Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy.

PubMed

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-02-01

The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. This qualitative study was based on interviews with clinical investigators and parents of sons with Duchenne and Becker muscular dystrophy (DBMD) who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Participants were 12 parents of affected boys receiving active drug and 9 clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents' expectations; several worried about their own involvement in increasing parents' expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents' expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for the

Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy

PubMed Central

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-01-01

Background The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families, but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. Purpose We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. Methods This qualitative study was based on interviews with clinical investigators and parents of sons with DBMD who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Results Participants were twelve parents of affected boys receiving active drug and nine clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents’ expectations; several worried about their own involvement in increasing parents’ expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents’ expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for

Standardization of clinical pharmacist's activities: Methodology.

PubMed

Gregorová, Jana; Rychlíčková, Jitka; Šaloun, Jan

2017-09-01

Establishing standardized and controlled system of work at a clinical pharmacy department and establishing effective recording of activities of a group of four clinical pharmacist when providing clinical pharmaceutical care (CPC) in a hospital. The duration of evaluated period is 5.5 years. The first part was defining the purpose, methods and activities of clinical pharmaceutical care, the next part was designing the software for recording patient's data and CPC activities. To verify the functionality of our system the third part was conducted (from January 1, 2015 to June 30, 2015). CPC activities were defined precisely. During the 6 months period, 3946 patients were reviewed (17% of patients admitted), in this group, 41% patients was labeled as risk (these patients had one or more risk factor). 1722 repeated reviews were performed, 884 drug therapy recommendations were recorded. The calculated average time necessary for one CPC activity is 28 min. During the 5 year period, standardized system of work in clinical pharmacy department was established. This system is based on clearly defined activities and it enables external control. Our results supply data for negotiations with health insurance companies.

An academic writing needs assessment of English-as-a-second-language clinical investigators.

PubMed

Wang, Min-Fen; Bakken, Lori L

2004-01-01

Academic writing for publication is competitive and demanding for researchers. For the novice English-as-a-second-language (ESL) researcher, the pressure to publish compounds the difficulties of mastering the English language. Very few studies have used ESL graduate and post-graduate students as academic writing research subjects. The purpose of this project was to assess the learning needs of ESL clinical investigators regarding academic writing for English scholarly publication. A qualitative evaluation approach was used to examine the gap between the current and desired proficiency level for the academic writing of ESL clinical investigators. We considered the perspectives of seven ESL clinical investigators plus three mentors and three writing instructors. Semi-structured questions were asked. Field notes were organized using a field-work recording system. They were analyzed using the constant comparative method. ESL clinical investigators do not accurately perceive their writing deficiencies. They have little knowledge of criteria for academic writing and they are influenced by their prior English learning experiences in their home culture, which engender passive attitudes toward seeking appropriate writing resources. Adequate time is especially needed to develop successful writing skills. Four basic steps are recommended to guide program planners in developing ESL writing activities for professional learning: (1) recognize discrepancies, (2) establish clear standards and performance criteria for scholarly writing, (3) develop individual plans, and (4) organize long-term writing assistance.

21 CFR 812.119 - Disqualification of a clinical investigator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Disqualification of a clinical investigator. 812.119 Section 812.119 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 812.119 Disqualification of a clinical investigator. (a) If FDA has information indicating that an...

The value of formal clinical research training in initiating a career as a clinical investigator.

PubMed

Kapoor, Karan; Wu, Bechien U; Banks, Peter A

2011-12-01

The aim of this study was to determine whether formal clinical research training is of value in the initiation of a successful career as a clinical investigator. We conducted a retrospective review of the career choices of all 25 fellows who entered the Academic Clinical Research Track at Brigham and Women's Hospital since its inception in 1995 and examined the impact of formal clinical research training during their fellowship on their career choice. The primary measure of a successful career as a clinical investigator was the obtainment of external funding for clinical research within 3 years of completion of fellowship. Thirteen of the 25 fellows (52%) received a Master of Public Health (MPH) degree at the Harvard School of Public Health during their fellowship. Ten of these 13 fellows (77%) obtained external funding for clinical research within 3 years of completion of their fellowship. None of the 5 fellows who had already obtained an MPH degree prior to their fellowship and none of the 7 fellows who completed a 7-week summer Program in Clinical Effectiveness but did not complete an MPH degree attempted to receive external funding for clinical research within 3 years of completion of their fellowship. We conclude that formal clinical research training culminating in an MPH degree was extremely valuable in the initiation of a successful career as a clinical investigator.

Applying Active Learning to Assertion Classification of Concepts in Clinical Text

PubMed Central

Chen, Yukun; Mani, Subramani; Xu, Hua

2012-01-01

Supervised machine learning methods for clinical natural language processing (NLP) research require a large number of annotated samples, which are very expensive to build because of the involvement of physicians. Active learning, an approach that actively samples from a large pool, provides an alternative solution. Its major goal in classification is to reduce the annotation effort while maintaining the quality of the predictive model. However, few studies have investigated its uses in clinical NLP. This paper reports an application of active learning to a clinical text classification task: to determine the assertion status of clinical concepts. The annotated corpus for the assertion classification task in the 2010 i2b2/VA Clinical NLP Challenge was used in this study. We implemented several existing and newly developed active learning algorithms and assessed their uses. The outcome is reported in the global ALC score, based on the Area under the average Learning Curve of the AUC (Area Under the Curve) score. Results showed that when the same number of annotated samples was used, active learning strategies could generate better classification models (best ALC – 0.7715) than the passive learning method (random sampling) (ALC – 0.7411). Moreover, to achieve the same classification performance, active learning strategies required fewer samples than the random sampling method. For example, to achieve an AUC of 0.79, the random sampling method used 32 samples, while our best active learning algorithm required only 12 samples, a reduction of 62.5% in manual annotation effort. PMID:22127105

Do Urinary Cystine Parameters Predict Clinical Stone Activity?

PubMed

Friedlander, Justin I; Antonelli, Jodi A; Canvasser, Noah E; Morgan, Monica S C; Mollengarden, Daniel; Best, Sara; Pearle, Margaret S

2018-02-01

An accurate urinary predictor of stone recurrence would be clinically advantageous for patients with cystinuria. A proprietary assay (Litholink, Chicago, Illinois) measures cystine capacity as a potentially more reliable estimate of stone forming propensity. The recommended capacity level to prevent stone formation, which is greater than 150 mg/l, has not been directly correlated with clinical stone activity. We investigated the relationship between urinary cystine parameters and clinical stone activity. We prospectively followed 48 patients with cystinuria using 24-hour urine collections and serial imaging, and recorded stone activity. We compared cystine urinary parameters at times of stone activity with those obtained during periods of stone quiescence. We then performed correlation and ROC analysis to evaluate the performance of cystine parameters to predict stone activity. During a median followup of 70.6 months (range 2.2 to 274.6) 85 stone events occurred which could be linked to a recent urine collection. Cystine capacity was significantly greater for quiescent urine than for stone event urine (mean ± SD 48 ± 107 vs -38 ± 163 mg/l, p <0.001). Cystine capacity significantly correlated inversely with stone activity (r = -0.29, p <0.001). Capacity also correlated highly negatively with supersaturation (r = -0.88, p <0.001) and concentration (r = -0.87, p <0.001). Using the suggested cutoff of greater than 150 mg/l had only 8.0% sensitivity to predict stone quiescence. Decreasing the cutoff to 90 mg/l or greater improved sensitivity to 25.2% while maintaining specificity at 90.9%. Our results suggest that the target for capacity should be lower than previously advised. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

21 CFR 50.51 - Clinical investigations not involving greater than minimal risk.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Clinical investigations not involving greater than... HUMAN SERVICES GENERAL PROTECTION OF HUMAN SUBJECTS Additional Safeguards for Children in Clinical Investigations § 50.51 Clinical investigations not involving greater than minimal risk. Any clinical...

Diagnostic medical physicists and their clinical activities.

PubMed

Cypel, Yasmin S; Sunshine, Jonathan H

2004-02-01

The primary objective of this study was to obtain basic, descriptive information about medical physicists involved in diagnostic radiology-related activities, the diagnostic-related activities that they performed, and the time spent on these activities. A survey was sent to a randomly selected sample of 1511 medical physicists from July through October 2001 using primarily e-mail methods; a total of 851 surveys was received, for a response rate of 56%. Of these, 427 were responses from physicists who do partly or only clinical diagnostic medical physics; it is this group for which results are presented. Fifty-four percent of the physicists who reported doing any clinical diagnostic medical physics performed clinical activities only in diagnostic medical physics. Fourteen percent of all those doing clinical diagnostic medical physics were women. Over 97% of the physicists doing clinical diagnostic medical physics reported having graduate degrees in physics; 53% had PhDs. The mean total weekly hours worked by physicists doing clinical diagnostic medical physics was 42. Medical physicists doing only clinical diagnostic activities reported working approximately 40 hours weekly, whereas those doing partly clinical diagnostic medical physics reported working 14 hours weekly in the field (approximately one-third of their work time). Radiography and fluoroscopy, computed tomography, nuclear medicine, and mammography are all fields in which the majority of those doing any clinical diagnostic medical physics are active. Full-time physicists working only in diagnostic medical physics were responsible for a median of 25 units of equipment, compared with a median of 10 units for those working only partly in the field. Number of units evaluated, frequency of evaluation, and hours per evaluation were reported for almost 20 types of equipment. Medical physicists performing diagnostic clinical activities typically are responsible for a large number and wide variety of imaging

[The role of gonadal peptides in clinical investigation].

PubMed

Lahlou, N; Bouvattier, C; Linglart, A; Rodrigue, D; Teinturier, C

2009-01-01

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement. Inhibins, activins, and AMH are also reliable markers of gonadal tumors. They are extensively used as indexes of fertility: in the male the production of inhibin B reflects the spermatogenetic activity, in women both inhibin B and AMH levels are correlated with the number of preantral and early antral follicles and reflect the ovarian reserve of follicles available for recruitment.

Clinical Investigator Development Program | Center for Cancer Research

Cancer.gov

Clinical Investigator Development Program Application Deadline:  September 30, 2018 Program Starts: July 1, 2019 The NCI Center for Cancer Research (CCR) is pleased to announce our annual call for applications for an exciting training opportunity intended for physicians interested in dedicating their careers to clinical research. Come join a vibrant, multidisciplinary research

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

PubMed

Chess, Laura E; Gagnier, Joel J

2016-02-17

Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. The most recent 100 systematic reviews from the top five journals in medicine-JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine-and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81% of Cochrane reviews and 90% of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1% of non-Cochrane reviews and 8% of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very

A Data Accounting System for Clinical Investigators

PubMed Central

Kashner, T. Michael; Hinson, Robert; Holland, Gloria J.; Mickey, Don D.; Hoffman, Keith; Lind, Lisa; Johnson, Linda D.; Chang, Barbara K.; Golden, Richard M.; Henley, Steven S.

2007-01-01

Clinical investigators often preprocess, process, and analyze their data without benefit of formally organized research centers to oversee data management. This article outlines a practical three-file structure to help guide these investigators track and document their data through processing and analyses. The proposed process can be implemented without additional training or specialized software. Thus, it is particularly well suited for research projects with small budgets or limited access to viable research/data coordinating centers. PMID:17460138

brief report: Burnout Among Early Career Clinical Investigators

PubMed Central

Primack, Brian A.; Dilmore, Terri C.; Switzer, Galen E.; Bryce, Cindy L.; Seltzer, Deborah L.; Li, Jie; Landsittel, Douglas P.; Kapoor, Wishwa N.; Rubio, Doris M.

2010-01-01

Abstract Burnout is a pervasive problem among clinicians. However, little is known about burnout among early career clinical investigators, who must balance clinical responsibilities with challenges related to research. We aimed to determine the prevalence of and demographic associations with burnout in a cohort of early career clinical investigators. A cross‐sectional questionnaire was administered to 179 trainees at the University of Pittsburgh Institute for Clinical Research Education in 2007–2008. We used chi‐square analyses and Fisher’s exact test to determine whether associations between demographic characteristics and burnout were significant. Of the participants, 29 (16%) reported feeling burned out. Burnout was more prevalent among those over 35 years of age relative to their younger counterparts (29% vs. 13%, p= 0.01) and among females relative to males (22% vs. 10%, p= 0.03). With regard to race and ethnicity, burnout was most common among underrepresented minorities (30%) followed by Caucasians (18%) and Asians (3%); these differences were significant (p= 0.02). Considering the early career status of these research trainees, rates of burnout were concerning. Certain demographic subgroups—including older trainees, females, and underrepresented minorities—had particularly high rates of burnout and may benefit from interventions that provide them with skills needed to sustain successful clinical research careers. Clin Trans Sci 2010; Volume 3: 186–188 PMID:20718821

77 FR 60440 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Clinical Investigator Training Course AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration's (FDA) Center for Drug Evaluation and Research/Office of Medical...

Clinical investigations for SUS, the Brazilian public health system.

PubMed

Paula, Ana Patrícia de; Giozza, Silvana Pereira; Pereira, Michelle Zanon; Boaventura, Patrícia Souza; Santos, Leonor Maria Pacheco; Sachetti, Camile Giaretta; Tamayo, César Omar Carranza; Kowalski, Clarissa Campos Guaragna; Elias, Flavia Tavares Silva; Serruya, Suzanne Jacob; Guimarães, Reinaldo

2012-01-01

Scientific and technological development is crucial for advancing the Brazilian health system and for promoting quality of life. The way in which the Brazilian Ministry of Health has supported clinical research to provide autonomy, self-sufficiency, competitiveness and innovation for the healthcare industrial production complex, in accordance with the National Policy on Science, Technology and Innovation in Healthcare, was analyzed. Descriptive investigation, based on secondary data, conducted at the Department of Science and Technology, Ministry of Health. The Ministry of Health's research management database, PesquisaSaúde, was analyzed from 2002 to 2009, using the key word "clinical research" in the fields "primary sub-agenda" or "secondary sub-agenda". The 368 projects retrieved were sorted into six categories: basic biomedical research, preclinical studies, expanded clinical research, clinical trials, infrastructure support and health technology assessment. From a structured review on "clinical research funding", results from selected countries are presented and discussed. The amount invested was R$ 140 million. The largest number of projects supported "basic biomedical research", while the highest amounts invested were in "clinical trials" and "infrastructure support". The southeastern region had the greatest proportion of projects and financial resources. In some respects, Brazil is ahead of other BRICS countries (Russia, India, China and South Africa), especially with regard to establishing a National Clinical Research Network. The Ministry of Health ensured investments to encourage clinical research in Brazil and contributed towards promoting cohesion between investigators, health policies and the healthcare industrial production complex.

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation.

PubMed

Asaduzzaman Khan, Md; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-08-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics.

Antifungal activity of low molecular weight chitosan against clinical isolates of Candida spp.

PubMed

Alburquenque, Claudio; Bucarey, Sergio A; Neira-Carrillo, Andrónico; Urzúa, Blanca; Hermosilla, Germán; Tapia, Cecilia V

2010-12-01

Chitosan is a natural polymer derived from chitin, a structural component of fungi, insects and shrimp, which exerts antimicrobial effects against bacteria and fungi. The aim of this study was to investigate the in vitro antifungal activity of low molecular weight chitosan (LMWC), and the potential synergy between chitosan and a currently used antifungal drug, fluconazole. The in vitro minimal inhibitory concentrations (MICs) of chitosan and fluconazole against 105 clinical Candida isolates were measured by the broth microdilution method. LMWC exhibited a significant antifungal activity, inhibiting over 89.9% of the clinical isolates examined (68.6% of which was completely inhibited). The species included several fluconazole-resistant strains and less susceptible species such as C. glabrata, which was inhibited at a concentration of 4.8 mg/l LMWC. Although some strains were susceptible at pH 7.0, a greater antifungal activity of LMWC was observed at pH 4.0. There was no evidence of a synergistic effect of the combination of LMWC and fluconazole at pH 7.0. This is the first report in which the antifungal activity of LMWC was investigated with clinical Candida strains. The use of LMWC as an antifungal compound opens new therapeutic perspectives, as the low toxicity of LMWC in humans supports its use in new applications in an environment of pH 4.0-4.5, such as a topical agent for vulvovaginal candidiasis.

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

PubMed

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

2018-05-03

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

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

PubMed Central

Asaduzzaman Khan, Md.; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-01-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics. PMID:28881699

[The antibacterial activity of oregano essential oil (Origanum heracleoticum L.) against clinical strains of Escherichia coli and Pseudomonas aeruginosa].

PubMed

Sienkiewicz, Monika; Wasiela, Małgorzata; Głowacka, Anna

2012-01-01

The aim of this study was to investigate the antibacterial properties of oregano (Origanum heracleoticum L.) essential oil against clinical strains of Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity of oregano essential oil was investigate against 2 tested and 20 clinical bacterial strains of Escherichia coli and 20 clinical strains o Pseudomonas aeruginosa come from patients with different clinical conditions. The agar dilution method was used for microbial growth inhibition at various concentrations ofoil. Susceptibility testing to antibiotics was carried out using disc-diffusion method. The results of experiments showed that the tested oil was active against all of the clinical strains from both genus of bacteria, but strains of Escherichia coli were more sensitive to tested oil. Essential oil from Origanum heracleoticum L. inhibited the growth of Escherichia coli and Pseudomonas aeruginosa clinical strains with different patters of resistance. The obtained outcomes will enable further investigations using oregano essential oil obtained from Origanum heracleoticum L. as alternative antibacterial remedies enhancing healing process in bacterial infections and as an effective means for the prevention of antibiotic-resistant strain development.

76 FR 1173 - Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations; Availability... Documentation in Clinical Investigations.'' This document provides guidance to sponsors, contract research organizations (CROs), data management centers, and clinical investigators on capturing, using, and archiving...

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

PubMed Central

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-01-01

Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

PubMed

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-09-01

This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

PERSPECTIVE: Is acuity enough? Other considerations in clinical investigations of visual prostheses

NASA Astrophysics Data System (ADS)

Lepri, Bernard P.

2009-06-01

Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in visual acuity alone enough to improve the function and quality of life of visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond visual acuity that will yield outcomes that are measured by improved function in the visual world and quality of life. The visually impaired population is the primary consideration in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment. The views and opinions are those of the author and do not necessarily reflect those of the US Food and Drug Administration, the US Department of Health and Human Services or the Public Health Service.

77 FR 11555 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... either http://www.regulations.gov or http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinical...] Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional Review Board Continuing Review After Clinical Investigation Approval; Availability AGENCY: Food and Drug Administration...

An investigation of nurse educator's perceptions and experiences of undertaking clinical practice.

PubMed

Williams, Angela; Taylor, Cathy

2008-11-01

Educational policy (DOH, 1999. Making a difference: strengthening the nursing, midwifery and health visiting contribution to health and healthcare. Department of Health, London; UKCC, 1999. Fitness for Practice. United Kingdom Central Council for Nursing, Midwifery and Health Visiting, London; Nursing and Midwifery Council, 2006. Standards to support learning and assessment in practice. Nursing and Midwifery Council, London) and current nursing literature (Griscti, O., Jacono, B., Jacono, J., 2005. The nurse educator's clinical role. Journal of Advanced Nursing 50 (1), 84-92; Owen, S., Ferguson, K., Baguley, I., 2005. The clinical activity of mental health nurse lecturers. Journal of Psychiatric and Mental Health Nursing 12, 310-316), place increasing emphasis on nurse educators undertaking clinical practice to facilitate their clinical confidence and competence. This study investigated nurse educators' perceptions and experiences of undertaking clinical practice. A qualitative design and descriptive, exploratory approach were used. A purposive sample of 11 nurse educators in one nursing department, took part in two focus group interviews, one with 5 and the other with 6 respondents, to identify and discuss their perceptions and experiences of undertaking clinical practice. A process of thematic content analysis revealed three broad themes relating to the meaning and importance of clinical practice, perceived benefits and barriers which are examined and discussed. The paper concludes that despite policy recommendations, barriers highlighted in this study such as insufficient time, heavy workload and a lack of valuing of the clinical role have been raised over the past few decades. The effect of undertaking clinical practice, particularly on the quality of teaching is argued to be valuable armoury in the battle to secure sufficient resources to support engagement in clinical practice. Financial and organisational commitment; valuing of clinical practice and research

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

PubMed

Shimada, Yasuhiro

2016-04-01

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

Assessing student clinical learning experiences.

PubMed

Nehyba, Katrine; Miller, Susan; Connaughton, Joanne; Singer, Barbara

2017-08-01

This article describes the use of an activity worksheet and questionnaire to investigate the learning experience of students on clinical placement. The worksheet measures the amount of time students spend in different learning activities, and the questionnaire explores student satisfaction and preferred learning activities. An activity worksheet and questionnaire … investigate[d] the learning experiences of students on clinical placement METHODS: The activity worksheet and questionnaire were used in a cohort pilot study of physiotherapy students on clinical placement. The activity worksheet provides details of the amount of time students engage in a range of clinical and non-clinical tasks while on placement, such as time spent treating patients, working individually, working with their peers and engaging in reflective practice. In combination with the questionnaire results, it allows clinicians to gain an understanding of the clinical learning environment experienced by their students. The data collected using these tools provide a description of the students' activities while undertaking the clinical placement. This information may guide the refinement of the clinical experience, and offers an opportunity to individualise learning activities to match students' needs and preferences. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

PubMed

McKenna, Dennis J

2004-05-01

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

PubMed

Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

2014-11-01

To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Antibacterial activity of essential oils extracted from Satureja hortensis against selected clinical pathogens

NASA Astrophysics Data System (ADS)

Görmez, Arzu; Yanmiş, Derya; Bozari, Sedat; Gürkök, Sumeyra

2017-04-01

The antibiotic resistance of pathogenic microorganisms has become a worldwide concern to public health. To overcome the current resistance problem, new antimicrobial agents are extremely needed. The aim of the present study was to evaluate the antibacterial activity of Satureja hortensis essential oils against seven clinical pathogens. Chemical compositions of hydro distillated essential oils from S. hortensis were analyzed by GS-MS. The antibacterial activity was investigated against Corynebacterium diphtheria, Salmonella typhimurium, Serratia plymuthica Yersinia enterocolitica, Y. frederiksenii, Y. pseudotuberculosis and Vibrio cholerae by the use of disc diffusion method and broth micro dilution method. The minimum inhibitory concentration (MIC) values of essential oils were found as low as 7.81 µg/mL. Notably, essential oils of S. hortensis exhibited remarkable antimicrobial activities against the tested clinical pathogens. The results indicate that these essential oils can be used in treatment of different infectious diseases.

75 FR 1790 - Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: IRB...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

....gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ProposedRegulationsandDraftGuidances/default...] Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: IRB Continuing Review After Clinical Investigation Approval; Availability AGENCY: Food and Drug Administration, HHS...

Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

PubMed

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

2017-10-27

Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

78 FR 57395 - Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

...] Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability AGENCY: Food and... the availability of a guidance for industry entitled ``Electronic Source Data in Clinical Investigations.'' This document provides guidance to sponsors, contract research organizations (CROs), clinical...

Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1.

PubMed

Mallegol, Julia; Fernandes, Prabhavathi; Melano, Roberto G; Guyard, Cyril

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis.

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

PubMed Central

Mallegol, Julia; Fernandes, Prabhavathi

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis. PMID:24277019

Clinical Investigator Development Program | Center for Cancer Research

Cancer.gov

The Center for Cancer Research (CCR), a division of the National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), is pleased to announce its annual call for applications for the Clinical Investigator Development Program (CIDP). This is an exciting training opportunity intended for physicians interested in dedicating

Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual

PubMed Central

Tang, Chad; Hess, Kenneth R.; Sanders, Dwana; Davis, Suzanne; Buzdar, Aman; Kurzrock, Razelle; Lee, J. Jack; Meric-Bernstam, Funda; Hong, David

2017-01-01

Purpose Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center and analyzed their effects on the trial activation timeline and enrollment. Experimental Design Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results We identified 3 facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship (industry [133 ICT and 133 non-ICT trials] or institutional [68 ICT and 68 non-ICT trials]). ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrollment (median difference of 0.3 months for industry vs. 1.2 months for institutional) (all matched P<0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional) (all matched P<0.05). Conclusions Use of a clinical research–focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. PMID:27852698

Peer assisted learning in the clinical setting: an activity systems analysis.

PubMed

Bennett, Deirdre; O'Flynn, Siun; Kelly, Martina

2015-08-01

Peer assisted learning (PAL) is a common feature of medical education. Understanding of PAL has been based on processes and outcomes in controlled settings, such as clinical skills labs. PAL in the clinical setting, a complex learning environment, requires fresh evaluation. Socio-cultural theory is proposed as a means to understand educational interventions in ways that are practical and meaningful. We describe the evaluation of a PAL intervention, introduced to support students' transition into full time clinical attachments, using activity theory and activity systems analysis (ASA). Our research question was How does PAL transfer to the clinical environment? Junior students on their first clinical attachments undertook a weekly same-level, reciprocal PAL activity. Qualitative data was collected after each session, and focus groups (n = 3) were held on completion. Data was analysed using ASA. ASA revealed two competing activity systems on clinical attachment; Learning from Experts, which students saw as the primary function of the attachment and Learning with Peers, the PAL intervention. The latter took time from the first and was in tension with it. Tensions arose from student beliefs about how learning takes place in clinical settings, and the importance of social relationships, leading to variable engagement with PAL. Differing perspectives within the group were opportunities for expansive learning. PAL in the clinical environment presents challenges specific to that context. Using ASA helped to describe student activity on clinical attachment and to highlight tensions and contradictions relating PAL in that setting. Planning learning opportunities on clinical placements, must take account of how students learn in workplaces, and the complexity of the multiple competing activity systems related to learning and social activities.

Clinical and laboratory characteristics of active and healthy aging (AHA) in octogenarian men.

PubMed

Rantanen, Kirsi K; Strandberg, Timo E; Stenholm, Sari S; Strandberg, Arto Y; Pitkälä, Kaisu H; Salomaa, Veikko V; Tilvis, Reijo S

2015-10-01

To investigate clinical and laboratory variables associated with good subjective and objective health ("active and healthy aging", AHA) in a cohort of octogenarian men. Cross-sectional analyses of a longitudinal study. The Helsinki Businessmen Study in Finland. A socioeconomically homogenous cohort of men (baseline n = 3293), born in 1919-1934, has been followed up from the 1960s. From 2000, the men have been regularly sent mailed questionnaires and mortality has been retrieved from national registers. In 2010 survey, AHA was defined as independently responding to the mailed survey, feeling happy without cognitive or functional impairments and without major diseases. In 2010/11, a random subgroup men was clinically investigated and survivors with healthy and nonhealthy aging were compared. By 2010, 1788 men of the baseline cohort had died, and 894 men responded to the mailed survey. 154 (17.2 %) of those fulfilled the present AHA criteria. Increasing number of criteria were negatively (P < 0.001) related to short-term mortality. In 2011, a random sample of 458 men were clinically investigated, 90 of them with AHA. Men with AHA had higher serum LDL cholesterol and diastolic blood pressure (partially explained by less frequent drug use) but no significant difference was observed in other risk factors. Men with AHA had significantly faster walking speed (P < 0.001), stronger handgrip (P = 0.017), better self-rated health and less phenotypic frailty (P = 0.02). Less than 5 % enjoyed active and healthy aging over their life course, which was significantly related to markers of frailty but not to the traditional vascular risk factors.

77 FR 69631 - Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

...://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ProposedRegulationsandDraftGuidances...] Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the... IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing the Qualifications of...

78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsand...] (formerly 1999D-4396) Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial Disclosure by Clinical Investigators; Availability AGENCY: Food and Drug Administration, HHS...

77 FR 69632 - Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

...] Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``Electronic Source Data in Clinical... in Clinical Investigations.'' This revised draft document provides guidance to sponsors, contract...

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

PubMed

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P < 0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional; all matched P < 0.05). Conclusions: Use of a clinical research-focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

A meta-meta-analysis of the effect of physical activity on depression and anxiety in non-clinical adult populations.

PubMed

Rebar, Amanda L; Stanton, Robert; Geard, David; Short, Camille; Duncan, Mitch J; Vandelanotte, Corneel

2015-01-01

Amidst strong efforts to promote the therapeutic benefits of physical activity for reducing depression and anxiety in clinical populations, little focus has been directed towards the mental health benefits of activity for non-clinical populations. The objective of this meta-meta-analysis was to systematically aggregate and quantify high-quality meta-analytic findings of the effects of physical activity on depression and anxiety for non-clinical populations. A systematic search identified eight meta-analytic outcomes of randomised trials that investigated the effects of physical activity on depression or anxiety. The subsequent meta-meta-analyses were based on a total of 92 studies with 4310 participants for the effect of physical activity on depression and 306 study effects with 10,755 participants for the effect of physical activity on anxiety. Physical activity reduced depression by a medium effect [standardised mean difference (SMD) = -0.50; 95% CI: -0.93 to -0.06] and anxiety by a small effect (SMD = -0.38; 95% CI: -0.66 to -0.11). Neither effect showed significant heterogeneity across meta-analyses. These findings represent a comprehensive body of high-quality evidence that physical activity reduces depression and anxiety in non-clinical populations.

Clinical and Histopathological Investigation of Seborrheic Keratosis

PubMed Central

Roh, Nam Kyung; Hahn, Hyung Jin; Lee, Yang Won; Choe, Yong Beom

2016-01-01

Background Seborrheic keratosis (SK) is one of the most common epidermal tumors of the skin. However, only a few large-scale clinicohistopathological investigations have been conducted on SK or on the possible correlation between histopathological SK subtype and location. Objective The aim of this study was to analyze the clinical and histopathological features of a relatively large number of cases of diagnosed SK. Methods Two hundred and seventy-one pathology slides of skin tissue from patients with clinically diagnosed SK and 206 cases of biopsy-proven SK were analyzed. The biopsy-proven cases of SK were assessed for histopathological subclassification. The demographic, clinical, and histopathological data of the patients were collected for analysis of associated factors. Results The most frequent histopathological subtype was the acanthotic type, followed by mixed, hyperkeratotic, melanoacanthoma, clonal, irritated, and adenoid types; an unexpectedly high percentage (9.2%) of the melanoacanthoma variant was observed. The adenoid type was more common in sun-exposed sites than in sun-protected sites (p=0.028). Premalignant and malignant entities together represented almost one-quarter (24.2%) of the clinicopathological mismatch cases (i.e., mismatch between the clinical and histopathological diagnoses). Regarding the location of SK development, the frequency of mismatch for the sun-exposed areas was significantly higher than that for sun-protected areas (p=0.043). Conclusion The adenoid type was more common in sun-exposed sites. Biopsy sampling should be performed for lesions situated in sun-exposed areas to exclude other premalignant or malignant diseases. PMID:27081260

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

PubMed

Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

A history of the American Society for Clinical Investigation

PubMed Central

Howell, Joel D.

2009-01-01

One hundred years ago, in 1909, the American Society for Clinical Investigation (ASCI) held its first annual meeting. The founding members based this new society on a revolutionary approach to research that emphasized newer physiological methods. In 1924 the ASCI started a new journal, the Journal of Clinical Investigation. The ASCI has also held an annual meeting almost every year. The society has long debated who could be a member, with discussions about whether members must be physicians, what sorts of research they could do, and the role of women within the society. The ASCI has also grappled with what else the society should do, especially whether it ought to take a stand on policy issues. ASCI history has reflected changing social, political, and economic contexts, including several wars, concerns about the ethics of biomedical research, massive increases in federal research funding, and an increasingly large and specialized medical environment. PMID:19348041

Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.

PubMed

Steiman, Amanda J; Gladman, Dafna D; Ibañez, Dominique; Noamani, Babak; Landolt-Marticorena, Carolina; Urowitz, Murray B; Wither, Joan E

2015-12-01

Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) remain clinically quiescent for prolonged periods despite anti-dsDNA antibodies and/or low complements, indicating the presence of immune complexes. The immune mechanisms leading to this quiescence are unknown. However, in addition to activating complement, immune complex uptake by various cells leads to the production of interferon (IFN)-α and other proinflammatory factors that are also involved in tissue damage. Here we investigate whether production of these factors is reduced in SACQ patients. The levels of 5 IFN-induced genes and 19 cyto/chemokines were measured in SACQ patients and were compared with those in serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients. SACQ and SQCQ were defined as ≥ 2 years without clinical activity, with/without persistent serologic activity, respectively, and off corticosteroids/immunosuppressives. SACA was defined as disease activity compelling immunosuppression. Levels of OAS1, IFIT1, MX1, LY6E, and ISG15 were measured by quantitative real-time polymerase chain reaction (PCR) and a composite score (IFN-5) derived from this. Plasma cyto/chemokines were measured by Luminex assay. Nonparametric univariate and logistic regression analyses were conducted. There were no differences in gene expression or cyto/chemokine levels between SACQ and SQCQ patients. The SACQ IFN-5 score was significantly lower than that of SACA (p = 0.003) and was driven by SACQ status, not by autoantibody profile or disease duration. Levels of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 6, IL-10, IFN-γ-inducible protein 10, monocyte chemoattractant protein 1, and tumor necrosis factor-α were significantly lower in SACQ than SACA. The levels of proinflammatory factors in SACQ mirror those of SQCQ patients, indicating reduced production of these factors despite the presence of immune

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

21 CFR 50.52 - Clinical investigations involving greater than minimal risk but presenting the prospect of direct...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Clinical investigations involving greater than... OF HUMAN SUBJECTS Additional Safeguards for Children in Clinical Investigations § 50.52 Clinical... subjects. Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in...

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

PubMed

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these

Students' Performance in Investigative Activity and Their Understanding of Activity Aims

ERIC Educational Resources Information Center

Gomes, Alessandro Damasio Trani; Borges, A. Tarciso; Justi, Rosaria

2008-01-01

This study investigates the relationship between the students' understanding of the aims of an investigative activity and their performance when conducting it. One hundred and eighty-one year nine students from a public middle school in Brazil took part in the study. Students working in pairs were asked to investigate two problems using a…

Australian doctors' non-clinical activities: results from the Medicine in Australia: Balancing Employment and Life (MABEL) survey of doctors.

PubMed

Joyce, Catherine; Eyre, Harris; Wang, Wei Chun; Laurence, Caroline

2015-11-01

The aim of the present study was to investigate non-clinical work conducted by Australian doctors. This study was an exploratory descriptive study using data from Wave 5 of the Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey, collected in 2012 from Australian medical practitioners (2200 general practitioners (GPs), 3455 specialists, 1270 specialists in training and 1656 hospital non-specialists). The main outcome measure was the number of hours worked per week in non-clinical work. Regression analysis was used to determine associations between non-clinical activities (i.e. education-related, management and administration and other) and personal and professional characteristics, including age, gender, job and life satisfaction, total clinical working hours, sector of practice (public or private) and doctor type. Australian doctors spend an average of just under 7 h per week, or 16% of their working time, on non-clinical activities. Doctors who worked more hours on non-clinical activities overall, and in education-related and management and administration specifically, were male, younger, had lower life satisfaction and generally spent fewer hours on clinical work. Lower job satisfaction was associated with longer management and administration hours, but not with time spent in education-related activities. Specialists were more likely to work long non-clinical hours, whereas GPs were more likely to report none. Hospital non-specialists reported relatively high management and administration hours. Further work is required to better understand the full range of non-clinical activities doctors are involved in and how this may impact future workforce projections.

Active learning reduces annotation time for clinical concept extraction.

PubMed

Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

2017-10-01

To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models.

PubMed

Baker, Amanda F; Hanke, Neale T; Sands, Barbara J; Carbajal, Liliana; Anderl, Janet L; Garland, Linda L

2014-12-31

Carfilzomib (CFZ) is a proteasome inhibitor that selectively and irreversibly binds to its target and has been approved in the US for treatment of relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported signals of clinical activity in solid tumors, including small cell lung cancer (SCLC). The aim of this study was to investigate the activity of CFZ in lung cancer models. A diverse panel of human lung cancer cell lines and a SHP77 small cell lung cancer xenograft model were used to investigate the anti-tumor activity of CFZ. CFZ treatment inhibited both the constitutive proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell lung cancer (NSCLC) cell lines, with IC50 values after 96 hour exposure from <1.0 nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell lines, with IC50 values at 96 hours from <1 nM to 203 nM. Western blot analysis of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy. In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and prolonged survival, while no additive or synergistic anti-tumor efficacy was observed for CFZ + cisplatin (CDDP). CFZ demonstrated anti-proliferative activity in lung cancer cell lines in vitro and resulted in a significant survival advantage in mice with SHP77 SCLC xenografts, supporting further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.

Gamete activation: basic knowledge and clinical applications

PubMed Central

Tosti, Elisabetta; Ménézo, Yves

2016-01-01

Background The first clues to the process of gamete activation date back to nearly 60 years ago. The mutual activation of gametes is a crucial event during fertilization. In the testis and ovaries, spermatozoa and oocytes are in a state of meiotic and metabolic quiescence and require reciprocal signals in order to undergo functional changes that lead to competence for fertilization. First, the oocyte activates sperm by triggering motility, chemoattraction, binding and the acrosome reaction, culminating with the fusion of the two plasma membranes. At the end of this cascade of events, collectively known as sperm capacitation, sperm-induced oocyte activation occurs, generating electrical, morphological and metabolic modifications in the oocyte. Objective and rationale The aim of this review is to provide the current state of knowledge regarding the entire process of gamete activation in selected specific animal models that have contributed to our understanding of fertilization in mammals, including humans. Here we describe in detail the reciprocal induction of the two activation processes, the molecules involved and the mechanisms of cell interaction and signal transduction that ultimately result in successful embryo development and creation of a new individual. Search methods We carried out a literature survey with no restrictions on publication date (from the early 1950s to March 2016) using PubMed/Medline, Google Scholar and Web of Knowledge by utilizing common keywords applied in the field of fertilization and embryo development. We also screened the complete list of references published in the most recent research articles and relevant reviews published in English (both animal and human studies) on the topics investigated. Outcomes Literature on the principal animal models demonstrates that gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date. We provide a detailed description of the dramatic

A study of warning letters issued to clinical investigators and institutional review boards by the United States Food and Drug Administration.

PubMed

Gogtay, N J; Doshi, B M; Kannan, S; Thatte, U

2011-01-01

Warning letters (WLs) issued by the US FDA (United States Food and Drug Administration) mention the nature of violations by clinical investigators and institutional review boards (IRBS) and can help as training tools. WLs issued by the US FDA between January 2005 and December 2010 to clinical investigators and IRBs were reviewed for various violation themes. A total of 129 WLs were issued to investigators and 40 to IRBs. Among the WLs issued to investigators, 67 (51.95%) were issued for drug-related research and 62 (48.06%) were for device-related research. For investigators, deviation from the investigational plan was the most common violation (81%) followed by failure to maintain accurate and adequate case histories (58.1%) and then informed consent issues (48.06%). Among WLs issued to IRBs, failure to have and follow standard operating procedures (SOPs) was seen in 93.89% followed by issues pertaining to membership (59.4%). When compared to a similar study published in 2004, for clinical investigators, no improvement was seen with respect to deviation from the investigational plan and study supervision. However, a significant improvement was seen in reporting of adverse events to IRBs, and some improvement was seen in the area of informed consent. For IRBs, no improvement was seen in most areas which included maintaining and following SOPs, membership, quorum requirements, misuse of expedited review and informed consent. WLs serve as indicators of an active regulatory agency which should translate into greater safety for participants in clinical trials. For developing countries with weak regulatory systems, these can serve as useful learning tools to help improve systems and put in patient safeguards.

Clinical case series: treatment of PTSD with transcendental meditation in active duty military personnel.

PubMed

Barnes, Vernon A; Rigg, John L; Williams, Jennifer J

2013-07-01

Active duty U.S. Army Service Members previously diagnosed with post-traumatic stress disorder (PTSD) were selected from review of patient records in the Traumatic Brain Injury Clinic at the Department of Defense Eisenhower Army Medical Center at Fort Gordon in Augusta, Georgia. Patients agreed to practice the Transcendental Meditation (TM) technique for 20 minutes twice a day for the duration of a 2-month follow-up period. Three cases are presented with results that show the feasibility of providing TM training to active duty soldiers with PTSD in a Department of Defense medical facility. Further investigation is suggested to determine if a TM program could be used as an adjunct for treatment of PTSD. Impact of this report is expected to expand the complementary and alternative evidence base for clinical care of PTSD. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

76 FR 70151 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0790] Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and Drug Administration Staff; Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

An interactive data management and analysis system for clinical investigators.

PubMed

Groner, G F; Hopwood, M D; Palley, N A; Sibley, W L; Baker, W R; Christopher, T G; Thompson, H K

1978-09-01

An interactive minicomputer-based system has been developed that enables the clinical research investigator to personally explore and analyze his research data and, as a consequence of these explorations, to acquire more information. This system, which does not require extensive training or computer programming, enables the investigator to describe his data interactively in his own terms, enter data values while having them checked for validity, store time-oriented patient data in a carefully controlled on-line data base, retrieve data by patient, variable, and time, create subsets of patients with common characteristics, perform statistical analyses, and produce tables and graphs. It also permits data to be transferred to and from other computers. The system is well accepted and is being used by a variety of medical specialists at the three clinical research centers where it is operational. Reported benefits include less elapsed and nonproductive time, more thorough analysis of more data, greater and earlier insight into the meaning of research data, and increased publishable results.

Acetyl aspartic acid, a novel active ingredient, demonstrates potential to improve signs of skin ageing: from consumer need to clinical proof.

PubMed

Mavon, A

2015-10-01

The megatrend of population ageing is leading to a growing demand for "anti-ageing" treatments, especially to prevent or treat skin ageing. Facing an increasing offer, consumers are choosing more and more skin care products supported by a scientific rationale, active ingredients and clinical proof of efficacy. Considering consumer expectations, this research led to the discovery of acetyl aspartic acid (A-A-A), a novel active ingredient to improve sagging skin and loss of skin firmness. This supplement is featuring seven manuscripts aiming at presenting the research and investigations from consumer insights, discovery of A-A-A, its in vitro activity confirmation, safety assessment, formulation and its dermal absorption to the clinical proof of efficacy, investigated through two pilots' double bind randomized and placebo controlled studies on photo-aged skin. This extensive research enabled us to discover A-A-A, as an active ingredient with potential to repair sign of skin ageing and supported by clinical proof of efficacy. This active ingredient will be soon launched in a commercial innovative skin care range, delivering desirable anti-wrinkle and skin lifting benefits. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

78 FR 60291 - Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

...] Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human Studies; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY... Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Through the...

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

PubMed

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

Investigation of Voltage-Activated BAW Devices and Filters

DTIC Science & Technology

2016-09-04

strontium titanate (STO) and barium-strontium titanate (BST), with the ultimate objective of creating high- performance, reconfigurable filters and...Distribution Unlimited UU UU UU UU 04-09-2016 1-Sep-2010 31-Aug-2014 Final Report: Investigation of Voltage-Activated BAW Devices and Filters The views...2016 Investigation of Voltage-Activated BAW Devices and Filters Final Report Award Information: Contract Number: W911NF1010286 Period of Work

Synergistic Activity of Econazole-Nitrate and Chelerythrine against Clinical Isolates of Candida albicans.

PubMed

Chen, Zhibao; Li, Xinran; Wu, Xiuping; Wang, Wei; Wang, Wendong; Xin, Mingxun; Shen, Fengge; Liu, Lihui; Liang, Junchao; Li, Lei; Yu, Lu

2014-01-01

The aim of this investigation was to assess the in-vitro interaction of two antifungal agents, econazole-nitrate and chelerythrine, against ten fluconazole-resistant clinical isolates and one ATCC type strain 10231 of Candida albicans. The checkerboard microdilution method was performed according to the recommendations of the National Committee for Clinical Laboratory Standards, and the results were determined by visual examination. The interaction intensity was tested in all isolates using the fractional inhibitory concentration index (FICI). These experiments showed synergism between econazole-nitrate and chelerythrine in antifungal activity against C. albicans, and no antagonistic activity was observed in any of the strains tested. Moreover, time-kill curves were performed with selected strains to confirm the positive interactions. The similarity between the results of the FICI values and the time-kill curves revealed that chelerythrine greatly enhances the antifungal effects of econazole-nitrate against isolates of C. albicans. This synergistic effect may markedly reduce the dose of econazole-nitrate required to treat candidiasis, thereby decreasing the econazole-nitrate toxic side effects. This novel synergism might provide a potential combination treatment against fungal infections.

Problem Posing Based on Investigation Activities by University Students

ERIC Educational Resources Information Center

da Ponte, Joao Pedro; Henriques, Ana

2013-01-01

This paper reports a classroom-based study involving investigation activities in a university numerical analysis course. The study aims to analyse students' mathematical processes and to understand how these activities provide opportunities for problem posing. The investigations were intended to stimulate students in asking questions, to trigger…

78 FR 48173 - Guidance for Industry on Oversight of Clinical Investigations-A Risk-Based Approach to Monitoring...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-07

...] Guidance for Industry on Oversight of Clinical Investigations--A Risk-Based Approach to Monitoring... Administration (FDA) is announcing the availability of a guidance for industry entitled ``Oversight of Clinical... monitoring strategies and plans for clinical investigations of human drugs, biologics, medical devices, and...

Clinical markers of vitiligo activity.

PubMed

Benzekri, Laila; Gauthier, Yvon

2017-05-01

Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8 + T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8 + T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots.

PubMed

Zeng, Xiangfeng; Zhu, Guoli; Zhang, Mingming; Xie, Sheng Q

2018-01-01

This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of "Ankle ∗ " AND "Robot ∗ " AND "Effect ∗ OR Improv ∗ OR Increas ∗ ." Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR) game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF) training. Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy.

Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness of investigation in Wilson's disease and in hepatic encephalopathy.

PubMed

Siotto, Mariacristina; Pasqualetti, Patrizio; Marano, Massimo; Squitti, Rosanna

2014-10-01

Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron metabolism. It is routinely tested by immunoturbidimetric assays that quantify the concentration of the protein both in its active and inactive forms. Cp activity is generally analyzed manually; the process is time-consuming, has a limited repeatability, and is not suitable for a clinical setting. To overcome these inconveniences, we have set the automation of the o-dianisidine Cp activity assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable, and the data were provided in terms of IU/L. The assay was adapted for human sera and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and activity in the same run allowed us to calculate the Cp-specific activity that provides a better index of the overall Cp status. To test the usefulness of this automation, we tested this assay on 104 healthy volunteers and 36 patients with Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity and specific activity distinguished better patients between groups with respect to Cp concentration alone, and providing support for the clinical investigation of neurological diseases in which liver failure is one of the clinical hallmarks.

"There are too many, but never enough": qualitative case study investigating routine coding of clinical information in depression.

PubMed

Cresswell, Kathrin; Morrison, Zoe; Kalra, Dipak; Sheikh, Aziz

2012-01-01

We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined.

Emotion Understanding in Clinically Anxious Children: A Preliminary Investigation

PubMed Central

Bender, Patrick K.; Pons, Francisco; Harris, Paul L.; Esbjørn, Barbara H.; Reinholdt-Dunne, Marie L.

2015-01-01

Children’s understanding of the nature, origins and consequences of emotions has been intensively investigated over the last 30–40 years. However, few empirical studies have looked at the relation between emotion understanding and anxiety in children and their results are mixed. The aim of the present study was to perform a preliminary investigation of the relationships between emotion understanding, anxiety, emotion dysregulation, and attachment security in clinically anxious children. A sample of 16 clinically anxious children (age 8–12, eight girls/boys) was assessed for emotion understanding (Test of Emotion Comprehension), anxiety (Screening for Child Anxiety Related Emotional Disorders-Revised and Anxiety Disorder Interview Schedule), emotion dysregulation (Difficulties in Emotion Regulation Scale) and attachment security (Security Scale). Children who reported more overall anxiety also reported greater difficulties in regulating their emotions, and were less securely attached to their parents. The results also showed that more specific symptoms of anxiety (i.e., OCD and PTSD) correlated not only with emotion dysregulation and attachment insecurity but also with emotion understanding. Finally, there were interrelations among emotion understanding, attachment security, and emotion dysregulation. The present results provide the first comprehensive evidence for a socio-emotional framework and its relevance to childhood anxiety. PMID:26733909

In vitro activity of AT-4140 against clinical bacterial isolates.

PubMed

Kojima, T; Inoue, M; Mitsuhashi, S

1989-11-01

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.

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

PubMed

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

2014-11-01

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

[Topic on clinical anthropology in scientific activity of docent Antanas Adomaitis].

PubMed

Tutkuviene, Janina

2006-01-01

The present paper is dedicated to docent Antanas Adomaitis, anatomist and anthropologist, former member of editorial board of journal "Medicina", on the occasion of his 65th birthday and 40 years of scientific activity. First publications of Antanas Adomatis appeared in the 1960s, and now the list of his scientific publications exceeds 140 in number. The research field of docent Antanas Adomaitis is wide and covers problems from growth and development to physical status of adult people and its changes associated with a particular period. However, his most important scientific works are in the field of clinical anthropology. Antanas Adomaitis investigated growth and maturation under pathological circumstances, body composition of adult people, prevalence of obesity, growth diversity and secular trend: in 1975 he defended his thesis entitled "Physical development and sexual maturation of children with congenital heart defects" for the degree of Doctor of Medicine, later focused on growth and development of children with congenital facial anomalies, also blind and weak-sighted children. Recently docent together with the other scientists of our Department investigates growth variety of children from different towns and rural areas of Lithuania. Antanas Adomaitis collected probably most anthropological data on Lithuanians (children and adults)--this is ponderable contribution to Lithuanian auxology and clinical anthropology, valuable material for the future researches of growth and maturation, also physical status of adult people and secular trend.

Citalopram in mentally retarded patients with depression: a long-term clinical investigation.

PubMed

Verhoeven, W M; Veendrik-Meekes, M J; Jacobs, G A; van den Berg, Y W; Tuinier, S

2001-03-01

The effect of citalopram was investigated in 20 mentally retarded patients suffering from a depressive disorder characterized by alterations in the domains of affectivity, motivation, motor activity and vital signs. The study followed a baseline-controlled open design. Citalopram was started in a daily dosage of 20 mg that was kept unchanged for 6 weeks. Thereafter dosage was adjusted to maximally 60 mg per day. Treatment effects were assessed according to the Clinical Global Improvement Scale (CGIS) after at least 6 months. In 12 of the 20 patients a moderate to marked improvement in all domains was observed upon treatment with 20-40 mg citalopram daily. Treatment for one year in the effective dose prevented recurrence of depressive symptomatology. Concomitant use of sedative anticonvulsants reduced responsiveness to treatment. No interactions were observed. It is concluded that citalopram is a well-tolerated, safe and effective antidepressant in mentally retarded subjects with depressive disorders.

Therapeutic horticulture in clinical depression: a prospective study of active components.

PubMed

Gonzalez, Marianne Thorsen; Hartig, Terry; Patil, Grete Grindal; Martinsen, Egil W; Kirkevold, Marit

2010-09-01

This paper is a report of a study conducted to assess change in depression severity, perceived attentional capacity and rumination (brooding) in individuals with clinical depression during a therapeutic horticulture programme and to investigate if the changes were mediated by experiences of being away and fascination. Individuals with clinical depression suffer from distortion of attention and rumination. Interventions can help to disrupt maladaptive rumination and promote restoration of depleted attentional capacity. A single-group study was conducted with a convenience sample of 28 people with clinical depression in 2009. Data were collected before, twice during, and immediately after a 12-week therapeutic horticulture programme, and at 3-month follow-up. Assessment instruments were the Beck Depression Inventory, Attentional Function Index, Brooding Scale, and Being Away and Fascination subscales from the Perceived Restorativeness Scale. Mean Beck Depression Inventory scores declined by 4.5 points during the intervention (F = 5.49, P = 0.002). The decline was clinically relevant for 50% of participants. Attentional Function Index scores increased (F = 4.14, P = 0.009), while Brooding scores decreased (F = 4.51, P = 0.015). The changes in Beck Depression Inventory and Attentional Function Index scores were mediated by increases in Being Away and Fascination, and decline in Beck Depression Inventory scores was also mediated by decline in Brooding. Participants maintained their improvements in Beck Depression Inventory scores at 3-month follow-up. Being away and fascination appear to work as active components in a therapeutic horticulture intervention for clinical depression.

Iranian Clinical Nurses’ Activities for Self-Directed Learning: A Qualitative Study

PubMed Central

Ghiyasvandian, Shahrzad; Malekian, Morteza; Cheraghi, Mohammad Ali

2016-01-01

Background: Clinical nurses need lifelong learning skills for responding to the rapid changes of clinical settings. One of the best strategies for lifelong learning is self-directed learning. The aim of this study was to explore Iranian clinical nurses’ activities for self-directed learning. Methods: In this qualitative study, 23 semi-structured personal interviews were conducted with nineteen clinical nurses working in all four hospitals affiliated to Isfahan Social Security Organization, Isfahan, Iran. Study data were analyzed by using the content analysis approach. The study was conducted from June 2013 to October 2014. Findings: Study participants’ activities for self-directed learning fell into two main categories of striving for knowledge acquisition and striving for skill development. The main theme of the study was ‘Revising personal performance based on intellectual-experiential activities’. Conclusions: Study findings suggest that Iranian clinical nurses continually revise their personal performance by performing self-directed intellectual and experiential activities to acquire expertise. The process of acquiring expertise is a linear process which includes two key steps of knowledge acquisition and knowledge development. In order to acquire and advance their knowledge, nurses perform mental learning activities such as sensory perception, self-evaluation, and suspended judgment step-by-step. Moreover, they develop their skills through doing activities like apprenticeship, masterly performance, and self-regulation. The absolute prerequisite to expertise acquisition is that a nurse needs to follow these two steps in a sequential manner. PMID:26652072

78 FR 35937 - Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0790] Food and Drug Administration Decisions for Investigational Device Exemption Clinical Investigations; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug...

Critical factors influencing physicians' intention to use computerized clinical practice guidelines: an integrative model of activity theory and the technology acceptance model.

PubMed

Hsiao, Ju-Ling; Chen, Rai-Fu

2016-01-16

With the widespread use of information communication technologies, computerized clinical practice guidelines are developed and considered as effective decision supporting tools in assisting the processes of clinical activities. However, the development of computerized clinical practice guidelines in Taiwan is still at the early stage and acceptance level among major users (physicians) of computerized clinical practice guidelines is not satisfactory. This study aims to investigate critical factors influencing physicians' intention to computerized clinical practice guideline use through an integrative model of activity theory and the technology acceptance model. The survey methodology was employed to collect data from physicians of the investigated hospitals that have implemented computerized clinical practice guidelines. A total of 505 questionnaires were sent out, with 238 completed copies returned, indicating a valid response rate of 47.1 %. The collected data was then analyzed by structural equation modeling technique. The results showed that attitudes toward using computerized clinical practice guidelines (γ = 0.451, p < 0.001), organizational support (γ = 0.285, p < 0.001), perceived usefulness of computerized clinical practice guidelines (γ = 0.219, p < 0.05), and social influence (γ = 0.213, p < 0.05) were critical factors influencing physicians' intention to use computerized clinical practice guidelines, and these factors can explain 68.6 % of the variance in intention to use computerized clinical practice guidelines. This study confirmed that some subject (human) factors, environment (organization) factors, tool (technology) factors mentioned in the activity theory should be carefully considered when introducing computerized clinical practice guidelines. Managers should pay much attention on those identified factors and provide adequate resources and incentives to help the promotion and use of computerized clinical

Epileptic activity in Alzheimer’s disease: causes and clinical relevance

PubMed Central

Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

2018-01-01

Epileptic activity is frequently associated with Alzheimer’s disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer’s disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer’s disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer’s disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer’s disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer’s disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer’s disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline. PMID:28327340

Engaging clinical nurses in quality and performance improvement activities.

PubMed

Albanese, Madeline P; Evans, Dietra A; Schantz, Cathy A; Bowen, Margaret; Disbot, Maureen; Moffa, Joseph S; Piesieski, Patricia; Polomano, Rosemary C

2010-01-01

Nursing performance measures are an integral part of quality initiatives in acute care; however, organizations face numerous challenges in developing infrastructures to support quality improvement processes and timely dissemination of outcomes data. At the Hospital of the University of Pennsylvania, a Magnet-designated organization, extensive work has been conducted to incorporate nursing-related outcomes in the organization's quality plan and to integrate roles for clinical nurses into the Department of Nursing and organization's core performance-based programs. Content and strategies that promote active involvement of nurses and prepare them to be competent and confident stakeholders in quality initiatives are presented. Engaging clinical nurses in the work of quality and performance improvement is essential to achieving excellence in clinical care. It is important to have structures and processes in place to bring meaningful data to the bedside; however, it is equally important to incorporate outcomes into practice. When nurses are educated about performance and quality measures, are engaged in identifying outcomes and collecting meaningful data, are active participants in disseminating quality reports, and are able to recognize the value of these activities, data become one with practice.

[Air conducted ocular VEMP: II. First clinical investigations].

PubMed

Walther, L E; Schaaf, H; Sommer, D; Hörmann, K

2011-10-01

Vestibular-evoked myogenic potentials (VEMP) are widely used to assess vestibular function. Air conducted (AC) cervical VEMP (cVEMP) reflect sacculus and inferior vestibular nerve function. Ocular VEMP (oVEMP) however has been hardly examined up to now. In recent studies it has been assumed that AC oVEMP probably reflects superior vestibular nerve function. The aim of this pilot study was to evaluate clinical application of the AC oVEMP. AC oVEMP were recorded in patients with peripheral vestibular disorders (n=21). In addition thermal irritation and head impulse test were performed and AC cVEMP were recorded. For intense AC-sound stimulation tone bursts (500 Hz) with 100 dB nHL were used. In peripheral vestibular disorders AC oVEMP and AC cVEMP could be classified into: • type 1 (inferior vestibular neuritis) with loss of AC oVEMP but normal AC cVEMP, • type 2, probable type of superior vestibular neuritis, showing present AC cVEMP but loss of AC oVEMP, • type 3, probable complete vestibular neuritis, without AC oVEMP and AC cVEMP. AC oVEMP may be used as an appropriate test for clinical investigation in patients with vestibular disorders. AC oVEMP is an additional, essential test for assessing otolith function beside AC cVEMP. Further vestibular test are necessary for precise clinical interpretation. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical and genetic investigation of pediatric cases of Wolff-Parkinson-White syndrome in Tunisian families.

PubMed

Nouira, Sonia; Ouarda, Fatma; Charfeddine, Cherine; Arfa, Imen; Ouragini, Houyem; Abid, Fekria; Abdelhak, Sonia

2010-01-01

Wolff-Parkinson-White (WPW) syndrome is an autosomal-dominant heart disease characterized by an accessory pathway that arises from an aberrant conduction from the atria to the ventricles. Several mutations within the PRKAG2 gene were shown to be responsible for WPW. This gene encodes the γ2 regulatory subunit of adenosine monophosphate (AMP)-activated protein kinase, which functions as a metabolic sensor in cells, responding to cellular energy demands. This first study of WPW in a North African population comprises the clinical and genetic investigation of 3 Tunisian families, including 11 affected members. The involvement of the PRKAG2 and NKX2-5 genes was investigated. Mutation screening showed that with the exception of two already reported single-nucleotide polymorphisms, no mutations were detected within the coding region of PRKAG2 or in the NKX2-5 gene. This study provides further evidence of the genetic heterogeneity of WPW. Copyright © 2010 Elsevier Inc. All rights reserved.

Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988

DTIC Science & Technology

1988-10-01

Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation Key Words: arginine vasopressin (AVP); vascular smooth muscle responses...Kullama, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr. Kenneth T. Nakamura, M.D.; John R. Claybaugh, Ph.D. Department/Section...Harrison Hassell, MC Associate Investigators: John R. Claybaugh, Ph.D.; Arnold Siemsen, MD; Jon Streltzer, MD Department/Section: Medicine/ Nephrology

The content of the work of clinical nurse specialists described by use of daily activity diaries.

PubMed

Oddsdóttir, Elín Jakobína; Sveinsdóttir, Herdís

2011-05-01

Evaluate the usefulness of the role of clinical nurse specialists and the content of their work by mapping their activities. The clinical work of advanced practice nursing differs in different countries, and a clear picture is lacking on what exactly advanced practice nurses do. Prospective exploratory study. The setting of the study was the largest hospital in Iceland where over half of the country's active nursing workforce are employed, including the only clinical nurse specialists. Of 19 clinical nurse specialists working at the hospital, 15 participated. Data were collected over seven days with a structured activity diary that lists 65 activities, classified into six roles and three domains. In 17 instances, the 'role activities' and 'domain activities' overlap and form 17 categories of practice. The clinical nurse specialists coded their activities at 15-minutes interval and could code up to four activities simultaneously. Daily, the clinical nurse specialists evaluated their clinical nurse specialist background. The roles that occupied the greatest proportion of the clinical nurse specialists' time were education, expert practice and 'other' activities, while the smallest proportions were in counselling, research and practice development. The domain they worked in most was the institutional domain, followed by the client/family domain and the clinical outcome management domain. All of the clinical nurse specialists reported working on two activities simultaneously, 11 of them on three activities and six on four activities. They self-assessed their background as clinical nurse specialists as being very useful. The activity diary is a useful tool for assessing the content of practice. Clinical nurse specialists spend too much time on activities related to the institution. Nurse managers are advised to provide clinical nurse specialists with ample time to develop the direct practice role in the client/family domain. The development of advanced nursing practice

Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route.

PubMed

Vimalnath, K V; Chakraborty, Sudipta; Rajeswari, A; Sarma, H D; Nuwad, Jitendra; Pandey, Usha; Kamaleshwaran, K; Shinto, Ajit; Dash, Ashutosh

2015-05-01

The scope of using no carrier added (NCA) (90)Y [T(1/2) = 64.1 h, Eβ(max) = 2.28 MeV] obtained from (90)Sr/(90)Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using (90)Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. Yttrium-90 was produced by thermal neutron irradiation of Y(2)O(3) target at a neutron flux of ~1×10(14) n/cm(2).s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of (90)Y labeled hydroxyapatite (HA) using HA particles of 1-10 μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of (90)Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of (90)Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq (90)Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. (90)Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (>99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of (90)Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using (90)Y produced via (n,γ) route in the management of the disease. The studies revealed that effective utilization of (90)Y produced via (n,γ) route in a medium flux research reactor coupled with the developed

Math Activities Using LogoWriter--Investigations.

ERIC Educational Resources Information Center

Flewelling, Gary

This book is one in a series of teacher resource books developed to: (1) rescue students from the clutches of computers that drill and control; and (2) supply teachers with computer activities compatible with a mathematics program that emphasizes investigation, problem solving, creativity, and hypothesis making and testing. This is not a book…

Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots

PubMed Central

2018-01-01

Objective This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. Method English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of “Ankle∗” AND “Robot∗” AND “Effect∗ OR Improv∗ OR Increas∗.” Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. Result A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR) game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF) training. Conclusion Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy. PMID:29675142

[The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

PubMed

Yamaguchi, H; Igari, J; Kume, H; Abe, M; Oguri, T; Kanno, H; Kawakami, S; Okuzumi, K; Fukayama, M; Ito, A; Kawata, K; Uchida, K

1997-09-01

The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

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

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

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

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy.

PubMed

Bandinelli, Francesca; Milla, Monica; Genise, Stefania; Giovannini, Leonardo; Bagnoli, Siro; Candelieri, Antonio; Collaku, Ledio; Biagini, Silvia; Cerinic, Marco Matucci

2011-07-01

To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. A total of 81 IBD patients [55 Crohn's disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

Leisure-Time Physical Activity and the Risk of Incident Dementia: The Mayo Clinic Study of Aging.

PubMed

Krell-Roesch, Janina; Feder, Nathanael T; Roberts, Rosebud O; Mielke, Michelle M; Christianson, Teresa J; Knopman, David S; Petersen, Ronald C; Geda, Yonas E

2018-01-01

We conducted a prospective cohort study derived from the population-based Mayo Clinic Study of Aging. We investigated if leisure-time physical activity among individuals with mild cognitive impairment (MCI) was associated with a decreased risk of developing dementia. 280 persons aged≥70 years (median 81 years, 165 males) with MCI and available data from neurologic evaluation, neuropsychological testing, and questionnaire-based physical activity assessment, were followed for a median of 3 years to the outcomes of incident dementia or censoring variables. We conducted Cox proportional hazards regression analyses with age as a time scale and adjusted for sex, education, medical comorbidity, depression, and APOE ɛ4 status. Moderate intensity midlife physical activity among MCI participants was significantly associated with a decreased risk of incident dementia (HR = 0.64; 95% CI, 0.41-0.98). There was a non-significant trend for a decreased risk of dementia for light and vigorous intensity midlife physical activity, as well as light and moderate intensity late-life physical activity. In conclusion, we observed that physical activity may be associated with a reduced risk of dementia among individuals with MCI. Furthermore, intensity and timing of physical activity may be important factors when investigating this association.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

PubMed

Cao, Jia-Li; Yang, Yu-Qing; Nabeel, Dookhun Muhammad; Sun, Ya-Li; Zou, Hua-Yi-Yang; Kong, Xiang-Qing; Lu, Xin-Zheng

The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH. © 2018 S. Karger AG, Basel.

[A report on clinical PET activities in Germany].

PubMed

Tashiro, M; Kubota, K; Itoh, M; Sasaki, H; Moser, E

1999-09-01

Clinical diagnostic procedure using positron emission tomography (PET) requires high costs. To promote clinical use of PET, sociomedical evaluation is necessary. In this paper, sociomedical situations concerning clinical use of PET in Germany is reported. Some comparisons are made between Japan and this country putting emphases on several points such as 1) number of cyclotron and PET facilities, 2) social restriction to transportation of radioisotopes, 3) activities of satellite PET facilities, and 4) clinical indications for PET studies. Number of cyclotron was larger in Japan (29) than in Germany (17), but number of PET facilities was larger in Germany (47) than in Japan (29). The reason seems that in Germany transportation and buying of radioisotopes is less restricted. Hence, more than half of PET facilities in Germany are "satellite facilities" which do not have their own cyclotrons. Radioisotope distribution seems to serve as a backbone of "satellite concept." Additionally in Germany, list of clinical indications for PET study is almost completed and now is widely in applied to most cases. To promote clinical use of PET in Japan, the German system might serve as an important socioeconomic model in Europe instead of the United States.

Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: a multicenter clinical trial.

PubMed

Naydeck, B L; Sutton-Tyrrell, K; Burek, K; Sopko, G S

1996-06-01

Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization.

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

CLINICAL SURFACES - Activity-Based Computing for Distributed Multi-Display Environments in Hospitals

NASA Astrophysics Data System (ADS)

Bardram, Jakob E.; Bunde-Pedersen, Jonathan; Doryab, Afsaneh; Sørensen, Steffen

A multi-display environment (MDE) is made up of co-located and networked personal and public devices that form an integrated workspace enabling co-located group work. Traditionally, MDEs have, however, mainly been designed to support a single “smart room”, and have had little sense of the tasks and activities that the MDE is being used for. This paper presents a novel approach to support activity-based computing in distributed MDEs, where displays are physically distributed across a large building. CLINICAL SURFACES was designed for clinical work in hospitals, and enables context-sensitive retrieval and browsing of patient data on public displays. We present the design and implementation of CLINICAL SURFACES, and report from an evaluation of the system at a large hospital. The evaluation shows that using distributed public displays to support activity-based computing inside a hospital is very useful for clinical work, and that the apparent contradiction between maintaining privacy of medical data in a public display environment can be mitigated by the use of CLINICAL SURFACES.

“There Are Too Many, but Never Enough": Qualitative Case Study Investigating Routine Coding of Clinical Information in Depression

PubMed Central

Cresswell, Kathrin; Morrison, Zoe; Sheikh, Aziz; Kalra, Dipak

2012-01-01

Background We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Materials and Methods Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Results Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. Conclusions There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined. PMID:22937106

An Investigation into the Clinical Reasoning Development of Veterinary Students.

PubMed

Vinten, Claire E K; Cobb, Kate A; Freeman, Sarah L; Mossop, Liz H

Clinical reasoning is a fundamental skill for veterinary clinicians and a competency required of graduates by the Royal College of Veterinary Surgeons. However, it is unknown how veterinary students develop reasoning skills and where strengths and shortcomings of curricula lie. This research aimed to use the University of Nottingham School of Veterinary Medicine and Science (SVMS) as a case study to investigate the development of clinical reasoning among veterinary students. The analysis was framed in consideration of the taught, learned, and declared curricula. Sixteen staff and sixteen students from the SVMS participated separately in a total of four focus groups. In addition, five interviews were conducted with recent SVMS graduates. Audio transcriptions were used to conduct a thematic analysis. A content analysis was performed on all curriculum documentation. It was found that SVMS graduates feel they have a good level of reasoning ability, but they still experience a deficit in their reasoning capabilities when starting their first job. Overarching themes arising from the data suggest that a lack of responsibility for clinical decisions during the program and the embedded nature of the clinical reasoning skill within the curriculum could be restricting development. In addition, SVMS students would benefit from clinical reasoning training where factors influencing "real life" decisions (e.g., finances) are explored in more depth. Integrating these factors into the curriculum could lead to improved decision-making ability among SVMS graduates and better prepare students for the stressful transition to practice. These findings are likely to have implications for other veterinary curricula.

Age at first sexual activity: Clinical and cognitive associations.

PubMed

Harries, Michael D; Paglia, Helen A; Redden, Sarah A; Grant, Jon E-Mail

2018-05-01

Engagement in sexual activity is common among adolescents and can be considered part of adolescent development, but it carries potential life-changing consequences. This study examined if clinical and cognitive differences existed between adolescents who engaged in voluntary sexual behavior before age 15, between ages 15 to 18, and after age 18. All participants were part of a larger study examining impulsive behavior in young adults. Participants were assessed on measures including demographics, comorbid psychiatric disorders, and clinical scales and cognitive tasks assessing impulsivity, obsessive-compulsive traits, emotion regulation, depression, anxiety, and quality of life. Those who engaged in voluntary sexual activity before age 15 were more likely to have increased depression and anxiety symptoms, to score higher on the Yale Brown Obsessive-Compulsive Scale for Pathologic Gambling, and to make poorer decisions on the Cambridge Gambling Task. The results of this study suggest that the decision to engage in sexual activity at a young age is not an act of thinking before acting or impatience, but rather a decision to engage in sensation-seeking behavior. This finding carries implications for interventions targeting healthy sexual activity in adolescents.

Doing Pre-operative Investigations in Emergency Department; a Clinical Audit.

PubMed

Rafiq, Muhammad Salman; Rafiq, Maria; Rafiq, Muhammad Imran; Salman, Seema Gul; Hafeez, Sania

2017-01-01

Pre-operative investigations for emergency surgical patients differ between centers. Following established guidelines can reduce unnecessary investigation, cost of treatment and hospital stay. The present audit was carried out to evaluate the condition of doing pre-operative investigations for three common surgical emergencies compared to National Institute for Health and Care Excellence (NICE) guidelines and local criteria. A retrospective clinical audit of acute-appendicitis, abscess and hernia patients admitted to the emergency department was carried out over a one-year period from July 2014 to July 2015. Data of laboratory investigations, their indication, cost and duration of hospital stay was collected and compared with NICE-guidelines. A total of 201 patients were admitted to the emergency department during the audit period. These included 77(38.3%) cases of acute-appendicitis, 112 (55.7%) cases of abscesses, and 12 (6%) cases of hernia. Investigations not indicated by NICE-guidelines included 42 (20.9%) full blood counts, 29 (14.4%) random blood sugars, 26 (12.9%) urea tests, 4 (2%) chest x-rays, 13 (6.5%) electrocardiographs, and 58 (28.9%) urine analyses. These cost 25,675 Rupees (245.46 Dollars) in unnecessary investigation costs and 65.7 days of additional hospital stay. Unnecessary investigations for emergency surgical patients can be reduced by following NICE-guidelines. This will reduce workload on emergency services, treatment costs and the length of hospital stay.

In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes.

PubMed

Sanguinetti, M; Posteraro, B; Romano, L; Battaglia, F; Lopizzo, T; De Carolis, E; Fadda, G

2007-02-01

Recently, bergamot oil was shown to be a potent antifungal agent in vitro against clinically important Candida species. In this study, the activities of bergamot natural essence and its furocoumarin-free and distilled extracts on dermatophytes such as Trichophyton, Microsporum and Epidermophyton species were investigated. In vitro susceptibility testing assays on 92 clinical isolates of dermatophytes (Trichophyton mentagrophytes n = 20, Trichophyton rubrum n = 18, Trichophyton interdigitale n = 15, Trichophyton tonsurans n = 2, Microsporum canis n = 24, Microsporum gypseum n = 1 and Epidermophyton floccosum n = 12) were performed using the CLSI M38-A broth microdilution method, except for employing an inoculum of 1-3 x 10(3) cfu/mL. MICs were determined at a visual endpoint reading of 80% inhibition compared with the growth control. MICs (v/v) of all fungi ranged from 0.156% to 2.5% for the natural essence, from 0.02% to 2.5% for the distilled extract, and from 0.08% to 1.25% for the furocoumarin-free extract. The three isolates of T. tonsurans and M. gypseum exhibited the highest MIC values. Data from this study indicate that bergamot oil is active in vitro against several common species of dermatophytes, suggesting its potential use for topical treatment of dermatophytoses.

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

PubMed Central

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

2015-01-01

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

[Methods of investigation in clinical cardiology. VIII. Socioeconomic evaluation of clinical cardiology practice].

PubMed

Lázaro de Mercado, P

1997-06-01

Health services are systems whose mission is to improve the health status of both individuals and society in general. In recent decades, these systems have faced challenges such as their increasing complexity, limited resources, rapid innovation and diffusion of medical technologies, pressures on demand from society and professionals, and the lack of knowledge of the effects of these factors on costs and society's health. In addition, health care expenditures have grown twice as fast as wealth in industrialized countries during the last 25 years. These problems have prompted cost containment as a key issue in health policy and, at the same time, have promoted the development of socioeconomic evaluation as a scientific activity in the frame of health services research. Socioeconomic evaluation tries to determine if the sacrifice made by society, which devotes part of its limited resources to health care, maximizes the outcomes for population. This article describes basic concepts and methods of economic appraisal in health services which are illustrated with examples of clinical practice in cardiology. Common methods of evaluation are described; the relation between the clinical outcome of a procedure and its associated costs is emphasized in explaining the types of efficiency analysis (cost-efficacy, cost-effectiveness, cost-utility, and cost-benefit); and finally a guide for socioeconomic evaluation is provided.

In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates.

PubMed

Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

2016-01-01

The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants' potential for developing new antimicrobials.

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

PubMed Central

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

2018-01-01

Background Thyrotoxicosis is a common disease caused by an excess of thyroid hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis cases are caused by Graves' disease, an autoimmune disease, which has a high recurrence rate when treated with antithyroid drugs such as methimazole or propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include palpitation, weight loss, restlessness, and difficulty sleeping. Although these clinical changes in thyrotoxicosis can be detected by currently available wearable activity trackers, there have been few trials of the clinical application of wearable devices in patients with thyrotoxicosis. Objective The aim of this study is to investigate the clinical applicability of wearable device-generated data to the management of thyrotoxicosis. We are analyzing continuously monitored data for heart rate, physical activity, and sleep in patients with thyrotoxicosis during their clinical course after treatment. Methods Thirty thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul National University Bundang Hospital. Heart rate, physical activity, and sleep are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data including anthropometric measures, thyroid function test, and hyperthyroidism symptom scale are recorded. Results Study enrollment began in December 2016, and the intervention and follow-up phases are ongoing. The results of the data analysis are expected to be available by September 2017. Conclusions This study will provide a foundational feasibility trial of the clinical applications of biosignal measurements to the differential diagnosis, prediction of clinical course, early detection of recurrence, and treatment in patients with thyrotoxicosis. Trial Registration ClinicalTrials.gov NCT03009357; https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at http://www.webcitation.org/6wh4MWPm2) PMID:29467121

Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators.

PubMed

Robinson, Georgeanna F W B; Schwartz, Lisa S; DiMeglio, Linda A; Ahluwalia, Jasjit S; Gabrilove, Janice L

2016-04-01

To understand the factors that facilitate career success for career development awardees in clinical and translational science and reconceptualize understand ing of career success for this population. In 2013-2014, the authors conducted semistructured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators' transition to independent funding. Interviews were recorded and transcribed, and the transcripts were analyzed thematically. Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included appropriate mentorship, protected research time, and institutional resources and support.Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgment of successes. Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator.

Running Memory for Clinical Handoffs: A Look at Active and Passive Processing.

PubMed

Anderson-Montoya, Brittany L; Scerbo, Mark W; Ramirez, Dana E; Hubbard, Thomas W

2017-05-01

The goal of the present study was to examine the effects of domain-relevant expertise on running memory and the ability to process handoffs of information. In addition, the role of active or passive processing was examined. Currently, there is little research that addresses how individuals with different levels of expertise process information in running memory when the information is needed to perform a real-world task. Three groups of participants differing in their level of clinical expertise (novice, intermediate, and expert) performed an abstract running memory span task and two tasks resembling real-world activities, a clinical handoff task and an air traffic control (ATC) handoff task. For all tasks, list length and the amount of information to be recalled were manipulated. Regarding processing strategy, all participants used passive processing for the running memory span and ATC tasks. The novices also used passive processing for the clinical task. The experts, however, appeared to use more active processing, and the intermediates fell in between. Overall, the results indicated that individuals with clinical expertise and a developed mental model rely more on active processing of incoming information for the clinical task while individuals with little or no knowledge rely on passive processing. The results have implications about how training should be developed to aid less experienced personnel identify what information should be included in a handoff and what should not.

NHS Trusts' clinical research activity and overall CQC performance - Is there a correlation?

PubMed

Jonker, L; Fisher, S J

2015-11-01

Since the late 2000's, the creation of the National Institute for Health Research (NIHR) has transformed clinical research activity in the United Kingdom. This study sought to establish if there is a link between clinical research activity and overall NHS Trust performance. Retrospective cohort study. Data for NHS Trust performance were obtained from public databases, namely the Care Quality Commission (CQC) 2013 risk rating for overall performance, and 2012-13 NIHR records for clinical research activity. Applying Spearman's rank analysis, none of the Trust categories showed a correlation with CQC risk rating: small hospitals, r = -0.062 (P = 0.76; n = 27); medium, r = -0.224 (P = 0.13; n = 47); large, r = -0.008 (P = 0.96; n = 57); academic, r = -0.18 (P = 0.41; n = 24). Similar results were observed when CQC risk rating was compared with the number of different clinical research studies conducted per Trust. The degree of NIHR National Portfolio clinical research activity is not significantly related to CQC risk rating, used as an indicator of overall NHS Trust performance. Other studies have previously shown that increased research activity correlates with improved mortality rates, one component of CQC risk rating scores. Alternative tools may have to be explored to evaluate the impact of clinical research on NHS Trusts and its patients. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

In Vitro Activities of Panduratin A against Clinical Staphylococcus Strains▿

PubMed Central

Rukayadi, Yaya; Lee, Kwanghyung; Han, Sunghwa; Yong, Dongeun; Hwang, Jae-Kwan

2009-01-01

In vitro antistaphylococcal activities of panduratin A, a natural chalcone compound isolated from Kaempferia pandurata Roxb, were compared to those of commonly used antimicrobials against clinical staphylococcal isolates. Panduratin A had a MIC at which 90% of bacteria were inhibited of 1 μg/ml for clinical staphylococcal isolates and generally was more potent than commonly used antimicrobials. PMID:19651906

[Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

PubMed

Subauste, M C

1989-01-01

A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

Missed Opportunities for TB Investigation in Primary Care Clinics in South Africa: Experience from the XTEND Trial.

PubMed

Chihota, Violet N; Ginindza, Sibuse; McCarthy, Kerrigan; Grant, Alison D; Churchyard, Gavin; Fielding, Katherine

2015-01-01

40 primary health clinics (PHCs) in four provinces in South Africa, June 2012 -February 2013. To determine whether health care worker (HCW) practice in investigating people with TB symptoms was altered when the initial test for TB was changed from smear microscopy to Xpert MTB/RIF. Cross-sectional substudy at clinics participating in a pragmatic cluster randomised trial, Xpert for TB: Evaluating a New Diagnostic "XTEND", which evaluated the effect of Xpert MTB/RIF implementation in South Africa. Consecutive adults exiting PHCs reporting at least one TB symptom (defined as any of cough, weight loss, night sweats and fever) were enrolled. The main outcome was the proportion who self-reported having sputum requested by HCW during the clinic encounter just completed. 3604 adults exiting PHCs (1676 in Xpert arm, 1928 in microscopy arm) were enrolled (median age 38 years, 71.4% female, 38.8% reported being HIV-positive, 70% reported cough). For 1267 participants (35.2%) the main reason for attending the clinic was TB symptom(s). Overall 2130/3604 (59.1%) said they reported their symptom(s) to HCW. 22.7% (818/3604) reported having been asked to give sputum for TB investigation. Though participants in the Xpert vs. microscopy arm were more likely to have sputum requested by HCW, this was not significantly different: overall (26.0% [436/1676] vs 19.8% [382/1928]; adjusted prevalence ratio [aPR] 1.31, [95% CI 0.78-2.20]) and when restricted to those presenting at clinics due to symptoms (49.1% [260/530] vs 29.9% [220/737]; aPR 1.38 [0.89-2.13]) and those reporting being HIV-positive (29.4% [190/647] vs 20.8% [156/749]; aPR 1.38[0.88-2.16]). Those attending clinic due to TB symptoms, were more likely to have sputum requested if they had increasing number of symptoms; longer duration of cough, unintentional weight loss and night sweats and if they reported symptoms to HCW. A large proportion of people exiting PHCs reporting TB symptoms did not get tested. Implementation of

Clinical efficacy of EDTA ultrasonic activation in the reduction of endotoxins and cultivable bacteria.

PubMed

Herrera, D R; Martinho, F C; de-Jesus-Soares, A; Zaia, A A; Ferraz, C C R; Almeida, J F A; Gomes, B P F A

2017-10-01

This clinical study was conducted to investigate the influence of 17% ethylenediaminetetraacetic acid (EDTA) ultrasonic activation after chemomechanical preparation (CMP) on eliminating/reducing oral bacterial lipopolysaccharides (known as endotoxins) and cultivable bacteria in teeth with pulp necrosis and apical periodontitis. Samples were taken from 24 root canals at several clinical periods: S1 - before CMP; S2 - after CMP; S3 - after EDTA: G1 - with ultrasonic activation (n = 12) and G2 - without ultrasonic activation (n = 12). Root canals were instrumented using Mtwo rotary files. Culture techniques were used to determine the number of colony-forming units (CFU). Limulus amebocyte lysate (LAL) was used to measure endotoxin levels. Friedman's and Wilcoxon signed-rank tests were used to compare the amount of bacteria and endotoxin levels in each period (P < 0.05). Endotoxins and cultivable bacteria were recovered in 100% of the initial samples (S1). CMP was effective in reducing endotoxins and bacterial load (all with P < 0.05). Higher values of endotoxin reduction were achieved with EDTA ultrasonic activation [G1, 0.02 EU mL -1 (range 0.01-0.75)] compared with the no activation group [G2, 1.13 EU mL -1 (range 0.01-8.34)] (P < 0.05). Regarding bacterial reduction, no statistically significant difference was found in S3, regardless of the group (G1, G2, P > 0.05). Chemomechanical preparation was effective in reducing bacteria and endotoxins, but could not completely eliminate them. The ultrasonic activation of EDTA was effective in further reducing endotoxin levels in the root canals of teeth with pulp necrosis and apical periodontitis. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

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

PubMed

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

2013-11-12

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

Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach

PubMed Central

Wytra̦żek, Marcin; Huber, Juliusz; Lisiński, Przemysław

Summary Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett’s scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome PMID:22152435

How do interprofessional student teams interact in a primary care clinic? A qualitative analysis using activity theory.

PubMed

Kent, Fiona; Francis-Cracknell, Alison; McDonald, Rachael; Newton, Jennifer M; Keating, Jennifer L; Dodic, Miodrag

2016-10-01

Practice based interprofessional education opportunities are proposed as a mechanism for health professionals to learn teamwork skills and gain an understanding of the roles of others. Primary care is an area of practice that offers a promising option for interprofessional student learning. In this study, we investigated what and how students from differing professions learn together. Our findings inform the design of future interprofessional education initiatives. Using activity theory, we conducted an ethnographic investigation of interprofessional education in primary care. During a 5 months period, we observed 14 clinic sessions involving mixed discipline student teams who interviewed people with chronic disease. Teams were comprised of senior medicine, nursing, occupational therapy, pharmacy and physiotherapy entry level students. Semi-structured interviews were also conducted with seven clinical educators. Data were analysed to ascertain the objectives, tools, rules and division of labour. Two integrated activity systems were identified: (1) student teams gathering information to determine patients' health care needs and (2) patients either as health consumers or student educators. Unwritten rules regarding 'shared contribution', 'patient as key information source' and 'time constraints' were identified. Both the significance of software literacy on team leadership, and a pre-determined structure of enquiry, highlighted the importance of careful consideration of the tools used in interprofessional education, and the way they can influence practice. The systems of practice identified provide evidence of differing priorities and values, and multiple perspectives of how to manage health. The work reinforced the value of the patients' voice in clinical and education processes.

The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

PubMed

Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

2014-07-01

The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design

Genomic biomarkers and clinical outcomes of physical activity.

PubMed

Izzotti, Alberto

2011-07-01

Clinical and experimental studies in humans provide evidence that moderate physical activity significantly decreases artery oxidative damage to nuclear DNA, DNA-adducts related to age and dyslipedemia, and mitochondrial DNA damage. Maintenance of adequate mitochondrial function is crucial for preventing lipid accumulation and peroxidation occurring in atherosclerosis. Studies performed on human muscle biopsies analyzing gene expression in living humans reveal that physically active subjects improve the expression of genes involved in mitochondrial function and of related microRNAs. The attenuation of oxidative damage to nuclear and mitochondrial DNA by physical activity resulted in beneficial effects due to polymorphisms of glutathione S-transferases genes. Subjects bearing null GSTM1/T1 polymorphisms have poor life expectancy in the case of being sedentary, which was increased 2.6-fold in case they performed physical activity. These findings indicate that the preventive effect of physical activity undergoes interindividual variation affected by genetic polymorphisms. © 2011 New York Academy of Sciences.

A short version of the revised 'experience of close relationships questionnaire': investigating non-clinical and clinical samples.

PubMed

Wongpakaran, Tinakon; Wongpakaran, Nahathai

2012-01-01

This study seeks to investigate the psychometric properties of the short version of the revised 'Experience of Close Relationships' questionnaire, comparing non-clinical and clinical samples. In total 702 subjects participated in this study, of whom 531 were non-clinical participants and 171 were psychiatric patients. They completed the short version of the revised 'Experience of Close Relationships' questionnaire (ECR-R-18), the Perceived Stress Scale-10(PSS-10), the Rosenberg Self-Esteem Scale (RSES) and the UCLA Loneliness scale. A retest of the ECR-R-18 was then performed at four-week intervals. Then, confirmatory factor analyses were performed to test the validity of the new scale. The ECR-R-18 showed a fair to good internal consistency (α 0.77 to 0.87) for both samples, and the test-retest reliability was found to be satisfactory (ICC = 0.75). The anxiety sub-scale demonstrated concurrent validity with PSS-10 and RSES, while the avoidance sub-scale showed concurrent validity with the UCLA Loneliness Scale. Confirmatory factor analysis using method factors yielded two factors with an acceptable model fit for both groups. An invariance test revealed that the ECR-R-18 when used on the clinical group differed from when used with the non-clinical group. The ECR-R-18 questionnaire revealed an overall better level of fit than the original 36 item questionnaire, indicating its suitability for use with a broader group of samples, including clinical samples. The reliability of the ECR-R- 18 might be increased if a modified scoring system is used and if our suggestions with regard to future studies are followed up.

Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice.

PubMed

Anderson, Jaclyn; Caplan, Liron; Yazdany, Jinoos; Robbins, Mark L; Neogi, Tuhina; Michaud, Kaleb; Saag, Kenneth G; O'Dell, James R; Kazi, Salahuddin

2012-05-01

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice. The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations. Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures. We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings. Copyright © 2012 by the American College of Rheumatology.

Associations of prepartum body condition score with occurrence of clinical endometritis and resumption of postpartum ovarian activity in dairy cattle.

PubMed

Kadivar, Ali; Ahmadi, Mohammad Rahim; Vatankhah, Mahmood

2014-01-01

This study was performed to investigate the effect of periparturient body condition score on the occurrence of clinical endometritis and postpartum resumption of ovarian activity in dairy cows. Eighty-seven lactating Holstein cows, fed with a total mixed ration diet, were included into the study. Body condition scoring (using a 5-point scale with quarter-point divisions) was performed by the same investigator using the visual technique every 2 weeks, from 2 weeks before until 6 weeks after calving. Palpation of the reproductive tract and ultrasonographic assessment of ovaries for detection of corpus luteum using a rectal linear probe was also performed at 2, 4, and 6 weeks after calving. Cows with clinical endometritis had significantly lower body condition score (BCS) than normal cows at all weeks pre- and postcalving, and cows that did not ovulate until 45 days after calving had a significantly lower BCS pre- and postpartum. Cows that did not ovulate until 45 days after calving also lost more BCS from 2 weeks before to 4 weeks after calving. Besides, first ovulation after calving take occurred later in cows with clinical endometritis compared to normal cows (P < 0.05). In conclusion, low BCS is a risk factor for postpartum endometritis and delayed cyclicity in dairy cows. BCS loss from dry-off to early lactation and occurrence of clinical endometritis can significantly affect postpartum ovarian activity.

Clinical and financial burden of active lupus in Greece: a nationwide study.

PubMed

Bertsias, G; Karampli, E; Sidiropoulos, P; Gergianaki, I; Drosos, A; Sakkas, L; Garyfallos, A; Tzioufas, A; Vassilopoulos, D; Tsalapaki, C; Sfikakis, P; Panopoulos, S; Athanasakis, K; Perna, A; Psomali, D; Kyriopoulos, J; Boumpas, D

2016-10-01

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need. © The Author(s) 2016.

Clinical Investigation Program Report.

DTIC Science & Technology

1983-10-01

metastatic to liver. (0) H-83-63. Double-blind, randomized parallel comparison of two different dosage regimens of naproxen sodium in patients with...different dosage regimens of naproxen sodium in patients with bone pain due to m etastatic cancer. Start Date: May 83 Est Comp Date: Indefinite Principal...Investigator: Facility: LTC D Gandara, MD LAMC CPT R Mansour, MD D ept/Svc: Associate Investigators: Hematology-Oncology Key Words: naproxen sodium

Comparison of the antibiotic activities of Daptomycin, Vancomycin, and the investigational Fluoroquinolone Delafloxacin against biofilms from Staphylococcus aureus clinical isolates.

PubMed

Siala, Wafi; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M; Hallin, Marie; Denis, Olivier; Van Bambeke, Françoise

2014-11-01

Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local

Comparison of the Antibiotic Activities of Daptomycin, Vancomycin, and the Investigational Fluoroquinolone Delafloxacin against Biofilms from Staphylococcus aureus Clinical Isolates

PubMed Central

Siala, Wafi; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M.; Hallin, Marie; Denis, Olivier

2014-01-01

Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726–2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local

In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates

PubMed Central

Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

2016-01-01

Aim/Background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Materials and Methods: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. Results: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants’ potential for developing new antimicrobials. PMID:27366345

25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Do covered services include the conduct of clinical studies and investigations and the provision of emergency services, including the operation of emergency... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and the...

Activities of Intellectual Disability Clinical Nurse Specialists in Ireland.

PubMed

Doody, Owen; Slevin, Eamonn; Taggart, Laurence

The aim of this study was to identify the contribution of Irish intellectual disability clinical nurse specialists (ID CNSs) to service delivery. A nonexperimental descriptive design was selected to survey ID CNSs presently working in Ireland. The questionnaire was developed based on focus group interviews, available literature, and expert panel views. Ethical approval and access were granted to all ID CNSs in Ireland. Thirty-two responded (33.68% response rate) from all work areas (voluntary organizations or health service executive) practicing within residential, community, or school services. Respondents were surveyed across a range of areas (demographic details and support to client, staff, family, organization, community, other agencies, and professional development). Findings identify that ID CNSs are active in all aspects of their roles as clinical specialist, educator, communicator, researcher, change agent, and leader, thus supporting person-centered care and improving service delivery. To meet changing healthcare demands, promote person-centered care, and improve service delivery, the CNS role in ID should be developed and supported. The findings merit a further study on ID CNS role activity, possible variables influencing role activity, and team members' views.

Activation of QA devices and phantom materials under clinical scanning proton beams—a gamma spectrometry study

NASA Astrophysics Data System (ADS)

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-01

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Activation of QA devices and phantom materials under clinical scanning proton beams-a gamma spectrometry study.

PubMed

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-07

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion.

PubMed

Chen, Jian-Ling; Yang, Jian-Ming; Huang, Ya-Zhe; Li, Ying

2016-11-01

This study aims to investigate the clinical curative effect of lymphocyte active immunotherapy (LAI) on unexplained recurrent spontaneous abortion (RSA). A total of 749 RSA patients who received medical service in our hospital from October 2009 to June 2013 were enrolled into this study. These patients were randomly divided into two groups: LAI group (treatment group) and routine progesterone for maintenance tocolysis group (control group). A comparative analysis on the pregnancy outcomes in these two groups was conducted. Abortion rate was significantly lower in the LAI group than in the control group (P<0.05). Furthermore, pregnancy success rates were 89.7% and 32.2% in patients who received LAI and routine progesterone for maintenance tocolysis, respectively, and the difference was statistically significant (P<0.05). Our analysis suggested that LAI can treat RSA effectively and has an excellent clinical effect. Furthermore, the detection of blocking antibodies showed a positive prediction on pregnancy outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Activities of Tannins--From In Vitro Studies to Clinical Trials.

PubMed

Sieniawska, Elwira

2015-11-01

Tannins are considered as valuable plant secondary metabolites providing many benefits for human health. In this review information was gathered about bioactivity in vitro and in vivo, as well as about conducted clinical trials. The literature research was based on ScienceDirect, Scopus, and Cochrane databases and presents a wide range of tested activities of tannins. The described clinical trials verify laboratory tests and show the effective health benefits taken from supplementation with tannins.

Perspectives on barriers and facilitators to minority recruitment for clinical trials among cancer center leaders, investigators, research staff, and referring clinicians: enhancing minority participation in clinical trials (EMPaCT).

PubMed

Durant, Raegan W; Wenzel, Jennifer A; Scarinci, Isabel C; Paterniti, Debora A; Fouad, Mona N; Hurd, Thelma C; Martin, Michelle Y

2014-04-01

The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, the authors assessed the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment. In total, 91 qualitative interviews were conducted at 5 US cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment. The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation, 2) potential minority participants often face multilevel barriers that preclude them from being offered an opportunity to participate in a clinical trial, 3) facilitators at both the institutional and participant level potentially encourage minority recruitment, and 4) variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities. Multilevel approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials. © 2014 American Cancer Society.

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

PubMed

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

2018-02-21

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

Analysis of immune activation and clinical events in acute infectious mononucleosis.

PubMed

Williams, Hilary; Macsween, Karen; McAulay, Karen; Higgins, Craig; Harrison, Nadine; Swerdlow, Anthony; Britton, Kate; Crawford, Dorothy

2004-07-01

The symptoms of infectious mononucleosis (IM) are thought to be caused by T cell activation and cytokine production. Surface lymphocyte activation marker (SLAM)-associated protein (SAP) regulates lymphocyte activation via signals from cell-surface CD244 (2B4) and SLAM (CD150). We followed T cell activation via this SAP/SLAM/CD244 pathway in IM and analyzed whether the results were associated with clinical severity. At diagnosis, SAP, SLAM, and CD244 were significantly up-regulated on CD4 and CD8 T cells; expression decreased during IM, but CD244 and SLAM levels remained higher on CD8 cells 40 days later. There were significantly more lymphocytes expressing CD8 and CD244/CD8 in patients with severe sore throat. The expression of CD8 alone and CD244 on CD8 cells correlated with increased virus load. We suggest that T cells expressing CD244 and SLAM are responsible for the clinical features of IM but that the control of activation is maintained by parallel increased expression of SAP.

Using Hermeneutic Phenomenology to Investigate How Experienced Practitioners Learn to Communicate Clinical Reasoning

ERIC Educational Resources Information Center

Ajjawi, Rola; Higgs, Joy

2007-01-01

This paper is primarily targeted at doctoral students and other researchers considering using hermeneutic phenomenology as a research strategy. We present interpretive paradigm research designed to investigate how experienced practitioners learn to communicate their clinical reasoning in professional practice. Twelve experienced physiotherapy…

Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

ERIC Educational Resources Information Center

Lammert, Marilyn; Dolan, Mary M.

1983-01-01

Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

[In-vitro activity of panipenem against clinical isolates in 2006].

PubMed

Yoshida, Sanae; Koga, Tetsufumi; Kakuta, Masayo; Kobayashi, Intetsu; Matsuzaki, Kaoru; Urabe, Eriko; Omika, Kaoru; Hasegawa, Miyuki; Sato, Yumie

2008-02-01

The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately. Panipenem (PAPM), imipenem (IPM), meropenem (MEPM), biapenem (BIPM), doripenem (DRPM), cefozopran (CZOP), cefepime (CFPM), and sulbactam/cefoperazone (SBT/CPZ) were used as test antibiotics. PAPM, IPM and DRPM exhibited excellent in vitro antibacterial activities against methicillin-susceptible Staphylococcus, with all isolates exhibiting a MIC of < or =0.06 microg/mL. Against Streptococcus including penicillin-resistant S. pneumoniae, PAPM demonstrated the strongest antibacterial activity among the carbapenems with a MIC range of < or =0.06 to 0.12 microg/mL. Against Enterobacteriaceae, MEPM showed the strongest antibacterial activity, and PAPM had comparable activity to IPM. Against the extended-spectrum beta-lactamase producing Escherichia coli, Klebsiella species and Proteus species, the MICs for the cephems were high, however, those for the carbepenems were low. Against H. influenzae, PAPM had comparable activity to IPM. With respect to anaerobes, each of the carbapenems tested demonstrated almost the same strong antibacterial activity. In conclusion, 13 years has passed since PAPM was launched in 1993, PAPM still maintains potent antibacterial activity and is considered an effective antimicrobial agent for various types of infectious diseases.

Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome.

PubMed

Abe, Ichiro; Sugimoto, Kaoru; Miyajima, Tetsumasa; Ide, Tomoko; Minezaki, Midori; Takeshita, Kaori; Takahara, Saori; Nakagawa, Midori; Fujimura, Yuki; Kudo, Tadachika; Miyajima, Shigero; Taira, Hiroshi; Ohe, Kenji; Ishii, Tatsu; Yanase, Toshihiko; Kobayashi, Kunihisa

2018-04-27

Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas. Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning ACTH level (<10 pg/mL) and a loss of the diurnal serum cortisol rhythm. Results Of the 61 patients, none (0%) had malignant tumors, 8 (13.1%) had pheochromocytoma, and 15 (24.6%) had primary aldosteronism; when diagnosed by our revised criteria, 13 (21.3%) had cortisol-secreting adenomas (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly lower rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index. Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

Clinical Investigation Program

DTIC Science & Technology

1992-10-01

Tick-Borne Disease Surveillance in Febrile, Hospitalized Patients KEYWORDS: tick-borne disease, Lyme disease, Rocky Mountain Spotted Fever PRINCIPAL...tick-borne diseases such as Lyme disease, Ehrlichiosis, Q fever, and Rocky Mountain Spotted Fever in the patients admitted to Womack Army Medical...several common tick-borne diseases such as Lyme disease, ehrlichiosis, Q fever, and Rocky Mountain Spotted Fever (RMSF) in a non-active duty military

Sex-specific issues in eating disorders: a clinical and psychopathological investigation.

PubMed

Valente, Stefano; Di Girolamo, Giulia; Forlani, Martina; Biondini, Anna; Scudellari, Paolo; De Ronchi, Diana; Atti, Anna Rita

2017-12-01

To highlight the characteristics of eating disorders (ED) in males, with particular attention to sex-related clinical features and psychiatric co-morbidities. Out of 280 persons, referred to our outpatients ED clinic between January 2011 and June 2014, 267 with complete information were included in this retrospective observational study. The men/women ratio was one to five (male 16.5% vs female 83.5%) with an increasing proportion of male patients over the years. The most frequent ED in males was binge eating disorder, whereas in females anorexia nervosa and bulimia nervosa prevailed. Excessive exercising and fasting were the most common compensation behaviours in males; while self-induced vomiting and laxative-diuretic abuse were more typical in females. Among women, the most represented psychiatric co-morbidities were mood and somatoform disorders, whereas among men, anxiety and psychosis spectrum disorders were the most frequent ones. Borderline and histrionic personality disorders were prevalent in female ED, while narcissistic and antisocial personality disorders prevailed in males. ED in men is a growing phenomenon. Male ED, compared to female ED, show differences in clinical presentation, symptoms and co-morbidities. Despite the use of clinical and psychometric evaluating tools targeting female patients, sex differences do exist and additional studies are required to investigate male specific issues in ED. Level of Evidence Level V, cross-sectional descriptive study.

Recommendations from the Investigational New Drug/Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

PubMed

Holbein, M E Blair; Berglund, Jelena Petrovic; O'Reilly, Erin K; Hartman, Karen; Speicher, Lisa A; Adamo, Joan E; O'Riordan, Gerri; Brown, Jennifer Swanton; Schuff, Kathryn G

2014-06-01

The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration-regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

Improving management of student clinical placements: insights from activity theory.

PubMed

O'Keefe, Maree; Wade, Victoria; McAllister, Sue; Stupans, Ieva; Burgess, Teresa

2016-08-24

An approach to improve management of student clinical placements, the Building Teams for Quality Learning project, was trialed in three different health services. In a previous paper the authors explored in some detail the factors associated with considerable success of this approach at one of these services. In this paper, the authors extend this work with further analysis to determine if the more limited outcomes observed with participants at the other two services could be explained by application of activity theory and in particular the expansive learning cycle. Staff at three health services participated in the Building Teams for Quality Learning project: a dental clinic, a community aged care facility and a rural hospital. At each site a team of seven multi-disciplinary staff completed the project over 9 to 12 months (total 21 participants). Evaluation data were collected through interviews, focus groups and direct observation of staff and students. Following initial thematic analysis, further analysis was conducted to compare the processes and outcomes at each participating health service drawing on activity theory and the expansive learning cycle. Fifty-one interview transcripts, 33 h of workplace observation and 31 sets of workshop field notes (from 36 h of workshops) were generated. All participants were individually supportive of, and committed to, high quality student learning experiences. As was observed with staff at the dental clinic, a number of potentially effective strategies were discussed at the aged care facility and the rural hospital workshops. However, participants in these two health services could not develop a successful implementation plan. The expansive learning cycle element of modeling and testing new solutions was not achieved and participants were unable, collectively to reassess and reinterpret the object of their activities. The application of activity theory and the expansive learning cycle assisted a deeper understanding of

In vitro antimicrobial activities of cinnamon bark oil, anethole, carvacrol, eugenol and guaiazulene against Mycoplasma hominis clinical isolates.

PubMed

Sleha, Radek; Mosio, Petra; Vydrzalova, Marketa; Jantovska, Alexandra; Bostikova, Vanda; Mazurova, Jaroslava

2014-06-01

The aim of this study was to evaluate the antimicrobial effects of five natural substances against 50 clinical isolates of Mycoplasma hominis. The in vitro activity of selected natural compounds, cinnamon bark oil, anethole, carvacrol, eugenol and guaiazulene, was investigated against 50 M. hominis isolates cultivated from cervical swabs by the broth dilution method. All showed valuable antimicrobial activity against the tested isolates. Oil from the bark of Cinnamomum zeylanicum (MBC90 = 500 µg/mL) however was found to be the most effective. Carvacrol (MBC90 = 600 µg/mL) and eugenol (MBC90 = 1000 µg/mL) also possessed strong antimycoplasmal activity. The results indicate that cinnamon bark oil, carvacrol and eugenol have strong antimycoplasmal activity and the potential for use as antimicrobial agents in the treatment of mycoplasmal infections.

Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity

ERIC Educational Resources Information Center

Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.

2010-01-01

This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD-'Assessing QbTest Utility in ADHD' (AQUA): a randomised controlled trial.

PubMed

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-12-01

The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current 'gold standard' ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. This multisite randomised controlled trial will recruit young people (aged 6-17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young

Antifungal Activity of Hydroalcoholic Extract of Chrysobalanus icaco Against Oral Clinical Isolates of Candida Species

PubMed Central

Silva, João Paulo Bastos; Peres, Ana Regina Maués Noronha; Paixão, Thiago Portal; Silva, Andressa Santa Brígida; Baetas, Ana Cristina; Barbosa, Wagner Luiz Ramos; Monteiro, Marta Chagas; Andrade, Marcieni Ataíde

2017-01-01

Background: Chrysobalanus icaco is a medicinal plant commonly used to treat fungal infections in Brazilian Amazonian region. Objective: This work aimed to evaluate the antifungal activity of the hydroalcoholic extract of C. icaco (HECi) against oral clinical isolates of Candida spp. and to determine the pharmacognostic parameters of the herbal drug and the phytochemical characteristics of HECi. Materials and Methods: The pharmacognostic characterization was performed using pharmacopoeial techniques. Phytochemical screening, total flavonoid content, and high-performance liquid chromatography (HPLC) analysis were used to investigate the chemical composition of the HECi. A broth microdilution method was used to determine the antifungal activity of the extract against 11 oral clinical isolates of Candida spp. Results: Herbal drug presented parameters which were within the limits set forth in current Brazilian legislation. A high amount of flavonoid content (132,959.33 ± 12,598.23 μg quercetin equivalent/g of extract) was found in HECi. Flavonoids such as myricetin and rutin were detected in the extract by HPLC analyses. HECi showed antifungal activity against oral isolates of Candida albicans and Candida parapsilosis (minimum inhibitory concentrations [MIC] 3.12 and 6.25 mg/mL, respectively), and C. albicans American American Type Culture Collection (MIC <1.56 mg/mL). Conclusion: HECi was shown to possess antifungal activity against Candida species with clinical importance in the development of oral candidiasis, and these activities may be related to its chemical composition. The antifungal activity detected for C. icaco against Candida species with clinical importance in the development of oral candidiasis can be attributed to the presence of flavonoids in HECi, characterized by chromatographic and spectroscopic techniques. SUMMARY Chrysobalanus icaco presents a high amount of flavonoids in its constitutionLC analysis was able to identify the flavonoids myricetin

Understanding the investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia

PubMed Central

Franzen, Samuel R P; Chandler, Clare; Enquselassie, Fikre; Siribaddana, Sisira; Atashili, Julius; Angus, Brian; Lang, Trudie

2013-01-01

Objectives Clinical trials provide ‘gold standard’ evidence for policy, but insufficient locally relevant trials are conducted in low-income and middle-income countries. Local investigator-initiated trials could generate highly relevant data for national governments, but information is lacking on how to facilitate them. We aimed to identify barriers and enablers to investigator-initiated trials in Ethiopia to inform and direct capacity strengthening initiatives. Design Exploratory, qualitative study comprising of in-depth interviews (n=7) and focus group discussions (n=3). Setting Fieldwork took place in Ethiopia during March 2011. Participants Local health researchers with previous experiences of clinical trials or stakeholders with an interest in trials were recruited through snowball sampling (n=20). Outcome measures Detailed discussion notes were analysed using thematic coding analysis and key themes were identified. Results All participants perceived investigator-initiated trials as important for generating local evidence. System and organisational barriers included: limited funding allocation, weak regulatory and administrative systems, few learning opportunities, limited human and material capacity and poor incentives for conducting research. Operational hurdles were symptomatic of these barriers. Lack of awareness, confidence and motivation to undertake trials were important individual barriers. Training, knowledge sharing and experience exchange were key enablers to trial conduct and collaboration was unanimously regarded as important for improving capacity. Conclusions Barriers to trial conduct were found at individual, operational, organisational and system levels. These findings indicate that to increase locally led trial conduct in Ethiopia, system wide changes are needed to create a more receptive and enabling research environment. Crucially, the creation of research networks between potential trial groups could provide much needed practical

Using thermographic cameras to investigate eye temperature and clinical severity in depression

NASA Astrophysics Data System (ADS)

Maller, Jerome J.; George, Shefin Sam; Viswanathan, Rekha Puzhavakkathumadom; Fitzgerald, Paul B.; Junor, Paul

2016-02-01

Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression.

Clinical descriptive measures of shoulder range of motion for a healthy, young and physically active cohort.

PubMed

Vairo, Giampietr L; Duffey, Michele L; Owens, Brett D; Cameron, Kenneth L

2012-09-10

The objective of this innovative research study was to describe clinical shoulder complex range of motion (ROM) measures for a young, healthy, and physically active population. This investigation represents a cross-sectional experiment conducted at a military academy-based sports medicine center. Military cadets with no history of shoulder complex injury were assessed within two months of enrollment in the academy; 548 men (18.8 ± 1.0 yr, 75.2 ± 12.2 kg, 178.3 ± 7.4 cm) and 74 women (18.7 ± 0.9 yr, 63.2 ± 8.9 kg, 165.2 ± 6.9 cm) participated. Descriptive measures included cross-body adduction (CAD), flexion (FLX), external rotation (ER0) with the shoulder complex in adduction and elbow flexed to 90°, internal and external rotation (IR, ER) with the shoulder complex at 90° of abduction and elbow flexed to 90° as well as arc (ARC) of IR-ER using standardized clinical quantification techniques. Bilateral and sex differences were evaluated using dependent and independent t-tests, respectively. Percentiles by arm dominance and sex were also calculated for all ROM measures. Data were normally distributed. Active and passive ROM measures indicated significant bilateral differences (P < 0.05) except for ARC. Sex differences (P < 0.05) were noted for active and passive CAD, FLX and ER0 for the dominant arm as well as active and passive CAD, FLX and ARC for the non-dominant arm. These original data provide descriptive measures for shoulder complex ROM excursions, assisting sports medicine practitioners in potentially identifying clinical deficiencies and functional outcomes following shoulder injury.

Physical activity intervention for elderly patients with reduced physical performance after acute coronary syndrome (HULK study): rationale and design of a randomized clinical trial.

PubMed

Tonet, Elisabetta; Maietti, Elisa; Chiaranda, Giorgio; Vitali, Francesco; Serenelli, Matteo; Bugani, Giulia; Mazzoni, Gianni; Ruggiero, Rossella; Myers, Jonathan; Villani, Giovanni Quinto; Corvi, Ursula; Pasanisi, Giovanni; Biscaglia, Simone; Pavasini, Rita; Lucchi, Giulia Ricci; Sella, Gianluigi; Ferrari, Roberto; Volpato, Stefano; Campo, Gianluca; Grazzi, Giovanni

2018-05-21

Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance. HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed. The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance. Clinicaltrials.gov, identifier NCT03021044 , first posted January, 13th 2017.

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

PubMed Central

Munro, Malcolm G

2014-01-01

Postmenopausal uterine bleeding is defined as uterine bleeding after permanent cessation of menstruation resulting from loss of ovarian follicular activity. Bleeding can be spontaneous or related to ovarian hormone replacement therapy or to use of selective estrogen receptor modulators (eg, tamoxifen adjuvant therapy for breast carcinoma). Because anovulatory “cycles” with episodes of multimonth amenorrhea frequently precede menopause, no consensus exists regarding the appropriate interval of amenorrhea before an episode of bleeding that allows for the definition of postmenopausal bleeding. The clinician faces the possibility that an underlying malignancy exists, knowing that most often the bleeding comes from a benign source. Formerly, the gold-standard clinical investigation of postmenopausal uterine bleeding was institution-based dilation and curettage, but there now exist office-based methods for the evaluation of women with this complaint. Strategies designed to implement these diagnostic methods must be applied in a balanced way considering the resource utilization issues of overinvestigation and the risk of missing a malignancy with underinvestigation. Consequently, guidelines and recommendations were developed to consider these issues and the diverse spectrum of practitioners who evaluate women with postmenopausal bleeding. The guideline development group determined that, for initial management of spontaneous postmenopausal bleeding, primary assessment may be with either endometrial sampling or transvaginal ultrasonography, allowing patients with an endometrial echo complex thickness of 4 mm or less to be managed expectantly. Guidelines are also provided for patients receiving selective estrogen receptor modulators or hormone replacement therapy, and for an endometrial echo complex with findings consistent with fluid in the endometrial cavity. PMID:24377427

Clinical Investigation Program

DTIC Science & Technology

1990-09-30

with Subretinal Hemorrhage: A Case Report. Ann Ophthalmol, 22:259-262, 1990. Walton WT, Enzenauer RW: " Nutritional Disease" in Levin AV, Enzenauer RW...adequate means of maintaining nutritional status. Publications and Presentations: None. 1 135 FAMC A.P.R. (RCS MED 300) Detail Summary Sheet (HSCR 40-23 as...4) Title: The Effect of Liposucticn on Myocutaneous Flaps in the Yucatan Micro Pig (5) Start Date: (6) Est Compl Date: (7) Principal Investigator: (8

Improving surveillance of sexually transmitted infections using mandatory electronic clinical reporting: the genitourinary medicine clinic activity dataset, England, 2009 to 2013.

PubMed

Savage, E J; Mohammed, H; Leong, G; Duffell, S; Hughes, G

2014-12-04

A new electronic surveillance system for sexually transmitted infections (STIs) was introduced in England in 2009. The genitourinary medicine clinic activity dataset (GUMCAD) is a mandatory, disaggregated, pseudo-anonymised data return submitted by all STI clinics across England. The dataset includes information on all STI diagnoses made and services provided alongside demographic characteristics for every patient attendance at a clinic. The new system enables the timely analysis and publication of routine STI data, detailed analyses of risk groups and longitudinal analyses of clinic attendees. The system offers flexibility so new codes can be introduced to help monitor outbreaks or unusual STI activity. From January 2009 to December 2013 inclusive, over twenty-five million records from a total of 6,668,648 patients of STI clinics have been submitted. This article describes the successful implementation of this new surveillance system and the types of epidemiological outputs and analyses that GUMCAD enables. The challenges faced are discussed and forthcoming developments in STI surveillance in England are described.

How GPs implement clinical guidelines in everyday clinical practice--a qualitative interview study.

PubMed

Le, Jette V; Hansen, Helle P; Riisgaard, Helle; Lykkegaard, Jesper; Nexøe, Jørgen; Bro, Flemming; Søndergaard, Jens

2015-12-01

Clinical guidelines are considered to be essential for improving quality and safety of health care. However, interventions to promote implementation of guidelines have demonstrated only partial effectiveness and the reasons for this apparent failure are not yet fully understood. To investigate how GPs implement clinical guidelines in everyday clinical practice and how implementation approaches differ between practices. Individual semi-structured open-ended interviews with seven GPs who were purposefully sampled with regard to gender, age and practice form. Interviews were recorded, transcribed verbatim and then analysed using systematic text condensation. Analysis of the interviews revealed three different approaches to the implementation of guidelines in clinical practice. In some practices the GPs prioritized time and resources on collective implementation activities and organized their everyday practice to support these activities. In other practices GPs discussed guidelines collectively but left the application up to the individual GP whilst others again saw no need for discussion or collective activities depending entirely on the individual GP's decision on whether and how to manage implementation. Approaches to implementation of clinical guidelines vary substantially between practices. Supporting activities should take this into account. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Factors Related to Healthy Diet and Physical Activity in Hospital-Based Clinical Nurses.

PubMed

Albert, Nancy M; Butler, Robert; Sorrell, Jeanne

2014-09-30

Hospitals often promote healthy lifestyles, but little is known about nurses' actual diet and physical activity. Greater understanding about these lifestyle choices for clinical nurses may improve existing hospital-based programs and/or create desirable services. This article discusses a study that considered diet and physical activity of clinical nurses, using elements of Pender's self-care theory as a conceptual framework. Study methods included a cross-sectional, correlational design and a convenience sample of 278 nurses who worked on units with 24 hours/day and seven days-per-week responsibilities. Participants completed diet and exercise questionnaires about perceptions of attitudes and opinions, barriers, diet benefits/exercise motivators, self-efficacy, and locus of control, and personal and work characteristics. Diet and activity categories were created. Study results demonstrated that over 50% of nurses had moderately healthy diets but were insufficiently active. Healthy diet and physical activity levels were associated with higher self-efficacy, more diet benefits and physical activity motivators, fewer perceived barriers, and confidence in body image. The article discussion and conclusion sections note areas for future research and suggest that focused interventions that address benefits, motivators, and self-efficacy may increase participation in hospital-based programs and enhance healthy lifestyle for hospital-based clinical nurses.

Student and staff opinion of electronic capture of data related to clinical activity.

PubMed

Oliver, R G

1997-02-01

To seek the opinion of staff and students of a new electronic method for collection of data related to student clinical activity. Questionnaire survey. Staff and students in the Department of Child Dental Health, Dental School, Cardiff, and staff in the Community Dental Service who undertake clinical supervision. A questionnaire was circulated to all 2nd and 3rd clinical year dental undergraduate students seeking their opinion on a range of issues associated with the recently introduced bar code system of data gathering of their clinical activity and achievement. A similar questionnaire was circulated to staff who have responsibility for clinical supervision of these students. A total of 102 replies were received. With the exception of 2 aspects, there was no disagreement between staff and students. An overall majority preferred the use of bar codes to other methods of data collection; bar codes were perceived to be more accurate and reliable than other methods; students were satisfied with the method of quality assessment; staff were dissatisfied (P < 0.05). Staff were strongly in favour of extension of the use of bar codes to other clinics, whereas students were less strongly in favour (P < 0.001); there was little enthusiasm to extend bar codes for recording attendance at lectures, seminars and other such activity. The new system has been accepted by staff and students alike. It has proven to be satisfactory for its intended purpose. As a result of this survey, minor adjustments to procedures will take place, and the method of assessment of clinical work will be reconsidered.

Research nurse manager perceptions about research activities performed by non-nurse clinical research coordinators.

PubMed

Jones, Carolynn Thomas; Hastings, Clare; Wilson, Lynda Law

2015-01-01

There has been limited research to document differences in roles between nurses and non-nurses who assume clinical research coordination and management roles. Several authors have suggested that there is no acknowledged guidance for the licensure requirements for research study coordinators and that some non-nurse research coordinators may be assuming roles that are outside of their legal scopes of practice. There is a need for further research on issues related to the delegation of clinical research activities to non-nurses. This study used nominal group process focus groups to identify perceptions of experienced research nurse managers at an academic health science center in the Southern United States about the clinical research activities that are being performed by non-nurse clinical research coordinators without supervision that they believed should only be performed by a nurse or under the supervision of a nurse. A total of 13 research nurse managers volunteered to be contacted about the study. Of those, 8 participated in two separate nominal group process focus group sessions. The group members initially identified 22 activities that they felt should only be performed by a nurse or under the direct supervision of a nurse. After discussion and clarification of results, activities were combined into 12 categories of clinical research activities that participants believed should only be performed by a nurse or under the direct supervision of a nurse. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of Influenza Virus Polymerase Activity in Pig Cells

PubMed Central

Moncorgé, Olivier; Long, Jason S.; Cauldwell, Anna V.; Zhou, Hongbo; Lycett, Samantha J.

2013-01-01

Reassortant influenza viruses with combinations of avian, human, and/or swine genomic segments have been detected frequently in pigs. As a consequence, pigs have been accused of being a “mixing vessel” for influenza viruses. This implies that pig cells support transcription and replication of avian influenza viruses, in contrast to human cells, in which most avian influenza virus polymerases display limited activity. Although influenza virus polymerase activity has been studied in human and avian cells for many years by use of a minigenome assay, similar investigations in pig cells have not been reported. We developed the first minigenome assay for pig cells and compared the activities of polymerases of avian or human influenza virus origin in pig, human, and avian cells. We also investigated in pig cells the consequences of some known mammalian host range determinants that enhance influenza virus polymerase activity in human cells, such as PB2 mutations E627K, D701N, G590S/Q591R, and T271A. The two typical avian influenza virus polymerases used in this study were poorly active in pig cells, similar to what is seen in human cells, and mutations that adapt the avian influenza virus polymerase for human cells also increased activity in pig cells. In contrast, a different pattern was observed in avian cells. Finally, highly pathogenic avian influenza virus H5N1 polymerase activity was tested because this subtype has been reported to replicate only poorly in pigs. H5N1 polymerase was active in swine cells, suggesting that other barriers restrict these viruses from becoming endemic in pigs. PMID:23077313

Informed consent in clinical research at a general hospital in Mexico: opinions of the investigators.

PubMed

Vargas-Parada, Laura; Kawa, Simon; Salazar, Alberto; Mazön, Juan José; Flisser, Ana

2006-03-01

In Mexico informed consent is a legal requirement that ensures that patients who are invited to participate in clinical trials are provided with all the information needed to decide whether to participate, or not, in a research protocol. To improve our understanding of the problems physicians in developing countries encounter, when obtaining informed consent (IC), we examined their opinion on the importance of IC in clinical research, the quantity and quality of the information provided to the participant, and the conditions in which the IC is obtained. Investigators considered that IC was useful to the patients, providing information that helped the patient to make a decision about his/her participation. Nevertheless, they felt that for some aspects of the research, like drug development in general, the use of placebos, and the randomization process, many of the patients were not capable of fully understanding the information provided, referring to the complexity of the information and illiteracy as the main reasons. Many investigators were not acquainted with some of the guidelines established in the Mexican General Law of Health,(1) 36% of them admitting to not having completed their IC letters. Most investigators gave only minutes to the patient to make a decision and 20% of ICs were obtained while the patient was hospitalized. Except for one investigator, all of them considered that specific training in medical ethics would be useful for the daily clinical work.

Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators

PubMed Central

Robinson, Georgeanna F.W.B.; Schwartz, Lisa S.; DiMeglio, Linda A.; Ahluwalia, Jasjit S.; Gabrilove, Janice L.

2015-01-01

Purpose To understand the factors that facilitate career success for career development awardees in clinical and translational science and to reconceptualize understanding of career success for this population. Method In 2013–2014, the authors conducted semi-structured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators’ transition to independent funding. Interviews were recorded and transcribed and the transcripts analyzed thematically. Results Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included: networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included: appropriate mentorship, protected research time, and institutional resources and support. Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included: improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgement of successes. Conclusions Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator. PMID:26509600

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD—‘Assessing QbTest Utility in ADHD’ (AQUA): a randomised controlled trial

PubMed Central

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-01-01

Introduction The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current ‘gold standard’ ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. Methods and analysis This multisite randomised controlled trial will recruit young people (aged 6–17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. Ethics and dissemination The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost

Investigating the physiology of brain activation with MRI

NASA Astrophysics Data System (ADS)

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Tools to investigate how interprofessional education activities link to competencies.

PubMed

West, Courtney; Veronin, Michael; Landry, Karen; Kurz, Terri; Watzak, Bree; Quiram, Barbara; Graham, Lori

2015-01-01

Integrating interprofessional education (IPE) activities and curricular components in health professions education has been emphasized recently by the inclusion of accreditation standards across disciplines. The Interprofessional Education Collaborative (IPEC) established IPE competencies in 2009, but evaluating how activities link to competencies has not been investigated in depth. The purpose of this project is to investigate how well two IPE activities align with IPEC competencies. To evaluate how our IPE activities met IPEC competencies, we developed a checklist and an observation instrument. A brief description of each is included as well as the outcomes. We analyzed Disaster Day, a simulation exercise that includes participants from Nursing, Medicine, and Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that introduced medical, nursing, and pharmacy students to ethical issues using didactic sessions and case discussions. While both activities appeared to facilitate the development of IPE competencies, Disaster Day aligned more with IPEC competencies than the IPHCE course and appears to be a more comprehensive way of addressing IPEC competencies. However, offering one IPE activity or curricular element is not sufficient. Having several IPE options available, utilizing the tools we developed to map the IPE curriculum and evaluating competency coverage is recommended.

An investigation into non-invasive physical activity recognition using smartphones.

PubMed

Kelly, Daniel; Caulfield, Brian

2012-01-01

Technology utilized to automatically monitor Activities of Daily Living (ADL) could be a key component in identifying deviations from normal functional profiles and providing feedback on interventions aimed at improving health. However, if activity recognition systems are to be implemented in real world scenarios such as health and wellness monitoring, the activity sensing modality must unobtrusively fit the human environment rather than forcing humans to adhere to sensor specific conditions. Modern smart phones represent a ubiquitous computing device which has already undergone mainstream adoption. In this paper, we investigate the feasibility of using a modern smartphone, with limited placement constraints, as the sensing modality for an activity recognition system. A dataset of 4 subjects performing 7 activities, using varying sensor placement conditions, is utilized to investigate this. Initial experiments show that a decision tree classifier performs activity classification with precision and recall scores of 0.75 and 0.73 respectively. More importantly, as part of this initial experiment, 3 main problems, and subsequently 3 solutions, relating to unconstrained sensor placement were identified. Using our proposed solutions, classification precision and recall scores were improved by +13% and +14.6% respectively.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

PubMed

Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Structural Investigation of Alkali Activated Clay Minerals for Application in Water Treatment Systems

NASA Astrophysics Data System (ADS)

Bumanis, G.; Bajare, D.; Dembovska, L.

2015-11-01

Alkali activation technology can be applied for a wide range of alumo-silicates to produce innovative materials with various areas of application. Most researches focuse on the application of alumo-silicate materials in building industry as cement binder replacement to produce mortar and concrete [1]. However, alkali activation technology offers high potential also in biotechnologies [2]. In the processes where certain pH level, especially alkaline environment, must be ensured, alkali activated materials can be applied. One of such fields is water treatment systems where high level pH (up to pH 10.5) ensures efficient removal of water pollutants such as manganese [3]. Previous investigations had shown that alkali activation technology can be applied to calcined clay powder and aluminium scrap recycling waste as a foam forming agent to create porous alkali activated materials. This investigation focuses on the structural investigation of calcined kaolin and illite clay alkali activation processes. Chemical and mineralogical composition of both clays were determined and structural investigation of alkali activated materials was made by using XRD, DTA, FTIR analysis; the microstructure of hardened specimens was observed by SEM. Physical properties of the obtained material were determined. Investigation indicates the essential role of chemical composition of the clay used in the alkali activation process, and potential use of the obtained material in water treatment systems.

Laboratory investigation of hypercoagulability.

PubMed

Francis, J L

1998-01-01

For many years, the laboratory investigation of patients with thrombophilia has lagged behind that of patients with bleeding diathesis. Improved understanding of the mechanisms that control and regulate coagulation, and the resultant recognition of new defects, have greatly stimulated clinical laboratory interest in this area. Assays to detect resistance to activated protein C; deficiencies of antithrombin, protein C, and protein S; and the presence of antiphospholipid antibodies are widely available and should form part of the investigation of patients that present with idiopathic thrombosis. Such a work-up will likely provide an explanation for thrombosis in 40 to 60% of patients. Abnormalities of fibrinogen and fibrinolysis may explain still more, although such defects are currently considered rare. In addition, presently unrecognized defects almost certainly exist, and the identification of such individuals will undoubtedly improve our understanding of the hemostatic mechanism. Laboratory tests to define the hypercoagulable state are continually being developed. They include whole blood coagulation and platelet function tests and novel activation markers. However, acceptance of these approaches by clinical laboratories has been slow.

Infantile Autism. A Clinical and Phenomenological-Anthropological Investigation Taking Language as the Guide.

ERIC Educational Resources Information Center

Bosch, Gerhard

A clinical and phenomenological-anthropological investigation taking language as the guide, the study of infantile autism concentrates upon an analysis of the idiosyncratic language of autistic children and of what is revealed by the way they use it. Following the presentation of very detailed case histories of five of the autistic children…

Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management.

PubMed

Shah, Shaheen P; Taylor, Amy E; Sowden, Jane C; Ragge, Nicky; Russell-Eggitt, Isabelle; Rahi, Jugnoo S; Gilbert, Clare E

2012-02-01

To describe the clinical features of children with anophthalmos, microphthalmos, and typical coloboma (AMC). Descriptive, observational, cross-sectional study of the United Kingdom. A total of 135 children with AMC newly diagnosed over an 18-month period beginning in October 2006. Cases were identified using active surveillance through an established ophthalmic surveillance system. Eligible cases were followed up 6 months after first notification. Phenotypic characteristics, both ocular and systemic, clinical investigations, causes, and interventions. A total of 210 eyes (of 135 children) were affected by AMC, of which 153 had isolated coloboma or coloboma with microphthalmos. The most common colobomatous anomaly was a chorioretinal defect present in 109 eyes (71.2%). Some 44% of children were bilaterally visually impaired. Systemic abnormalities were present in 59.7% of children, with craniofacial anomalies being the most common. Children with bilateral disease had a 2.7 times higher odds (95% confidence interval, 1.3-5.5, P = 0.006) of having systemic involvement than unilaterally affected children. Neurologic imaging was the most frequent investigation (58.5%) performed. Less than one third (30.3%) of the children with microphthalmos had ocular axial lengths measured. Eight children had confirmed genetic mutations. Approximately half (49.2%) of the children required ocular intervention. Colobomatous defects were the most common phenotype within this spectrum of anomalies in the United Kingdom. The high frequency of posterior segment colobomatous involvement means that a dilated fundal examination should be made in all cases. The significant visual and systemic morbidity in affected children underlines the importance of a multidisciplinary approach to management. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical management of musculoskeletal injuries in active children and youth.

PubMed

Mazer, Barbara; Shrier, Ian; Feldman, Debbie Ehrmann; Swaine, Bonnie; Majnemer, Annette; Kennedy, Eileen; Chilingaryan, Gevorg

2010-07-01

To describe how different health care specialists manage musculoskeletal injury in children and examine factors influencing return to play decisions. National survey. Secure Web site hosting online questionnaire. Medical doctors, physical therapists, and athletic therapists who were members of their respective sport medicine specialty organizations. Professional affiliation and the effect of the following factors were examined: pushy parent, cautious parent, protective equipment, previous injury, musculoskeletal maturity, game importance, position played, team versus individual sport, and time since injury. Recommendation of return to activity after common injuries seen in children and adolescents as described in 5 vignettes; consistency of responses across vignettes. The survey was completed by 464 respondents (34%). There were several differences between the professional groups in their recommendations to return to activity. Most factors studied did not tend to influence the decision to return to activity, although protective equipment often increased the response to return sooner. The number of participants who would return a child to activity sooner or later for each factor varied greatly across the 5 vignettes, except for pushy parent or cautious parent. Management practices of sport medicine clinicians vary according to profession, child, clinical factors, and sport-related factors. Decisions regarding return to play vary according to 5 specific characteristics of each clinical case. These findings help establish areas of consensus and disagreement in the management of children with injuries and safe return to physical activity.

A Preliminary Investigation of Accelerometer-Derived Sleep and Physical Activity Following Sport-Related Concussion.

PubMed

Sufrinko, Alicia M; Howie, Erin K; Elbin, R J; Collins, Michael W; Kontos, Anthony P

2018-03-29

Describe changes in postconcussion activity levels and sleep throughout recovery in a sample of pediatric sport-related concussion (SRC) patients, and examine the predictive value of accelerometer-derived activity and sleep on subsequent clinical outcomes at a follow-up clinic visit. Outpatient concussion clinic. Twenty athletes aged 12 to 19 years with diagnosed SRC. Prospective study including visit 1 (<72 hours postinjury) and visit 2 (6-18 days postinjury). Linear regressions used to predict scores (ie, neurocognitive, vestibular/oculomotor) at visit 2 from accelerometer-derived data collected 0 to 6 days postinjury. Linear mixed models evaluated changes in activity and sleep across recovery. Symptom, neurocognitive, and vestibular/oculomotor scores; sleep and activity data (Actigraph GT3x+) RESULTS:: The maximum intensity of physical activity increased (P = .009) and time in bed decreased throughout recovery (P = .026). Several physical activity metrics from 0 to 6 days postinjury were predictive of worse vestibular/oculomotor scores at visit 2 (P < .05). Metrics indicative of poor sleep 0 to 6 days postinjury were associated with worse reaction time at visit 2 (P < .05). This exploratory study suggests physical activity and sleep change from the acute to subacute postinjury time period in adolescent SRC patients. In our small sample, excess physical activity and poor sleep the first week postinjury may be associated with worse outcomes at follow-up in the subacute stage of recovery. This study further supported the feasibility of research utilizing wearable technology in concussion patients, and future research in a large, diverse sample of concussion patients examined at concise time intervals postinjury is needed.

[Clinical investigation on administration method of gatifloxacin based on PK/PD theory].

PubMed

Mikamo, Hiroshige; Tanaka, Kaori; Watanabe, Kunitomo; Tamaya, Teruhiko; Izumi, Koji

2006-10-01

There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone antibacterial, we influenzae investigated clinical efficacies and adverse events for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a day or four times a day. The number of leukocyte and the value of CRP were significantly reduced by chemotherapy in twice a day group, compared with four times a day group. We were able to measure the blood level in 4 cases. The AUC/MIC values for presumption causative bacteria (causative bacteria in both cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in therapy-failed patients, the AUC/MIC value to presumption causative bacterium were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria: Pseudomonas aeruginosa). These results suggested the importance of the therapeutic method based on PK/PD theory.

How can we improve clinical research in pneumonia?

PubMed

Ramirez, Julio A

2018-05-01

The primary challenges in the field of clinical research include a lack of support within existing infrastructure, insufficient number of clinical research training programs and a paucity of qualified mentors. Most medical centers offer infrastructure support for investigators working with industry sponsors or government-funded clinical trials, yet there are a significant amount of clinical studies performed in the field of pneumonia which are observational studies. For this type of research, which is frequently unfunded, support is usually lacking. In an attempt to optimize clinical research in pneumonia, at the University of Louisville, we developed a clinical research coordinating center (CRCC). The center manages clinical studies in the field of respiratory infections, with the primary focus being pneumonia. Other activities of the CRCC include the organization of an annual clinical research training course for physicians and other healthcare workers, and the facilitation of international research mentoring by a process of connecting new pneumonia investigators with established clinical investigators. To improve clinical research in pneumonia, institutions need to have the appropriate infrastructure in place to support investigators in all aspects of the clinical research process.

Investigating the connections between health lean management and clinical risk management.

PubMed

Crema, Maria; Verbano, Chiara

2015-01-01

The purpose of this paper is to investigate connections and overlaps between health lean management (HLM) and clinical risk management (CRM) understanding whether and how these two approaches can be combined together to pursue efficiency and patient safety improvements simultaneously. A systematic literature review has been carried out. Searching in academic databases, papers that focus not only on HLM, but also on clinical errors and risk reduction, were included. The general characteristics of the selected papers were analysed and a content analysis was conducted. In most of the papers, pursing objectives of HLM and CRM and adopting tools and practices of both approaches, results of quality and, particularly, of safety improvements were obtained. A two-way arrow between HLM and CRM emerged but so far, none of the studies has been focused on the relationship between HLM and CRM. Results highlight an emerging research stream, with many useful theoretical and practical implications and opportunities for further research.

Investigation of Clinically Significant Change by Severity Level in College Counseling Center Clients

ERIC Educational Resources Information Center

Wolgast, Brad M.; Rader, Jill; Roche, Deborah; Thompson, C. Patricia; von Zuben, F. Christian; Goldberg, Allan

2005-01-01

The authors investigated the number of sessions necessary for college counseling center clients of different levels of severity of distress at intake to achieve clinically significant change (CS) in therapy. The Outcome Questionnaire-45 (M. J. Lambert, N. B. Hansen, et al., 1996) was used to categorize 914 clients by severity of distress. Analyses…

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

PubMed

Mano, Tadaaki; Iwase, Satoshi; Toma, Shinobu

2006-11-01

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be

Investigation of plant latices of Asteraceae and Campanulaceae regarding proteolytic activity.

PubMed

Sytwala, Sonja; Domsalla, André; Melzig, Matthias F

2015-12-01

Occurrence of plant latices is widespread, there are more than 40 families of plants characterized to establish lactiferous structures. The appearance of hydrolytic active proteins, incorporated in latices is already characterized, and hydrolytic active proteins are considerable, and for several plant families, the occurrence of hydrolytic active proteins is already specified e.g. Apocynaceae Juss., Caricaceae Dumort, Euphorbiaceae Juss., Moraceae Gaudich and Papaveraceae Juss. In our investigation, focused on latex bearing plants of order Asterales, Asteraceae and Campanulaceae in particular. The present outcomes represent a comprehensive study, relating to the occurrence of proteolytic active enzymes of order Asterales for the first time. 131 different species of Asteraceae and Campanulaceae were tested, and the appearance of plant latex proteases were determined in different quantities. Proteolytic activity was investigated by inhibitory studies and determination of residual activity in the following, enable us to characterize the proteases. Most of the considered species exhibit a serine protease activity and a multiplicity of species exhibited two or more subclasses of proteases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Flexible statistical modelling detects clinical functional magnetic resonance imaging activation in partially compliant subjects.

PubMed

Waites, Anthony B; Mannfolk, Peter; Shaw, Marnie E; Olsrud, Johan; Jackson, Graeme D

2007-02-01

Clinical functional magnetic resonance imaging (fMRI) occasionally fails to detect significant activation, often due to variability in task performance. The present study seeks to test whether a more flexible statistical analysis can better detect activation, by accounting for variance associated with variable compliance to the task over time. Experimental results and simulated data both confirm that even at 80% compliance to the task, such a flexible model outperforms standard statistical analysis when assessed using the extent of activation (experimental data), goodness of fit (experimental data), and area under the operator characteristic curve (simulated data). Furthermore, retrospective examination of 14 clinical fMRI examinations reveals that in patients where the standard statistical approach yields activation, there is a measurable gain in model performance in adopting the flexible statistical model, with little or no penalty in lost sensitivity. This indicates that a flexible model should be considered, particularly for clinical patients who may have difficulty complying fully with the study task.

A retrospective investigation of the clinical management of patients attending an out of hours dental clinic in Merseyside under the new NHS dental contract.

PubMed

Tulip, D E; Palmer, N O A

2008-12-20

To investigate the clinical management of patients attending for emergency dental treatment. A retrospective analysis of clinical record cards. Information was collected from patient record cards concerning the patient's reason for attendance and their management at an emergency dental clinic in South Sefton, Liverpool. Over a nine month period, 1,718 patients attended the clinic; 1,472 record cards were analysed. Over 80% of the patients attending the out of hours (OOH) clinic had pain associated with a localised dental infection or dental abscess. Where a diagnosis was recorded, only 67% of patients received appropriate treatment. Over 50% of patients received antibiotics alone with no other definitive treatment provided. The principal antibiotic prescribed for both adult and child patients was amoxicillin. The current study has highlighted that GDPs working within the OOH services are not adhering to current clinical and best practice guidelines with respect to patient examination, diagnosis, management, in particular the correct prescribing of antibiotics for dental infections, and clinical record keeping.

Geometric investigation of a gaming active device

NASA Astrophysics Data System (ADS)

Menna, Fabio; Remondino, Fabio; Battisti, Roberto; Nocerino, Erica

2011-07-01

3D imaging systems are widely available and used for surveying, modeling and entertainment applications, but clear statements regarding their characteristics, performances and limitations are still missing. The VDI/VDE and the ASTME57 committees are trying to set some standards but the commercial market is not reacting properly. Since many new users are approaching these 3D recording methodologies, clear statements and information clarifying if a package or system satisfies certain requirements before investing are fundamental for those users who are not really familiar with these technologies. Recently small and portable consumer-grade active sensors came on the market, like TOF rangeimaging cameras or low-cost triangulation-based range sensor. A quite interesting active system was produced by PrimeSense and launched on the market thanks to the Microsoft Xbox project with the name of Kinect. The article reports the geometric investigation of the Kinect active sensors, considering its measurement performances, the accuracy of the retrieved range data and the possibility to use it for 3D modeling application.

Investigation of spherical loudspeaker arrays for local active control of sound.

PubMed

Peleg, Tomer; Rafaely, Boaz

2011-10-01

Active control of sound can be employed globally to reduce noise levels in an entire enclosure, or locally around a listener's head. Recently, spherical loudspeaker arrays have been studied as multiple-channel sources for local active control of sound, presenting the fundamental theory and several active control configurations. In this paper, important aspects of using a spherical loudspeaker array for local active control of sound are further investigated. First, the feasibility of creating sphere-shaped quiet zones away from the source is studied both theoretically and numerically, showing that these quiet zones are associated with sound amplification and poor system robustness. To mitigate the latter, the design of shell-shaped quiet zones around the source is investigated. A combination of two spherical sources is then studied with the aim of enlarging the quiet zone. The two sources are employed to generate quiet zones that surround a rigid sphere, investigating the application of active control around a listener's head. A significant improvement in performance is demonstrated in this case over a conventional headrest-type system that uses two monopole secondary sources. Finally, several simulations are presented to support the theoretical work and to demonstrate the performance and limitations of the system. © 2011 Acoustical Society of America

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant.

PubMed

Robertson, W; Robertson, A S; Burge, C B S G; Moore, V C; Jaakkola, M S; Dawkins, P A; Burd, M; Rawbone, R; Gardner, I; Kinoulty, M; Crook, B; Evans, G S; Harris-Roberts, J; Rice, S; Burge, P S

2007-11-01

Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. The outbreak was investigated in a three-phase cross-sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7

Supporting and activating clinical governance development in Ireland: sharing our learning.

PubMed

Flynn, Maureen A; Burgess, Thora; Crowley, Philip

2015-01-01

The purpose of this paper is to present a description of the Irish national clinical governance development initiative and an evaluation of the initiative with the purpose of sharing the learning and proposing actions to activate structures and processes for quality and safety. The Quality and Patient Safety Division of the Health Service Executive established the initiative to counterbalance a possible focus on finances during the economic crisis in Ireland and bring attention to the quality of clinical care. A clinical governance framework for quality in healthcare in Ireland was developed to clearly articulate the fundamentals of clinical governance. The project plan involved three overlapping phases. The first was designing resources for practice; the second testing the implementation of the national resources in practice; and the third phase focused on gathering feedback and learning. Staff responded positively to the clinical governance framework. At a time when there are a lot of demands (measurement and scrutiny) the health services leads and responds well to focused support as they improve the quality and safety of services. Promoting the use of the term "governance for quality and safety" assisted in gaining an understanding of the more traditional term "clinical governance". The experience and outcome of the initiative informed the identification of 12 key learning points and a series of recommendations The initial evaluation was conducted at 24 months so at this stage it is not possible to assess the broader impact of the clinical governance framework beyond the action project hospitals. The single most important obligation for any health system is patient safety and improving the quality of care. The easily accessible, practical resources assisted project teams to lead changes in structures and processes within their services. This paper describes the fundamentals of the clinical governance framework which might serve as a guide for more integrative

Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

ERIC Educational Resources Information Center

Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

2013-01-01

Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

Clinical trial will investigate targeted radionuclide therapy for inoperable rare tumors | Center for Cancer Research

Cancer.gov

In an upcoming phase II clinical trial, Center for Cancer Research investigators will explore the ability of a targeted radioactive drug to treat inoperable pheochromocytoma and paraganglioma, both rare tumors.  Learn more...

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

PubMed

Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation.

PubMed

Cambruzzi, Eduardo

2018-05-01

Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB. WNT-activated MDB is associated to monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear immunoexpression, and a better prognosis than SHH-activated MDB. WNT-activated tumors account approximately for 10% of cases of MDBs, and are thought to arise from cells in the dorsal brain stem/lower rhombic lip progenitor cells. SHH-activated MDB more frequently arises in the lateral hemispheres of the cerebellum, and clinical outcome in this group is variable. TP53-mutant SHHactivated MDB usually shows the large cell/anaplastic pattern, and can be related to MYCN amplification, GLI2 amplification and 17p loss. TP53-wildtype SHH-activated MDB is more commonly of desmoplastic/nodular morphology, and can be related to PTCH1 deletion and 10q loss. Gene expression and methylation profiling is the gold standard for defining molecular groups of MDB. In immunohistochemistry assays, anti-GAB1 antibody expression is positive in tumors showing SHH pathway activation or PTCH mutation, while positive immunoexpression for YAP1 antibody can be only found in WNT-activated and SHH-activated MDB.

Practising Active Science with Child Refugees: A Clinical Perspective

ERIC Educational Resources Information Center

Perrier, Frédéric

2004-01-01

In this paper, pilot sessions in Rwanda and Nepal are analysed to evaluate the therapeutic benefit of active science for traumatised child refugees. The nature of the activities, choice of tools, organisation of the sessions, group size, and the role of the educators are investigated. Despite the lack of quantitative assessment, practical…

An empirical investigation of incompleteness in a large clinical sample of obsessive compulsive disorder.

PubMed

Sibrava, Nicholas J; Boisseau, Christina L; Eisen, Jane L; Mancebo, Maria C; Rasmussen, Steven A

2016-08-01

Obsessive Compulsive Disorder (OCD) is a disorder with heterogeneous clinical presentations. To advance our understanding of this heterogeneity we investigated the prevalence and clinical features associated with incompleteness (INC), a putative underlying core feature of OCD. We predicted INC would be prominent in individuals with OCD and associated with greater severity and impairment. We examined the impact of INC in 307 adults with primary OCD. Participants with clinically significant INC (22.8% of the sample) had significantly greater OCD severity, greater rates of comorbidity, poorer ratings of functioning, lower quality of life, and higher rates of unemployment and disability. Participants with clinically significant INC were also more likely to be diagnosed with OCPD and to endorse symmetry/exactness obsessions and ordering/arranging compulsions than those who reported low INC. Our findings provide evidence that INC is associated with greater severity, comorbidity, and impairment, highlighting the need for improved assessment and treatment of INC in OCD. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Empirical Investigation of Incompleteness in a Large Clinical Sample of Obsessive Compulsive Disorder

PubMed Central

Sibrava, Nicholas J.; Boisseau, Christina L.; Eisen, Jane L.; Mancebo, Maria C.; Rasmussen, Steven A.

2016-01-01

Obsessive Compulsive Disorder (OCD) is a disorder with heterogeneous clinical presentations. To advance our understanding of this heterogeneity we investigated the prevalence and clinical features associated with incompleteness (INC), a putative underlying core feature of OCD. We predicted INC would be prominent in individuals with OCD and associated with greater severity and impairment. We examined the impact of INC in 307 adults with primary OCD. Participants with clinically significant INC (22.8% of the sample) had significantly greater OCD severity, greater rates of comorbidity, poorer ratings of functioning, lower quality of life, and higher rates of unemployment and disability. Participants with clinically significant INC were also more likely to be diagnosed with OCPD and to endorse symmetry/exactness obsessions and ordering/arranging compulsions than those who reported low INC. Our findings provide evidence that INC is associated with greater severity, comorbidity, and impairment, highlighting the need for improved assessment and treatment of INC in OCD. PMID:27268401

Case Report: Activity Diagrams for Integrating Electronic Prescribing Tools into Clinical Workflow

PubMed Central

Johnson, Kevin B.; FitzHenry, Fern

2006-01-01

To facilitate the future implementation of an electronic prescribing system, this case study modeled prescription management processes in various primary care settings. The Vanderbilt e-prescribing design team conducted initial interviews with clinic managers, physicians and nurses, and then represented the sequences of steps carried out to complete prescriptions in activity diagrams. The diagrams covered outpatient prescribing for patients during a clinic visit and between clinic visits. Practice size, practice setting, and practice specialty type influenced the prescribing processes used. The model developed may be useful to others engaged in building or tailoring an e-prescribing system to meet the specific workflows of various clinic settings. PMID:16622168

[What role for paraclinical investigations within clinical trials conducted in psychiatric patients?

PubMed

Kaladjian, A; Adida, M; Simon, N; Belzeaux, R; Blin, O; Fakra, E; Azorin, J-M

2016-12-01

As in the usual care of patients, paraclinical investigations have today only a very modest role in clinical trials in psychiatry, mainly to complete the pre-therapeutical assessments prior to inclusion of subjects or to monitor treatment tolerance. Yet, the accumulation of data in neurosciences suggests the next emergence of biomarkers, whose interest is that they are closely associated to the biological disturbances underlying psychiatric illnesses, and that they are accessible by means of technological tools such as imaging devices. These tools allow to explore the effects on brain of psychotropic medications, such as antidepressants, antipsychotics, or mood stabilizers, in relation to their therapeutic action. The obtained results allow to consider the use of such biomarkers in clinical trials in addition to more conventional approaches. In particular, they could be used as targets to measure brain response to treatment in association with clinical response, to predict a therapeutic response from the neurofunctional characteristics of patients, or to establish the safety profile of drugs on the nervous system. The use of such biomarkers in clinical trials would help to better define the explored populations and their characteristics, as well as the variables to assess, and to better measure the impact of the treatments and their potential harmful effects on the nervous system. © L’Encéphale, Paris, 2016.

Immediate Wheal Reactivity to Autologous Sweat in Atopic Dermatitis Is Associated with Clinical Severity, Serum Total and Specific IgE and Sweat Tryptase Activity.

PubMed

Ilves, Tiina; Virolainen, Anu; Harvima, Ilkka Tapani

2016-01-01

Sweating can worsen atopic dermatitis (AD). The purpose of this work was to study the associations between reactivity to autologous sweat and the clinical severity of AD as well as investigate the possible wheal-inducing factors of sweat. Intracutaneous skin tests with autologous sweat were performed on 50 AD patients and 24 control subjects. In skin biopsies, tryptase and PAR-2 were enzyme and immunohistochemically stained. The associations between skin test reactivity and sweat histamine concentration, tryptase or chymase activity levels, tryptase or PAR-2 expression and AD clinical severity or IgE levels were investigated. The wheal reactions in the intracutaneous tests with autologous sweat were positive, weakly positive and negative in 38, 34 and 28% of the AD patients, respectively, and in 4, 46 and 50% of the healthy controls, respectively (p = 0.008). In AD, the wheal reaction was associated significantly with clinical severity, serum total and specific IgE levels and sweat tryptase activity, but not with sweat histamine and chymase. In nonlesional AD skin, the percentage of PAR-2+ mast cells (MCs) or the number of tryptase+ MCs did not differ significantly between the intracutaneous test reactivity groups. Reactivity to autologous sweat correlates with the clinical severity of AD, and tryptase may be one of the factors involved in the sweat-induced wheal. © 2016 S. Karger AG, Basel.

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

NASA Astrophysics Data System (ADS)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

Code of Federal Regulations, 2014 CFR

2014-04-01

..., after consultation with a panel of experts in pertinent disciplines (for example: science, medicine... the clinical investigation in fact satisfies the conditions of § 50.51, § 50.52, or § 50.53, as...

21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

Code of Federal Regulations, 2013 CFR

2013-04-01

..., after consultation with a panel of experts in pertinent disciplines (for example: science, medicine... the clinical investigation in fact satisfies the conditions of § 50.51, § 50.52, or § 50.53, as...

Drilling to investigate processes in active tectonics and magmatism

NASA Astrophysics Data System (ADS)

Shervais, J.; Evans, J.; Toy, V.; Kirkpatrick, J.; Clarke, A.; Eichelberger, J.

2014-12-01

Coordinated drilling efforts are an important method to investigate active tectonics and magmatic processes related to faults and volcanoes. The US National Science Foundation (NSF) recently sponsored a series of workshops to define the nature of future continental drilling efforts. As part of this series, we convened a workshop to explore how continental scientific drilling can be used to better understand active tectonic and magmatic processes. The workshop, held in Park City, Utah, in May 2013, was attended by 41 investigators from seven countries. Participants were asked to define compelling scientific justifications for examining problems that can be addressed by coordinated programs of continental scientific drilling and related site investigations. They were also asked to evaluate a wide range of proposed drilling projects, based on white papers submitted prior to the workshop. Participants working on faults and fault zone processes highlighted two overarching topics with exciting potential for future scientific drilling research: (1) the seismic cycle and (2) the mechanics and architecture of fault zones. Recommended projects target fundamental mechanical processes and controls on faulting, and range from induced earthquakes and earthquake initiation to investigations of detachment fault mechanics and fluid flow in fault zones. Participants working on active volcanism identified five themes: the volcano eruption cycle; eruption sustainability, near-field stresses, and system recovery; eruption hazards; verification of geophysical models; and interactions with other Earth systems. Recommended projects address problems that are transferrable to other volcanic systems, such as improved methods for identifying eruption history and constraining the rheological structure of shallow caldera regions. Participants working on chemical geodynamics identified four major themes: large igneous provinces (LIPs), ocean islands, continental hotspot tracks and rifts, and

Phytochemical investigation and anti-microbial activity of Clausena anisata (Willd), Hook.

PubMed

Agyepong, Nicholas; Agyare, Christian; Adarkwa-Yiadom, Martin; Gbedema, Stephen Yao

2014-01-01

Clausena anisata belongs to the family Rutaceae, a shrub widely used in West Africa for the treatment of bacterial and fungal infections of the skin including boils, ringworm and eczema. The study was designed to evaluate the antimicrobial activity and phytochemical screening of ethanol leaf extract of C. anisata (CLE). Antimicrobial activity of CLE was investigated using agar well diffusion and micro-dilution methods against four Gram-positive bacteria (Bacillus substilis NCTC 10073, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Bacillus thuringiensis ATCC 13838) and two Gram-negative bacteria (Pseudomonas aeruginosa ATCC 4853, Proteus vulgaris ATCC 4175) and a clinical isolate of Candida albicans. CLE was active against all test organisms with minimum inhibitory concentration (MIC), range of 0.5 to 7.0 mg/mL against Gram-positive bacteria, 2.5 to 1.0 mg/mL against Gram-negative bacteria and 5.5mg/mL against C. albicans. The MICs of the methanol fraction of CLE were 0.6 mg to 5.0/mL and 1.0 to 3.0 mg/mL for Gram-positive and Gram-negative bacteria respectively. Chloroform fraction had MIC of 3.0 to 7.5 mg/mL and 2.0 to 6.5 mg/mL for Gram-positive and Gram-negative bacteria, respectively and petroleum ether fraction had 4.5 to 8.0 mg/mL for Gram-positive and Gram-negative bacteria. The CLE exhibited static action against all test organisms within a range of 0.5 to 22.0 mg/mL. Phytochemical screening of C. anisata revealed the presence of tannins, flavonoids, steroids, saponins, glycosides and alkaloids. HPLC finger-printing of the CLE and its fractions were determined. These results may justify the medicinal uses of C. anisata for the treatment of microbial infections.

Recombination activity of human RAG2 mutations and correlation with the clinical phenotype.

PubMed

Tirosh, Irit; Yamazaki, Yasuhiro; Frugoni, Francesco; Ververs, Francesca A; Allenspach, Eric J; Zhang, Yu; Burns, Siobhan; Al-Herz, Waleed; Noroski, Lenora; Walter, Jolan E; Gennery, Andrew R; van der Burg, Mirjam; Notarangelo, Luigi D; Lee, Yu Nee

2018-05-14

Mutations in the Recombinase Activating Gene 1 and 2 (RAG1, RAG2) are associated with a broad range of clinical and immunological phenotypes in humans. Using a flow cytometry-based assay, we aimed to measure the recombinase activity of naturally occurring RAG2 mutant proteins, and to correlate results with the severity of the clinical and immunological phenotype. Abelson virus-transformed Rag2 -/- pro-B cells engineered to contain an inverted GFP cassette flanked by recombination signal sequences (RSS) were transduced with retroviruses encoding either wild-type or 41 naturally occurring RAG2 variants. Bicistronic vectors were used to introduce compound heterozygous RAG2 variants.The percentage of GFP-expressing cells was evaluated by flow cytometry, and high throughput sequencing was used to analyze rearrangements at the endogenous Igh locus.. The RAG2 variants showed a wide range of recombination activity. Mutations associated with severe combined immune deficiency (SCID) and Omenn syndrome had significantly lower activity than those detected in patients with less severe clinical presentations. Four variants (P253R, F386L, N474S, and M502V) previously thought to be pathogenic were found to have wild-type levels of activity. Use of bicistronic vectors permitted to assess more carefully the effect of compound heterozygous mutations, with good correlation between GFP expression and number and diversity of Igh rearrangements. Our data support genotype-phenotype correlation in RAG2 deficiency. The assay described can be used to define the possible disease-causing role of novel RAG2 variants and may help predict the severity of the clinical phenotype. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[THE RESULTS OF CLINICAL AND PSYCHOPATHOLOGICAL AND PSYCHOLOGICAL DIAGNOSTIC INVESTIGATIONS EMPLOYEES OF FINANCIAL INSTITUTIONS WHICH WERE IDENTIFIED NEUROTIC DISORDERS].

PubMed

Solovyova, M

2014-12-01

The article presents the results of the clinical and psychopathological and psychological diagnostic, investigations mental health employees of financial institutions, description and analysis of clinical forms identified disorders.

Experimental investigation of active loads control for aircraft landing gear

NASA Technical Reports Server (NTRS)

Mcgehee, J. R.; Dreher, R. C.

1982-01-01

Aircraft dynamic loads and vibrations resulting from landing impact and from runway and taxiway unevenness are recognized as significant in causing fatigue damage, dynamic stress on the airframe, crew and passenger discomfort, and reduction of the pilot's ability to control the aircraft during ground operations. One potential method for improving operational characteistics of aircraft on the ground is the application of active control technology to the landing gears to reduce ground loads applied to the airframe. An experimental investigation was conducted which simulated the landing dynamics of a light airplane to determine the feasibility and potential of a series hydraulic active control main landing gear. The experiments involved a passive gear and an active control gear. Results of this investigation show that a series hydraulically controlled gear is feasible and that such a gear is very effective in reducing the loads transmitted by the gear to the airframe during ground operations.

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

PubMed

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

2015-09-29

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

Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population.

PubMed

Jamshidi, Ahmad-Reza; Banihashemi, Arash Tehrani; Paragomi, Pedram; Hasanzadeh, Maryam; Barghamdi, Mozhgan; Ghoroghi, Shima

2016-08-01

Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck's and Cattell's inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients' disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman's rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.

[Clinical and genetic investigation of families with Waardenburg syndrome type 2].

PubMed

Chen, H S; Liao, X B; Liu, Y L; He, C F; Zhang, H; Jiang, L; Feng, Y; Mei, L Y

2016-12-01

Objective: To investigate the clinical chacteration and molecular pathology of Waardenburg syndrome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Method: Clinical data of seven families with WS2（14 patients）were collected. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of microphthalmia associated transcription factor (MITF), sex-determining region Y-box 10(SOX10), snail family zinc finger 2 (SNAI2) and endothelin receptor type B（EDNRB）were analyzed by polymerase chain reaction and DNA sequencing. Then the raw data was analyzed. Result: The most common manifestations of WS2 are sensorineural hearing loss(10/14,71.4%), freckle(7/14, 50.0%)，heterochromia iridis(6/14, 42.9%) and premature greying(5/14,35.7%). All the deafness phenotype is congenital, bilateral profound sensorineural hearing loss. Freckles phenotype is different from cutaneous pigment abnormalities of WS in Westerners. The heterozygous mutation, c.328C>T in exon 3 of the MITF gene was detected in the proband and all patients of pedigree 2. However, no pathological mutation of the relevant genes (SOX10,SNAI2 and EDNRB) was detected in other pedigrees. Conclusion: There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pigment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedigree WS02.However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Sustaining the Clinical Translational Research Workforce: Training and Empowering the Next Generation of Investigators

PubMed Central

Yin, Helen L.; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M.; Toto, Robert

2015-01-01

There is mounting concern that clinician scientists are a vanishing species, and that the pipeline for clinical translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH) funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional “culture shift” are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the timeframe, increasing the rate of K2R transition, and identifying strategies that improve success. PMID:26414054

21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs, after consultation with a panel of experts in pertinent disciplines (for example: science... either: (1) That the clinical investigation in fact satisfies the conditions of § 50.51, § 50.52, or § 50...

21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Drugs, after consultation with a panel of experts in pertinent disciplines (for example: science... either: (1) That the clinical investigation in fact satisfies the conditions of § 50.51, § 50.52, or § 50...

21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Drugs, after consultation with a panel of experts in pertinent disciplines (for example: science... either: (1) That the clinical investigation in fact satisfies the conditions of § 50.51, § 50.52, or § 50...

The cost of resident scholarly activity and its effect on resident clinical experience.

PubMed

Schott, Nicholas J; Emerick, Trent D; Metro, David G; Sakai, Tetsuro

2013-11-01

Scholarly activity is an important aspect of the academic training of future anesthesiologists. However, residents' scholarly activity may reduce training caseloads and increase departmental costs. We conducted this study within a large academic anesthesiology residency program with data from the 4 graduating classes of 2009 through 2012. Scholarly activity included peer-reviewed manuscripts, case reports, poster presentations at conferences, book chapters, or any other publications. It was not distinguished whether a resident was the principal investigator or a coinvestigator on a project. The following data were collected on each resident: months spent on a resident research rotation, number of scholarly projects completed, number of research conferences attended, and Accreditation Council for Graduate Medical Education case entries. Comparison was made between residents electing a resident research rotation with those who did not for (1) scholarly projects, (2) research conference attendance, and (3) Accreditation Council for Graduate Medical Education case numbers. Cost to the department for extra clinical coverage during residents' time spent on research activities was calculated using an estimated average cost of $675 ± $176 (mean ± SD) per day with local certified registered nurse anesthetist pay scales. Sixty-eight residents were included in the analyses. Twenty-four residents (35.3%) completed resident research rotations with an average duration of 3.7 months. Residents who elected resident research rotations completed more scholarly projects (5 projects [4-6]: median [25%-75% interquartile range] vs 2 [0-3]; P < 0.0001), attended more research conferences (2 conferences [2-4] vs 1 [0-2]; P < 0.0001), but experienced fewer cases (980 cases [886-1333] vs 1182 [930-1420]; P ≤ 0.002) compared with those who did not elect resident research rotations. The estimated average cost to the department per resident who elected a resident research rotation was $13

Electrochemical impedance spectroscopy investigation on the clinical lifetime of ProTaper rotary file system.

PubMed

Penta, Virgil; Pirvu, Cristian; Demetrescu, Ioana

2014-01-01

The main objective of the current paper is to show that electrochemical impedance spectroscopy (EIS) could be a method for evaluating and predicting of ProTaper rotary file system clinical lifespan. This particular aspect of everyday use of the endodontic files is of great importance in each dental practice and has profound clinical implications. The method used for quantification resides in the electrochemical impedance spectroscopy theory and has in its main focus the characteristics of the surface titanium oxide layer. This electrochemical technique has been adapted successfully to identify the quality of the Ni-Ti files oxide layer. The modification of this protective layer induces changes in corrosion behavior of the alloy modifying the impedance value of the file. In order to assess the method, 14 ProTaper sets utilized on different patients in a dental clinic have been submitted for testing using EIS. The information obtained in regard to the surface oxide layer has offered an indication of use and proves that the said layer evolves with each clinical application. The novelty of this research is related to an electrochemical technique successfully adapted for Ni-Ti file investigation and correlation with surface and clinical aspects.

The Role of the Clinical and Translational Science Awards Program in Improving the Quality and Efficiency of Clinical Research

PubMed Central

Rosenblum, Daniel

2011-01-01

Recognizing the need to increase the efficiency and quality of translating basic discovery into treatment and prevention strategies for patients and the public, the National Institutes of Health (NIH) announced the Clinical and Translational Science Awards (CTSAs) in 2006. Academic health centers that competed successfully for these awards agreed to work as a consortium and in cooperation with the NIH to improve the translation process by training the next generation of investigators to work in interdisciplinary teams, developing public-private partnerships in the movement of basic discovery to preclinical and clinical studies and trials, improving clinical research management, and engaging with communities to ensure their involvement in shaping research questions and in implementing research results. The CTSAs have addressed the crucial need to improve the quality and efficiency of clinical research by (1) providing training for clinical investigators and for bench researchers to facilitate their participation in the clinical and translational research environment, (2) developing more systematic approaches to clinical research management, and (3) engaging communities as active participants in the design and conduct of clinical research studies and trials and as leaders in implementing health advances that are of high importance to them. We provide an overview of the CTSA activities with attention to these three areas, which are essential to developing efficient clinical research efforts and effective implementation of research results on a national level. PMID:21896519

Antimicrobial activity of the imipenem/rifampicin combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures.

PubMed

Wang, Yang; Bao, Wanguo; Guo, Na; Chen, Haiying; Cheng, Wei; Jin, Kunqi; Shen, Fengge; Xu, Jiancheng; Zhang, Qiaoli; Wang, Chao; An, Yanan; Zhang, Kaiyu; Wang, Feng; Yu, Lu

2014-12-01

To investigate the antimicrobial activity of imipenem and rifampicin alone and in combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures. Minimum inhibitory concentrations were determined for each isolate grown in suspension and in biofilm using a microbroth dilution method. Chequerboard assays and the agar disk diffusion assay were used to determine synergistic, indifferent or antagonistic interactions between imipenem and rifampicin. We used the tissue culture plate method for A. baumannii biofilm formation to measure the percentage of biofilm inhibition and the amount of extracellular DNA after the treatment. To understand the synergistic mechanisms, we conducted hydroxyl radical formation assays. The results were verified by confocal laser scanning microscopy. Imipenem and rifampicin showed effective antimicrobial activity against suspensions and biofilm cultures of A. baumannii, respectively. Synergistic antimicrobial effects between imipenem and rifampicin were observed in 13 and 17 of the 20 clinical isolates when in suspension and in biofilms, respectively. Imipenem and rifampicin alone and in combination generated hydroxyl radicals, which are highly reactive oxygen forms and the major components of bactericidal agents. Furthermore, treatment with imipenem and rifampicin individually or in combination has obvious antibiofilm effects. The synergistic activity of imipenem and rifampicin against clinical isolates of A. baumannii (in suspension and in biofilms) was observed in vitro. Therefore, we conclude that imipenem combined with rifampicin has the potential to be used as a combinatorial therapy for the treatment of infectious diseases caused by A. baumannii.

Mass spectrometric detection of ricin and its activity in food and clinical samples.

PubMed

Kalb, Suzanne R; Barr, John R

2009-03-15

Ricin is a potent toxin capable of inhibiting protein synthesis and causing death or respiratory failure. Because of its high availability and lethality, ricin is considered a likely agent for bioterrorism. Rapidly determining contamination of food product with ricin and human exposure to ricin is therefore an important public health goal. In this work, we report the development of a method that detects ricin and its activity in food or clinical samples. This method involves immunocapture of the toxin, an examination of the activity of the ricin protein upon a DNA substrate that mimics the toxin's natural RNA target, and analysis of tryptic fragments of the toxin itself. It is the combination of these three techniques, all performed on the same sample, which allows for a sensitive and selective analysis of ricin isolated from a food or clinical sample. This measurement includes a measure of the toxin's activity. The utility of this method was demonstrated on ricin spiked into food and clinical samples consisting of milk, apple juice, serum, and saliva.

Dosimetry investigation of MOSFET for clinical IMRT dose verification.

PubMed

Deshpande, Sudesh; Kumar, Rajesh; Ghadi, Yogesh; Neharu, R M; Kannan, V

2013-06-01

In IMRT, patient-specific dose verification is followed regularly at each centre. Simple and efficient dosimetry techniques play a very important role in routine clinical dosimetry QA. The MOSFET dosimeter offers several advantages over the conventional dosimeters such as its small detector size, immediate readout, immediate reuse, multiple point dose measurements. To use the MOSFET as routine clinical dosimetry system for pre-treatment dose verification in IMRT, a comprehensive set of experiments has been conducted, to investigate its linearity, reproducibility, dose rate effect and angular dependence for 6 MV x-ray beam. The MOSFETs shows a linear response with linearity coefficient of 0.992 for a dose range of 35 cGy to 427 cGy. The reproducibility of the MOSFET was measured by irradiating the MOSFET for ten consecutive irradiations in the dose range of 35 cGy to 427 cGy. The measured reproducibility of MOSFET was found to be within 4% up to 70 cGy and within 1.4% above 70 cGy. The dose rate effect on the MOSFET was investigated in the dose rate range 100 MU/min to 600 MU/min. The response of the MOSFET varies from -1.7% to 2.1%. The angular responses of the MOSFETs were measured at 10 degrees intervals from 90 to 270 degrees in an anticlockwise direction and normalized at gantry angle zero and it was found to be in the range of 0.98 ± 0.014 to 1.01 ± 0.014. The MOSFETs were calibrated in a phantom which was later used for IMRT verification. The measured calibration coefficients were found to be 1 mV/cGy and 2.995 mV/cGy in standard and high sensitivity mode respectively. The MOSFETs were used for pre-treatment dose verification in IMRT. Nine dosimeters were used for each patient to measure the dose in different plane. The average variation between calculated and measured dose at any location was within 3%. Dose verification using MOSFET and IMRT phantom was found to quick and efficient and well suited for a busy radiotherapy

Microbiological investigation and clinical significance of Corynebacterium spp. in respiratory specimens.

PubMed

Nhan, Tu-Xuan; Parienti, Jean-Jacques; Badiou, Guillaume; Leclercq, Roland; Cattoir, Vincent

2012-11-01

The purpose of this retrospective study was to evaluate the pathogenic role of Corynebacterium species in lower respiratory tract infections as well as their routine laboratory investigation. From April 2007 to August 2009, 27 clinical isolates were significantly recovered from respiratory specimens of 27 different patients clinically suspected of having lower respiratory tract infections. The average age of patients was 65 years, while 22 (81%) patients presented at least 1 predisposing condition. Of the 27 patients, 15 (56%) were classified as infected according to Centers for Disease Control and Prevention/National Healthcare Safety Network criteria, with 93% of infections being hospital acquired. All isolates were accurately identified to the species level using molecular methods (i.e., 17 Corynebacterium pseudodiphtheriticum, 7 Corynebacterium striatum, and 3 Corynebacterium accolens), whereas phenotypic methods remained frequently unreliable for identifying C. striatum and C. accolens strains. All tested isolates were susceptible to amoxicillin, imipenem, vancomycin, linezolid, and tigecycline, whereas most of them were resistant to erythromycin. Copyright © 2012 Elsevier Inc. All rights reserved.

Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

2016-03-22

To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

Pilot study: Investigating the effects of Kinesio Taping® on functional activities in children with cerebral palsy.

PubMed

da Costa, Carolina Souza Neves; Rodrigues, Fernanda Simioni; Leal, Fernanda Mustafe; Rocha, Nelci Adriana Cicuto Ferreira

2013-01-01

To investigate the immediate effects of Kinesio Taping® (KT) on sit-to-stand (STS) movement, balance and dynamic postural control in children with cerebral palsy (CP). Four children diagnosed with left hemiplegic CP level I by the Gross Motor Function Classification System were evaluated under conditions without taping as control condition (CC); and with KT as kinesio condition. A motion analysis system was used to measure total duration of STS movement and angular movements of each joint. Clinical instruments such as Pediatric Balance Scale (PBS) and Timed up and Go (TUG) were also applied. Compared to CC, decreased total duration of STS, lower peak ankle flexion, higher knee extension at the end of STS, and decreased total time in TUG; but no differences were obtained on PBS score in KT. Neuromuscular taping seems to be beneficial on dynamic activities, but not have the same performance in predominantly static activities studied.

Duplex investigations in children: Are clinical signs in children with venous disorders relevant?

PubMed

Birgitte Maessen-Visch, M; Smeets, L; van Vleuten, C

2015-12-01

Ultra sound colored duplex sonography is the preferred method in diagnosing chronic venous disease. Data in children on incidence, indications, and results are lacking. From the total of 9180 duplex investigations performed in our hospital from 2009 to 2012, data on indication and results of the investigation as well as patient characteristics were evaluated retrospectively for the proportion of pediatric patients. Duplex investigations were performed 49 times in 38 children (6-18 years), with an average of 1.3 times (1-6 times) per child. Forty percent showed abnormalities: 17 times deep venous thrombosis was suspected; deep venous thrombosis was objectified in 18%. In the 21 investigations performed for varicosis-related complaints, varicose veins or venous malformations were objectified in 57%. Edema was never a symptom of chronic venous disease. Duplex investigation is not often performed in children. In children with established deep venous thrombosis, a family history with deep venous thrombosis is common. In general, edema was not seen in children with varicose veins and, therefore, does not seem a reliable clinical sign at young age. © The Author(s) 2014.

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up.

PubMed

Kauhanen, Lotta; Järvelä, Liisa; Lähteenmäki, Päivi M; Arola, Mikko; Heinonen, Olli J; Axelin, Anna; Lilius, Johan; Vahlberg, Tero; Salanterä, Sanna

2014-04-05

Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children's cancer treatment. The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children's perceptions of the most enjoyable activation methods are explored through an interview at 2 months. This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012).

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

PubMed

Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

In Vitro Activity of E1210, a Novel Antifungal, against Clinically Important Yeasts and Molds▿

PubMed Central

Miyazaki, Mamiko; Horii, Takaaki; Hata, Katsura; Watanabe, Nao-aki; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

2011-01-01

E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC90 of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC90 of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections. PMID:21825291

Clinical pharmacists in general practice: an initial evaluation of activity in one English primary care organisation.

PubMed

Bush, Joseph; Langley, Christopher A; Jenkins, Duncan; Johal, Jaspal; Huckerby, Clair

2017-12-27

This aim of this research was to characterise the breadth and volume of activity conducted by clinical pharmacists in general practice in Dudley Clinical Commissioning Group (CCG), and to provide quantitative estimates of both the savings in general practitioner (GP) time and the financial savings attributable to such activity. This descriptive observational study retrospectively analysed quantitative data collected by Dudley CCG concerning the activity of clinical pharmacists in GP practices during 2015. Over the 9-month period for which data were available, the 5.4 whole time equivalent clinical pharmacists operating in GP practices within Dudley CCG identified 23 172 interventions. Ninety-five per cent of the interventions identified were completed within the study period saving the CCG in excess of £1 000 000. During the 4 months for which resource allocation data were available, the clinical pharmacists saved 628 GP appointments plus an additional 647 h that GPs currently devote to medication review and the management of repeat prescribing. This research suggests that clinical pharmacists in general practice in Dudley CCG are able to deliver clinical interventions efficiently and in high volume. In doing so, clinical pharmacists were able to generate considerable financial returns on investment. Further work is recommended to examine the effectiveness and cost-effectiveness of clinical pharmacists in general practice in improving outcomes for patients. © 2017 Royal Pharmaceutical Society.

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

PubMed Central

Robertson, W; Robertson, A S; Burge, C B S G; Moore, V C; Jaakkola, M S; Dawkins, P A; Burd, M; Rawbone, R; Gardner, I; Kinoulty, M; Crook, B; Evans, G S; Harris‐Roberts, J; Rice, S; Burge, P S

2007-01-01

Background Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work‐related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. Methods The outbreak was investigated in a three‐phase cross‐sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work‐related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those

Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

PubMed Central

Cheng, Jie; Shah, Yatrik M.; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W.

2010-01-01

Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS- and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor κB (NF-κB) target genes were markedly down-regulated in hPXR mice by rifaximin treatment. In vitro NF-κB reporter assays demonstrated inhibition of NF-κB activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-κB signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD. PMID:20627999

Investigation on physiological and clinical effects of different light sources in TMJ photobiomodulation therapy

NASA Astrophysics Data System (ADS)

Kamenoff, J.

2017-02-01

Introduction Laser light Electromagnetic energy has some typical properties for discussions on laser irradiation abilities to control the acute and chronic disorders in TMJ. Material and Methods During the last six years we have been completed well controlled clinical trials based on the criteria of the American Academy of orofacial pain. The study over the 600 patients (300 women and 300 men), mean age of 47 years have been developed. Patients have been selected on the main clinical sign of TMJ pain and have been divided into four main groups according to the type of PDT method. Based on the action spectra, various wavelengths have been used for TMJ Photodynamic Therapy. Constant dose and time of exposition, as well as various range of frequencies have been applied. In this way the Laser biostimulation response has been directly proportional to the total energy dose, depending of light intensity. Physiological and clinical effects of the followed "active regions"- 660 - 680, 760 - 780, 810 - 830 and 904 - 987 nm have been valued by method of comparative analysis. Methods applied: LLLT - TENS - red surface laser acupuncture (LA), PIPBM - LA, Laser bioenergetics approach, Complex therapeutic program (CTP). Results evaluation will be demonstrated by comparative digital ortopantomograph analysis, EEG brain maps, VAS, a metric analysis of the level of the maximum active Mandible opening and EPST through electrophysiological signal evaluation of the patient's body.

Headache associated with sexual activity: demography, clinical features, and comorbidity.

PubMed

Frese, A; Eikermann, A; Frese, K; Schwaag, S; Husstedt, I-W; Evers, S

2003-09-23

S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

Telephone Coaching to Enhance a Home-Based Physical Activity Program for Knee Osteoarthritis: A Randomized Clinical Trial.

PubMed

Bennell, Kim L; Campbell, Penny K; Egerton, Thorlene; Metcalf, Ben; Kasza, Jessica; Forbes, Andrew; Bills, Caroline; Gale, Janette; Harris, Anthony; Kolt, Gregory S; Bunker, Stephen J; Hunter, David J; Brand, Caroline A; Hinman, Rana S

2017-01-01

To investigate whether simultaneous telephone coaching improves the clinical effectiveness of a physiotherapist-prescribed home-based physical activity program for knee osteoarthritis (OA). A total of 168 inactive adults ages ≥50 years with knee pain on a numeric rating scale ≥4 (NRS; range 0-10) and knee OA were recruited from the community and randomly assigned to a physiotherapy (PT) and coaching group (n = 84) or PT-only (n = 84) group. All participants received five 30-minute consultations with a physiotherapist over 6 months for education, home exercise, and physical activity advice. PT+coaching participants also received 6-12 telephone coaching sessions by clinicians trained in behavioral-change support for exercise and physical activity. Primary outcomes were pain (NRS) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC; score range 0-68]) at 6 months. Secondary outcomes were these same measures at 12 and 18 months, as well as physical activity, exercise adherence, other pain and function measures, and quality of life. Analyses were intent-to-treat with multiple imputation for missing data. A total of 142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements, respectively. The change in NRS pain (mean difference 0.4 unit [95% confidence interval (95% CI) -0.4, 1.3]) and in WOMAC function (1.8 [95% CI -1.9, 5.5]) did not differ between groups at 6 months, with both groups showing clinically relevant improvements. Some secondary outcomes related to physical activity and exercise behavior favored PT+coaching at 6 months but generally not at 12 or 18 months. There were no between-group differences in most other outcomes. The addition of simultaneous telephone coaching did not augment the pain and function benefits of a physiotherapist-prescribed home-based physical activity program. © 2016, American College of Rheumatology.

Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia

PubMed Central

Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.

2013-01-01

Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups. PMID:24961619

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Investigating motivational regulations and physical activity over 25 weeks.

PubMed

Sweet, Shane N; Fortier, Michelle S; Blanchard, Chris M

2014-07-01

Because motivation has been deemed a key barrier to physical activity, it is imperative that we know how motivational levels change over time and how that change relates to physical activity. Based in Self-Determination Theory, this study investigated fluctuations in physical activity and motivational regulations over 25 weeks and tested the relationship between these 2 variables. Data from the Physical Activity Counseling trial were examined. Inactive adults recruited from a primary care center (N = 120) answered motivation and physical activity questionnaires during the intervention and postintervention phases. Hierarchical linear modeling was used to test the hypotheses. Quadratic changes were found for external regulation (γ20= 0.02, P < .05) and physical activity (γ20 = -2.64, P < .001), while identified (γ10= 0.04, P = .03) and intrinsic (γ10= 0.04, P = .01) regulations increased linearly over the course of the 25 weeks. Only identified regulation (γ30= 3.15, P = .01) and intrinsic motivation (γ30= 4.68, P < .001) were significantly and positively related with physical activity. Physical activity, external and identified regulations and intrinsic motivation changed over the 25 weeks. Intervention should aim at fostering identified regulation and intrinsic motivation as greater levels of these regulations were related with physical activity.

Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function.

PubMed

Jääskeläinen, Satu K

2004-01-01

Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions

Activities of Available and Investigational Antifungal Agents against Rhodotorula Species

PubMed Central

Diekema, D. J.; Petroelje, B.; Messer, S. A.; Hollis, R. J.; Pfaller, M. A

2005-01-01

Rhodotorula species are emerging pathogens in immunocompromised patients. We report the in vitro activities of eight antifungals against 64 Rhodotorula isolates collected in surveillance programs between 1987 and 2003. Rhodotorula strains are resistant in vitro to fluconazole (MIC at which 50% of the isolates tested are inhibited [MIC50], >128 μg/ml) and caspofungin (MIC50, >8 μg/ml). Amphotericin B (MIC50,1 μg/ml) and flucytosine (MIC50, 0.12 μg/ml) are both active in vitro, and the new and investigational triazoles all have some in vitro activity, with ravuconazole being the most active (MIC50, 0.25 μg/ml). PMID:15635020

Determination of antimicrobial activity of sorrel (Hibiscus sabdariffa) on Escherichia coli O157:H7 isolated from food, veterinary, and clinical samples.

PubMed

Fullerton, Marjorie; Khatiwada, Janak; Johnson, Jacqueline U; Davis, Shurrita; Williams, Leonard L

2011-09-01

The use of medicinal plants as natural antimicrobial agents is gaining popularity. Sorrel (Hibiscus sabdariffa) is widely used for the treatment of diseases. The objective of this study was to investigate the antimicrobial activity of sorrel on Escherichia coli O157:H7 isolates from food, veterinary, and clinical samples. Phenolics of the calyces were extracted from 10 g of ground, freeze-dried samples using 100 mL of 80% aqueous methanol. Concentrations of 10%, 5%, and 2.5% methanol extract of sorrel were investigated for its antimicrobial activity. Inhibition zones were indicated by a lack of microbial growth due to inhibitory concentrations of sorrel diffused into semisolid culture medium beneath the sorrel-impregnated disk. The results of this experiment showed that the most potent sorrel concentration was 10%, then 5%, and finally 2.5%. The overall mean zone of inhibition for the sorrel extract was 12.66 mm for 10%, 10.75 mm for 5%, and 8.9 mm for 2.5%. The highest inhibition zones (11.16 mm) were observed in veterinary samples, and the lowest (10.57 mm) in the food samples. There were significant (P<.05) differences among mean zones of inhibition found in the food, veterinary, and clinical sources. Based on the source of samples and concentration of sorrel extract, the lowest mean inhibition was 7.00±0.04 mm from clinical samples, and the highest was 15.37±0.61 mm from a food source. These findings indicated that sorrel was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent.

Investigation of antiulcer and antioxidant activity of moclobemide in rats.

PubMed

Albayrak, Abdulmecit; Alp, Hamit H; Suleyman, Halis

2015-02-01

Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its anti-ulcer effect mechanisms.

Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

PubMed Central

Busetti, Alessandro; Thompson, Thomas P.; Tegazzini, Diana; Megaw, Julianne; Maggs, Christine A.; Gilmore, Brendan F.

2015-01-01

The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds. PMID:26058011

[The clinical investigation of peripheral retinal changes of anterior uveitis].

PubMed

Guo, Chunying; Qiao, Lijun; Yang, Liu

2015-10-01

To observe the peripheral retinal changes of anterior uveitis patients using ultra-wide field fluorescein angiography. Retrospective case series study. Thirty-three eyes of 20 patients diagnosed as anterior uveitis from September to November 2013 in the ophthalmic clinic of Peking University First Hospital was included. All the patients underwent routine ocular examination, followed by ultra-wide field Fluorescein. There were 13 male patients and 7 female patients, aged 23-66, an average of 46 years old. The anterior uveitis recurrent in both eyes in 13 patients and only one eye in 7 patients. Uveitis duration ranging from months to 30 years. Twenty eyes were at the active stage of the anterior uveitis while 13 eyes in the quiescent stage. Peripheral retinal vessels leakage was detected in 57.6% (19/33) of the eyes, among which in eyes with active disease the rate of peripheral retinal vessels leakage was 75% (15/20), and in eyes with quiescent disease the rate was 30.8% (4/13). Optic disk hyperfluorescence was found in 6 of 20 eyes with active disease. Cystoid macular edema was found in 4 eyes. In addition, peripheral retinal hyperfluorescence dot and zone were detected in 2 eyes. Peripheral retinal vessels were detected to have inflammative leakage in patients of anterior uveitis by ultra-wide field fluorescein agiography. Peripheral retinal inflammation may still exist even in the quiescent stage of the anterior uveitis.

Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods.

PubMed

Esquinas, Pedro L; Uribe, Carlos F; Gonzalez, M; Rodríguez-Rodríguez, Cristina; Häfeli, Urs O; Celler, Anna

2017-07-20

The main applications of 188 Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188 Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188 Re images. In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188 Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object's true activity. Each object's activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial [Formula: see text]-camera were performed to investigate the accuracy of the TEW method. Good quantification accuracy (errors  <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods

76 FR 80948 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...The Food and Drug Administration (FDA) is extending the comment period for the notice that appeared in the Federal Register of Thursday, November, 10, 2011 (76 FR 70151). In the notice, FDA requested comments on the draft guidance that has been developed to promote the initiation of clinical investigations to evaluate the medical devices under FDA's Investigational Device Exemptions (IDE) regulations. The Agency is taking this action to allow interested persons additional time to submit comments.

Resveratrol-Induced AMP-Activated Protein Kinase Activation Is Cell-Type Dependent: Lessons from Basic Research for Clinical Application.

PubMed

Lan, Fan; Weikel, Karen A; Cacicedo, Jose M; Ido, Yasuo

2017-07-14

Despite the promising effects of resveratrol, its efficacy in the clinic remains controversial. We were the first group to report that the SIRT1 activator resveratrol activates AMP-activated protein kinase (AMPK) (Diabetes 2005; 54: A383), and we think that the variability of this cascade may be responsible for the inconsistency of resveratrol's effects. Our current studies suggest that the effect of SIRT1 activators such as resveratrol may not be solely through activation of SIRT1, but also through an integrated effect of SIRT1-liver kinase B1 (LKB1)-AMPK. In this context, resveratrol activates SIRT1 (1) by directly binding to SIRT1; and (2) by increasing NAD⁺ levels by upregulating the salvage pathway through Nampt activation, an effect mediated by AMPK. The first mechanism promotes deacetylation of a limited number of SIRT1 substrate proteins (e.g., PGC-1). The second mechanism (which may be more important than the first) activates other sirtuins in addition to SIRT1, which affects a broad spectrum of substrates. Despite these findings, detailed mechanisms of how resveratrol activates AMPK have not been reported. Here, we show that (1) resveratrol-induced activation of AMPK requires the presence of functional LKB1; (2) Resveratrol increases LKB1 activity, which involves translocation and phosphorylation at T336 and S428; (3) Activation of LKB1 causes proteasomal degradation of LKB1; (4) At high concentrations (50-100 µM), resveratrol also activates AMPK through increasing AMP levels; and (5) The above-mentioned activation mechanisms vary among cell types, and in some cell types, resveratrol fails to activate AMPK. These results suggest that resveratrol-induced activation of AMPK is not a ubiquitous phenomenon. In addition, AMPK-mediated increases in NAD⁺ in the second mechanism require several ATPs, which may not be available in many pathological conditions. These phenomena may explain why resveratrol is not always consistently beneficial in a clinical

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up

PubMed Central

2014-01-01

Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children’s perceptions of the most enjoyable activation methods are explored through an interview at 2 months. Discussion This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. Trial registration ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012). PMID:24708773

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy.

PubMed

Mistry, Ishna N; Thomas, Matthew; Calder, Ewen D D; Conway, Stuart J; Hammond, Ester M

2017-08-01

With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy. Therefore, the combination of radiation therapy and bioreductive drugs presents an attractive opportunity for synergistic effects, because the HAP targets the radiation-resistant hypoxic cells. Hypoxia-activated prodrugs have typically been precursors of DNA-damaging agents, but a new generation of molecularly targeted HAPs is emerging. By targeting proteins associated with tumorigenesis and survival, these compounds may result in greater selectivity over healthy tissue. We review the clinical progress of HAPs as adjuncts to radiation therapy and conclude that the use of HAPs alongside radiation is vastly underexplored at the clinical level. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical medicine between science, ethics and economy: a complex activity.

PubMed

Federspil, Giovanni

2004-01-01

Until recently the common opinion was that medicine was substantially a natural science. In recent years, this has completely changed because two non-naturalistic disciplines have become part of the physician's activity; ethics and economy. These new disciplines have evidenced many problems to which doctors did not pay much attention before; however, they had an impact on the clinician's sensibility. At present, clinical medicine represents a complex knowledge as well as an activity: it is both a "historical" and a "technological" science characterized by a specific goal, the recovery or maintenance of health, and by a series of values.

Preliminary investigation of a sealed, remotely activated silver-zinc battery

NASA Technical Reports Server (NTRS)

Wheat, C. G.

1977-01-01

Methods necessary to provide a remotely activated, silver zinc battery capable of an extended activated stand while in a sealed condition were investigated. These requirements were to be accomplished in a battery package demonstrating an energy density of at least 35 watt hours per pound. Several methods of gas suppression were considered in view of the primary nature of this unit and utilized the electroplated dendritic zinc electrode. Amalgamation of the electrode provided the greatest suppression of gas at the zinc electrode. The approach to extending the activated stand capability of the remotely activated battery was through evaluation of three basic methods of remote, multi-cell activation; 1) the electrolyte manifold, 2) the gas manifold and 3) the individual cell. All three methods of activation can be incorporated into units which will meet the minimum energy density requirement.

[Closed-loop management model of clinical investigational product for new drug of traditional Chinese medicine].

PubMed

Wu, Ping; Zhang, Jian-Wu

2013-09-01

This paper discussed the management regulations and technical requirements of clinical investigational product for new drug of traditional Chinese medicine, analyzed some common problems on the management of them, and proposed the establishment of closed-loop management model and management requirements in various aspects.

Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

PubMed Central

Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

2014-01-01

Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis.

PubMed

Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

2016-01-01

Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Study population included 15 smoker male patients in the age group of 35-55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

Storm Surges. Teacher Guide and Activity Book. OEAGLS Investigation No. 25.

ERIC Educational Resources Information Center

Keir, John; Mayer, Victor J.

This investigation is designed to help students understand storm surges on Lake Erie. Activity A includes experiments and discussions intended to help students understand what causes storm surges on Lake Erie. Activity B considers how storm surges affect water levels and, in turn, coastal areas. The student booklet contains questions, experiments,…

Determinants of Broader Impacts Activities: A Survey of NSF-Funded Investigators

ERIC Educational Resources Information Center

Nagy, Dianne

2016-01-01

This study investigated the factors that shape the broader impacts activities of NSF grant recipients. A random sample of NSF grantees was surveyed about the type and quality of their broader impacts activities, their views on knowledge production and the democratization of science, their experience and training, and the existence of a supportive…

Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies.

PubMed

Lee, Edmund C; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P; Subakan, Ozlem; Silva, Matthew D; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T; Berger, Allison J; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B; Van Ness, Brian; Janz, Siegfried

2011-12-01

The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Both cell line-derived OCI-Ly10 and primary human lymphoma-derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMyc(Cα)/Bcl-X(L) GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc-disseminated model of iMyc(Cα)/Bcl-X(L) was used to determine antitumor activity and effects on osteolytic bone disease. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. ©2011 AACR.

Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies

PubMed Central

Lee, Edmund C.; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P.; Subakan, Ozlem; Silva, Matthew D.; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T.; Berger, Allison J.; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B.; Van Ness, Brian; Janz, Siegfried

2012-01-01

Purpose The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Experimental Design Both cell line–derived OCI-Ly10 and primary human lymphoma–derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMycCα/Bcl-XL GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc–disseminated model of iMycCα/ Bcl-XL was used to determine antitumor activity and effects on osteolytic bone disease. Results MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMycCα/Bcl-XL GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Conclusions Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. PMID:21903769

Investigate the Child's Scientific Activities on Practical Child's Activity Books for the Kindergarten's Children

ERIC Educational Resources Information Center

Aldarabah, Intisar Turki; Al-Mouhtadi, Reham

2015-01-01

This research aimed to investigate the extent to which the interactive international curriculum is included in the "Child's Scientific Activities" issued by the Ministry of Education in Jordan, for the kindergarten stage according to the global criterion (NRC). In order to answer the study questions, an instrument was developed to…

Feasibility and acceptability of active book clubs in cancer survivors - an explorative investigation.

PubMed

Hammer, Nanna Maria; Egestad, Lisbeth Kofoed; Nielsen, Susanne Grøn; Bjerre, Eik; Johansen, Christoffer; Egerod, Ingrid; Pinto, Bernardine; Midtgaard, Julie

2017-03-01

While the increasing number of people surviving cancer is promising, the long-term health effects warrant broad, innovative interventions. We investigated the feasibility and acceptability of a 24-week intervention called 'Active Book Club' comprising audio book listening, pedometer walking and supervised book club meetings. An exploratory and descriptive design was applied. Qualitative data included baseline and post-intervention focus group interviews as well as post-intervention individual interviews. The study also included data on retention, attendance, and adherence. Seventeen self-referred cancer survivors with various oncological and sociodemographic backgrounds were included. Eight (47%) participants completed the entire intervention. Their median attendance at the book club meetings was eight [interquartile range (IQR) 6-9] of nine possible, and they reached the walking step goal in a median of 11 (IQR 7-12) of the first 12 weeks, and seven (IQR 1-10) of the last 12 weeks. The qualitative analysis revealed five themes including: Motivation and expectations (i.e. reasons for enrollment), Attentive listening (i.e. experiences of the audio book format), Affected by the story (i.e. experiences of the content of the books), Group involvement (i.e. experiences of the book club meetings) and Walking regularly (i.e. experiences of the walking program). Overall, findings revealed that while audio books may bring new meaning to physical activity and serve as a relief from own concerns, certain stories may affect some individuals negatively. The substantial dropout rate, however, suggested that modification is necessary and that patient involvement in choice of literature may be critical to enhance acceptability. The 'Active Book Club' represents a novel psychosocial intervention potentially supporting physical activity adoption and mental health in cancer survivors. However, several issues related to feasibility and acceptability including choice of

Wearable Internet of Things - from human activity tracking to clinical integration.

PubMed

Kumari, Poonam; Lopez-Benitez, Miguel; Gyu Myoung Lee; Tae-Seong Kim; Minhas, Atul S

2017-07-01

Wearable devices for human activity tracking have been emerging rapidly. Most of them are capable of sending health statistics to smartphones, smartwatches or smart bands. However, they only provide the data for individual analysis and their data is not integrated into clinical practice. Leveraging on the Internet of Things (IoT), edge and cloud computing technologies, we propose an architecture which is capable of providing cloud based clinical services using human activity data. Such services could supplement the shortage of staff in primary healthcare centers thereby reducing the burden on healthcare service providers. The enormous amount of data created from such services could also be utilized for planning future therapies by studying recovery cycles of existing patients. We provide a prototype based on our architecture and discuss its salient features. We also provide use cases of our system in personalized and home based healthcare services. We propose an International Telecommunication Union based standardization (ITU-T) for our design and discuss future directions in wearable IoT.

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0792] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example.

PubMed

Landewé, Robert B M; Smolen, Josef S; Weinblatt, Michael E; Emery, Paul; Dougados, Maxime; Fleischmann, Roy; Aletaha, Daniel; Kavanaugh, Arthur; van der Heijde, Désirée

2014-10-01

Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A patient presenting a 22q13 deletion associated with an apparently balanced translocation t(16;22): An illustrative case in the investigation of patients with low ARSA activity

PubMed Central

Artigalás, Osvaldo; Paskulin, Giorgio; Riegel, Mariluce; Burin, Maira; Saraiva-Pereira, Maria Luiza; Maluf, Sharbel; Kiss, Andrea; Schwartz, Ida Vanessa D.

2012-01-01

A 10-year-old speechless, mentally deficient male, with low arylsulfatase A (ARSA) activity, and presumably, methachromatic leukodystrophy, underwent genetic evaluation. As the clinical picture was not compatible with this diagnosisan ARSA gene and chromosome analysis were performed, showing the presence of a pseudodeficiency ARSA allele and a de novo apparently balanced t(16;22)(p11.2;q13) translocation. A deletion on the long arm of chromosome 22 encompassing the ARSA gene, as shown by FISH and array-CGH, indicated a 22q13 deletion syndrome. This case illustrates the importance of detailed cytogenetic investigation in patients presenting low arylsulfatase A activity and atypical/unspecific clinical features. PMID:22888290

Clinical staging: its importance in therapeutic decisions and clinical trials.

PubMed

Denis, L J

1992-02-01

International collaboration has resulted in a revised and unified 1987 formulation for the TNM classification in solid tumors. The simplification and eliminations of most variables caused difficulties for the clinical use of the system in some tumors such as bladder cancer. The approval of the proposed adaptation covering the tumor mass, subdividing the T4 category and adapting the stage grouping, resolves these difficulties. Published reports demonstrate support for the TNM system as a clinical base for treatment decisions and prognosis. The TNMG stage and grade are important basic prognostic factors, but other prognostic factors, especially biologic tumor activity, are under clinical investigation. The TNM classification is the initial evaluation after histologic confirmation of cancer to guide treatment and prognosis. The quality of the evaluation is enhanced by precise communication on the employed methodology.

STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

EPA Science Inventory

Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

Sustaining the Clinical and Translational Research Workforce: Training and Empowering the Next Generation of Investigators.

PubMed

Yin, Helen L; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M; Toto, Robert

2015-07-01

There is mounting concern that clinician-scientists are a vanishing species and that the pipeline for clinical and translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH)-funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional "culture shift" are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical and Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the time frame, increasing the rate of K2R transition, and identifying strategies that improve success.

Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: Experimental and clinical investigations

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

Suga, Kazuyoshi; Uchisako, Hiromichi; Nishigauchi, Kazuya

1994-09-01

The authors evaluated the ability of {sup 99m}Tc-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) to serve as a sensitive marker of lung injury. Two experiment rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, they clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of {sup 99m}Tc-HMPAO in the lungs. Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of {supmore » 99m}Tc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of {sup 99m}Tc-HMPAO activity in the patients who received chemotherapy (0.649{+-}0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387{+-}0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. These findings suggest that {sup 99m}Tc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury. 53 refs., 5 figs., 3 tabs.« less

Nanoparticles in the clinic

PubMed Central

Anselmo, Aaron C.

2016-01-01

Abstract Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems. PMID:29313004

Physician to investigator: clinical practice to clinical research--ethical, operational, and financial considerations.

PubMed

Pierre, Christine

2008-01-01

Physicians who participate in clinical research studies gain benefits for themselves, their practice, and their patients. Historically, private practice physicians have chosen to defer to their counterparts in academic medicine when it comes to contributing to scientific advancement through clinical studies. A growing number of private practice physicians are now taking a serious second look and deciding that there are unique benefits for both the practice and the patient. Physicians who decide to participate in clinical research should give serious consideration to the time and resources that are required to meet both federal regulations and industry standards. In addition, ethical and scientific principles for assuring the protection of human research subjects must be a paramount commitment.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Determination of Antimicrobial Activity of Sorrel (Hibiscus sabdariffa) on Esherichia coli O157:H7 Isolated from Food, Veterinary, and Clinical Samples

PubMed Central

Fullerton, Marjorie; Khatiwada, Janak; Johnson, Jacqueline U.; Davis, Shurrita

2011-01-01

Abstract The use of medicinal plants as natural antimicrobial agents is gaining popularity. Sorrel (Hibiscus sabdariffa) is widely used for the treatment of diseases. The objective of this study was to investigate the antimicrobial activity of sorrel on Escherichia coli O157:H7 isolates from food, veterinary, and clinical samples. Phenolics of the calyces were extracted from 10 g of ground, freeze-dried samples using 100 mL of 80% aqueous methanol. Concentrations of 10%, 5%, and 2.5% methanol extract of sorrel were investigated for its antimicrobial activity. Inhibition zones were indicated by a lack of microbial growth due to inhibitory concentrations of sorrel diffused into semisolid culture medium beneath the sorrel-impregnated disk. The results of this experiment showed that the most potent sorrel concentration was 10%, then 5%, and finally 2.5%. The overall mean zone of inhibition for the sorrel extract was 12.66 mm for 10%, 10.75 mm for 5%, and 8.9 mm for 2.5%. The highest inhibition zones (11.16 mm) were observed in veterinary samples, and the lowest (10.57 mm) in the food samples. There were significant (P<.05) differences among mean zones of inhibition found in the food, veterinary, and clinical sources. Based on the source of samples and concentration of sorrel extract, the lowest mean inhibition was 7.00±0.04 mm from clinical samples, and the highest was 15.37±0.61 mm from a food source. These findings indicated that sorrel was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent. PMID:21548802

Medicinal Mushrooms in Human Clinical Studies. Part I. Anticancer, Oncoimmunological, and Immunomodulatory Activities: A Review.

PubMed

Wasser, Solomon P

2017-01-01

More than 130 medicinal functions are thought to be produced by medicinal mushrooms (MMs) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemic, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, antidiabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelia, and cultured broth. Special attention has been paid to mushroom polysaccharides. Numerous bioactive polysaccharides or polysaccharide-protein complexes from MMs seem to enhance innate and cell-mediated immune responses, and they exhibit antitumor activities in animals and humans. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds seems to be central. Most important for modern medicine are polysaccharides and low-molecular weight secondary metabolites with antitumor and immunostimulating properties. More than 600 studies have been conducted worldwide, and numerous human clinical trials on MMs have been published. Several of the mushroom compounds have proceeded through phase I, II, and III clinical studies and are used extensively and successfully in Asia to treat various cancers and other diseases. The aim of this review is to provide an overview of and analyze the literature on clinical trials using MMs with human anticancer, oncoimmunological, and immunomodulatory activities. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies of MMs, including well-sized population studies are definitely needed in order to yield statistical power showing their efficacy and safety. Clinical trials must obtain sufficient data on the efficacy and safety of MM-derived drugs and preparations. Discussion of results based on clinical studies of the anticancer, oncoimmunological, and

The effect of active video games on cognitive functioning in clinical and non-clinical populations: A meta-analysis of randomized controlled trials.

PubMed

Stanmore, Emma; Stubbs, Brendon; Vancampfort, Davy; de Bruin, Eling D; Firth, Joseph

2017-07-01

Physically-active video games ('exergames') have recently gained popularity for leisure and entertainment purposes. Using exergames to combine physical activity and cognitively-demanding tasks may offer a novel strategy to improve cognitive functioning. Therefore, this systematic review and meta-analysis was performed to establish effects of exergames on overall cognition and specific cognitive domains in clinical and non-clinical populations. We identified 17 eligible RCTs with cognitive outcome data for 926 participants. Random-effects meta-analyses found exergames significantly improved global cognition (g=0.436, 95% CI=0.18-0.69, p=0.001). Significant effects still existed when excluding waitlist-only controlled studies, and when comparing to physical activity interventions. Furthermore, benefits of exergames where observed for both healthy older adults and clinical populations with conditions associated with neurocognitive impairments (all p<0.05). Domain-specific analyses found exergames improved executive functions, attentional processing and visuospatial skills. The findings present the first meta-analytic evidence for effects of exergames on cognition. Future research must establish which patient/treatment factors influence efficacy of exergames, and explore neurobiological mechanisms of action. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

PubMed

Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

2003-09-01

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective

Experimental protocol of a randomized controlled clinical trial investigating the effects of personalized exercise rehabilitation on kidney transplant recipients' outcomes.

PubMed

Kastelz, Alexandra; Tzvetanov, Ivo G; Fernhall, Bo; Shetty, Aneesha; Gallon, Lorenzo; West-Thielke, Patricia; Hachaj, Greg; Grazman, Mark; Benedetti, Enrico

2015-11-01

This randomized controlled trial (RCT) will investigate the effects of a personalized exercise rehabilitation regimen on return to work and find work rate, vascular health, functional capacity, quality of life, kidney function, and body composition in kidney transplant (KT) recipients. This RCT will recruit 120 men and/or women who have had a KT to participate in a 12 month exercise intervention or control (standard clinical care only) group. The 12 month exercise intervention will consist of one-on-one, progressive exercise rehabilitation sessions twice a week, for 60 min each session. The control group will continue standard clinical care as recommended by their post-transplant medical team without any intervention. The primary outcomes will be assessments of vascular structure and function, walking and strength measures to assess functional capacity, blood markers to assess kidney function, questionnaires to assess quality of life, DXA body scan to assess body composition, and a 1-week free living physical activity assessment. Additionally, employment status will be assessed. These assessments will be performed at baseline, 6 months, and 12 months. This investigation will increase the understanding of the role exercise rehabilitation has on managing the physiological and psychological health of the individual as well as on the individual's personal economic impact (via employment status). This study design has the potential to assist in constructing an effective exercise rehabilitation program that can be incorporated into part of standard post-transplant care. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical effects of deep cervical flexor muscle activation in patients with chronic neck pain

PubMed Central

Kim, Jin Young; Kwag, Kwang Il

2016-01-01

[Purpose] The purpose of this study was to investigate clinical effects of deep cervical flexor (DCF) muscles exercise on pain, Neck Disability Index (NDI), and neck and shoulder postures in patients with chronic neck pain. [Subjects and Methods] Twenty-eight patients with chronic neck pain were randomly assigned into either the general strengthening exercise (GSE) group or the DCF activation group as control and experimental groups, respectively. All exercises were performed three times per week over 4 weeks. NDI and numeric rating scale (NRS) score for pain were determined and radiological assessment of neck-shoulder postures (head tilt angle [HTA], neck flexion angle [NFA], and forward shoulder angle [FSA]) was performed before (baseline), 4 weeks after, and 8 weeks after exercise in order to directly compare the exercise effects between the groups. [Results] In the DCF group, the NDI, NRS score, and neck-shoulder postures (analyzed by uisng HTA, NFA, and FSA) were significantly improved. [Conclusion] DCF activation exercise was effective to alleviate pain, recover functions, and correct forward head posture in the patients with neck pain. Hence, it might be recommended in the rehabilitation of patients with chronic neck pain. PMID:26957772

Research Capacity at Traditional Chinese Medicine (TCM) Centers in China: A Survey of Clinical Investigators.

PubMed

Feng, Shuo; Han, Mei; Lai, Lily; Wang, Si-Cheng; Liu, Jian-Ping

2017-01-01

Background. The development of an evidence-based approach to traditional Chinese medicine (TCM), which depends on the generation of good quality evidence, requires an adequate workforce. However, the research capacity of TCM investigators is not known. Study Design. This cross-sectional study was conducted to describe the research capacity of TCM clinical investigators in China. Participants. A total of 584 participants from TCM hospitals and research centers were included. They were asked about the academic and research characteristics, needs for research capacity building, and barriers to clinical research. Results. The majority (80.82%) were qualified to at least a Master's degree, whilst a smaller proportion (40.24%) held a senior professional title. We found that academic outputs were low with the majority (62.16%) authoring less than five publications in total. The most pressing needs for building research capacity identified were training in research methodology (97.43%) and identification of research questions (86.81%), whilst the highest ranking barriers to conducting research were limited motivation, funding (40.72%), and time (37.15%). Conclusion. The methodology training, along with investment in the research workforce, needs to be urgently addressed to improve investigators' research capacity and the development of an evidence-based approach of TCM.

Investigating Invariant Item Ordering in Personality and Clinical Scales: Some Empirical Findings and a Discussion

ERIC Educational Resources Information Center

Meijer, Rob R.; Egberink, Iris J. L.

2012-01-01

In recent studies, different methods were proposed to investigate invariant item ordering (IIO), but practical IIO research is an unexploited field in questionnaire construction and evaluation. In the present study, the authors explored the usefulness of different IIO methods to analyze personality scales and clinical scales. From the authors'…

Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease.

PubMed

Engel, Tal; Ben-Horin, Shomron; Beer-Gabel, Marc

2015-10-01

Autonomic dysfunction has been implicated in Crohn's disease (CD). We aimed to investigate heart rate variability (HRV) as a marker of possible autonomic imbalance in patients with CD. Thirty patients with CD and 30 age- and gender-matched healthy controls were enrolled in a prospective cohort study and underwent HRV study. Anxiety level was scored using the STAI questionnaire and CD clinical activity was assessed by Harvey-Bradshaw index. Blood tests including inflammatory markers were obtained for all participants. CD subjects had lower mean blood pressure (85.51 ± 11.07 mm Hg, 91.51 ± 6.99, P = 0.015) and albumin and significantly higher CRP and IL-6 compared with controls (P < 0.002 for all comparisons). Mean HRV values of very low-frequency power and low-frequency power components were significantly lower among CD subjects (P = 0.038 and 0.027, respectively), implying a predominant sympathetic tone. Anxiety level scores were significantly higher among patients with CD for both state anxiety (P = 0.001) and trait anxiety (P < 0.0001). However, patients with active disease had similar anxiety scores as patients in remission, yet had a significantly lower BMI, lower albumin level, and higher CRP and IL-6 levels (P < 0.05 for all comparisons). Moreover, despite similar anxiety scores, patients with active disease had higher pulse rate (P = 0.02) and lower HRV indexes, which correlated with albumin levels(r = 0.7, P = 0.001). Although patients with CD have higher anxiety levels compared with controls, they exhibit depressed HRV independent of this anxiety state and in direct correlation with disease activity and inflammatory markers. These observations suggest an inherent imbalance of autonomic function associated with active inflammation.

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

PubMed

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

2014-01-01

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

The relationship between senior management team culture and clinical governance: Empirical investigation and managerial implications.

PubMed

Prenestini, Anna; Calciolari, Stefano; Lega, Federico; Grilli, Roberto

2015-01-01

Health care organizations are pressured to improve the cost-effectiveness of service delivery. Clinical governance is an important trigger to improve care quality and safety and rank high in the reform agenda of health systems. The senior management team culture plays a major role in establishing clinical governance practices, because it strongly influences the values, attitudes, and behaviors of the members of an organization. The aim of this study was to investigate the relationship between senior management team culture and clinical governance in the public health care organizations of three Italian regions. The assessment of senior management culture was conducted using the Competing Values Framework and a corresponding instrument adapted for the Italian context. Clinical governance was assessed using an ad hoc instrument focused on the senior management team's perception and attitude toward clinical governance. The survey achieved a 54% response rate. The results of four different models demonstrate that organizations characterized by different dominant cultures are associated with significant differences in attitudes toward clinical governance. In particular, on average, dominant cultures with a prevailing external focus are associated with a more positive attitude toward clinical governance. The selection and appointments of top managers should consider the style of leadership that is most apt to facilitate the growth of rational and developmental cultures. Furthermore, the training of top managers and leading doctors should reinforce leadership aptitude and approaches that are consistent with the desired organizational cultures.

Ethical problems in clinical psychopharmacology.

PubMed

Müller-Oerlinghausen, B

1978-10-01

The present article originates from some intriguing problems which the author, working as a clinical pharmacologist and psychiatrist, was faced with during clinical investigations. Practical difficulties appearing at first glance as of a rather methodological nature often reveal themselves as ethical questions. Investigation of psychotropic drugs in normal volunteers as well as in psychiatric patients is taken as a model to exemplify certain fundamental ethical aspects of medical research. It is emphasized that the "solution" of ethical problems cannot be achieved by referring to a given code of norms which themselves depend on certain historical circumstances, but rather by recognizing and reasoning the conflicts which result from various moral maxims. Clinical psychopharmacology should not only be conscious of its methodological shortcomings and future goals but also accept the justification of discussions about the ethical and legal questions involved in its dealings and take an active part in these debates. With regard to the relationship between patient and investigator, "solidarity" [23] instead of ongoing paternalism or legal formalism, appears to be a realistic goal. This is also true in the area of psychopharmacological research.

Active multimodal psychotherapy in children and adolescents with suicidality: description, evaluation and clinical profile.

PubMed

Högberg, Goran; Hällström, Tore

2008-07-01

The aim of this study was to describe and evaluate the clinical pattern of 14 youths with presenting suicidality, to describe an integrative treatment approach, and to estimate therapy effectiveness. Fourteen patients aged 10 to 18 years from a child and adolescent outpatient clinic in Stockholm were followed in a case series. The patients were treated with active multimodal psychotherapy. This consisted of mood charting by mood-maps, psycho-education, wellbeing practice and trauma resolution. Active techniques were psychodrama and body-mind focused techniques including eye movement desensitization and reprocessing. The patients were assessed before treatment, immediately after treatment and at 22 months post treatment with the Global Assessment of Functioning Scale. The clinical pattern of the group was observed. After treatment there was a significant change towards normality in the Global Assessment of Functioning scale both immediately post-treatment and at 22 months. A clinical pattern, post trauma suicidal reaction, was observed with a combination of suicidality, insomnia, bodily symptoms and disturbed mood regulation. We conclude that in the post trauma reaction suicidality might be a presenting symptom in young people. Despite the shortcomings of a case series the results of this study suggest that a mood-map-based multimodal treatment approach with active techniques might be of value in the treatment of children and youth with suicidality.

Clinical Investigation Program Annual Progress Report

DTIC Science & Technology

1989-09-30

initiatives for the study of relatedness of bacterial and HLA antigens as they influence autoimmune diseases. Microbiology Service - FY 89 An in-house...1030 87/103 0 Identification of Those at Risk for Osteoporotic Hip Fractures, by an Noninvasive Measurement (P) (PR)... 105 87/104 0 SWOG 8600 - A...233 82/302 0 The Evaluation of Recently Introduced, Commercially Available Clinical Microbiology Products for Possible

Active control: an investigation method for combustion instabilities

NASA Astrophysics Data System (ADS)

Poinsot, T.; Yip, B.; Veynante, D.; Trouvé, A.; Samaniego, J. M.; Candel, S.

1992-07-01

Closed-loop active control methods and their application to combustion instabilities are discussed. In these methods the instability development is impeded with a feedback control loop: the signal provided by a sensor monitoring the flame or pressure oscillations is processed and sent back to actuators mounted on the combustor or on the feeding system. Different active control systems tested on a non-premixed multiple-flame turbulent combustor are described. These systems can suppress all unstable plane modes of oscillation (i.e. low frequency modes). The active instability control (AIC) also constitutes an original and powerful technique for studies of mechanisms leading to instability or resulting from the instability. Two basic applications of this kind are described. In the first case the flame is initially controlled with AIC, the feedback loop is then switched off and the growth of the instability is analysed through high speed Schlieren cinematography and simultaneous sound pressure and reaction rate measurements. Three phases are identified during th growth of the oscillations: (1) a linear phase where acoustic waves induce a flapping motion of the flame sheets without interaction between sheets, (2) a modulation phase, where flame sheets interact randomly and (3) a nonlinear phase where the flame sheets are broken and a limit cycle is reached. In the second case we investigate different types of flame extinctions associated with combustion instability. It is shown that pressure oscillations may lead to partial or total extinctions. Extinctions occur in various forms but usually follow a rapid growth of pressure oscillations. The flame is extinguished during the modulation phase observed in the initiation experiments. In these studies devoted to transient instability phenomena, the control system constitutes a unique investigation tool because it is difficult to obtain the same information by other means. Implications for modelling and prediction of

Investigation on the Activity Activation and Cementitious Property of Coal Gangue with High Iron and Silica Contents

NASA Astrophysics Data System (ADS)

Wu, Hong; Li, Yu; Teng, Min; Yang, Yu

2017-11-01

The activity of coal gangue by thermal activation and composite activation technologies was investigated. The crystal composition, framework structure and morphology change were analyzed by XRD, FT-IR and SEM, respectively. The cementitious property of coal gangue was measured by strength test. The results showed that thermal activation decomposed kaolinite in coal gangue, and formed the metastable structure with a porous state, multiple internal broken bonds and large specific surface areas. Based on thermal activation, the added lime provided the alkaline environment, then this reduced the bond energy of reactant particles and the degree of crystallinity of quartz in coal gangue. The two activation methods could effectively improve the cementitious property of coal gangue based unburned bricks, and that the composite activation technology was superior performance.

Physical Activity of Nurse Clinical Practitioners and Managers.

PubMed

Jirathananuwat, Areeya; Pongpirul, Krit

2017-11-01

This study was aimed (1) to compare the level of physical activity (PA) between working and nonworking hours and (2) to compare the level of PA during working hours of nurse clinical practitioners (NCPs) with that of nurse managers (NMs). This cross-sectional survey was conducted at a Thai university hospital from October 2015 to March 2016. All randomly selected participants wore an activity tracker on their hip for 5 days, except during bathing and sleeping periods, to record step counts and time points. Of 884 nurses, 289 (142 NCPs and 147 NMs) were randomly selected. The average age was 35.87 years. They spent 9.76 and 6.01 hours on work and nonwork activities, respectively. Daily steps per hour were significantly lower during work than nonwork periods (P < .001). An NCP had significantly higher overall hourly PA (P = .002). The number of steps per hour during work period of NCP was significantly higher than that of NM even after adjusting for age, work experience, and body mass index (P = .034). NCP had higher overall PA than NM, which was partly contributed by work-related PA. Level of PA for a professional with variation of actual work hours should be measured on hourly basis.

Manifestations of Metacognitive Activity during the Collaborative Planning of Chemistry Practical Investigations

ERIC Educational Resources Information Center

Mathabathe, Kgadi Clarrie; Potgieter, Marietjie

2017-01-01

This paper elaborates a process followed to characterise manifestations of cognitive regulation during the collaborative planning of chemistry practical investigations. Metacognitive activity was defined as the demonstration of planning, monitoring, control and evaluation of cognitive activities by students while carrying out the chemistry task.…

Developing a primary dental care outreach (PDCO) course--part 1: practical issues and evaluation of clinical activity.

PubMed

Hind, V; Waterhouse, P J; Maguire, A; Tabari, D; Lloyd, J

2009-11-01

The primary dental care outreach (PDCO) course in Newcastle, UK commenced in September 2004 with dental undergraduates attending outreach clinics on a fortnightly rotation over a 2 year continuous placement. To evaluate the PDCO with respect to practical issues and clinical activity. Clinical activity data were collected using data sheets and Access software together with data on patient attendances and Structured Clinical Operative Tests (SCOTs). Comparative clinical data were collected from the same group of students in Child Dental Health (CDH) in the School of Dental Sciences. In 2004/2005, 1683 clinical procedures were undertaken in PDCO and 1362 in CDH. Of the treatment undertaken in PDCO, 37.1% was examination and treatment planning, 17.1% basic intracoronal restorations and 13.1% fissure sealing, the activity representative of day to day in general practice. Completion rates for the five piloted SCOTs in cross infection control, writing a prescription, writing a referral letter, taking a valid consent and taking a radiograph ranged from 74% to 97% in 2004/2006. The practical issues and challenges of delivering a new clinical course broadly related to induction of new PDCO staff, support of staff, establishing effective communication, timetabling logistics, delivery of clinical teaching and quality assurance. Once the practical issues and challenges of setting up a new clinical course have been overcome PDCO has a valuable role to play in preparing undergraduates for their future practising careers.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

PubMed

Coulter, Tanya I; Chandra, Anita; Bacon, Chris M; Babar, Judith; Curtis, James; Screaton, Nick; Goodlad, John R; Farmer, George; Steele, Cathal Laurence; Leahy, Timothy Ronan; Doffinger, Rainer; Baxendale, Helen; Bernatoniene, Jolanta; Edgar, J David M; Longhurst, Hilary J; Ehl, Stephan; Speckmann, Carsten; Grimbacher, Bodo; Sediva, Anna; Milota, Tomas; Faust, Saul N; Williams, Anthony P; Hayman, Grant; Kucuk, Zeynep Yesim; Hague, Rosie; French, Paul; Brooker, Richard; Forsyth, Peter; Herriot, Richard; Cancrini, Caterina; Palma, Paolo; Ariganello, Paola; Conlon, Niall; Feighery, Conleth; Gavin, Patrick J; Jones, Alison; Imai, Kohsuke; Ibrahim, Mohammad A A; Markelj, Gašper; Abinun, Mario; Rieux-Laucat, Frédéric; Latour, Sylvain; Pellier, Isabelle; Fischer, Alain; Touzot, Fabien; Casanova, Jean-Laurent; Durandy, Anne; Burns, Siobhan O; Savic, Sinisa; Kumararatne, D S; Moshous, Despina; Kracker, Sven; Vanhaesebroeck, Bart; Okkenhaug, Klaus; Picard, Capucine; Nejentsev, Sergey; Condliffe, Alison M; Cant, Andrew James

2017-02-01

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights

[Is the structure of surgical clinics in Germany changing? A current investigation into the structure of surgical clinics in the Federal Republic of Germany].

PubMed

Lob, G; Lob, T; Bauer, H; Niethard, F; Polonius, J; Siebert, H

2009-04-01

Medical developments have led to extensive specialization in the field of surgery. This has already been reflected for many years in altered structure and organization forms of surgical clinics. Indispensable quality standards, statutory general conditions, increasing competition in service providers and health insurance with transparency of the service procedure all intensify this trend. The aim of this investigation was, therefore, to determine how far this differentiation of service supply in the field of surgery is also reflected in the area and in surgical departments and clinics of basic and routine supply. To achieve this, all available published information on the structure and organization of surgical clinics in the Federal Republic of Germany was classified according to current departmentalization into "undivided" or general/visceral surgery facilities compared to orthopedic/trauma surgery departments.

[CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

PubMed

Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi

2016-04-01

T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

Experimental and analytical investigation of active loads control for aircraft landing gear

NASA Technical Reports Server (NTRS)

Morris, D. L.; Mcgehee, J. R.

1983-01-01

A series hydraulic, active loads control main landing gear from a light, twin-engine civil aircraft was investigated. Tests included landing impact and traversal of simulated runway roughness. It is shown that the active gear is feasible and very effective in reducing the force transmitted to the airframe. Preliminary validation of a multidegree of freedom active gear flexible airframe takeoff and landing analysis computer program, which may be used as a design tool for active gear systems, is accomplished by comparing experimental and computed data for the passive and active gears.

Pharmacological Activity and Clinical Use of PDRN

PubMed Central

Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

2017-01-01

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

An Investigation of Factors Influencing Nurses' Clinical Decision-Making Skills.

PubMed

Wu, Min; Yang, Jinqiu; Liu, Lingying; Ye, Benlan

2016-08-01

This study aims to investigate the influencing factors on nurses' clinical decision-making (CDM) skills. A cross-sectional nonexperimental research design was conducted in the medical, surgical, and emergency departments of two university hospitals, between May and June 2014. We used a quantile regression method to identify the influencing factors across different quantiles of the CDM skills distribution and compared the results with the corresponding ordinary least squares (OLS) estimates. Our findings revealed that nurses were best at the skills of managing oneself. Educational level, experience, and the total structural empowerment had significant positive impacts on nurses' CDM skills, while the nurse-patient relationship, patient care and interaction, formal empowerment, and information empowerment were negatively correlated with nurses' CDM skills. These variables explained no more than 30% of the variance in nurses' CDM skills and mainly explained the lower quantiles of nurses' CDM skills distribution. © The Author(s) 2016.

Investigation of photodynamic activity of water-soluble porphyrins in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Arsenyan, Flora H.; Gyulkhandanyan, Aram G.

2006-02-01

Photodynamic therapy (PDT) is the method of photosensitized tumor treatment. It is based on the photosensitizer (PS) selective accumulation in tumors, its subsequent activation under the light influence and oxygen active form formation that results in tumor destruction. Photodynamic action of some new water-soluble porphyrins was investigated in our laboratory. Dose-dependent effect of these porphyrins was shown on PC-12 murine pheochromocytoma cell line. The results revealed that the efficiency of the investigated porphyrins decreased in the following way: TOEPyP (meso-tetra-(4-N-oxyethylpyridyl)porphyrin) > Zn-TOEPyP > Ag-TOEPyP. It was shown that TOEPyP possessed nearly the same photodynamic activity (LD50) as well-known photosensitizer chlorin e6. These porphyrins have also demonstrated quite high photodynamic activity in vivo. The results were obtained in the experiments on white mice with engrafted C-180 (Croker's sarcoma). Antitumor activity of these porphyrins in the dark was 30-40%, whereas photodynamic activity was 45-60%.

LDEF meteoroid and debris special investigation group investigations and activities at the Johnson Space Center

NASA Technical Reports Server (NTRS)

See, Thomas H.; Warren, Jack L.; Zolensky, Michael E.; Sapp, Clyde A.; Bernhard, Ronald P.; Dardano, Claire B.

1995-01-01

Since the return of the Long Duration Exposure Facility (LDEF) in January, 1990, members of the Meteoroid and Debris Special Investigation Group (M&D SIG) at the Johnson Space Center (JSC) in Houston, Texas have been examining LDEF hardware in an effort to expand the knowledge base regarding the low-Earth orbit (LEO) particulate environment. In addition to the various investigative activities, JSC is also the location of the general Meteoroid & Debris database. This publicly accessible database contains information obtained from the various M&D SIG investigations, as well as limited data obtained by individual LDEF Principal Investigators. LDEF exposed approximately 130 m(exp 2) of surface area to the LEO particulate environment, approximately 15.4 m(exp 2) of which was occupied by structural frame components (i.e., longerons and intercoastals) of the spacecraft. The data reported here was obtained as a result of detailed scans of LDEF intercoastals, 68 of which reside at JSC. The limited amount of data presently available on the A0178 thermal control blankets was reported last year and will not be reiterated here. The data presented here are limited to measurements of crater diameters and their frequency of occurrence (i.e., flux).

LDEF meteoroid and debris special investigation group investigations and activities at the Johnson Space Center

NASA Astrophysics Data System (ADS)

See, Thomas H.; Warren, Jack L.; Zolensky, Michael E.; Sapp, Clyde A.; Bernhard, Ronald P.; Dardano, Claire B.

1995-02-01

Since the return of the Long Duration Exposure Facility (LDEF) in January, 1990, members of the Meteoroid and Debris Special Investigation Group (M&D SIG) at the Johnson Space Center (JSC) in Houston, Texas have been examining LDEF hardware in an effort to expand the knowledge base regarding the low-Earth orbit (LEO) particulate environment. In addition to the various investigative activities, JSC is also the location of the general Meteoroid & Debris database. This publicly accessible database contains information obtained from the various M&D SIG investigations, as well as limited data obtained by individual LDEF Principal Investigators. LDEF exposed approximately 130 m(exp 2) of surface area to the LEO particulate environment, approximately 15.4 m(exp 2) of which was occupied by structural frame components (i.e., longerons and intercoastals) of the spacecraft. The data reported here was obtained as a result of detailed scans of LDEF intercoastals, 68 of which reside at JSC. The limited amount of data presently available on the A0178 thermal control blankets was reported last year and will not be reiterated here. The data presented here are limited to measurements of crater diameters and their frequency of occurrence (i.e., flux).

The gap between available knowledge and its use in clinical psychiatry.

PubMed

Munk-Jørgensen, P; Blanner Kristiansen, C; Uwawke, R; Larsen, J I; Okkels, N; Christiansen, B; Hjorth, P

2015-12-01

The time span between knowledge becoming available and its integration into daily clinical routine is lengthy. This phenomenon is explored in this study. We used the outcomes of our activities for investigating and strengthening the research-based activities to improve physical health in the routines of clinical psychiatric wards as examples for our analyses. The time span between new knowledge becoming available and its implementation into general clinical treatment is very long. However, a shortening of this time span is seen through active leadership backup and clinical research experience among psychiatrists and staff in the wards. In particular, the involvement of medical students interested in clinical research activities seems to have a positive impact. Academia needs to be re-implemented into clinical psychiatry. Staff with research experience is needed in all professions to increase evidence-based practice. Leaders must take responsibility for implementing new knowledge into the routines of the department and must support staff in these activities on a daily basis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The EXCITE Trial: Predicting a Clinically Meaningful Motor Activity Log Outcome

PubMed Central

Park, Si-Woon; Wolf, Steven L.; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S.

2013-01-01

Background and Objective This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. Methods A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Results Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Conclusions Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT. PMID:18780883

The EXCITE Trial: Predicting a clinically meaningful motor activity log outcome.

PubMed

Park, Si-Woon; Wolf, Steven L; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S

2008-01-01

This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT.

Is daily routine important for sleep? An investigation of social rhythms in a clinical insomnia population.

PubMed

Moss, Taryn G; Carney, Colleen E; Haynes, Patricia; Harris, Andrea L

2015-02-01

Social rhythms, also known as daily routines (e.g. exercise, of school or work, recreation, social activities), have been identified as potential time cues to help to regulate the biological clock. Past research has shown links between regularity and healthy sleep. This study examined the regularity and frequency of daytime activities in a clinical insomnia population and a good sleeper comparison group. Participants (N = 69) prospectively monitored their sleep and daily activities for a 2-week period. Although participants with insomnia and good sleepers had similar levels of activity, relative to good sleepers, those with insomnia were less regular in their activities. Findings from this study add to the growing number of studies that highlight the relative importance of the regularity of daytime activities on sleep. Accordingly, future research should test treatment components that focus on regulating daytime activities, which would likely improve treatment outcomes.

Natural clinical tolerance to peanut in African patients is caused by poor allergenic activity of peanut IgE.

PubMed

Wollmann, E; Hamsten, C; Sibanda, E; Ochome, M; Focke-Tejkl, M; Asarnoj, A; Önell, A; Lilja, G; Gallerano, D; Lupinek, C; Thalhamer, T; Weiss, R; Thalhamer, J; Wickman, M; Valenta, R; van Hage, M

2015-06-01

In Africa, peanuts are frequently consumed, but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut-sensitized but asymptomatic patients from central Africa compared to peanut-allergic and peanut-sensitized but asymptomatic patients from Sweden. Sera from allergic patients (n = 54) from Zimbabwe sensitized to peanut but without allergic symptoms to peanut, and sera from peanut-allergic (n = 25) and peanut-sensitized but asymptomatic (n = 25) patients from Sweden were analyzed toward peanut allergen components (Ara h 1-3, 6, 8-9) and other allergen molecules from important allergen sources using microarray. IgE to Ara h 2 peptide epitopes was analyzed, and allergenic activity was assessed by basophil activation assay. Forty-six percent of the African and all peanut-allergic Swedish patients showed IgE toward one of the highly allergenic peanut allergens (Ara h 1-3, 6, 9). However, 48% of the African patients had IgE to cross-reactive carbohydrate determinants (CCDs) with low allergenic activity and 60% of the Swedish asymptomatic patients had IgE against the PR protein Ara h 8. IgG and IgG4 specificities and levels could not discriminate between the African asymptomatic and Swedish peanut-allergic patients. Asymptomatic patients almost lacked IgE to Ara h 2 peptides, which were recognized by peanut-allergic patients. Peanut IgE from peanut asymptomatic patients showed poor allergenic activity compared with IgE from peanut-allergic patients. Natural clinical tolerance to peanut in the African patients can be caused by IgE to low allergenic peanut components and by poor allergenic activity of peanut-specific IgE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

PubMed Central

Leite, Pauline M.; Gomes, Rodrigo S.; Figueiredo, Amanda B.; Serafim, Tiago D.; Tafuri, Wagner L.; de Souza, Carolina C.; Moura, Sandra A. L.; Fietto, Juliana L. R.; Melo, Maria N.; Ribeiro-Dias, Fátima; Oliveira, Milton A. P.; Rabello, Ana; Afonso, Luís C. C.

2012-01-01

Background Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. Methodology/Principal Findings Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. Conclusions/Significance Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important

Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages

PubMed Central

Idh, Jonna; Andersson, Blanka; Lerm, Maria; Raffetseder, Johanna; Eklund, Daniel; Woksepp, Hanna; Werngren, Jim; Mansjö, Mikael; Sundqvist, Tommy; Stendahl, Olle

2017-01-01

Background Drugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis. Method Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry. NO-dependent intracellular killing in a selection of strains was assessed in interferon gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L-NMMA. Results When M. tuberculosis H37Rv was compared to six clinical isolates and CDC1551, three isolates with inhA mediated INH resistance showed significantly reduced NO-susceptibility in broth culture. All strains showed a variable but dose-dependent susceptibility to RNS donors. Two clinical isolates with increased susceptibility to NO exposure in broth compared to H37Rv were significantly inhibited by activated macrophages whereas there was no effect on growth inhibition when activated macrophages were infected by clinical strains with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant clinical isolate showed increased resistance to PRT both in broth culture and the macrophage model compared to H37Rv in the absence of mutational resistance in genes associated to reduced susceptibility against PRT or NO. Conclusion In a limited number of clinical M. tuberculosis isolates we found a significant difference in susceptibility to NO between clinical isolates, both in broth cultures and in macrophages. Our results indicate that mycobacterial susceptibility to cellular host defence mechanisms such as NO need to be taken into consideration when designing new therapeutic strategies. PMID:28704501

Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder.

PubMed

Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

2017-01-01

Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief

In Vitro Antibacterial and Antibiofilm Activities of Chlorogenic Acid against Clinical Isolates of Stenotrophomonas maltophilia including the Trimethoprim/Sulfamethoxazole Resistant Strain

PubMed Central

Karunanidhi, Arunkumar; Thomas, Renjan; van Belkum, Alex; Neela, Vasanthakumari

2013-01-01

The in vitro antibacterial and antibiofilm activity of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia was investigated through disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill and biofilm assays. A total of 9 clinical S. maltophilia isolates including one isolate resistant to trimethoprim/sulfamethoxazole (TMP/SMX) were tested. The inhibition zone sizes for the isolates ranged from 17 to 29 mm, while the MIC and MBC values ranged from 8 to 16 μg mL−1 and 16 to 32 μg mL−1. Chlorogenic acid appeared to be strongly bactericidal at 4x MIC, with a 2-log reduction in viable bacteria at 10 h. In vitro antibiofilm testing showed a 4-fold reduction in biofilm viability at 4x MIC compared to 1x MIC values (0.085 < 0.397 A 490 nm) of chlorogenic acid. The data from this study support the notion that the chlorogenic acid has promising in vitro antibacterial and antibiofilm activities against S. maltophilia. PMID:23509719

Diagnosis and Treatment of Gastroenteropancreatic Neuroendocrine Tumors: Current Data on a Prospectively Collected, Retrospectively Analyzed Clinical Multicenter Investigation

PubMed Central

Niederle, Bruno

2011-01-01

Background. The aim of this prospectively collected, retrospectively analyzed clinical investigation was to describe “unmasked” clinical symptoms and methods of diagnosis, treatment, and short-term follow-up of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) diagnosed during 1 year in Austria. Methods. In total, 277 patients with GEP-NETs were documented. All tumors were immunhistochemically defined according to recently summarized criteria (World Health Organization, European Neuroendocrine Tumour Society). A standardized questionnaire comprising 50 clinical and biochemical parameters (clinical symptoms, mode of diagnosis, treatment, follow-up) was completed by attending physicians. Results. The most common initial symptoms were episodes of abdominal pain, diarrhea, weight loss, gastrointestinal bleeding, flushing, and bowel obstruction. Overall, 48.1% of tumors were diagnosed by endoscopy, 43.7% were diagnosed during surgery, 5% were diagnosed by fine-needle aspiration of the primary or metastases, and 2.5% were diagnosed during autopsy; 44.5% of tumors were not suspected clinically and were diagnosed incidentally during various surgical procedures. Overall, 18.7% of tumors were removed endoscopically and 67.6% were removed surgically; 13.7% of patients were followed without interventional treatment. Endoscopic or surgical intervention was curative in 81.4% of patients and palliative in 18.6% of patients. At the time of diagnosis, information on metastasis was available in 83.7% of patients with malignant NETs. Lymph node or distant metastases were documented in 74.7% of patients. In 19.3% of patients, 41 secondary tumors were documented, with 78.0% classified histologically as adenocarcinomas. Conclusion. This investigation summarizes the clinical presentation and current practice of management of GEP-NETs and thereby extends the understanding and clinical experience. PMID:21467149

Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.

PubMed Central

Johnson, Abdul-Wahab B. R.; Adedoyin, Olanrewaju T.; Abdul-Karim, Aishat A.; Olanrewaju, Abdul-Waheed I.

2007-01-01

The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID:17722674

Hemispheric Activation Differences in Novice and Expert Clinicians during Clinical Decision Making

ERIC Educational Resources Information Center

Hruska, Pam; Hecker, Kent G.; Coderre, Sylvain; McLaughlin, Kevin; Cortese, Filomeno; Doig, Christopher; Beran, Tanya; Wright, Bruce; Krigolson, Olav

2016-01-01

Clinical decision making requires knowledge, experience and analytical/non-analytical types of decision processes. As clinicians progress from novice to expert, research indicates decision-making becomes less reliant on foundational biomedical knowledge and more on previous experience. In this study, we investigated how knowledge and experience…

Exercise and physical activity in mental disorders: clinical and experimental evidence.

PubMed

Zschucke, Elisabeth; Gaudlitz, Katharina; Ströhle, Andreas

2013-01-01

Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

Clinical investigations of polymethylmethacrylate cement viscosity during vertebroplasty and related in vitro measurements

PubMed Central

Boger, A.; Schenk, B.; Heini, P. F.

2009-01-01

Percutaneous vertebroplasty, comprising an injection of polymethylmethacrylate (PMMA) into vertebral bodies, is a practical procedure for the stabilization of osteoporotic compression fractures as well as other weakening lesions. Cement leakage is considered to be one of the major and most severe complications during percutaneous vertebroplasty. The viscosity of the material plays a key role in this context. In order to enhance the safety for the patient, a rheometer system was developed to measure the cement viscosity intraoperatively. For this development, it is of great importance to know the proper viscosity to start the procedure determined by experienced surgeons and the relation between the time period when different injection devices are used and the cement viscosity. The purpose of the study was to investigate the viscosity ranges for different injection systems during conventional vertebroplasty. Clinically observed viscosity values and related time periods showed high scattering. In order to get a better understanding of the clinical observations, cement viscosity during hardening at different ambient temperatures and by simulation of the body temperature was investigated in vitro. It could be concluded, that the direct viscosity assessment with a rheometer during vertebroplasty can help clinicians to define a lower threshold viscosity and thereby decrease the risk of leakage and make adjustments to their injection technique in real time. Secondly, the acceleration in hardening of PMMA-based cements at body temperature can be useful in minimizing leakages by addressing them with a short injection break. PMID:19479285

ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

PubMed Central

Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

2012-01-01

The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

Antiplasmodial activity of flavonol quercetin and its analogues in Plasmodium falciparum: evidence from clinical isolates in Bangladesh and standardized parasite clones.

PubMed

Ganesh, Deepa; Fuehrer, Hans-Peter; Starzengrüber, Peter; Swoboda, Paul; Khan, Wasif Ali; Reismann, Johannes A B; Mueller, Milena S K; Chiba, Peter; Noedl, Harald

2012-06-01

Malaria is still a major threat in many parts of the world with resistance spreading to almost all classes of antimalarials. The limited arsenal of available antimalarial drugs emphasizes the urgent need for novel antimalarial compounds. Owing to the fact that novel leads from nature have traditionally played a pivotal role in the development of various classes of antimalarials, we investigated a set of eight naturally occurring dietary flavonoids and their analogues for their antiplasmodial activity on clinical field isolates in southeastern Bangladesh and culture-adapted chloroquine-sensitive and chloroquine-resistant parasite clones. Except for taxifolin, all the other flavonoids had 50% inhibitory concentrations below 14 μM, both in the field and laboratory-adapted parasites. Neither of the flavonoids showed any activity correlation with chloroquine. The quercetin analogue rutin (7.10 ± 10.32 μM) was the most active substance in field isolates as well as laboratory-adapted cultures (3.53 ± 13.34 μM in 3D7 and 10.38 ± 15.08 μM in K1), providing the first evidence of its activity against Plasmodium falciparum parasites. Thus, our results provide important evidence of the antimalarial activity of flavonoids in traditional use and thus warrant further investigation of these compounds as potential antiplasmodial agents.

Beyond Readability: Investigating Coherence of Clinical Text for Consumers

PubMed Central

Hetzel, Scott; Dalrymple, Prudence; Keselman, Alla

2011-01-01

Background A basic tenet of consumer health informatics is that understandable health resources empower the public. Text comprehension holds great promise for helping to characterize consumer problems in understanding health texts. The need for efficient ways to assess consumer-oriented health texts and the availability of computationally supported tools led us to explore the effect of various text characteristics on readers’ understanding of health texts, as well as to develop novel approaches to assessing these characteristics. Objective The goal of this study was to compare the impact of two different approaches to enhancing readability, and three interventions, on individuals’ comprehension of short, complex passages of health text. Methods Participants were 80 university staff, faculty, or students. Each participant was asked to “retell” the content of two health texts: one a clinical trial in the domain of diabetes mellitus, and the other typical Visit Notes. These texts were transformed for the intervention arms of the study. Two interventions provided terminology support via (1) standard dictionary or (2) contextualized vocabulary definitions. The third intervention provided coherence improvement. We assessed participants’ comprehension of the clinical texts through propositional analysis, an open-ended questionnaire, and analysis of the number of errors made. Results For the clinical trial text, the effect of text condition was not significant in any of the comparisons, suggesting no differences in recall, despite the varying levels of support (P = .84). For the Visit Note, however, the difference in the median total propositions recalled between the Coherent and the (Original + Dictionary) conditions was significant (P = .04). This suggests that participants in the Coherent condition recalled more of the original Visit Notes content than did participants in the Original and the Dictionary conditions combined. However, no difference was seen

Manifestations of metacognitive activity during the collaborative planning of chemistry practical investigations

NASA Astrophysics Data System (ADS)

Mathabathe, Kgadi Clarrie; Potgieter, Marietjie

2017-07-01

This paper elaborates a process followed to characterise manifestations of cognitive regulation during the collaborative planning of chemistry practical investigations. Metacognitive activity was defined as the demonstration of planning, monitoring, control and evaluation of cognitive activities by students while carrying out the chemistry task. Inherent in collaborative learning is the social aspect of metacognition, which in this study was evidenced in social cognitive regulation (notably of intra- and interpersonal metacognitive regulations) as groups of students went about planning their practical investigations. Discussions of two of the learning groups (n = 4; n = 3) as they planned the extended practical investigation were recorded, transcribed and analysed for indicators of any inherent metacognitive activity. The process of characterising the manifestations of metacognition resulted in the development of a coding system which specifies not only the regulatory strategies at play but the type of regulation (self or other), the area of regulation (cognition, task performance or behaviour) as well as the depth of regulatory contributions (high or low). The fine-grained coding system allowed for a finer theoretical elucidation of the social nature of metacognition. The implications of this study for metacognition and chemistry education research are highlighted.

Peering into the pharmaceutical "pipeline": investigational drugs, clinical trials, and industry priorities.

PubMed

Fisher, Jill A; Cottingham, Marci D; Kalbaugh, Corey A

2015-04-01

In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry's investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding--and often problematic--role of pharmaceuticals in society. To access the pharmaceutical industry's pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2477 different drugs in 4182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline was being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Keeping Clinicians in Clinical Research: The Clinical Research/Reproductive Scientist Training Program

PubMed Central

Armstrong, Alicia Y.; DeCherney, Alan; Leppert, Phyllis; Rebar, Robert; Maddox, Yvonne T.

2009-01-01

In recent years the need for translational and clinical research has increased while the number of physicians involved in clinical research has diminished. There is clearly a need for formalized academic training in the quantitative and methodological principles of clinical research in reproductive medicine. The Clinical Research/Reproductive Scientist Training Program (CREST), a program supported by the National Institute of Child Health and Human Development, the Clinical Research Training Program (CRTP) at Duke University, and the American Society for Reproductive Medicine,(ASRM) meets this existing need. In addition, this program is specifically designed for physicians in private or academic clinical practice in reproductive medicine. Innovative programs such as CREST encourage the practicing physician to engage in clinical research while maintaining an active role in clinical practice. Participants in the program receive didactic on-line training from the CRTP, attend intensive weekend seminars at the National Institutes of Health (NIH) and CREST seminars at the annual meeting of ASRM. Successful participants in the program receive a Certificate in Clinical Research from the CRTP. The program’s goal is to provide practicing physicians with the tools and research credentials that will facilitate collaborations with investigators involved in large clinical trials. PMID:19144332

Annual Research Progress Report Fiscal Year 1990. Volume 2. Department of Clinical Investigation (Brooke Army Medical Center)

DTIC Science & Technology

1990-10-01

outcome based on these tests. Fifty-one genotypes have been completed, and BCL - 2 appears to be significant. In addition, those patients who lack...INSTRUCTIONSREPOT DOUMENATIOPAGEBEFORE COMPLETING FORM. fREPORT 14UMBER 2 . GOVT ACCESSION NO, 3 REC1PIENt-S CATALOG NUMOCR RCS MED-300 ___________ I. ltLF...Whan Daa 3ntotod) Block 20. Abstract 2 conducted under the provisions of AR 40-38, Clinical Investigation Program; AR 40-7, Use of Investigational

Antiplasmodial activity of two medicinal plants against clinical isolates of Plasmodium falciparum and Plasmodium berghei infected mice.

PubMed

Attemene, Serge David Dago; Beourou, Sylvain; Tuo, Karim; Gnondjui, Albert Alloh; Konate, Abibatou; Toure, Andre Offianan; Kati-Coulibaly, Seraphin; Djaman, Joseph Alico

2018-03-01

Malaria is an infectious and deadly parasitic disease, associated with fever, anaemia and other ailments. Unfortunately the upsurge of plasmodium multidrug resistant constrained researchers to look for new effective drugs. Medicinal plants seem to be an unquenchable source of bioactive principles in the treatment of various diseases. The aim of this study was to assess the antiplasmodial activity of two Ivorian medicinal plants. The in vitro activity was evaluated against clinical isolates and Plasmodium falciparum K1 multidrug resistant strain using the fluorescence based SYBR green I assay. The in vivo bioassay was carried out using the classical 4 day suppressive and curative tests on Plasmodium berghei infected mice. Results showed that the in vitro bioassay of both plant extracts were found to exhibit a promising and moderate antiparasitic effects on clinical isolates (5 µg/mL < IC 50  < 15 µg/mL) and Plasmodium falciparum multidrug resistant K1 strain (15 µg/mL < IC 50  < 50 µg/mL). Furthermore, the in vivo antiplasmodial screening of both extracts showed a significant decrease in parasitemia, which was dose-dependent. Body temperature in mice treated with both extracts at experimental doses increased, compared to the negative control group and was dose-dependent. As for mice body weight a significant decrease ( p  < 0.001) was noticed in the negative control group compared to tested groups of animals. The hydroethanolic stem bark extract of Anthocleista djalonensis A Chev and leaves extract of Ziziphus mauritiana Lam exhibited anti-malarial activities. Therefore, the bioactive compounds of both plant extracts need to be investigated.

75 FR 57472 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0456... scientific, regulatory, and ethical considerations involved in the conduct of clinical trials. DATES: The... development of medical products. They bear the responsibility for ensuring the safe and ethical treatment of...

Genomic investigation of Staphylococcus aureus isolates from bulk tank milk and dairy cows with clinical mastitis.

PubMed

Ronco, Troels; Klaas, Ilka C; Stegger, Marc; Svennesen, Line; Astrup, Lærke B; Farre, Michael; Pedersen, Karl

2018-02-01

Staphylococcus aureus is one of the most common pathogens that cause mastitis in dairy cows. Various subtypes, virulence genes and mobile genetic elements have been associated with isolates from bulk tank milk and clinical mastitis. So far, no Danish cattle associated S. aureus isolates have been whole-genome sequenced and further analyzed. Thus, the main objective was to investigate the population structure and genomic content of isolates from bulk tank milk and clinical mastitis, using whole-genome sequencing. This may reveal the origin of strains that cause clinical mastitis. S. aureus isolates from bulk tank milk (n = 94) and clinical mastitis (n = 63) were collected from 91 and 24 different farms, respectively and whole-genome sequenced. The genomic content was analyzed and a phylogenetic tree based on single nucleotide polymorphisms was constructed. In general, the isolates from both bulk tank milk and clinical mastitis were of similar genetic background. This suggests that dairy cows are natural carriers of the S. aureus subtypes that cause clinical mastitis if the right conditions are present and that a broad range of subtypes cause mastitis. A phylogenetic cluster that mostly consisted of ST151 isolates carried three mobile genetic elements that were primarily found in this group. The prevalence of resistance genes was generally low. However, the first ST398 methicillin resistant S. aureus isolate from a Danish dairy cow with clinical mastitis was detected. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigation of Factors Affecting Body Temperature Changes During Routine Clinical Head Magnetic Resonance Imaging

PubMed Central

Kim, Myeong Seong

2016-01-01

Background Pulsed radiofrequency (RF) magnetic fields, required to produce magnetic resonance imaging (MRI) signals from tissue during the MRI procedure have been shown to heat tissues. Objectives To investigate the relationship between body temperature rise and the RF power deposited during routine clinical MRI procedures, and to determine the correlation between this effect and the body’s physiological response. Patients and Methods We investigated 69 patients from the Korean national cancer center to identify the main factors that contribute to an increase in body temperature (external factors and the body’s response) during a clinical brain MRI. A routine protocol sequence of MRI scans (1.5 T and 3.0 T) was performed. The patient’s tympanic temperature was recorded before and immediately after the MRI procedure and compared with changes in variables related to the body’s physiological response to heat. Results Our investigation of the physiological response to RF heating indicated a link between increasing age and body temperature. A higher increase in body temperature was observed in older patients after a 3.0-T MRI (r = 0.07, P = 0.29 for 1.5-T MRI; r = 0.45, P = 0.002 for 3.0-T MRI). The relationship between age and body heat was related to the heart rate (HR) and changes in HR during the MRI procedure; a higher RF power combined with a reduction in HR resulted in an increase in body temperature. Conclusion A higher magnetic field strength and a decrease in the HR resulted in an increase in body temperature during the MRI procedure. PMID:27895872

76 FR 45577 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-29

... course at the registration/ information Web site at https://www.trialstransformation.org/fda-clinical... be made at https://www.supportnlc.org/Room_Reservations.html or by calling 301-431-6400. FDA has... information, and a detailed description of the course can be found at https://www.trialstransformation.org/fda...

An investigation of the mimetic enzyme activity of two-dimensional Pd-based nanostructures

NASA Astrophysics Data System (ADS)

Wei, Jingping; Chen, Xiaolan; Shi, Saige; Mo, Shiguang; Zheng, Nanfeng

2015-11-01

In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis.In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis. Electronic supplementary information (ESI) available: TEM images, EDX and dispersion stability of Pd-based nanomaterials

[Activities of women's consultation clinics in prevention of unplanned pregnancy].

PubMed

Allenova, I A

1990-01-01

The data on women of reproductive age residing in the area serviced by an obstetrician-gynaecologist were provided; the proportion of women requiring the prevention of unintended pregnancy was determined, their socio-hygienic characteristics were established. The peculiarities in the activities of an obstetrician-gynaecologist in the field of preventing abortions and regulating women's reproductive functions were identified. On the basis of these data measures to improve the performance of women's consultation clinic in preventing the unintended pregnancy were determined.

[How good are clinical investigative procedures for diagnosing meniscus lesions?].

PubMed

Jerosch, J; Riemer, S

2004-06-01

The purpose of this study was to evaluate different clinical meniscus tests. During 13 months we evaluated 64 patients with a suspected meniscus lesion in a prospective study. The age ranged from 16 to 76 years (average: 38.5 years). 66 % were male patients. Between the clinical examination and the arthroscopy there was no additional trauma to the knee. All patients were clinically examined in a standard manner by two independent orthopaedic surgeons. Clinical findings of the menisci were documented according to 12 well-described and commonly used meniscus tests. The arthroscopy was performed by a single surgeon who was not aware of the results of the clinical examination. This surgeon documented the intraarticular findings in a standardized operating report. A meniscus lesion/degeneration was documented when this was evident either by inspection or by palpation. The results showed either clinical meniscus tests with a high specificity and a low sensitivity or tests with a high sensitivity, but only a low specificity. We were not able to identify meniscus tests which showed both a high sensitivity and a high specificity. Even with access to MRI the clinical findings in knee joint with injured menisci still have a high diagnostic value. However, it seems to be necessary to combine different tests.

Association between patterns of jaw motor activity during sleep and clinical signs and symptoms of sleep bruxism.

PubMed

Yoshida, Yuya; Suganuma, Takeshi; Takaba, Masayuki; Ono, Yasuhiro; Abe, Yuka; Yoshizawa, Shuichiro; Sakai, Takuro; Yoshizawa, Ayako; Nakamura, Hirotaka; Kawana, Fusae; Baba, Kazuyoshi

2017-08-01

The aim of this study was to investigate the association between patterns of jaw motor activity during sleep and clinical signs and symptoms of sleep bruxism. A total of 35 university students and staff members participated in this study after providing informed consent. All participants were divided into either a sleep bruxism group (n = 21) or a control group (n = 14), based on the following clinical diagnostic criteria: (1) reports of tooth-grinding sounds for at least two nights a week during the preceding 6 months by their sleep partner; (2) presence of tooth attrition with exposed dentin; (3) reports of morning masticatory muscle fatigue or tenderness; and (4) presence of masseter muscle hypertrophy. Video-polysomnography was performed in the sleep laboratory for two nights. Sleep bruxism episodes were measured using masseter electromyography, visually inspected and then categorized into phasic or tonic episodes. Phasic episodes were categorized further into episodes with or without grinding sounds as evaluated by audio signals. Sleep bruxism subjects with reported grinding sounds had a significantly higher total number of phasic episodes with grinding sounds than subjects without reported grinding sounds or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). Similarly, sleep bruxism subjects with tooth attrition exhibited significantly longer phasic burst durations than those without or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). Furthermore, sleep bruxism subjects with morning masticatory muscle fatigue or tenderness exhibited significantly longer tonic burst durations than those without or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). These results suggest that each clinical sign and symptom of sleep bruxism represents different aspects of jaw motor activity during sleep. © 2016 European Sleep Research Society.

Paffenbarger Physical Activity Questionnaire as an additional tool in clinical assessment of patients with coronary artery disease treated with angioplasty.

PubMed

Nowak, Zbigniew; Plewa, Michał; Skowron, Małgorzata; Markiewicz, Andrzej; Kucio, Cezary; Osiadło, Grazyna

2010-01-01

The association between frequency, intensity and duration of physical activity and the risk of cardiovascular disease has been investigated in several studies. Out of many methods used for assessment of physical activity, a questionnaire seems to be a simple and affordable method of assessing the risk of coronary artery disease (CAD). However, the number of clinical studies investigating the usefulness of physical activity questionnaires is limited. To analyse the usefulness of Paffenbarger Physical Activity Questionnaire (PPAQ) in assessment of the correlation between the magnitude of physical activity-related energy expenditure and physical capacity assessed with treadmill exercise test (ET), risk of early onset of major adverse cardiovascular events (MACE) and selected haemodynamic parameters in patients with CAD. The study group consisted of 211 patients aged 34-79 years (mean 59) with CAD, with or without previous myocardial infarction (MI). All patients were surveyed using PPAQ at the time of PCI and then 6 months later together with ET and echocardiography. There was a significant correlation between the value of activity-related weekly energy expenditure assessed with the PPAQ and selected parameters of ET (duration: r = 0.2966, p < 0.0001; METs: r = 0.2221, p < 0.001; VO(2)max: r = 0.3075, p < 0.0001; resting HR: r = 0.1615, p < 0.01 and maximal HR: r = -0.1475, p < 0.01) and echocardiography (LVESD r = 0.2346, p < 0.0001). After the PCI procedure, there was a considerable increase in physical capacity (ET duration: 5.82 vs. 7.48 min, p < 0.0001; MET: 7.57 vs. 9.18, p < 0.0001; VO(2)max: 29.23 vs. 34.79 ml, p < 0.0001; HRmax: 123 vs. 132 beats/min, p < 0.0001) and LV function (EF% 51.64 vs. 52.45%, p < 0.01). There was an insignificant change in total physical activity-related energy expenditure of low intensity (< 4 MET), not exceeding 2000 kcal/week (from 3120.13 to 3139.18 kcal/week, p > 0.05). Thirty-seven patients with MACE had a trend towards a lower

[Etiological, clinical and neuroradiological investigation of deaf children with additional neuropsychiatric disabilities].

PubMed

Chilosi, A M; Scusa, M F; Comparini, A; Genovese, E; Forli, F; Berrettini, S; Cipriani, P

2012-04-01

Sensorineural hearing loss (SNHL) is complicated by additional disabilities in about 30% of cases, but the epidemiology of associated disorders, in terms of type, frequency and aetiology is still not clearly defined. Additional disabilities in a deaf child have important consequences in assessing and choosing a therapeutic treatment, in particular when considering cochlear implantation (CI) or hearing aids (HA). The aim of this paper was to evaluate frequency, type and severity of additional neurodevelopmental disabilities in children with profound bilateral sensorineural hearing loss and to investigate the relationship between disability and the etiology of deafness. Eighty children with profound bilateral sensorineural hearing loss (mean age 5.4 years) were investigated by means of a diagnostic protocol including clinical, neurodevelopmental, and audiological procedures together with genetic and neurometabolic tests and neuroradiological investigation by brain MRI. Fifty-five percent of the sample exhibited one or more disabilities in addition to deafness, with cognitive, behavioural-emotional and motor disorders being the most frequent. The risk of additional disabilities varied according to aetiology, with a higher incidence in hereditary syndromic deafness, in cases due to pre-perinatal pathology (in comparison to unknown and hereditary non syndromic forms) and in the presence of major brain abnormalities at MRI. Our results suggest that the aetiology of deafness may be a significant risk indicator for the presence of neuropsychiatric disorders. A multidimensional evaluation, including aetiological, neurodevelopmental and MRI investigation is needed for formulating prognosis and for planning therapeutic intervention, especially in those children candidated to cochlear implant.

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

PubMed

Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

What prevents youth at clinical high risk for psychosis from engaging in physical activity? An examination of the barriers to physical activity.

PubMed

Newberry, Raeana E; Dean, Derek J; Sayyah, Madison D; Mittal, Vijay A

2018-06-13

Exercise has increasingly been proposed as a healthful intervention prior to and after the onset of psychosis. There is some evidence to suggest that youth at clinical high risk (CHR) for psychosis are less physically active and report more barriers to engaging in exercise; however, there has been relatively limited empirical work documenting this phenomenon, and to date, relationships between physical activity, barriers, and clinical phenomenology have been unclear. CHR (N = 51) and healthy control (N = 37) participants completed a structured clinical interview assessing attenuated psychotic symptoms and substance use, and an exercise survey that assessed current exercise practices, perceived physical fitness, and barriers related to engaging in exercise. CHR youth engaged in less physical activity, exhibited lower perception of fitness, and endorsed more barriers related to motivation for exercise. The CHR group showed significant negative correlations where lower perceptions of fitness were associated with increased negative, disorganized, and general symptoms. Decreased frequency of activity was related to more barriers of motivation. Interestingly, greater symptomatology in the CHR group was associated with more barriers of self-perception and motivation for engaging in exercise. However, findings suggested a nuanced relationship in this area; for example, increased physical activity was associated with increased substance use. The results of the current study support the notion that sedentary behavior is common in CHR youth, and more broadly, provide an impetus to target motivation through supervised exercise and fitness tracking to promote the health and well-being of CHR individuals. Copyright © 2018. Published by Elsevier B.V.

Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies.

PubMed

Anfinsen, Kristin P; Berghoff, Nora; Priestnall, Simon L; Suchodolski, Jan S; Steiner, Jörg M; Allenspach, Karin

2014-12-21

This study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography-mass spectrometry. There was no correlation between the CCECAI and faecal or urinary NMH concentrations, mast cell numbers, or histopathological score - or between faecal or urinary NMH concentration and mast cell numbers. Post hoc analysis revealed a statistically significant difference in toluidine blue positive mast cells between two treatment groups (exclusion diet with/without metronidazole versus immunosuppression (IS)), with higher numbers among dogs not requiring IS. Faecal and urinary NMH concentrations and duodenal mast cell numbers were not useful indicators of severity of disease as assessed by the CCECAI or histological evaluation. The number of duodenal mast cells was higher in dogs that did not need IS, i.e. in dogs responding to an exclusion diet (with/without metronidazole), than in dogs requiring IS. Further studies comparing the role of mast cells in dogs with different forms of CE are needed.

Dental hygiene work in a clinical trial.

PubMed

Luís, H S; Morgado, I; Assunção, V; Bernardo, M F; Leroux, B; Martin, M D; DeRouen, T A; Leitão, J

2008-08-01

Dental hygiene activities were developed as part of a randomized clinical trial designed to assess the safety of low-level mercury exposure from dental amalgam restorations. Along with dental-hygiene clinical work, a community programme was implemented after investigators noticed the poor oral hygiene habits of participants, and the need for urgent action to minimize oral health problems in the study population. Clinical and community activity goal was to promote oral health and prevent new disease. Community activities involved participants and their fellow students and were aimed at providing education on oral health in a school environment. Dental hygienists developed clinical work with prophylaxis, sealants application and topical fluoride and implemented the community programme with in-class sessions on oral health themes. Twice a month fluoride mouthrinses and bi-annual tooth brushing instructional activity took place. Participation at dental-hygiene activities, sealed teeth with no need of restoration and dental-plaque-index were measures used to evaluate success of the programme for the participants. Improvement in dental hygiene is shown by the decrease in dental plaque index scores (P < 0.0001); also sealants integrity is achieved in 86.3% of teeth. 888 (13.7%) teeth with sealants had to be restored or were lost. Children participated actively on dental hygiene activities. Teachers became aware of the problem and included oral-health in school curricula. Dental hygiene activities have shown to be helpful to promote dental hygiene, promote oral health and to provide school-age children with education on habits that will be important for their future good health.

[Antibacterial activity of rare Streptomyces species against clinical resistant bacteria].

PubMed

Boughachiche, Faiza; Reghioua, Sihem; Zerizer, Habiba; Boulahrouf, Abderrahmane

2012-01-01

In the search for new antibiotics from Steptomyces, investigating extremes habitats enhances the probability of isolating novel producers. In this context, the antibacterial activity of four Streptomyces strains isolated from Ezzmoul saltpans was studied. Two of them showed antibacterial activity against antibiotic's resistant bacteria (Bacillus cereus: β-lactamines and sulfamides resistant, Streptococcus faecalis: penicillin, tetracycline and cotrimoxazole resistant, and Staphylococcus aureus Mu 50: vancomycine resistant). The most active Streptomyces strain produces one type of polar bioactive molecules that resists to temperature variation and light exposition. Its activity appears in the first culture day and reaches its maximal value in the fourth day. The second strain presents themoresistant activity that reaches its maximal value in the first culture day. It produces two types of bioactive molecules, one is polar and the second is non polar (according to thin layer chromatography technique results).

Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

ERIC Educational Resources Information Center

Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

2011-01-01

Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. II. Features of and lessons from the follow-up investigations].

PubMed

Jermendy, György

2018-04-01

Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615-619.

Mapping South African allied health primary care clinical guideline activity: establishing a stakeholder reference sample.

PubMed

Dizon, Janine Margarita; Grimmer, Karen; Machingaidze, Shingai; McLaren, Pam; Louw, Quinette

2016-10-10

Little is known about allied health (AH) clinical practice guideline (CPG) activity in South Africa, and particularly in relation to primary health care (PHC). This paper reports on a scoping study undertaken to establish a reference framework, from which a comprehensive maximum variation sample could be selected. This was required to underpin robust sampling for a qualitative study aimed at understanding South African primary care AH therapy CPG activities. This paper builds on findings from the South African Guidelines Evaluation (Project SAGE) Flagship grant. South African government websites were searched for structures of departments and portfolios, and available CPGs. Professional AH association websites were searched for CPGs, purposively-identified key informants were interviewed, and CPGs previously identified for priority South African primary care conditions were critiqued for AH therapy involvement. Key informants described potentially complex relationships between players who may be engaged in South African AH CPGs, in both public and private sectors. There were disability/rehabilitation portfolios at national and provincial governments, but no uniformity in provincial government organisation of, or support for, PHC AH services. There were no AH primary care therapy CPGs on government websites, although there was 'clinical guidance' in various forms on professional association websites. Only two CPGs of priority South African PHC conditions included mention of any AH therapy (physiotherapy for adult asthma and chronic obstructive pulmonary disease). A comprehensive and wide-reaching stakeholder reference framework would be required in order to capture the heterogeneity of AH primary care CPG activity in South Africa. This should involve the voices of national and purposively-selected provincial governments, academic institutions, consultants, public sector managers and clinicians, private practitioners, professional associations, and private sector

A study of active learning methods for named entity recognition in clinical text.

PubMed

Chen, Yukun; Lasko, Thomas A; Mei, Qiaozhu; Denny, Joshua C; Xu, Hua

2015-12-01

Named entity recognition (NER), a sequential labeling task, is one of the fundamental tasks for building clinical natural language processing (NLP) systems. Machine learning (ML) based approaches can achieve good performance, but they often require large amounts of annotated samples, which are expensive to build due to the requirement of domain experts in annotation. Active learning (AL), a sample selection approach integrated with supervised ML, aims to minimize the annotation cost while maximizing the performance of ML-based models. In this study, our goal was to develop and evaluate both existing and new AL methods for a clinical NER task to identify concepts of medical problems, treatments, and lab tests from the clinical notes. Using the annotated NER corpus from the 2010 i2b2/VA NLP challenge that contained 349 clinical documents with 20,423 unique sentences, we simulated AL experiments using a number of existing and novel algorithms in three different categories including uncertainty-based, diversity-based, and baseline sampling strategies. They were compared with the passive learning that uses random sampling. Learning curves that plot performance of the NER model against the estimated annotation cost (based on number of sentences or words in the training set) were generated to evaluate different active learning and the passive learning methods and the area under the learning curve (ALC) score was computed. Based on the learning curves of F-measure vs. number of sentences, uncertainty sampling algorithms outperformed all other methods in ALC. Most diversity-based methods also performed better than random sampling in ALC. To achieve an F-measure of 0.80, the best method based on uncertainty sampling could save 66% annotations in sentences, as compared to random sampling. For the learning curves of F-measure vs. number of words, uncertainty sampling methods again outperformed all other methods in ALC. To achieve 0.80 in F-measure, in comparison to random

Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

PubMed

Whop, Lisa J; Baade, Peter D; Brotherton, Julia Ml; Canfell, Karen; Cunningham, Joan; Gertig, Dorota; Lokuge, Kamalini; Garvey, Gail; Moore, Suzanne P; Diaz, Abbey; O'Connell, Dianne L; Valery, Patricia; Roder, David M; Condon, John R

2017-02-06

To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear. Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010. Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months. The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up. Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

Investigation of PVdF active diaphragms for synthetic jets

NASA Astrophysics Data System (ADS)

Bailo, Kelly C.; Brei, Diann E.; Calkins, Frederick T.

2000-06-01

Current research has shown that aircraft can gain significant aerodynamic performance benefits by employing active flow control (AFC). One of the enabling technologies of AFC is the synthetic jet. Synthetic jets, also known as zero-net-mass flux actuators, act as bi-directional pumps injecting high momentum air into the local aerodynamic flow. Previous work has concentrated on high frequency synthetic jets based on piezoelectric active diaphragms such as Thunder actuators. Low frequency synthetic jets present a unique challenge requiring large displacements, which current technology has difficulty meeting. Boeing is investigating novel shaped low frequency synthetic jets that can modify the flow over fixed aircraft wings. This paper present the initial study of two promising active diaphragm concepts: a crescent shape and an opposing bender shape. These active diaphragms were numerically modeled utilizing the general-purpose finite element code ABAQUS. Using the ABAQUS results, the dynamic volume change within each jet was calculated and incorporated into an analytical linear Bernoulli model to predict the velocities and pressures at the nozzle. Simulations were performed to determine trends to assist in selection of prototype configurations. Prototypes of both diaphragm concepts were constructed from polyvinylidene fluoride and experimentally tested at Boeing with promising results.

In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

PubMed Central

Golparian, Daniel; Fernandes, Prabhavathi; Ohnishi, Makoto; Jensen, Jörgen S.

2012-01-01

Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea. PMID:22354296

Experimental Investigation on Minimum Frame Rate Requirements of High-Speed Videoendoscopy for Clinical Voice Assessment

PubMed Central

Deliyski, Dimitar D; Powell, Maria EG; Zacharias, Stephanie RC; Gerlach, Terri Treman; de Alarcon, Alessandro

2015-01-01

This study investigated the impact of high-speed videoendoscopy (HSV) frame rates on the assessment of nine clinically-relevant vocal-fold vibratory features. Fourteen adult patients with voice disorder and 14 adult normal controls were recorded using monochromatic rigid HSV at a rate of 16000 frames per second (fps) and spatial resolution of 639×639 pixels. The 16000-fps data were downsampled to 16 other rate denominations. Using paired comparisons design, nine common clinical vibratory features were visually compared between the downsampled and the original images. Three raters reported the thresholds at which: (1) a detectable difference between the two videos was first noticed, and (2) differences between the two videos would result in a change of clinical rating. Results indicated that glottal edge, mucosal wave magnitude and extent, aperiodicity, contact and loss of contact of the vocal folds were the vibratory features most sensitive to frame rate. Of these vibratory features, the glottal edge was selected for further analysis, due to its higher rating reliability, universal prevalence and consistent definition. Rates of 8000 fps were found to be free from visually-perceivable feature degradation, and for rates of 5333 fps, degradation was minimal. For rates of 4000 fps and higher, clinical assessments of glottal edge were not affected. Rates of 2000 fps changed the clinical ratings in over 16% of the samples, which could lead to inaccurate functional assessment. PMID:28989342

Clinical applications of bioactive milk components

PubMed Central

Newburg, David S.

2015-01-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications. PMID:26011900

Clinical applications of bioactive milk components.

PubMed

Hill, David R; Newburg, David S

2015-07-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.

Investigation of Participation Motivations in Exercises of Students Participating in Archery in Extra Curricular Activities

ERIC Educational Resources Information Center

Gündüz, Nevin; Keskin, Muzaffer Toprak; Erdugan, Fuat

2017-01-01

The aim of this research is to investigate Investigation of Participation Motivations in Exercises of Students Participating in Archery in Extra Curricular Activities. While the study's universe consists of all 11th graders studying at High school, the sample includes 32 of the 11th grade students who participated in arrow shooting activities in…

Ocimum basilicum: Antibacterial activity and association study with antibiotics against bacteria of clinical importance.

PubMed

Araújo Silva, Viviane; Pereira da Sousa, Janiere; de Luna Freire Pessôa, Hilzeth; Fernanda Ramos de Freitas, Andrea; Douglas Melo Coutinho, Henrique; Beuttenmuller Nogueira Alves, Larissa; Oliveira Lima, Edeltrudes

2016-01-01

Ocimum basilicum L. (Lamiaceae), popularly known as basil, is part of a group of medicinal plants widely used in cooking and known for its beneficial health properties, possessing significant antioxidant effects, antinociceptive, and others. The objective of this study is to determine the pharmacological effects produced on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa when standard antibiotics and O. basilicum essential oil are combined. The extraction of O. basilicum (leaves) components was done by steam distillation. The Minimum inhibitory concentration (MIC) was calculated using microdilution technique, where the oil concentrations varied from 2 to 1024 μg/mL. The combinations of O. basilicum oil with ciprofloxacin or imipenem were analyzed by the checkerboard method where fractional inhibitory concentration (FIC) indices were calculated. Ocimum basilicum essential oil, imipenem, and ciprofloxacin showed respective MIC antibacterial activities of 1024, 4, and 2 μg/mL, against S. aureus. In S. aureus, the oil with imipenem association showed synergistic effect (FIC = 0.0625), while the oil with ciprofloxacin showed antagonism (FIC value = 4.25). In P. aeruginosa, the imipenem/oil association showed additive effect for ATCC strains, and synergism for the clinical strain (FIC values = 0.75 and 0.0625). The association of O. basilicum essential oil with ciprofloxacin showed synergism for clinical strains (FIC value = 0.09). Ocimum basilicum essential oil associated with existing standard antibiotics may increase their antibacterial activity, resulting in a synergistic activity against bacterial strains of clinical importance. The antibacterial activity of O. basilicum essential oil may be associated with linalool.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

PubMed

Garay, Hilda; Espinosa, Luis Ariel; Perera, Yasser; Sánchez, Aniel; Diago, David; Perea, Silvio E; Besada, Vladimir; Reyes, Osvaldo; González, Luis Javier

2018-04-20

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met 17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

Active hydrothermal and non-active massive sulfide mound investigation using a new multiparameter chemical sensor

NASA Astrophysics Data System (ADS)

Han, C.; Wu, G.; Qin, H.; Wang, Z.

2012-12-01

Investigation of active hydrothermal mound as well as non-active massive sulfide mound are studied recently. However, there is still lack of in-situ detection method for the non-active massive sulfide mound. Even though Transient ElectroMagnetic (TEM) and Electric Self-potential (SP) methods are good, they both are labour, time and money cost work. We proposed a new multiparameter chemical sensor method to study the seafloor active hydrothermal mound as well as non-active massive sulfide mound. This sensor integrates Eh, S2- ions concentration and pH electrochemical electrodes together, and could found chemical change caused by the active hydrothermal vent, even weak chemical abnormalities by non-active massive sulfide hydrothermal mound which MARP and CTD sometimes cannot detect. In 2012, the 1st Leg of the Chinese 26th cruise, the multiparameter chemical sensor was carried out with the deepsea camera system over the Carlsberg Ridge in Indian Ocean by R/V DAYANGYIHAO. It was shown small Eh and S2- ions concentration abnormal around a site at Northwest Indian ridge. This site was also evidenced by the TV grab. In the 2nd Leg of the same cruise in June, this chemical sensor was carried out with TEM and SP survey system. The chemical abnormalities are matched very well with both TEM and SP survey results. The results show that the multiparameter chemical sensor method not only can detect active hydrothermal mound, but also can find the non-active massive sulfide hydrothermal mound.

Supporting Placement Supervision in Clinical Exercise Physiology

ERIC Educational Resources Information Center

Sealey, Rebecca M.; Raymond, Jacqueline; Groeller, Herb; Rooney, Kieron; Crabb, Meagan; Watt, Kerrianne

2015-01-01

The continued engagement of the professional workforce as supervisors is critical for the sustainability and growth of work-integrated learning activities in university degrees. This study investigated factors that influence the willingness and ability of clinicians to continue to supervise clinical exercise physiology work-integrated learning…

Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.

PubMed

Park, Sunhee; Abdi, Tsion; Gentry, Mark; Laine, Loren

2016-12-01

Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission. Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present. Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission

Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between self-rated clinimetric evaluation and clinical evaluation with activity indexes: DAS28, CDAI and SDAI.

PubMed

Horta-Baas, Gabriel; Pérez Bolde-Hernández, Arturo; Hernández-Cabrera, María Fernanda; Vergara-Sánchez, Imelda; Romero-Figueroa, María Del Socorro

2017-10-11

To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Electronic dental record use and clinical information management patterns among practitioner-investigators in The Dental Practice-Based Research Network

PubMed Central

Schleyer, Titus; Song, Mei; Gilbert, Gregg H.; Rindal, D. Brad; Fellows, Jeffrey L.; Gordan, Valeria V.; Funkhouser, Ellen

2012-01-01

Objectives Determine the: (1) extent of computer use for managing clinical information among practitioner-investigators in The Dental Practice-Based Research Network (DPBRN); (2) type of patient information kept electronically; and (3) willingness to reuse electronic dental record (EDR) data for research. Methods Web-based survey of 991 U.S. and Scandinavian practitioner-investigators. Results 729 (74%) practitioner-investigators responded. Seventy-four percent of US solo and 78.7% of group practitioners used a computer to manage clinical information, and 14.3% and 15.9%, respectively, were paperless. U.S. practitioners stored appointments, treatment plans, completed treatment and images most often electronically, and the periodontal chart, diagnoses, medical history, progress notes and chief complaint least often. Over 90% of Scandinavian practitioners stored all information electronically. Fifty-one percent of all respondents were willing to re-use EDR data for research and 63% preferred electronic forms for data collection. Conclusion The results of this study demonstrate that the trend towards increased adoption of EDRs in the US is continuing, potentially making more data in electronic form available for research. Respondents appear to be willing to reuse EDR data for research and collect data electronically. Clinical implications The rising adoption of EDRs may offer increased opportunities for reusing electronic data for quality assurance and research. PMID:23283926

Review of Maxillary Expansion Appliance Activation Methods: Engineering and Clinical Perspectives

PubMed Central

Romanyk, D. L.; Lagravere, M. O.; Toogood, R. W.; Major, P. W.; Carey, J. P.

2010-01-01

Objective. Review the reported activation methods of maxillary expansion devices for midpalatal suture separation from an engineering perspective and suggest areas of improvement. Materials and Methods. A literature search of Scopus and PubMed was used to determine current expansion methods. A U.S. and Canadian patent database search was also conducted using patent classification and keywords. Any paper presenting a new method of expansion was included. Results. Expansion methods in use, or patented, can be classified as either a screw- or spring-type, magnetic, or shape memory alloy expansion appliance. Conclusions. Each activation method presented unique advantages and disadvantages from both clinical and engineering perspectives. Areas for improvement still remain and are identified in the paper. PMID:20948570

Direct-detection EPID dosimetry: investigation of a potential clinical configuration for IMRT verification.

PubMed

Vial, Philip; Gustafsson, Helen; Oliver, Lyn; Baldock, Clive; Greer, Peter B

2009-12-07

The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with d(max) solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with d(max) solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery.

76 FR 53683 - Draft Guidance for Industry on Oversight of Clinical Investigations: A Risk-Based Approach to...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-29

... risk-based approach to the oversight of clinical investigations. It does not create or confer any... a range of approaches to monitoring. FDA currently has OMB approval for the information collection... Interested persons may submit to the Division of Dockets Management (see ADDRESSES) either electronic or...

Development and use of active clinical decision support for preemptive pharmacogenomics

PubMed Central

Bell, Gillian C; Crews, Kristine R; Wilkinson, Mark R; Haidar, Cyrine E; Hicks, J Kevin; Baker, Donald K; Kornegay, Nancy M; Yang, Wenjian; Cross, Shane J; Howard, Scott C; Freimuth, Robert R; Evans, William E; Broeckel, Ulrich; Relling, Mary V; Hoffman, James M

2014-01-01

Background Active clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care. Objective We describe the development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively. Materials and methods Clinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed. Problem list entries created for high-risk phenotypes provide an unambiguous trigger for delivery of post-test alerts to clinicians when high-risk drugs are prescribed. In addition, pre-test alerts are issued if a very-high risk medication is prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test result being entered into the EHR. Our CDS can be readily modified to incorporate new genes or high-risk drugs as they emerge. Results Through November 2012, 35 customized pharmacogenetic rules have been implemented, including rules for TPMT with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine, tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and November 2012, the pre-test alerts were electronically issued 1106 times (76 for thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert outcomes revealed that the interruptive CDS appropriately guided prescribing in 95% of patients for whom they were issued. Conclusions Our experience illustrates the feasibility of developing computational systems that provide clinicians with actionable alerts for gene-based drug prescribing at the point of care. PMID:23978487

Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling.

PubMed

Ding, Xuan; He, Minxia; Kulkarni, Rajesh; Patel, Nita; Zhang, Xiaoyu

2013-08-01

Identifying the source of inter- and/or intrasubject variability in pharmacokinetics (PK) provides fundamental information in understanding the pharmacokinetics-pharmacodynamics relationship of a drug and project its efficacy and safety in clinical populations. This identification process can be challenging given that a large number of potential causes could lead to PK variability. Here we present an integrated approach of physiologically based absorption modeling to investigate the root cause of unexpectedly high PK variability of a Phase I clinical trial drug. LY2196044 exhibited high intersubject variability in the absorption phase of plasma concentration-time profiles in humans. This could not be explained by in vitro measurements of drug properties and excellent bioavailability with low variability observed in preclinical species. GastroPlus™ modeling suggested that the compound's optimal solubility and permeability characteristics would enable rapid and complete absorption in preclinical species and in humans. However, simulations of human plasma concentration-time profiles indicated that despite sufficient solubility and rapid dissolution of LY2196044 in humans, permeability and/or transit in the gastrointestinal (GI) tract may have been negatively affected. It was concluded that clinical PK variability was potentially due to the drug's antagonism on opioid receptors that affected its transit and absorption in the GI tract. Copyright © 2013 Wiley Periodicals, Inc.

Phenotypic characterization of enzymatic activity of clinical dermatophyte isolates from animals with and without skin lesions and humans.

PubMed

Gnat, Sebastian; Łagowski, Dominik; Nowakiewicz, Aneta; Zięba, Przemysław

2018-05-20

The pathogenesis of dermatophytoses is associated with the secretion of enzymes degrading the infected tissue components. Although many studies on enzymatic activity of dermatophytes have been conducted over the years, there have been no concrete proposals on construction of the profile of enzymes characteristic of individual species, genus, or ecological types of dermatophytes. The aim of this study was to assess the capability of clinical dermatophyte isolates from both symptomatic and asymptomatic animals and humans to produce different enzymes. Clinical isolates of 234 dermatophyte strains collected during routine examination of animal health were used in this study. The enzymatic production of keratinase, elastase, phospholipase, lipase, protease, DNase, and gelatinase as well as the haemolytic activity were evaluated using specific test media. The overall degree of enzymatic activity of the analysed clinical isolates of the dermatophytes was 67%. All tested clinical isolates of different species of dermatophytes showed keratinase activity and 96% additionally exhibited phospholipase activity. The weakest activity among the tested enzymes was demonstrated for elastase and gelatinase. 83% of the isolates of the dermatophytes showed haemolytic activity. Our data indicate that clinical isolates of dermatophytes from different species produce enzymes with different levels of activities. Profile of enzymes characteristic of individual species, genus, or ecological types of dermatophytes is possibly dependent upon factors related to the host. The relationship between each enzyme and the occurrence of skin lesions in animals and humans or asymptomatic animal carriers varies on whether the infection is caused by T. mentagrophytes, T. verrucosum, or M. canis. Interestingly, only keratinase seems to be correlated with the appearance of dermatophyte infections, irrespective of the pathogen species, and elastase is a characteristic enzyme for dermatophyte strains

Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists' Clinical Activities and Team Members' Satisfaction.

PubMed

McDaniel, Joshua; Bass, Lynn; Pate, Toni; DeValve, Michael; Miller, Susan

2017-09-01

Background: National professional organizations have recognized pharmacists as essential members of the intensive care unit (ICU) team. Critical care pharmacists' clinical activities have been categorized as fundamental, desirable, and optimal, providing a structure for gauging ICU pharmacy services being provided. Objective: To determine the impact the addition of a second ICU pharmacist covering 30 adult ICU beds at a large regional medical center has on the complexity of pharmacists' interventions, the types of clinical activities performed by the pharmacists, and the ICU team members' satisfaction. Methods: A prospective mixed-method descriptive study was conducted. Pharmacists recorded their interventions and clinical activities performed. A focus group composed of randomly selected ICU team members was held to qualitatively describe the impact of the additional pharmacist coverage on patient care, team dynamics, and pharmacy services provided. Results: The baseline period consisted of 33 days, and the intervention period consisted of 20 days. The average complexity of interventions was 1.72 during the baseline period (mode = 2) versus 1.69 (mode = 2) during the intervention period. The number of desirable and optimal clinical activities performed daily increased during the intervention from 8.4 (n = 279) to 16.4 (n = 328) and 2.3 (n = 75) to 8.6 (n = 171) compared with the baseline, respectively. Focus group members qualitatively described additional pharmacist coverage as beneficial. Conclusion: The additional critical care pharmacist did not increase pharmacy intervention complexity; however, more interventions were performed per day. Additional pharmacist coverage increased the daily number of desirable and optimal clinical activities performed and positively impacted ICU team members' satisfaction.

Electrophysiological activity is associated with vulnerability of Internet addiction in non-clinical population.

PubMed

Wang, Grace Y; Griskova-Bulanova, Inga

2018-09-01

This study investigated the electrophysiological activity associated with vulnerability of problematic Internet use in non-clinical population. The resting EEG spectrum of alpha (8-13 Hz) rhythm was measured in 22 healthy subjects who have used the Internet for recreational purpose. The vulnerability of Internet addiction was assessed using Young's Internet Addiction Test (IAT) and Assessment for Computer and Internet Addiction-Screener (AICA-S) respectively. Depression and impulsivity were also measured with Beck Depression Inventory (BDI) and Barratt Impulsiveness Scale 11(BIS-11) respectively. The IAT was positively correlated with alpha power obtained during eyes closed (EC, r = 0.50, p = 0.02) but not during eyes open (EO). This was further supported by a negative correlation (r = -0.48, p = 0.02) between IAT scores and alpha desynchronization (EO-EC). These relationships remained significant following correction for multiple comparisons. Furthermore, The BDI score showed positive correlation with alpha asymmetry at mid-lateral (r = 0.54, p = 0.01) and mid-frontal (r = 0.46, p = 0.03) regions during EC, and at mid-frontal (r = 0.53, p = 0.01) region during EO. The current findings suggest that there are associations between neural activity and the vulnerability of problematic Internet use. Understanding of the neurobiological mechanisms underlying problematic Internet use would contribute to improved early intervention and treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

An Investigation of Individual Variability in Brain Activity During Episodic Encoding and Retrieval

DTIC Science & Technology

2008-12-01

variability in mnemonic strategy use is, at least in part, related to the extensive variability observed in brain activity patterns. While a number of...1 AN INVESTIGATION OF INDIVIDUAL VARIABILITY IN BRAIN ACTIVITY DURING EPISODIC ENCODING AND RETRIEVAL C.L. Donovan*, and M.B. Miller Department of...strategy measures for predicting differences in brain activity patterns during a learning and memory task and to compare their predictive value to other

Oliveria decumbens essential oil: Chemical compositions and antimicrobial activity against the growth of some clinical and standard strains causing infection.

PubMed

Alizadeh Behbahani, Behrooz; Tabatabaei Yazdi, Farideh; Vasiee, Alireza; Mortazavi, Seyed Ali

2018-01-01

Oliveria decumbens as a valuable medicinal plant is extensively used in traditional medicine. clinical and standard strains causing infection resistance to antimicrobial agents, is one of the important problems in medicine. The aim of this study was to investigate the antibacterial activities and phytochemical analysis of Oliveria decumbens essential oil on the growth of some clinical and standard strains causing infection (Pseudomonas aerogenes, Escherichia coli, Streptococcus pyogenes and Staphylococcus epidermidis). Oliveria decumbens essential oil composition was identified by gas chromatography/mass spectrometry. Phytochemical analysis (alkaloids, saponins, flavone and phenolic) essential oil of the Oliveria decumbens were appraised based on qualitative methods. Several methods (disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) were used to appraise the antibacterial activity of the Oliveria decumbens essential oil. Thymol (28.45%) was the major compound of Oliveria decumbens essential oil. The total phenolics content (TPC) of the essential oil positively correlated with antioxidant activity (AA). The TPC and AA of Oliveria decumbens essential oil was equal to 92.45 ± 0.70 μg GAE/mg and 164.45 ± 1.20 μg/ml, respectively. The MIC of Oliveria decumbens essential oil ranged from 1 to 8 mg/ml depending on the type of bacteria (clinical and standard strains). The MBC of Oliveria decumbens essential oil varied from 1 mg/ml to 16 mg/ml. The smallest inhibition zone diameter (IZD) on different Oliveria decumbens essential oil concentrations on P. aeruginosa. Results indicate that Oliveria decumbens essential oil can prove to be an important source of AA and antibacterial and may be used for the treatment of infection diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

PubMed

Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

2017-10-01

The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates.

PubMed

Heunis, Tiaan; Dippenaar, Anzaan; Warren, Robin M; van Helden, Paul D; van der Merwe, Ruben G; Gey van Pittius, Nicolaas C; Pain, Arnab; Sampson, Samantha L; Tabb, David L

2017-10-06

Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of the utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study, we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach, we identified 59 peptides containing single amino acid variants, which covered ∼9% of all coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here, we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e., large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.

Clinical and investigative profile of biopsy-proven sarcoid uveitis in India.

PubMed

Ganesh, Sudha K; Agarwal, Manisha

2008-01-01

Retrospective analysis of the clinical features, investigative profile, response to treatment, and final visual outcome in histopathologically confirmed cases of sarcoid uveitis. Retrospective case series analysis was done of 15 eyes of 9 patients seen between July 1999 and August 2003 with biopsy-proven sarcoid uveitis. There were 3 were males and 6 females. The mean age at presentation was 44.1 years (range 11-62 years), The mean follow-up was 28.4 months. Six patients had bilateral ocular involvement and 3 had unilateral involvement. Five out of 9 patients had primarily ocular involvement. The most common presentation was intermediate uveitis and granulomatous anterior uveitis in 7 patients. Eight of 9 patients responded well to the medical treatment with systemic and periocular steroids. Ocular lesions can be the primary manifestation of systemic sarcoidosis. Sarcoid uveitis in the Asian Indian population often presents an intermediate uveitis with granulomatous anterior uveitis.

The Ethics of Clinical Care and the Ethics of Clinical Research: Yin and Yang.

PubMed

Kowalski, Charles J; Hutchinson, Raymond J; Mrdjenovich, Adam J

2017-02-01

The Belmont Report's distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Investigation of antibacterial activities of Albizia gummifera and Ferula communis on Streptococcus pneumoniae and Streptoccus pyogenes.

PubMed

Unasho, Abayneh; Geyid, Aberra; Melaku, Abebe; Debela, Asfaw; Mekasha, Amha; Girma, Samson; Kebede, Tesfaye; Fantaw, Surafael; Asaminew, Nega; Mamo, Kidanemariam

2009-01-01

Respiratory Tract infections continue to be a major cause of morbidity and mortality world wide. There is a failure to treat respiratory infections due to the emergence of antibiotic resistant strains among the most common respiratory pathogens. To evaluate the in vitro antibacterial activities of two traditionally used plants: Albizia gummifera (Ambabesa-Muka, Oromifa, Sessa-Amharic.) and Ferula communis (Doge-Oromifa, Dog-Amharic) against clinical isolates of S. pyogenes and S. pneumoniae. The study involving the antibacterial susceptibility test of traditionally used plant species against Gram-positive bacterial pathogens was conducted over a period of 5 months (January - August, 2004) at the Ethiopian Health, and Nutrition Research Institute. The in vitro antibacterial activities of 80% methanol crude extracts prepared from the seeds of Ablizia gummifera and, roots of Ferula communis as well as their respective hydro alcoholic solvent fractionates of both plant species were tested for inhibitory activity against the clinical isolates of six S. pneumonae and twenty two S. pyogenes using agar dilution method. Eighty percent ethanol solubilized fractions of both plants were found to have antibacterial effects to all assayed bacteria while aqueous solubilized fractions did not exhibit any effect. Minimum inhibitory concentration (MIC) of the 80% ethanol solubilized fractions was determined and the MIC of the fractions ranged from 500 mg/ ml to 1000 mg/ml for both plants showing the extracts may contain bioactive compounds of therapeutic interest. All extracts showed antibacterial activities against clinical isolates of S. pyogenes and S. pneumoniae. The extracts may contain compounds with potential therapeutic activity. Further purification and identification are needed to be tested using animal models.

Community Representatives’ Involvement in Clinical and Translational Science Awardee Activities

PubMed Central

Spofford, Mark; Williams, Neely; McKeever, Corliss; Allen, Shauntice; Brown, Jen; Opp, Jennifer; Richmond, Alan; Strelnick, A. Hal

2013-01-01

Abstract Objectives To understand the formal roles of community representatives (CRs) in Clinical and Translational Science Awardee (CTSA) activities, to evaluate the extent of integration into the organizational and governance structures and to identify barriers to effective integration. Methods The inventory tool was distributed to each of the 60 CTSAs using a secure web application. Results Forty‐seven (78%) completed the inventory. The mean number of CRs per CTSA is 21.4 (SD: 14.8). Most CTSAs had community advisory boards (89%) and 94% included CRs in Community Engagement (CE) cores. Only 11% reported a CR being a member of the CTSA leadership team and 19% reported that CRs advise core programs beyond CE. CRs are compensated by 79% of CTSAs. Mean annual compensation is $753 (median: $400). Compensation directly correlated with the number of hours that CRs worked in CTSA activities (r = 0.64; P = 0.001). Conclusions This inventory allows CTSAs to better understand how CRs have engaged in activities and brings attention to the limited representation among cores and in leadership roles. CTSAs should, with substantive input from CRs, develop strategies to provide the resources and compensation necessary to better integrate the community in CTSA activities and fully realize the goals of the CTSA vision. PMID:23919364

Stock market returns and clinical trial results of investigational compounds: an event study analysis of large biopharmaceutical companies.

PubMed

Hwang, Thomas J

2013-01-01

For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: -2.3, 13.4%; P = 0.02) for positive events and -2.0% (95% CI: -9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: -3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were -1.7% (95% CI: -9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return underperformance due to negative events is greater in magnitude and persists longer than

Stock Market Returns and Clinical Trial Results of Investigational Compounds: An Event Study Analysis of Large Biopharmaceutical Companies

PubMed Central

Hwang, Thomas J.

2013-01-01

Background For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Methods Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. Results We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: –2.3, 13.4%; P = 0.02) for positive events and –2.0% (95% CI: –9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: –3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were –1.7% (95% CI: –9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. Conclusions The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return

A fluid collection system for dermal wounds in clinical investigations

PubMed Central

Klopfer, Michael; Li, G.-P.; Widgerow, Alan; Bachman, Mark

2016-01-01

In this work, we demonstrate the use of a thin, self adherent, and clinically durable patch device that can collect fluid from a wound site for analysis. This device is manufactured from laminated silicone layers using a novel all-silicone double-molding process. In vitro studies for flow and delivery were followed by a clinical demonstration for exudate collection efficiency from a clinically presented partial thickness burn. The demonstrated utility of this device lends itself for use as a research implement used to clinically sample wound exudate for analysis. This device can serve as a platform for future integration of wearable technology into wound monitoring and care. The demonstrated fabrication method can be used for devices requiring thin membrane construction. PMID:27051470

The Need to Objectively Measure Physical Activity During Pregnancy: Considerations for Clinical Research and Public Health Impact.

PubMed

Guérin, Eva; Ferraro, Zachary M; Adamo, Kristi B; Prud'homme, Denis

2018-05-01

Engaging in recommended levels of physical activity during pregnancy can provide a host of physical and mental health benefits for the expecting mother and her child. However, methodological issues related to physical activity measurement have plagued many studies examining the effects of physical activity during this important life stage. Burgeoning support exists for the more widespread use of objective methods, and accelerometers specifically, for an accurate appraisal of maternal physical activity. In this commentary, we highlight discrepancies between activity estimates obtained via self-report and objective measures and describe the implications of erroneous measurement when making clinical recommendations and in conducting future physical activity and pregnancy research. Most importantly, we aim to foster academic discussion and propose a call to action requiring a paradigm shift where we acknowledge the shortcomings of self-report and move toward an empirically driven approach for physical activity measurement. Results from more high-quality research studies will help support public health messaging and facilitate trust among health care providers, clinical researchers, and expecting mothers regarding the health benefits of physical activity recommendations.

Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

PubMed Central

Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L.; Silva, Pedro A.; Viveiros, Miguel

2015-01-01

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates. PMID:25972842