Daniels, Christine; Raffanti, Stephen; Thompson, Melanie; Golin, Carol

    2009-01-01

    The Centers for Disease Control and Prevention have recommended that HIV care clinics incorporate prevention into clinical practice. This report summarizes HIV care providers' attitudes and counseling practices before and after they received training to deliver a counseling intervention to patients. Providers at seven HIV clinics received training…

  15. Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

    Science.gov (United States)

    Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

    2013-01-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

  16. Markers of oxidant stress that are clinically relevant in aging and age-related disease.

    Science.gov (United States)

    Jacob, Kimberly D; Noren Hooten, Nicole; Trzeciak, Andrzej R; Evans, Michele K

    2013-03-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. Published by Elsevier Ireland Ltd.

  17. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease.

    Science.gov (United States)

    Diana, T; Krause, J; Olivo, P D; König, J; Kanitz, M; Decallonne, B; Kahaly, G J

    2017-09-01

    The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P  70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism. © 2017 British Society for Immunology.

  18. 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.

  19. 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.

  20. Photonics-based in vivo total hemoglobin monitoring and clinical relevance.

    Science.gov (United States)

    McMurdy, John; Jay, Gregory; Suner, Selim; Crawford, Gregory

    2009-05-01

    Anemia is a serious disorder which, as a result of antiquated invasive blood testing, is undiagnosed in millions of people in the U.S. As a result of the clinical need, many technological solutions have been proposed to measure total blood hemoglobin, and thus diagnose anemia, noninvasively. Because hemoglobin is the strongest chromophore in tissue, spectroscopic methods have been the most prevalently investigated. Difficulties in extracting a quantitative estimation of hemoglobin based on tissue absorption include variability in the absorption spectra of hemoglobin derivatives, interference from other tissue chromophores, and interpatient physiological variations affecting the effective optical path length of light propagating in tissue. In spite of these challenges, studies with a high degree of correlation between in vitro and in vivo measured total hemoglobin have been disclosed using variants of transmission and diffuse reflection spectroscopy in assorted physiological locations. A review of these technologies and the relevant advantages/disadvantages are presented here.

  1. 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.

  2. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin

    2017-01-01

    was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC....... Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more...... and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients....

  3. 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.

  4. Peripheral Blood Mononuclear Cells Spontaneous Osteoclastogenesis: Mechanisms Driving the Process and Clinical Relevance in Skeletal Disease.

    Science.gov (United States)

    Salamanna, Francesca; Maglio, Melania; Borsari, Veronica; Giavaresi, Gianluca; Aldini, Nicolò Nicoli; Fini, Milena

    2016-03-01

    In vitro peripheral blood mononuclear cells differentiate into osteoclasts under the influence of osteoclast-stimulating factors. However, accumulating evidence suggests spontaneous osteoclasts formation and activity in patients affected by local or systemic bone remodeling diseases in comparison with healthy controls. Therefore, within this review, we summarize the studies where spontaneous osteoclastogenesis of peripheral blood mononuclear cells was observed in pathological conditions of the skeletal system. We indicate a linkage between immunoregulation by T cells and spontaneous osteoclasts formation with increased levels of tumor necrosis factors-α, receptor activator of nuclear factor kappa-B ligand and inteleukin-7 production. In the light of these results, it would be of crucial importance to deepen the correlation between systemic bone remodeling diseases and spontaneous osteoclastogenesis as well as to investigate in detail the mechanisms underlying this phenomenon and the clinical relevance in bone remodeling disease diagnosis and monitoring. © 2015 Wiley Periodicals, Inc.

  5. Bandit solutions provide unified ethical models for randomized clinical trials and comparative effectiveness research

    OpenAIRE

    Press, William H.

    2009-01-01

    As electronic medical records enable increasingly ambitious studies of treatment outcomes, ethical issues previously important only to limited clinical trials become relevant to unlimited whole populations. For randomized clinical trials, adaptive assignment strategies are known to expose substantially fewer patients to avoidable treatment failures than strategies with fixed assignments (e.g., equal sample sizes). An idealized adaptive case—the two-armed Bernoulli bandit problem—can be exactl...

  6. What efficacy measures are clinically relevant and should be used in Cochrane Reviews of acute migraine trials?

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer

    2015-01-01

    BACKGROUND: Cochrane Reviews are methodologically of high quality but the clinical relevance of analysed efficacy measures (EMs) should also be assessed. METHODS: The clinical relevance of EMs used in one systematic Cochrane review of oral zolmitriptan for migraine headache was evaluated. RESULTS......: The following EMs were used: pain free at two hours (30%), headache relief at two hours (60%), sustained pain free for 24 hours (19%) and sustained headache relief for 24 hours (39%). These EMs were also used in four other Cochrane reviews of acute migraine treatment. Of these EMs sustained headache relief...... for 24 h is not judged clinically relevant. CONCLUSION: Pain free and sustained pain free are clinically relevant, but the responses are rather low, demonstrating that there is a need for improvement of acute drug treatment in migraine....

  7. LEFT VENTRICULAR ROTATION, TWIST AND UNTWIST: PHYSIOLOGICAL ROLE AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2015-09-01

    Full Text Available The helical ventricular myocardial band of Torrent-Guasp is a new concept, which provides strong grounds for reconciliation of some important aspects in cardiovascular medicine. Oblique fiber orientation provides left ventricular rotation, which in addition to radial thickening and longitudinal shortening, is predicted as an essential component of the effective left ventricular pumping. Left ventricular rotation can be measured in clinical practice noninvasively using echocardiography and this provides new opportunities for the assessment of different aspects of left ventricular mechanical function.

  8. 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

  9. Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure.

    Science.gov (United States)

    Damman, Kevin; Valente, Mattia A E; van Veldhuisen, Dirk J; Cleland, John G F; O'Connor, Christopher M; Metra, Marco; Ponikowski, Piotr; Cotter, Gad; Davison, Beth; Givertz, Michael M; Bloomfield, Daniel M; Hillege, Hans L; Voors, Adriaan A

    2017-07-08

    The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF ( p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.

  10. Understanding the Supersensitive Anti-Drug Antibody Assay: Unexpected High Anti-Drug Antibody Incidence and Its Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Sam Song

    2016-01-01

    Full Text Available Numbers of biotherapeutic products in development have increased over past decade. Despite providing significant benefits to patients with unmet needs, almost all protein-based biotherapeutics could induce unwanted immunogenicity, which result in a loss of efficacy and/or increase the risk of adverse reactions, such as infusion reactions, anaphylaxis, and even life-threatening response to endogenous proteins. Recognizing these possibilities, regulatory agencies request that immunogenicity be assessed as part of the approval process for biotherapeutics. Great efforts have been made to reduce drug immunogenicity through protein engineering. Accordingly the immunogenicity incidence has been reduced from around 80% in murine derived products to 0–10% in fully human products. However, recent improvements in immunogenicity assays have led to unexpectedly high immunogenicity rates, even in fully human products, leading to new challenges in assessing immunogenicity and its clinical relevance. These new immunogenicity assays are becoming supersensitive and able to detect more of anti-drug antibodies (ADA than with earlier assays. This paper intends to review and discuss our understanding of the supersensitive ADA assay and the unexpected high ADA incidence and its potential clinical relevance.

  11. Molecular Classification of Diffuse Large B-cell Lymphoma: What Is Clinically Relevant?

    Science.gov (United States)

    Sujobert, Pierre; Salles, Gilles; Bachy, Emmanuel

    2016-12-01

    Major progress in the understanding of diffuse large B-cell lymphoma (DLBCL) biology has been made in the last decade. Many specific compounds have now entered early phase clinical trials. However, further efforts are needed to find an accurate, fast, reproducible, and affordable technique to translate DLBCL subtype determination by gene expression profiles into clinical application. This article discusses the advantages and drawbacks of the currently available techniques of DLBCL subtype determination as well as important prognostic implications related to the cell of origin. Furthermore, the article provides a schematic description of how molecularly defined DLBCL subtypes could guide tailored therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

    Science.gov (United States)

    Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.

    2015-01-01

    Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

  13. 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

    2016-05-01

    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.

  14. Design of a clinically relevant upper-limb exoskeleton robot for stroke patients with spasticity.

    Science.gov (United States)

    Lee, Dong Jin; Bae, Sung Jin; Jang, Sung Ho; Chang, Pyung Hun

    2017-07-01

    The purpose of this research is to propose a design of a clinically relevant upper-limb (hand, wrist, and elbow) exoskeleton that meets the clinical requirements. At first, the proposed robot was designed to have sufficient torque for passive exercise therapy and spasticity measurement of post-stroke patients with spasticity (grade 3 or lower in Modified Ashworth Scale). Because the therapy of patients with high level spasticity could be laborious for therapists by increased muscle tone, and the patients tend not to get enough rehabilitation treatment. Secondly, this robot was designed to have user friendly features like as modularity, so that users have easy approach to assemble and disassemble for practical use. Thirdly, this robot system was designed to guarantee the safety for robot-aided passive training of patients with spasticity. As a result, we were able to see the usability of the robot system, even though it was a pilot test. This shows the possibility of measuring and classifying the spasticity.

  15. The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

    Science.gov (United States)

    Tall, F; Dechomet, M; Riviere, S; Cottin, V; Ballot, E; Tiev, K P; Montin, R; Morin, C; Chantran, Y; Grange, C; Jullien, D; Ninet, J; Chretien, P; Cabane, J; Fabien, N; Johanet, C

    2017-01-01

    Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  16. 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.

  17. Clinical Relevance of Sleep Duration: Results from a Cross-Sectional Analysis Using NHANES

    Science.gov (United States)

    Cepeda, M. Soledad; Stang, Paul; Blacketer, Clair; Kent, Justine M.; Wittenberg, Gayle M.

    2016-01-01

    Study Objectives: To assess the clinical relevance of sleep duration, hours slept were compared by health status, presence of insomnia, and presence of depression, and the association of sleep duration with BMI and cardiovascular risk was quantified. Methods: Cross-sectional analysis of subjects in the US National Health and Nutrition Examination Surveys using adjusted linear and logistic regressions. Results: A total of 22,281 adults were included, 37% slept ≤ 6 hours, 36% were obese, and 45% reported cardiovascular conditions. Mean sleep duration was 6.87 hours. Better health was associated with more hours of sleep. Subjects with poor health reported sleeping 46 min, (95% CI −56.85 to −35.67) less than subjects with excellent health. Individuals with depression (vs. not depressed) reported 40 min less sleep, (95% CI −47.14 to −32.85). Individuals with insomnia (vs. without insomnia) reported 39 min less sleep, (95% CI −56.24 to −22.45). Duration of sleep was inversely related to BMI; for every additional hour of sleep, there was a decrease of 0.18 kg/m2 in BMI, (95% CI −0.30 to −0.06). The odds of reporting cardiovascular problems were 6.0% lower for every hour of sleep (odds ratio = 0.94, 95% CI [0.91 to 0.97]). Compared with subjects who slept ≤ 6 h, subjects who slept more had lower odds of reporting cardiovascular problems, with the exception of subjects ≥ 55 years old who slept ≥ 9 hours. Conclusions: Long sleep duration is associated with better health. The fewer the hours of sleep, the greater the BMI and reported cardiovascular disease. A difference of 30 minutes of sleep is associated with substantive impact on clinical well-being. Citation: Cepeda MS, Stang P, Blacketer C, Kent JM, Wittenberg GM. Clinical relevance of sleep duration: results from a cross-sectional analysis using NHANES. J Clin Sleep Med 2016;12(6):813–819. PMID:26951419

  18. The clinical relevance of outcomes used in late-onset Pompe disease: can we do better?

    Science.gov (United States)

    Lachmann, Robin; Schoser, Benedikt

    2013-10-12

    Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. Clinical improvement was perceived by patients in 6 of the 10 studies. In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be

  19. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

    Science.gov (United States)

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L

    2014-10-01

    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans. © 2014 American Heart Association, Inc.

  20. Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder.

    Science.gov (United States)

    Köhler-Forsberg, Ole; Sylvia, Louisa; Deckersbach, Thilo; Ostacher, Michael Joshua; McInnis, Melvin; Iosifescu, Dan; Bowden, Charles; McElroy, Susan; Calabrese, Joseph; Thase, Michael; Shelton, Richard Charles; Tohen, Mauricio; Kocsis, James; Friedman, Edward; Ketter, Terence; Nierenberg, Andrew Alan

    2017-12-07

    Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature

  1. 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.

  2. Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data

    NARCIS (Netherlands)

    Winters, Bart; Montaner, Julio; Harrigan, P. Richard; Gazzard, Brian; Pozniak, Anton; Miller, Michael D.; Emery, Sean; van Leth, Frank; Robinson, Patrick; Baxter, John D.; Perez-Elias, Marie; Castor, Delivette; Hammer, Scott; Rinehart, Alex; Vermeiren, Hans; van Craenenbroeck, Elke; Bacheler, Lee

    2008-01-01

    BACKGROUND: Clinically relevant cutoffs are needed for the interpretation of HIV-1 phenotypic resistance estimates as predicted by "virtual" phenotype HIV resistance analysis. METHODS: Using a clinical data set containing 2596 treatment change episodes in 2217 patients in 8 clinical trials and 2

  3. ANALYSIS OF ‘QIYAFAH’ PERSPECTIVE OF IMAM SYAFI`I IN PROVIDING THE LINEAGE AND ITS RELEVANCE WITH GENETICS

    Directory of Open Access Journals (Sweden)

    Abdul Hakim

    2017-09-01

    Full Text Available In the tradition of Arab and Islamic Scientifics, research on genetics has been done since thousands of years ago. However, the information is not found in the books of genetic history. This indicates the existence of historical distortion of genetic history writers to include Arabs or Muslims within the span of history. Therefore, the follow-up and dissemination of information from various parties, especially the parties associated with genetic studies explain that this science has been found in Arab society and Muslims. Qiyafah is a method term used to recognize a person's trace in determining lineage based on traits and likeness. While qa`if, is a person who has special skills to see other people in connecting, determine the lineage based on the signs and similarities between the parties studied. According to asy-Shafi'i, qa'if services in determining one's lineage can be accepted as a legal provision. Therefore, if a lineage dispute arises where there is no other evidence or the parties have strong evidence, then the matter is solved by qa'if research. In support of his opinion, the school of ash-Shafi'i argued with the hadith of the Prophet Muhammad and the opinions of his companions. Therefore qiyafah practice is believed to have syariah justification.Genetika is one of the branches of biological science that discusses the nature of hereditary inheritance and variations that may arise in it. The practice of qiyafah and genetics are both aimed to examine the hereditary traits that are passed down from generation to generation. Judging from the similarity of function and purpose, then qiyafah has relevance to the science of genetics in establishing one's nasab. And the provision of modern science based on DNA test results with the same legal force with the provision of qiyafah perspective priest Shafi`i.

  4. Salient features of the coronary collateral circulation and its clinical relevance.

    Science.gov (United States)

    Stoller, Michael; Seiler, Christian

    2015-01-01

    The coronary collateral circulation provides an alternative source of blood supply to myocardium jeopardised by ischaemia. Collaterals enlarge with obstructive coronary artery disease to allow bulk flow, but blood flow deliverable by the native, pre-formed collateral extent can already be sizeable. Genetic determinants contribute significantly to the wide variability observed in both native collateral extent and its capacity to enlarge, and the severity of the coronary stenosis is the most significant environmental determinant for collateral enlargement. The protective effect of a well-developed coronary collateral circulation translates into relevant improvements in all-cause and cardiac mortality in the acute and chronic phases of coronary artery disease, as well as into a reduction of future adverse cardiovascular events.

  5. Interventions for providers to promote a patient-centred approach in clinical consultations.

    Science.gov (United States)

    Dwamena, Francesca; Holmes-Rovner, Margaret; Gaulden, Carolyn M; Jorgenson, Sarah; Sadigh, Gelareh; Sikorskii, Alla; Lewin, Simon; Smith, Robert C; Coffey, John; Olomu, Adesuwa

    2012-12-12

    Communication problems in health care may arise as a result of healthcare providers focusing on diseases and their management, rather than people, their lives and their health problems. Patient-centred approaches to care delivery in the patient encounter are increasingly advocated by consumers and clinicians and incorporated into training for healthcare providers. However, the impact of these interventions directly on clinical encounters and indirectly on patient satisfaction, healthcare behaviour and health status has not been adequately evaluated. To assess the effects of interventions for healthcare providers that aim to promote patient-centred care (PCC) approaches in clinical consultations. For this update, we searched: MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), and CINAHL (EbscoHOST) from January 2000 to June 2010. The earlier version of this review searched MEDLINE (1966 to December 1999), EMBASE (1985 to December 1999), PsycLIT (1987 to December 1999), CINAHL (1982 to December 1999) and HEALTH STAR (1975 to December 1999). We searched the bibliographies of studies assessed for inclusion and contacted study authors to identify other relevant studies. Any study authors who were contacted for further information on their studies were also asked if they were aware of any other published or ongoing studies that would meet our inclusion criteria. In the original review, study designs included randomized controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series studies of interventions for healthcare providers that promote patient-centred care in clinical consultations. In the present update, we were able to limit the studies to randomized controlled trials, thus limiting the likelihood of sampling error. This is especially important because the providers who volunteer for studies of PCC methods are likely to be different from the general population of providers. Patient-centred care was defined as a

  6. Standardized Patients Provide a Reliable Assessment of Athletic Training Students' Clinical Skills

    Science.gov (United States)

    Armstrong, Kirk J.; Jarriel, Amanda J.

    2016-01-01

    Context: Providing students reliable objective feedback regarding their clinical performance is of great value for ongoing clinical skill assessment. Since a standardized patient (SP) is trained to consistently portray the case, students can be assessed and receive immediate feedback within the same clinical encounter; however, no research, to our…

  7. Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania.

    Directory of Open Access Journals (Sweden)

    Francis Mhimbira

    2017-02-01

    Full Text Available Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.Between November 2013 and October 2015, we enrolled adult (≥18 years sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB.A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972 were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597 and 25.9% (97/375 among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161, followed by hookworm (9.0%, 87 and Schistosoma mansoni (5.7%, 55. An infection with any helminth was not associated with TB (adjusted odds ratio (aOR 1.26, 95% confidence interval (CI: 0.88-1.80, p = 0.22, but S. mansoni infection was (aOR 2.15, 95% CI: 1.03-4.45, p = 0.040. Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38-5.26, p = 0.004 and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12-1.16, p = 0.088.S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB. Treatment of helminths should be considered in clinical management of

  8. Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical relevance of histological findings.

    Science.gov (United States)

    Pratschke, K M; Ryan, J; McAlinden, A; McLauchlan, G

    2015-01-01

    To assess the immediate postoperative complications associated with pancreatic biopsy in dogs and cats and review the clinical relevance of biopsy findings. Retrospective review of clinical records from two referral institutions for cases undergoing pancreatic biopsy between 2000 and 2013. Twenty-four dogs and 19 cats that had surgical pancreatic biopsy had sufficient detail in their clinical records and fulfilled the inclusion criteria. Postoperative complications were seen in 10 cases of which 5 were suggestive of post-surgical pancreatitis. Two patients were euthanased within 10 days of surgery because of the underlying disease; neither suffered postoperative complications. Pancreatic pathology was found in 19 cases, 7 cases showed no change other than benign pancreatic nodular hyperplasia, and no abnormalities were seen in 18 cases. Complications may be encountered following surgical pancreatic biopsy, although the risk should be minimal with good surgical technique. Pancreatic biopsy may provide a useful contribution to case management but it is not clear whether a negative pancreatic biopsy should be used to rule out pancreatic disease. Dogs were more likely to have no significant pathology found on pancreatic biopsy than cats, where chronic pancreatitis was the most common finding. © 2014 British Small Animal Veterinary Association.

  9. The relevance of clinical ethnography: reflections on 10 years of a cultural consultation service.

    Science.gov (United States)

    Dominicé Dao, Melissa; Inglin, Sophie; Vilpert, Sarah; Hudelson, Patricia

    2018-01-11

    Training health professionals in culturally sensitive medical interviewing has been widely promoted as a strategy for improving intercultural communication and for helping clinicians to consider patients' social and cultural contexts and improve patient outcomes. Clinical ethnography encourages clinicians to explore the patient's explanatory model of illness, recourse to traditional and alternative healing practices, healthcare expectations and social context, and to use this information to negotiate a mutually acceptable treatment plan. However, while clinical ethnographic interviewing skills can be successfully taught and learned, the "real-world" context of medical practice may impose barriers to such patient-centered interviewing. Creating opportunities for role modeling and critical reflection may help overcome some of these barriers, and contribute to improved intercultural communication in healthcare. We report and reflect on a retrospective analysis of 10 years experience with a "cultural consultation service" (CCS) whose aim is to provide direct support to clinicians who encounter intercultural difficulties and to model the usefulness of clinical ethnographic interviewing for patient care. We analyzed 236 cultural consultation requests in order to identify key patient, provider and consultation characteristics, as well as the cross cultural communication challenges that motivate health care professionals to request a cultural consultation. In addition, we interviewed 51 clinicians about their experience and satisfaction with the CCS. Requests for cultural consultations tended to involve patient care situations with complex social, cultural and medical issues. All patients had a migration background, two-thirds spoke French less than fluently. In over half the cases, patients had a high degree of social vulnerability, compromising illness management. Effective communication was hindered by language barriers and undetected or underestimated patient/provider

  10. Clinical relevance of [i]Corylus[/i] pollen in Poznań, western Poland

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    Łukasz Grewling

    2014-03-01

    Full Text Available Background. In Central Europe, hazel ([i]Corylus[/i] sp. pollen is considered to be an important aeroallergen in early spring. Objective. This study examines hazel pollen levels in Poznań, western Poland, and the clinical relevance of this aeroallergen in the city. Methods. [i]Corylus[/i] pollen data (1996–2010 were obtained by volumetric spore trap located near the centre of Poznań. Clinical data (2006–2010, i.e. skin prick test (SPT and allergen-specific IgE measurements (asIgE, were supplied by the Allergy Diseases Diagnostic Centre in Poznań. Results. Mean diurnal hazel pollen concentrations peaked around 14:00–16:00 when mean bi-hourly pollen concentrations were ~60 P m-3. Onset of the hazel pollen season varied up to 87 days annually, and was significantly (r=–0.647; p<0.01 related to mean maximum temperature during late December. SPT data revealed that ~11% of allergy patients had positive skin reactions to [i]Corylus[/i] pollen allergens, and most of these (94.4% reacted to pollen allergens from other members of the Betulaceae family – alder or birch. Of those sensitized, 53% suffered from atopic dermatitis. Of patients examined for serum asIgE, 26.0% had asIgE measurements in classes 5 and 6. Conclusions. Hazel pollen has a detrimental effect on the allergic population of Poznań, with more than half of those sensitised to hazel pollen allergens showing symptoms of atopic dermatitis. Hazel pollen concentrations reach levels recognized as being able to induce allergy symptoms, especially in the afternoon and early evening when many people are returning home from work. The cross-reactivity with other members of the Fagales order also increases the allergenic potential of hazel pollen.

  11. CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients.

    Science.gov (United States)

    Maouia, A; Youssef, M; Leban, N; Ben Chibani, J; Helal, A N; Kassab, A

    2017-12-01

    Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least six weeks. Multifactorial origin is suggested such as oxidative stress. This latter may play a double role as a trigger and remnant agent. The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: desloratadine 5 mg/d on these different parameters. This study enrolled 30 CSU patients and same number of controls. We assessed the urticaria activity score (UAS), total antioxidant status (TAS), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), albumin, alpha1, alpha2, beta1 beta2, gamma globulins, c-reactive protein (CRP) and hematologic numeration. At baseline alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus controls (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were significantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CRP, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p < 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 d-antihistaminic treatment. Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients' remission was synergistic to CRP attenuation emphasizing CRP relevance for CSU clinical assessment.

  12. Clinical Relevance of Sleep Duration: Results from a Cross-Sectional Analysis Using NHANES.

    Science.gov (United States)

    Cepeda, M Soledad; Stang, Paul; Blacketer, Clair; Kent, Justine M; Wittenberg, Gayle M

    2016-06-15

    To assess the clinical relevance of sleep duration, hours slept were compared by health status, presence of insomnia, and presence of depression, and the association of sleep duration with BMI and cardiovascular risk was quantified. Cross-sectional analysis of subjects in the US National Health and Nutrition Examination Surveys using adjusted linear and logistic regressions. A total of 22,281 adults were included, 37% slept ≤ 6 hours, 36% were obese, and 45% reported cardiovascular conditions. Mean sleep duration was 6.87 hours. Better health was associated with more hours of sleep. Subjects with poor health reported sleeping 46 min, (95% CI -56.85 to -35.67) less than subjects with excellent health. Individuals with depression (vs. not depressed) reported 40 min less sleep, (95% CI -47.14 to -32.85). Individuals with insomnia (vs. without insomnia) reported 39 min less sleep, (95% CI -56.24 to -22.45). Duration of sleep was inversely related to BMI; for every additional hour of sleep, there was a decrease of 0.18 kg/m(2) in BMI, (95% CI -0.30 to -0.06). The odds of reporting cardiovascular problems were 6.0% lower for every hour of sleep (odds ratio = 0.94, 95% CI [0.91 to 0.97]). Compared with subjects who slept ≤ 6 h, subjects who slept more had lower odds of reporting cardiovascular problems, with the exception of subjects ≥ 55 years old who slept ≥ 9 hours. Long sleep duration is associated with better health. The fewer the hours of sleep, the greater the BMI and reported cardiovascular disease. A difference of 30 minutes of sleep is associated with substantive impact on clinical well-being. © 2016 American Academy of Sleep Medicine.

  13. Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats.

    Science.gov (United States)

    Turner, Ryan C; Naser, Zachary J; Logsdon, Aric F; DiPasquale, Kenneth H; Jackson, Garrett J; Robson, Matthew J; Gettens, Robert T T; Matsumoto, Rae R; Huber, Jason D; Rosen, Charles L

    2013-10-01

    Blast-induced traumatic brain injury represents a leading cause of injury in modern warfare with injury pathogenesis poorly understood. Preclinical models of blast injury remain poorly standardized across laboratories and the clinical relevance unclear based upon pulmonary injury scaling laws. Models capable of high peak overpressures and of short duration may better replicate clinical exposure when scaling principles are considered. In this work we demonstrate a tabletop shock tube model capable of high peak overpressures and of short duration. By varying the thickness of the polyester membrane, peak overpressure can be controlled. We used membranes with a thickness of 0.003, 0.005, 0.007, and 0.010 in to generate peak reflected overpressures of 31.47, 50.72, 72.05, and 90.10 PSI, respectively. Blast exposure was shown to decrease total activity and produce neural degeneration as indicated by fluoro-jade B staining. Similarly, blast exposure resulted in increased glial activation as indicated by an increase in the number of glial fibrillary acidic protein expressing astrocytes compared to control within the corpus callosum, the region of greatest apparent injury following blast exposure. Similar findings were observed with regard to activated microglia, some of which displayed phagocytic-like morphology within the corpus callosum following blast exposure, particularly with higher peak overpressures. Furthermore, hematoxylin and eosin staining showed the presence of red blood cells within the parenchyma and red, swollen neurons following blast injury. Exposure to blast with 90.10 PSI peak reflected overpressure resulted in immediate mortality associated with extensive intracranial bleeding. This work demonstrates one of the first examples of blast-induced brain injury in the rodent when exposed to a blast wave scaled from human exposure based on scaling principles derived from pulmonary injury lethality curves. © 2013.

  14. A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling.

    Science.gov (United States)

    Eyckmans, J; Roberts, S J; Schrooten, J; Luyten, F P

    2010-06-01

    In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the 'osteoinductive program'. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.

  15. Clinical relevance of infections with zoonotic and human oral species of Campylobacter.

    Science.gov (United States)

    Lee, Soomin; Lee, Jeeyeon; Ha, Jimyeong; Choi, Yukyung; Kim, Sejeong; Lee, Heeyoung; Yoon, Yohan; Choi, Kyoung-Hee

    2016-07-01

    Genus Campylobacter has been recognized as a causative bacterial agent of animal and human diseases. Human Campylobacter infections have caused more concern. Campylobacters can be classified into two groups in terms of their original host: zoonotic and human oral species. The major zoonotic species are Campylobacter jejuni and Campylobacter coli, which mostly reside in the intestines of avian species and are transmitted to humans via consumption of contaminated poultry products, thus causing human gastroenteritis and other diseases as sequelae. The other campylobacters, human oral species, include C. concisus, C. showae, C. gracilis, C. ureolyticus, C. curvus, and C. rectus. These species are isolated from the oral cavity, natural colonization site, but have potential clinical relevance in the periodontal region to varying extent. Two species, C. jejuni and C. coli, are believed to be mainly associated with intestinal diseases, but recent studies suggested that oral Campylobacter species also play a significant role in intestinal diseases. This review offers an outline of the two Campylobacter groups (zoonotic and human oral), their virulence traits, and the associated illnesses including gastroenteritis.

  16. Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.

    Science.gov (United States)

    König, Maximilian; Spira, Dominik; Demuth, Ilja; Steinhagen-Thiessen, Elisabeth; Norman, Kristina

    2017-12-12

    Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI.

  17. Analysis of clinically relevant mechanical and thermal characteristics of titanium foam spinal implants during drilling.

    Science.gov (United States)

    Ito, Kiyoshi; Horiuchi, Tetsuyoshi; Murata, Takahiro; Hongo, Kazuhiro

    2015-09-01

    Although high biocompatibility promotes the use of titanium (Ti) alloy in spinal implants, this material shows high stiffness, which is an issue for removal by drilling. The recently developed, porous Ti foam implants, which have shown enhanced osteoformation, may overcome this flaw. Thus, this study aimed to compare the mechanical and thermal characteristics of Ti-foam (80 % porosity) and conventional Ti alloy (0 % porosity) implants drilled in clinically relevant conditions. Mechanical properties were analyzed by measuring axial and torque forces using a pressure sensor with a drill of 2.5-mm diameter at a rotation frequency of 20 Hz. Thermography was used to evaluate the heat generated by a diamond burr attached to a high-speed (80,000 rpm) drill. The torque and axial strengths of Ti foam (13.63 ± 1.43 and 82.60 ± 7.78 N, respectively) were significantly lower (P = 0.001) than those of Ti alloy (73.58 ± 13.60 and 850.72 ± 146.99 N, respectively). Furthermore, irrigation reduced the area of local heating for Ti foam to 56-82 % of that for Ti alloy, indicating lower thermal conductivity. These data suggest that the use of Ti foam implants may be advantageous in cases with a probability of implant drilling in the future.

  18. Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium

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    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.

  19. NT-ProBNP levels in saliva and its clinical relevance to heart failure.

    Science.gov (United States)

    Foo, Jared Yong Yang; Wan, Yunxia; Kostner, Karam; Arivalagan, Alicia; Atherton, John; Cooper-White, Justin; Dimeski, Goce; Punyadeera, Chamindie

    2012-01-01

    Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (pdiagnostic accuracy of 90.6%. We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

  20. Silica desiccant packets for storage and transport of Streptococcus pneumoniae and other clinically relevant species.

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    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.

  1. Update on the Human Broad Tapeworm (Genus Diphyllobothrium), Including Clinical Relevance

    Science.gov (United States)

    Scholz, Tomáš; Garcia, Hector H.; Kuchta, Roman; Wicht, Barbara

    2009-01-01

    Summary: Tapeworms (Cestoda) continue to be an important cause of morbidity in humans worldwide. Diphyllobothriosis, a human disease caused by tapeworms of the genus Diphyllobothrium, is the most important fish-borne zoonosis caused by a cestode parasite. Up to 20 million humans are estimated to be infected worldwide. Besides humans, definitive hosts of Diphyllobothrium include piscivorous birds and mammals, which represent a significant zoonotic reservoir. The second intermediate hosts include both freshwater and marine fish, especially anadromous species such as salmonids. The zoonosis occurs most commonly in countries where the consumption of raw or marinated fish is a frequent practice. Due to the increasing popularity of dishes utilizing uncooked fish, numerous cases of human infections have appeared recently, even in the most developed countries. As many as 14 valid species of Diphyllobothrium can cause human diphyllobothriosis, with D. latum and D. nihonkaiense being the most important pathogens. In this paper, all taxa from humans reported are reviewed, with brief information on their life history and their current distribution. Data on diagnostics, epidemiology, clinical relevance, and control of the disease are also summarized. The importance of reliable identification of human-infecting species with molecular tools (sequences of mitochondrial genes) as well as the necessity of epidemiological studies aimed at determining the sources of infections are pointed out. PMID:19136438

  2. Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance

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    Yunfei Zha

    2017-01-01

    Full Text Available Purpose. To investigate the reproducibility of aortic distensibility (D measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA. Methods. 54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1. and at the level of its maximal diameter (level 2. by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aortic D and anthropometric and biochemical parameters. Results. A mean distensibility of Dlevel  1.=(1.05±0.22×10-5  Pa-1 and Dlevel  2.=(0.49±0.18×10-5  Pa-1 was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2=0.68 to BMI, diastolic blood pressure, and AAA diameter. Conclusions. Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

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

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    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.

  4. Clinical relevancy and risks of potential drug-drug interactions in intensive therapy.

    Science.gov (United States)

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava

    2015-09-01

    Evaluate the potential Drug-Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Prospective study (January-December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to "avoid concomitant use" or "suspension of medication", while 306 had as recommendation "continuous and adequate monitoring". The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management.

  5. Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects

    Science.gov (United States)

    Schlumpf, Yolanda; Spinelli, Simona; Späti, Jakub; Brakowski, Janis; Quednow, Boris B.; Seifritz, Erich; Grosse Holtforth, Martin

    2014-01-01

    Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus–amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top–down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material. PMID:23887820

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

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    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.

  7. 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.

  8. Clinically relevant depressive symptoms in young stroke patients - results of the sifap1 study.

    Science.gov (United States)

    Tanislav, Christian; Kropp, Peter; Grittner, Ulrike; Holzhausen, Martin; Fazekas, Franz; Jungehülsing, Gerhard Jan; Tatlisumak, Turgut; von Sarnowski, Bettina; Putaala, Jukka; Huber, Roman; Thijs, Vincent; Schmidt, Reinhold; Kaps, Manfred; Enzinger, Christian; Dichgans, Martin; Norrving, Bo; Rolfs, Arndt

    2015-01-01

    Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort. The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed. From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found. Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings. © 2015 S. Karger AG, Basel.

  9. [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.

  10. Protein engineering strategies with potential applications for altering clinically relevant cellular pathways at the protein level.

    Science.gov (United States)

    Regan, Lynne; Hinrichsen, Michael R; Oi, Curran

    2016-05-01

    All diseases can be fundamentally viewed as the result of malfunctioning cellular pathways. Protein engineering offers the potential to develop new tools that will allow these dysfunctional pathways to be better understood, in addition to potentially providing new routes to restore proper function. Here we discuss different approaches that can be used to change the intracellular activity of a protein by intervening at the protein level: targeted protein sequestration, protein recruitment, protein degradation, and selective inhibition of binding interfaces. The potential of each of these tools to be developed into effective therapeutic treatments will also be discussed, along with any major barriers that currently block their translation into the clinic.

  11. Cultural differences in assessing dietary intake and providing relevant dietary information to British African-Caribbean populations.

    Science.gov (United States)

    Sharma, S; Cruickshank, J K

    2001-12-01

    Diet can play a key role in the management of disorders such as obesity, diabetes and hypertension, conditions highly prevalent in the British African Caribbean population. In this paper, information not previously available is provided on the dietary habits and foods consumed by a British African-Caribbean population representative of the local community. Food frequency questionnaires were obtained from 255 randomly selected subjects in Manchester (78% of Jamaican origin), the nutrient intake results of which are available elsewhere. Here, suggestions are given to ensure that complete and valid dietary assessments (by diet history) are obtained, and the need for the approach to be somewhat different to that used in the White European population, highlighted with examples. Suggestions have also been listed for methods of dietary modification for obesity, diabetes and hypertension, taking into account differences in cultural understanding and food practices. People of Caribbean origin are not from just one territory: food habits and cultural context play an important role in every island, with clear differences between each which persist in first and later generations in Britain. In this paper, we attempt to integrate experience of learning from patients themselves during consultations and from participants in this study, with direct quantitative data on types of foods and their frequency in the local African-Caribbean diet.

  12. The inter-relationship of clinical parameters in congenital talipes equinovarus: relevance to pathological anatomy and clinical classification.

    Science.gov (United States)

    Siddique, I; Choudry, Q; Paton, R W

    2012-03-01

    The clinical features that define congenital talipes equinovarus (CTEV) are the presence of four principal components, equinus, varus, adductus and cavus. Classification systems in CTEV often include a form of assessment of these components and also other concurrent clinical parameters which feature in the condition. Over a 14-year period from 1992 to 2006, 95 consecutive cases of CTEV were prospectively assessed and data recorded in order to investigate the relationships between the clinical parameters in CTEV and to compare these relationships with those that one would expect from our knowledge of the pathological anatomy and mechanics of the condition, relating these findings to the commonly used systems for classification. Ninety-five cases of CTEV had failed conservative treatment and had undergone surgical release. The mean age at surgical release and assessment was 9 months. Cluster analysis demonstrated that there were, broadly, two groups of patients. The first group was those patients with a greater equinus deformity (greater than 31°). This group had a greater adductus deformity and the presence of other parameters indicating increased severity (multiplanar stiffness with the presence of cavus and medial skin crease). The second group was those patients with a smaller equinus deformity (less than 31°) who were more heterogenous with regards to the other parameters. We analysed on a statistical basis the relevant aspects of the deformity in CTEV. We have demonstrated that there are certain parameters, namely, equinus and adductus, whose severity can reasonably predict the severity of other components of the deformity. With regards to hindfoot parameters, increased equinus is related to less sagittal plane reducibility and to stiff hindfoot varus (coronal plane stiffness). In terms of midfoot parameters, the degree of adductus is related to the presence of cavus deformity and the presence of a medial skin crease is associated with less reducibility of

  13. Paper-based microfluidic devices for analysis of clinically relevant analytes present in urine and saliva.

    Science.gov (United States)

    Klasner, Scott A; Price, Alexander K; Hoeman, Kurt W; Wilson, Rashaun S; Bell, Kayla J; Culbertson, Christopher T

    2010-07-01

    We report the use of paper-based microfluidic devices fabricated from a novel polymer blend for the monitoring of urinary ketones, glucose, and salivary nitrite. Paper-based devices were fabricated via photolithography in less than 3 min and were immediately ready for use for these diagnostically relevant assays. Patterned channels on filter paper as small as 90 microm wide with barriers as narrow as 250 microm could be reliably patterned to permit and block fluid wicking, respectively. Colorimetric assays for ketones and nitrite were adapted from the dipstick format to this paper microfluidic chip for the quantification of acetoacetate in artificial urine, as well as nitrite in artificial saliva. Glucose assays were based on those previously demonstrated (Martinez et al., Angew Chem Int Ed 8:1318-1320, 1; Martinez et al., Anal Chem 10:3699-3707, 2; Martinez et al., Proc Nat Acad Sci USA 50:19606-19611, 3; Lu et al., Electrophoresis 9:1497-1500, 4; Abe et al., Anal Chem 18:6928-6934, 5). Reagents were spotted on the detection pad of the paper device and allowed to dry prior to spotting of samples. The ketone test was a two-step reaction requiring a derivitization step between the sample spotting pad and the detection pad, thus for the first time, confirming the ability of these paper devices to perform online multi-step chemical reactions. Following the spotting of the reagents and sample solution onto the paper device and subsequent drying, color images of the paper chips were recorded using a flatbed scanner, and images were converted to CMYK format in Adobe Photoshop CS4 where the intensity of the color change was quantified using the same software. The limit of detection (LOD) for acetoacetate in artificial urine was 0.5 mM, while the LOD for salivary nitrite was 5 microM, placing both of these analytes within the clinically relevant range for these assays. Calibration curves for urinary ketone (5 to 16 mM) and salivary nitrite (5 to 2,000 microM) were

  14. Communication latencies of Apple push notification messages relevant for delivery of time-critical information to anesthesia providers.

    Science.gov (United States)

    Rothman, Brian S; Dexter, Franklin; Epstein, Richard H

    2013-08-01

    Tablet computers and smart phones have gained popularity in anesthesia departments for educational and patient care purposes. VigiVU(™) is an iOS application developed at Vanderbilt University for remote viewing of perioperative information, including text message notifications delivered via the Apple Push Notification (APN) service. In this study, we assessed the reliability of the APN service. Custom software was written to send a message every minute to iOS devices (iPad(®), iPod Touch(®), and iPhone(®)) via wireless local area network (WLAN) and cellular pathways 24 hours a day over a 4-month period. Transmission and receipt times were recorded and batched by days, with latencies calculated as their differences. The mean, SEM, and the exact 95% upper confidence limits for the percent of days with ≥1 prolonged (>100 seconds) latency were calculated. Acceptable performance was defined as mean latency 100 seconds. Testing conditions included fixed locations of devices in high signal strength locations. Mean latencies were 173,000 iPad and iPod latencies, none were >100 seconds. For iPhone latencies, 0.03% ± 0.01% were >100 seconds. The 95% upper confidence limits of days with ≥1 prolonged latency were 42% (iPhone) and 5% to 8% (iPad, iPod). The APN service was reliable for all studied devices over WLAN and cellular pathways, and performance was better than third party paging systems using Internet connections previously investigated using the same criteria. However, since our study was a best-case assessment, testing is required at individual sites considering use of this technology for critical messaging. Furthermore, since the APN service may fail due to Internet or service provider disruptions, a backup paging system is recommended if the APN service were to be used for critical messaging.

  15. A Clinically Relevant Method of Analyzing Continuous Change in Robotic Upper Extremity Chronic Stroke Rehabilitation.

    Science.gov (United States)

    Massie, Crystal L; Du, Yue; Conroy, Susan S; Krebs, H Igo; Wittenberg, George F; Bever, Christopher T; Whitall, Jill

    2016-09-01

    Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. Significant improvement (P robotic interventions. © The Author(s) 2015.

  16. Digital photo documentation of forensically relevant injuries as part of the clinical first response protocol.

    Science.gov (United States)

    Verhoff, Marcel A; Kettner, Mattias; Lászik, András; Ramsthaler, Frank

    2012-09-01

    A problem encountered by medical examiners is that they have to assess injuries that have already been medically treated. Thus, they have to base their reports on clinical forensic examinations performed hours or days after an injury was sustained, or even base their assessment solely on information gleaned from medical files. In both scenarios, the forensic examiner has to rely heavily on the first responder's documentation of the original injury pattern. Medical priority will be to immediately treat a patient's injuries, and the first responder may, in addition, initially be unaware of a possibly criminal origin of an injury. As a result, the documentation of injuries is frequently of limited value for forensic purposes. This situation could be improved if photographic records were briefly made of injuries before they were treated. German-language medicolegal, criminal, and photography journals and books were selectively searched with the help of PubMed and other databases. In addition, the authors' experiences in creating and evaluating photographic records for clinical forensic use were assessed. This paper is an aid to creating photographic records of sufficient quality for forensic purposes. The options provided by digital photography in particular make this endeavor feasible even in a clinical setting. In addition, our paper illuminates some technical aspects of creating and archiving photographic records for forensic use, and addresses possible error sources. With the requisite technical background knowledge, injuries can be photographically recorded to forensic standards during patient care.

  17. 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.

  18. DGIdb 2.0: mining clinically relevant drug–gene interactions

    Science.gov (United States)

    Wagner, Alex H.; Coffman, Adam C.; Ainscough, Benjamin J.; Spies, Nicholas C.; Skidmore, Zachary L.; Campbell, Katie M.; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F.; Eldred, James M.; Walker, Jason R.; Wilson, Richard K.; Mardis, Elaine R.; Griffith, Malachi; Griffith, Obi L.

    2016-01-01

    The Drug–Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug–gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug–gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug–gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation. PMID:26531824

  19. 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.

  20. Planning clinically relevant biomarker validation studies using the "number needed to treat" concept.

    Science.gov (United States)

    Day, Roger S

    2016-05-04

    Despite an explosion of translational research to exploit biomarkers in diagnosis, prediction and prognosis, the impact of biomarkers on clinical practice has been limited. The elusiveness of clinical utility may partly originate when validation studies are planned, from a failure to articulate precisely how the biomarker, if successful, will improve clinical decision-making for patients. Clarifying what performance would suffice if the test is to improve medical care makes it possible to design meaningful validation studies. But methods for tackling this part of validation study design are undeveloped, because it demands uncomfortable judgments about the relative values of good and bad outcomes resulting from a medical decision. An unconventional use of "number needed to treat" (NNT) can structure communication for the trial design team, to elicit purely value-based outcome tradeoffs, conveyed as the endpoints of an NNT "discomfort range". The study biostatistician can convert the endpoints into desired predictive values, providing criteria for designing a prospective validation study. Next, a novel "contra-Bayes" theorem converts those predictive values into target sensitivity and specificity criteria, to guide design of a retrospective validation study. Several examples demonstrate the approach. In practice, NNT-guided dialogues have contributed to validation study planning by tying it closely to specific patient-oriented translational goals. The ultimate payoff comes when the report of the completed study includes motivation in the form of a biomarker test framework directly reflecting the clinical decision challenge to be solved. Then readers will understand better what the biomarker test has to offer patients.

  1. Validation and clinical relevance of a French-Canadian version of the spinal appearance questionnaire in adolescent patients.

    Science.gov (United States)

    Roy-Beaudry, Marjolaine; Beauséjour, Marie; Joncas, Julie; Forcier, Martin; Bekhiche, Sara; Labelle, Hubert; Grimard, Guy; Parent, Stefan

    2011-04-20

    discriminate between relevant clinical values, thus providing useful information for the clinical management of adolescent idiopathic scoliosis patients.

  2. Clinically Relevant Cut-off Points for the Diagnosis of Sarcopenia in Older Korean People.

    Science.gov (United States)

    Choe, Yu-Ri; Joh, Ju-Youn; Kim, Yeon-Pyo

    2017-11-09

    The optimal criteria applied to older Korean people have not been defined. We aimed to define clinically relevant cut-off points for older Korean people and to compare the predictive validity with other definitions of sarcopenia. Nine hundred and sixteen older Koreans (≥65 years) were included in this cross-sectional observational study. We used conditional inference tree analysis to determine cut-off points for height-adjusted grip strength (GS) and appendicular skeletal muscle mass (ASM), for use in the diagnosis of sarcopenia. We then compared the Korean sarcopenia criteria with the Foundation for the National Institutes of Health and Asian Working Group for Sarcopenia criteria, using frailty, assessed with the Korean Frailty Index, as an outcome variable. For men, a residual GS (GSre) of ≤ 0.25 was defined as weak, and a residual ASM (ASMre) of ≤ 1.29 was defined as low. Corresponding cut-off points for women were a GSre of ≤ 0.17 and an ASMre of ≤ 0.69. GSre and ASMre values were adjusted for height. In logistic regression analysis with new cut-off points, the adjusted odds ratios for pre-frail or frail status in the sarcopenia group were 3.23 (95% confidence interval [CI] 1.33-7.83) for the men and 1.74 (95% CI 0.91-3.35) for the women. In receiver operating characteristic curve analysis, the unadjusted area under the curve for Korean sarcopenia criteria in men and women were 0.653 and 0.608, respectively (p sarcopenia in older Korean people.

  3. Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species.

    Science.gov (United States)

    Correia, Amabel Fernandes; Silveira, Dâmaris; Fonseca-Bazzo, Yris Maria; Magalhães, Pérola Oliveira; Fagg, Christopher William; da Silva, Elton Clementino; Gomes, Suelí Maria; Gandolfi, Lenora; Pratesi, Riccardo; de Medeiros Nóbrega, Yanna Karla

    2016-07-11

    Medicinal plants have traditionally been used in many parts of the world as alternative medicine. Many extracts and essential oils isolated from plants have disclosed biological activity, justifying the investigation of their potential antimicrobial activity. In this study, the in vitro antifungal activity of six Brazilian Cerrado medicinal plant species were evaluated against clinically relevant Candida species. The crude extract plants were evaluated against American Type Culture Collection (ATCC) standard strains of Candida spp. using disk diffusion method and determining the minimum inhibitory concentration (MIC). The chemical study results were confirmed by HPLC method. All six plant species showed antifungal activity. Among the species studied, Eugenia dysenterica and Pouteria ramiflora showed significant inhibitory activity against C. tropicalis at lowest MIC value of 125 and 500 μg/disc, respectively. The Eugenia dysenterica also disclosed MIC value of 125 μg/disc against C. famata, 250 μg/disc against C. krusei and 500 μg/disc against C. guilliermondii and C. parapsilosis. Pouteria torta, Bauhinia rufa, Erythroxylum daphnites and Erythroxylum subrotundum showed activity against the yeast strains with MIC value of 1000 μg/disc. The chemical study of the most bioactive extracts of Eugenia dysenterica and Pouteria ramiflora revealed catechin derivatives and flavonoids as main components. All six evaluated plant species showed good antifungal potential against several Candida strains. However, E .dysenterica and P. ramiflora showed the higher inhibitory effect against the non-albicans Candida species. Our results may contribute to the continuing search of new natural occurring products with antifungal activity.

  4. 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.

  5. 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.

  6. Pharmacokinetics of (synthetic) cannabinoids in pigs and their relevance for clinical and forensic toxicology.

    Science.gov (United States)

    Schaefer, Nadine; Wojtyniak, Jan-Georg; Kettner, Mattias; Schlote, Julia; Laschke, Matthias W; Ewald, Andreas H; Lehr, Thorsten; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

    2016-06-24

    Synthetic cannabinoids (SCs) are gaining increasing importance in clinical and forensic toxicology. They are consumed without any preclinical safety studies. Thus, controlled human pharmacokinetic (PK) studies are not allowed, although being relevant for interpretation of analytical results in cases of misuse or poisoning. As alternative, in a controlled animal experiment, six pigs per drug received a single intravenous dose of 200μg/kg BW each of Δ(9)-tetrahydrocannabinol (THC), 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210), or 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4). In addition, six pigs received a combination of the three drugs with the identical dose each. The drugs were determined in serum using LC-MS/MS. A population (pop) PK analysis revealed that a three-compartment model described best the PK data of all three cannabinoids. Central volumes of distribution were estimated at 0.29L/kg, 0.20L/kg, and 0.67L/kg for THC, JWH-210, and RCS-4, respectively. Clearances were 0.042L/min/kg, 0.048L/min/kg, and 0.093L/min/kg for THC, JWH-210, and RCS-4, respectively. The popPK THC pig model was upscaled to humans using allometric techniques. Comparison with published human data revealed that the concentration-time profiles could successfully be predicted. These findings indicate that pigs in conjunction with PK modeling technique may serve as a tool for prediction of human PK of SCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Anatomical masking of pressure footprints based on the Oxford Foot Model: validation and clinical relevance.

    Science.gov (United States)

    Giacomozzi, Claudia; Stebbins, Julie A

    2017-03-01

    Plantar pressure analysis is widely used in the assessment of foot function. In order to assess regional loading, a mask is applied to the footprint to sub-divide it into regions of interest (ROIs). The most common masking method is based on geometric features of the footprint (GM). Footprint masking based on anatomical landmarks of the foot has been implemented more recently, and involves the integration of a 3D motion capture system, plantar pressure measurement device, and a multi-segment foot model. However, thorough validation of anatomical masking (AM) using pathological footprints has not yet been presented. In the present study, an AM method based on the Oxford Foot Model (OFM) was compared to an equivalent GM. Pressure footprints from 20 young healthy subjects (HG) and 20 patients with clubfoot (CF) were anatomically divided into 5 ROIs using a subset of the OFM markers. The same foot regions were also identified by using a standard GM method. Comparisons of intra-subject coefficient of variation (CV) showed that the OFM-based AM was at least as reliable as the GM for all investigated pressure parameters in all foot regions. Clinical relevance of AM was investigated by comparing footprints from HG and CF groups. Contact time, maximum force, force-time integral and contact area proved to be sensitive parameters that were able to distinguish HG and CF groups, using both AM and GM methods However, the AM method revealed statistically significant differences between groups in 75% of measured variables, compared to 62% using a standard GM method, indicating that the AM method is more sensitive for revealing differences between groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Key differences between 13 KRAS mutation detection technologies and their relevance for clinical practice

    Science.gov (United States)

    Sherwood, James L; Brown, Helen; Rettino, Alessandro; Schreieck, Amelie; Clark, Graeme; Claes, Bart; Agrawal, Bhuwnesh; Chaston, Ria; Kong, Benjamin S G; Choppa, Paul; Nygren, Anders O H; Deras, Ina L; Kohlmann, Alexander

    2017-01-01

    Introduction This study assessed KRAS mutation detection and functional characteristics across 13 distinct technologies and assays available in clinical practice, in a blinded manner. Methods Five distinct KRAS-mutant cell lines were used to study five clinically relevant KRAS mutations: p.G12C, p.G12D, p.G12V, p.G13D and p.Q61H. 50 cell line admixtures with low (50 and 100) mutant KRAS allele copies at 20%, 10%, 5%, 1% and 0.5% frequency were processed using quantitative PCR (qPCR) (n=3), matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) (n=2), next-generation sequencing (NGS) (n=6), digital PCR (n=1) and Sanger capillary sequencing (n=1) assays. Important performance differences were revealed, particularly assay sensitivity and turnaround time. Results Overall 406/728 data points across all 13 technologies were identified correctly. Successful genotyping of admixtures ranged from 0% (Sanger sequencing) to 100% (NGS). 5/6 NGS platforms reported similar allelic frequency for each sample. One NGS assay detected mutations down to a frequency of 0.5% and correctly identified all 56 samples (Oncomine Focus Assay, Thermo Fisher Scientific). One qPCR (Idylla, Biocartis) and MALDI-TOF (UltraSEEK, Agena Bioscience) assay identified 96% (all 100 copies and 23/25 at 50 copies input) and 92% (23/25 at 100 copies and 23/25 at 50 copies input) of samples, respectively. The digital PCR assay (KRAS PrimePCR ddPCR, Bio-Rad Laboratories) identified 60% (100 copies) and 52% (50 copies) of samples correctly. Turnaround time from sample to results ranged from ~2 hours (Idylla CE-IVD) to 2 days (TruSight Tumor 15 and Sentosa CE-IVD), to 2 weeks for certain NGS assays; the level of required expertise ranged from minimal (Idylla CE-IVD) to high for some technologies. Discussion This comprehensive parallel assessment used high molecular weight cell line DNA as a model system to address key questions for a laboratory when implementing routine

  9. NT-ProBNP levels in saliva and its clinical relevance to heart failure.

    Directory of Open Access Journals (Sweden)

    Jared Yong Yang Foo

    Full Text Available BACKGROUND: Current blood based diagnostic assays to detect heart failure (HF have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. METHODS: Saliva samples were collected from healthy volunteers (n = 40 who had no underlying heart conditions and HF patients (n = 45 at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R immunoassay was used to quantify NT-proBNP levels in saliva. RESULTS: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37 and the correlation was r(2 = 0.78 (p<0.01, y = 1.705× +1910.8. The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. CONCLUSION: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

  10. Clinical relevance of circulating cell-free microRNAs in ovarian cancer.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Yoshimura, Akihiko; Kinose, Yasuto; Nakatsuka, Erika; Kimura, Tadashi

    2016-06-24

    Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to

  11. Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia.

    Science.gov (United States)

    Yamada, S; Hongo, T; Okada, S; Watanabe, C; Fujii, Y; Ohzeki, T

    2001-12-01

    To determine the clinical relevance of in vitro drug chemoresistance in childhood acute myeloid leukemia, we used an MTT assay to test leukemic cells from 132 newly diagnosed children. Patients were diagnosed according to the French-American-British (FAB) classification as follows: M0 (n = 12), M1 (n = 16), M2 (n = 53), M4 (n = 17), M5 (n = 19) and M7 (n = 15). The results revealed that, compared to leukemic cells from complete-responders (n = 107), those from non-responders who failed induction therapy (n = 17) were 1.4 to 5.0 times more resistant in vitro to cytarabine (P = 0.005), melphalan (P = 0.003), etoposide (P = 0.011), L-asparaginase (P = 0.017), aclarubicin (P = 0.026) and dexamethasone (P = 0.039). For seven other drugs tested, the median lethal dose of 70% and leukemic cell survival of non-responders were higher than those of complete-responders, but the difference was not statistically significant. We sought correlations between FAB subtypes and in vitro drug resistance. Leukemias of the FAB M4 and M5 subtype were more sensitive to L-asparaginase (P = 0.01, P = 0.0036) than those of the FAB M2 subtype. FAB M5 leukemia was more sensitive to etoposide than were the FAB M2, M4 and M7 subtypes (P = 0.001, P = 0.034, P = 0.023, respectively). By contrast, FAB M5 leukemia was significantly more resistant to prednisolone and dexamethasone than were the FAB M0, M1, M2, M4 and M7 subtypes. We sought correlations between in vitro drug resistance and long-term clinical outcome, but found no associations in this case. These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy. Selecting an appropriate anti-cancer drug according to the FAB classification together with drug sensitivity testing may contribute to improved prognoses in childhood acute myeloid leukemia.

  12. The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers | Office of Cancer Genomics

    Science.gov (United States)

    Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions.

  13. Changing Provider Behavior in the Context of Chronic Disease Management: Focus on Clinical Inertia.

    Science.gov (United States)

    Lavoie, Kim L; Rash, Joshua A; Campbell, Tavis S

    2017-01-06

    Widespread acceptance of evidence-based medicine has led to the proliferation of clinical practice guidelines as the primary mode of communicating current best practices across a range of chronic diseases. Despite overwhelming evidence supporting the benefits of their use, there is a long history of poor uptake by providers. Nonadherence to clinical practice guidelines is referred to as clinical inertia and represents provider failure to initiate or intensify treatment despite a clear indication to do so. Here we review evidence for the ubiquity of clinical inertia across a variety of chronic health conditions, as well as the organizational and system, patient, and provider factors that serve to maintain it. Limitations are highlighted in the emerging literature examining interventions to reduce clinical inertia. An evidence-based framework to address these limitations is proposed that uses behavior change theory and advocates for shared decision making and enhanced guideline development and dissemination.

  14. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

    Science.gov (United States)

    Sommese, Linda; Zullo, Alberto; Mancini, Francesco Paolo; Fabbricini, Rossella; Soricelli, Andrea; Napoli, Claudio

    2017-01-01

    ABSTRACT Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease. PMID:28059593

  15. Cardiac Magnetic Resonance T1-Mapping of the Myocardium: Technical Background and Clinical Relevance.

    Science.gov (United States)

    Muscogiuri, Giuseppe; Suranyi, Pal; Schoepf, U Joseph; De Cecco, Carlo N; Secinaro, Aurelio; Wichmann, Julian L; Fuller, Stephen R; Lesslie, Virginia W; Varga-Szemes, Akos

    2017-05-02

    Myocardial T1-mapping has become feasible over the past decade as emerging technological magnetic resonance imaging advances enable increasingly rapid and reliable acquisition techniques. A variety of T1-mapping sequences are in development, with most allowing for the acquisition of a single-slice T1-map in a single breath-hold. The development of these protocols has spurred investigation into a wide range of potential clinical uses, including the characterization of cardiomyopathies. Although native T1-mapping provides superior tissue characterization, postcontrast T1-mapping is still indispensable for extracellular volume quantification. Ongoing and future studies should investigate the reliability, reproducibility, accuracy, and precision of available techniques and establish disease-specific reference values for T1-mapping-based parameters.

  16. Mass spectrometric immunoassays for discovery, screening and quantification of clinically relevant proteoforms.

    Science.gov (United States)

    Trenchevska, Olgica; Nelson, Randall W; Nedelkov, Dobrin

    2016-08-01

    Human proteins can exist as multiple proteoforms with potential diagnostic or prognostic significance. MS top-down approaches are ideally suited for proteoforms identification because there is no prerequisite for a priori knowledge of the specific proteoform. One such top-down approach, termed mass spectrometric immunoassay utilizes antibody-derivatized microcolumns for rapid and contained proteoforms isolation and detection via MALDI-TOF MS. The mass spectrometric immunoassay can also provide quantitative measurement of the proteoforms through inclusion of an internal reference standard into the analytical sample, serving as normalizer for all sample processing and data acquisition steps. Reviewed here are recent developments and results from the application of mass spectrometric immunoassays for discovery of clinical correlations of specific proteoforms for the protein biomarkers RANTES, retinol binding protein, serum amyloid A and apolipoprotein C-III.

  17. Is There Value in Having Radiology Provide a Second Reading in Pediatric Orthopaedic Clinic?

    Science.gov (United States)

    Natarajan, Vivek; Bosch, Patrick; Dede, Ozgur; Deeney, Vincent; Mendelson, Stephen; Ward, Timothy; Brooks, Maria; Kenkre, Tanya; Roach, James

    2017-06-01

    The Joint Commission on Accreditation of Healthcare Organizations specifically mandates the dual interpretation of musculoskeletal radiographs by a radiologist in addition to the orthopaedist in all hospital-based orthopaedic clinics. Previous studies have questioned the utility of this practice. The purpose of this study was to further investigate the clinical significance of having the radiologist provide a second interpretation in a hospital-based pediatric orthopaedic clinic. A retrospective review was performed of all patients who had plain radiographs obtained in the pediatric orthopaedic clinic at an academic children's hospital over a 4-month period. For each radiographic series, the orthopaedist's note and the radiology interpretation were reviewed and a determination was made of whether the radiology read provided new clinically useful information and/or a new diagnosis, whether it recommended further imaging, or if it missed a diagnosis that was reflected in the orthopaedist's note. The hospital charges associated with the radiology read for each study were also quantified. The charts of 1570 consecutive clinic patients who were seen in the pediatric orthopaedic clinic from January to April, 2012 were reviewed. There were 2509 radiographic studies performed, of which 2264 had both a documented orthopaedist's note and radiologist's read. The radiologist's interpretation added new, clinically important information in 1.0% (23/2264) of these studies. In 1.7% (38/2264) of the studies, it was determined that the radiologist missed the diagnosis or clinically important information that could affect treatment. The total amount of the professional fees charged for the radiologists' interpretations was $87,362. On average, the hospital charges for each occurrence in which the radiologist's read provided an additional diagnosis or clinically important information beyond the orthopaedist's note were $3798. The results of this study suggest that eliminating the

  18. Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant.

    Science.gov (United States)

    Steenwijk, Martijn D; Geurts, Jeroen J G; Daams, Marita; Tijms, Betty M; Wink, Alle Meije; Balk, Lisanne J; Tewarie, Prejaas K; Uitdehaag, Bernard M J; Barkhof, Frederik; Vrenken, Hugo; Pouwels, Petra J W

    2016-01-01

    %). Several cortical atrophy patterns relevant for multiple sclerosis were found. This suggests that cortical atrophy in multiple sclerosis occurs largely in a non-random manner and develops (at least partly) according to distinct anatomical patterns. In addition, these cortical atrophy patterns showed stronger associations with clinical (especially cognitive) dysfunction than global cortical atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. 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

  20. 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...

  1. 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

  2. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    NARCIS (Netherlands)

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.

    2016-01-01

    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and

  3. Comparative Evaluation of Etest, EUCAST, and CLSI Methods for Amphotericin B, Voriconazole, and Posaconazole against Clinically Relevant Fusarium Species

    NARCIS (Netherlands)

    Al-Hatmi, A.M.; Normand, A.C.; Ranque, S.; Piarroux, R.; Hoog, G.S. de; Meletiadis, J.; Meis, J.F.G.M.

    2017-01-01

    We compared EUCAST and CLSI methods versus Etest for antifungal susceptibility testing of 20 clinically relevant Fusarium species against amphotericin B, posaconazole, and voriconazole. The median Etest amphotericin B and posaconazole MICs were 1 dilution higher than the median EUCAST and the CLSI

  4. 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

    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...

  5. 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.

  6. From Systematic Reviews to Clinical Recommendations for Evidence-Based Health Care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.

    Science.gov (United States)

    Kung, Jason; Chiappelli, Francesco; Cajulis, Olivia O; Avezova, Raisa; Kossan, George; Chew, Laura; Maida, Carl A

    2010-07-16

    Research synthesis seeks to gather, examine and evaluate systematically research reports that converge toward answering a carefully crafted research question, which states the problem patient population, the intervention under consideration, and the clinical outcome of interest. The product of the process of systematically reviewing the research literature pertinent to the research question thusly stated is the "systematic review".The objective and transparent approach of the systematic review aims to minimize bias. Most systematic reviews yield quantitative analyses of measurable data (e.g., acceptable sampling analysis, meta-analysis). Systematic reviews may also be qualitative, while adhering to accepted standards for gathering, evaluating, and reporting evidence. Systematic reviews provide highly rated recommendations for evidence-based health care; but, systematic reviews are not equally reliable and successful in minimizing bias.Several instruments are available to evaluate the quality of systematic reviews. The 'assessment of multiple systematic reviews' (AMSTAR) was derived from factor analysis of the most relevant items among them. AMSTAR consists of eleven items with good face and content validity for measuring the methodological quality of systematic reviews, has been widely accepted and utilized, and has gained in reliability, reproducibility. AMSTAR does not produce quantifiable assessments of systematic review quality and clinical relevance. In this study, we have revised the AMSTAR instrument, detracting nothing from its content and construct validity, and utilizing the very criteria employed in the development of the original tool, with the aim of yielding an instrument that can quantify the quality of systematic reviews. We present validation data of the revised AMSTAR (R-AMSTAR), and discuss its implications and application in evidence-based health care.

  7. Providing support to nursing students in the clinical environment: a nursing standard requirement.

    Science.gov (United States)

    Anderson, Carina; Moxham, Lorna; Broadbent, Marc

    2016-10-01

    This discussion paper poses the question 'What enables or deters Registered Nurses to take up their professional responsibility to support undergraduate nursing students through the provision of clinical education?'. Embedded within many nursing standards are expectations that Registered Nurses provide support and professional development to undergraduate nursing students undertaking clinical placements. Expectations within nursing standards that Registered Nurses provide support and professional development to nursing students are important because nursing students depend on Registered Nurses to help them to become competent practitioners. Contributing factors that enable and deter Registered Nurses from fulfilling this expectation to support nursing students in their clinical learning include; workloads, preparedness for the teaching role, confidence in teaching and awareness of the competency requirement to support students. Factors exist which can enable or deter Registered Nurses from carrying out the licence requirement to provide clinical education and support to nursing students.

  8. Knowledge and Attitudes Towards Clinical Depression among Community Medical Providers in Gujarat, India.

    Science.gov (United States)

    Loh, Daniella A; Joshi, Amul; Taku, Kanako; Mendelsohn, Nathaniel; Katz, Craig L

    2017-09-16

    There is limited data on how community medical providers in India attempt to diagnose and treat depression, as well as on their general knowledge of and attitudes toward depression. A cross-sectional survey was conducted assessing knowledge and views of clinical depression with 80 non-psychiatric physicians and physician trainees recruited from community clinics and hospitals in Gujarat, India. Interviews were also held with 29 of the physicians to assess what they do in their own practices in regards to detection of and treatment of clinical depression. Although subjects showed a generally good basic understanding of the definition of clinical depression and its treatment, their responses reflected the presence of some negative and/or stigmatized attitudes toward clinical depression. Our findings raise the question of possible stigma among physicians themselves and underscore the importance of combatting physicians' stigma against and increasing awareness of how to detect and treat clinical depression.

  9. 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.

  10. 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

  11. 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...

  12. Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm

    Science.gov (United States)

    Tuan, Rocky S.

    2014-01-01

    Tendon and ligament (T/L) are dense connective tissues connecting bone to muscle and bone to bone, respectively. Similar to other musculoskeletal tissues, T/L arise from the somitic mesoderm, but they are derived from a recently discovered somitic compartment, the syndetome. The adjacent sclerotome and myotome provide inductive signals to the interposing syndetome, thereby upregulating the expression of the transcription factor Scleraxis, which in turn leads to further tenogenic and ligamentogenic differentiation. These advances in the understanding of T/L development have been sought to provide a knowledge base for improving the healing of T/L injuries, a common clinical challenge due to the intrinsically poor natural healing response. Specifically, the three most common tendon injuries involve tearing of the rotator cuff of the shoulder, the flexor tendon of the hand, and the Achilles tendon. At present, injuries to these tissues are treated by surgical repair and/or conservative approaches, including biophysical modalities such as physical rehabilitation and cryotherapy. Unfortunately, the healing tissue forms fibrovascular scar and possesses inferior mechanical and biochemical properties as compared to native T/L. Therefore, tissue engineers have sought to improve upon the natural healing response by augmenting the injured tissue with cells, scaffolds, bioactive agents, and mechanical stimulation. These strategies show promise, both in vitro and in vivo, for improving T/L healing. However, several challenges remain in restoring full T/L function following injury, including uncertainties over the optimal combination of these biological agents as well how to best deliver tissue engineered elements to the injury site. A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple growth factors with high spatiotemporal resolution and specificity

  13. 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

  14. New insights on classification, identification, and clinical relevance of Blastocystis spp.

    Science.gov (United States)

    Tan, Kevin S W

    2008-10-01

    Blastocystis is an unusual enteric protozoan parasite of humans and many animals. It has a worldwide distribution and is often the most commonly isolated organism in parasitological surveys. The parasite has been described since the early 1900s, but only in the last decade or so have there been significant advances in our understanding of Blastocystis biology. However, the pleomorphic nature of the parasite and the lack of standardization in techniques have led to confusion and, in some cases, misinterpretation of data. This has hindered laboratory diagnosis and efforts to understand its mode of reproduction, life cycle, prevalence, and pathogenesis. Accumulating epidemiological, in vivo, and in vitro data strongly suggest that Blastocystis is a pathogen. Many genotypes exist in nature, and recent observations indicate that humans are, in reality, hosts to numerous zoonotic genotypes. Such genetic diversity has led to a suggestion that previously conflicting observations on the pathogenesis of Blastocystis are due to pathogenic and nonpathogenic genotypes. Recent epidemiological, animal infection, and in vitro host-Blastocystis interaction studies suggest that this may indeed be the case. This review focuses on such recent advances and also provides updates on laboratory and clinical aspects of Blastocystis spp.

  15. [Regional anesthesia for carotid surgery : An overview of anatomy, techniques and their clinical relevance].

    Science.gov (United States)

    Koköfer, A; Nawratil, J; Opperer, M

    2017-04-01

    Perioperative care for patients undergoing carotid endarterectomy (CEA) often presents a challenge to the anesthesia provider, as this patient group commonly suffers from a wide range of comorbidities. Although clinical trials could not demonstrate a significant benefit associated with regional anesthesia for outcomes such as insult, cardiac infarction or mortality, many authors concur that regional anesthetic techniques might be preferential in specific patient populations for this type of surgery. This article aims to present an overview of the currently used techniques for regional anesthesia in CEA, as well as discussing their influence on the perioperative outcome. After performing an extensive search of medical databases (Pubmed/Medline) the authors present a narrative analysis and interpretation of recent literature. Currently there is a clear trend towards ultrasound guided regional anesthesia and away from classic landmark based techniques. The literature seems to support the notion that superior and intermediate cervical blocks are safer and less invasive than deep blocks. With regional anesthetic techniques evolving to be more and more complex, the use of ultrasound is becoming increasingly indispensable in the operating theatre. For anesthesiologists with sufficient training and a profound knowledge of the respective anatomy, regional anesthesia seems to be a veritable alternative to general anesthesia for CEA.

  16. The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

    Directory of Open Access Journals (Sweden)

    Georg Ferber

    2015-01-01

    Full Text Available Concentration-effect (CE models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around tmax are missed.

  17. Natural language processing of radiology reports for the detection of thromboembolic diseases and clinically relevant incidental findings.

    Science.gov (United States)

    Pham, Anne-Dominique; Névéol, Aurélie; Lavergne, Thomas; Yasunaga, Daisuke; Clément, Olivier; Meyer, Guy; Morello, Rémy; Burgun, Anita

    2014-08-07

    Natural Language Processing (NLP) has been shown effective to analyze the content of radiology reports and identify diagnosis or patient characteristics. We evaluate the combination of NLP and machine learning to detect thromboembolic disease diagnosis and incidental clinically relevant findings from angiography and venography reports written in French. We model thromboembolic diagnosis and incidental findings as a set of concepts, modalities and relations between concepts that can be used as features by a supervised machine learning algorithm. A corpus of 573 radiology reports was de-identified and manually annotated with the support of NLP tools by a physician for relevant concepts, modalities and relations. A machine learning classifier was trained on the dataset interpreted by a physician for diagnosis of deep-vein thrombosis, pulmonary embolism and clinically relevant incidental findings. Decision models accounted for the imbalanced nature of the data and exploited the structure of the reports. The best model achieved an F measure of 0.98 for pulmonary embolism identification, 1.00 for deep vein thrombosis, and 0.80 for incidental clinically relevant findings. The use of concepts, modalities and relations improved performances in all cases. This study demonstrates the benefits of developing an automated method to identify medical concepts, modality and relations from radiology reports in French. An end-to-end automatic system for annotation and classification which could be applied to other radiology reports databases would be valuable for epidemiological surveillance, performance monitoring, and accreditation in French hospitals.

  18. 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

  19. 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...

  20. Exploring internal features of 16S rRNA gene for identification of clinically relevant species of the genus Streptococcus

    Science.gov (United States)

    2011-01-01

    Background Streptococcus is an economically important genus as a number of species belonging to this genus are human and animal pathogens. The genus has been divided into different groups based on 16S rRNA gene sequence similarity. The variability observed among the members of these groups is low and it is difficult to distinguish them. The present study was taken up to explore 16S rRNA gene sequence to develop methods that can be used for preliminary identification and can supplement the existing methods for identification of clinically-relevant isolates of the genus Streptococcus. Methods 16S rRNA gene sequences belonging to the isolates of S. dysgalactiae, S. equi, S. pyogenes, S. agalactiae, S. bovis, S. gallolyticus, S. mutans, S. sobrinus, S. mitis, S. pneumoniae, S. thermophilus and S. anginosus were analyzed with the purpose to define genetic variability within each species to generate a phylogenetic framework, to identify species-specific signatures and in-silico restriction enzyme analysis. Results The framework based analysis was used to segregate Streptococcus spp. previously identified upto genus level. This segregation was validated using species-specific signatures and in-silico restriction enzyme analysis. 43 uncharacterized Streptococcus spp. could be identified using this approach. Conclusions The markers generated exploring 16S rRNA gene sequences provided useful tool that can be further used for identification of different species of the genus Streptococcus. PMID:21702978

  1. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.

    Science.gov (United States)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M

    2014-06-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. Copyright© Ferrata Storti Foundation.

  2. Exploring internal features of 16S rRNA gene for identification of clinically relevant species of the genus Streptococcus.

    Science.gov (United States)

    Lal, Devi; Verma, Mansi; Lal, Rup

    2011-06-25

    Streptococcus is an economically important genus as a number of species belonging to this genus are human and animal pathogens. The genus has been divided into different groups based on 16S rRNA gene sequence similarity. The variability observed among the members of these groups is low and it is difficult to distinguish them. The present study was taken up to explore 16S rRNA gene sequence to develop methods that can be used for preliminary identification and can supplement the existing methods for identification of clinically-relevant isolates of the genus Streptococcus. 16S rRNA gene sequences belonging to the isolates of S. dysgalactiae, S. equi, S. pyogenes, S. agalactiae, S. bovis, S. gallolyticus, S. mutans, S. sobrinus, S. mitis, S. pneumoniae, S. thermophilus and S. anginosus were analyzed with the purpose to define genetic variability within each species to generate a phylogenetic framework, to identify species-specific signatures and in-silico restriction enzyme analysis. The framework based analysis was used to segregate Streptococcus spp. previously identified upto genus level. This segregation was validated using species-specific signatures and in-silico restriction enzyme analysis. 43 uncharacterized Streptococcus spp. could be identified using this approach. The markers generated exploring 16S rRNA gene sequences provided useful tool that can be further used for identification of different species of the genus Streptococcus.

  3. Quantitative analysis of clinically relevant mutations occurring in lymphoid cells harboring γ-retrovirus-encoded hsvtk suicide genes

    Science.gov (United States)

    Wang, X; Olszewska, M; Capacio, V; Stefanski, J; Przybylowski, M; Samakoglu, S; Chang, AH; Sadelain, M; Rivière, I

    2015-01-01

    The in vivo regulation of T lymphocyte activity by the activation of a suicide mechanism is an essential paradigm for the safety of adoptive cell therapies. In light of reports showing that γ-retroviral vector-encoded herpes simplex virus thymidine kinase (hsvtk) undergoes recombination, we undertook a thorough investigation of the genomic stability of SFG-based vectors using two variants of the wild-type hsvtk gene. In a large panel of independent clones, we demonstrate that both hsvtk genes undergo recombination with molecular signatures indicative of template switching in GC-rich regions displaying homology at the deletion junctions or RNA splicing. In the absence of ganciclovir selection, the frequency of recombination is 3% per retroviral replication cycle. Our results underscore the importance of the five nucleotide difference between the two hsvtk genes that account for the presence of recombinogenic hot spots in one variant and not the other, indicating that the probability of RNA splicing is influenced by minute nucleotide changes in sequences adjacent to the splice donor and acceptor sites. Furthermore, our mutational analysis in an unbiased panel of human lymphoid cells (that is, without immune or ganciclovir-mediated selective pressure) provides a robust in vitro assay to predict and quantify clinically relevant mutations in hsvtk suicide genes, which can be applied to studying and improving the stability of any transgene expressed in γ-retroviral or lentiviral vectors. PMID:18563185

  4. Quantitative analysis of clinically relevant mutations occurring in lymphoid cells harboring gamma-retrovirus-encoded hsvtk suicide genes.

    Science.gov (United States)

    Wang, X; Olszewska, M; Capacio, V; Stefanski, J; Przybylowski, M; Samakoglu, S; Chang, A H; Sadelain, M; Rivière, I

    2008-11-01

    The in vivo regulation of T lymphocyte activity by the activation of a suicide mechanism is an essential paradigm for the safety of adoptive cell therapies. In light of reports showing that gamma-retroviral vector-encoded herpes simplex virus thymidine kinase (hsvtk) undergoes recombination, we undertook a thorough investigation of the genomic stability of SFG-based vectors using two variants of the wild-type hsvtk gene. In a large panel of independent clones, we demonstrate that both hsvtk genes undergo recombination with molecular signatures indicative of template switching in GC-rich regions displaying homology at the deletion junctions or RNA splicing. In the absence of ganciclovir selection, the frequency of recombination is 3% per retroviral replication cycle. Our results underscore the importance of the five nucleotide difference between the two hsvtk genes that account for the presence of recombinogenic hot spots in one variant and not the other, indicating that the probability of RNA splicing is influenced by minute nucleotide changes in sequences adjacent to the splice donor and acceptor sites. Furthermore, our mutational analysis in an unbiased panel of human lymphoid cells (that is, without immune or ganciclovir-mediated selective pressure) provides a robust in vitro assay to predict and quantify clinically relevant mutations in hsvtk suicide genes, which can be applied to studying and improving the stability of any transgene expressed in gamma-retroviral or lentiviral vectors.

  5. Clinically relevant weakness in diverse populations of older adults participating in the International Mobility in Aging Study.

    Science.gov (United States)

    de Souza Barbosa, Juliana Fernandes; Zepeda, Mario Ulises Perez; Béland, François; Guralnik, Jack M; Zunzunegui, Maria Victoria; Guerra, Ricardo Oliveira

    2016-02-01

    The aims of this study were to compare cut points for weakness proposed by Foundation for the National Institutes of Health (FNIH) Sarcopenia Project with cut points estimated with our own data; to assess the prevalence of clinically relevant handgrip strength (HGS) weakness according to published criteria across distinct populations of older adults; to estimate the ability of HGS weakness to identify slowness. This is a cross-sectional analysis of International Mobility in Aging Study (IMIAS) involving 1935 community-dwelling older adults, between 65 and 74 years, who completed HGS and gait speed assessment. We used baseline data from Tirana (Albania), Natal (Brazil), Manizales (Colombia), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). Weakness was defined according to sex-specific HGS cut points associated with slowness proposed by FNIH Sarcopenia Project. Slowness was defined as gait speed <0.8 m/s. IMIAS cut points for clinical weakness had good agreement with those proposed by FNIH. Weakness prevalence across the research sites ranged from 1.1 % (Saint-Hyacinthe) to 19.2 % (Manizales) among men. Women from Manizales (13.5 %) and Natal (19.3 %) had higher prevalence of weakness than their counterparts. FNIH cut points had a strong association with slowness, for both sexes. The IMIAS population generated cut points which were close to those proposed by FNIH. There was large variability in prevalence of weakness across our research sites. The HGS cut points for weakness proposed by FNIH performed well in IMIAS populations, providing a useful tool for screening older adults at risk for functional problems.

  6. Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats.

    Science.gov (United States)

    Kandasamy, Ram; Calsbeek, Jonas J; Morgan, Michael M

    2016-04-01

    The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Injection of Complete Freund's Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in male and female rats. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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...

  8. Perspectives on Palliative Care in Cancer Clinical Trials: Diverse Meanings from Multidisciplinary Cancer Care Providers.

    Science.gov (United States)

    Mollica, Michelle A; Kent, Erin E; Castro, Kathleen M; Ellis, Erin M; Ferrer, Rebecca A; Falisi, Angela L; Gaysynsky, Anna; Huang, Grace C; Palan, Martha A; Chou, Wen-Ying Sylvia

    2018-02-01

    Palliative care (PC) is often misunderstood as exclusively pertaining to end-of-life care, which may be consequential for its delivery. There is little research on how PC is operationalized and delivered to cancer patients enrolled in clinical trials. We sought to understand the diverse perspectives of multidisciplinary oncology care providers caring for such patients in a teaching hospital. We conducted qualitative semistructured interviews with 19 key informants, including clinical trial principal investigators, oncology fellows, research nurses, inpatient and outpatient nurses, spiritual care providers, and PC fellows. Questions elicited information about the meaning providers assigned to the term "palliative care," as well as their experiences with the delivery of PC in the clinical trial context. Using grounded theory, a team-based coding method was employed to identify major themes. Four main themes emerged regarding the meaning of PC: (1) the holistic nature of PC, (2) the importance of symptom care, (3) conflict between PC and curative care, and (4) conflation between PC and end-of-life care. Three key themes emerged with regard to the delivery of PC: (1) dynamics among providers, (2) discussing PC with patients and family, and (3) the timing of PC delivery. There was great variability in personal meanings of PC, conflation with hospice/end-of-life care, and appropriateness of PC delivery and timing, particularly within cancer clinical trials. A standard and acceptable model for integrating PC concurrently with treatment in clinical trials is needed.

  9. Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications.

    Science.gov (United States)

    Ishiguro, Tatsuya; Ohata, Hirokazu; Sato, Ai; Yamawaki, Kaoru; Enomoto, Takayuki; Okamoto, Koji

    2017-03-01

    Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor-derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell-related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC-related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor-derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor-derived spheroids may prove to be instrumental for a high-throughput screening platform or for the cultivation of CSC-related tumor cells found in the circulation or body fluids. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. Stability of the elbow joint: relevant anatomy and clinical implications of in vitro biomechanical studies

    NARCIS (Netherlands)

    de Haan, J.; Schep, N. W. L.; Eygendaal, D.; Kleinrensink, G.-J.; Tuinebreijer, W. E.; den Hartog, D.

    2011-01-01

    The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint dislocation.The PubMed

  11. Usability evaluation of pharmacogenomics clinical decision support aids and clinical knowledge resources in a computerized provider order entry system: a mixed methods approach.

    Science.gov (United States)

    Devine, Emily Beth; Lee, Chia-Ju; Overby, Casey L; Abernethy, Neil; McCune, Jeannine; Smith, Joe W; Tarczy-Hornoch, Peter

    2014-07-01

    Pharmacogenomics (PGx) is positioned to have a widespread impact on the practice of medicine, yet physician acceptance is low. The presentation of context-specific PGx information, in the form of clinical decision support (CDS) alerts embedded in a computerized provider order entry (CPOE) system, can aid uptake. Usability evaluations can inform optimal design, which, in turn, can spur adoption. The study objectives were to: (1) evaluate an early prototype, commercial CPOE system with PGx-CDS alerts in a simulated environment, (2) identify potential improvements to the system user interface, and (3) understand the contexts under which PGx knowledge embedded in an electronic health record is useful to prescribers. Using a mixed methods approach, we presented seven cardiologists and three oncologists with five hypothetical clinical case scenarios. Each scenario featured a drug for which a gene encoding drug metabolizing enzyme required consideration of dosage adjustment. We used Morae(®) to capture comments and on-screen movements as participants prescribed each drug. In addition to PGx-CDS alerts, 'Infobutton(®)' and 'Evidence' icons provided participants with clinical knowledge resources to aid decision-making. Nine themes emerged. Five suggested minor improvements to the CPOE user interface; two suggested presenting PGx information through PGx-CDS alerts using an 'Infobutton' or 'Evidence' icon. The remaining themes were strong recommendations to provide succinct, relevant guidelines and dosing recommendations of phenotypic information from credible and trustworthy sources; any more information was overwhelming. Participants' median rating of PGx-CDS system usability was 2 on a Likert scale ranging from 1 (strongly agree) to 7 (strongly disagree). Usability evaluation results suggest that participants considered PGx information important for improving prescribing decisions; and that they would incorporate PGx-CDS when information is presented in relevant and

  12. Study of photoacoustic measurement of bone health based on clinically relevant models

    Science.gov (United States)

    Feng, Ting; Kozloff, Ken; Cao, Meng; Cheng, Qian; Yuan, Jie; Wang, Xueding

    2016-02-01

    Photoacoustic (PA) technique involving both ultrasound and light has been explored for potential application in the assessment of bone health. The optical and ultrasound penetration in bone have been studied. The feasibility of conducting 3D PA imaging of bone, and performing quantitative evaluation of bone microstructures by using photoacoustic spectrum analysis (PASA) has also been investigated. The findings from the experiments demonstrate that PA measurement could offer information of bone mineral density and bone microstructure, both relevant to bone health.

  13. Criteria for clinical audit of women friendly care and providers' perception in Malawi

    Directory of Open Access Journals (Sweden)

    van den Broek Nynke

    2008-07-01

    Full Text Available Abstract Background There are two dimensions of quality of maternity care, namely quality of health outcomes and quality as perceived by clients. The feasibility of using clinical audit to assess and improve the quality of maternity care as perceived by women was studied in Malawi. Objective We sought to (a establish standards for women friendly care and (b explore attitudinal barriers which could impede the proper implementation of clinical audit. Methods We used evidence from Malawi national guidelines and World Health Organisation manuals to establish local standards for women friendly care in three districts. We equally conducted a survey of health care providers to explore their attitudes towards criterion based audit. Results The standards addressed different aspects of care given to women in maternity units, namely (i reception, (ii attitudes towards women, (iii respect for culture, (iv respect for women, (v waiting time, (vi enabling environment, (vii provision of information, (viii individualised care, (ix provision of skilled attendance at birth and emergency obstetric care, (x confidentiality, and (xi proper management of patient information. The health providers in Malawi generally held a favourable attitude towards clinical audit: 100.0% (54/54 agreed that criterion based audit will improve the quality of care and 92.6% believed that clinical audit is a good educational tool. However, there are concerns that criterion based audit would create a feeling of blame among providers (35.2%, and that manager would use clinical audit to identify and punish providers who fail to meet standards (27.8%. Conclusion Developing standards of maternity care that are acceptable to, and valued by, women requires consideration of both the research evidence and cultural values. Clinical audit is acceptable to health professionals in Malawi although there are concerns about its negative implications to the providers.

  14. Patient Satisfaction Is Associated With Time With Provider But Not Clinic Wait Time Among Orthopedic Patients.

    Science.gov (United States)

    Patterson, Brendan M; Eskildsen, Scott M; Clement, R Carter; Lin, Feng-Chang; Olcott, Christopher W; Del Gaizo, Daniel J; Tennant, Joshua N

    2017-01-01

    Clinic wait time is considered an important predictor of patient satisfaction. The goal of this study was to determine whether patient satisfaction among orthopedic patients is associated with clinic wait time and time with the provider. The authors prospectively enrolled 182 patients at their outpatient orthopedic clinic. Clinic wait time was defined as the time between patient check-in and being seen by the surgeon. Time spent with the provider was defined as the total time the patient spent in the examination room with the surgeon. The Consumer Assessment of Healthcare Providers and Systems survey was used to measure patient satisfaction. Factors associated with increased patient satisfaction included patient age and increased time with the surgeon (P=.024 and P=.037, respectively), but not clinic wait time (P=.625). Perceived wait time was subject to a high level of error, and most patients did not accurately report whether they had been waiting longer than 15 minutes to see a provider until they had waited at least 60 minutes (P=.007). If the results of the current study are generalizable, time with the surgeon is associated with patient satisfaction in orthopedic clinics, but wait time is not. Further, the study findings showed that patients in this setting did not have an accurate perception of actual wait time, with many patients underestimating the time they waited to see a provider. Thus, a potential strategy for improving patient satisfaction is to spend more time with each patient, even at the expense of increased wait time. [Orthopedics. 2017; 40(1):43-48.]. Copyright 2016, SLACK Incorporated.

  15. Experience in implementing inpatient clinical note capture via a provider order entry system.

    Science.gov (United States)

    Rosenbloom, S Trent; Grande, Jonathan; Geissbuhler, Antoine; Miller, Randolph A

    2004-01-01

    Care providers' adoption of computer-based health-related documentation ("note capture") tools has been limited, even though such tools have the potential to facilitate information gathering and to promote efficiency of clinical charting. The authors have developed and deployed a computerized note-capture tool that has been made available to end users through a care provider order entry (CPOE) system already in wide use at Vanderbilt. Overall note-capture tool usage between January 1, 1999, and December 31, 2001, increased substantially, both in the number of users and in their frequency of use. This case report is provided as an example of how an existing care provider order entry environment can facilitate clinical end-user adoption of a computer-assisted documentation tool-a concept that may seem counterintuitive to some.

  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. 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.

  18. A clinical audit of provider-initiated HIV counselling and testing in a ...

    African Journals Online (AJOL)

    Background. Early initiation of antiretroviral therapy reduces transmission of HIV and prolongs life. Expansion of HIV testing is therefore pivotal in overcoming the HIV pandemic. Provider-initiated counselling and testing (PICT) at first clinical contact is one way of increasing the number of individuals tested. Our impression is ...

  19. Factors Predicting Oncology Care Providers' Behavioral Intention to Adopt Clinical Decision Support Systems

    Science.gov (United States)

    Wolfenden, Andrew

    2012-01-01

    The purpose of this quantitative correlation study was to examine the predictors of user behavioral intention on the decision of oncology care providers to adopt or reject the clinical decision support system. The Unified Theory of Acceptance and Use of Technology (UTAUT) formed the foundation of the research model and survey instrument. The…

  20. [The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014].

    Science.gov (United States)

    Giraldo, Newar A; Amariles, Pedro; Pino Marín, Daniel E; Faus, María José

    2016-10-01

    To update information about drug interactions in patients with HIV/AIDS. Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

  1. "We're Almost Guests in Their Clinical Care": Inpatient Provider Attitudes Toward Chronic Disease Management.

    Science.gov (United States)

    Blecker, Saul; Meisel, Talia; Dickson, Victoria Vaughan; Shelley, Donna; Horwitz, Leora I

    2017-03-01

    Many hospitalized patients have at least 1 chronic disease that is not optimally controlled. The purpose of this study was to explore inpatient provider attitudes about chronic disease management and, in particular, barriers and facilitators of chronic disease management in the hospital. We conducted a qualitative study of semi-structured interviews of 31 inpatient providers from an academic medical center. We interviewed attending physicians, resident physicians, physician assistants, and nurse practitioners from various specialties about attitudes, experiences with, and barriers and facilitators towards chronic disease management in the hospital. Qualitative data were analyzed using constant comparative analysis. Providers perceived that hospitalizations offer an opportunity to improve chronic disease management, as patients are evaluated by a new care team and observed in a controlled environment. Providers perceived clinical benefits to in-hospital chronic care, including improvements in readmission and length of stay, but expressed concerns for risks related to adverse events and distraction from the acute problem. Barriers included provider lack of comfort with managing chronic diseases, poor communication between inpatient and outpatient providers, and hospital-system focus on patient discharge. A strong relationship with the outpatient provider and involvement of specialists were facilitators of inpatient chronic disease management. Providers perceived benefits to in-hospital chronic disease management for both processes of care and clinical outcomes. Efforts to increase inpatient chronic disease management will need to overcome barriers in multiple domains. Journal of Hospital Medicine 2017;12:162-167.

  2. The business case for provider participation in clinical trials research: an application to the National Cancer Institute's community clinical oncology program.

    Science.gov (United States)

    Song, Paula H; Reiter, Kristin L; Weiner, Bryan J; Minasian, Lori; McAlearney, Ann Scheck

    2013-01-01

    Provider-based research networks (PBRNs) make clinical trials available in community-based practice settings, where most people receive their care, but provider participation requires both financial and in-kind contributions. The aim of this study was to explore whether providers believe there is a business case for participating in PBRNs and what factors contribute to the business case. We use a multiple case study methodology approach to examine the National Cancer Institute's community clinical oncology program, a long-standing federally funded PBRN. Interviews with 41 key informants across five sites, selected on the basis of organizational maturity, were conducted using a semistructured interview guide. We analyzed interview transcripts using an iterative, deductive process to identify themes and subthemes in the data. We found that a business case for provider participation in PBRNs may exist if both direct and indirect financial benefits are identified and included in the analysis and if the time horizon is long enough to allow those benefits to be realized. We identified specific direct and indirect financial benefits that were perceived as important contributors to the business case and the perceived length of time required for a positive return to accrue. As the lack of a business case may result in provider reluctance to participate in PBRNs, knowledge of the benefits we identified may be crucial to encouraging and sustaining participation, thereby preserving patient access to innovative community-based treatments. The results are also relevant to federally funded PBRNs outside of oncology or to providers considering participation in any clinical trials research.

  3. 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.

  4. Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

    Science.gov (United States)

    Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

    2010-07-01

    Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

  5. Putting the Pieces Together: Clinically Relevant Genetic and Genomic Resources for Hospitalists and Neonatologists.

    Science.gov (United States)

    Miller, Rebecca; Khromykh, Alina; Babcock, Holly; Jenevein, Callie; Solomon, Benjamin D

    2017-02-01

    Genetic conditions are individually rare but are common in aggregate, and they often present in the neonatal and early pediatric periods. These conditions are often severe, can be difficult to diagnose and manage, and may heavily affect patients, families, health care systems, and society. Because of recent technological advances, the availability and uptake of genetic and genomic testing are increasing rapidly. However, there is a dearth of trained geneticists and genetic counselors to help guide and explain these conditions and relevant tests. To help hospitalists, neonatologists, and related practitioners navigate this complex and evolving field, we have compiled a list of free (mostly Web-based) resources relevant to the diagnosis and management of genetic conditions and related disorders. These resources, which we describe individually, can be useful for nongeneticist clinicians, and some also include material that can be used to explain concepts and conditions to patients or families. The resources presented are divided into the following categories (which overlap): general information, databases of genetic conditions, resources that can help generate differential diagnoses, databases of genetic testing laboratories (to help with logistics of ordering tests), information on newborn screening, and other resources. We also include a separate list of helpful textbooks and manuals. We conclude with 2 examples describing how some of these resources would be used by a pediatric hospitalist or neonatologist during the inpatient management of a child with a suspected genetic condition. Copyright © 2017 by the American Academy of Pediatrics.

  6. The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings

    Science.gov (United States)

    de Boer, Marrit K.; Castelein, Stynke; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

    2015-01-01

    A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce. PMID:25721311

  7. Team dynamics, clinical work satisfaction, and patient care coordination between primary care providers: A mixed methods study.

    Science.gov (United States)

    Song, Hummy; Ryan, Molly; Tendulkar, Shalini; Fisher, Josephine; Martin, Julia; Peters, Antoinette S; Frolkis, Joseph P; Rosenthal, Meredith B; Chien, Alyna T; Singer, Sara J

    Team-based care is essential for delivering high-quality, comprehensive, and coordinated care. Despite considerable research about the effects of team-based care on patient outcomes, few studies have examined how team dynamics relate to provider outcomes. The aim of this study was to examine relationships among team dynamics, primary care provider (PCP) clinical work satisfaction, and patient care coordination between PCPs in 18 Harvard-affiliated primary care practices participating in Harvard's Academic Innovations Collaborative. First, we administered a cross-sectional survey to all 548 PCPs (267 attending clinicians, 281 resident physicians) working at participating practices; 65% responded. We assessed the relationship of team dynamics with PCPs' clinical work satisfaction and perception of patient care coordination between PCPs, respectively, and the potential mediating effect of patient care coordination on the relationship between team dynamics and work satisfaction. In addition, we embedded a qualitative evaluation within the quantitative evaluation to achieve a convergent mixed methods design to help us better understand our findings and illuminate relationships among key variables. Better team dynamics were positively associated with clinical work satisfaction and quality of patient care coordination between PCPs. Coordination partially mediated the relationship between team dynamics and satisfaction for attending clinicians, suggesting that higher satisfaction depends, in part, on better teamwork, yielding more coordinated patient care. We found no mediating effects for resident physicians. Qualitative results suggest that sources of satisfaction from positive team dynamics for PCPs may be most relevant to attending clinicians. Improving primary care team dynamics could improve clinical work satisfaction among PCPs and patient care coordination between PCPs. In addition to improving outcomes that directly concern health care providers, efforts to

  8. Primary palliative care clinic pilot project demonstrates benefits of a nurse practitioner-directed clinic providing primary and palliative care.

    Science.gov (United States)

    Owens, Darrell; Eby, Kerry; Burson, Sean; Green, Meghan; McGoodwin, Wendy; Isaac, Margaret

    2012-01-01

    The purpose of the Primary Palliative Care Pilot Project was to determine if patients with a life-limiting illness who receive their primary care and palliative care from a consistent provider via a nurse practitioner (NP)-founded and-directed Primary Palliative Care Clinic at a public hospital would have improved symptom management and decreased emergency department utilization over time. All patients followed in the Harborview Primary Palliative Care Clinic from January to March 2010. The results of this project demonstrate that patients with a life-limiting illness who receive their primary care and palliative care in an NP-founded and -directed Primary Palliative Care Clinic have decreased utilization of the emergency department, and some experience improvement in symptom assessment scores. Palliative care providers and administrators should explore opportunities to expand outpatient palliative care clinics with an emphasis on primary care and continuity of care. NPs by experience and education are ideally suited to manage both primary and palliative care needs for people at the end of life. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

  9. 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

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

    Science.gov (United States)

    de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; Del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara

    2015-01-01

    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 normalization of

  11. [Interatrial block and its clinical relevance. Renaissance of an ECG change].

    Science.gov (United States)

    Tomcsányi, János

    2018-01-01

    Interatrial block involves conduction delay between the right and left atria during sinus rhythm. The review describes the classification, pathomechanism and clinical significance of this under-recognised ECG sign, nominated Bayés syndrome. The presented ECGs help to recognise the differentypes of interatrial blocks. Orv Hetil. 2018; 159(3): 91-95.

  12. Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine.

    Science.gov (United States)

    Bray, Christopher; Bell, Lauren N; Liang, Hong; Haykal, Rasha; Kaiksow, Farah; Mazza, Joseph J; Yale, Steven H

    2016-12-01

    Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used laboratory markers of systemic inflammation. A thorough understanding of the similarities and differences between these two serological markers, including factors that affect measurements, is necessary for the proper utilization and interpretation of ESR and CRP. This review summarizes the current published literature (searched on MEDLINE through February 2016) surrounding the history and utilization of ESR and CRP, and examines factors that affect ESR and CRP measurements and discordance amongst these two inflammatory markers. As ESR and CRP lack sensitivity or specificity, these tests should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions. The clinical application of these tests in diagnosis is best applied to conditions in which there is high or low clinical probability of disease. Importantly, discrepancies between ESR and CRP measurements commonly have been reported in both inpatient and outpatient settings and this problem may be particularly prevalent in chronic inflammatory diseases. Numerous physiological factors, including noninfectious conditions and resolution of inflammation can contribute to abnormally high ESR/low CRP readings or vice versa. Although discordance may be encountered in certain settings, proper utilization of ESR and CRP measurements continues to play an important role in clinical management of many inflammatory and other conditions.

  13. The relevance of clinical and radiographic features of jaw lesions: A prospective study

    Directory of Open Access Journals (Sweden)

    Juliane Piragine ARAUJO

    Full Text Available Abstract The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years ± 17.86. Among these, 71 were women (54.62% and 87 were Caucasian (66.92%. The mandible was affected more frequently (71.43% than the maxilla (28.57%. Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85% and 38 (27.14% cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%. Radiolucent lesions accounted for 89 cases (63.57% and the unilocular form was present in 114 cases (81.43%. A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams.

  14. Quantitative 3D high resolution transmission ultrasound tomography: creating clinically relevant images (Conference Presentation)

    Science.gov (United States)

    Wiskin, James; Klock, John; Iuanow, Elaine; Borup, Dave T.; Terry, Robin; Malik, Bilal H.; Lenox, Mark

    2017-03-01

    There has been a great deal of research into ultrasound tomography for breast imaging over the past 35 years. Few successful attempts have been made to reconstruct high-resolution images using transmission ultrasound. To this end, advances have been made in 2D and 3D algorithms that utilize either time of arrival or full wave data to reconstruct images with high spatial and contrast resolution suitable for clinical interpretation. The highest resolution and quantitative accuracy result from inverse scattering applied to full wave data in 3D. However, this has been prohibitively computationally expensive, meaning that full inverse scattering ultrasound tomography has not been considered clinically viable. Here we show the results of applying a nonlinear inverse scattering algorithm to 3D data in a clinically useful time frame. This method yields Quantitative Transmission (QT) ultrasound images with high spatial and contrast resolution. We reconstruct sound speeds for various 2D and 3D phantoms and verify these values with independent measurements. The data are fully 3D as is the reconstruction algorithm, with no 2D approximations. We show that 2D reconstruction algorithms can introduce artifacts into the QT breast image which are avoided by using a full 3D algorithm and data. We show high resolution gross and microscopic anatomic correlations comparing cadaveric breast QT images with MRI to establish imaging capability and accuracy. Finally, we show reconstructions of data from volunteers, as well as an objective visual grading analysis to confirm clinical imaging capability and accuracy.

  15. Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

    NARCIS (Netherlands)

    Kubben, Francois Jozef Gerard Marie

    2007-01-01

    The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were

  16. Risk factors for the development of clinical leprosy among contacts, and their relevance for targeted interventions

    NARCIS (Netherlands)

    Moet, F. J.; Meima, A.; Oskam, L.; Richardus, J. H.

    2004-01-01

    Existing knowledge on risk factors for the development of clinical leprosy among contacts of known leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential for developing effective targeted interventions in leprosy control. Different

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

    Science.gov (United States)

    2016-10-01

    on the commercial use of the molecular diagnostics. What was the impact on society beyond science and technology ? Successful execution of this...clinical practice to predict aggressive disease. The accuracy of each biomarker for predicting short- and long-term progression will be characterized...multiple established and analytically validated quantitative molecular biomarkers to predict PCa progression in a multi- center active surveillance

  18. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance : A Review

    NARCIS (Netherlands)

    Kamal, Rama M; van Noorden, Martijn S; Franzek, Ernst; Dijkstra, Boukje A G; Loonen, Antonius; De Jong, Cornelius A J

    2016-01-01

    OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  19. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review

    NARCIS (Netherlands)

    Kamal, R.M.; Noorden, M.S. van; Franzek, E.; Dijkstra, B.A.; Loonen, A.J.; Jong, C.A.J. de

    2016-01-01

    OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  20. The neurobiological mechanisms of gamma-hydroxybutyrate dependence and withdrawal and their clinical relevance: A review

    NARCIS (Netherlands)

    Kamal, R.M.; Noorden, M.S. van; Franzek, E.; Dijkstra, B.A.G.; Loonen, A.J.M.; Jong, C.A.J. de

    2016-01-01

    Objective: gamma-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  1. Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

    Science.gov (United States)

    Bialosky, Joel E.; Robinson, Michael E.

    2014-01-01

    Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm

  2. 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.

  3. Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis.

    Science.gov (United States)

    Laban, Kamil G; Vergouwen, Mervyn D I; Dijkhuizen, Rick M; Sena, Emily S; Macleod, Malcolm R; Rinkel, Gabriel J E; van der Worp, H Bart

    2015-07-01

    In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

  4. NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection.

    Science.gov (United States)

    Dikshit, N; Kale, S D; Khameneh, H J; Balamuralidhar, V; Tang, C Y; Kumar, P; Lim, T P; Tan, T T; Kwa, A L; Mortellaro, A; Sukumaran, B

    2018-01-01

    The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A. baumannii infection is unknown. Using a sublethal mouse pneumonia model, we demonstrate that an extensively drug-resistant clinical isolate (ICII) of A. baumannii exhibits reduced/delayed early pulmonary neutrophil recruitment, higher lung persistence, and, most importantly, elicits enhanced IL-1β/IL-18 production and lung damage through NLRP3 inflammasome, in comparison with A. baumannii-type strain. A. baumannii infection-induced IL-1β/IL-18 production is entirely dependent on NLRP3-ASC-caspase-1/caspase-11 pathway. Using Nlrp3 -/- mice infection models, we further show that while NLRP3 inflammasome pathway contributes to host defense against A. baumannii clinical isolate, it is dispensable for protection against A. baumannii-type strain. Our study reveals a novel differential role for NLRP3 inflammasome pathway in the immunity against clinically relevant A. baumannii infections, and highlights inflammasome pathway as a potential immunomodulatory target.

  5. A qualitative study examining methods of accessing and identifying research relevant to clinical practice among rehabilitation clinicians

    Directory of Open Access Journals (Sweden)

    Patel D

    2017-12-01

    Full Text Available Drasti Patel,1 Christine Koehmstedt,1 Rebecca Jones,1 Nathan T Coffey,1 Xinsheng Cai,2 Steven Garfinkel,2 Dahlia M Shaewitz,2 Ali A Weinstein1 1Center for Study of Chronic Illness and Disability, College of Health and Human Services, George Mason University, Fairfax, VA, 2American Institutes for Research, Washington, DC, USA Purpose: Research examining the utilization of evidence-based practice (EBP specifically among rehabilitation clinicians is limited. The objective of this study was to examine how various rehabilitative clinicians including physical therapists, occupational therapists, rehabilitation counselors, and physiatrists are gaining access to literature and whether they are able to implement the available research into practice.Methods: A total of 21 total clinicians were interviewed via telephone. Using NVivo, a qualitative analysis of the responses was performed.Results: There were similarities found with respect to the information-seeking behaviors and translation of research across the different clinician types. Lack of time was reported to be a barrier for both access to literature and implementation of research across all clinician types. The majority of clinicians who reported having difficulty with utilizing the published literature indicated that the literature was not applicable to their practice, the research was not specific enough to be put into practice, or the research found was too outdated to be relevant. In addition, having a supportive work environment aided in the search and utilization of research through providing resources central to assisting clinicians in gaining access to health information.Conclusion: Our study identified several barriers that affect EBP for rehabilitation clinicians. The findings suggest the need for researchers to ensure that their work is applicable and specific to clinical practice for implementation to occur. Keywords: health information, information behavior, knowledge utilization

  6. PROFOUND AND SEXUALLY DIMORPHIC EFFECTS OF CLINICALLY-RELEVANT LOW DOSE SCATTER IRRADIATION ON THE BRAIN AND BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Anna eKovalchuk

    2016-06-01

    Full Text Available Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders. While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  7. Bandit solutions provide unified ethical models for randomized clinical trials and comparative effectiveness research.

    Science.gov (United States)

    Press, William H

    2009-12-29

    As electronic medical records enable increasingly ambitious studies of treatment outcomes, ethical issues previously important only to limited clinical trials become relevant to unlimited whole populations. For randomized clinical trials, adaptive assignment strategies are known to expose substantially fewer patients to avoidable treatment failures than strategies with fixed assignments (e.g., equal sample sizes). An idealized adaptive case--the two-armed Bernoulli bandit problem--can be exactly optimized for a variety of ethically motivated cost functions that embody principles of duty-to-patient, but the solutions have been thought computationally infeasible when the numbers of patients in the study (the "horizon") is large. We report numerical experiments that yield a heuristic approximation that applies even to very large horizons, and we propose a near-optimal strategy that remains valid even when the horizon is unknown or unbounded, thus applicable to comparative effectiveness studies on large populations or to standard-of-care recommendations. For the case in which the economic cost of treatment is a parameter, we give a heuristic, near-optimal strategy for determining the superior treatment (whether more or less costly) while minimizing resources wasted on any inferior, more expensive, treatment. Key features of our heuristics can be generalized to more complicated protocols.

  8. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes.

    Science.gov (United States)

    Della Porta, Matteo Giovanni; Malcovati, Luca; Boveri, Emanuela; Travaglino, Erica; Pietra, Daniela; Pascutto, Cristiana; Passamonti, Francesco; Invernizzi, Rosangela; Castello, Alessandro; Magrini, Umberto; Lazzarino, Mario; Cazzola, Mario

    2009-02-10

    We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P WHO categories with excess of blasts (P according to International Prognostic Scoring System and WHO classification-based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

  9. Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples

    DEFF Research Database (Denmark)

    Fackenthal, James D; Yoshimatsu, Toshio; Zhang, Bifeng

    2016-01-01

    BACKGROUND: BRCA1 and BRCA2 are the two principal tumour suppressor genes associated with inherited high risk of breast and ovarian cancer. Genetic testing of BRCA1/2 will often reveal one or more sequence variants of uncertain clinical significance, some of which may affect normal splicing...... patterns and thereby disrupt gene function. mRNA analyses are therefore among the tests used to interpret the clinical significance of some genetic variants. However, these could be confounded by the appearance of naturally occurring alternative transcripts unrelated to germline sequence variation...... or defects in gene function. To understand which novel splicing events are associated with splicing mutations and which are part of the normal BRCA2 splicing repertoire, a study was undertaken by members of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium...

  10. 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.

  11. Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

    OpenAIRE

    Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

    2013-01-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implicat...

  12. CLINICAL AND BIOLOGICAL RELEVANCE OF EZH2 IN TRIPLE NEGATIVE BREAST CANCER

    OpenAIRE

    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba

    2012-01-01

    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with ...

  13. 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.

  14. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

    Science.gov (United States)

    Sibbing, D; Spannagl, M

    2014-01-01

    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

  15. General Anesthetics to Treat Major Depressive Disorder: Clinical Relevance and Underlying Mechanisms.

    Science.gov (United States)

    Vutskits, Laszlo

    2018-01-01

    Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases. Clinical observations over the past few decades appear to confirm this possibility. Indeed, equipotency of general anesthesia alone in comparison with electroconvulsive therapy under general anesthesia has been demonstrated in several clinical trials. Importantly, in the past 15 years, intravenous administration of subanesthetic doses of ketamine have also been demonstrated to have rapid antidepressant effects. The molecular, cellular, and network mechanisms underlying these therapeutic effects have been partially identified. Although several important questions remain to be addressed, the ensemble of these experimental and clinical observations opens new therapeutic possibilities in the treatment of depressive disorders. Importantly, they also suggest a new therapeutic role for anesthetics that goes beyond their principal use in the perioperative period to facilitate surgery.

  16. Free radicals and other reactive oxygen metabolites: clinical relevance and the therapeutic efficacy of antioxidant therapy.

    Science.gov (United States)

    Bulkley, G B

    1993-05-01

    As in any new field, justifiable enthusiasm for the potential for antioxidant therapy has led to hyperbole, hastily designed, poorly conceived clinical trials, and premature reporting of uncontrolled, anecdotal indicators of efficacy that have not held up when subjected to close scrutiny or more careful, controlled trial design. This tendency has been augmented by strong pressure for early positive results from a few, but not most, members of the pharmaceutical industry and by a few clinicians in highly competitive fields who were anxious not to be left behind. The sobering reality of negative or, even worse, indeterminate clinical trials has culled the field and educated those that remain. As a result, we are beginning to see the publication of quite promising results from large, well-controlled, carefully designed clinical studies, many, but not all, of which are quite promising. This has been associated with a much better understanding of the basic mechanism of free radical-mediated human disease, without which further substantial progress would be quite limited. Because the manipulation of oxidant-mediated tissue injury represents treating disease at its most basic level, the therapeutic potential of this approach remains not only promising but exciting.

  17. 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.

  18. Evaluation of Immunogenicity of Nivolumab Monotherapy and Its Clinical Relevance in Patients With Metastatic Solid Tumors.

    Science.gov (United States)

    Agrawal, Shruti; Statkevich, Paul; Bajaj, Gaurav; Feng, Yan; Saeger, Sally; Desai, Dharmesh D; Park, Jong-Soon; Waxman, Ian M; Roy, Amit; Gupta, Manish

    2017-03-01

    Nivolumab is a fully human IgG4 monoclonal antibody targeting the programmed death-1 (PD-1) receptor that blocks interactions between PD-1 and its ligands on tumor cells to prevent T-cell exhaustion in patients with cancer. It has demonstrated efficacy in multiple tumor types, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. This analysis assessed the immunogenicity of nivolumab and its impact on pharmacokinetics, safety, and efficacy in patients with solid tumors enrolled in 6 clinical studies. The incidence and prevalence of antidrug antibodies (ADAs) were determined by validated electrochemiluminescence assays in samples collected during nivolumab treatment and up to 100 days after the last dose. Confirmed positive samples from the 6 studies were also tested for presence of neutralizing antibodies (NAbs). Among 1086 nivolumab-treated patients, 138 patients (12.7%) were ADA positive (relative to baseline), only 3 (0.3%) of whom were persistently positive for ADA, and 9 (0.8%) were NAb positive at 1 time point. The presence of ADAs was not associated with hypersensitivity, infusion reactions, or loss of efficacy and had minimal impact on nivolumab clearance. Additionally, the presence of NAbs was not associated with loss of efficacy. In conclusion, immunogenicity of nivolumab is not clinically meaningful. © 2016, The American College of Clinical Pharmacology.

  19. Rapid differentiation between clinically relevant mycobacteria in microscopy positive clinical specimens and mycobacterial isolates by line probe assay

    DEFF Research Database (Denmark)

    Johansen, Isik Somuncu; Lundgren, Bettina H; Thyssen, Jacob Pontoppidan

    2002-01-01

    The Inno LiPA Mycobacteria assay, based on PCR amplification of the 16-23S rRNA spacer region of Mycobacterium species, has been designed for identification of mycobacteria grown in culture media and discrimination between Mycobacterium tuberculosis complex, M. avium, M. intracellulare, M. kansas...... mycobacteria in microscopy positive clinical specimens and isolates within 6 h in the same procedural run.......The Inno LiPA Mycobacteria assay, based on PCR amplification of the 16-23S rRNA spacer region of Mycobacterium species, has been designed for identification of mycobacteria grown in culture media and discrimination between Mycobacterium tuberculosis complex, M. avium, M. intracellulare, M. kansasii......, M. gordonae, M. xenopi, scrofulaceum and M. chelonae group including M. abscessus. In order to evaluate the system as a fast diagnostic tool, the assay was for the first time used directly on 14 microscopy positive clinical specimens and 71 isolates and the results were compared to those...

  20. Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients

    NARCIS (Netherlands)

    Lukas, C.; Sombekke, M.H.; Bellenberg, B.; Hahn, H.K.; Popescu, V.; Bendfeldt, K.; Radue, E.W.; Gass, A.; Borgwardt, S.J.; Kappos, L.; Naegelin, Y.; Knol, D.L.; Polman, C.H.; Geurts, J.J.G.; Barkhof, F.; Vrenken, H.

    2013-01-01

    Purpose: To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers. Materials and Methods: The institutional review

  1. Latarjet procedure: evolution of the bone block and correspondent clinical relevance-a clinical and radiological study.

    Science.gov (United States)

    Vadalà, A; Lanzetti, R M; De Carli, A; Lupariello, D; Guzzini, M; Desideri, D; Ferretti, A

    2017-12-01

    The purpose of this study was to correlate the bone block graft position, its dimension, its reabsorption and its integration with clinical outcome in patients operated on for recurrent anterior shoulder instability. Twenty-four patients affected by recurrent anterior shoulder dislocation and operated on using the Latarjet procedure were enrolled in this study. At 6 and 24 months, patients were evaluated with the following scales: ROWE, WOSI, Oxford instability score, UCLA, DASH and Constant score. Patients underwent two postoperative CT scans: immediately after surgery (T0) and at 24 months post-op (T1). At 24 months, none of the 24 patients reported further episodes of dislocation. Clinically at the final follow-up, we found excellent results in all the evaluation scales. Mean reduction in bone graft from T0 to T1 was 42% of the overall volume; similarly reduction in the overall surface was 29.3%; decrease in length, width and depth was, respectively, 3.4, 2.2 and 1.0 mm; all these parameters decreased significantly (p Latarjet procedure, but they do not significantly affect the clinical and functional results.

  2. In-Center Nutrition Practices of Clinics within a Large Hemodialysis Provider in the United States.

    Science.gov (United States)

    Benner, Debbie; Burgess, Mary; Stasios, Maria; Brosch, Becky; Wilund, Ken; Shen, Sa; Kistler, Brandon

    2016-05-06

    Eating during hemodialysis treatment remains a controversial topic. It is perceived that more restrictive practices in the United States contribute to poorer nutritional status and elevated mortality compared with some other parts of the world. However, in-center food practices in the United States have not been previously described. In 2011, we conducted a survey of clinic practices and clinician (dietitian, facility administrator, and medical director) opinions related to in-center food consumption within a large dialysis organization. After the initial survey, we provided clinicians with educational materials about eating during treatment. In 2014, we performed a follow-up survey. Differences in practices and opinions were analyzed using chi-squared tests and logistic regression. In 2011, 343 of 1199 clinics (28.6%) did not allow eating during treatment, 222 clinics (18.2%) did not allow drinking during treatment, and 19 clinics (1.6%) did not allow eating at the facility before or after treatment. In 2014, the proportion of clinics that did not allow eating during treatment had declined to 22.6% (321 of 1422 clinics), a significant shift in practice (Pnutritional status. Among clinicians, a higher percentage encouraged eating during treatment (53.1% versus 37.4%; P<0.05), and facility administrators and medical directors were less concerned about the seven reasons commonly cited for restricting eating during treatment in 2014 compared with 2011 (P<0.05 for all). We found that 28.6% and 22.6% of hemodialysis clinics within the United States restricted eating during treatment in 2011 and 2014, respectively, a rate more than double that found in an international cohort on which we previously published. However, practices and clinician opinions are shifting toward allowing patients to eat. Additional research is warranted to understand the effect that these practices have on patient outcomes and outline best practices. Copyright © 2016 by the American Society of

  3. Helping Health Care Providers and Clinical Scientists Understand Apparently Irrational Policy Decisions.

    Science.gov (United States)

    Demeter, Sandor J

    2016-12-21

    Health care providers (HCP) and clinical scientists (CS) are generally most comfortable using evidence-based rational decision-making models. They become very frustrated when policymakers make decisions that, on the surface, seem irrational and unreasonable. However, such decisions usually make sense when analysed properly. The goal of this paper to provide a basic theoretical understanding of major policy models, to illustrate which models are most prevalent in publicly funded health care systems, and to propose a policy analysis framework to better understand the elements that drive policy decision-making. The proposed policy framework will also assist HCP and CS achieve greater success with their own proposals.

  4. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  5. The anatomy of the sacrococcygeal cornual region and its clinical relevance.

    Science.gov (United States)

    Woon, Jason T K; Stringer, Mark D

    2014-09-01

    There has been no systematic study of the anatomy of the region between the sacral and coccygeal cornua. Reference texts describe an intercornual ligament connecting these structures. The aim of this study was to investigate the anatomy of this region, which may be relevant to unexplained cases of coccygeal pain (coccydynia) and local nerve blocks. The bony anatomy of the sacrococcygeal (SC) cornual region was analyzed in 33 CT scans obtained from supine adults of mostly European origin with no known SC pathology, 7 μCT scans of cadaver SC specimens, and 105 Asian Indian adult skeletons. A further five cadaver SC specimens were examined histologically. SC cornual fusion was seen in 45% of CT/μCT scans (mean age 67 years, 20 males) and in 20% of adult skeletons (78 males); there was no association with age or sex. In the absence of SC fusion, the mean intersacrococcygeal cornual gap was 7.1 ± 2.4 mm; this was bridged by an intercornual ligament composed of parallel vertical collagen fibers reinforced by elastin fibers on its anterior surface. Small nerve branches were observed adjacent to the ventral aspect of the intercornual ligament and, in one case, traversing the ligament. Ipsilateral sacral and coccygeal cornua are therefore normally bridged by an intercornual ligament that is probably innervated. The cornua are fused on one or both sides in 20-45% of adults. These findings may have implications for some cases of coccydynia and for anesthetists performing local nerve blocks.

  6. Psycho- and immunopharmacological factors relevant to selection of volunteers in clinical studies.

    Science.gov (United States)

    Meyer, F P

    2001-07-01

    There are many well-known factors and variables which play a role in the evaluation of pharmacokinetic and pharmacodynamic results gained from healthy volunteers. The genetic constitution is influenced by age, sex, circadian and seasonal variations, dietary factors, immunological function, alcohol intake, smoking, etc. Vesell repeatedly pointed out these facts some time ago [Vesell 1982, Vesell and Passananti 1977]. Since Janke [1964], we have suspected that personality traits can also influence the drug response. The following overview is dedicated to this field designated as differential psychopharmacology which, from the point of view ofthe author, has been given too little attention by pharmacologists and clinical pharmacologists. It has been demonstrated that the effect of psychotropic drugs, including placebo, can be differentially influenced by personality traits, e.g. introversion/extroversion, high level neuroticism/low level neuroticism and success motivation/failure motivation. For example, relatively high doses of diazepam (0.3 mg/kg), when compared to placebo, only impaired the psychophysical performance of extroverted volunteers whereas introverted volunteers remained unaffected. Pharmacokinetic parameters, e.g. absorption, biotransformation, can also be affected by the level of neuroticism or by anxiety, as demonstrated for diazepam, caffeine, paracetamol and theophylline. The absorption kinetics of diazepam and caffeine clearly differ between volunteers with high neuroticism scores and those with low neuroticism scores. Emotionally unstable volunteers absorbed the substances more quickly and more completely than emotionally stable volunteers. There were surprising differences in various immunological indices between dominant and submissive subjects. In dominant volunteers the immune system was more activated than in submissive volunteers. In the future, it will become increasingly necessary to obtain results for such target groups and to avoid

  7. Biotransformation of diazepam in a clinically relevant flat membrane bioreactor model using primary porcine hepatocytes.

    Science.gov (United States)

    Maringka, Michael; Giri, Shibashish; Nieber, Karen; Acikgöz, Ali; Bader, Augustinus

    2011-06-01

    In vitro biotransformation of drug using commercial culture medium with serum may not be the ideal culture medium for clinical application in extracorporeal bioartificial liver support (BAL) systems. In these systems, patient's blood or plasma is plumbed to primary hepatocytes within a seeded bioreactor, creating interaction between plasma and seeded hepatocytes. To address this situation, we investigated the biotransformation potential of diazepam in primary porcine hepatocytes with a flat membrane bioreactor (FMB); we used human plasma exposure and serum-free media in organotypical double gel culture model for long-term culture. We investigated diazepam clearance and all major metabolites of diazepam, such as oxazepam, temazepam, and desmethyldiazepam, in conventional single gel and organotypical sandwich models and compared them to the FMB model. Diazepam elimination was higher in double gel cultures with exposure to both SF 3 medium conditions and plasma, when compared to the single gel model in a Petri dish. It was observed that in the FMB, diazepam elimination was stable at about 3 pg/h/cell in plasma and SF 3 exposure. Oxazepam synthesis in the bioreactor was approximately one quarter less than in the Petri dish, but there were no differences between N-desmethyldiazepam and temazepam synthesis in double gel culture. In the flat membrane bioreactor, there was no decrease in the biotransformation of diazepam in plasma exposure compared with the control group. Our results suggest that this plasma exposure bioreactor may offer a useful approach in clinical use of extracorporeal BAL, as well as for drug metabolite investigation into toxicological research. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

  8. Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis.

    Science.gov (United States)

    Gall, Julie; Frisdal, Eric; Bittar, Randa; Le Goff, Wilfried; Bruckert, Eric; Lesnik, Philippe; Guerin, Maryse; Giral, Philippe

    2016-11-23

    The contribution of high-density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to evaluate the extent to which clinical and biological anomalies associated with the establishment of the metabolic syndrome modulate cholesterol efflux capacity and contribute to development of atherosclerosis. This study involved patients (n=1202) displaying atherogenic dyslipidemia in primary prevention who were referred to our prevention center. Among these patients, 25% presented at least 3 criteria of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. We measured the capacity of 40-fold diluted serum to mediate cholesterol efflux from cholesterol-loaded human THP-1 macrophages. Cholesterol efflux capacity was reduced progressively by 4% to 11% (Pmetabolic syndrome from 1 to 5. This observation was primarily related to reductions in scavenger receptor class B member 1 and ATP binding cassette subfamily G member 1-dependent efflux. Multivariate analyses indicate that serum efflux capacity was significantly associated with established metabolic syndrome (odds ratio 0.45; 95% CI 0.28-0.72; P=0.009) independent of age, low-density lipoprotein cholesterol, status with regard to lipid-lowering therapy, smoking status, and alcohol consumption. Our study revealed that individual criteria of metabolic syndrome are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Clinical implementation of total skin electron beam (TSEB) therapy: a review of the relevant literature.

    Science.gov (United States)

    Diamantopoulos, S; Platoni, K; Dilvoi, M; Nazos, I; Geropantas, K; Maravelis, G; Tolia, M; Beli, I; Efstathopoulos, E; Pantelakos, P; Panayiotakis, G; Kouloulias, V

    2011-04-01

    Total skin electron beam therapy has been in medical service since the middle of the last century in order to confront rare skin malignancies. Since then various techniques have been developed, all aiming at better clinical results in conjunction with less post-irradiation complications. In this article every available technique is presented in addition to physical parameters of technique establishment and common dose fractionation. This study also revealed the preference of the majority of institutes the last 20 years in "six dual field technique" at a high dose rate, which is a safe and effective treatment. Copyright © 2010 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  10. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M

    2017-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  11. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben

    2011-01-01

    Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically...... (Caw). All patients had spirometry, assessment of symptoms with questionnaires and low-dose CT scan as well as assessment of weight and body composition. We examined the following subgroups of COPD: Patients with 1) Severe emphysema, 2) Chronic bronchitis, 3) Frequent exacerbations, 4) Loss of lean...

  12. Teaching clinically relevant dental anatomy in the dental curriculum: description and assessment of an innovative module.

    Science.gov (United States)

    Obrez, Ales; Briggs, Charlotte; Buckman, James; Goldstein, Loren; Lamb, Courtney; Knight, William G

    2011-06-01

    The primary objective of the preclinical dental anatomy course in the predoctoral dental curriculum is to introduce students to cognitive and psychomotor skills related to the morphology and spatial and functional relationships of human dentition. Traditionally, didactic content for the subject is found in textbooks and course manuals and summarized by the faculty in lectures to the entire class. Psychomotor skills associated with recognition and reproduction of tooth morphology are traditionally learned by examining preserved tooth specimens and their cross-sections, combined with producing two-dimensional line drawings and carving teeth from wax blocks. These activities have little direct clinical application. In most cases, students are passive in the learning process, and assessment of student performance is unilateral and subjective. A recently revised dental anatomy module at the University of Illinois at Chicago College of Dentistry integrates independent class preparation with active small-group discussion and patient scenario-based wax-up exercises to replace missing tooth structure on manikin teeth. The goal of the revision is to shift emphasis away from decontextualized technical learning toward more active and clinically applicable learning that improves conceptual understanding while contributing to early acquisition of psychomotor skills. This article describes the rationale, components, and advantages of the revised module and presents a pre-post comparison of student learning outcomes for three class cohorts (N=203).

  13. Phylogeny of the clinically relevant species of the emerging fungus Trichoderma and their antifungal susceptibilities.

    Science.gov (United States)

    Sandoval-Denis, Marcelo; Sutton, Deanna A; Cano-Lira, José F; Gené, Josepa; Fothergill, Annette W; Wiederhold, Nathan P; Guarro, Josep

    2014-06-01

    A set of 73 isolates of the emerging fungus Trichoderma isolated from human and animal clinical specimens were characterized morphologically and molecularly using a multilocus sequence analysis that included the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and fragments of the translation elongation factor 1 alpha (Tef1), endochitinase CHI18-5 (Chi18-5), and actin 1 (Act1) genes. The most frequent species was Trichoderma longibrachiatum (26%), followed by Trichoderma citrinoviride (18%), the Hypocrea lixii/Trichoderma harzianum species complex (15%), the newly described species Trichoderma bissettii (12%), and Trichoderma orientale (11%). The most common anatomical sites of isolation in human clinical specimens were the respiratory tract (40%), followed by deep tissue (30%) and superficial tissues (26%), while all the animal-associated isolates were obtained from superficial tissue samples. Susceptibilities of the isolates to eight antifungal drugs in vitro showed mostly high MICs, except for voriconazole and the echinocandins. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. No clinically relevant effects in children after accidental ingestion of Panaeolina foenisecii (lawn mower's mushroom).

    Science.gov (United States)

    Schenk-Jaeger, Katharina M; Hofer-Lentner, Katharina E; Plenert, Bettina; Eckart, Dagmar; Haberl, Bettina; Schulze, Gabriele; Borchert-Avalone, Janine; Stedtler, Uwe; Pfab, Rudolph

    2017-03-01

    Panaeolina foenisecii is one of the most common and widely distributed lawn mushrooms in Europe and North America, and frequently involved in accidental mushroom ingestion, mainly in children. Nevertheless, there is contradictory information regarding the toxicity profile of P. foenisecii in the literature. Objective of the study was to assess clinical effects with particular attention on psychoactive properties of P. foenisecii in case of accidental oral exposure. This observational case series is based on prospectively collected data on mushroom poisoning using a structured data collection form, and it was performed in seven poisons centres in Germany and Switzerland. Inclusion criteria were accidental ingestion of at least one cap of P. foenisecii identified by a mycologist, and a follow up of at least 4 hours. Nineteen cases met all inclusion criteria, and only children were involved with a mean age of 3 years. They ingested 1-2 mushrooms in 14 cases and 3-5 mushrooms in five cases. Three patients received a single dose of activated charcoal. Sixteen out of 19 cases did not develop any symptoms, 2/19 complained of minor abdominal discomfort. One child was temporarily mildly hyperactive, and this was the only patient observed in a hospital for 12 hours. None of the children showed signs of hallucinations. This multicentre study demonstrates that the typically small amounts of P. foenisecii ingested by children probably do not lead to clinically significant symptoms.

  15. Assessment of elasticity of colorectal cancer tissue, clinical utility, pathological and phenotypical relevance

    Science.gov (United States)

    Kawano, Shingo; Kojima, Motohiro; Higuchi, Yoichi; Sugimoto, Motokazu; Ikeda, Koji; Sakuyama, Naoki; Takahashi, Shinichiro; Hayashi, Ryuichi; Ochiai, Atsushi; Saito, Norio

    2015-01-01

    Generally, cancer tissue is palpated as a hard mass. However, the elastic nature of cancer tissue is not well understood. The aim of the present study was to evaluate the clinical utility of measuring the elastic modulus (EM) in colorectal cancer tissue. Using a tactile sensor, we measured the EM of 106 surgically resected colorectal cancer tissues. Data on the EM were compared with clinicopathological findings, including stromal features represented by Azan staining and the α-SMA positive area ratio of the tumor area. Finally, a cDNA microarray profile of the tumors with high EM were compared with the findings of tumors with low EM. A higher EM in tumors was associated with pathological T, N, and M-stage tumors (P elasticity of colorectal cancer tissue may allow a more accurate clinical stage and prognosis estimation. The distinct phenotypical features of the high EM tumors and their strong association with stromal features suggest the existence of a biological mechanism involved in this phenomenon that may contribute to future therapy. PMID:26083008

  16. Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

    Science.gov (United States)

    Toris, Carol B; Gelfman, Claire; Whitlock, Andy; Sponsel, William E; Rowe-Rendleman, Cheryl L

    2017-09-01

    Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems. Here, we present the case for the development of such maps and consensus statements, which are critical for faster development of the most efficacious glaucoma therapy. We underscore that interrogating the preclinical path of both successful and unsuccessful clinical programs is essential to defining future research. One aspect of this is evaluation of available preclinical research tools. To begin this process, we highlight the utility of currently available animal models for glaucoma and emphasize that there is a particular need for models of glaucoma with normal intraocular pressure. In addition, we outline a series of discoveries from cell-based, animal, and translational research that begin to reveal a map of glaucoma from cell biology to physiology to disease pathology. Completion of these maps requires input and consensus from the global glaucoma research community. This article sets the stage by outlining various approaches to such a consensus. Together, these efforts will help accelerate basic science research, leading to discoveries with significant clinical impact for people with glaucoma.

  17. 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.

  18. Congenital left ventricular aneurysms and diverticula: definition, pathophysiology, clinical relevance and treatment.

    Science.gov (United States)

    Ohlow, Marc-Alexander

    2006-01-01

    A congenital left ventricular aneurysm or diverticulum is a rare cardiac malformation; 411 cases have been reported since its first description in 1816, and other cardiac, vascular or thoraco-abdominal abnormalities have been shown in about 70%. It appears to be a developmental anomaly, starting in the 4th embryonic week. Diagnosis can be made after exclusion of coronary artery disease, local or systemic inflammation or traumatic causes as well as cardiomyopathies. Clinically, most congenital left ventricular aneurysms and diverticula are asymptomatic or may cause systemic embolization, heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia or sudden cardiac death. Diagnosis is established by imaging studies such as echocardiography, magnetic resonance imaging or left ventricular angiography, visualizing the structural changes and accompanying abnormalities. Mode of treatment has to be individually tailored and depends on clinical presentation, accompanying abnormalities and possible complications; treatment options include surgical resection especially in symptomatic patients, anticoagulation after systemic embolization, radiofrequency ablation or implantation of an implantable cardioverter defibrillator in case of symptomatic ventricular tachycardia, occasionally combined with class I or III antiarrhythmic drugs. Copyright 2006 S. Karger AG, Basel.

  19. The trends of relevance about telling lung cancer diagnosis: social constraints, medical practice in several clinics.

    Science.gov (United States)

    Doruk, Sibel; Sevinç, Can; Sever, Fidan; Itil, Oya; Akkoçlu, Atila

    2012-01-01

    The aim of this study is to assess the opinions of relatives about telling the lung cancer diagnosis to the patient and evaluate the implementation in our hospital. A survey questionnaire was designed, and applied on nurses and physicians working in oncology care units, 4th-6th grade medical students, and relatives of cancer and non-cancer patients. Totally 347 (228 males, 119 females) participants (64 physicians, 100 nurses, 61 medical students, and 122 relatives of patients) with a mean age of 28 were enrolled in the study. 62.5% of doctors, 53.2% of nurses, 59.5% of medical students and 45.9% of relatives of lung cancer patients thought that the patient should be informed about his/her cancer diagnosis. 29.5% of the physicians told their patients about their diagnosis of cancer. Gender, age, abroad experience, academic career, speciality, and period of professional experience were not determined to have any impact on physician's opinion and clinical practices. It was determined that physicians care more about patients' right to be informed than other participating groups. Generally, although physicians agree that the diagnosis of cancer should be told to the patient, their routine clinical practices do not reflect this viewpoint.

  20. 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. PMID:26105141

  1. A Combined Patient and Provider Intervention for Management of Osteoarthritis in Veterans: A Randomized Clinical Trial.

    Science.gov (United States)

    Allen, Kelli D; Yancy, William S; Bosworth, Hayden B; Coffman, Cynthia J; Jeffreys, Amy S; Datta, Santanu K; McDuffie, Jennifer; Strauss, Jennifer L; Oddone, Eugene Z

    2016-01-19

    Management of osteoarthritis requires both medical and behavioral strategies, but some recommended therapies are underused. To examine the effectiveness of a combined patient and provider intervention for improving osteoarthritis outcomes. Cluster randomized clinical trial with assignment to osteoarthritis intervention and usual care groups. (ClinicalTrials.gov: NCT01130740). Department of Veterans Affairs Medical Center in Durham, North Carolina. 30 providers (clusters) and 300 outpatients with symptomatic hip or knee osteoarthritis. The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved delivery of patient-specific osteoarthritis treatment recommendations to primary care providers through the electronic medical record. The primary outcome was total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 12 months. Secondary outcomes were WOMAC function and pain subscale scores, physical performance (Short Physical Performance Battery), and depressive symptoms (Patient Health Questionnaire-8). Linear mixed models that were adjusted for clustering of providers assessed between-group differences in improvement in outcomes. At 12 months, WOMAC scores were 4.1 points lower (indicating improvement) in the osteoarthritis intervention group versus usual care (95% CI, -7.2 to -1.1 points; P = 0.009). WOMAC function subscale scores were 3.3 points lower in the intervention group (CI, -5.7 to -1.0 points; P = 0.005). WOMAC pain subscale scores (P = 0.126), physical performance, and depressive symptoms did not differ between groups. Although more patients in the osteoarthritis intervention group received provider referral for recommended osteoarthritis treatments, the numbers who received them did not differ. The study was conducted in a single Veterans Affairs medical center. The combined patient and provider intervention resulted in

  2. Effects of performance measure implementation on clinical manager and provider motivation.

    Science.gov (United States)

    Damschroder, Laura J; Robinson, Claire H; Francis, Joseph; Bentley, Douglas R; Krein, Sarah L; Rosland, Ann-Marie; Hofer, Timothy P; Kerr, Eve A

    2014-12-01

    Clinical performance measurement has been a key element of efforts to transform the Veterans Health Administration (VHA). However, there are a number of signs that current performance measurement systems used within and outside the VHA may be reaching the point of maximum benefit to care and in some settings, may be resulting in negative consequences to care, including overtreatment and diminished attention to patient needs and preferences. Our research group has been involved in a long-standing partnership with the office responsible for clinical performance measurement in the VHA to understand and develop potential strategies to mitigate the unintended consequences of measurement. Our aim was to understand how the implementation of diabetes performance measures (PMs) influences management actions and day-to-day clinical practice. This is a mixed methods study design based on quantitative administrative data to select study facilities and quantitative data from semi-structured interviews. Sixty-two network-level and facility-level executives, managers, front-line providers and staff participated in the study. Qualitative content analyses were guided by a team-based consensus approach using verbatim interview transcripts. A published interpretive motivation theory framework is used to describe potential contributions of local implementation strategies to unintended consequences of PMs. Implementation strategies used by management affect providers' response to PMs, which in turn potentially undermines provision of high-quality patient-centered care. These include: 1) feedback reports to providers that are dissociated from a realistic capability to address performance gaps; 2) evaluative criteria set by managers that are at odds with patient-centered care; and 3) pressure created by managers' narrow focus on gaps in PMs that is viewed as more punitive than motivating. Next steps include working with VHA leaders to develop and test implementation approaches to help

  3. Abortion providers seek to use RICO law as redress for clinic violence.

    Science.gov (United States)

    1993-12-17

    Abortion rights groups pursue multiple avenues for redress against abortion protesters at clinics around the US. The Supreme Court opinion in January 1993 in Bray vs. Alexandria Women's Health Clinic states that the Ku Klux Klan Act may not be used to protect clinics. A federal appeals court opinion states that a provision of the act does provide some protection for clinics. Both the Senate and House of Representatives passed bills making damage to an abortion clinic or intimidation of patients and staff a federal crime. The passage of this legislation into law is expected in early 1994. The case of NOW (the National Organization for Women) vs. Scheidler, initiated in 1986, is not expected to be ruled on until the summer of 1994. Depending upon the ruling, NOW will file another suit in a lower court referring to RICO (Racketeer Influenced and Corrupt Organizations Act) violations and a pattern of criminal activity. NOW's lawyer Fay Clayton puts forth the argument that clinic violence is a "nationwide campaign of terror" designed to halt the practice of abortion and is illegal under RICO. Robert Blakely, one of the original authors of RICO, represents Operation Rescue and the ProLife Action League. RICO was used in the past against mobsters, stock manipulators, and pornographers. Lower courts are inconsistent in the interpretation of whether the economic motive is essential for enforcement of RICO. RICO refers to "affairs" of an "enterprise" engaging in two or more incidents of criminal activity such as extortion, arson, and kidnapping. The Supreme Court criticized Congress for vague wording in the law and for not fulfilling its responsibility to refine the language. Congress has, since 1970, tried to rewrite the law without success. The US Solicitor General, attorney Miguel Estrada, argued that the economic motive requirement limits the role Congress intended for RICO. The administration may use RICO to prosecute terrorists in the World Trade Center bombing and

  4. The Swedish Family-Cancer Database: Update, Application to Colorectal Cancer and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hemminki Kari

    2005-01-01

    Full Text Available Abstract The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00 was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for

  5. Identification of clinically relevant Trichosporon species = Identifizierung von Triochosporon-Arten mit klinischer Bedeutung

    NARCIS (Netherlands)

    Middelhoven, W.J.

    2003-01-01

    A dichotomous identification key to pathogenic species of the basisiomycetous genus Trichosporon Behrend is provided. It is based on growth tests with carbon sources not traditionally used in yeast taxonomy, viz. uric acid, ethylamine, l-4-hydroxyproline, tyramine and L-phenylalanine as sources of

  6. Positive nickel patch tests in infants are of low clinical relevance and rarely reproducible

    DEFF Research Database (Denmark)

    Mortz, Charlotte G; Kjaer, Henrik F; Eller, Esben

    2013-01-01

    We have previously reported patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3-18 months of age. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity provided a patch test with an empty Finn chamber was ne...

  7. Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death

    Science.gov (United States)

    Novaleski, Carolyn K.; Carter, Bruce D.; Sivasankar, M. Preeti; Ridner, Sheila H.; Dietrich, Mary S.; Rousseau, Bernard

    2017-01-01

    Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold…

  8. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    Science.gov (United States)

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Characterising the myocardial interstitial space: the clinical relevance of non-invasive imaging.

    Science.gov (United States)

    White, Steven K; Sado, Daniel M; Flett, Andrew S; Moon, James C

    2012-05-01

    The myocardial interstitial or extracellular space exists as a complex and dynamic environment, vital for normal cardiac structure and function. The physiological pathways for normal control of collagen turnover, and the pathological development of fibrosis are beginning to be understood, as are their relationships to cardiac remodelling and adverse outcomes. Emerging non-invasive imaging techniques (echocardiography, cardiovascular magnetic resonance, positron emission tomography) may allow a clearer understanding and measurement of these processes in vivo. Preliminary results are exciting, spanning valvular and congenital heart disease, cardiomyopathy and rarer diseases such as amyloid. In this review, such developments and research directions are explored, including the rapid developments in cardiovascular magnetic resonance T1 mapping and its use with contrast to derive extracellular volume. The authors present a state-of-the-art assessment of the strengths and weaknesses of each modality, and distil a framework to equip the reader with an understanding of the technical issues useful for the interpretation of emerging clinical studies.

  10. [Formula: see text]The statistical crisis in science: how is it relevant to clinical neuropsychology?

    Science.gov (United States)

    Gelman, Andrew; Geurts, Hilde M

    There is currently increased attention to the statistical (and replication) crisis in science. Biomedicine and social psychology have been at the heart of this crisis, but similar problems are evident in a wide range of fields. We discuss three examples of replication challenges from the field of social psychology and some proposed solutions, and then consider the applicability of these ideas to clinical neuropsychology. In addition to procedural developments such as preregistration and open data and criticism, we recommend that data be collected and analyzed with more recognition that each new study is a part of a learning process. The goal of improving neuropsychological assessment, care, and cure is too important to not take good scientific practice seriously.

  11. Detection and clinical relevance of Staphylococcus aureus nasal carriage: an update.

    Science.gov (United States)

    Verhoeven, Paul O; Gagnaire, Julie; Botelho-Nevers, Elisabeth; Grattard, Florence; Carricajo, Anne; Lucht, Frédéric; Pozzetto, Bruno; Berthelot, Philippe

    2014-01-01

    Staphylococcus aureus nasal carriage is a well-defined risk factor of infection with this bacterium. The increased risk of S. aureus infection in nasal carriers is supported by the fact that the strains isolated from both colonization and infection sites are indistinguishable in most of the cases. Persistent nasal carriage seems to be associated with an increased risk of infection and this status could be defined now in clinical routine by using one or two quantitative nasal samples. There is evidence for supporting the detection of nasal carriage of S. aureus in patients undergoing cardiac surgery and in those undergoing hemodialysis in order to implement decolonization measures. More studies are needed to determine which carriers have the highest risk of infection and why decolonization strategies failed to reduce S. aureus infection in some other groups of patients.

  12. Pulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically relevant conditions

    DEFF Research Database (Denmark)

    Boissy, P; Levin Andersen, Thomas; Lund, T

    2008-01-01

    Myeloma bone disease is due to bone degradation by osteoclasts, and absence of repair by bone forming osteoblasts. Recent observations suggest that the anti-myeloma drug bortezomib, a proteasome inhibitor, stimulates bone formation and may inhibit bone resorption. Here, we tested bortezomib...... on cultured osteoclasts in conditions mimicking the pulse treatment used in the clinic, thereby avoiding continuous proteasome inhibition and unselective toxicity. A 3h pulse with 25nM bortezomib followed by a 3-day culture in its absence markedly inhibited osteoclast activity as evaluated through bone...... cells drastically reduced their survival. We measured next the levels of two bone resorption markers in patients during the 3 days following five and seven therapeutic bortezomib administrations, respectively. These levels decreased significantly already 1-2 days after injection, and then increased...

  13. Clinically relevant characteristics associated with early treatment drug use versus abstinence.

    Science.gov (United States)

    Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

    2014-04-04

    This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

  14. Visual Analytics for Pattern Discovery in Home Care. Clinical Relevance for Quality Improvement.

    Science.gov (United States)

    Radhakrishnan, Kavita; Monsen, Karen A; Bae, Sung-Heui; Zhang, Wenhui

    2016-07-27

    Visualization can reduce the cognitive load of information, allowing users to easily interpret and assess large amounts of data. The purpose of our study was to examine home health data using visual analysis techniques to discover clinically salient associations between patient characteristics with problem-oriented health outcomes of older adult home health patients during the home health service period. Knowledge, Behavior and Status ratings at discharge as well as change from admission to discharge that was coded using the Omaha System was collected from a dataset on 988 de-identified patient data from 15 home health agencies. SPSS Visualization Designer v1.0 was used to visually analyze patterns between independent and outcome variables using heat maps and histograms. Visualizations suggesting clinical salience were tested for significance using correlation analysis. The mean age of the patients was 80 years, with the majority female (66%). Of the 150 visualizations, 69 potentially meaningful patterns were statistically evaluated through bivariate associations, revealing 21 significant associations. Further, 14 associations between episode length and Charlson co-morbidity index mainly with urinary related diagnoses and problems remained significant after adjustment analyses. Through visual analysis, the adverse association of the longer home health episode length and higher Charlson co-morbidity index with behavior or status outcomes for patients with impaired urinary function was revealed. We have demonstrated the use of visual analysis to discover novel patterns that described high-needs subgroups among the older home health patient population. The effective presentation of these data patterns can allow clinicians to identify areas of patient improvement, and time periods that are most effective for implementing home health interventions to improve patient outcomes.

  15. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review.

    Science.gov (United States)

    Kamal, Rama M; van Noorden, Martijn S; Franzek, Ernst; Dijkstra, Boukje A G; Loonen, Anton J M; De Jong, Cornelius A J

    2016-01-01

    x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB. Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on x03B3;-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABAB receptors (GABABR; subunits GABAB1 and GABAB2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and β1-subunits of α4-GABAAR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse. The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant. © 2016 S. Karger AG, Basel.

  16. The morphology of acute disc herniation: a clinically relevant model defining the role of flexion.

    Science.gov (United States)

    Veres, Samuel P; Robertson, Peter A; Broom, Neil D

    2009-10-01

    Hydrostatically induced disruption of flexed lumbar intervertebral discs followed by microstructural investigation. To investigate how flexion affects the anulus' ability to resist rupture during hydrostatic loading, and determine how the characteristics of the resulting disc failures compare with those observed clinically. While compression of neutrally positioned motion segments consistently causes vertebral failure, compression of flexed segments can induce herniation. Why flexion has this effect remains unclear. A vast range of herniation characteristics have been documented clinically; whether flexion-related herniations are likely to possess a subset of these is unknown. Forty-two ovine lumbar motion segments, dissected from the same 3 levels of 14 spines, were each flexed 7 degrees or 10 degrees from the neutral position. While maintained at one of these angles, the nucleus of each segment was gradually injected with a viscous radio-opaque gel via an injection screw placed longitudinally within the inferior vertebra, until failure occurred. Each segment was then inspected using microcomputed tomography and oblique illumination microscopy in tandem. RESULTS.: Eighteen segments suffered disc failure; 14 of these were caused by direct radial rupture of the anular wall. All radial ruptures were located in the central posterior anulus. Nine radial ruptures contained nuclear material, which had breached the posterior longitudinal ligament in 1 disc, and reached it in 5 others forming transligamentous and subligamentous nuclear extrusions, respectively. The most common radial rupture route, occurring in 10 discs, involved a systematic anulus-endplate-anulus failure pattern. Flexion places the anulus at risk by facilitating nuclear flow, limiting circumferential disruption while promoting radial rupture, and rendering the endplate/vertebra junction vulnerable to failure. Flexion may play a developmental role in those herniations possessing a central posterior radial

  17. DNA Polymerase ɛ Deficiency Leading to an Ultramutator Phenotype: A Novel Clinically Relevant Entity.

    Science.gov (United States)

    Castellucci, Enrico; He, Tianfang; Goldstein, D Yitzchak; Halmos, Balazs; Chuy, Jennifer

    2017-05-01

    Deficiencies in DNA repair due to mutations in the exonuclease domain of DNA polymerase ɛ have recently been described in a subset of cancers characterized by an ultramutated and microsatellite stable (MSS) phenotype. This alteration in DNA repair is distinct from the better-known mismatch repair deficiencies which lead to microsatellite instability (MSI) and an increased tumor mutation burden. Instead, mutations in POLE lead to impaired proofreading intrinsic to Pol ɛ during DNA replication resulting in a dramatically increased mutation rate. Somatic mutations of Pol ɛ have been found most frequently in endometrial and colorectal cancers (CRC) and can lead to a unique familial syndrome in the case of germline mutations. While other key genomic abnormalities, such as MSI, have known prognostic and treatment implications, in this case it is less clear. As molecular genotyping of tumors becomes routine in the care of cancer patients, less common, but potentially actionable findings such as these POLE mutations could be overlooked unless appropriate algorithms are in place. We present two cases of metastatic CRC with a POLE mutation, both of which are ultramutated and MSS. The basic biochemical mechanisms leading to a unique phenotype in POLE deficiency as well as challenges faced with interpreting the genomic profiling of tumors in this important subset of patients and the potential clinical implications will be discussed here. The Oncologist 2017;22:497-502 KEY POINTS: Clinicians should recognize that tumors with high tumor mutation burden and that are microsatellite stable may harbor a POLE mutation, which is associated with an ultramutated phenotype.Work-up for POLE deficiency should indeed become part of the routine molecular testing paradigm for patients with colorectal cancer.This subset of patients may benefit from clinical trials where the higher number of mutation-associated neoantigens and defect in DNA repair may be exploited therapeutically. © Alpha

  18. Relationship of premenstrual syndrome and premenstrual dysphoric disorder with major depression: relevance to clinical practice.

    Science.gov (United States)

    Padhy, Susanta Kumar; Sarkar, Sidharth; Beherre, Prakash B; Rathi, Rajesh; Panigrahi, Mahima; Patil, Pradeep Sriram

    2015-01-01

    Premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD) and depressive disorder are fairly common; symptoms do overlap, often under-identified and under-emphasized, particularly in rural India. The objective was to assess the occurrence of PMS and PMDD in a sample of students and staff of a nursing college and to find their correlation with depression. A prospective cohort study; Tertiary Care Hospital in Rural India (Wardha, Maharashtra); 118 female nursing students or staff aged between 18 and 40 years, who were likely to stay within the institution for the study period. The participants were rated on Penn daily symptom report prospectively for a period of 3-month. Those who scored positive were applied diagnostic and statistical manual of mental disorders, 4(th) edition, text revision (DSM-IV TR) criteria for PMDD; and were applied primary care evaluation of mental disorders depression screening followed by DSM-IV TR criteria for depression. Severity of depression was measured using Hamilton Depression Rating Scale. Main outcome measures were frequency and severity of depression in individuals with PMS and PMDD and their clinical and sociodemographic correlation. The age range of the sample was 18-37 years. Some PMS symptoms were observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the sample. 46.4% of those with depressive symptoms had major depression. The diagnosis of major depression was significantly associated with the severity of PMS symptoms as well as the presence of PMDD. Premenstrual syndrome is present in a substantial proportion of young females. Concurrent depression is increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist needs to screen such subjects for depression and refer to mental-health professional early, in routine clinical practice.

  19. [Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population].

    Science.gov (United States)

    Cabrera-Mendoza, F; Gainza-Lagunes, S; Castañeda-Andrade, I; Castro-Zárate, A

    2014-01-01

    Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  20. A rapid evidence-based service by librarians provided information to answer primary care clinical questions.

    Science.gov (United States)

    McGowan, Jessie; Hogg, William; Rader, Tamara; Salzwedel, Doug; Worster, Danielle; Cogo, Elise; Rowan, Margo

    2010-03-01

    A librarian consultation service was offered to 88 primary care clinicians during office hours. This included a streamlined evidence-based process to answer questions in fewer than 20 min. This included a contact centre accessed through a Web-based platform and using hand-held devices and computers with Web access. Librarians were given technical training in evidence-based medicine, including how to summarise evidence. To describe the process and lessons learned from developing and operating a rapid response librarian consultation service for primary care clinicians. Evaluation included librarian interviews and a clinician exit satisfaction survey. Clinicians were positive about its impact on their clinical practice and decision making. The project revealed some important 'lessons learned' in the clinical use of hand-held devices, knowledge translation and training for clinicians and librarians. The Just-in-Time Librarian Consultation Service showed that it was possible to provide evidence-based answers to clinical questions in 15 min or less. The project overcame a number of barriers using innovative solutions. There are many opportunities to build on this experience for future joint projects of librarians and healthcare providers.

  1. Using a Standardized Clinical Quantitative Sensory Testing Battery to Judge the Clinical Relevance of Sensory Differences Between Adjacent Body Areas.

    Science.gov (United States)

    Dimova, Violeta; Oertel, Bruno G; Lötsch, Jörn

    2017-01-01

    Skin sensitivity to sensory stimuli varies among different body areas. A standardized clinical quantitative sensory testing (QST) battery, established for the diagnosis of neuropathic pain, was used to assess whether the magnitude of differences between test sites reaches clinical significance. Ten different sensory QST measures derived from thermal and mechanical stimuli were obtained from 21 healthy volunteers (10 men) and used to create somatosensory profiles bilateral from the dorsum of the hands (the standard area for the assessment of normative values for the upper extremities as proposed by the German Research Network on Neuropathic Pain) and bilateral at volar forearms as a neighboring nonstandard area. The parameters obtained were statistically compared between test sites. Three of the 10 QST parameters differed significantly with respect to the "body area," that is, warmth detection, thermal sensory limen, and mechanical pain thresholds. After z-transformation and interpretation according to the QST battery's standard instructions, 22 abnormal values were obtained at the hand. Applying the same procedure to parameters assessed at the nonstandard site forearm, that is, z-transforming them to the reference values for the hand, 24 measurements values emerged as abnormal, which was not significantly different compared with the hand (P=0.4185). Sensory differences between neighboring body areas are statistically significant, reproducing prior knowledge. This has to be considered in scientific assessments where a small variation of the tested body areas may not be an option. However, the magnitude of these differences was below the difference in sensory parameters that is judged as abnormal, indicating a robustness of the QST instrument against protocol deviations with respect to the test area when using the method of comparison with a 95 % confidence interval of a reference dataset.

  2. The difficulty of making psychology research and clinical practice relevant to medicine: experiences and observations.

    Science.gov (United States)

    Kessler, Rodger

    2008-03-01

    Psychology and medicine research and practice have demonstrated substantial and unique bodies of knowledge designed to both improve patient care and respond to contemporary health care needs for use of evidence and cost consciousness. At their full potential they represent a significant paradigm shift in healthcare. Despite impressive successes, it is clear that we are just on the cusp of such a change. These findings have had limited impact and penetration into medical practice, particularly outside of academic medicine and large, organized systems of health care, and there are multiple examples of such limitations in various arenas of health care. There also appear to be common themes to such examples which provide us opportunities to consider how psychologists might move things ahead. They also suggest how our unique position in academic medicine can both limit our impact and provide ways of creating continued shifts in the healthcare paradigm.

  3. Effects of computer-aided clinical decision support systems in improving antibiotic prescribing by primary care providers: a systematic review.

    Science.gov (United States)

    Holstiege, Jakob; Mathes, Tim; Pieper, Dawid

    2015-01-01

    To assess the effectiveness of computer-aided clinical decision support systems (CDSS) in improving antibiotic prescribing in primary care. A literature search utilizing Medline (via PubMed) and Embase (via Embase) was conducted up to November 2013. Randomized controlled trials (RCTs) and cluster randomized trials (CRTs) that evaluated the effects of CDSS aiming at improving antibiotic prescribing practice in an ambulatory primary care setting were included for review. Two investigators independently extracted data about study design and quality, participant characteristics, interventions, and outcomes. Seven studies (4 CRTs, 3 RCTs) met our inclusion criteria. All studies were performed in the USA. Proportions of eligible patient visits that triggered CDSS use varied substantially between intervention arms of studies (range 2.8-62.8%). Five out of seven trials showed marginal to moderate statistically significant effects of CDSS in improving antibiotic prescribing behavior. CDSS that automatically provided decision support were more likely to improve prescribing practice in contrast to systems that had to be actively initiated by healthcare providers. CDSS show promising effectiveness in improving antibiotic prescribing behavior in primary care. Magnitude of effects compared to no intervention, appeared to be similar to other moderately effective single interventions directed at primary care providers. Additional research is warranted to determine CDSS characteristics crucial to triggering high adoption by providers as a perquisite of clinically relevant improvement of antibiotic prescribing. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.comFor numbered affiliations see end of article.

  4. Knowledge of and attitudes toward clinical depression among health providers in Gujarat, India.

    Science.gov (United States)

    Almanzar, Santiago; Shah, Nirsarg; Vithalani, Suril; Shah, Sandip; Squires, James; Appasani, Raghu; Katz, Craig L

    2014-01-01

    Clinical depression is a major leading cause of morbidity and mortality but it is oftentimes overlooked and undertreated. The negative perception and lack of understanding of this condition prevents millions of people from seeking appropriate and on-time medical help, leading to distress and increased burden for affected people and their families. The implementation of public education campaigns and training of non-psychiatric health professionals on mental health and clinical depression has been neglected in several countries, including India, which is the second most populous country in the world with a population of more than 1.2 billion people, almost one-fifth of the world's population. This study sought to explore the knowledge and attitudes toward the diagnosis and treatment of clinical depression in nonpsychiatric health care providers in Vadodara, Gujarat, India. A cross-sectional survey was conducted over a 4-week period In Gujarat, India among resident physicians and community health workers about their knowledge and views on clinical depression. We found considerable stigma and misinformation about depression especially among health care workers in India. Most of the community health workers had a great deal of difficulty when defining clinical depression, and a large majority said that they never heard about depression or its definition and although the overwhelming majority of respondents did not believe that clinical depression results from a punishment from God (82% disagreed or strongly disagreed with this belief) or evil spirits (77.5%), a much smaller proportion disagreed with the assertions that depression was either solely due to difficult circumstances (38.2%) or that sufferers only had themselves to blame (47.2%). Meanwhile, only 32.6% disagreed with the position that clinical depression is a sign of weakness and 39.4% disagreed with the statement that suicide was a sign of weakness. Our findings underscore the considerable public health

  5. 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.

  6. Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy.

    Science.gov (United States)

    Grobben, R B; Vrijenhoek, J E P; Nathoe, H M; Den Ruijter, H M; van Waes, J A R; Peelen, L M; van Klei, W A; de Borst, G J

    2016-04-01

    Myocardial infarction (MI) is a frequent complication of carotid endarterectomy (CEA), yet most events are silent. Routine post-operative monitoring of cardiac troponin was implemented to facilitate timely recognition of MI and stratify high risk patients. The aim was to evaluate the incidence of troponin elevation after CEA and its association with adverse cardiovascular events. This analysis included patients ≥60 years old who underwent CEA, whose troponin-I levels were routinely monitored post-operatively and were included in a cohort study that assessed clinical outcomes. A clinical troponin cutoff of 60 ng/L was used. The primary endpoint was the composite of MI, stroke, and cardiovascular death. Secondary endpoints were MI, stroke, coronary intervention, cardiovascular death, and all cause death. 225 consecutive patients were included in the analysis. Troponin elevation occurred in 34 patients (15%) and a post-operative MI was diagnosed in eight patients. After a median follow up of 1.8 years (IQR 1.0-2.6), the primary endpoint occurred in 29% of patients with troponin elevation versus 6.3% without (HR 5.6, 95% CI 2.4-13), MI in 24% versus 1.6% (HR 18.0, 95% CI 4.7-68), stroke in 5.9% versus 4.2% (HR 1.4, 95% CI 0.3-6.7), coronary intervention in 5.9% versus 2.6% (HR 2.7, 95% CI 0.5-14), cardiovascular death in 5.9% versus 0.5% (HR 11.8, 95% CI 1.1-131), and all cause death in 15% versus 5.8% (HR 3.0, 95% CI 1.0-8.7), respectively. Incidences of the primary endpoint and all cause mortality in patients with a post-operative MI versus "troponin only" were 25% versus 7.7% and 25% versus 12%, respectively. Troponin elevation after CEA occurred in 15% of patients. The incidence of adverse cardiovascular events was significantly higher in patients with troponin elevation, which was mainly attributable to silent non-ST segment elevation MIs that occurred in the early post-operative phase. Copyright © 2015 European Society for Vascular Surgery. Published by

  7. Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial.

    Science.gov (United States)

    Harks, Inga; Koch, Raphael; Eickholz, Peter; Hoffmann, Thomas; Kim, Ti-Sun; Kocher, Thomas; Meyle, Joerg; Kaner, Doğan; Schlagenhauf, Ulrich; Doering, Stephan; Holtfreter, Birte; Gravemeier, Martina; Harmsen, Dag; Ehmke, Benjamin

    2015-09-01

    We investigated the long-term impact of adjunctive systemic antibiotics on periodontal disease progression. Periodontal therapy is frequently supplemented by systemic antibiotics, although its impact on the course of disease is still unclear. This prospective, randomized, double-blind, placebo-controlled multi-centre trial comprising patients suffering from moderate to severe periodontitis evaluated the impact of rational adjunctive use of systemic amoxicillin 500 mg plus metronidazole 400 mg (3x/day, 7 days) on attachment loss. The primary outcome was the percentage of sites showing further attachment loss (PSAL) ≥1.3 mm after the 27.5 months observation period. Standardized therapy comprised mechanical debridement in conjunction with antibiotics or placebo administration, and maintenance therapy at 3 months intervals. From 506 participating patients, 406 were included in the intention to treat analysis. Median PSAL observed in placebo group was 7.8% compared to 5.3% in antibiotics group (Q25 4.7%/Q75 14.1%; Q25 3.1%/Q75 9.9%; p antibiotics showed a small absolute, although statistically significant, additional reduction in further attachment loss. Therapists should consider the patient's overall risk for periodontal disease when deciding for or against adjunctive antibiotics prescription. © 2015 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  8. Resistance to antibiotics of clinical relevance in the fecal microbiota of Mexican wildlife.

    Directory of Open Access Journals (Sweden)

    Jurgi Cristóbal-Azkarate

    Full Text Available There are a growing number of reports of antibiotic resistance (ATBR in bacteria living in wildlife. This is a cause for concern as ATBR in wildlife represents a potential public health threat. However, little is known about the factors that might determine the presence, abundance and dispersion of ATBR bacteria in wildlife. Here, we used culture and molecular methods to assess ATBR in bacteria in fecal samples from howler monkeys (Alouatta palliata, spider monkeys (Ateles geoffroyi, tapirs (Tapirus bairdii and felids (jaguars, Panthera onca; pumas, Puma concolor; jaguarundis, Puma yagouaroundi; and ocelots, Leopardus pardalis living freely in two regions of the Mexican state of Veracruz under different degrees of human influence. Overall, our study shows that ATBR is commonplace in bacteria isolated from wildlife in southeast Mexico. Most of the resistances were towards old and naturally occurring antibiotics, but we also observed resistances of potential clinical significance. We found that proximity to humans positively affected the presence of ATBR and that ATBR was higher in terrestrial than arboreal species. We also found evidence suggesting different terrestrial and aerial routes for the transmission of ATBR between humans and wildlife. The prevalence and potential ATBR transfer mechanisms between humans and wildlife observed in this study highlight the need for further studies to identify the factors that might determine ATBR presence, abundance and distribution.

  9. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura

    2014-01-01

    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  10. Addition of benzalkonium chloride to self-adhesive resin-cements: some clinically relevant properties.

    Science.gov (United States)

    Oguz Ahmet, Serra; Mutluay, M Murat; Seyfioglu Polat, Zelal; Seseogullari Dirihan, Roda; Bek, Bulent; Tezvergil-Mutluay, Arzu

    2014-11-01

    The clinical survival rates of the adhesive restorations are limited due to the deterioration of resin-dentin bonds over time, partly due to the endogenous enzymatic activity of dentin. Recently, benzalkonium chloride (BAC) has been shown to effectively inhibit endogenous protease activity of dentin. This study evaluated the effect of different concentrations of benzalkonium chloride (BAC) on the degree of conversion (DC), vickers hardness (VH), setting time (ST) and biaxial flexural strength (FS) of two self-adhesive resin luting cements (RC). Two RC SpeedCEM (Ivoclar-Vivadent) and BisCem (Bisco) were modified by addition of 0.1, 0.5, 1, 1.5, 2 wt% BAC. The luting cements without the addition of BAC served as control. The DC (FT-IR/ATR from the bottom of the resin disc), vickers hardness (from top and bottom of the light-cured specimen), setting time (ISO 4049) and biaxial flexural strength (0.6 × 6 mm discs) of the specimens were tested. Data were analyzed using ANOVA and Tukeys HSD. DC results were in the range of 70-80%, with some significant changes in BisCem (p adhesive resin luting cements during the mixing procedure does not significantly affect the degree of conversion or flexural strength of the luting agent and may be a good option to improve the durability of adhesive interface.

  11. Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification.

    LENUS (Irish Health Repository)

    Levis, J

    2012-02-03

    BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient\\'s first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168\\/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7\\/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33\\/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

  12. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

    Directory of Open Access Journals (Sweden)

    Christopher M Bryant

    Full Text Available Lung adenocarcinoma (AD represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87 and Europe (N = 89 using the identical analytic procedures.

  13. Clinical relevance and evaluation of genitoanal papilloma virus infection in the male.

    Science.gov (United States)

    von Krogh, G

    1992-09-01

    In the light of current epidemiological data, demonstrating a high prevalence of genitoanal papilloma virus infection (GPVI) existing merely in a subclinical or latent form, ambiguity has emanated on the level of ambition that should be considered optimal for the management of GPVI in the male. This review addresses a pragmatic approach to the problem, with an emphasis on diagnosing and treating overt condylomas causing psychosexual disturbance because of the growth of disfiguring but medically rather innocent condylomas, and of flat acetowhite lesions that cause symptoms such as itching, burning, and dyspareunia. The evaluation of children afflicted with genitoanal warts is elucidated. The significance of intraepithelial neoplastic transformation associated with high-risk human papillomavirus (HPV) types such as HPV 16 is discussed, with reference to immunocompetent and immunosuppressed men. Although unequivocal histopathological signs of HPV influence often are absent, conventional light microscopy is usually adequate for differential diagnostic evaluation in clinical routine. In situ hybridization for the detection of HPV DNA may improve histopathologic accuracy.

  14. Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult personality disorders: A clinically relevant empirical investigation.

    Science.gov (United States)

    Gazzillo, Francesco; Lingiardi, Vittorio; Del Corno, Franco; Genova, Federica; Bornstein, Robert F; Gordon, Robert M; McWilliams, Nancy

    2015-06-01

    The aim of this study is to explore the relationship between level of personality organization and type of personality disorder as assessed with the categories in the Psychodynamic Diagnostic Manual (PDM; PDM Task Force, 2006) and the emotional responses of treating clinicians. We asked 148 Italian clinicians to assess 1 of their adult patients in treatment for personality disorders with the Psychodiagnostic Chart (PDC; Gordon & Bornstein, 2012) and the Personality Diagnostic Prototype (PDP; Gazzillo, Lingiardi, & Del Corno, 2012) and to complete the Therapist Response Questionnaire (TRQ; Betan, Heim, Zittel-Conklin, & Westen, 2005). The patients' level of overall personality pathology was positively associated with helpless and overwhelmed responses in clinicians and negatively associated with positive emotional responses. A parental and disengaged response was associated with the depressive, anxious, and dependent personality disorders; an exclusively parental response with the phobic personality disorder; and a parental and criticized response with narcissistic disorder. Dissociative disorder evoked a helpless and parental response in the treating clinicians whereas somatizing disorder elicited a disengaged reaction. An overwhelmed and disengaged response was associated with sadistic and masochistic personality disorders, with the latter also associated with a parental and hostile/criticized reaction; an exclusively overwhelmed response with psychopathic patients; and a helpless response with paranoid patients. Finally, patients with histrionic personality disorder evoked an overwhelmed and sexualized response in their clinicians whereas there was no specific emotional reaction associated with the schizoid and the obsessive-compulsive disorders. Clinical implications of these findings were discussed. (c) 2015 APA, all rights reserved).

  15. Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma.

    Science.gov (United States)

    Eckert, Alexander W; Wickenhauser, Claudia; Salins, Paul C; Kappler, Matthias; Bukur, Juergen; Seliger, Barbara

    2016-04-05

    Changes in the tumor microenvironment and immune surveillance represent crucial hallmarks of various kinds of cancer, including oral squamous cell carcinoma (OSCC), and a close crosstalk of hypoxia regulating genes, an activation of chemokines and immune cells has been described. A review about the pivotal role of HIF-1, its crosstalk to various cornerstones in OSCC tumorigenesis is presented. Hypoxia is a frequent event in OSCC and leads to a reprogramming of the cellular metabolism in order to prevent cell death. Hypoxic OSCC cells induce different adaptive changes such as anaerobic glycolysis, pH stabilisation and alterations of the gene and protein expression profile. This complex metabolic program is orchestrated by the hypoxia inducible factor (HIF)-1, the master regulator of early tumor progression. Hypoxia-dependent and -independent alterations in immune surveillance lead to different immune evasion strategies, which are partially mediated by alterations of the tumor cells, changes in the frequency, activity and repertoire of immune cell infiltrates and of soluble and environmental factors of the tumor micromilieu with consecutive generation of an immune escape phenotype, progression of disease and poor clinical outcome of OSCC patients. This review focusses on the importance of HIF-1 in the adaption and reprogramming of the metabolic system to reduced oxygen values as well as on the role of the tumor microenvironment for evasion of OSCC from immune recognition and destruction.

  16. Donepezil across the spectrum of Alzheimer's disease: dose optimization and clinical relevance.

    Science.gov (United States)

    Lee, J-H; Jeong, S-K; Kim, B C; Park, K W; Dash, A

    2015-05-01

    Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. AD is the most common cause of dementia worldwide, and its incidence is increasing in line with population aging. The primary feature of AD is progressive cognitive decline, and severe AD is characterized by reduced communication skills and mobility. However, successful treatment can substantially improve quality of life. Donepezil is an acetylcholinesterase inhibitor approved for use across the full spectrum of mild, moderate, and severe AD. Donepezil has been available at doses of 5 or 10 mg once daily for more than a decade and, more recently, a single high once-daily sustained-release 23-mg dose has been approved for treatment of patients with moderate to severe AD. The rationale for the higher dose formulation was the expected increase in acetylcholinesterase inhibition given the dose-response relationship of donepezil, with the benefits of the higher dose being most apparent in patients with more advanced AD. Donepezil 5 and 10 mg/day have been well studied in mild-to-moderate AD, and a clinical trial has confirmed the benefits of donepezil 23 mg/day in patients with moderate to severe AD, particularly for language and visuospatial ability. This review presents an overview of the evidence for donepezil across the spectrum of AD, with a focus on dose optimization for disease progression. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Microbiological Features and Clinical Relevance of New Species of the Genus Mycobacterium

    Science.gov (United States)

    2014-01-01

    SUMMARY Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact that NTM are characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the “new” mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of the Mycobacterium tuberculosis complex described in the last few years are also an object of the present review. PMID:25278573

  18. Clinical relevance of the study of hepatitis B virus covalently closed circular DNA.

    Science.gov (United States)

    Kumar, Rajneesh; Pérez-Del-Pulgar, Sofía; Testoni, Barbara; Lebossé, Fanny; Zoulim, Fabien

    2016-01-01

    Hepatitis B virus (HBV) remains a public health concern with 240 million people affected worldwide. HBV is an hepadnavirus that replicates its genome in hepatocytes. One of the key steps of the viral life cycle is the formation of cccDNA - covalently closed circular DNA - in the nucleus, the equivalent of a viral mini-chromosome that acts as a template for subsequent virus replication. Current antiviral medications are not effective in eradicating cccDNA, which can persist in the infected liver even in the absence of detectable HBV DNA or HBsAg in the blood. cccDNA cannot be measured in serum, and few surrogate markers have been proposed. Persistent cccDNA has been associated with various clinical events, including viral reactivation induced by immunosuppressive therapies, HBV recurrence after liver transplantation and hepatocellular carcinoma (HCC). cccDNA remains the main target to achieve a cure of HBV infection, thus extensive efforts are being made to develop new antiviral concepts to degrade or silence cccDNA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases.

    Science.gov (United States)

    Iranzo, Alex; Santamaria, Joan; Tolosa, Eduard

    2009-12-01

    REM sleep behavior disorder (RBD) is characterized by vigorous movements associated with unpleasant dreams and increased electromyographic activity during REM sleep. Polysomnography with audiovisual recording is needed to confirm the diagnosis of RBD and to exclude other sleep disorders that can mimic its symptoms including obstructive sleep apnea, nocturnal hallucinations and confusional awakenings. RBD may be idiopathic or related to neurodegenerative diseases, particularly multiple system atrophy, Parkinson's disease and dementia with Lewy bodies. RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years. RBD should thus be considered an integral part of the disease process. When effective, neuroprotective strategies should be considered in subjects with idiopathic RBD. Patients with other neurodegenerative diseases, though, such as spinocerebellar ataxias, may also present with RBD. When clinically required, clonazepam at bedtime is effective in decreasing the intensity of dream-enacting behaviors and unpleasant dreams in both the idiopathic and secondary forms. When part of a neurodegenerative disorder the development of RBD is thought to reflect the location and extent of the underlying lesions involving the REM sleep centers of the brain (e.g., locus subceruleus, amygdala, etc.), leading to a complex multiple neurotransmitter dysfunction that involves GABAergic, glutamatergic and monoaminergic systems. RBD is mediated neither by direct abnormal alpha-synuclein inclusions nor by striatonigral dopaminergic deficiency alone.

  20. Clinician perceptions of providing natural family planning methods in Title X funded clinics.

    Science.gov (United States)

    Kelly, Patricia J; Witt, Jacki; McEvers, Kimberly; Enriquez, Maithe; Abshier, Patricia; Vasquez, Magda; McGee, Eve

    2012-01-01

    Natural family planning (NFP) methods are effective for contraception with proper and consistent use. However, only 1% of patients at federally funded Title X family planning clinics select NFP as a contraceptive method. The goal of this study was to understand from clinicians' perspectives the barriers and facilitators to providing NFP methods. Six telephone focus groups were conducted with 29 clinicians from Title X clinics across the United States and Puerto Rico. A hermeneutic method was used to analyze data for related themes. The overarching theme from the study was that participants had a strong desire to teach their patients how their bodies work and to empower them to learn to control fertility. Four subthemes emerged: patient misinformation and misunderstanding about fertility; provider ideas about ideal types of candidates for NFP; inconsistent patient teaching strategies; and lack of time to teach NFP methods. There is a need for increased NFP training for providers and efficient NFP patient teaching strategies to meet the needs of patients with limited knowledge about fertility. © 2011 by the American College of Nurse-Midwives.

  1. Current transcatheter devices to treat functional tricuspid regurgitation with discussion of issues relevant to clinical trial design.

    Science.gov (United States)

    Hahn, Rebecca T

    2017-05-01

    Functional or secondary tricuspid regurgitation (TR) has seen increased attention in recent times as relationships with clinically-relevant outcomes have come to light. Despite the association of increased mortality with significant TR, the disease remains under-recognized and thus relatively untreated. In addition, the disease itself has not been extensively studied and the interactions between annular dilatation, right heart disease and pulmonary hypertension are poorly understood. However, the high mortality and recurrence rate with current surgical replacement or repair techniques is well recognised, opening the door to transcatheter therapies for functional TR. The current perspective reviews the rationale for transcatheter solutions, describes some of the current approaches and discusses the ongoing questions of a poorly-studied condition which may limit the design of clinical trials for this disease.

  2. Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion

    Science.gov (United States)

    2014-01-01

    Background Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure. Methods Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion. Results Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3 ± 6.9% of initial value vs. 28.5 ± 5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0 ± 16.3% while in

  3. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction.

    Science.gov (United States)

    Gufford, Brandon T; Chen, Gang; Vergara, Ana G; Lazarus, Philip; Oberlies, Nicholas H; Paine, Mary F

    2015-09-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Key constituents in milk thistle, flavonolignans, were previously shown to be potent inhibitors of intestinal UDP-glucuronosyl transferases (UGTs), with IC50s ≤ 10 μM. Taken together, milk thistle preparations may perpetrate unwanted interactions with raloxifene. The objective of this work was to evaluate the inhibitory effects of individual milk thistle constituents on the intestinal glucuronidation of raloxifene using human intestinal microsomes and human embryonic kidney cell lysates overexpressing UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine that are critical to raloxifene clearance. The flavonolignans silybin A and silybin B were potent inhibitors of both raloxifene 4'- and 6-glucuronidation in all enzyme systems. The Kis (human intestinal microsomes, 27-66 µM; UGT1A1, 3.2-8.3 µM; UGT1A8, 19-73 µM; and UGT1A10, 65-120 µM) encompassed reported intestinal tissue concentrations (20-310 µM), prompting prediction of clinical interaction risk using a mechanistic static model. Silibinin and silymarin were predicted to increase raloxifene systemic exposure by 4- to 5-fold, indicating high interaction risk that merits further evaluation. This systematic investigation of the potential interaction between a widely used herbal product and chemopreventive agent underscores the importance of understanding natural product-drug interactions in the context of cancer prevention. Copyright © 2015 by The American Society for Pharmacology and Experimental

  4. Molecular identification, genotyping, and antifungal susceptibility testing of clinically relevant Trichosporon species from Argentina.

    Science.gov (United States)

    Taverna, Constanza Giselle; Córdoba, Susana; Murisengo, Omar Alejandro; Vivot, Walter; Davel, Graciela; Bosco-Borgeat, María Eugenia

    2014-05-01

    Trichosporon species are emerging causative agents of mycoses; most are documented in immunocompromised patients. Species identification is important for epidemiological purposes in order to better define species clinical associations and to improve antifungal treatment. Here, we studied a collection of 41 Trichosporon strains recovered from hospitalized patients in Argentina. All strains were identified by sequencing the D1/D2 domain of 26S, internal transcribed spacer (ITS) regions, and intergenic spacer 1 (IGS1) region. In addition, we determined the IGS1 region genotypes of the suspected T. asahii strains. Antifungal susceptibility of all strains was investigated. Thirty-eight of the 41 strains in this study were identified as follows: 29 T. asahii, 3 T. inkin, 3 T. montevideense, 2 T. faecale, and 1 T. dermatis. The identity of the three remaining strains could not be confirmed. Strain DMic 114126 (Culture collection of the Mycology Department (DMic), National Institute of Infectious Diseases "Dr. Carlos G. Malbrán".) may represent a T. asahii subspecies or a new Trichosporon species, strain DMic 94750 was identified as T. cf. guehoae and strain DMic 114132 as T. cf. akiyoshidainum. The distribution of T. asahii genotypes was as follows: 12 genotype 3, 9 genotype 1, 4 genotype 4, 2 genotype 5, and 2 genotype 7. Amphotericin B minimal inhibitory concentrations (MICs) were ≤1 mg/l for 78% (32/41) of the strains. Fluconazole MICs were ≥2 mg/l for 90% of the strains. However, itraconazole, voriconazole, ketoconazole, and posaconazole MICs were ≤1 mg/l for 100% of the strains. Terbinafine MICs were ≤1 mg/l for 98% 40/41 of the strains.

  5. [Clinical relevance of a routinely performed magnetic resonance cholangiopancreatography (MRCP) prior to cholecystectomy].

    Science.gov (United States)

    Schmidt, R; Tannheimer, M; Danz, B; Benesch, S; Geue, R

    2012-12-01

    A preoperative diagnostic imaging procedure is essential for therapy in cholecystolithiasis. According to the S3-Guidelines of the German Society for General and Visceral Surgery only an ultrasound scan is needed before a cholecystectomy. But an anatomic variant of the bile ducts or choledocholithiasis is poorly shown by an ultrasound. Because of this, we performed a magnetic resonance cholangiopancreatography (MRCP) routinely. This study was designed to show if the MRCP changed the treatment plan or changed the operation method. Furthermore, the sensitivity and specificity concerning abnormalities of the cystic duct, accessory bile ducts and choledocholithiasis should be determined. During the time between January 1st 2005 and September 30th 2009 541 patients were included in this retrospective study. Among the 541 cases 98 pathologies were found. These included 51 choledocholithiasis, 20 accessory bile ducts and 13 abnormal cystic ducts. In 29 of the 51 cases of choledocholithiasis a therapeutic splitting was performed only because of the MRCP. In 22 cases the diagnosis was also possible because of the basic diagnostic procedures like ultrasound, laboratory tests and clinical appearance. So the diagnostic aimprovement due to the MRCP is 5.3 %. Four of the 20 accessory bile ducts and 6 of the abnormal cystic ducts were found during the subsequent operation. The sensitivity concerning the anatomic variants is very low (38.5 % concerning the accessory bile ducts and 50 % for the abnormal cystic ducts). But the sensitivity in detecting a choledocholithiasis is very high (94.7 %). There was no evidence in our study that MRCP prevented any complications. The operation method was not changed in any case because of the MRCP result. A routinely performed preoperative MRCP cannot be recommended. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Anaerobic Bacteria with Clinical Relevance: Morphologic and Taxonomic Classification, Distribution among Human Microbiota and Microbiologic Diagnosis

    Directory of Open Access Journals (Sweden)

    João Alves

    2017-05-01

    Full Text Available The wide burden of anaerobic bacteria colonizing human body comprises about 90% of its total biomass. The biotic relationship between humans and its microbiota sets reciprocal benefits, albeit with pathogenic potencial for the human being in particular dysbiosis situations. Infections adjacent to or originating from the skin or mucous membranes of the intestinal, genitourinary and upper respiratory tracts are often polymicrobial in nature, whereby should anaerobes be invariably included in the etiological differential diagnosis of these conditions. Gram negative bacilli such as Bacteroides fragilis group, Fusobacterium spp., Porphyromonas spp., Prevotella spp. and Gram positive cocci such as Peptostreptococcus spp. stand out for their high virulence and frequence of isolation in suppurative infections and abcesses with metastatic or contiguous relation to human microbiota. The fastidious nature of anaerobic bacteria, especially of less aerotolerant species, compels to particular techniques of sample collection, transport and cultural isolation that challenge clinicians and microbiologists for a full efficient practice. Such requirements bring on a poor identification of anaerobic bacteria in the clinical practice and undervaluation of its aetiopathogenic potential amongst common polymicrobial infections. An approach over microbial flora’s composition in the different human anatomical sites is a primary goal of the present article. Clinicians are intended to recognize the variability and proportion of likely involved anaerobic microorganisms in certain infectious processes related to human microbiota, in order to optimize samples processing and the establishment of an appropriate empirical antibiotic therapy, mindful of anaerobic coverage and according to known susceptibility profiles.

  7. CLINICAL AND BIOLOGICAL RELEVANCE OF EZH2 IN TRIPLE NEGATIVE BREAST CANCER

    Science.gov (United States)

    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba

    2014-01-01

    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with clinicopathologic variables and patients’ outcome. Furthermore, in vivo EZH2 gene silencing was achieved using siRNA incorporated into chitosan nanoparticles. Out of 261 cases of invasive breast cancer, high expression of EZH2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype (P<.001) compared to all other non-triple negative breast cancers. Furthermore, high EZH2 was significantly associated with high histologic grade (P=.01), estrogen receptor negativity (P<.001), progesterone receptor negativity (P<.001), EGFR positivity (P=.04), and high p53 expression (P<.001). Survival analysis demonstrated that patients with high EZH2 had a poorer overall survival, compared to those with low EZH2 (P=.03), and it retained its significance as an independent prognostic factor (P=.02). In addition, EZH2 gene silencing resulted in significant reduction in tumor growth (P<.01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high EZH2 expression is significantly associated with triple-negative breast cancer and decreased survival. EZH2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation. PMID:22436627

  8. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    Science.gov (United States)

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  9. Distribution of cerebral amyloid deposition and its relevance to clinical phenotype in Lewy body dementia.

    Science.gov (United States)

    Fujishiro, Hiroshige; Iseki, Eizo; Higashi, Shinji; Kasanuki, Koji; Murayama, Norio; Togo, Takashi; Katsuse, Omi; Uchikado, Hirotake; Aoki, Naoya; Kosaka, Kenji; Arai, Heii; Sato, Kiyoshi

    2010-12-03

    Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are clinically distinguished based only on the duration of parkinsonism prior to dementia. It is known that there is considerable pathological overlap between these two conditions, but the pathological difference between them remains unknown. We evaluated Alzheimer-type pathology in 30 brains of patients with Lewy body dementia using standardized methods based on those of the Brain-Net Europe (BNE) Consortium. Only 2 of 13 PDD cases (15%) showed Aβ-immunoreactive pathology in the midbrain (amyloid phase IV). In contrast, 12 of 17 DLB cases (71%) exhibited midbrain involvement. Four of the DLB cases (24%) but none of the PDD cases exhibited Aβ-immunoreactive pathology in the cerebellum (amyloid phase V). The ratio of cases with subtentorial involvement of amyloid deposition was significantly higher in DLB than in PDD. The median of amyloid phases was significantly greater in DLB than in PDD, but there was no difference in neurofibrillary tangle (NFT) Braak stages or in Lewy body scores. When patients were classified according to whether dementia or parkinsonism had occurred first, the rate of dementia having occurred first was significantly greater in amyloid phase IV and V than in phase 0-I, with phase III in the middle, though there was no significant difference in median NFT Braak stage or mean Lewy body score associated with amyloid phase. These results suggest that amyloid deposition may contribute to the timing of the onset of dementia relative to that of parkinsonism in Lewy body dementia. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Relevance of anxiety in clinical practice of Guillain-Barre syndrome: a cohort study.

    Science.gov (United States)

    Sharshar, Tarek; Polito, Andrea; Porcher, Raphaël; Merhbene, Takoua; Blanc, Morgane; Antona, Marion; Durand, Marie-Christine; Friedman, Diane; Orlikowski, David; Annane, Djillali; Marcadet, Marie-Hélène

    2012-01-01

    Illness is often associated with anxiety, but few data exist about the prognostic significance of this phenomenon. To address this issue, we assessed whether patient anxiety is associated with subsequent need for intubation in Guillain-Barré syndrome (GBS). Incident case-cohort study. Acute secondary care in a teaching hospital (France) from 2006 to 2010. 110 adult GBS patients. Either language barrier or cognitive decline that precluded understanding was considered as exclusion criteria. Acute respiratory failure. At admission, anxiety and clinical factors (including known predictors of respiratory failure: delay between GBS onset and admission, inability to lift head, vital capacity (VC)) were assessed and related to subsequent need for mechanical ventilation (MV). Anxiety was assessed using a Visual Analogical Scale (VAS), the State Anxiety Inventory form Y1 (STAI-Y1) score and a novel-specific questionnaire, evaluating fears potentially triggered by GBS. Patients were asked to choose which they found most stressful from weakness, pain, breathlessness and uncertainty. 23 (22%) were subsequently ventilated. Mean STAI-Y1 was 47.2 (range 22-77) and anxiety VAS 5.2 (range 0-10). STAI was above 60/80 in 22 (21%) patients and anxiety VAS above 7/10 in 28 (27%) patients. Fear of remaining paralysed, uncertainty as to how the disease would progress and fear of intubation were the most stressful. Factors significantly associated with anxiety were weakness and bulbar dysfunction. STAI-Y1 was higher and uncertainty more frequent in subsequently ventilated patients, who had shorter onset-admission delay and greater weakness but not a lower VC. Uncertainty was independently associated with subsequent MV. Early management of patients with GBS should evaluate anxiety and assess its causes both to adjust psychological support and to anticipate subsequent deterioration.

  11. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    Directory of Open Access Journals (Sweden)

    Dezzutti Charlene

    2011-03-01

    Full Text Available Abstract Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic. Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

  12. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations.

    Science.gov (United States)

    Wang, Lin; Schnaare, Roger L; Dezzutti, Charlene; Anton, Peter A; Rohan, Lisa C

    2011-03-07

    The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

  13. The J curve in hypertension. Physiopathologic speculation or a relevant issue in clinical practice?

    Directory of Open Access Journals (Sweden)

    Giuliano Pinna

    2013-03-01

    Full Text Available Introduction: The J curve phenomenon in the treatment of hypertension refers to the view that reducing blood pressure below a certain critical point (diastolic pressure in particular is no longer beneficial and may actually increase the risk of cardiovascular events. The existence of this phenomenon has been debated for many years. Many autors deny that it exists, at least within the range of pressure values commonly observed in clinical practice. Aim of the study: The aim of this article is to verify whether in 2010 it is still possible to talk about a J curve or whether the inverse relationship between diastolic pressure and cardiovascular events depends on pre-existent diseases. Materials and methods: The authors carried out a search of the PubMed database for articles published in 2004 or later with the following Keywords J-curve, antihypertensive treatment, and blood pressure goals. Results: Most of the studies reviewed confirmed the existence of a J curve, but the role played by serious comorbidities is still unclear. In most cases, patients with major diseases have lower blood pressures. Moreover, cardiac patients already have impairments involving the coronary circulation. It is quite obvious that these patients are more exposed to pressure drops, especially those occurring during diastole, when the vast majority of blood flow to the coronary circulation is delivered. Conclusions: A J curve certainly exists: there is obviously a threshold value under which an excessively low blood pressure can no longer guarantee adequate perfusion of vital organs. The problem lies in the identification of this threshold value. Furthermore, considering the undeniable impact on this phenomenon of concurrent diseases, timely intervention is essential to avoid transforming low-risk patients (those less likely to experience J curve-related complications into high-risk patients (more likely to experience these complications.

  14. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product–Drug Interaction

    Science.gov (United States)

    Gufford, Brandon T.; Chen, Gang; Vergara, Ana G.; Lazarus, Philip; Oberlies, Nicholas H.

    2015-01-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Key constituents in milk thistle, flavonolignans, were previously shown to be potent inhibitors of intestinal UDP-glucuronosyl transferases (UGTs), with IC50s ≤ 10 μM. Taken together, milk thistle preparations may perpetrate unwanted interactions with raloxifene. The objective of this work was to evaluate the inhibitory effects of individual milk thistle constituents on the intestinal glucuronidation of raloxifene using human intestinal microsomes and human embryonic kidney cell lysates overexpressing UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine that are critical to raloxifene clearance. The flavonolignans silybin A and silybin B were potent inhibitors of both raloxifene 4′- and 6-glucuronidation in all enzyme systems. The Kis (human intestinal microsomes, 27–66 µM; UGT1A1, 3.2–8.3 µM; UGT1A8, 19–73 µM; and UGT1A10, 65–120 µM) encompassed reported intestinal tissue concentrations (20–310 µM), prompting prediction of clinical interaction risk using a mechanistic static model. Silibinin and silymarin were predicted to increase raloxifene systemic exposure by 4- to 5-fold, indicating high interaction risk that merits further evaluation. This systematic investigation of the potential interaction between a widely used herbal product and chemopreventive agent underscores the importance of understanding natural product–drug interactions in the context of cancer prevention. PMID:26070840

  15. A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival.

    Science.gov (United States)

    Lee, Karla C L; Palacios Jimenez, Carolina; Alibhai, Hatim; Chang, Yu-Mei; Leckie, Pamela J; Baker, Luisa A; Stanzani, Giacomo; L Priestnall, Simon; Mookerjee, Rajeshwar P; Jalan, Rajiv; Davies, Nathan A

    2013-04-01

    A clinically relevant, translational large animal model of acute liver failure (ALF) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation. The aim was to establish a pig model of acetaminophen-induced ALF that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time. Nine female pigs were anaesthetised and instrumented for continuous intensive care monitoring and management using: target-driven protocols for treatment of cardiovascular collapse, metabolic acidosis and electrolyte abnormalities; intermittent positive pressure ventilation; and continuous renal replacement therapy. Six animals were induced to ALF with acetaminophen (paracetamol). Three animals acted as controls. Irreversible acute liver failure, defined as rise in prothrombin time >3 times normal, occurred 19.3 ± 1.8 h after the onset of acetaminophen administration. Death occurred predictably 12.6 ± 2.7 h thereafter, with acute hepatocellular necrosis in all animals. Clinical progression of liver failure mimicked the human condition including development of coagulopathy, intracranial hypertension, hyperammonaemia, cardiovascular collapse, elevation in creatinine, metabolic acidosis and hyperlactataemia. In addition, cardiovascular monitoring clearly demonstrated progressive cardiac dysfunction in ALF. A reproducible, clinically relevant, intensively managed, large animal model of acute liver failure, with death as a result of multi-organ failure, has been successfully validated for translational studies of disease progression and therapies designed to prolong survival in man. © 2012 John Wiley & Sons A/S.

  16. The clinical relevance of embolic events detected by transesophageal echocardiography during cemented total hip arthroplasty: a randomized clinical trial.

    Science.gov (United States)

    Koessler, M J; Fabiani, R; Hamer, H; Pitto, R P

    2001-01-01

    The first aim of this prospective clinical study was to characterize the relationship between embolic events observed during cemented total hip arthroplasty using transesophageal echocardiography (TEE), and changes in cardiopulmonary function. The second aim was to assess the efficiency of a modified cementing technique that was developed to reduce the risk of embolism. The modification consists in a vacuum drainage placed in the proximal femur to reduce the increase of intramedullary pressure during insertion of the prosthesis. One hundred twenty patients were randomized into two groups. Group 1 received a total hip arthroplasty cemented conventionally, whereas Group 2 was cemented with the modified technique. Continuous TEE, hemodynamic monitoring, and blood gas analysis were done during the perioperative period. Severe embolic events were imaged during the insertion of the femoral component and the reduction of the hip joint. Embolism occurred in 93.3% of patients operated on with the conventional cementing technique, compared with 13.3% of patients operated on with the modified technique (P syndrome in any study patient. The results of the study indicate that embolic events observed using TEE can cause increased pulmonary shunt values during hip arthroplasty, especially in patients with systemic disease (ASA physical status III). The modified surgical technique effectively reduced the incidence of embolization during cemented hip arthroplasty. Use of conventional cementing techniques is associated with echocardiographic evidence of embolism in 93% of patients and with a significant increase in pulmonary shunting. The incidence of embolism and change in shunting are reduced with a modified cementing technique that limits increases in intramedullary pressure.

  17. Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seungil; Zaniewski, Richard P.; Marr, Eric S.; Lacey, Brian M.; Tomaras, Andrew P.; Evdokimov, Artem; Miller, J. Richard; Shanmugasundaram, Veerabahu (Pfizer)

    2012-02-08

    Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes nosocomial infections for which there are limited treatment options. Penicillin-binding protein PBP3, a key therapeutic target, is an essential enzyme responsible for the final steps of peptidoglycan synthesis and is covalently inactivated by {beta}-lactam antibiotics. Here we disclose the first high resolution cocrystal structures of the P. aeruginosa PBP3 with both novel and marketed {beta}-lactams. These structures reveal a conformational rearrangement of Tyr532 and Phe533 and a ligand-induced conformational change of Tyr409 and Arg489. The well-known affinity of the monobactam aztreonam for P. aeruginosa PBP3 is due to a distinct hydrophobic aromatic wall composed of Tyr503, Tyr532, and Phe533 interacting with the gem-dimethyl group. The structure of MC-1, a new siderophore-conjugated monocarbam complexed with PBP3 provides molecular insights for lead optimization. Importantly, we have identified a novel conformation that is distinct to the high-molecular-weight class B PBP subfamily, which is identifiable by common features such as a hydrophobic aromatic wall formed by Tyr503, Tyr532, and Phe533 and the structural flexibility of Tyr409 flanked by two glycine residues. This is also the first example of a siderophore-conjugated triazolone-linked monocarbam complexed with any PBP. Energetic analysis of tightly and loosely held computed hydration sites indicates protein desolvation effects contribute significantly to PBP3 binding, and analysis of hydration site energies allows rank ordering of the second-order acylation rate constants. Taken together, these structural, biochemical, and computational studies provide a molecular basis for recognition of P. aeruginosa PBP3 and open avenues for future design of inhibitors of this class of PBPs.

  18. Patient greeting preferences for themselves and their providers in a military family medicine clinic.

    Science.gov (United States)

    Laird, John E; Tolentino, Jerlyn C; Gray, Cynthia

    2013-10-01

    Using the proper greeting may be important to help establish rapport between health care providers and their patients. It may be particularly useful for family medicine physicians working in a military medical facility, where military rank and traditions are important. A total of 259 anonymous surveys were co