Can non‐clinical repolarization assays predict the results of clinical thorough QT studies? Results from a research consortium

PubMed Central

Park, Eunjung; Gintant, Gary A; Bi, Daoqin; Kozeli, Devi; Pettit, Syril D; Skinner, Matthew; Willard, James; Wisialowski, Todd; Koerner, John; Valentin, Jean‐Pierre

2018-01-01

Background and Purpose Translation of non‐clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 drug applications in a US Food and Drug Administration database to determine the utility of established non‐clinical in vitro IKr current human ether‐à‐go‐go‐related gene (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation. Experimental Approach The predictive performance of three non‐clinical assays was compared with clinical thorough QT study outcomes based on free clinical plasma drug concentrations using sensitivity and specificity, receiver operating characteristic (ROC) curves, positive (PPVs) and negative predictive values (NPVs) and likelihood ratios (LRs). Key Results Non‐clinical assays demonstrated robust specificity (high true negative rate) but poor sensitivity (low true positive rate) for clinical QTc prolongation at low‐intermediate (1×–30×) clinical exposure multiples. The QTc assay provided the most robust PPVs and NPVs (ability to predict clinical QTc prolongation). ROC curves (overall test accuracy) and LRs (ability to influence post‐test probabilities) demonstrated overall marginal performance for hERG and QTc assays (best at 30× exposures), while the APD assay demonstrated minimal value. Conclusions and Implications The predictive value of hERG, APD and QTc assays varies, with drug concentrations strongly affecting translational performance. While useful in guiding preclinical candidates without clinical QT prolongation, hERG and QTc repolarization assays provide greater value compared with the APD assay. PMID:29181850

Midwives׳ clinical reasoning during second stage labour: Report on an interpretive study.

PubMed

Jefford, Elaine; Fahy, Kathleen

2015-05-01

clinical reasoning was once thought to be the exclusive domain of medicine - setting it apart from 'non-scientific' occupations like midwifery. Poor assessment, clinical reasoning and decision-making skills are well known contributors to adverse outcomes in maternity care. Midwifery decision-making models share a common deficit: they are insufficiently detailed to guide reasoning processes for midwives in practice. For these reasons we wanted to explore if midwives actively engaged in clinical reasoning processes within their clinical practice and if so to what extent. The study was conducted using post structural, feminist methodology. to what extent do midwives engage in clinical reasoning processes when making decisions in the second stage labour? twenty-six practising midwives were interviewed. Feminist interpretive analysis was conducted by two researchers guided by the steps of a model of clinical reasoning process. Six narratives were excluded from analysis because they did not sufficiently address the research question. The midwives narratives were prepared via data reduction. A theoretically informed analysis and interpretation was conducted. using a feminist, interpretive approach we created a model of midwifery clinical reasoning grounded in the literature and consistent with the data. Thirteen of the 20 participant narratives demonstrate analytical clinical reasoning abilities but only nine completed the process and implemented the decision. Seven midwives used non-analytical decision-making without adequately checking against assessment data. over half of the participants demonstrated the ability to use clinical reasoning skills. Less than half of the midwives demonstrated clinical reasoning as their way of making decisions. The new model of Midwifery Clinical Reasoning includes 'intuition' as a valued way of knowing. Using intuition, however, should not replace clinical reasoning which promotes through decision-making can be made transparent and be consensually validated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnosis of cystocele--the correlation between clinical and radiological evaluation.

PubMed

Altman, Daniel; Mellgren, Anders; Kierkegaard, Jonas; Zetterström, Jan; Falconer, Christian; López, Annika

2004-01-01

In patients with genital prolapse involving several compartments simultaneously, radiologic investigation can be used to complement the clinical assessment. Contrast medium in the urinary bladder enables visualization of the bladder base at cystodefecoperitoneography (CDP). The aim of the present study was to evaluate the correlation between clinical examination using the Pelvic Organ Prolapse Quantification system (POP-Q) and CDP. Thirty-three women underwent clinical assessment and CDP. Statistical analysis using Pearson's correlation coefficient ( r) demonstrated a wide variability between the current definition of cystocele at CDP and POP-Q ( r=0.67). An attempt to provide an alternative definition of cystocele at CDP had a similar outcome ( r=0.63). The present study demonstrates a moderate correlation between clinical and radiologic findings in patients with anterior vaginal wall prolapse. It does not support the use of bladder contrast at radiologic investigation in the routine preoperative assessment of patients with genital prolapse.

From Theory to Application: A Study of Knowledge Transfer in Dental Education

ERIC Educational Resources Information Center

Peltz, Ivy D.

2014-01-01

Traditionally, dental education is divided into two phases: pre-clinical and clinical education. The pre-clinical phase of dental education includes the assimilation of theoretical topical knowledge in addition to the completion of simulated exercises. Upon completion of and demonstration of competency in their pre-clinical courses, students begin…

[Clinical features of focal brain lesions in the left-handed and ambidextrous].

PubMed

Chebysheva, L N; Bragina, N N; Dobrokhotova, T A

1977-01-01

On the basis of a study of 31 patients who demonstrated deviations from dextrality (Simistrals and ambidextrals) the authors describe some traits of the nervous and mental changes in focal brain lesions. There are insignificant correlations between the character of nervous and mental changes and the side of a brain lesion. The study demonstrated a wide variability of the clinical symptomatology, a peculiarity of each neurological and psychopathological phenomenon, distinguishing them from similar changes in dextrals. The studied contingent revealed prevalence of a disturbed sensory cognition in the clinical picture; the presence of special phenomena which most likely are not seen in dextrals and which are also related to a pathology of sensory cognition. It is being assumed that these clinical traits may testify to an insufficiency of speech lateralization in sinistrals and that an insufficient speech lateralization is accompanied by other than in dextrals organization of sensory processes.

The MMPI-2 Restructured Clinical Scales in the Assessment of Posttraumatic Stress Disorder and Comorbid Disorders

PubMed Central

Wolf, Erika J.; Miller, Mark W.; Orazem, Robert J.; Weierich, Mariann R.; Castillo, Diane T.; Milford, Jaime; Kaloupek, Danny G.; Keane, Terence M.

2008-01-01

This study examined the psychometric properties of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Restructured Clinical Scales (RCSs) in individuals with posttraumatic stress disorder (PTSD) receiving clinical services at Veterans Affairs medical centers. Study 1 included 1,098 men who completed the MMPI-2 and were assessed for a range of psychological disorders via structured clinical interview. Study 2 included 136 women who completed the MMPI-2 and were interviewed with the Clinician Administered Scale for PTSD. The utility of the RCSs was compared to that of the Clinical Scales (CSs) and the Keane PTSD (PK) scale. The RCSs demonstrated good psychometric properties along with patterns of associations with other measures of psychopathology that corresponded to current theory regarding the structure of comorbidity. A notable advantage of the RCSs compared to the MMPI-2 CSs was their enhanced construct validity and clinical utility in the assessment of comorbid internalizing and externalizing psychopathology. The PK scale demonstrated incremental validity in the prediction of PTSD beyond that of the RCSs or CSs. PMID:19086756

Accelerating Translational Research by Clinically Driven Development of an Informatics Platform–A Case Study

PubMed Central

Abugessaisa, Imad; Saevarsdottir, Saedis; Tsipras, Giorgos; Lindblad, Staffan; Sandin, Charlotta; Nikamo, Pernilla; Ståhle, Mona; Malmström, Vivianne; Klareskog, Lars; Tegnér, Jesper

2014-01-01

Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected. In conclusion, the system can readily be used by clinicians and biomedical researchers in a translational medicine setting. PMID:25203647

Accelerating translational research by clinically driven development of an informatics platform--a case study.

PubMed

Abugessaisa, Imad; Saevarsdottir, Saedis; Tsipras, Giorgos; Lindblad, Staffan; Sandin, Charlotta; Nikamo, Pernilla; Ståhle, Mona; Malmström, Vivianne; Klareskog, Lars; Tegnér, Jesper

2014-01-01

Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected. In conclusion, the system can readily be used by clinicians and biomedical researchers in a translational medicine setting.

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra Abdominal Hemorrhagic Shock using Continuous Vital Signs

DTIC Science & Technology

2016-03-01

AWARD NUMBER: W81XWH-15-1-0025 TITLE: Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic...Intra-Abdominal Hemorrhagic Shock 5b. GRANT NUMBER W81XWH-15-1-0025 Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta ...sites. Resuscitative balloon occlusion of the aorta (REBOA) has been clinically demonstrated to stop bleeding below the diaphragm. It has the potential

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

Students' description of factors contributing to a meaningful clinical experience in entry-level physical therapist professional education.

PubMed

Rindflesch, Aaron; Hoversten, Kelsey; Patterson, Britta; Thomas, Laura; Dunfee, Heidi

2013-01-01

The objective of this study was to identify student, clinical instructor (CI), and environmental characteristics and behaviors that make for positive clinical experiences as perceived by physical therapy students. Nine third-year physical therapist students from entry-level physial therapist education programs around the United States participated in this study. In this phenomenologic study, participants were interviewed using open-ended questions designed to facilitate rich description. Interviews were recorded, transcribed, validated, and analyzed. Themes were identified through collaborative analysis using constant comparative coding. Students described student, CI, and environmental factors and behaviors that contribute to a quality clinical experience, including: the students' demonstration of initiative to prepare for the clinical experience and preparation after clinic hours; the importance of the CI's insight, allowing CIs to ascertain how much guidance to give in order to foster independence in the student; and the clinical environment's ability to welcome a student and provide the student with novel learning experiences. The student descriptions, including positive and negative examples shared by the interviewees, demonstrate essential characteristics that contribute to a positive clinical experience. Many of the factors identified by students can be influenced by student and CI training and preparation prior to the clinical experience.

Use of betahistine in the treatment of peripheral vertigo.

PubMed

Ramos Alcocer, Rubén; Ledezma Rodríguez, José Gregorio; Navas Romero, Antonio; Cardenas Nuñez, José Luis; Rodríguez Montoya, Vicente; Deschamps, Jose Junior; Liviac Ticse, Jorge Anibal

2015-01-01

Clinical studies and meta-analyses demonstrated that betahistine is effective and safe in the treatment of Ménière's disease, BPPV (benign paroxysmal positional vertigo), vestibular neuronitis, and other types of peripheral vertigo. The goal of this paper is to review the pharmacological profile of betahistine and the evidence for its effectiveness and safety in the treatment of peripheral vertigo. Selection criteria for the publications on betahistine included randomized clinical trials that evaluated the effectiveness and safety of betahistine vs placebo or active control in the treatment of peripheral vertigo. Recent meta-analyses were also included. Databases searched included PubMed, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, and ICTRP. The review also presents an update on the mechanisms of action, pharmacodynamics, and pharmacokinetics of betahistine. Efficacy and safety of betahistine has been demonstrated in numerous clinical trials. The precise mechanism of action of betahistine is still not completely understood, but the clinical experience demonstrated the benefit of betahistine in different types of peripheral vertigo. In more than 40 years of clinical use, betahistine has shown an excellent safety profile with the usual dose range from 8-48 mg daily. According to clinical studies, betahistine 48 mg daily during 3 months is an effective and safe option for the treatment of peripheral vertigo.

Regression of Moral Reasoning during Medical Education: Combined Design Study to Evaluate the Effect of Clinical Study Years

PubMed Central

Hren, Darko; Marušić, Matko; Marušić, Ana

2011-01-01

Background Moral reasoning is important for developing medical professionalism but current evidence for the relationship between education and moral reasoning does not clearly apply to medical students. We used a combined study design to test the effect of clinical teaching on moral reasoning. Methods We used the Defining Issues Test-2 as a measure of moral judgment, with 3 general moral schemas: Personal Interest, Maintaining Norms, and Postconventional Schema. The test was applied to 3 consecutive cohorts of second year students in 2002 (n = 207), 2003 (n = 192), and 2004 (n = 139), and to 707 students of all 6 study years in 2004 cross-sectional study. We also tested 298 age-matched controls without university education. Results In the cross-sectional study, there was significant main effect of the study year for Postconventional (F(5,679) = 3.67, P = 0.003) and Personal Interest scores (F(5,679) = 3.38, P = 0.005). There was no effect of the study year for Maintaining Norms scores. 3rd year medical students scored higher on Postconventional schema score than all other study years (p<0.001). There were no statistically significant differences among 3 cohorts of 2nd year medical students, demonstrating the absence of cohort or point-of-measurement effects. Longitudinal study of 3 cohorts demonstrated that students regressed from Postconventional to Maintaining Norms schema-based reasoning after entering the clinical part of the curriculum. Interpretation Our study demonstrated direct causative relationship between the regression in moral reasoning development and clinical teaching during medical curriculum. The reasons may include hierarchical organization of clinical practice, specific nature of moral dilemmas faced by medical students, and hidden medical curriculum. PMID:21479204

42 CFR 21.44 - Clinical or other practical demonstration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Clinical or other practical demonstration. 21.44... COMMISSIONED OFFICERS Appointment § 21.44 Clinical or other practical demonstration. In the discretion of the... the Regular Corps may be required to perform successfully a clinical or other practical demonstration...

Combinations of Radiotherapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

PubMed Central

Barker, Christopher A.; Postow, Michael A.

2015-01-01

Radiotherapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiotherapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiotherapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiotherapy. The cytokines interferon-alpha and interleukin-2 have been combined with radiotherapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiotherapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested radiotherapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiotherapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study. PMID:24661650

Periowave demonstrates bactericidal activity against periopathogens and leads to improved clinical outcomes in the treatment of adult periodontitis

NASA Astrophysics Data System (ADS)

Street, Cale N.; Andersen, Roger; Loebel, Nicolas G.

2009-02-01

Periodontitis affects half of the U.S. population over 50, and is the leading cause of tooth loss after 35. It is believed to be caused by growth of complex bacterial biofilms on the tooth surface below the gumline. Photodynamic therapy, a technology used commonly in antitumor applications, has more recently been shown to exhibit antimicrobial efficacy. We have demonstrated eradication of the periopathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans in vitro using PeriowaveTM; a commercial photodisinfection system. In addition, several clinical studies have now demonstrated the efficacy of this treatment. A pilot study in the U.S. showed that 68% of patients treated with PeriowaveTM adjunctively to scaling and root planing (SRP) showed clinical attachment level increase of >1 mm, as opposed to 30% with SRP alone. In a subsequent larger study, a second PeriowaveTM treatment 6 weeks after initial treatment led to pocket depth improvements of >1.5 mm in 89% of patients. Finally, in the most recent multicenter, randomized, examiner-blinded study conducted on 121 subjects in Canada, PeriowaveTM treatment produced highly significant gains in attachment level (0.88 mm vs. 0.57 mm; p=0.003) and pocket depth (0.87 mm vs. 0.63 mm; p=0.01) as compared to SRP alone. In summary, PeriowaveTM demonstrated strong bactericidal activity against known periopathogens, and treatment of periodontitis using this system produced significantly better clinical outcomes than SRP alone. This, along with the absence of any adverse events in patients treated to date demonstrates that PDT is a safe and effective treatment for adult chronic periodontitis.

Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome.

PubMed

Maslak, P; Chanel, S; Camacho, L H; Soignet, S; Pandolfi, P P; Guernah, I; Warrell, R; Nimer, S

2006-02-01

Epigenetic mechanisms underlying tumorigenesis have recently received much attention as potential therapeutic targets of human cancer. We designed a pilot study to target DNA methylation and histone deacetylation through the sequential administration of 5-azacytidine followed by sodium phenylbutyrate (PB) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Ten evaluable patients (eight AML, two MDS) were treated with seven consecutive daily subcutaneous injections of 5-azacytidine at 75 mg/m2 followed by 5 days of sodium PB given intravenously at a dose of 200 mg/kg. Five patients (50%) were able to achieve a beneficial clinical response (partial remission or stable disease). One patient with MDS proceeded to allogeneic stem cell transplantation and is alive without evidence of disease 39 months later. The combination regimen was well tolerated with common toxicities of injection site skin reaction (90% of the patients) from 5-azacytidine, and somnolence/fatigue from the sodium PB infusion (80% of the patients). Correlative laboratory studies demonstrated the consistent reacetylation of histone H4, although no relationship with the clinical response could be demonstrated. Results from this pilot study demonstrate that a combination approach targeting different mechanisms of transcriptional modulation is clinically feasible with acceptable toxicity and measurable biologic and clinical outcomes.

The impact of complete denture making instructional videos on self-directed learning of clinical skills.

PubMed

Kon, Haruka; Botelho, Michael George; Bridges, Susan; Leung, Katherine Chiu Man

2015-04-01

The aim of this research was to evaluate the effectiveness of a clinical instructional video with a structured worksheet for independent self-study in a complete denture program. 47 multilingual dental students completed a task by watching an instructional video with subtitles regarding clinical complete denture procedures. After completion, students evaluated their learning experience, and 11 students participated in focus group interviews to gain further insight. A mixed-methods approach to data collection and analysis provided descriptive statistical results and a grounded theory approach to coding identified key concepts and categories from the qualitative data. Over 70% of students had favorable opinions of the learning experience and indicated that the speed and length of the video were appropriate. Highly positive and conflicting negative comments regarding the use of subtitles showed both preferences for subtitles over audio and vice versa. The use of a video resource was considered valuable as the replay and review functions allowed better visualization of the procedures, which was considered a good recap tool for the clinical demonstration. It was also a better revision aid than textbooks. So, if the students were able to view these videos at will, they believed that videos supplemented their self-study. Despite the positive response, videos were not considered to replace live clinical demonstrations. While students preferred live demonstrations over the clinical videos they did express a realization of these as a supplemental learning material for self-study based on their ease of access, use for revision, and prior to clinical preparation. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

PubMed Central

Bartus, Raymond T; Weinberg, Marc S; Samulski, R. Jude

2014-01-01

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits. PMID:24356252

Implementing Single Source: The STARBRITE Proof-of-Concept Study

PubMed Central

Kush, Rebecca; Alschuler, Liora; Ruggeri, Roberto; Cassells, Sally; Gupta, Nitin; Bain, Landen; Claise, Karen; Shah, Monica; Nahm, Meredith

2007-01-01

Objective Inefficiencies in clinical trial data collection cause delays, increase costs, and may reduce clinician participation in medical research. In this proof-of-concept study, we examine the feasibility of using point-of-care data capture for both the medical record and clinical research in the setting of a working clinical trial. We hypothesized that by doing so, we could increase reuse of patient data, eliminate redundant data entry, and minimize disruption to clinic workflow. Design We developed and used a point-of-care electronic data capture system to record data during patient visits. The standards-based system was used for clinical research and to generate the clinic note for the medical record. The system worked in parallel with data collection procedures already in place for an ongoing multicenter clinical trial. Our system was iteratively designed after analyzing case report forms and clinic notes, and observing clinic workflow patterns and business procedures. Existing data standards from CDISC and HL7 were used for database insertion and clinical document exchange. Results Our system was successfully integrated into the clinic environment and used in two live test cases without disrupting existing workflow. Analyses performed during system design yielded detailed information on practical issues affecting implementation of systems that automatically extract, store, and reuse healthcare data. Conclusion Although subject to the limitations of a small feasibility study, our study demonstrates that electronic patient data can be reused for prospective multicenter clinical research and patient care, and demonstrates a need for further development of therapeutic area standards that can facilitate researcher use of healthcare data. PMID:17600107

The effect of exercise on skeletal muscle fibre type distribution in obesity: From cellular levels to clinical application.

PubMed

Pattanakuhar, Sintip; Pongchaidecha, Anchalee; Chattipakorn, Nipon; Chattipakorn, Siriporn C

Skeletal muscles play important roles in metabolism, energy expenditure, physical strength, and locomotive activity. Skeletal muscle fibre types in the body are heterogeneous. They can be classified as oxidative types and glycolytic types with oxidative-type are fatigue-resistant and use oxidative metabolism, while fibres with glycolytic-type are fatigue-sensitive and prefer glycolytic metabolism. Several studies demonstrated that an obese condition with abnormal metabolic parameters has been negatively correlated with the distribution of oxidative-type skeletal muscle fibres, but positively associated with that of glycolytic-type muscle fibres. However, some studies demonstrated otherwise. In addition, several studies demonstrated that an exercise training programme caused the redistribution of oxidative-type skeletal muscle fibres in obesity. In contrast, some studies showed inconsistent findings. Therefore, the present review comprehensively summarizes and discusses those consistent and inconsistent findings from clinical studies, regarding the association among the distribution of skeletal muscle fibre types, obese condition, and exercise training programmes. Furthermore, the possible underlying mechanisms and clinical application of the alterations in muscle fibre type following obesity are presented and discussed. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis.

PubMed

Veale, Douglas J; McGonagle, Dennis; McInnes, Iain B; Krueger, James G; Ritchlin, Christopher T; Elewaut, Dirk; Kanik, Keith S; Hendrikx, Thijs; Berstein, Gabriel; Hodge, Jennifer; Telliez, Jean-Baptiste

2018-04-03

The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.

Research staff training in a multisite randomized clinical trial: Methods and recommendations from the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial.

PubMed

Walker, Robrina; Morris, David W; Greer, Tracy L; Trivedi, Madhukar H

2014-01-01

Descriptions of and recommendations for meeting the challenges of training research staff for multisite studies are limited despite the recognized importance of training on trial outcomes. The STRIDE (STimulant Reduction Intervention using Dosed Exercise) study is a multisite randomized clinical trial that was conducted at nine addiction treatment programs across the United States within the National Drug Abuse Treatment Clinical Trials Network (CTN) and evaluated the addition of exercise to addiction treatment as usual (TAU), compared to health education added to TAU, for individuals with stimulant abuse or dependence. Research staff administered a variety of measures that required a range of interviewing, technical, and clinical skills. In order to address the absence of information on how research staff are trained for multisite clinical studies, the current manuscript describes the conceptual process of training and certifying research assistants for STRIDE. Training was conducted using a three-stage process to allow staff sufficient time for distributive learning, practice, and calibration leading up to implementation of this complex study. Training was successfully implemented with staff across nine sites. Staff demonstrated evidence of study and procedural knowledge via quizzes and skill demonstration on six measures requiring certification. Overall, while the majority of staff had little to no experience in the six measures, all research assistants demonstrated ability to correctly and reliably administer the measures throughout the study. Practical recommendations are provided for training research staff and are particularly applicable to the challenges encountered with large, multisite trials.

Clinical Utility of Cancellation on the WISC-IV

ERIC Educational Resources Information Center

Zhu, Jianjun; Chen, Hsinyi

2013-01-01

This study examined empirical evidence for clinical utility of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV) cancellation subtest by comparing data from 597 clinical and 597 matched control children. The results of dependent t and sequential logistic regression analyses demonstrated that (a) children with intellectual…

Clinical detection of dysplasia using angle-resolved low coherence interferometry

NASA Astrophysics Data System (ADS)

Terry, Neil Gordon

2011-12-01

Cancer is now the leading cause of death in developed countries. Despite advances in strategies aimed at the prevention and treatment of the disease, early detection of precancerous growths remains the most effective method of reducing associated morbidity and mortality. Pathological examination of physical tissues that are collected via systematic biopsy is the current "gold standard" in this pursuit. Despite widespread acceptance of this methodology and high confidence in its performance, it is not without limitations. Recently, much attention has been given to the development of optical biopsy techniques that can be used clinically and are able to overcome these limitations. This dissertation describes one such optical biopsy technique, angle-resolved low coherence interferometry (a/LCI), its adaptation to a clinical technology, and its evaluation in clinical studies. The dissertation presents the theory that underlies the operation of the a/LCI technique, the design and validation of the clinical instrument, and its evaluation by means of two clinical trials. First, an account of the manner in which the depth-resolved angular scattering profiles that are collected by a/LCI can be used to determine nuclear characteristics of the investigated tissues is given. The design of the clinical system that is able to collect these scattering profiles through an optical fiber probe that can be passed through the accessory channel of an endoscope for in vivo use is presented. To demonstrate the ability of this system to accurately determine the size of cell nuclei, a set of validation experiments are described. In order to evaluate the clinical utility of this a/LCI system, two clinical trials intended to assess the ability of a/LCI to detect the presence of early, pre-cancerous dysplasias in human tissues are presented. The first of these, an in vivo study of Barrett's esophagus (BE) patients undergoing routine surveillance for the early signs of esophageal adenocarcinoma, is described. This study represents the first use of the a/LCI technique in vivo, and confirms its ability to provide clinically useful information regarding the disease state of the tissue that it examines, with performance that compares favorably to other optical biopsy techniques. Next, an ex vivo study of resected intestinal tissue is presented. The results of this study demonstrate the ability of a/LCI to provide information that can be used to detect dysplasia in the lower gastrointestinal tract with high accuracy. This study will enable future development of the technology to allow conduction of in vivo trials of intestinal tissue. The results of these two clinical studies demonstrate the clinical utility a/LCI, illustrating its potential as an optical biopsy technique that has great potential to provide diagnostically relevant information during surveillance procedures. This is particularly relevant in the case of BE, where its successful use has been demonstrated in vivo.

Calculating Clinically Significant Change: Applications of the Clinical Global Impressions (CGI) Scale to Evaluate Client Outcomes in Private Practice

ERIC Educational Resources Information Center

Kelly, Peter James

2010-01-01

The Clinical Global Impressions (CGI) scale is a therapist-rated measure of client outcome that has been widely used within the research literature. The current study aimed to develop reliable and clinically significant change indices for the CGI, and to demonstrate its application in private psychological practice. Following the guidelines…

Test set readings predict clinical performance to a limited extent: preliminary findings

NASA Astrophysics Data System (ADS)

Soh, BaoLin P.; Lee, Warwick M.; Kench, Peter L.; Reed, Warren M.; McEntee, Mark F.; Brennan, Patrick C.

2013-03-01

Aim: To investigate the level of agreement between test sets and actual clinical reading Background: The performance of screen readers in detecting breast cancer is being assessed in some countries by using mammographic test sets. However, previous studies have provided little evidence that performance assessed by test sets strongly correlate to performance in clinical reading. Methods: Five clinicians from BreastScreen New South Wales participated in this study. Each clinician was asked to read 200 de-identified mammographic examinations gathered from their own case history within the BreastScreen NSW Digital Imaging Library. All test sets were designed with specific proportions of true positive, true negative, false positive and false negative examinations from the previous actual clinical reads of each reader. A prior mammogram examination for comparison (when available) was also provided for each case. Results: Preliminary analyses have shown that there is a moderate level of agreement (Kappa 0.42-0.56, p < 0.001) between laboratory test sets and actual clinical reading. In addition, a mean increase of 38% in sensitivity in the laboratory test sets as compared to their actual clinical readings was demonstrated. Specificity is similar between the laboratory test sets and actual clinical reading. Conclusion: This study demonstrated a moderate level of agreement between actual clinical reading and test set reading, which suggests that test sets have a role in reflecting clinical performance.

Embolic Protection Devices During TAVI: Current Evidence and Uncertainties.

PubMed

Abdul-Jawad Altisent, Omar; Puri, Rishi; Rodés-Cabau, Josep

2016-10-01

Transcatheter aortic valve implantation (TAVI) is now the principal therapeutic option in patients with severe aortic stenosis deemed inoperable or at high surgical risk. Implementing TAVI in a lower risk profile population could be limited by relatively high cerebrovascular event rates related to the procedure. Diffusion-weighted magnetic resonance imaging studies have demonstrated the ubiquitous presence of silent embolic cerebral infarcts after TAVI, with some data relating these lesions to subsequent cognitive decline. Embolic protection devices provide a mechanical barrier against debris embolizing to the brain during TAVI. We review the current evidence and ongoing uncertainties faced with the 3 currently available devices (Embrella, TriGuard and Claret) in TAVI. Studies evaluated neurological damage at 3 levels: clinical, subclinical, and cognitive. Feasibility and safety were analyzed for the 3 devices. In terms of efficacy, all studies were exploratory, but none demonstrated significant reductions in clinical event rates. The Embrella and Claret devices demonstrated significant reductions of the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging. Studies evaluating the effects on cognition were also somewhat inconclusive. In conclusion, despite embolic protection devices demonstrating reductions in the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging, the clinical efficacy in terms of preventing stroke/cognitive decline requires confirmation in larger studies. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Using a handbook to improve nurses' continence care.

PubMed

Williams, K; Roe, B; Sindhu, F

Nursing care should be based on sound research evidence with demonstrated clinical effectiveness. Dissemination of this research evidence is, therefore, of paramount importance. A study using focus groups was undertaken during 1993-1994 to evaluate the dissemination of a clinical handbook for continence care to qualified nurses, in relation to reported nursing practice in care of the elderly wards/units in one health authority. A total of 124 nurses participated in the study and 98 variables were included. Improvements were recorded in nurses' responses between the pre-test and post-test for 84 (86 per cent) variables in the experimental group and 58 (59 per cent) in the control group. This demonstrates the positive value of the clinical handbook as a method of disseminating research evidence.

Latinos with obsessive-compulsive disorder: Mental healthcare utilization and inclusion in clinical trials.

PubMed

Wetterneck, Chad T; Little, Tannah E; Rinehart, Kimberly L; Cervantes, Maritza E; Hyde, Emma; Williams, Monnica

2012-04-01

Previous research has documented that ethnic minorities, particularly Latinos, obtain fewer mental health services than Caucasians (Kearney, Draper, & Baron 2005; Sue, Fujino, Hu, Takeuchi, & Zane, 1991). Conceivably, this may be due to a wide array of cultural issues (e.g., negative stigma attached to mental health, and language, socio-economic, and acculturation barriers), symptom disparities across Caucasian and Latino groups, or lack of effective outreach methods by clinicians and researchers. However, research is limited. As a result, Latinos may be insufficiently represented in clinical studies for OCD, making it unclear whether evidence-based treatments demonstrate the same efficacy and effectiveness for Latinos as has been demonstrated for Caucasians. The current study takes an in-depth analysis of 98 efficacy and effectiveness studies for OCD from across the Western hemisphere and reports the rates of Latino inclusion from each sample. Ninety clinical studies in the US and Canada, as well as eight clinical studies in Mexico and Central America were reviewed. Findings showed that only 11 (24%) US and Canadian studies included Latino participants, illustrating an overwhelming underrepresentation of Latinos in clinical studies for OCD. Further explanation of the results and their implications are discussed, along with suggestions for effectively improving access to mental health research and appropriate treatments.

Latinos with obsessive-compulsive disorder: Mental healthcare utilization and inclusion in clinical trials

PubMed Central

Wetterneck, Chad T.; Little, Tannah E.; Rinehart, Kimberly L.; Cervantes, Maritza E.; Hyde, Emma; Williams, Monnica

2014-01-01

Previous research has documented that ethnic minorities, particularly Latinos, obtain fewer mental health services than Caucasians (Kearney, Draper, & Baron 2005; Sue, Fujino, Hu, Takeuchi, & Zane, 1991). Conceivably, this may be due to a wide array of cultural issues (e.g., negative stigma attached to mental health, and language, socio-economic, and acculturation barriers), symptom disparities across Caucasian and Latino groups, or lack of effective outreach methods by clinicians and researchers. However, research is limited. As a result, Latinos may be insufficiently represented in clinical studies for OCD, making it unclear whether evidence-based treatments demonstrate the same efficacy and effectiveness for Latinos as has been demonstrated for Caucasians. The current study takes an in-depth analysis of 98 efficacy and effectiveness studies for OCD from across the Western hemisphere and reports the rates of Latino inclusion from each sample. Ninety clinical studies in the US and Canada, as well as eight clinical studies in Mexico and Central America were reviewed. Findings showed that only 11 (24%) US and Canadian studies included Latino participants, illustrating an overwhelming underrepresentation of Latinos in clinical studies for OCD. Further explanation of the results and their implications are discussed, along with suggestions for effectively improving access to mental health research and appropriate treatments. PMID:29057210

Psychological and Social Predictors of Suicidal Ideation among Young Adolescents

ERIC Educational Resources Information Center

Kirkcaldy, Bruce D.; Eysenck, Michael W.; Siefen, Georg R.

2004-01-01

Although there is an enormous amount of literature demonstrating socio-psychological determinants of suicide and self-injurious behaviour among adults or clinical samples of children and adolescents, there is a scarcity of studies focussing on non-clinical adolescent samples. The current study examined associations between self-reported data on…

Interpersonal Psychotherapy Group (IPT-G) for Depression

PubMed Central

MacKenzie, K. Roy; Grabovac, A.D.

2001-01-01

A case study of a time-limited interpersonal psychotherapy group (IPT-G) is presented to illustrate the use of interpersonal therapy (IPT) to treat patients with major depression in a group psychotherapy format. The use of individual outcome measures as a helpful adjunct to clinical psychotherapeutic practice is demonstrated. Because IPT-G has only a few exclusion criteria (active suicidality and significant borderline personality features), it can be used in a broad range of clinical settings. This clinical example demonstrates IPT-G to be a useful modality for addressing a common and difficult patient population. PMID:11121007

The applications of regenerative medicine in sinus lift procedures: A systematic review.

PubMed

Correia, Francisco; Pozza, Daniel Humberto; Gouveia, Sónia; Felino, António; Faria E Almeida, Ricardo

2018-04-01

Findings in regenerative medicine applied to the sinus lift procedures. Evaluate the effectiveness of regenerative medicine in sinus lift. An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results. © 2017 Wiley Periodicals, Inc.

Coordinating resources for prospective medication risk management of older home care clients in primary care: procedure development and RCT study design for demonstrating its effectiveness.

PubMed

Toivo, Terhi; Dimitrow, Maarit; Puustinen, Juha; Savela, Eeva; Pelkonen, Katariina; Kiuru, Valtteri; Suominen, Tuula; Kinnunen, Sirkka; Uunimäki, Mira; Kivelä, Sirkka-Liisa; Leikola, Saija; Airaksinen, Marja

2018-03-16

The magnitude of safety risks related to medications of the older adults has been evidenced by numerous studies, but less is known of how to manage and prevent these risks in different health care settings. The aim of this study was to coordinate resources for prospective medication risk management of home care clients ≥ 65 years in primary care and to develop a study design for demonstrating effectiveness of the procedure. Health care units involved in the study are from primary care in Lohja, Southern Finland: home care (191 consented clients), the public healthcare center, and a private community pharmacy. System based risk management theory and action research method was applied to construct the collaborative procedure utilizing each profession's existing resources in medication risk management of older home care clients. An inventory of clinical measures in usual clinical practice and systematic review of rigorous study designs was utilized in effectiveness study design. The new coordinated medication management model (CoMM) has the following 5 stages: 1) practical nurses are trained to identify clinically significant drug-related problems (DRPs) during home visits and report those to the clinical pharmacist. Clinical pharmacist prepares the cases for 2) an interprofessional triage meeting (50-70 cases/meeting of 2 h) where decisions are made on further action, e.g., more detailed medication reviews, 3) community pharmacists conduct necessary medication reviews and each patients' physician makes final decisions on medication changes needed. The final stages concern 4) implementation and 5) follow-up of medication changes. Randomized controlled trial (RCT) was developed to demonstrate the effectiveness of the procedure. The developed procedure is feasible for screening and reviewing medications of a high number of older home care clients to identify clients with severe DRPs and provide interventions to solve them utilizing existing primary care resources. The study is registered in the Clinical Trials.gov ( NCT02545257 ). Registration date September 9 2015.

Case-controlled clinical and histopathological study of conjunctivochalasis.

PubMed

Francis, I C; Chan, D G; Kim, P; Wilcsek, G; Filipic, M; Yong, J; Coroneo, M T

2005-03-01

Conjunctivochalasis, a secondary cause of the watery eye, is frequently seen in the older age group as an elevation of the bulbar conjunctiva lying along the lateral or central lower lid margin. A prospective, interventional, case-controlled clinical and histopathological study was conducted. The relevant features of 18 patients (29 eyes) who had their conjunctivochalasis resected as part of the surgical management of their watery eye syndrome were examined. In the control group, tissue was obtained from an age matched series of 24 normal subjects undergoing routine cataract surgery. 24 controls (24 specimens) and 18 patients (29 specimens) had conjunctival strip biopsies, taken from the usual lid margin level bulbar conjunctiva in line with the inferior limbus (controls), and the clinically apparent conjunctivochalasis (patients). These were submitted for histological study. 23 of 24 control sections demonstrated normal conjunctival variation. Four of 29 patient specimens demonstrated a chronic non-granulomatous conjunctivitis, while three eyes of the patient group (two patients) demonstrated features of elastosis. Of the four patients who had the inflammatory infiltrates, three had functional nasolacrimal duct obstructions (FNLDOs) and one had a primary acquired nasolacrimal duct obstruction (PANDO). Of the two patients who had elastosis, one had an FNLDO and the other had normal lacrimal drainage and was Jones 1 positive. Six of 18 patients--that is, seven of 29 specimens of conjunctivochalasis demonstrated signs of elastosis or of chronic non-granulomatous inflammation. Clinically, patients had a spectrum of aetiologies of their watery eye syndrome.

Current knowledge about the hydrophilic and nanostructured SLActive surface

PubMed Central

Wennerberg, Ann; Galli, Silvia; Albrektsson, Tomas

2011-01-01

This review summarizes the present documentation for the SLActive surface, a hydrophilic and nanostructured surface produced by Straumann Company in Switzerland, and covers the results from 15 in vitro, 17 in vivo, and 16 clinical studies. The SLActive surface is a development of the large grit-blasted and acid-etched SLA surface, and is further processed to a high degree of hydrophilicity. In general, the in vitro and in vivo studies of the SLActive surface demonstrate a stronger cell and bone tissue response than for the predecessor, the SLA surface, produced by the same company. However, in most studies, this difference disappears after 6–8 weeks. In the clinical studies, a stronger bone response was reported for the SLActive surface during the early healing phase when compared with the SLA surface. However, the later biological response was quite similar for the two surfaces and both demonstrated very good clinical results. PMID:23674916

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

PubMed

Ridenour, Ty A; Wittenborn, Andrea K; Raiff, Bethany R; Benedict, Neal; Kane-Gill, Sandra

2016-03-01

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

PubMed

Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

2018-01-01

With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified the suggested association. Increased homocysteine is thought to be associated with vitamin B12 deficiency - evaluation for potential clinical relevance is suggested. While considerations for clinical metabolic profiling are recommended, including adjustment approaches for clinical confounders, AutoML presents an exciting tool to enhance clinical metabolic profiling and advance translational research endeavors.

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

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

2016-08-01

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

A Comparison of In-service Teaching Methods on Clinical Aspesis for Dental Personnel.

ERIC Educational Resources Information Center

Fotos, Pete G.; And Others

1990-01-01

Results of a study with dental assistants and hygienists, clinic clerks, supply and sterilization personnel, receptionists, and housekeeping and secretarial staff (n=80) suggest that inservice training programs on infection control and clinical asepsis procedures may be better accomplished by practical demonstration than by lecture or seminar.…

Short-Term Memory and Auditory Processing Disorders: Concurrent Validity and Clinical Diagnostic Markers

ERIC Educational Resources Information Center

Maerlender, Arthur

2010-01-01

Auditory processing disorders (APDs) are of interest to educators and clinicians, as they impact school functioning. Little work has been completed to demonstrate how children with APDs perform on clinical tests. In a series of studies, standard clinical (psychometric) tests from the Wechsler Intelligence Scale for Children, Fourth Edition…

Is cold or warm blood cardioplegia superior for myocardial protection?

PubMed Central

Abah, Udo; Roberts, Patrick Garfjeld; Ishaq, Muhammad; De Silva, Ravi

2012-01-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of warm or cold blood cardioplegia has superior myocardial protection. More than 192 papers were found using the reported search, of which 20 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. A good breadth of high-level evidence addressing this clinical dilemma is available, including a recent meta-analysis and multiple large randomized clinical trials. Yet despite this level of evidence, no clear significant clinical benefit has been demonstrated by warm or cold blood cardioplegia. This suggests that neither method is significantly superior and that both provide similar efficacy of myocardial protection. The meta-analysis, including 41 randomized control trials (5879 patients in total), concluded that although a lower cardiac enzyme release and improved postoperative cardiac index was demonstrated in the warm cardioplegia group, this benefit was not reflected in clinical outcomes, which were similar in both groups. This theme of benefit in biochemical markers, physiological metrics and non-fatal postoperative events in the warm cardioplegia group ran throughout the literature, in particular the ‘Warm Heart investigators’ who conducted a randomized trial of 1732 patients, demonstrated a reduction in postoperative low output syndrome (6.1 versus 9.3%, P = 0.01) in the warm cardioplegia group, but no significant drop in 30-day all-cause mortality (1.4 versus 2.5%, P = 0.12). However, their later follow-up indicates non-fatal postoperative events predict reduced late survival, independent of cardioplegia. A minority of studies suggested a benefit of cold cardioplegia over warm in particular patient subgroups: One group conducted a retrospective study of 520 patients who required prolonged aortic cross-clamp times, results demonstrated less myocardial damage and reduced postoperative cardiac mortality and morbidity in the cold group. The clinical bottom line is that warm and cold cardioplegia result in similar short-term mortality. However, large studies have shown that warm cardioplegia reduces adverse post-operative events; the significance of which is unclear. PMID:22402501

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Cultivation and grafting of human keratinocytes on a poly(hydroxyethyl methacrylate) support to the wound bed: a clinical study.

PubMed

Dvoránková, B; Smetana, K; Königová, R; Singerová, H; Vacík, J; Jelínková, M; Kapounková, Z; Zahradník, M

1998-01-01

Cultured epithelial sheets on a textile support are used for the treatment of seriously burned patients. In this study we demonstrate a new procedure for the grafting of keratinocytes directly on a polymer cultivation support. This procedure is much easier in comparison with classical techniques, and encouraging results of clinical trials demonstrate the improved healing of the wound bed after the use of this procedure. There is no difference in the cytokeratine pattern (LP-34, cytokeratin-10) of the reconstructed epidermis and normal human skin.

Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demonstrate clinical efficacy.

PubMed

Bush, Karen; Heep, Markus; Macielag, Mark J; Noel, Gary J

2007-04-01

Ceftobiprole is the first of the investigational beta-lactam antibiotics with in vitro activity against methicillin-resistant staphylococci to reach and complete Phase III therapeutic trials. Its antibacterial spectrum includes methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens. It has demonstrated in vivo activity against many experimental infections caused by these pathogens. Ceftobiprole has completed Phase III clinical trials for complicated skin and skin structure infections, is being studied in Phase III pneumonia trials and has demonstrated non-inferiority compared with vancomycin in a Phase III complicated skin and skin structure infections trial, resulting in > 90% clinical cures of infections caused by MRSA. Other anti-MRSA beta-lactams in therapeutic clinical trials include the carbapenem CS-023/RO-4908463 and the cephalosporin ceftaroline (PPI-0903). The future of all of these agents will depend on their clinical efficacy, safety and their ability to be accepted as beta-lactams for the reliable treatment of a broad spectrum of infections, including those caused by MRSA.

The Preservation of Cued Recall in the Acute Mentally Fatigued State: A Randomised Crossover Study.

PubMed

Flindall, Ian Richard; Leff, Daniel Richard; Pucks, Neysan; Sugden, Colin; Darzi, Ara

2016-01-01

The objective of this study is to investigate the impact of acute mental fatigue on the recall of clinical information in the non-sleep-deprived state. Acute mental fatigue in the non-sleep-deprived subject is rarely studied in the medical workforce. Patient handover has been highlighted as an area of high risk especially in fatigued subjects. This study evaluates the deterioration in recall of clinical information over 2 h with cognitively demanding work in non-sleep-deprived subjects. A randomised crossover study involving twenty medical students assessed free (presentation) and cued (MCQ) recall of clinical case histories at 0 and 2 h under low and high cognitive load using the N-Back task. Acute mental fatigue was assessed through the Visual Analogue Scale, Stanford Scale and NASA-TLX Mental Workload Rating Scale. Free recall is significantly impaired by increased cognitive load (p < 0.05) with subjects demonstrating perceived mental fatigue during the high cognitive load assessment. There was no significant difference in the amount of information retrieved by cued recall under high and low cognitive load conditions (p = 1). This study demonstrates the loss of clinical information over a short time period involving a mentally fatiguing, high cognitive load task. Free recall for the handover of clinical information is unreliable. Memory cues maintain recall of clinical information. This study provides evidence towards the requirement for standardisation of a structured patient handover. The use of memory cues (involving recognition memory and cued recall methodology) would be beneficial in a handover checklist to aid recall of clinical information and supports evidence for their adoption into clinical practice.

Clinical outcomes of a specialised inpatient unit for adults with mild to severe intellectual disability and mental illness.

PubMed

Lunsky, Y; White, S E; Palucka, A M; Weiss, J; Bockus, S; Gofine, T

2010-01-01

Limitations of general psychiatric services have led to the development of specialised psychiatric programmes for patients with intellectual disability (ID) and mental health needs. Few studies have examined treatment outcomes of specialised inpatient units, and no studies have explored how the effects of intervention may differ for individuals at varying levels of cognitive ability. The present study examined clinical outcomes of inpatients with mild ID in contrast to inpatients with moderate to severe ID within the same service. Thirty-three patients (17 with mild ID and 16 with moderate to severe ID) discharged between 2006 and 2008 from a specialised inpatient unit in Canada for adults with ID and mental illness were studied. In addition to examining change in scores on clinical measures, outcomes with regard to length of stay, diagnostic change, residential change and re-admission to hospital were explored. Both groups demonstrated clinical improvement from admission to discharge. However, only patients with mild ID demonstrated improvements on the Global Assessment of Functioning. This study is one of the first to consider outcomes of higher and lower functioning individuals with ID on a specialised inpatient unit. Results suggest that outcomes may be different for these groups, and some clinical measures may be more sensitive to changes in patients with more severe disabilities.

Clinical, chemical, and hematological parameters in cattle kept in a cadmium-contaminated area

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

Kessels, B.G.F.; Wensing, Th.; Schotman, A.J.H.

1990-02-01

In cattle exposure to cadmium may effect various clinical abnormalities such as loss of appetite, anemia, poor growth, abortions and teratogenic lesions or may pass without clinical abnormalities. Considerably less is known about the effects of chronic exposure to low levels of cadmium on clinical, chemical and hematological parameters. With respect to the way cattle can ingest cadmium from the environment, a relationship was demonstrated between cadmium content of the organs and soil cadmium content. This demonstration that, raising roughage on cadmium contaminated soil or in fields treated with cadmium containing fertilizers like sewage sludge can lead to accumulation ofmore » cadmium in the cattle in question. This study aims to investigate whether a low, chronic exposure to cadmium effects changes in some hematological, clinical and chemical parameters in cattle.« less

Assessment of critical thinking: a Delphi study.

PubMed

Paul, Sheila A

2014-11-01

Nurse educators are responsible for preparing nurses who critically analyze patient information and provide meaningful interventions in today's complex health care system. By using the Delphi research method, this study, utilized the specialized and experiential knowledge of Certified Nurse Educators. This original Delphi research study asked Certified Nurse Educators how to assess the critical-thinking ability of nursing students in the clinical setting. The results showed that nurse educators need time, during the clinical experience, to accurately assess each individual nursing student. This study demonstrated the need for extended student clinical time, and a variety of clinical learning assessment tools. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluations of refraction competencies of ophthalmic technicians in Mozambique.

PubMed

Shah, Kajal; Naidoo, Kovin; Chagunda, Margarida; Loughman, James

2016-01-01

Ophthalmic technicians (OT) work at health facilities in Mozambique and are trained to provide primary and secondary eye care services including basic refraction. This study was designed to assess OT competence and confidence in refraction, and investigate whether an upskilling programme is effective in developing their competence and confidence at refraction. Thirty-one trainee OTs and 16 qualified OTs were recruited to the study. A background questionnaire was administered to determine the demographic profile of the OTs. A confidence levels questionnaire explored their self-reported skills. Clinical competencies were assessed in relation to knowledge (theory exam) and clinical skills (patient exams). 11 OTs were upskilled and the clinical evaluations carried out post training. Initial evaluations demonstrated that confidence and competence levels varied depending on the OTs training (location and duration), and their location of work (clinical load, availability of equipment and other eye care personnel). The qualified OTs were more competent than trainee OTs in most of the evaluations. Post upskilling results demonstrated significant positive impact on confidence and competence levels. These evaluations identified factors affecting the refraction competencies of the OTs and demonstrated that upskilling is effective in improving confidence and competence levels for refraction. They demonstrate the need for a refraction competency framework. The overarching aim of this research was to inform the development of a nationwide programme of OT mentoring, upskilling and leading to the establishment of clinical competency standards for the new OT curricula, relevant to the professional demands. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Computerized scintigraphic technique for the evaluation of adult respiratory distress syndrome: initial clinical trials

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

Tatum, J.L.; Burke, T.S.; Sugerman, H.T.

1982-04-01

Eleven patients with suspected adult respiratory distress syndrome (ARDS) and five control patients were studied using a computerized gamma imaging and analysis technique and /sup 99m/Tc-labeled human serum albumin. The heart and right lung were imaged, lung:heart ratio was plotted vs. time, and a linear regression was fitted to the data points displayed. The slope of this fit was termed the ''slope index.'' An index value of 2 standard deviations greater than the control mean was considered positive. Radiographs from the six positive studies revealed typical diffuse air-space disease. Radiographs from two of the five negative studies demonstrated air-space consolidation.more » Both of these patients had elevated pulmonary capillary wedge pressure, cardiomegaly, and clinical course consistent with cardiogenic pulmonary edema. These preliminary data demonstrated a good correlation between positive slope index and clinical ARDS.« less

Computerized scintigraphic technique for the evaluation of adult respiratory distress syndrome: initial clinical trials

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

Tatum, J.L.; Burke, T.S.; Sugerman, H.J.

1982-04-01

Eleven patients with suspected adult respiratory distress syndrome (ARDS) and five control patients were studied using a computerized gamma imaging and analysis technique and 99mTc-labeled human serum albumin. The heart and right lung were imaged, lung:heart ratio was plotted vs. time, and a linear regression was fitted to the data points displayed. The slope of this fit was termed the ''slope index.'' An index value of 2 standard deviations greater than the control mean was considered positive. Radiographs from the six positive studies revealed typical diffuse air-space disease. Radiographs from two of the five negative studies demonstrated air-space consolidation. Bothmore » of these patients had elevated pulmonary capillary wedge pressure, cardiomegaly, and clinical course consistent with cardiogenic pulmonary edema. These preliminary data demonstrated a good correlation between positive slope index and clinical ARDS.« less

Cannabinoids and Dementia: A Review of Clinical and Preclinical Data

PubMed Central

Walther, Sebastian; Halpern, Michael

2010-01-01

The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia. We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD). Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro. However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce. While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia. Further research is needed, including in vivo models of dementia and human studies. PMID:27713372

Introducing practice-based learning and improvement ACGME core competencies into a family medicine residency curriculum.

PubMed

Coleman, Mary Thoesen; Nasraty, Soraya; Ostapchuk, Michael; Wheeler, Stephen; Looney, Stephen; Rhodes, Sandra

2003-05-01

The Accreditation Council for Graduate Medical Education (ACGME) recommends integrating improvement activities into residency training. A curricular change was designed at the Department of Family and Community Medicine, University of Louisville, to address selected ACGME competencies by incorporating practice-based improvement activities into the routine clinical work of family medicine residents. Teams of residents, faculty, and office staff completed clinical improvement projects at three ambulatory care training sites. Residents were given academic credit for participation in team meetings. After 6 months, residents presented results to faculty, medical students, other residents, and staff from all three training sites. Residents, staff, and faculty were recognized for their participation. Resident teams demonstrated ACGME competencies in practice-based improvement: Chart audits indicated improvement in clinical projects; quality improvement tools demonstrated analysis of root causes and understanding of the process; plan-do-study-act cycle worksheets demonstrated the change process. Improvement activities that affect patient care and demonstrate selected ACGME competencies can be successfully incorporated into the daily work of family medicine residents.

Magnetic resonance neurography and diffusion tensor imaging: origins, history, and clinical impact of the first 50,000 cases with an assessment of efficacy and utility in a prospective 5000-patient study group.

PubMed

Filler, Aaron

2009-10-01

Methods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. The history, physical basis, and dyadic tensor concept underlying the methods are reviewed. Over a 15-year period, these techniques-magnetic resonance neurography (MRN) and diffusion tensor imaging-were deployed in the clinical and research community in more than 2500 published research reports and applied to approximately 50,000 patients. Within this group, approximately 5000 patients having MRN were carefully tracked on a prospective basis. A uniform Neurography imaging methodology was applied in the study group, and all images were reviewed and registered by referral source, clinical indication, efficacy of imaging, and quality. Various classes of image findings were identified and subjected to a variety of small targeted prospective outcome studies. Those findings demonstrated to be clinically significant were then tracked in the larger clinical volume data set. MRN demonstrates mechanical distortion of nerves, hyperintensity consistent with nerve irritation, nerve swelling, discontinuity, relations of nerves to masses, and image features revealing distortion of nerves at entrapment points. These findings are often clinically relevant and warrant full consideration in the diagnostic process. They result in specific pathological diagnoses that are comparable to electrodiagnostic testing in clinical efficacy. A review of clinical outcome studies with diffusion tensor imaging also shows convincing utility. MRN and diffusion tensor imaging neural tract imaging have been validated as indispensable clinical diagnostic methods that provide reliable anatomic pathological information. There is no alternative diagnostic method in many situations. With the elapsing of 15 years, tens of thousands of imaging studies, and thousands of publications, these methods should no longer be considered experimental.

Patient-Reported Outcomes of Periacetabular Osteotomy from the Prospective ANCHOR Cohort Study

PubMed Central

Clohisy, John C.; Ackerman, Jeffrey; Baca, Geneva; Baty, Jack; Beaulé, Paul E.; Kim, Young-Jo; Millis, Michael B.; Podeszwa, David A.; Schoenecker, Perry L.; Sierra, Rafael J.; Sink, Ernest L.; Sucato, Daniel J.; Trousdale, Robert T.; Zaltz, Ira

2017-01-01

Background: Current literature describing the periacetabular osteotomy (PAO) is mostly limited to retrospective case series. Larger, prospective cohort studies are needed to provide better clinical evidence regarding this procedure. The goals of the current study were to (1) report minimum 2-year patient-reported outcomes (pain, hip function, activity, overall health, and quality of life), (2) investigate preoperative clinical and disease characteristics as predictors of clinical outcomes, and (3) report the rate of early failures and reoperations in patients undergoing contemporary PAO surgery. Methods: A large, prospective, multicenter cohort of PAO procedures was established, and outcomes at a minimum of 2 years were analyzed. A total of 391 hips were included for analysis (79% of the patients were female, and the average patient age was 25.4 years). Patient-reported outcomes, conversion to total hip replacement, reoperations, and major complications were documented. Variables with a p value of ≤0.10 in the univariate linear regressions were included in the multivariate linear regression. The backward stepwise selection method was used to determine the final risk factors of clinical outcomes. Results: Clinical outcome analysis demonstrated major clinically important improvements in pain, function, quality of life, overall health, and activity level. Increasing age and a body mass index status of overweight or obese were predictive of improved results for certain outcome metrics. Male sex and mild acetabular dysplasia were predictive of lesser improvements in certain outcome measures. Three (0.8%) of the hips underwent early conversion to total hip arthroplasty, 12 (3%) required reoperation, and 26 (7%) experienced a major complication. Conclusions: This large, prospective cohort study demonstrated the clinical success of contemporary PAO surgery for the treatment of symptomatic acetabular dysplasia. Patient and disease characteristics demonstrated predictive value that should be considered in surgical decision-making. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:28060231

The role of point of care ultrasound in prehospital critical care: a systematic review.

PubMed

Bøtker, Morten Thingemann; Jacobsen, Lars; Rudolph, Søren Steemann; Knudsen, Lars

2018-06-26

In 2011, the role of Point of Care Ultrasound (POCUS) was defined as one of the top five research priorities in physician-provided prehospital critical care and future research topics were proposed; the feasibility of prehospital POCUS, changes in patient management induced by POCUS and education of providers. This systematic review aimed to assess these three topics by including studies examining all kinds of prehospital patients undergoing all kinds of prehospital POCUS examinations and studies examining any kind of POCUS education in prehospital critical care providers. By a systematic literature search in MEDLINE, EMBASE, and Cochrane databases, we identified and screened titles and abstracts of 3264 studies published from 2012 to 2017. Of these, 65 studies were read in full-text for assessment of eligibility and 27 studies were ultimately included and assessed for quality by SIGN-50 checklists. No studies compared patient outcome with and without prehospital POCUS. Four studies of acceptable quality demonstrated feasibility and changes in patient management in trauma. Two studies of acceptable quality demonstrated feasibility and changes in patient management in breathing difficulties. Four studies of acceptable quality demonstrated feasibility, outcome prediction and changes in patient management in cardiac arrest, but also that POCUS may prolong pauses in compressions. Two studies of acceptable quality demonstrated that short (few hours) teaching sessions are sufficient for obtaining simple interpretation skills, but not image acquisition skills. Three studies of acceptable quality demonstrated that longer one- or two-day courses including hands-on training are sufficient for learning simple, but not advanced, image acquisition skills. Three studies of acceptable quality demonstrated that systematic educational programs including supervised examinations are sufficient for learning advanced image acquisition skills in healthy volunteers, but that more than 50 clinical examinations are required for expertise in a clinical setting. Prehospital POCUS is feasible and changes patient management in trauma, breathing difficulties and cardiac arrest, but it is unknown if this improves outcome. Expertise in POCUS requires extensive training by a combination of theory, hands-on training and a substantial amount of clinical examinations - a large part of these needs to be supervised.

Treatment of periodontal intrabony defects using β-TCP alone or in combination with rhPDGF-BB: a randomized controlled clinical and radiographic study.

PubMed

Maroo, Sneha; Murthy, K Raja V

2014-01-01

The need to increase the predictability of periodontal regeneration has encouraged clinicians and researchers to employ cell-stimulating proteins in combination with osteoconductive scaffolds, based on the principles of tissue engineering. The purpose of this clinical and radiographic study was to compare the regenerative potential of the combination of β-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB (rhPDGF-BB) in the grafting of intraosseous defects with the established technique of bone grafting with (β-TCP alone. A total of 30 sites from 15 patients with infrabony defects in two different quadrants were selected, and the sites were randomly divided into test sites (rhPDGF + β-TCP) and control sites (β-TCP alone) using a split-mouth design. Clinical parameters, including probing pocket depth, clinical attachment level, and gingival recession, were recorded at baseline, 6 months, and 9 months. Radiographic evaluation was carried out to evaluate defect fill, change in alveolar crest height, and percentage of defect fill at baseline, 6 months, and 9 months. Both the experimental groups showed statistically significant reduction in probing pocket depth and gain in clinical attachment level. On intergroup comparison, sites treated with rhPDGF + β-TCP demonstrated a significantly greater pocket depth reduction (P < .05) and greater gain in clinical attachment level (P < .01). Mean percentage defect fill was significantly greater in test sites as compared with control sites at 6 and 9 months (P < .01). rhPDGF + β-TCP-treated sites demonstrated a significant gain in mean alveolar crest height at 6 and 9 months (P < .05), while β-TCP-treated sites demonstrated crestal resorption. Both groups demonstrated potential in enhancing periodontal regeneration; however, on comparison between the two groups, the results obtained by rhPDGF + β-TCP were significantly better with respect to both clinical and radiographic parameters.

The Impact of Patient-to-Patient Interaction in Health Facility Waiting Rooms on Their Perception of Health Professionals.

PubMed

Willis, William Kent; Ozturk, Ahmet Ozzie; Chandra, Ashish

2015-01-01

Patients have to wait in waiting rooms prior to seeing the physician. But there are few studies that demonstrate what they are actually doing in the waiting room. This exploratory study was designed to investigate the types of discussions that patients in the waiting room typically engage in with other patients and how the conversations affected their opinion on general reputation of the clinic, injections/blocks as treatment procedures, waiting time, time spent with the caregiver, overall patient satisfaction, and the pain medication usage policy. The study demonstrates that patient interaction in the waiting room has a positive effect on patient opinion of the pain clinic and the caregivers.

Eslicarbazepine acetate: its effectiveness as adjunctive therapy in clinical trials and open studies.

PubMed

Shorvon, S D; Trinka, E; Steinhoff, B J; Holtkamp, M; Villanueva, V; Peltola, J; Ben-Menachem, E

2017-03-01

Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug that is approved as adjunctive therapy in adults with focal-onset seizures. Following oral administration, ESL is rapidly metabolized to its active metabolite, eslicarbazepine, which acts primarily by enhancing slow inactivation of voltage-gated sodium channels. The efficacy and safety/tolerability of ESL in the adjunctive setting were established in a comprehensive Phase III program (n = 1702 randomized patients) and this evidence has been supported by several open studies (n = 864). ESL treatment has demonstrated improvements in health-related quality of life, in both randomized clinical trials and open studies. ESL has also been shown to be usually well tolerated and efficacious when used in the adjunctive setting in elderly patients. The effectiveness of ESL as the only add-on to antiepileptic drug monotherapy has been demonstrated in a multinational study (n = 219), subgroup analyses of which have also shown it to be efficacious and generally well tolerated in patients who had previously not responded to carbamazepine therapy. Open studies have also demonstrated improvements in tolerability in patients switched overnight from oxcarbazepine to ESL. Due to differences in pharmacokinetics, pharmacodynamics, and metabolism, there may be clinical situations in which it is appropriate to consider switching patients from oxcarbazepine or carbamazepine to ESL.

The effects of Clinical Pilates exercises on patients with shoulder pain: A randomised clinical trial.

PubMed

Atılgan, Esra; Aytar, Aydan; Çağlar, Aslıcan; Tığlı, Ayça Aytar; Arın, Gamze; Yapalı, Gökmen; Kısacık, Pınar; Berberoğlu, Utku; Şener, Hülya Özlem; Ünal, Edibe

2017-10-01

The purpose of this study was to determine the effect of Clinical Pilates exercises on patients with shoulder pain. Thirty-three patients, experiencing shoulder pain continuously for at least four weeks were selected as study subjects. The patients were randomly divided into two groups, namely Clinical Pilates exercise (n = 17) group and conventional exercise (n = 16) group. The patients were treated for five days a week, the total treatment being carried out for 10 days. The assessment of pain and disability amongst the patients were done at the baseline and at the end of the treatment sessions, using Visual Analogue Scale (VAS) and Shoulder Pain and Disability Index (SPADI). The clinical Pilates exercise group showed a significant improvement in all scores used for assessment (p < 0.05), while the conventional exercise group demonstrated a significant improvement only in the SPADI total score (p < 0.05). A comparison of scores for the VAS, SPADI-Pain and SPADI-Total between the two groups, revealed a significant improvement in the Clinical Pilates exercise group (p < 0.05). It was demonstrated by the study that Clinical Pilates exercise is an efficient technique for patients experiencing shoulder pain, as it helps reduce pain and disability among them. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing new BSN RN self skills assessment to actual skills demonstration.

PubMed

Adair, Jean; Hughes, Lin; Davis, Sue; Wolcott-Breci, Mary

2014-01-01

The purpose of the study was to compare the self-skills assessment with the skill competence during an actual skills demonstration of newly hired bachelor of science in nursing (BSN) registered nurse graduates. This retrospective study included 32 randomly selected BSN registered nurse graduates from January 2010 to December 31, 2010. The participants were already hired into a midwest health system. Because this was a retrospective study, no demographic data were collected, and no consent from participants was needed. This study included a clinical skills check list where the participants rated themselves on specific skills utilizing a Likert scale ranging from 1 (no knowledge) to 4 (able to perform independently). The same clinical check list was utilized by an expert registered nurse when the skill was demonstrated. This study compared the difference between the subject's self-rating of skills and the clinical demonstration of the skills. We used t tests in the analysis to demonstrate the differences between the participant's self-rating of skills and the expert evaluation of the clinical demonstration of the skills. The data were inserted into the Statistical Package for the Social Sciences 19 software program to assist in the analysis process. The study demonstrated 17 significant differences in the skills ratings between the participant and competency demonstration of new BSN graduates. These significant results (2 tailed) ranged from .000 to .048.The 17 out of 46 specific skills where differences were noted included the following: staple removal, nasal pharyngeal suctioning, urinary catheter specimen collection, site care dressing change, urinary catheter irrigation, Juzo application and measurement, 5-lead telemetry, oral airway insertion, hemovac/Jackson Pratt, oral pharyngeal suctioning, urinary catheter insertion, dry suction chest drainage, bed to cart/slider board, urinary catheter removal, antiembolism stockings, measurement and application, removal of iv and sit-and-stand alarm. Overall, the participants rated their skill levels lower in 15 out of 17 significant skills when compared with their competency assessment (t test: -3.284, df = 31, P = .003). In two skill ratings (urinary catheter specimen collection and oral pharyngeal suction), the participants rated themselves higher than the competency demonstration. Two skills that had a mean participant and expert score between 1 (no knowledge) and 2 (able to perform with 1-to-1 coaching) were oral airway insertion and dry suction chest drainage. Some possible reasons why the participants rated themselves lower could be the use of different or unfamiliar terms or uncertainty of the procedure at a different health institution. Some newly graduated BSN nurses may have not performed the skills on a regular basis or only in simulation. © 2014.

WE-G-217BCD-04: Diagnostic Image Quality Evaluation of a Dedicated Extremity Cone- Beam CT Scanner: Pre-Clinical Studies and First Clinical Results.

PubMed

Muhit, A; Zbijewski, W; Stayman, J; Thawait, G; Yorkston, J; Foos, D; Packard, N; Yang, D; Senn, R; Carrino, J; Siewerdsen, J

2012-06-01

To assess the diagnostic performance of a prototype cone-beam CT (CBCT) scanner developed for musculoskeletal extremity imaging. Studies involved controlled observer studies conducted subsequent to rigorous technical assessment as well as patient images from the first clinical trial in imaging the hand and knee. Performance assessment included: 1.) rigorous technical assessment; 2.) controlled observer studies using CBCT images of cadaveric specimens; and 3.) first clinical images. Technical assessment included measurement of spatial resolution (MTF), constrast, and noise (SDNR) versus kVp and dose using standard CT phantoms. Diagnostic performance in comparison to multi- detector CT (MDCT) was assessed in controlled observer studies involving 12 cadaveric hands and knees scanned with and without abnormality (fracture). Observer studies involved five radiologists rating pertinent diagnostics tasks in 9-point preference and 10-point diagnostic satisfaction scales. Finally, the first clinical images from an ongoing pilot study were assessed in terms of diagnostic utility in disease assessment and overall workflow in patient setup. Quantitative assessment demonstrated sub-mm spatial resolution (MTF exceeding 10% out to 15-20 cm-1) and SDNR sufficient for relevant soft-tissue visualization tasks at dose <10 mGy. Observer studies confirmed optimal acquisition techniques and demonstrated superior utility of combined soft-tissue visualization and isotropic spatial resolution in diagnostic tasks. Images from the patient trial demonstrate exquisite contrast and detail and the ability to detect tissue impingement in weight-bearing exams. The prototype CBCT scanner provides isotropic spatial resolution superior to standard-protocol MDCT with soft-tissue visibility sufficient for a broad range of diagnostic tasks in musculoskeletal radiology. Dosimetry and workflow were advantageous in comparison to whole-body MDCT. Multi-mode and weight-bearing capabilities add valuable functionality. An ongoing clinical study further assesses diagnostic utility and defines the role of such technology in the diagnostic arsenal. - Research Grant, Carestream Health - Research Grant, National Institutes of Health 2R01-CA-112163. © 2012 American Association of Physicists in Medicine.

Clinical studies of the High-Intensity Narrow-Spectrum light Environmental Decontamination System (HINS-light EDS), for continuous disinfection in the burn unit inpatient and outpatient settings.

PubMed

Bache, Sarah E; Maclean, Michelle; MacGregor, Scott J; Anderson, John G; Gettinby, George; Coia, John E; Taggart, Ian

2012-02-01

Infections are the leading cause of morbidity and mortality in burn patients and prevention of contamination from exogenous sources including the hospital environment is becoming increasingly emphasised. The High-Intensity Narrow-Spectrum light Environmental Decontamination System (HINS-light EDS) is bactericidal yet safe for humans, allowing continuous disinfection of the environment surrounding burn patients. Environmental samples were collected from inpatient isolation rooms and the outpatient clinic in the burn unit, and comparisons were then made between the bacterial contamination levels observed with and without use of the HINS-light EDS. Over 1000 samples were taken. Inpatient studies, with sampling carried out at 0800 h, demonstrated a significant reduction in the average number of bacterial colonies following HINS-light EDS use of between 27% and 75%, (p<0.05). There was more variation when samples were taken at times of increased activity in the room. Outpatient studies during clinics demonstrated a 61% efficacy in the reduction of bacterial contamination on surfaces throughout the room during the course of a clinic (p=0.02). The results demonstrate that use of the HINS-light EDS allows efficacious bacterial reductions over and above that achieved by standard cleaning and infection control measures in both inpatient and outpatient settings in the burn unit. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Patient-specific analysis of post-operative aortic hemodynamics: a focus on thoracic endovascular repair (TEVAR)

NASA Astrophysics Data System (ADS)

Auricchio, F.; Conti, M.; Lefieux, A.; Morganti, S.; Reali, A.; Sardanelli, F.; Secchi, F.; Trimarchi, S.; Veneziani, A.

2014-10-01

The purpose of this study is to quantitatively evaluate the impact of endovascular repair on aortic hemodynamics. The study addresses the assessment of post-operative hemodynamic conditions of a real clinical case through patient-specific analysis, combining accurate medical image analysis and advanced computational fluid-dynamics (CFD). Although the main clinical concern was firstly directed to the endoluminal protrusion of the prosthesis, the CFD simulations have demonstrated that there are two other important areas where the local hemodynamics is impaired and a disturbed blood flow is present: the first one is the ostium of the subclavian artery, which is partially closed by the graft; the second one is the stenosis of the distal thoracic aorta. Besides the clinical relevance of these specific findings, this study highlights how CFD analyses allow to observe important flow effects resulting from the specific features of patient vessel geometries. Consequently, our results demonstrate the potential impact of computational biomechanics not only on the basic knowledge of physiopathology, but also on the clinical practice, thanks to a quantitative extraction of knowledge made possible by merging medical data and mathematical models.

Usefulness of two clinical chorioamnionitis definitions in predicting neonatal infectious outcomes: a systematic review.

PubMed

Avila, Cecilia; Willins, Jennifer L; Jackson, Matthew; Mathai, Jacob; Jabsky, Marina; Kong, Alex; Callaghan, Fiona; Ishkin, Selda; Shroyer, A Laurie W

2015-09-01

To assess the usefulness of two definitions of acute clinical chorioamnionitis (ACCA) in predicting risk of neonatal infectious outcomes (NIO) and mortality, the first definition requiring maternal fever alone (Fever), and the second requiring ≥ 1 Gibbs criterion besides fever (Fever + 1). PubMed, Web of Science, and the Cochrane Database of Systematic Reviews were searched from January 1, 1979 to April 9, 2013. Twelve studies were reviewed (of 316 articles identified): three studies with term patients, four with preterm premature rupture of membranes (PPROM) patients, and five mixed studies with mixed gestational ages and/or membrane status (intact and/or ruptured). Both definitions demonstrated an increased NIO risk for ACCA versus non-ACCA patients, with an odds ratio increase for the Fever + 1 definition that was about twofold larger than the Fever definition. As the Fever definition demonstrated increased NIO risk for ACCA versus non-ACCA patients, the Fever alone ACCA definition should be used to trigger future clinical treatment in many clinical situations. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies.

PubMed

Arnold, Ria; Kwai, Natalie C G; Krishnan, Arun V

2013-11-01

The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Spontaneous Swallow Frequency Compared with Clinical Screening in the Identification of Dysphagia in Acute Stroke

PubMed Central

Crary, Michael A.; Carnaby, Giselle D.; Sia, Isaac

2017-01-01

Background The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. Methods In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Results Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Conclusions Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. PMID:25088166

Spontaneous swallow frequency compared with clinical screening in the identification of dysphagia in acute stroke.

PubMed

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac

2014-09-01

The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

Barker, Christopher A., E-mail: barkerc@mskcc.org; Postow, Michael A.

Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicitymore » and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.« less

Unconscious race and class bias: its association with decision making by trauma and acute care surgeons.

PubMed

Haider, Adil H; Schneider, Eric B; Sriram, N; Dossick, Deborah S; Scott, Valerie K; Swoboda, Sandra M; Losonczy, Lia; Haut, Elliott R; Efron, David T; Pronovost, Peter J; Freischlag, Julie A; Lipsett, Pamela A; Cornwell, Edward E; MacKenzie, Ellen J; Cooper, Lisa A

2014-09-01

Recent studies have found that unconscious biases may influence physicians' clinical decision making. The objective of our study was to determine, using clinical vignettes, if unconscious race and class biases exist specifically among trauma/acute care surgeons and, if so, whether those biases impact surgeons' clinical decision making. A prospective Web-based survey was administered to active members of the Eastern Association for the Surgery of Trauma. Participants completed nine clinical vignettes, each with three trauma/acute care surgery management questions. Race Implicit Association Test (IAT) and social class IAT assessments were completed by each participant. Multivariable, ordered logistic regression analysis was then used to determine whether implicit biases reflected on the IAT tests were associated with vignette responses. In total, 248 members of the Eastern Association for the Surgery of Trauma participated. Of these, 79% explicitly stated that they had no race preferences and 55% stated they had no social class preferences. However, 73.5% of the participants had IAT scores demonstrating an unconscious preference toward white persons; 90.7% demonstrated an implicit preference toward upper social class persons. Only 2 of 27 vignette-based clinical decisions were associated with patient race or social class on univariate analyses. Multivariable analyses revealed no relationship between IAT scores and vignette-based clinical assessments. Unconscious preferences for white and upper-class persons are prevalent among trauma and acute care surgeons. In this study, these biases were not statistically significantly associated with clinical decision making. Further study of the factors that may prevent implicit biases from influencing patient management is warranted. Epidemiologic study, level II.

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin

PubMed Central

McDade, E.; Burrus, T.M.; Boot, B.P.; Kantarci, K.; Fields, J.; Lowe, V.J.; Peller, P.; Knopman, D.; Baker, M.; Finch, N.; Rademakers, R.; Petersen, R.

2012-01-01

Objective: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). Methods: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. Results: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. Conclusions: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease. PMID:22491866

New Kids on the Block: RNA-Based Influenza Virus Vaccines.

PubMed

Scorza, Francesco Berlanda; Pardi, Norbert

2018-04-01

RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

Patient costs in anticoagulation management: a comparison of primary and secondary care.

PubMed Central

Parry, D; Bryan, S; Gee, K; Murray, E; Fitzmaurice, D

2001-01-01

BACKGROUND: The demand for anticoagulation management is increasing. This has led to care being provided in non-hospital settings. While clinical studies have similarly demonstrated good clinical care in these settings, it is still unclear as to which alternative is the most efficient. AIM: To determine the costs borne by patients when attending an anticoagulation management clinic in either primary or secondary care and to use this information to consider the cost-effectiveness of anticoagulation management in primary and secondary care, both from the National Health Service and patient perspectives. DESIGN OF STUDY: Observational study comparing two cohorts of patients currently attending anticoagulation management clinics. SETTING: Four primary care clinics in Birmingham and one in Warwickshire, and the haematology clinics at the University of Birmingham Hospitals Trust and the City Hospital NHS Trust. METHOD: The survey of patients attending the clinics was used to ascertain patient costs. This information was then used in conjunction with the findings of a recent randomised controlled trial to establish cost-effectiveness. RESULTS: Patient costs were lower in primary care than in secondary care settings; the mean (standard deviation) costs per visit were Pound Sterling6.78 (Pound Sterling5.04) versus Pound Sterling14.58 (Pound Sterling9.08). While a previous cost-effectiveness analysis from a health sector perspective alone found a higher cost for primary care, the adoption of the societal perspective lead to a marked change in the result: a similar total cost per patient in both sectors. CONCLUSION: There are significantly higher costs borne by patients attending secondary care anticoagulation management clinics than similar patients attending primary care clinics. This study also demonstrates that the perspective adopted in an economic evaluation can influence the final result. PMID:11766869

Comparative oncology evaluation of intravenous recombinant oncolytic Vesicular Stomatitis Virus therapy in spontaneous canine cancer

PubMed Central

Naik, Shruthi; Galyon, Gina D.; Jenks, Nathan J.; Steele, Michael B.; Miller, Amber C.; Allstadt, Sara D.; Suksanpaisan, Lukkana; Peng, Kah Whye; Federspiel, Mark J.; Russell, Stephen J.; LeBlanc, Amy K.

2017-01-01

Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single shot systemic therapy with a VSV-IFNβ-NIS, a novel recombinant oncolytic Vesicular stomatitis virus (VSV), can induce curative remission in tumor bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy, and potential biomarkers that correlate with therapeutic response. PMID:29158470

Educational videos for practitioners attending Baby Friendly Hospital Initiative workshops supporting breastfeeding positioning, attachment and hand expression skills: Effects on knowledge and confidence.

PubMed

Wallace, Louise M; Ma, Yuanying; Qiu, Li Qian; Dunn, Orla M

2018-04-26

UNICEF Baby Friendly Initiative (BFHI) is the global standard for maternity and community services requiring all practitioners to be trained to support mothers in the essential skills of supporting positioning and attachment, and hand expression. These studies aim to rigorously assess knowledge in nurses, midwives, and doctors in these skills, tested before and after watching short videos demonstrating these skills. Practitioners were attending BFHI education, and the video study was additional. In Phase 1 clinicians in England were randomised to one of two videos (practitioner role play or clinical demonstration). The results showed improvements in knowledge and confidence, and a preference for clinical demonstration by mothers and infants. The clinical demonstration video was evaluated in China in Phase 2 where expert trainers viewed the video after completing the BHFI workshop, and in Phase 3 practitioners viewed the video before the BHFI workshop. Phase 2 with expert trainers only showed improvement in knowledge of hand expression but not positioning and attachment. In Phase 3 clinicians showed improved knowledge for both skills. In all Phases there were statistically significant improvements in confidence in practice in both skills. Viewing short videos increased knowledge, particularly about teaching hand expression, and confidence in both skills. Copyright © 2018. Published by Elsevier Ltd.

Erythropoietin and its Carbamylated Derivative Prevent the Development of Experimental Diabetic Autonomic Neuropathy in STZ-Induced Diabetic NOD-SCID Mice

PubMed Central

Schmidt, Robert E.; Green, Karen G.; Feng, Dongyan; Dorsey, Denise A.; Parvin, Curtis A.; Lee, Jin-Moo; Xiao, Qinlgi; Brines, Michael

2008-01-01

Autonomic neuropathy is a significant diabetic complication resulting in increased morbidity and mortality. Studies of autopsied diabetic patients and several rodent models demonstrate that the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in prevertebral ganglia is the occurrence of synaptic pathology resulting in distinctive dystrophic neurites (“neuritic dystrophy”). Our prior studies show that neuritic dystrophy is reversed by exogenous IGF-I administration without altering the metabolic severity of diabetes, i.e. functioning as a neurotrophic substance. The description of erythropoietin (EPO) synergy with IGF-I function and the recent discovery of EPO’s multifaceted neuroprotective role suggested it might substitute for IGF-I in treatment of diabetic autonomic neuropathy. Our current studies demonstrate EPO receptor (EPO-R) mRNA in a cDNA set prepared from NGF-maintained rat sympathetic neuron cultures which decreased with NGF deprivation, a result which demonstrates clearly that sympathetic neurons express EPO-R, a result confirmed by immunohistochemistry. Treatment of STZ-diabetic NOD-SCID mice have demonstrated a dramatic preventative effect of EPO and carbamylated EPO (CEPO, which is neuroprotective but not hematopoietic) on the development of neuritic dystrophy. Neither EPO nor CEPO had a demonstrable effect on the metabolic severity of diabetes. Our results coupled with reported salutary effects of EPO on postural hypotension in a few clinical studies of EPO-treated anemic diabetic and non-diabetic patients may reflect a primary neurotrophic effect of EPO on the sympathetic autonomic nervous system, rather than a primary hematopoietic effect. These findings may represent a major clinical advance since EPO has been widely and safely used in anemic patients due to a variety of clinical conditions. PMID:17967455

Learning the futility of the thought suppression enterprise in normal experience and in obsessive compulsive disorder.

PubMed

Najmi, Sadia; Reese, Hannah; Wilhelm, Sabine; Fama, Jeanne; Beck, Celeste; Wegner, Daniel M

2010-01-01

The belief that we can control our thoughts is not inevitably adaptive, particularly when it fuels mental control activities that have ironic unintended consequences. The conviction that the mind can and should be controlled can prompt people to suppress unwanted thoughts, and so can set the stage for the intrusive return of those very thoughts. An important question is whether or not these beliefs about the control of thoughts can be reduced experimentally. One possibility is that behavioral experiments aimed at revealing the ironic return of suppressed thoughts might create a lesson that could reduce unrealistic beliefs about the control of thoughts. The present research assessed the influence of the thought suppression demonstration on beliefs about the control of thoughts in a non-clinical sample, and among individuals with obsessive-compulsive disorder (OCD). In Study 1, we assessed the effect of the thought suppression demonstration on beliefs about the control of thoughts among low and high obsessive individuals in the non-clinical population (N = 62). In Study 2, we conducted a similar study with individuals with OCD (N = 29). Results suggest that high obsessive individuals in the non-clinical population are able to learn the futility of suppression through the thought suppression demonstration and to alter their faulty beliefs about the control of thoughts; however, for individuals with OCD, the demonstration may be insufficient for altering underlying beliefs. For individuals with OCD, the connection between suppressing a neutral thought in the suppression demonstration and suppressing a personally relevant obsession may need to be stated explicitly in order to affect their obsessive beliefs.

Multi-exposure speckle imaging of cerebral blood flow: a pilot clinical study (Conference Presentation)

NASA Astrophysics Data System (ADS)

Richards, Lisa M.; Kazmi, S. M. S.; Olin, Katherine E.; Waldron, James S.; Fox, Douglas J.; Dunn, Andrew K.

2017-03-01

Monitoring cerebral blood flow (CBF) during neurosurgery is essential for detecting ischemia in a timely manner for a wide range of procedures. Multiple clinical studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable, label-free CBF monitoring technique during neurosurgery. LSCI is an optical imaging method that provides blood flow maps with high spatiotemporal resolution requiring only a coherent light source, a lens system, and a camera. However, the quantitative accuracy and sensitivity of LSCI is limited and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study (n = 7) recorded multiple exposure times from the same cortical tissue area, and demonstrates that shorter exposure times (≤1 ms) provide the highest dynamic range and sensitivity for sampling flow rates in human neurovasculature. This study also combined exposure times using the MESI model, demonstrating high correlation with proper image calibration and acquisition. The physiological accuracy of speckle-estimated flow was validated using conservation of flow analysis on vascular bifurcations. Flow estimates were highly conserved in MESI and 1 ms exposure LSCI, with percent errors at 6.4% ± 5.3% and 7.2% ± 7.2%, respectively, while 5 ms exposure LSCI had higher errors at 21% ± 10% (n = 14 bifurcations). Results from this study demonstrate the importance of exposure time selection for LSCI, and that intraoperative MESI can be performed with high quantitative accuracy.

Use and effect of clinical photographic records on the motivation and oral hygiene practices of a group of mentally handicapped adults.

PubMed

Bickley, S R; Shaw, L; Shaw, M J

1990-01-01

A study was undertaken to test the hypothesis that clinical photographic records can be used to motivate oral hygiene performance in mentally handicapped adults. Plaque reduction over the period of the study was shown to be higher in the test group than the control group but differences between the test and control groups were not statistically significant. The small numbers involved (29) and the difficulties in matching subjects may have mitigated against demonstrating a statistically significant difference between the two groups. All participants demonstrated high levels of toothbrushing ability during the practical aspects of the study but this was not maintained through daily oral hygiene practices in the majority of subjects.

Religion, Spirituality, and HIV Clinical Outcomes: A Systematic Review of the Literature.

PubMed

Doolittle, B R; Justice, A C; Fiellin, D A

2018-06-01

This systematic review evaluates the association between religion, spirituality and clinical outcomes in HIV-infected individuals. A systematic literature review was conducted for all English language articles published between 1980 and 2016 in relevant databases. Six hundred fourteen studies were evaluated. 15 met inclusion criteria. Ten (67%) studies reported a positive association between religion or spirituality and a clinical HIV outcome. Two (13%) studies failed to detect such an association; and two (13%) demonstrated a negative association. One study (7%) identified features of religiosity and spirituality that had both negative and positive associations with HIV clinical outcomes. Recognizing the religious or spiritual commitments of patients may serve as an important component of patient care. Further longitudinal studies and interventions might be required to further clarify the potential impact of religion and spirituality on HIV clinical outcomes.

Perspectives of academic faculty and clinical instructors on entry-level DPT preparation for pediatric physical therapist practice.

PubMed

Kenyon, Lisa K; Dole, Robin L; Kelly, Stephanie P

2013-12-01

To prepare students for pediatric practice, the professional (entry-level) curriculum must reflect the essential knowledge, skills, and abilities (KSA) required for pediatric physical therapist practice. The aim of this study was to develop consensus concerning the pediatric-specific KSA that should be expected of doctor of physical therapy (DPT) students at various points in the curriculum: prior to a pediatric clinical education experience, after a pediatric clinical education experience, and at the end of a DPT program. The study was conducted using the Delphi method. Purposive and snowball sampling were used to recruit pediatric academic faculty and pediatric clinical instructors. Three Web-based survey rounds were used to achieve consensus, defined as agreement among ≥70% of informants. The first round identified pediatric-specific KSA that were essential for DPT students to demonstrate at the identified points in the curriculum. In the second round, informants indicated their level of agreement with each item identified in the first round. Items that achieved consensus were included in the third round, in which informants rated the level of proficiency that DPT students should demonstrate related to pediatric-specific KSA. Consensus revealed the informants' perspectives concerning pediatric-specific KSA that a DPT student should be able to demonstrate at the identified curricular points. Consensus was reached on items in the curricular categories of basic science and foundations for practice; common pediatric diagnoses/pathologies, examination, interventions/plan of care/documentation; and general skills and abilities. Limitations included the small sample size and the potential for informants to feel uncomfortable prioritizing KSA. This study is an initial step toward identifying pediatric-specific KSA that should be demonstrated by DPT students.

Use of platelet rich plasma for the treatment of bicipital tendinopathy in spinal cord injury:: a pilot study.

PubMed

Ibrahim, Victor M; Groah, Suzanne L; Libin, Alexander; Ljungberg, Inger H

2012-01-01

The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) in the nonoperative management of shoulder tendinopathy amongst individuals with spinal cord injury. This objective was met by completing a pilot study on the effectiveness and safety of a PRP injection into the biceps tendon demonstrating clinical and ultrasonagraphic pathology. Recent analysis of the preliminary pilot data has demonstrated remarkably convincing results demonstrating both the safety and efficacy of this novel intervention.

Clinical Biomechanics of Wear in Total Hip Arthroplasty

PubMed Central

Callaghan, John J; Pedersen, Douglas R; Johnston, Richard C; Brown, Thomas D

2003-01-01

Complementary clinical and laboratory studies were performed to identify variables associated with polyethylene wear following total hip replacement, and to elucidate the mechanisms responsible for accelerated wear in the total hip arthroplasty construct. Observational cohort studies were performed using a prospective clinical database of more than 4000 consecutive primary total hip arthroplasties performed by a single surgeon, to identify wear-related variables. These variables included head size, acetabular/femoral component impingement, and third body debris. Novel digital edge detection techniques were developed and employed to accurately measure wear, and to determine the relationships of head size and third body debris to acceleration of wear. A novel slidingdistance-coupled finite element model was formulated and employed to examine the mechanisms responsible for wear. The long-term cohort studies demonstrated smaller head sizes to be associated with less wear. Third body debris generated from cable fretting was associated with an increase in wear, osteolysis, and acetabular loosening, especially with larger head sizes. The sliding-distance-coupled finite element model replicated the wear rates occurring in vitro and in vivo, demonstrating the importance of sliding distance on polyethylene wear following total hip arthroplasty. It also demonstrated substantial increases in wear associated with femoral head scratching from third body debris. Further extension of the finite element formulation demonstrated the potential for acetabular component rim damage from impingement wear, and the enhanced potential for third body ingress to the bearing surface with larger head sizes. Edge detection wear measurement techniques demonstrated that early wear rates were predictive of long-term wear rates. These complementary clinical and laboratory investigations have provided insight into 1) the significance of sliding distance and physiologic loci of motion as contributing factors in minimizing wear, 2) the deleterious effects of third body particulates in accelerating wear, 3) the potential for, and factors related to, impingement wear, and 4) the potential advantages and compromises related to the use of larger head sizes in the bearing surface construct. PMID:14575243

[Carcinomatous meningitis revealing a cancer: study of two cases].

PubMed

Samet, S; Belahsen, F; Triki, C; Masmoudi, H; Jlidi, R; Mhiri, C

2001-04-01

Meningeal Carcinomatosis (MC) is rare (4 to 5% of patients with solid tumors). We report two cases. The first case is a 53 year-old man presenting flaccid paraplegia and the second is a 76 year-old man presenting a clinical picture suggestive of normal pressure hydrocephalus. In the two cases, the diagnosis of MC was achieved by the demonstration of malignant cells in the CSF. Prognosis was poor in the two cases. The clinical presentation of MC is non specific and the diagnosis is only confirmed by demonstrating carcinomatous cells in CSF.

Factors Influencing Student Performance on the Carpal Bone Test as a Preliminary Evaluation of Anatomical Knowledge Retention

ERIC Educational Resources Information Center

Meyer, Amanda J.; Armson, Anthony; Losco, C. Dominique; Losco, Barrett; Walker, Bruce F.

2015-01-01

It has been demonstrated that a positive correlation exists between clinical knowledge and retained concepts in basic sciences. Studies have demonstrated a modest attrition of anatomy knowledge over time, which may be influenced by students' perceived importance of the basic sciences and the learning styles adopted. The aims of this study were to:…

An immunotherapeutic treatment against flea allergy dermatitis in cats by co-immunization of DNA and protein vaccines.

PubMed

Jin, Jin; Ding, Zheng; Meng, Fengxia; Liu, Qiyong; Ng, Terry; Hu, Yanxin; Zhao, Gan; Zhai, Bing; Chu, Hsien-Jue; Wang, Bin

2010-02-23

Flea allergy dermatitis (FAD) is considered a harmful and persistent allergic disease in cats, dogs and humans. Effective and safe antigen-specific treatments are lacking. Previously we reported that the simultaneous co-immunization with a DNA vaccine and its cognate coded protein antigen could induce antigen-specific iTreg cells (inducible Treg cells); demonstrating its potential to protect animals from FAD in a murine model. Its clinical efficacy however, remains to be demonstrated. In this report, we clinically tested this protocol to treat established FAD in cats following flea infestations. We present data showing a profound therapeutic improvement of dermatitis in these FAD cats following two co-immunizations, not only in relieving clinical symptoms, but also the amelioration of the allergic responses, including antigen-induced wheal formation, elevated T cell proliferation, infiltration of lymphocytes and migration of mast cells to the sites. This study demonstrates that a co-immunization approach as described can be used to treat flea-induced allergic disease in animals, thus implicating its potential for a practical clinical application. Copyright 2009 Elsevier Ltd. All rights reserved.

Enter the reverend: introduction to and application of Bayes' theorem in clinical ophthalmology.

PubMed

Thomas, Ravi; Mengersen, Kerrie; Parikh, Rajul S; Walland, Mark J; Muliyil, Jayprakash

2011-12-01

Ophthalmic practice utilizes numerous diagnostic tests, some of which are used to screen for disease. Interpretation of test results and many clinical management issues are actually problems in inverse probability that can be solved using Bayes' theorem. Use two-by-two tables to understand Bayes' theorem and apply it to clinical examples. Specific examples of the utility of Bayes' theorem in diagnosis and management. Two-by-two tables are used to introduce concepts and understand the theorem. The application in interpretation of diagnostic tests is explained. Clinical examples demonstrate its potential use in making management decisions. Positive predictive value and conditional probability. The theorem demonstrates the futility of testing when prior probability of disease is low. Application to untreated ocular hypertension demonstrates that the estimate of glaucomatous optic neuropathy is similar to that obtained from the Ocular Hypertension Treatment Study. Similar calculations are used to predict the risk of acute angle closure in a primary angle closure suspect, the risk of pupillary block in a diabetic undergoing cataract surgery, and the probability that an observed decrease in intraocular pressure is due to the medication that has been started. The examples demonstrate how data required for management can at times be easily obtained from available information. Knowledge of Bayes' theorem helps in interpreting test results and supports the clinical teaching that testing for conditions with a low prevalence has a poor predictive value. In some clinical situations Bayes' theorem can be used to calculate vital data required for patient management. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

DNA Vaccination Against Metastatic Breast Cancer

DTIC Science & Technology

2001-07-01

cells. Although DNA vaccines have shown effectiveness in clinical trials , it is essential to demonstrate pre- clinical effectiveness for anti-tumor... clinical trials for infectious diseases (4), it is essential to (5-7)demonstrate pre- clinical effectiveness for anti-tumor vaccines before clinical testing...Program Clinical Translational Research (CTR) award to perform a Phase I clinical trial of ELVIS2-neu. Our preliminary application was selected for

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

PubMed Central

Petkau, J; Reingold, SC; Held, U; Cutter, GR; Fleming, TR; Hughes, MD; Miller, DH; McFarland, HF; Wolinsky, JS

2009-01-01

Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy. PMID:18535021

Examining Curricular Integration Strategies To Optimize Learning Of The Anatomical Sciences

NASA Astrophysics Data System (ADS)

Lisk, Kristina Adriana Ayako

Background: Integration of basic and clinical science knowledge is essential to clinical practice. Although the importance of these two knowledge domains is well-recognized, successfully supporting the development of learners' integrated basic and clinical science knowledge, remains an educational challenge. In this dissertation, I examine curricular integration strategies to optimize learning of the anatomical sciences. Objectives: The studies were designed to achieve the following research aims: 1) to objectively identify clinically relevant content for an integrated musculoskeletal anatomy curriculum; 2) to examine the value of integrated anatomy and clinical science instruction compared to clinical science instruction alone on novices' diagnostic accuracy and diagnostic reasoning process; 3) to compare the effect of integrating and segregating anatomy and clinical science instruction along with a learning strategy (self-explanation) on novices' diagnostic accuracy. Methods: A modified Delphi was used to objectively select clinically relevant content for an integrated musculoskeletal anatomy curriculum. Two experimental studies were created to compare different instructional strategies to optimize learning of the curricular content. In both of these studies, novice learners were taught the clinical features of musculoskeletal pathologies using different learning approaches. Diagnostic performance was measured immediately after instruction and one-week later. Results: The results show that the Delphi method is an effective strategy to select clinically relevant content for integrated anatomy curricula. The findings also demonstrate that novices who were explicitly taught the clinical features of musculoskeletal diseases using causal basic science descriptions had superior diagnostic accuracy and a better understanding of the relative importance of key clinical features for disease categories. Conclusions: This research demonstrates how integration strategies can be applied at multiple levels of the curriculum. Further, this work shows the value of cognitive integration of anatomy and clinical science and it emphasizes the importance of purposefully linking the anatomical and clinical sciences in day-to-day teaching.

The Clinical Utility of Personality Subtypes in Patients with Anorexia Nervosa

ERIC Educational Resources Information Center

Wildes, Jennifer E.; Marcus, Marsha D.; Crosby, Ross D.; Ringham, Rebecca M.; Dapelo, Marcela Marin; Gaskill, Jill A.; Forbush, Kelsie T.

2011-01-01

Objective: Elucidation of clinically relevant subtypes has been proposed as a means of advancing treatment research, but classifying anorexia nervosa (AN) patients into restricting and binge-eating/purging types has demonstrated limited predictive validity. This study aimed to evaluate whether an approach to classifying eating disorder patients on…

Utilization of Portable Radios to Improve Ophthalmology Clinic Efficiency in an Academic Setting.

PubMed

Davis, Alexander S; Elkeeb, Ahmed M; Vizzeri, Gianmarco; Godley, Bernard F

2016-03-01

Improvement in clinic efficiency in the ambulatory setting is often looked at as an area for development of lean management strategies to deliver a higher quality of healthcare while reducing errors, costs, and delays. To examine the benefits of improving team communication and its impact on clinic flow and efficiency, we describe a time-motion study performed in an academic outpatient Ophthalmology clinic and its objective and subjective results. Compared to clinic encounters without the use of the portable radios, objective data demonstrated an overall significant decreases in mean workup time (15.18 vs. 13.10), room wait (13.10 vs. 10.47), and decreased the total time needed with an MD per encounter (9.45 vs. 6.63). Subjectively, significant improvements were seen in careprovider scores for patient flow (60.78 vs. 84.29), getting assistance (61.89 vs. 88.57), moving patient charts (54.44 vs. 85.71), teamwork (69.56 vs. 91.0), communications (62.33 vs. 90.43), providing quality patient care (76.22 vs. 89.57), and receiving input on the ability to see walk-in patients (80.11 vs. 90.43). For academic purposes, an improvement in engagement in patient care and learning opportunities was noted by the clinic resident-in-training during the pilot study. Portable radios in our pilot study were preferred over the previous method of communication and demonstrates significant improvements in certain areas of clinical efficiency, subjective perception of teamwork and communications, and academic learning.

Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

PubMed Central

Broekman, Winifred; Khedoe, Padmini P S J; Schepers, Koen; Roelofs, Helene; Stolk, Jan; Hiemstra, Pieter S

2018-01-01

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research. PMID:29653970

[Evidence based practice of nurses working in university hospitals in the French speaking part of Switzerland: a descriptive and correlational study

PubMed

Gentizon, Jenny; Borrero, Patricia; Vincent-Suter, Sonja; Ballabeni, Pierluigi; Morin, Diane; Eicher, Manuela

2016-12-01

Introduction : evidence-based practice (EBP) is too scarcely applied in nursing and is a key contemporary challenge for the discipline. Method and objective : This descriptive and correlational study invited 221 nurses working in three different clinical settings of university hospitals in Switzerland. The objective of this study was to describe their level of knowledge, beliefs and implementation of EBP. Results : of the 221 nurses in this study, only 67 were familiar EBP (30%). These demonstrate favorable beliefs and attitudes towards EBP, but indicate a lack of skills and knowledge to implement it. Compared to both internal medicine and geriatric nurses clinical nurse specialists (ISC) were significantly more familiar with EBP and its implementation. Results also indicate that positive nurses’ beliefs and attitudes toward EBP are predictive of better implementation in clinical practice. Discussion and Conclusion : as demonstrated in other studies, our results show that knowledge about EBP is not that widespread and its implementation remains a challenge even in university hospitals. Future work could include testing EBP implementation strategies to overcome the barriers identified.

[Development of Autogenic Training Clinical Effectiveness Scale (ATCES)].

PubMed

Ikezuki, Makoto; Miyauchi, Yuko; Yamaguchi, Hajime; Koshikawa, Fusako

2002-02-01

The purpose of the present study was to develop a scale measuring clinical effectiveness of autogenic training. In Study 1, 167 undergraduates completed a survey of items concerning physical and mental states, which were thought to vary in the course of autogenic training. With item and factor analyses, 20 items were selected, and the resulting scale (ATCES) had high discrimination and clear factor structure. In Study 2, reliability and concurrent and clinical validity of the scale were examined with three groups of respondents: 85 mentally healthy, 31 control, 13 clinical persons. The scale showed a high test-retest correlation (r = .83) and alpha coefficient (alpha = .86). ATCES had a Pearson correlation coefficient of r = .56 with General Health Questionnaire (GHQ-12), and r = .73 with trait anxiety (STAI-T). And ATCES successfully discriminated the mentally healthy and clinical groups in terms of clinical effectiveness. These results demonstrated high reliability and sufficient concurrent and clinical validity of the new scale.

A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Franconi, Giovanna; Schröder, Sven; Marchetti, Paolo; Robinson, Nicola

2013-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment. PMID:23983788

NBME subject examination in surgery scores correlate with surgery clerkship clinical experience.

PubMed

Myers, Jonathan A; Vigneswaran, Yalini; Gabryszak, Beth; Fogg, Louis F; Francescatti, Amanda B; Golner, Christine; Bines, Steven D

2014-01-01

Most medical schools in the United States use the National Board of Medical Examiners Subject Examinations as a method of at least partial assessment of student performance, yet there is still uncertainty of how well these examination scores correlate with clinical proficiency. Thus, we investigated which factors in a surgery clerkship curriculum have a positive effect on academic achievement on the National Board of Medical Examiners Subject Examination in Surgery. A retrospective analysis of 83 third-year medical students at our institution with 4 unique clinical experiences on the general surgery clerkship for the 2007-2008 academic year was conducted. Records of the United States Medical Licensing Examination Step 1 scores, National Board of Medical Examiners Subject Examination in Surgery scores, and essay examination scores for the groups were compared using 1-way analysis of variance testing. Rush University Medical Center, Chicago IL, an academic institution and tertiary care center. Our data demonstrated National Board of Medical Examiners Subject Examination in Surgery scores from the group with the heavier clinical loads and least time for self-study were statistically higher than the group with lighter clinical services and higher rated self-study time (p = 0.036). However, there was no statistical difference of National Board of Medical Examiners Subject Examination in Surgery scores between the groups with equal clinical loads (p = 0.751). Students experiencing higher clinical volumes on surgical services, but less self-study time demonstrated statistically higher academic performance on objective evaluation, suggesting clinical experience may be of higher value than self-study and reading. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Electrical Stimulation as a Means for Improving Vision.

PubMed

Sehic, Amer; Guo, Shuai; Cho, Kin-Sang; Corraya, Rima M; Chen, Dong F; Utheim, Tor P

2016-11-01

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen.

PubMed

Nakamura, Toshimichi; Toshimoto, Kota; Lee, Wooin; Imamura, Chiyo K; Tanigawara, Yusuke; Sugiyama, Yuichi

2018-06-19

The Tamoxifen Response by CYP2D6 Genotype-based Treatment-1 (TARGET-1) study (n = 180) was conducted from 2012-2017 in Japan to determine the efficacy of tamoxifen dosing guided by cytochrome P450 2D6 (CYP2D6) genotypes. To predict its outcomes prior to completion, we constructed the comprehensive physiologically based pharmacokinetic (PBPK) models of tamoxifen and its metabolites and performed virtual TARGET-1 studies. Our analyses indicated that the expected probability to achieve the end point (demonstrating the superior efficacy of the escalated tamoxifen dose over the standard dose in patients carrying CYP2D6 variants) was 0.469 on average. As the population size of this virtual clinical study (VCS) increased, the expected probability was substantially increased (0.674 for n = 260). Our analyses also informed that the probability to achieve the end point in the TARGET-1 study was negatively impacted by a large variability in endoxifen levels. Our current efforts demonstrate the promising utility of the PBPK modeling and VCS approaches in prospectively designing effective clinical trials. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review.

PubMed

Miron, Richard J; Fujioka-Kobayashi, Masako; Bishara, Mark; Zhang, Yufeng; Hernandez, Maria; Choukroun, Joseph

2017-02-01

The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and dentistry.

Suicidal Behaviors among Adolescents in Puerto Rico: Rates and Correlates in Clinical and Community Samples

ERIC Educational Resources Information Center

Jones, Jennifer; Ramirez, Rafael Roberto; Davies, Mark; Canino, Glorisa; Goodwin, Renee D.

2008-01-01

This study examined rates and correlates of suicidal behavior among youth on the island of Puerto Rico. Data were drawn from two probability samples, one clinical (n = 736) and one community-based sample (n = 1,896), of youth ages 12 to 17. Consistent with previous studies in U.S. mainland adolescent populations, our results demonstrate that most…

Open-source mobile digital platform for clinical trial data collection in low-resource settings.

PubMed

van Dam, Joris; Omondi Onyango, Kevin; Midamba, Brian; Groosman, Nele; Hooper, Norman; Spector, Jonathan; Pillai, Goonaseelan Colin; Ogutu, Bernhards

2017-02-01

Governments, universities and pan-African research networks are building durable infrastructure and capabilities for biomedical research in Africa. This offers the opportunity to adopt from the outset innovative approaches and technologies that would be challenging to retrofit into fully established research infrastructures such as those regularly found in high-income countries. In this context we piloted the use of a novel mobile digital health platform, designed specifically for low-resource environments, to support high-quality data collection in a clinical research study. Our primary aim was to assess the feasibility of a using a mobile digital platform for clinical trial data collection in a low-resource setting. Secondarily, we sought to explore the potential benefits of such an approach. The investigative site was a research institute in Nairobi, Kenya. We integrated an open-source platform for mobile data collection commonly used in the developing world with an open-source, standard platform for electronic data capture in clinical trials. The integration was developed using common data standards (Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model), maximising the potential to extend the approach to other platforms. The system was deployed in a pharmacokinetic study involving healthy human volunteers. The electronic data collection platform successfully supported conduct of the study. Multidisciplinary users reported high levels of satisfaction with the mobile application and highlighted substantial advantages when compared with traditional paper record systems. The new system also demonstrated a potential for expediting data quality review. This pilot study demonstrated the feasibility of using a mobile digital platform for clinical research data collection in low-resource settings. Sustainable scientific capabilities and infrastructure are essential to attract and support clinical research studies. Since many research structures in Africa are being developed anew, stakeholders should consider implementing innovative technologies and approaches.

The ABC’s of Suicide Risk Assessment: Applying a Tripartite Approach to Individual Evaluations

PubMed Central

Harris, Keith M.; Syu, Jia-Jia; Lello, Owen D.; Chew, Y. L. Eileen; Willcox, Christopher H.; Ho, Roger H. M.

2015-01-01

There is considerable need for accurate suicide risk assessment for clinical, screening, and research purposes. This study applied the tripartite affect-behavior-cognition theory, the suicidal barometer model, classical test theory, and item response theory (IRT), to develop a brief self-report measure of suicide risk that is theoretically-grounded, reliable and valid. An initial survey (n = 359) employed an iterative process to an item pool, resulting in the six-item Suicidal Affect-Behavior-Cognition Scale (SABCS). Three additional studies tested the SABCS and a highly endorsed comparison measure. Studies included two online surveys (Ns = 1007, and 713), and one prospective clinical survey (n = 72; Time 2, n = 54). Factor analyses demonstrated SABCS construct validity through unidimensionality. Internal reliability was high (α = .86-.93, split-half = .90-.94)). The scale was predictive of future suicidal behaviors and suicidality (r = .68, .73, respectively), showed convergent validity, and the SABCS-4 demonstrated clinically relevant sensitivity to change. IRT analyses revealed the SABCS captured more information than the comparison measure, and better defined participants at low, moderate, and high risk. The SABCS is the first suicide risk measure to demonstrate no differential item functioning by sex, age, or ethnicity. In all comparisons, the SABCS showed incremental improvements over a highly endorsed scale through stronger predictive ability, reliability, and other properties. The SABCS is in the public domain, with this publication, and is suitable for clinical evaluations, public screening, and research. PMID:26030590

Advances in stem cell therapy for the lower urinary tract.

PubMed

Lin, Ching-Shwun

2010-02-26

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.

Recruitment of black women with type 2 diabetes into a self-management intervention trial.

PubMed

Newlin, Kelley; Melkus, Gail D'Eramo; Jefferson, Vanessa; Langerman, Susan; Womack, Julie; Chyun, Deborah

2006-01-01

The purpose of this study was to evaluate the relationship of recruitment methods to enrollment status in Black women with type 2 diabetes screened for entry into a randomized clinical trial (RCT). Using a cross-sectional study design with convenience sampling procedures, data were collected on recruitment methods to which the women responded (N=236). Results demonstrated that the RCT had a moderate overall recruitment rate of 46% and achieved only 84% of its projected accrual goal (N=109). Chi-square analysis demonstrated that enrollment outcomes varied significantly according to recruitment methods (P=.05). Recruitment methods such as community health fairs (77.8%), private practice referrals (75.0%), participant referrals (61.5%), community clinic referrals (44.6%), community advertising and marketing (40.9%), and chart review (40.4%) demonstrated variable enrollment yields. Results confirm previous findings that indicate that Black Americans may be successfully recruited into research studies at moderate rates when traditional recruitment methods are enhanced and integrated with more culturally sensitive methods. Lessons learned are considered.

Partnership disengagement from primary community care networks (PCCNs): A qualitative study for a national demonstration project

PubMed Central

2010-01-01

Background The Primary Community Care Network (PCCN) Demonstration Project, launched by the Bureau of National Health Insurance (BNHI) in 2003, is still in progress. Partnership structures in PCCNs represent both contractual clinic-to-clinic and clinic-to-hospital member relationships of organizational aspects. The partnership structures are the formal relationships between individuals and the total network. Their organizational design aims to ensure effective communication, coordination, and integration across the total network. Previous studies have focused largely on how contractual integration among the partnerships works and on its effects. Few studies, however, have tried to understand partnership disengagement in PCCNs. This study explores why some partnerships in PCCNs disengage. Methods This study used a qualitative methodology with semi-structured questions for in-depth interviews. The semi-structured questions were pre-designed to explore the factors driving partnership disengagement. Thirty-seven clinic members who had withdrawn from their PCCNs were identified from the 2003-2005 Taiwan Primary Community Care Network Lists. Results Organization/participant factors (extra working time spend and facility competency), network factors (partner collaboration), and community factors (health policy design incompatibility, patient-physician relationship, and effectiveness) are reasons for clinic physicians to withdraw or change their partnerships within the PCCNs. Conclusions To strengthen partnership relationships, several suggestions are made, including to establish clinic and hospital member relationships, and to reduce administrative work. In addition, both educating the public about the concept of family doctors and ensuring well-organized national health policies could help health care providers improve the integration processes. PMID:20359369

Neuroactive steroids and PTSD treatment.

PubMed

Rasmusson, Ann M; Marx, Christine E; Pineles, Suzanne L; Locci, Andrea; Scioli-Salter, Erica R; Nillni, Yael I; Liang, Jennifer J; Pinna, Graziano

2017-05-10

This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain. Nevertheless, large naturalistic studies and a small placebo-controlled interventional study have revealed generally positive effects of glucocorticoid administration in preventing PTSD after trauma, possibly mediated by glucocorticoid receptor-mediated effects on other targets that impact PTSD risk, including other neuroactive steroid systems. In addition, clinical and preclinical studies show that administration of glucocorticoids, 17β-estradiol, and GABAergic neuroactive steroids or agents that enhance their synthesis can facilitate extinction and extinction retention, depending on dose and timing of dose in relation to these complex PTSD-relevant recovery processes. This suggests that clinical trials designed to test neuroactive steroid therapeutics in PTSD may benefit from such considerations; typical continuous dosing regimens may not be optimal. In addition, validated and clinically accessible methods for identifying specific neuroactive steroid system abnormalities at the individual level are needed to optimize both clinical trial design and precision medicine based treatment targeting. Copyright © 2017. Published by Elsevier B.V.

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

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

Detappe, A; Institut Lumiere-Matiere, Lyon, FR; Kunjachan, S

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods:more » The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible nanoplatform with strong translational potential for MR-guided radiation therapy.« less

In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

NASA Astrophysics Data System (ADS)

Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

2008-11-01

The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

Optimization of protocol design: a path to efficient, lower cost clinical trial execution

PubMed Central

Malikova, Marina A

2016-01-01

Managing clinical trials requires strategic planning and efficient execution. In order to achieve a timely delivery of important clinical trials’ outcomes, it is useful to establish standardized trial management guidelines and develop robust scoring methodology for evaluation of study protocol complexity. This review will explore the challenges clinical teams face in developing protocols to ensure that the right patients are enrolled and the right data are collected to demonstrate that a drug is safe and efficacious, while managing study costs and study complexity based on proposed comprehensive scoring model. Key factors to consider when developing protocols and techniques to minimize complexity will be discussed. A methodology to identify processes at planning phase, approaches to increase fiscal return and mitigate fiscal compliance risk for clinical trials will be addressed. PMID:28031939

Real-world clinical effectiveness, regulatory transparency and payer coverage: three ingredients for translating pharmacogenomics into clinical practice.

PubMed

Frueh, Felix W

2010-05-01

The past decade of pharmacogenomics was driven by the sequencing of the human genome to create ever denser maps of genetic variations for studying the diversity across individuals. Today, genotyping technology is available at a fraction of the cost of what it was 10 years ago and many pharmacogenomic variations have been studied in detail. Still, we are only starting to gain an understanding of how pharmacogenomic-guided drug therapy affects clinical outcomes: real-world studies that demonstrate the clinical effectiveness and address the economic implications of pharmacogenomics are needed to help decide when and how to implement pharmacogenomics in clinical practice, how to regulate pharmacogenomic testing and how the healthcare system will integrate this new science into an environment of rapidly increasing cost.

The role of patient narratives in healthcare innovation: supporting translation and meaning making.

PubMed

Pedersen, Anne Reff

2016-01-01

The purpose of this paper is to investigate the process and impact of patient involvement in locally defined improvement projects in two hospital clinics. The paper particularly aims to examine how patient narratives, in the form of diaries and radio montage, help to create new insights into patient experience for healthcare professionals, and support professionals' enrolment and mobilisation in innovation projects. Two case studies were undertaken. These drew upon qualitative interviews with staff and participant observation during innovation workshops. Patient diaries and a recorded montage of patient voices were also collected. The findings illuminate translation processes in healthcare innovation and the emergence of meaning making process for staff through the active use of patient narratives. The paper highlights the critical role of meaning making as an enabler of patient-centred change processes in healthcare via: local clinic mangers defining problems and ideas; collecting and sharing patient narratives in innovation workshops; and healthcare professionals' interpretation of patient narratives supporting new insights into patient experience. This study demonstrates how healthcare professionals' meaning making can be supported by articulating, constructing, listening and interpreting patient narratives. The two cases demonstrate how patient narratives serve as reflective devices for healthcare professionals. This study presents a novel demonstration of the importance of patient narratives for translating healthcare innovation in a clinical practice setting.

Couple-based Intervention for Depression: An Effectiveness Study in the National Health Service in England.

PubMed

Baucom, Donald H; Fischer, Melanie S; Worrell, Michael; Corrie, Sarah; Belus, Jennifer M; Molyva, Efthymia; Boeding, Sara E

2017-12-04

This study represents an effectiveness study and service evaluation of a cognitive behavioral, couple-based treatment for depression (BCT-D) provided in London services that are part of the "Improving Access to Psychological Therapies" (IAPT) program in England. Twenty-three therapists in community clinics were trained in BCT-D during a 5-day workshop, followed by monthly group supervision for 1 year. The BCT-D treatment outcome findings are based on 63 couples in which at least one partner was depressed and elected to receive BCT-D. Eighty-five percent of couples also demonstrated relationship distress, and 49% of the nonclient partners also met caseness for depression or anxiety. Findings demonstrated a recovery rate of 57% with BCT-D, compared to 41% for all IAPT treatments for depression in London. Nonclient partners who met caseness demonstrated a 48% recovery rate with BCT-D, although they were not the focus of treatment. BCT-D was equally effective for clients regardless of the clinical status of the nonclient partner, suggesting its effectiveness in assisting both members of the couple simultaneously. Likewise, treatment was equally effective whether or not both partners reported relationship distress. The findings are promising regarding the successful application of BCT-D in routine clinical settings. © 2017 Family Process Institute.

The pragmatics of therapeutic interaction: an empirical study.

PubMed

Lepper, Georgia

2009-10-01

The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

The FDA's role in medical device clinical studies of human subjects

NASA Astrophysics Data System (ADS)

Saviola, James

2005-03-01

This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.

An evaluation of the pharmacokinetics of methylphenidate for the treatment of attention-deficit/ hyperactivity disorder.

PubMed

Frölich, Jan; Banaschewski, Tobias; Döpfner, Manfred; Görtz-Dorten, Anja

2014-08-01

Methylphenidate (MPH) plays a principal role in the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Controlled studies have demonstrated an effective reduction in the core symptoms of the disorder following MPH therapy, although long-term studies also demonstrate that the therapeutic benefits dissipate in the absence of combined psychosocial interventions. This review article focuses on the pharmacological characteristics of MPH, examining its effects on brain metabolism and the neurotransmitter system. Neuropsychological and clinical effects of different immediate and extended release MPH formulations are discussed to aid clinicians in choosing the appropriate formulation. The drug's addictive potency and abuse potential is also discussed. Data came from a literature search of relevant studies performed using the PubMed database up to June 2013. MPH is effective in the treatment of the core symptoms of ADHD. Considerable clinical expertise is required to identify an individually well-adapted dosage which will produce the optimal clinical effects with potential side effects minimized. Due to low adherence to medication, especially in adolescents, motivation to treatment and attentive clinical monitoring is mandatory, as is the consideration of risks of abuse or the presence of a comorbid addictive disorder.

Diagnostic yield and accuracy of coronary CT angiography after abnormal nuclear myocardial perfusion imaging.

PubMed

Meinel, Felix G; Schoepf, U Joseph; Townsend, Jacob C; Flowers, Brian A; Geyer, Lucas L; Ebersberger, Ullrich; Krazinski, Aleksander W; Kunz, Wolfgang G; Thierfelder, Kolja M; Baker, Deborah W; Khan, Ashan M; Fernandes, Valerian L; O'Brien, Terrence X

2018-06-15

We aimed to determine the diagnostic yield and accuracy of coronary CT angiography (CCTA) in patients referred for invasive coronary angiography (ICA) based on clinical concern for coronary artery disease (CAD) and an abnormal nuclear stress myocardial perfusion imaging (MPI) study. We enrolled 100 patients (84 male, mean age 59.6 ± 8.9 years) with an abnormal MPI study and subsequent referral for ICA. Each patient underwent CCTA prior to ICA. We analyzed the prevalence of potentially obstructive CAD (≥50% stenosis) on CCTA and calculated the diagnostic accuracy of ≥50% stenosis on CCTA for the detection of clinically significant CAD on ICA (defined as any ≥70% stenosis or ≥50% left main stenosis). On CCTA, 54 patients had at least one ≥50% stenosis. With ICA, 45 patients demonstrated clinically significant CAD. A positive CCTA had 100% sensitivity and 84% specificity with a 100% negative predictive value and 83% positive predictive value for clinically significant CAD on a per patient basis in MPI positive symptomatic patients. In conclusion, almost half (48%) of patients with suspected CAD and an abnormal MPI study demonstrate no obstructive CAD on CCTA.

Using GIS for spatial analysis of rectal lesions in the human body.

PubMed

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-03-15

Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process.

Translating genomic discoveries to the clinic in pediatric oncology.

PubMed

Glade Bender, Julia; Verma, Anupam; Schiffman, Joshua D

2015-02-01

The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.

Using GIS for spatial analysis of rectal lesions in the human body

PubMed Central

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-01-01

Background Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Results Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. Conclusion This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process. PMID:17362510

Retroillumination Photography Analysis Enhances Clinical Definition of Severe Fuchs Corneal Dystrophy.

PubMed

Eghrari, Allen O; Garrett, Brian S; Mumtaz, Aisha A; Edalati, Armand E; Meadows, Danielle N; McGlumphy, Elyse J; Iliff, Benjamin W; Gottsch, John D

2015-12-01

Retroillumination photography analysis (RPA) provides an objective assessment of the number and distribution of guttae in Fuchs corneal dystrophy. Here, we assess its correlation with clinical grading using slit-lamp biomicroscopy across varying levels of severity. Retroillumination photographs were conducted for 95 affected corneas with slit-lamp flash photography after pupillary dilation. Individual guttae were counted manually and the position of individual points recorded. Clinical grading using the Krachmer scale was documented for each eye during examination, and regression analyses were performed to identify the strength of association with number of guttae. We assessed range at each stage of clinical grading and used the Mann-Whitney U test to assess whether clinical grading levels demonstrated successively higher numbers of guttae. Krachmer score ranged from 1 to 5, with mean of 2.6. Mean numbers of guttae at each level of severity were 289 (1+), 999 (2+), 2669 (3+), 5474 (4+), and 7133 (5+). Each stage demonstrated significantly higher numbers of guttae than its preceding level except from 4+ to 5+ (P = 0.30), consistent with the definition of 4+ as the highest level defined by the presence of guttae. Higher levels of clinical grading were associated with larger ranges of guttae (P < 0.01). A linear regression model resulted in a strong fit between RPA and Krachmer score (r = 0.81). In this largest study of RPA data and comparison with subjective clinical grading of Fuchs dystrophy severity, RPA correlates strongly and demonstrates enhanced definition of severity at advanced stages of disease.

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

PubMed

Meyer, C R; Boes, J L; Kim, B; Bland, P H; Zasadny, K R; Kison, P V; Koral, K; Frey, K A; Wahl, R L

1997-04-01

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Competitive bidding for Medicare Part B clinical laboratory services.

PubMed

Kautter, John; Pope, Gregory C

2014-06-01

The traditional Medicare fee-for-service program may be able to purchase clinical laboratory test services at a lower cost through competitive bidding. Demonstrations of competitive bidding for clinical laboratory tests have been twice mandated or authorized by Congress but never implemented. This article provides a summary and review of the final design of the laboratory competitive bidding demonstration mandated by the Medicare Modernization Act of 2003. The design was analogous to a sealed bid (first price), clearing price auction. Design elements presented include covered laboratory tests and beneficiaries, laboratory bidding and payment status under the demonstration, composite bids, determining bidding winners and the demonstration fee schedule, and quality under the demonstration. Expanded use of competitive bidding in Medicare, including specifically for clinical laboratory tests, has been recommended in some proposals for Medicare reform. The presented design may be a useful point of departure if Medicare clinical laboratory competitive bidding is revived in the future.

Vestibular Assessments in Children With Global Developmental Delay: An Exploratory Study.

PubMed

Dannenbaum, Elizabeth; Horne, Victoria; Malik, Farwa; Villeneuve, Myriam; Salvo, Lora; Chilingaryan, Gevorg; Lamontagne, Anouk

2016-01-01

To compare results of 3 clinical vestibular tests between children with global developmental delay (GDD) and children with typical development (TD) and investigate the test-retest reliability. Twenty children with GDD (aged 4.1-12.1 years) and 11 age-matched controls with TD participated. Participants with GDD underwent 2 sessions of testing. Each session consisted of the Clinical Test of Sensory Interaction and Balance (CTSIB), Dynamic Visual Acuity (DVA) test, and the modified Emory Clinical Vestibular Chair Test (m-ECVCT). Up to 33% of the children with GDD had abnormal DVA scores. m-ECVCT results of children with GDD demonstrated larger variance than children with TD. The CTSIB score was significantly reduced in the group with GDD. The test-retest reliability varied, with good reliability for the m-ECVCT and CTSIB, and fair reliability for the DVA. Findings suggest vestibular involvement in children in GDD. The clinical tests demonstrated moderate test-retest reliability.

High fidelity simulation effectiveness in nursing students' transfer of learning.

PubMed

Kirkman, Tera R

2013-07-13

Members of nursing faculty are utilizing interactive teaching tools to improve nursing student's clinical judgment; one method that has been found to be potentially effective is high fidelity simulation (HFS). The purpose of this time series design study was to determine whether undergraduate nursing students were able to transfer knowledge and skills learned from classroom lecture and a HFS clinical to the traditional clinical setting. Students (n=42) were observed and rated on their ability to perform a respiratory assessment. The observations and ratings took place at the bedside, prior to a respiratory lecture, following the respiratory lecture, and following simulation clinical. The findings indicated that there was a significant difference (p=0.000) in transfer of learning demonstrated over time. Transfer of learning was demonstrated and the use of HFS was found to be an effective learning and teaching method. Implications of results are discussed.

First experiences with a tool to measure the level of clinical information present in adverse drug reaction reports.

PubMed

Oosterhuis, Ingrid; Rolfes, Leàn; Ekhart, Corine; Muller-Hansma, Annemarie; Härmark, Linda

2018-02-01

To make a proper causality assessment of an adverse drug reaction (ADR) report, a certain level of clinical information is necessary. A tool was developed to measure the level of clinical information present in ADR reports. The aim of this study was to test the validity and reliability of the clinical documentation tool (ClinDoc) in an international setting. The tool was developed by a panel of pharmacovigilance experts. It includes four domains: ADR, chronology of the ADR, suspected drug and patient characteristics. The final score categorizes reports into: excellent, well, moderately or poorly documented. In two rounds, eight pharmacovigilance assessors of different countries made a total of 224 assessments using the tool, with the expert panels judgement as a standard. Sensitivity and specificity were calculated. The tool with four outcome-categories demonstrated low sensitivity. A lack of distinctiveness was demonstrated between the categories moderate and well. Results for the second round were re-analysed using three categories. This demonstrated a better validity. This is the first tool to give insight in the level of relevant clinical information present in ADR reports. It can be used internationally to compare reports coming from different reporting methods and different types of reporters in pharmacovigilance.

Building a Bridge or Digging a Pipeline? Clinical Data Mining in Evidence-Informed Knowledge Building

ERIC Educational Resources Information Center

Epstein, Irwin

2015-01-01

Challenging the "bridge metaphor" theme of this conference, this article contends that current practice-research integration strategies are more like research-to-practice "pipelines." The purpose of this article is to demonstrate the potential of clinical data-mining studies conducted by practitioners, practitioner-oriented PhD…

Randomized Clinical Trial: The Use of SpeechEasy® in Stuttering Treatment

ERIC Educational Resources Information Center

Ritto, Ana Paula; Juste, Fabiola Staróbole; Stuart, Andrew; Kalinowski, Joseph; de Andrade, Claudia Regina Furquim

2016-01-01

Background: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. Aims: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. Methods &…

Validation of a prediction model that allows direct comparison of the Oxford Knee Score and American Knee Society clinical rating system.

PubMed

Maempel, J F; Clement, N D; Brenkel, I J; Walmsley, P J

2015-04-01

This study demonstrates a significant correlation between the American Knee Society (AKS) Clinical Rating System and the Oxford Knee Score (OKS) and provides a validated prediction tool to estimate score conversion. A total of 1022 patients were prospectively clinically assessed five years after TKR and completed AKS assessments and an OKS questionnaire. Multivariate regression analysis demonstrated significant correlations between OKS and the AKS knee and function scores but a stronger correlation (r = 0.68, p < 0.001) when using the sum of the AKS knee and function scores. Addition of body mass index and age (other statistically significant predictors of OKS) to the algorithm did not significantly increase the predictive value. The simple regression model was used to predict the OKS in a group of 236 patients who were clinically assessed nine to ten years after TKR using the AKS system. The predicted OKS was compared with actual OKS in the second group. Intra-class correlation demonstrated excellent reliability (r = 0.81, 95% confidence intervals 0.75 to 0.85) for the combined knee and function score when used to predict OKS. Our findings will facilitate comparison of outcome data from studies and registries using either the OKS or the AKS scores and may also be of value for those undertaking meta-analyses and systematic reviews. ©2015 The British Editorial Society of Bone & Joint Surgery.

Pancreatic cancer ascites xenograft–an expeditious model mirroring advanced therapeutic resistant disease

PubMed Central

Schvimer, Michael; Atias, Dikla; Halperin, Sharon; Buzhor, Ella; Raitses-Gurevich, Maria; Cohen, Keren; Pri-Chen, Sara; Wilson, Julie; Denroche, Robert E.; Lungu, Ilinca; Bartlett, John M.S.; Mbabaali, Faridah; Yarden, Yosef; Nataraj, Nishanth Belugali; Gallinger, Steven; Berger, Raanan

2017-01-01

Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations. PMID:28489577

Prevalence of hip osteoarthritis in chiropractic practice in Denmark: a descriptive cross-sectional and prospective study.

PubMed

Poulsen, Erik; Christensen, Henrik W; Overgaard, Søren; Hartvigsen, Jan

2012-05-01

The purposes of this study were to measure the prevalence of clinical and radiographic hip osteoarthritis (OA) and first-time diagnosis of hip OA in consecutive patients presenting to chiropractic practices in Denmark and to report the components of the initial treatment rendered by the chiropractic practitioner. A total of 2000 patient records and 1000 radiographs were reviewed retrospectively in 20 chiropractic clinics throughout Denmark. Information obtained included patients' primary complaint, physical examination and radiographic findings of hip OA, and treatment. Subsequently, the 20 clinics participated in a prospective survey where they collected equivalent information over a 2-week period. Retrospective review of records revealed that 1.4% of patients in Danish chiropractic practice had signs of clinical hip OA. Of these, 59% demonstrated radiographic signs of hip OA. Prospective data collection revealed that 3.4% of new patients had signs of clinical hip OA. Fifty-four percent of these demonstrated radiographic signs of hip OA, and of these 70% were diagnosed as having OA of the hip for the first time. Initial treatment involved manual treatment and advice on over-the-counter pain medication and/or supplements. Of all 1000 retrospectively reviewed radiographs in patients 40 years or older, 19.2% demonstrated radiographic signs of hip OA. Osteoarthritis of the hip is diagnosed and managed in primary care chiropractic practice in Denmark; however, it is likely underdiagnosed. In those newly presenting to chiropractic practitioners, first-time diagnosis with clinical and radiographic signs of hip OA appears to be common. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

150-μm Spatial Resolution Using Photon-Counting Detector Computed Tomography Technology: Technical Performance and First Patient Images.

PubMed

Leng, Shuai; Rajendran, Kishore; Gong, Hao; Zhou, Wei; Halaweish, Ahmed F; Henning, Andre; Kappler, Steffen; Baer, Matthias; Fletcher, Joel G; McCollough, Cynthia H

2018-05-28

The aims of this study were to quantitatively assess two new scan modes on a photon-counting detector computed tomography system, each designed to maximize spatial resolution, and to qualitatively demonstrate potential clinical impact using patient data. This Health Insurance Portability Act-compliant study was approved by our institutional review board. Two high-spatial-resolution scan modes (Sharp and UHR) were evaluated using phantoms to quantify spatial resolution and image noise, and results were compared with the standard mode (Macro). Patients were scanned using a conventional energy-integrating detector scanner and the photon-counting detector scanner using the same radiation dose. In first patient images, anatomic details were qualitatively evaluated to demonstrate potential clinical impact. Sharp and UHR modes had a 69% and 87% improvement in in-plane spatial resolution, respectively, compared with Macro mode (10% modulation-translation-function values of 16.05, 17.69, and 9.48 lp/cm, respectively). The cutoff spatial frequency of the UHR mode (32.4 lp/cm) corresponded to a limiting spatial resolution of 150 μm. The full-width-at-half-maximum values of the section sensitivity profiles were 0.41, 0.44, and 0.67 mm for the thinnest image thickness for each mode (0.25, 0.25, and 0.5 mm, respectively). At the same in-plane spatial resolution, Sharp and UHR images had up to 15% lower noise than Macro images. Patient images acquired in Sharp mode demonstrated better delineation of fine anatomic structures compared with Macro mode images. Phantom studies demonstrated superior resolution and noise properties for the Sharp and UHR modes relative to the standard Macro mode and patient images demonstrated the potential benefit of these scan modes for clinical practice.

Derivation of vascular endothelial cells from human embryonic stem cells under GMP-compliant conditions: towards clinical studies in ischaemic disease.

PubMed

Kaupisch, A; Kennedy, L; Stelmanis, V; Tye, B; Kane, N M; Mountford, J C; Courtney, A; Baker, A H

2012-10-01

Revascularisation of ischaemic tissue remains an area of substantial unmet clinical need in cardiovascular disease. Strategies to induce therapeutic angiogenesis are therefore attractive. Our recent focus has been on human embryonic stem cell (hESC) strategies since hESC can be maintained in a pluripotent state or differentiated into any desired cell type, including endothelial cells (EC), under defined differentiation culture conditions. We recently published a protocol for non-good manufacturing practice (GMP) feeder- and serum-free hESC-EC-directed monolayer differentiation to vascular EC demonstrating the potential to generate hESC-derived EC in a GMP-compliant manner suitable for use in clinical trials. In this study we modified that laboratory protocol to GMP compliance. EC production was confirmed by flow cytometry, qRT-PCR and production of vascular structures in Matrigel®, yielding approximately 30 % mature VE-cadherin(+)/PECAM-1(+) cells using the GMP-compliant hESC line RC13. In conclusion, we have successfully demonstrated the production of vascular EC under GMP-compliant conditions suitable for clinical evaluation.

Discriminating Power of Localized Three-Dimensional Facial Morphology

PubMed Central

Hammond, Peter; Hutton, Tim J.; Allanson, Judith E.; Buxton, Bernard; Campbell, Linda E.; Clayton-Smith, Jill; Donnai, Dian; Karmiloff-Smith, Annette; Metcalfe, Kay; Murphy, Kieran C.; Patton, Michael; Pober, Barbara; Prescott, Katrina; Scambler, Pete; Shaw, Adam; Smith, Ann C. M.; Stevens, Angela F.; Temple, I. Karen; Hennekam, Raoul; Tassabehji, May

2005-01-01

Many genetic syndromes involve a facial gestalt that suggests a preliminary diagnosis to an experienced clinical geneticist even before a clinical examination and genotyping are undertaken. Previously, using visualization and pattern recognition, we showed that dense surface models (DSMs) of full face shape characterize facial dysmorphology in Noonan and in 22q11 deletion syndromes. In this much larger study of 696 individuals, we extend the use of DSMs of the full face to establish accurate discrimination between controls and individuals with Williams, Smith-Magenis, 22q11 deletion, or Noonan syndromes and between individuals with different syndromes in these groups. However, the full power of the DSM approach is demonstrated by the comparable discriminating abilities of localized facial features, such as periorbital, perinasal, and perioral patches, and the correlation of DSM-based predictions and molecular findings. This study demonstrates the potential of face shape models to assist clinical training through visualization, to support clinical diagnosis of affected individuals through pattern recognition, and to enable the objective comparison of individuals sharing other phenotypic or genotypic properties. PMID:16380911

Bilirubin and atherosclerotic diseases.

PubMed

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Validity and reliability of the NAB Naming Test.

PubMed

Sachs, Bonnie C; Rush, Beth K; Pedraza, Otto

2016-05-01

Confrontation naming is commonly assessed in neuropsychological practice, but few standardized measures of naming exist and those that do are susceptible to the effects of education and culture. The Neuropsychological Assessment Battery (NAB) Naming Test is a 31-item measure used to assess confrontation naming. Despite adequate psychometric information provided by the test publisher, there has been limited independent validation of the test. In this study, we investigated the convergent and discriminant validity, internal consistency, and alternate forms reliability of the NAB Naming Test in a sample of adults (Form 1: n = 247, Form 2: n = 151) clinically referred for neuropsychological evaluation. Results indicate adequate-to-good internal consistency and alternate forms reliability. We also found strong convergent validity as demonstrated by relationships with other neurocognitive measures. We found preliminary evidence that the NAB Naming Test demonstrates a more pronounced ceiling effect than other commonly used measures of naming. To our knowledge, this represents the largest published independent validation study of the NAB Naming Test in a clinical sample. Our findings suggest that the NAB Naming Test demonstrates adequate validity and reliability and merits consideration in the test arsenal of clinical neuropsychologists.

Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and Interpretation.

PubMed

Merali, Zamir; Wilson, Jefferson R

2017-11-01

Randomized clinical trials often represent the highest level of clinical evidence available to evaluate the efficacy of an intervention in clinical medicine. Although the process of randomization serves to maximize internal validity, the external validity, or generalizability, of such studies depends on several factors determined at the design phase of the trial including eligibility criteria, study setting, and outcomes of interest. In general, explanatory trials are optimized to demonstrate the efficacy of an intervention in a highly selected patient group; however, findings from these studies may not be generalizable to the larger clinical problem. In contrast, pragmatic trials attempt to understand the real-world benefit of an intervention by incorporating design elements that allow for greater generalizability and clinical applicability of study results. In this article we describe the explanatory-pragmatic continuum for clinical trials in greater detail. Further, a well-accepted tool for grading trials on this continuum is described, and applied, to 2 recently published trials pertaining to the surgical management of lumbar degenerative spondylolisthesis.

Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease☆

PubMed Central

Vandenberghe, Rik; Adamczuk, Katarzyna; Dupont, Patrick; Laere, Koen Van; Chételat, Gaël

2013-01-01

Amyloid imaging is currently introduced to the market for clinical use. We will review the evidence demonstrating that the different amyloid PET ligands that are currently available are valid biomarkers for Alzheimer-related β amyloidosis. Based on recent findings from cross-sectional and longitudinal imaging studies using different modalities, we will incorporate amyloid imaging into a multidimensional model of Alzheimer's disease. Aside from the critical role in improving clinical trial design for amyloid-lowering drugs, we will also propose a tentative algorithm for when it may be useful in a memory clinic environment. Gaps in our evidence-based knowledge of the added value of amyloid imaging in a clinical context will be identified and will need to be addressed by dedicated studies of clinical utility. PMID:24179802

Weighing Clinical Evidence Using Patient Preferences: An Application of Probabilistic Multi-Criteria Decision Analysis.

PubMed

Broekhuizen, Henk; IJzerman, Maarten J; Hauber, A Brett; Groothuis-Oudshoorn, Catharina G M

2017-03-01

The need for patient engagement has been recognized by regulatory agencies, but there is no consensus about how to operationalize this. One approach is the formal elicitation and use of patient preferences for weighing clinical outcomes. The aim of this study was to demonstrate how patient preferences can be used to weigh clinical outcomes when both preferences and clinical outcomes are uncertain by applying a probabilistic value-based multi-criteria decision analysis (MCDA) method. Probability distributions were used to model random variation and parameter uncertainty in preferences, and parameter uncertainty in clinical outcomes. The posterior value distributions and rank probabilities for each treatment were obtained using Monte-Carlo simulations. The probability of achieving the first rank is the probability that a treatment represents the highest value to patients. We illustrated our methodology for a simplified case on six HIV treatments. Preferences were modeled with normal distributions and clinical outcomes were modeled with beta distributions. The treatment value distributions showed the rank order of treatments according to patients and illustrate the remaining decision uncertainty. This study demonstrated how patient preference data can be used to weigh clinical evidence using MCDA. The model takes into account uncertainty in preferences and clinical outcomes. The model can support decision makers during the aggregation step of the MCDA process and provides a first step toward preference-based personalized medicine, yet requires further testing regarding its appropriate use in real-world settings.

Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension.

PubMed

Komaroff, A L; Flatley, M; Browne, C; Sherman, H; Fineberg, S E; Knopp, R H

1976-04-01

Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The care rendered by the protocol system was compared with care rendered by a "traditional" system in the same clinic in which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.

Efficacy of a crosslinked hyaluronic acid-based hydrogel as a tear film supplement: a masked controlled study.

PubMed

Williams, David L; Mann, Brenda K

2014-01-01

Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in both humans and dogs. Treating KCS often requires the daily application of more than one type of eye drop in order to both stimulate tear prodcution and provide a tear supplement to increase hydration and lubrication. A previous study demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a reduced dosing regimen of only twice-daily administration. The present study extended those results by comparing the use of the xCMHA-S to a standard HA-containing tear supplement in a masked, randomized clinical study in dogs with a clinical diagnosis of KCS. The xCMHA-S was found to significantly improve ocular surface health (conjunctival hyperaemia, ocular irritation, and ocular discharge) to a greater degree than the alternative tear supplement (P = 0.0003). Further, owners reported the xCMHA-S treatment as being more highly effective than the alternative tear supplement (P = 0.0024). These results further demonstrate the efficacy of the xCMHA-S in reducing the clinical signs associated with KCS, thereby improving patient health and owner happiness.

Clinical validation of the Tempus xO assay

PubMed Central

Beaubier, Nike; Tell, Robert; Huether, Robert; Bontrager, Martin; Bush, Stephen; Parsons, Jerod; Shah, Kaanan; Baker, Tim; Selkov, Gene; Taxter, Tim; Thomas, Amber; Bettis, Sam; Khan, Aly; Lau, Denise; Lee, Christina; Barber, Matthew; Cieslik, Marcin; Frankenberger, Casey; Franzen, Amy; Weiner, Ali; Palmer, Gary; Lonigro, Robert; Robinson, Dan; Wu, Yi-Mi; Cao, Xuhong; Lefkofsky, Eric; Chinnaiyan, Arul; White, Kevin P.

2018-01-01

We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. We apply this assay to clinical specimens and cell lines, and we demonstrate a clinical sensitivity of 98.4% and positive predictive value of 100% for the clinically actionable variants measured by the assay. We also demonstrate highly accurate copy number measurements and gene rearrangement identification. PMID:29899824

Enhancement of plaque removal efficacy by tooth brushing with baking soda dentifrices: results of five clinical studies.

PubMed

Putt, Mark S; Milleman, Kimberly R; Ghassemi, Annahita; Vorwerk, Linda M; Hooper, William J; Soparkar, Pramod M; Winston, Anthony E; Proskin, Howard M

2008-01-01

An earlier clinical study demonstrated that brushing with a commercial Arm & Hammer dentifrice containing baking soda physically removed significantly more plaque than brushing with either of two commercial dentifrices which did not contain baking soda. However, little has been done to confirm these results and to compare baking soda-containing dentifrices with more recently commercialized non-baking soda dentifrice formulations. The objective of this study was to compare commercial dentifrices containing 20% to 65% baking soda and commercial dentifrices without baking soda in enhancing plaque removal efficacy of tooth brushing. Five randomized, controlled, blinded, crossover clinical studies were performed among healthy adult volunteers who provided informed consent. After approximately 24 hours without oral hygiene, subjects with sufficient plaque were enrolled in the study phase. Plaque was scored before and after supervised brushing for one minute using the Turesky, et al. modification of the Quigley-Hein Plaque Index at six sites per tooth according to Soparkar's modification as described by Lobene, et al. In each study, wash-out periods with a regular dentifrice not evaluated in the study separated each product treatment. In all studies, every dentifrice exhibited a significant (p < 0.0001) reduction in 24-hour plaque scores. Between-group comparisons of whole mouth plaque scores in all five studies demonstrated that brushing with baking soda dentifrices resulted in statistically greater (p < 0.01) reductions in whole mouth mean plaque scores than brushing with dentifrices that did not contain baking soda. Results on other tooth surfaces, such as facial, lingual, proximal, and gingival surfaces also demonstrated statistically greater (p < 0.05) reductions in mean plaque scores for the baking soda-containing dentifrices as compared to the baking soda-free dentifrices. In three of the studies comparing different levels of baking soda, brushing with dentifrices with higher concentrations of baking soda consistently removed numerically more plaque than those containing lower levels. In one of these three studies, the difference in plaque removal between the baking soda dentifrices reached statistical significance. The results suggest a positive relationship between plaque removal efficiency and baking soda concentration. The collective results from the five controlled clinical studies on over 270 subjects reported in this paper, consistently demonstrate that Arm & Hammer baking soda dentifrices enhanced plaque removal effectiveness of tooth brushing to a significantly greater extent than the non-baking soda dentifrice products.

Is seborrhoeic dermatitis associated with a diffuse, low-grade folliculitis and progressive cicatricial alopecia?

PubMed

Pitney, Lucy; Weedon, David; Pitney, Michael

2016-08-01

An association between adult scalp seborrhoeic dermatitis and cicatricial hair loss has not previously been convincingly established. This study seeks to demonstrate a unique relationship between a clinically identifiable chronic scalp dermatitis-folliculitis with the characteristic histological features of low-grade inflammatory fibrosing alopecia, resulting in a distinctive progressive cicatricial alopecia which we believe is prevalent and hitherto unrecognised, and befits the description of seborrhoeic folliculitis. The clinical, epidemiological and histopathological features of seborrhoeic folliculitis are demonstrated to establish its unique status among the disorders of adult diffuse cicatricial alopecia. © 2015 The Australasian College of Dermatologists.

A prospective controlled study of diagnostic imaging for acute shin splints.

PubMed

Batt, M E; Ugalde, V; Anderson, M W; Shelton, D K

1998-11-01

The purpose of this prospective, observational study was to examine the relationship of clinical examination, plain radiograph (XR), triple-phase bone scan (TPBS), and magnetic resonance imaging (MRI) in the investigation of patients presenting with acute shin splints. 23 subjects with exercise induced lower leg pain and diffuse tibial tenderness of less than 3 months' duration were recruited. Subjects were excluded if there was clinical evidence of compartment syndrome, muscle hernia, or stress fracture. Each subject underwent XR, TPBS, and MRI within 2 wk of physical examination. Four asymptomatic controls underwent TPBS and MRI. Clinical findings, XR, TPBS, and MRI findings were independently recorded using a consistent template and subsequently analyzed. A single consensus lesion was chosen that provided the greatest overlap and highest grade to allow comparison of clinical and imaging findings. Sensitivity and specificity were calculated from data relating to clinical findings and diagnostic imaging. Eighteen subjects had bilateral symptoms and five unilateral with a mean duration of symptom of 5.4 wk (+/- 3.5). Of 41 symptomatic lower legs, there were TPBS abnormalities in 36 and MRI findings in 34. Analysis of clinical findings to TPBS and MRI demonstrated a sensitivity and specificity of 84%, 33% and 79%, 33%, respectively. Assuming TPBS as the "gold-standard," MRI findings demonstrated a sensitivity of 95% and specificity of 67%. There was poor agreement between the grading of TPBS and MRI (k = 0.3). In the 5/46 asymptomatic limbs, 3/5 demonstrated uptake on bone scan and 4/5 signal change with MRI. Imaging abnormalities were similarly seen in the four control patients. MRI may be used rather than TPBS and radiographs for evaluating acute tibial pain in athletes where avoidance of radiation exposure is desirable. Similar sensitivity and specificity may be expected from both investigations; however, in the light of abnormal TPBS and MRI findings in control and asymptomatic limbs, we recommend further studies be performed to define the extent of nonpathological TPBS and MRI changes.

Data Warehouse Design from HL7 Clinical Document Architecture Schema.

PubMed

Pecoraro, Fabrizio; Luzi, Daniela; Ricci, Fabrizio L

2015-01-01

This paper proposes a semi-automatic approach to extract clinical information structured in a HL7 Clinical Document Architecture (CDA) and transform it in a data warehouse dimensional model schema. It is based on a conceptual framework published in a previous work that maps the dimensional model primitives with CDA elements. Its feasibility is demonstrated providing a case study based on the analysis of vital signs gathered during laboratory tests.

Marketing and clinical trials: a case study.

PubMed

Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-11-20

Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

A comparison of dentifrices for clinical relief from dentin hypersensitivity using the Jay Sensitivity Sensor Probe.

PubMed

Hegde, Shashikanth; Rao, B H Sripathi; Kakar, Ravish Chander; Kakar, Ashish

2013-05-01

To evaluate the clinical relief from dentin hypersensitivity among subjects provided with a dentifrice formulated with 8% arginine, calcium carbonate and 1,000 ppm fluoride [sodium monofluorophosphate (MFP)] in comparison to those issued a commercially available dentifrice containing 1,000 ppm fluoride [as sodium monofluorophosphate (MFP)]. Clinical evaluations for hypersensitivity were performed with a novel tactile hypersensitivity measuring instrument--the Jay Sensitivity Sensor (Jay) Probe--in conjunction with evaporative triggers by air blast (Schiff scale) and Visual Analog Scores (VAS). Qualified adults from the Mangalore, India area who presented two teeth with dentin hypersensitivity were enrolled for this double-blind, randomized, parallel, controlled clinical trial conducted in an outpatient clinical setting. At baseline, dentin hypersensitivity was evaluated by the Jay Probe (tactile), air blast and VAS methods. Subjects were randomly issued a study dentifrice and instructed to brush their teeth for 1 minute twice daily with the provided dentifrice. Clinical evaluations for hypersensitivity were repeated after 2, 4 and 8 weeks of product use. 86 subjects (35 males and 51 females) complied with the study protocol and completed the entire study. At each recall visit, both treatment groups demonstrated significant reductions in dentin hypersensitivity from their corresponding baselines (P < 0.05). Subjects assigned the 8% arginine, calcium carbonate and 1,000 ppm fluoride dentifrice demonstrated statistically significant reductions in responses to tactile stimuli, air blast, and VAS responses in comparison to those using the dentifrice containing 1,000 ppm fluoride after 2, 4, and 8 weeks, respectively.

Comparison between videotape and personal teaching as methods of communicating clinical skills to medical students.

PubMed Central

Mir, M A; Marshall, R J; Evans, R W; Hall, R; Duthie, H L

1984-01-01

The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a randomly selected group of 12 students (personal group) from the first clinical year and then showing these recordings, under identical conditions, to 13 students from the same year (video group). The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a questionnaire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration. In answering the questionnaire the video group obtained a mean (SD) score of 20.8 (7.0) (maximum possible score 40), which was not significantly different from the score achieved by the personal group (17.4 (7.7)). The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)%. Videotaped demonstrations can be as effective as personal teaching of clinical methods, and video should be developed as a medium for first line clinical teaching. PMID:6428655

Reliability, Validity and Treatment Sensitivity of the Schizophrenia Cognition Rating Scale

PubMed Central

Keefe, Richard S.E.; Davis, Vicki G.; Spagnola, Nathan B.; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas L.; Narasimhan, Meera; Harvey, Philip D.

2014-01-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r= −0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient self-report is the sole information source. PMID:25028065

Reliability, validity and treatment sensitivity of the Schizophrenia Cognition Rating Scale.

PubMed

Keefe, Richard S E; Davis, Vicki G; Spagnola, Nathan B; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas D; Narasimhan, Meera; Harvey, Philip D

2015-02-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r=-0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient's self-report is the sole information source. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

TAS-102: a novel antimetabolite for the 21st century

PubMed Central

Uboha, Nataliya; Hochster, Howard S

2016-01-01

TAS-102, a novel antimetabolite combination chemotherapy agent, consists of a rediscovered antimetabolite agent, trifluorothymidine (trifluridine) combined with the metabolic inhibitor of thymidine phosphorylase, tipiracil, in a 1:0.5 molar ratio. Mechanism of action studies suggest that this agent works by incorporation into DNA. Both preclinical and clinical studies demonstrate that this agent is noncross-resistant with 5-fluorouracil. Tipiracil may also have antiangiogenic effects through inhibition of thymidine phosphorylase. Recent randomized Phase II and III trials demonstrate clinical activity (improved progression-free survival, time to decrease in performance status, prolonged overall survival) in metastatic colorectal cancer refractory to all standard agents. Monotherapy with TAS-102 has now been approved for this indication in Japan and in the USA. PMID:26616466

New insights on antimicrobial efficacy of copper surfaces in the healthcare environment: a systematic review.

PubMed

Chyderiotis, S; Legeay, C; Verjat-Trannoy, D; Le Gallou, F; Astagneau, P; Lepelletier, D

2018-03-29

Hospital-acquired infections (HAIs) are a major public health issue. The potential of antimicrobial copper surfaces in reducing HAIs' rates is of interest but remains unclear. We conducted a systematic review of studies assessing the activity of copper surfaces (colony-forming unit (CFU)/surface, both in vitro and in situ) as well as clinical studies. In vitro study protocols were analysed through a tailored checklist developed specifically for this review, in situ studies and non-randomized clinical studies were assessed using the ORION (Outbreak Reports and Intervention studies Of Nosocomial infection) checklist and randomized clinical studies using the CONSORT guidelines. The search was conducted using PubMed database with the keywords 'copper' and 'surfaces' and 'healthcare associated infections' or 'antimicrobial'. References from relevant articles, including reviews, were assessed and added when appropriate. Articles were added until 30 August 2016. Overall, 20 articles were selected for review including 10 in vitro, eight in situ and two clinical studies. Copper surfaces were found to have variable antimicrobial activity both in vitro and in situ, although the heterogeneity in the designs and the reporting of the results prevented conclusions from being drawn regarding their spectrum and activity/time compared to controls. Copper effect on HAIs incidence remains unclear because of the limited published data and the lack of robust designs. Most studies have potential conflicts of interest with copper industries. Copper surfaces have demonstrated an antimicrobial activity but the implications of this activity in healthcare settings are still unclear. No clear effect on healthcare associated infections has been demonstrated yet. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Application of laser Raman spectroscopy in concentration measurements of multiple analytes in human body fluids

NASA Astrophysics Data System (ADS)

Qu, Jianan Y.; Suria, David; Wilson, Brian C.

1998-05-01

The primary goal of these studies was to demonstrate that NIR Raman spectroscopy is feasible as a rapid and reagentless analytic method for clinical diagnostics. Raman spectra were collected on human serum and urine samples using a 785 nm excitation laser and a single-stage holographic spectrometer. A partial east squares method was used to predict the analyte concentrations of interest. The actual concentrations were determined by a standard clinical chemistry. The prediction accuracy of total protein, albumin, triglyceride and glucose in human sera ranged from 1.5 percent to 5 percent which is greatly acceptable for clinical diagnostics. The concentration measurements of acetaminophen, ethanol and codeine inhuman urine have demonstrated the potential of NIR Raman technology in screening of therapeutic drugs and substances of abuse.

Psychometric properties of the Penn State Worry Questionnaire for children in a large clinical sample.

PubMed

Pestle, Sarah L; Chorpita, Bruce F; Schiffman, Jason

2008-04-01

The Penn State Worry Questionnaire for Children (PSWQ-C; Chorpita, Tracey, Brown, Collica, & Barlow, 1997) is a 14-item self-report measure of worry in children and adolescents. Although the PSWQ-C has demonstrated favorable psychometric properties in small clinical and large community samples, this study represents the first psychometric evaluation of the PSWQ-C in a large clinical sample (N = 491). Factor analysis indicated a two-factor structure, in contrast to all previously published findings on the measure. The PSWQ-C demonstrated favorable psychometric properties in this sample, including high internal consistency, high convergent validity with related constructs, and acceptable discriminative validity between diagnostic categories. The performance of the 3 reverse-scored items was closely examined, and results indicated retaining all 14 items.

Clinical Utilisation and Usefullness of the Rating Scale of Mixed States, ("Gt-Msrs"): a Multicenter Study.

PubMed

Tavormina, Giuseppe; Franza, Francesco; Stranieri, Giuseppe; Juli, Luigi; Juli, Maria Rosaria

2017-09-01

The rating scale "G.T. MSRS" has been designed to improve the clinical effectiveness of the clinician psychiatrists, by enabling them to make an early "general" diagnosis of mixed states. The knowledge of the clinical features of the mixed states and of the symptoms of the "mixity" of mood disorders is crucial: to mis-diagnose or mis-treat patients with these symptoms may increase the suicide risk and make worse the evolution of mood disorders going to the dysphoric state. This study is the second validation study of the "G.T. MSRS" rating scale, in order to demonstrate its usefullness.

Radiation therapy oncology group gynecologic oncology working group: comprehensive results.

PubMed

Gaffney, David K; Jhingran, Anuja; Portelance, Lorraine; Viswanathan, Akila; Schefter, Tracey; Weidhaas, Joanne; Small, William

2014-06-01

The purpose of this report was to comprehensively describe the activities of the Gynecologic Oncology Working Group within the Radiation Therapy Oncology Group (RTOG). Clinical trials will be reviewed as well as translational science and ancillary activities. During the past 40 years, a myriad of clinical trials have been performed within the RTOG with the aim of improving overall survival (OS) and decreasing morbidity in women with cervical or endometrial cancer. Major study questions have included hyperbaric oxygen, neutron radiotherapy, altered fractionation, hypoxic cell sensitization, chemosensitization, and volume-directed radiotherapy.RTOG 7920 demonstrated improvement in OS in patients with stages IB through IIB cervical carcinoma receiving prophylactic para-aortic irradiation compared to pelvic radiation alone. RTOG 9001 demonstrated that cisplatin and 5-FU chemoradiotherapy to the pelvis for advanced cervix cancer markedly improved OS compared to extended field radiotherapy alone. More recent trials have used radioprotectors, molecular-targeted therapy, and intensity-modulated radiation therapy. Ancillary studies have developed clinical target volume atlases for research protocols and routine clinical use. Worldwide practice patterns have been investigated in cervix, endometrial, and vulvar cancer through the Gynecologic Cancer Intergroup. Translational studies have focused on immunohistochemical markers, changes in gene expression, and miRNA patterns impacting prognosis.The RTOG gynecologic working group has performed clinical trials that have defined the standard of care, improved survival, and added to our understanding of the biology of cervical and endometrial cancers.

Three-dimensional cluster formation and structure in heterogeneous dose distribution of intensity modulated radiation therapy.

PubMed

Chao, Ming; Wei, Jie; Narayanasamy, Ganesh; Yuan, Yading; Lo, Yeh-Chi; Peñagarícano, José A

2018-05-01

To investigate three-dimensional cluster structure and its correlation to clinical endpoint in heterogeneous dose distributions from intensity modulated radiation therapy. Twenty-five clinical plans from twenty-one head and neck (HN) patients were used for a phenomenological study of the cluster structure formed from the dose distributions of organs at risks (OARs) close to the planning target volumes (PTVs). Initially, OAR clusters were searched to examine the pattern consistence among ten HN patients and five clinically similar plans from another HN patient. Second, clusters of the esophagus from another ten HN patients were scrutinized to correlate their sizes to radiobiological parameters. Finally, an extensive Monte Carlo (MC) procedure was implemented to gain deeper insights into the behavioral properties of the cluster formation. Clinical studies showed that OAR clusters had drastic differences despite similar PTV coverage among different patients, and the radiobiological parameters failed to positively correlate with the cluster sizes. MC study demonstrated the inverse relationship between the cluster size and the cluster connectivity, and the nonlinear changes in cluster size with dose thresholds. In addition, the clusters were insensitive to the shape of OARs. The results demonstrated that the cluster size could serve as an insightful index of normal tissue damage. The clinical outcome of the same dose-volume might be potentially different. Copyright © 2018 Elsevier B.V. All rights reserved.

Rivastigmine From Capsules to Patch: Therapeutic Advances in the Management of Alzheimer’s Disease and Parkinson’s Disease Dementia

PubMed Central

Micca, Joseph L.; Grossberg, George T.; Velting, Drew M.

2014-01-01

Objective: To discuss the pharmacology, mechanism of action, and chemical properties of the cholinesterase inhibitor (ChEI) rivastigmine; to provide a rationale for transdermal delivery and supportive clinical data, along with practical guidance on rivastigmine patch use in Alzheimer’s disease and Parkinson’s disease dementia. Data Sources: Pivotal studies of rivastigmine capsules and patch were identified using PubMed and the rivastigmine US prescribing information. PubMed searches were performed in 2013 using rivastigmine as a keyword. Study Selection: English-language articles related to rivastigmine considered of relevance to primary care physicians were included. Data Synthesis: Pharmacologic differences exist between rivastigmine and ChEIs. Clinical studies demonstrate symptomatic efficacy of oral rivastigmine across all stages of Alzheimer’s disease and mild-to-moderate Parkinson’s disease dementia. However, gastrointestinal adverse events limit access to optimal therapeutic doses. Strategies that lower maximum plasma concentrations (Cmax) and prolong time to Cmax, ie, transdermal delivery, may improve tolerability. Clinical registration studies have demonstrated improved tolerability of rivastigmine 9.5-mg/24-h patch versus 6-mg twice-daily capsules in mild-to-moderate Alzheimer’s disease, and a positive benefit-risk profile of 13.3-mg/24-h versus 9.5-mg/24-h patch in patients needing enhanced efficacy. Clinical data comparing 13.3-mg/24-h versus 4.6-mg/24-h patch in severe Alzheimer’s disease demonstrated efficacy on cognition and activities of daily living. These data led to approval of rivastigmine patch in severe Alzheimer’s disease. Transdermal delivery also has practical advantages, including simple, once-daily administration and a visual indicator of compliance. Potential application site reactions can be minimized and need not be a barrier to treatment. Conclusions: In addition to practical advantages, rivastigmine patch may improve clinical outcomes throughout the course of Alzheimer’s disease by providing access to high-dose efficacy without compromising tolerability. PMID:25667813

Safety of famciclovir in patients with herpes zoster and genital herpes.

PubMed Central

Saltzman, R; Jurewicz, R; Boon, R

1994-01-01

Safety reporting from individual ongoing and completed clinical studies has demonstrated that famciclovir, the well-absorbed oral form of the antiherpesvirus agent penciclovir, has been well tolerated by more than 3,000 individuals worldwide. An integrated safety evaluation has been performed and includes over 1,600 patients from 11 completed, randomized, double-blind clinical trials and 2 open trials. The famciclovir population consisted of 816 herpes zoster patients (four trials), 409 patients with acute genital herpesvirus infections (seven trials), and 382 patients from two genital herpes suppression studies. Overall, the famciclovir-treated patient population was 57.7% female and ranged in age from 15 to 102 years (mean, 42.6 years), with 31.2% aged 50 years or more and 15.7% aged 65 years or more. The mean duration of exposure to famciclovir was 28.8 days (5.8 days excluding suppression studies). The total daily doses ranged from 125 mg to 2.25 g. The most common adverse experiences reported as related to study medication (famciclovir and placebo) were headache, nausea, and diarrhea. The frequencies of adverse experiences and laboratory abnormalities (hematology, clinical chemistry, and urinalysis parameters) were similar in both famciclovir and placebo recipients. Thus, safety data from the analysis of 13 completed clinical studies demonstrate that famciclovir is tolerated well by patients with either herpes zoster or genital and has a safety profile comparable to that of placebo. PMID:7840587

Clinical evaluation of the use of an intracardiac electrocardiogram to guide the tip positioning of peripherally inserted central catheters.

PubMed

Zhao, Ruiyi; Chen, Chunfang; Jin, Jingfen; Sharma, Komal; Jiang, Nan; Shentu, Yingqin; Wang, Xingang

2016-06-01

The use of peripherally inserted central catheters (PICCs) provides important central venous accesses for clinical treatments, tests and monitoring. Compared with the traditional methods, intracardiac electrocardiogram (ECG)-guided method has the potential to guide more accurate tip positioning of PICCs. This study aimed to clinically evaluate the effectiveness of an intracardiac ECG to guide the tip positioning by monitoring characteristic P-wave changes. In this study, eligible patients enrolled September 2011 to May 2012 according to the inclusion and exclusion criteria received the catheterization monitored by intracardiac ECG. Then chest radiography was performed to check the catheter position. The results revealed that, with 117 eligible patients, all bar one patient who died (n = 116) completed the study, including 60 males and 56 females aged 51.2 ± 15.1 years. Most (n = 113, > 97%) had characteristic P-wave changes. The intracardiac ECG-guided positioning procedure achieved correct placement for 112 patients (96.56%), demonstrating 99.12% sensitivity and 100% specificity. In conclusion, the intracardiac ECG can be a promising technique to guide tip positioning of PICCs. However, since the sample size in this study is limited, more experience and further study during clinical practice are needed to demonstrate achievement of optimal catheterization outcomes. © 2015 John Wiley & Sons Australia, Ltd.

Curcuma as a functional food in the control of cancer and inflammation.

PubMed

Schaffer, Moshe; Schaffer, Pamela M; Zidan, Jamal; Bar Sela, Gil

2011-11-01

Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Turmeric is a spice that comes from the root Curcuma longa. Extensive research over the past half century and especially in recent years has revealed important functions of curcumin and a timely review of clinical state-of-the-art using curcumin. In-vitro and in-vivo research has shown various activities, such as anti-inflammatory, antiviral, antifungal, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and antiangiogenic properties. Curcumin also have been shown to be a mediator of chemo-resistance and radio-resistance. Various in-vitro and in-vivo and scarce number of clinical studies on curcumin were identified. The various effects and properties of curcumin are summarized in this review, including preclinical and especially clinical studies. This review concentrates on recent knowledge and research with curcumin clinical applications, and clinical studies, focusing on studies published between 2008 and 2011 demonstrating the gap between preclinical and clinical research.

Beyond the Dedicated Education Unit: Using Cognitive Load Theory to Guide Clinical Placement.

PubMed

Mulcock, Pamela McPhie; Grassley, Jane; Davis, Michael; White, Kathryn

2017-02-01

Navigating multiple instructors and clinical agencies can impair students' learning by increasing their cognitive load and perceived stress. This study used cognitive load theory to guide the home base clinical model (HBCM), which assigned students to the same faculty and hospital unit for two consecutive medical-surgical clinical courses. The study used a quasi-experimental three-group design to evaluate the effects of the HBCM on students' perceived stress, compared with groups who changed hospital or instructor. A 10-point visual analog scale measured students' perceived stress on nine clinical tasks. The study recruited 140 participants. Reductions in mean stress were greater for the HBCM groups than the other two groups. The study findings challenge the current practice of placing students with changing faculty and facilities. The HBCM demonstrates potential as an effective model for increasing students' ability to learn by decreasing their cognitive load and subsequent stress in their clinical placements. [J Nurs Educ. 2017;56(2):105-109.]. Copyright 2017, SLACK Incorporated.

Age and aphasia: a review of presence, type, recovery and clinical outcomes.

PubMed

Ellis, Charles; Urban, Stephanie

2016-12-01

Each year approximately 100,000 stroke survivors are diagnosed with aphasia. Although stroke is associated with age, the relationship between age and aphasia is less clear. To complete a review of the literature to examine the relationship between age and: (a) presence or likelihood of aphasia after stroke, (b) aphasia type, (c) aphasia recovery patterns, and (d) aphasia clinical outcomes. Articles were identified by a comprehensive search of "OneSearch," PubMed, and individual journals: Aphasiology, Stroke and the Journal of Stroke and Cerebrovascular Diseases. Inclusion criteria included: age and incidence of aphasia, likelihood of aphasia, aphasia recovery, and aphasia clinical outcome. Independent searches were completed by the authors. Each author independently assessed the full text of reports meeting inclusion criteria. Differences regarding study eligibility and need to proceed with data extraction were resolved by consensus. 1617 articles were identified during the initial search. Forty studies including 14,795 study participants were included in the review. The review generally demonstrated that: (a) stroke patients with aphasia are typically older than stroke with patients without aphasia and (b) aphasia type and age are associated as younger patients with aphasia are more likely to exhibit non-fluent or Broca's type of aphasia. In contrast, studies examining aphasia recovery and aphasia clinical outcomes did not demonstrate a positive relationship between age and recovery or clinical outcomes. Stroke is a condition of the elderly. However, age appears to only influence likelihood of aphasia and aphasia type.

Understanding the Potential Interethnic Difference in Rosuvastatin Pharmacokinetics.

PubMed

Benet, Leslie Z; Wu, Hsin-Fang

2017-09-01

Here we address the potential difference in rosuvastatin pharmacokinetics in Asians vs. whites. Our prospective study, reported in this issue, shows no ethnic difference when all subjects are wild-type for OATP1B1 and BCRP. We argue that although our study may be under powered to prove no ethnic difference, and that further confirmatory study is required, the virtual clinical study analysis, also reported in this issue, does not contradict the results of our prospective clinical study and that previous retrospective analysis of clinical studies does not include enough relevant subjects to conclude that wild-type OATP1B1 and BCRP do still demonstrate ethnic differences. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An Effectiveness Study of a CBT Group Program for Women with Breast Cancer

ERIC Educational Resources Information Center

Beatty, Lisa; Koczwara, Bogda

2010-01-01

Cognitive Behaviour Stress Management for women with breast cancer has demonstrable empirical efficacy, however its effectiveness in the applied clinical setting has not been examined to date in an Australian setting. A 10-week group program was offered to five women with early stage breast cancer. Clinical changes in distress, coping, and social…

Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

ERIC Educational Resources Information Center

Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

2005-01-01

Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

Psychometric Properties of the Penn State Worry Questionnaire for Children in a Large Clinical Sample

ERIC Educational Resources Information Center

Pestle, Sarah L.; Chorpita, Bruce F.; Schiffman, Jason

2008-01-01

The Penn State Worry Questionnaire for Children (PSWQ-C; Chorpita, Tracey, Brown, Collica, & Barlow, 1997) is a 14-item self-report measure of worry in children and adolescents. Although the PSWQ-C has demonstrated favorable psychometric properties in small clinical and large community samples, this study represents the first psychometric…

Summer Enrichment Workshop (SEW): A Quality Component of the University of Alabama's Gifted Education Preservice Training Program

ERIC Educational Resources Information Center

Newman, Jane L.; Gregg, Madeleine; Dantzler, John

2009-01-01

Summer Enrichment Workshop (SEW) is a clinical experience in the teacher preservice training program for gifted and talented (GT) master's degree interns at the University of Alabama. This mixed design study investigated the effects of the SEW clinical experience on interns' preparation to teach. Quantitative analysis demonstrated a statistically…

A Serious Game for Clinical Assessment of Cognitive Status: Validation Study.

PubMed

Tong, Tiffany; Chignell, Mark; Tierney, Mary C; Lee, Jacques

2016-05-27

We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=-.339, P <.001) and MMSE (r=-.558, P <.001), and correlated (point-biserial correlation) with the CAM (r=.565, P <.001) and with other cognitive assessments. This research demonstrates the feasibility of using serious games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making.

A Serious Game for Clinical Assessment of Cognitive Status: Validation Study

PubMed Central

Chignell, Mark; Tierney, Mary C.; Lee, Jacques

2016-01-01

Background We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. Objective The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. Methods We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). Results After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=–.339, P <.001) and MMSE (r=–.558, P <.001), and correlated (point-biserial correlation) with the CAM (r=.565, P <.001) and with other cognitive assessments. Conclusions This research demonstrates the feasibility of using serious games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making. PMID:27234145

Genetic Basis of Autoantibody Positive and Negative Rheumatoid Arthritis Risk in a Multi-ethnic Cohort Derived from Electronic Health Records

PubMed Central

Kurreeman, Fina; Liao, Katherine; Chibnik, Lori; Hickey, Brendan; Stahl, Eli; Gainer, Vivian; Li, Gang; Bry, Lynn; Mahan, Scott; Ardlie, Kristin; Thomson, Brian; Szolovits, Peter; Churchill, Susanne; Murphy, Shawn N.; Cai, Tianxi; Raychaudhuri, Soumya; Kohane, Isaac; Karlson, Elizabeth; Plenge, Robert M.

2011-01-01

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies. PMID:21211616

AMO Teledioptric System for age-related macular degeneration

NASA Astrophysics Data System (ADS)

Chou, Jim-Son; Ting, Albert C.

1994-05-01

A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

Impact of Probiotics on Necrotizing Enterocolitis

PubMed Central

Underwood, Mark A.

2016-01-01

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention. PMID:27836423

Clinic Workflow Simulations using Secondary EHR Data

PubMed Central

Hribar, Michelle R.; Biermann, David; Read-Brown, Sarah; Reznick, Leah; Lombardi, Lorinna; Parikh, Mansi; Chamberlain, Winston; Yackel, Thomas R.; Chiang, Michael F.

2016-01-01

Clinicians today face increased patient loads, decreased reimbursements and potential negative productivity impacts of using electronic health records (EHR), but have little guidance on how to improve clinic efficiency. Discrete event simulation models are powerful tools for evaluating clinical workflow and improving efficiency, particularly when they are built from secondary EHR timing data. The purpose of this study is to demonstrate that these simulation models can be used for resource allocation decision making as well as for evaluating novel scheduling strategies in outpatient ophthalmology clinics. Key findings from this study are that: 1) secondary use of EHR timestamp data in simulation models represents clinic workflow, 2) simulations provide insight into the best allocation of resources in a clinic, 3) simulations provide critical information for schedule creation and decision making by clinic managers, and 4) simulation models built from EHR data are potentially generalizable. PMID:28269861

Increasing complexity of clinical research in gastroenterology: implications for the training of clinician-scientists.

PubMed

Scott, Frank I; McConnell, Ryan A; Lewis, Matthew E; Lewis, James D

2012-04-01

Significant advances have been made in clinical and epidemiologic research methods over the past 30 years. We sought to demonstrate the impact of these advances on published gastroenterology research from 1980 to 2010. Twenty original clinical articles were randomly selected from each of three journals from 1980, 1990, 2000, and 2010. Each article was assessed for topic, whether the outcome was clinical or physiologic, study design, sample size, number of authors and centers collaborating, reporting of various statistical methods, and external funding. From 1980 to 2010, there was a significant increase in analytic studies, clinical outcomes, number of authors per article, multicenter collaboration, sample size, and external funding. There was increased reporting of P values, confidence intervals, and power calculations, and increased use of large multicenter databases, multivariate analyses, and bioinformatics. The complexity of clinical gastroenterology and hepatology research has increased dramatically, highlighting the need for advanced training of clinical investigators.

Effectiveness of educational and administrative interventions in medical outpatient clinics.

PubMed Central

Pozen, M W; Bonnet, P D

1976-01-01

This study examines the popular belief that increased educational supervision and increased administrative support in university outpatient clinics will improve physician performance, which in turn will improve the process and outcome of patient care. Positive effects on house officers' attitudes and better functioning of clinics with respect to follow-up, information retrieval, and prescribing practices were demonstrated. However, no differences in the process and outcome of care were identified by faculty judges using implicit criteria. PMID:175666

Biosimilars: Here and Now.

PubMed

Lemery, Steven J; Esteva, Francisco J; Weise, Martina

2016-01-01

Congress passed the Biologics Price Competition and Innovation Act (BPCI Act) as part of the Affordable Care Act on March 23, 2010. The BPCI Act authorized an approval pathway for biosimilar and interchangeable products. It defines biosimilarity to mean "that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components" and that "there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency of the product." The biosimilar pathway has the potential to facilitate access to biologic products through increased competition, in the same manner as biosimilars have done for almost 10 years in Europe. The goal of a biosimilar program is not to independently establish safety and effectiveness for each condition of use. Rather, the goal is to demonstrate biosimilarity through an extensive analytical characterization and a targeted clinical program designed to assess for clinically meaningful differences, if they exist. The regulatory approaches in both the United States and Europe involve a totality-of-the-evidence approach to demonstrate biosimilarity. Importantly, the biosimilar pathway allows for extrapolation of data across indications so that a sponsor, with adequate scientific justification, need not conduct clinical studies in each intended condition of use. Without extrapolation, development may not be feasible for many products, and patients and resources could be diverted from clinical studies of newer agents for cancer.

Fluorescence lifetime technique for surgical imaging, guidance and augmented reality (Conference Presentation)

NASA Astrophysics Data System (ADS)

Marcu, Laura

2017-02-01

The surgeon's limited ability to accurately delineate the tumor margin during surgical interventions is one key challenge in clinical management of cancer. New methods for guiding tumor resection decisions are needed. Numerous studies have shown that tissue autofluorescence properties have the potential to asses biochemical features associates with distinct pathologies in tissue and to distinguish various cancers from normal tissues. However, despite these promising reports, autofluorescence techniques were sparsely adopted in clinical settings. Moreover, when adopted they were primarily used for pre-operative diagnosis rather than guiding interventions. To address this need, we have researched and engineered instrumentation that utilizes label-free fluorescence lifetime contrast to characterize tissue biochemical features in vivo in patients and methodologies conducive to real-time (few seconds) diagnosis of tissue pathologies during surgical procedures. This presentation overviews clinically-compatible multispectral fluorescence lifetime imaging techniques developed in our laboratory and their ability to operate as stand-alone tools, integrated in a biopsy needle and in conjunction with the da Vinci surgical robot. We present pre-clinical and clinical studies in patients that demonstrate the potential of these techniques for intraoperative assessment of brain tumors and head and neck cancer. Current results demonstrate that intrinsic fluorescence signals can provide useful contrast for delineation distinct types of tissues including tumors intraoperatively. Challenges and solutions in the clinical implementation of these techniques are discussed.

Driving clinical study efficiency by using a productivity breakdown model: comparative evaluation of a global clinical study and a similar Japanese study.

PubMed

Takahashi, K; Sengoku, S; Kimura, H

2011-02-01

A fundamental management imperative of pharmaceutical companies is to contain surging costs of developing and launching drugs globally. Clinical studies are a research and development (R&D) cost driver. The objective of this study was to develop a productivity breakdown model, or a key performance indicator (KPI) tree, for an entire clinical study and to use it to compare a global clinical study with a similar Japanese study. We, thereby, hope to identify means of improving study productivity. We developed the new clinical study productivity breakdown model, covering operational aspects and cost factors. Elements for improving clinical study productivity were assessed from a management viewpoint by comparing empirical tracking data from a global clinical study with a Japanese study with similar protocols. The following unique and material differences, beyond simple international difference in cost of living, that could affect the efficiency of future clinical trials were identified: (i) more frequent site visits in the Japanese study, (ii) head counts at the Japanese study sites more than double those of the global study and (iii) a shorter enrollment time window of about a third that of the global study at the Japanese study sites. We identified major differences in the performance of the two studies. These findings demonstrate the potential of the KPI tree for improving clinical study productivity. Trade-offs, such as those between reduction in head count at study sites and expansion of the enrollment time window, must be considered carefully. © 2010 Blackwell Publishing Ltd.

Pupillary motility: bringing neuroscience to the psychiatry clinic of the future.

PubMed

Graur, Simona; Siegle, Greg

2013-08-01

Modern pupillometry has expanded the study and utility of pupil responses in many new domains, including psychiatry, particularly for understanding aspects of cognitive and emotional information processing. Here, we review the applications of pupillometry in psychiatry for understanding patients' information processing styles, predicting treatment, and augmenting function. In the past year pupillometry has been shown to be useful in specifying cognitive/affective occurrences during experimental tasks and informing clinical diagnoses. Such studies demonstrate the potential of pupillary motility to be used in clinical psychiatry much as it has been in neurology for the past century.

Mother-infant home care drives quality in a managed care environment.

PubMed

Malnory, M

1997-04-01

Advocates of inpatient managed care employing clinical pathways are confident that this patient management strategy reduces cost while promoting equivalent patient outcomes. Other health care professionals are concerned that cost reductions place patients at higher risk for adverse health events. Research is needed to demonstrate the true impact of cost-containment strategies on clinical outcomes. The article describes a study in progress comparing patients conventionally managed by their physicians with similar patients whose overall management involved a nurse case manager. This study explores the issue of resource costs that can be linked to clinical and financial outcome measures.

Proving that less is more: linking resources to outcomes.

PubMed

Ebener, M K; Baugh, K; Formella, N M

1996-01-01

Advocates of inpatient managed care employing clinical pathways are confident that this patient management strategy reduces cost while promoting optimal patient outcomes. Other health care professionals are concerned that cost reductions place patients at higher risk for adverse health events. Research is needed to demonstrate the true impact of cost-containment strategies on clinical outcomes. The article describes a study in progress comparing patients conventionally managed by their physicians with similar patients whose overall management involved a nurse case manager. This study explores the issue of resource costs that can be linked to clinical and financial outcome measures.

Retroillumination photography analysis enhances clinical definition of severe Fuchs Corneal Dystrophy

PubMed Central

Eghrari, Allen O.; Garrett, Brian S.; Mumtaz, Aisha A.; Edalati, Armand E.; Meadows, Danielle N.; McGlumphy, Elyse J.; Iliff, Benjamin W.; Gottsch, John D.

2015-01-01

Purpose Retroillumination photography analysis (RPA) provides objective assessment of the number and distribution of guttae in Fuchs Corneal Dystrophy. Here, we assess its correlation with clinical grading using slit-lamp biomicroscopy across varying levels of severity. Methods Retroillumination photographs were conducted of 95 affected corneas with slit-lamp flash photography after pupillary dilation. Individual guttae were counted manually and the position of individual points recorded. Clinical grading using the Krachmer scale was documented for each eye during examination, and regression analyses were performed to identify the strength of association with number of guttae. We assessed range at each stage of clinical grading, and utilized the Mann-Whitney U test to assess whether clinical grading levels demonstrated successively higher numbers of guttae. Results Krachmer score ranged from 1 to 5, with mean of 2.6. Mean numbers of guttae at each level of severity were 289 (1+), 999 (2+), 2669 (3+), 5474 (4+), and 7133 (5+). Each stage demonstrated significantly higher numbers of guttae than its preceding level except from 4+ to 5+ (p=0.30), consistent with the definition of 4+ as the highest level defined by presence of guttae. Higher levels of clinical grading were associated with larger ranges of guttae (p<0.01). A linear regression model resulted in a strong fit between RPA and Krachmer score (r=0.81). Conclusion In this largest study of RPA data and comparison with subjective clinical grading of FCD severity, RPA correlates strongly and demonstrates enhanced definition of severity at advanced stages of disease. PMID:26488628

Subjective global assessment of nutritional status – A systematic review of the literature.

PubMed

da Silva Fink, Jaqueline; Daniel de Mello, Paula; Daniel de Mello, Elza

2015-10-01

Subjective Global Assessment (SGA) is a nutritional assessment tool widely used in hospital clinical practice, even though it is not exempted of limitations in relation to its use. This systematic review intended to update knowledge on the performance of SGA as a method for the assessment of the nutritional status of hospitalized adults. PubMed data base was consulted, using the search term "subjective global assessment". Studies published in English, Portuguese or Spanish, between 2002 and 2012 were selected, excluding those not found in full, letters to the editor, pilot studies, narrative reviews, studies with n < 30, studies with population younger than 18 years of age, research with non-hospitalized populations or those which used a modified version of the SGA. Of 454 eligible studies, 110 presented eligibility criteria. After applying the exclusion criteria, 21 studies were selected, 6 with surgical patients, 7 with clinical patients, and 8 with both. Most studies demonstrated SGA performance similar or better than the usual assessment methods for nutritional status, such as anthropometry and laboratory data, but the same result was not found when comparing SGA and nutritional screening methods. Recently published literature demonstrates SGA as a valid tool for the nutritional diagnosis of hospitalized clinical and surgical patients, and point to a potential superiority of nutritional screening methods in the early detection of malnutrition. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care.

PubMed

Bennett, Mike; Lucas, Viv; Brennan, Mary; Hughes, Andrew; O'Donnell, Valerie; Wee, Bee

2002-09-01

The management of 'death rattle' was reviewed by a task group on behalf of the Association for Palliative Medicine's Science Committee. Evidence was searched for the effectiveness of various anti-muscarinic drugs in drying oropharyngeal and bronchial secretions in dying patients. Clinical guidelines were constructed based on evidence from volunteer and clinical studies. Death rattle occurs in half of all dying patients and some response occurs in around 80% of treated patients. Clinical studies demonstrate that subcutaneous hyoscine hydrobromide 400 microg is more effective at improving symptoms at 30 min than glycopyrronium 200 microg by the same route. Volunteer studies demonstrate that intramuscular glycopyrronium 400 microg is as effective in drying secretions at 30 min as a dose of 200 microg given intravenously. Duration of response is shortest for hyoscine butylbromide (1 h) and longest for glycopyrronium (more than 6 h). There is insufficient evidence to support the use of one drug over another in a continuous infusion and prescribers should base decisions on different characteristics of each anti-muscarinic drug.

Evaluation of the challenges faced in increasing contraceptive access within a community college population.

PubMed

Lamme, Jacqueline; Edelman, Alison; Padua, Emily; Jensen, Jeffrey T

2017-01-01

Research demonstrates removing barriers to access, decreasing costs and offering same-day placement of long-acting reversible contraception (LARC) increases contraceptive uptake in young women. For those in community college (CC), LARC utilization might reduce the risk of dropout and improve degree completion. We identified a local school who had documented an unmet need for on-campus services through a recent student assessment. We then established an on-campus, same day contraceptive clinic at the CC as part of a clinical trial. We found that students did not use the service even after multiple attempts to increase awareness and we ended the study. Here, we report lessons learned from attempting research in this environment in addition to results from a follow-up survey to determine why students did not access the clinical resource. Students reported that they already had good access to contraception and preferred to get their healthcare off-campus. This study demonstrates the complexities of studying highly focused interventions to influence access to care in the current health care environment with ever changing regulations. NCT02735551 . Registered April 6, 2016.

Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery

PubMed Central

Ono, Akihiko; Ito, Sayami; Sakagami, Shun; Saito, Mio; Quan, Ying-Shu; Kamiyama, Fumio; Hirobe, Sachiko; Okada, Naoki

2017-01-01

Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the loaded vaccine antigen into the skin. To shorten skin application time for clinical practice, this study aims to develop novel faster-dissolving MNs. We designed two types of MNs made from a single thickening agent, carboxymethylcellulose (CMC) or hyaluronan (HN). Both CMC-MN and HN-MN completely dissolved in rat skin after a 5-min application. In pre-clinical studies, both MNs could demonstrably increase antigen-specific IgG levels after vaccination and prolong antigen deposition compared with conventional injections, and deliver antigens into resected human dermal tissue. In clinical research, we demonstrated that both MNs could reliably and safely puncture human skin without any significant skin irritation from transepidermal water loss measurements and ICDRG (International Contact Dermatitis Research Group) evaluation results. PMID:28771172

Gold nanoparticles for non-invasive cell tracking with CT imaging

NASA Astrophysics Data System (ADS)

Meir, Rinat; Betzer, Oshra; Barnoy, Eran; Motiei, Menachem; Popovtzer, Rachela

2018-02-01

Cell-based therapies use living cells with therapeutic traits to treat various diseases. This is a beneficial alternative for diseases that existing medicine cannot cure efficiently. However, inconsistent results in clinical trials are preventing the advancement and implementation of cell-based therapy. In order to explain such results, there is a need to discover the fate of the transplanted cells. To answer this need, we developed a technique for noninvasive in vivo cell tracking, which uses gold nanoparticles as contrast agents for CT imaging. Herein, we investigate the design principles of this technique for intramuscular transplantation of therapeutic cells. Longitudinal studies were performed, demonstrating the ability to track cells over long periods of time. As few as 500 cells could be detected and a way to quantify the number of cells visualized by CT was demonstrated. This cell-tracking technology has the potential to become an essential tool in pre-clinical studies as well as in clinical trials and advance cell therapy.

A comparative, randomized, controlled study on clinical efficacy and dental staining reduction of a mouthwash containing Chlorhexidine 0.20% and Anti Discoloration System (ADS).

PubMed

Marrelli, Massimo; Amantea, Massimiliano; Tatullo, Marco

2015-01-01

A good control of bacterial plaque is an essential factor for the success of periodontal therapy, therefore it is the main objective that the clinician together with the patient must get to have a healthy periodontium. The plaque control with mouthwashes is the most important home therapy as it helps to reduce the formation of plaque between the mechanical removal with a toothbrush. Authors analyzed the clinical data from a trial carried out with 3 different mouthwashes containing 0.2% Chlorhexidine (CHX). In addition, the ADS (Anti Discoloration System - Curaden Healthcare) was tested in comparison with the other mouthwashes without this system. We tested antiplaque activity showed by 3 of the most commercialized mouthwashes, moreover, we tested the ability in reducing the dental staining related to the oral assumption of Chlorhexidine. Our results demonstrated the clinical efficacy of the 3 mouthwashes with CHX. Particularly performing was the anti discoloration system (Curaden Healthcare), with a clinical detection of dental stainings significantly less than the others tested. This study demonstrated the clinical efficacy of ADS system in the reduction of tooth staining, without a loss of antiplaque activity with respect to the competing mouthwashes containing CHX.

Efficacy of Periarticular Injection With a Long-Acting Local Analgesic in Joint Arthroplasty.

PubMed

Barrington, John W

2015-10-01

Attention to patient satisfaction is critical in today's health care environment-satisfaction surveys inform the development of hospital performance standards and can influence an institution's rankings and reimbursement. The effectiveness of postoperative pain management can affect clinical outcomes and also influence the patient's perception of the overall surgical experience. Ample clinical- trial data now exist that demonstrate the benefits of periarticular injections as part of a multimodal regimen in patients undergoing joint arthroplasty. One option that surgeons now use widely is bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc), a long-acting local analgesic that the orthopedic surgeon can administer intraoperatively. The US Food and Drug Administration has approved liposomal bupivacaine for injection into the surgical site to produce postsurgical analgesia. The safety and efficacy of liposomal bupivacaine has been demonstrated in clinical studies in multiple types of surgical procedure, including double-blind, randomized, controlled clinical trials that involved over 1300 patients. In a case-control study comparing clinical and economic parameters before and after the introduction of liposomal bupivacaine as a component of the multimodal perioperative pain regimen for total joint arthroplasty, liposomal bupivacaine provided improved overall pain scores, an increase in patients reporting a pain score of 0, increased patient satisfaction, decreased length of stay, and a decrease in overall costs.

Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent.

PubMed

Sanada, Fumihiro; Taniyama, Yoshiaki; Azuma, Junya; Yuka, Ikeda-Iwabe; Kanbara, Yasuhiro; Iwabayashi, Masaaki; Rakugi, Hiromi; Morishita, Ryuichi

2014-04-01

Peripheral artery disease (PAD) is caused by atherosclerosis, hardening and narrowing arteries over time due to buildup of fatty deposit in vascular bed called plaque. Severe blockage of an artery of the lower extremity markedly reduce blood flow, resulting in critical limb ischemia (CLI) manifested by a variety of clinical syndromes including rest pain in the feet or toes, ulcer and gangrene with infection. Despite significant advances in clinical care and interventions for revascularization, patients with CLI remain at high risk for amputation and cardiovascular death. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to increase blood flow in ischemic limb. Initial animal studies and phase I clinical trials with vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) demonstrated promising results, inspiring scientists to progress forward. However, more rigorous phase II and III clinical trials have failed to demonstrate beneficial effects of these angiogenic growth factors to date. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (phase III) and US (phase II) demonstrated that hepatocyte growth factor (HGF) gene therapy for CLI significant improved primary end points and tissue oxygenation up to two years in comparison to placebo. These clinical results implicate a distinct action of HGF on cellular processes involved in vascular remodeling under pathological condition. This review presents data from phase I-III clinical trials of therapeutic angiogenesis by gene therapy in patients with PAD. Further, we discuss the potential explanation for the success or failure of clinical trials in the context of the biological mechanisms underlying angiogenesis and vascular remodeling, including cellular senescence, inflammation, and tissue fibrosis.

A Single-Case Experimental Demonstration of Functional Analytic Psychotherapy with Two Clients with Severe Interpersonal Problems

ERIC Educational Resources Information Center

Oshiro, Claudia Kami Bastos; Kanter, Jonathan; Meyer, Sonia Beatriz

2012-01-01

Functional Analytic Psychotherapy (FAP) is emerging as an effective psychotherapy for psychiatric clinical cases. However, there is little research demonstrating the process of change of FAP. The present study evaluated the introduction and withdrawal of FAP interventions on therapy-interfering verbal behaviors of two participants who were in…

Effective teaching behaviors in the emergency department: A qualitative study with Millennial nursing students in Shanghai.

PubMed

Jiang, Jinxia; Zeng, Li; Kue, Jennifer; Li, Hong; Shi, Yan; Chen, Cuiping

2018-02-01

Millennial nursing students are different from generations before especially with the rapid development of China's economy, their varieties of characteristics affect the clinical teaching and learning. But how their learning preference impact their learning outcomes remain unclear. The aim of this study is to explore effective teaching methods in the emergency department from the perspective of Millennial nursing students in Shanghai, China. One of the main objectives is to provide valuable information to help nursing programs in China to effectively educate Millennial students to deliver patient-centered care and to meet medical changes according to Chinese healthcare reform. Qualitative study design was used and semistructured interviews were conducted in a purposive sample of 16 nursing students from six colleges of nursing and five nursing high schools in Shanghai. They are from eight geographical areas across China and have a clinical practice in the teaching hospital. Colaizzi seven-step framework was applied for data analysis. Three themes were emerged including: demonstrating harmonious faculty-student relationship, possessing professional competence and being empathetic for teaching. The findings of this study provide valuable information for promoting the clinical teaching quality in China. It is crucial to put more emphasis on demonstrating harmonious faculty-student relationship, rendering Millennial students more caring behavior, possessing sufficient competence in both knowledge and skills, and taking full advantage of technology in clinical teaching. The results of this study are relevant to envision the future training of clinical nursing teachers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer1

PubMed Central

Kurhanewicz, John; Vigneron, Daniel B; Nelson, Sarah J

2000-01-01

Abstract Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy. PMID:10933075

Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies.

PubMed

Thu, Hnin Ei; Mohamed, Isa Naina; Hussain, Zahid; Jayusman, Putri Ayu; Shuid, Ahmad Nazrun

2017-01-01

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

[The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire].

PubMed

Goebel, G; Hiller, W

1994-03-01

The clinical examination of patients with severe and chronic tinnitus must include associated psychological disturbances. The present paper describes traditional diagnostic methods of ENT practice as well as the Tinnitus Questionnaire (TQ) which has been evaluated in a number of studies. This instrument differentiates between emotional and cognitive distress, auditory perceptual difficulties and self-experienced intrusiveness produced by the tinnitus. The results of a German multicenter study are presented which show that the TQ can be used to demonstrate differences of tinnitus distress under different clinical conditions (e.g., ENT clinic vs psychosomatic clinic and in- vs out-patient care). The TQ can be employed for comparative studies in different tinnitus-related institutions and for the evaluation of the relative effects of different treatment approaches.

Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

PubMed

Creticos, Peter Socrates; Pfaar, Oliver

2018-06-01

Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.

Dangers of "confirmatory" cancer trials that fail to actually test the original hypothesis.

PubMed

Markman, Maurie

2014-04-01

The concept of "confirmatory" studies is a standard and important component of the overall clinical trials strategy in oncology. However, it is critical that such studies are similar enough in basic design and how they are conducted that they actually have the realistic potential to confirm, or refute, objectively the findings of the original study. In this commentary, two examples of clinical studies in the gynecologic oncology arena suggested by some to serve as "confirmatory" trials for the original reports demonstrate both the dangers and potential inappropriateness of such conclusions.

Endovascular therapy for acute ischemic stroke.

PubMed

Broderick, Joseph P

2009-03-01

To review advances in endovascular therapy for acute ischemic stroke. Data from primate studies, randomized studies of intravenous recombinant tissue-type plasminogen activator, and nonrandomized and randomized studies of endovascular therapy were reviewed. Clinical trial data demonstrate the superiority of endovascular treatment with thrombolytic medication or mechanical methods to reopen arteries compared with control patients from the PROACT II Trial treated with heparin alone. However, these same clinical trials, as well as preclinical primate models, indicate that recanalization, whether by endovascular approaches or standard-dose recombinant tissue-type plasminogen activator, is unlikely to improve clinical outcome after a certain time point. Although the threshold beyond which reperfusion has no or little benefit has yet to be conclusively defined, accumulated data to this point indicate an overall threshold of approximately 6 to 7 hours. In addition, although the risk of symptomatic intracerebral hemorrhage is similar in trials of intravenous lytics and endovascular approaches, endovascular approaches have distinctive risk profiles that can impact outcome. The treatment of acute ischemic stroke is evolving with new tools to reopen arteries and salvage the ischemic brain. Ongoing randomized trials of these new approaches are prerequisite next steps to demonstrate whether reperfusion translates into clinical effectiveness. Physiologic time to reperfusion will remain critical no matter which tools prove most effective and safest.

Neuronal ceroid lipofuscinosis in Border Collie dogs in Japan: clinical and molecular epidemiological study (2000-2011).

PubMed

Mizukami, Keijiro; Kawamichi, Takuji; Koie, Hiroshi; Tamura, Shinji; Matsunaga, Satoru; Imamoto, Shigeki; Saito, Miyoko; Hasegawa, Daisuke; Matsuki, Naoaki; Tamahara, Satoshi; Sato, Shigenobu; Yabuki, Akira; Chang, Hye-Sook; Yamato, Osamu

2012-01-01

Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan.

Neuronal Ceroid Lipofuscinosis in Border Collie Dogs in Japan: Clinical and Molecular Epidemiological Study (2000–2011)

PubMed Central

Mizukami, Keijiro; Kawamichi, Takuji; Koie, Hiroshi; Tamura, Shinji; Matsunaga, Satoru; Imamoto, Shigeki; Saito, Miyoko; Hasegawa, Daisuke; Matsuki, Naoaki; Tamahara, Satoshi; Sato, Shigenobu; Yabuki, Akira; Chang, Hye-Sook; Yamato, Osamu

2012-01-01

Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan. PMID:22919312

A prospective study evaluating cochlear implant management skills: development and validation of the Cochlear Implant Management Skills survey.

PubMed

Bennett, R J; Jayakody, D M P; Eikelboom, R H; Taljaard, D S; Atlas, M D

2016-02-01

To investigate the ability of cochlear implant (CI) recipients to physically handle and care for their hearing implant device(s) and to identify factors that may influence skills. To assess device management skills, a clinical survey was developed and validated on a clinical cohort of CI recipients. Survey development and validation. A prospective convenience cohort design study. Specialist hearing implant clinic. Forty-nine post-lingually deafened, adult CI recipients, at least 12 months postoperative. Survey test-retest reliability, interobserver reliability and responsiveness. Correlations between management skills and participant demographic, audiometric, clinical outcomes and device factors. The Cochlear Implant Management Skills survey was developed, demonstrating high test-retest reliability (0.878), interobserver reliability (0.972) and responsiveness to intervention (skills training) [t(20) = -3.913, P = 0.001]. Cochlear Implant Management Skills survey scores range from 54.69% to 100% (mean: 83.45%, sd: 12.47). No associations were found between handling skills and participant factors. This is the first study to demonstrate a range in cochlear implant device handling skills in CI recipients and offers clinicians and researchers a tool to systematically and objectively identify shortcomings in CI recipients' device handling skills. © 2015 John Wiley & Sons Ltd.

Marketing and clinical trials: a case study

PubMed Central

Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-01-01

Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

[Effectiveness of cognitive-behavioral therapy in childhood anxiety disorders in a university psychiatric outpatient clinic].

PubMed

Goletz, Hildegard; Yang, Young-Im; Suhr-Dachs, Lydia; Walter, Daniel; Döpfner, Manfred

2013-07-01

Only few studies have examined whether the efficacy of cognitive-behavioral therapy for childhood anxiety disorders as demonstrated in randomized controlled trials (RCTs) generalizes to clinical practice. This study examines the effectiveness of cognitive-behavioral therapy for juvenile anxiety disorders under routine care conditions in a university-based psychiatric outpatient clinic. 92 children and adolescents with parent-ratings regarding anxiety and comorbid symptoms and 61 children and adolescents with self-ratings regarding anxiety and comorbid symptoms were treated with cognitive-behavioral interventions. Pre/post mean comparisons, effect sizes, and the clinical significance of changes in symptoms were examined. The effect size for reduction of anxiety symptoms was .81 for children whose parents had completed the rating scale and .79 for children who had filled in a self-rating scale. Effect sizes for reduction of comorbid symptoms varied between .37 and .84 for parent ratings and between .21 and .62 for self-ratings. The percentage of children and adolescents who achieved clinically significant improvements in anxiety symptoms was 55.1 % according to the parent ratings and 65.7 % according to the children's self-ratings. More than 50 % of parents and children reported clinically significant improvements in comorbid symptoms. Significant reductions in both anxiety and comorbid symptoms were demonstrated over the course of cognitive-behavioral therapy of juvenile anxiety disorders in a university psychiatric outpatient clinic. The effect sizes for anxiety symptoms were found to be comparable to the effect sizes reported in RCTs. Similarly, clinically significant improvements were as frequent as the rates of remission of anxiety symptoms reported in RCTs.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.

PubMed

Rao, Donald D; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-08-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma

PubMed Central

Rao, Donald D.; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-01-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85–92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing. PMID:27166877

Skin Sensitizing Potency of Halogenated Platinum Salts.

EPA Science Inventory

The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published tha...

Challenges of assessing critical thinking and clinical judgment in nurse practitioner students.

PubMed

Gorton, Karen L; Hayes, Janice

2014-03-01

The purpose of this study was to determine whether there was a relationship between critical thinking skills and clinical judgment in nurse practitioner students. The study used a convenience, nonprobability sampling technique, engaging participants from across the United States. Correlational analysis demonstrated no statistically significant relationship between critical thinking skills and examination-style questions, critical thinking skills and scores on the evaluation and reevaluation of consequences subscale of the Clinical Decision Making in Nursing Scale, and critical thinking skills and the preceptor evaluation tool. The study found no statistically significant relationships between critical thinking skills and clinical judgment. Educators and practitioners could consider further research in these areas to gain insight into how critical thinking is and could be measured, to gain insight into the clinical decision making skills of nurse practitioner students, and to gain insight into the development and measurement of critical thinking skills in advanced practice educational programs. Copyright 2014, SLACK Incorporated.

Photodynamic dosimetry in the treatment of periodontitis

NASA Astrophysics Data System (ADS)

Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

2009-06-01

Photodynamic therapy has been demonstrated to effectively kill human periopathogens in vitro. However, the translation of in vitro work to in vivo clinical efficacy has been difficult due to the number of variables present in any given patient. Parameters such as photosensitizer concentration, duration of light therapy and amount of light delivered to the target tissue all play a role in the dose response of PDT in vivo. In this 121 patient study we kept all parameters the same except for light dose which was delivered at either 150 mW or 220 mW. This clearly demonstrated the clinical benefits of a higher light dose in the treatment of periodontitis.

Evaluating an integrated approach to clinical quality improvement: clinical guidelines, quality measurement, and supportive system design.

PubMed

Cretin, S; Farley, D O; Dolter, K J; Nicholas, W

2001-08-01

Implementing clinical practice guidelines to change patient outcomes presents a challenge. Studies of single interventions focused on changing provider behavior demonstrate modest effects, suggesting that effective guideline implementation requires a multifaceted approach. Traditional biomedical research designs are not well suited to evaluating systems interventions. RAND and the Army Medical Department collaborated to develop and evaluate a system for implementing guidelines and documenting their effects on patient care. The evaluation design blended quality improvement, case study, and epidemiologic methods. A formative evaluation of implementation process and an outcome evaluation of patient impact were combined. Guidelines were implemented in 3 successive demonstrations targeting low back pain, asthma, and diabetes. This paper reports on the first wave of 4 facilities implementing a low back pain guideline. Organizational climate and culture, motivation, leadership commitment, and resources were assessed. Selected indicators of processes and outcomes of care were compared before, during, and after guideline implementation at the demonstration facilities and at comparison facilities. Logistic regression analysis was used to test for guideline effects on patient care. Process evaluation documented varied approaches to quality improvement across sites. Outcome evaluation revealed a significant downward trend in the percentage of acute low back pain patients referred to physical therapy or chiropractic care (10.7% to 7.2%) at demonstration sites and no such trend at control sites. Preliminary results suggest the power of this design to stimulate improvements in guideline implementation while retaining the power to evaluate rigorously effects on patient care.

Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature

PubMed Central

Masumori, Naoya

2013-01-01

Imidafenacin is an antimuscarinic agent with high affinity for the M3 and M1 muscarinic receptor subtypes and low affinity for the M2 subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese. PMID:23390360

Rewards of bridging the divide between measurement and clinical theory: demonstration of a bifactor model for the Brief Symptom Inventory.

PubMed

Thomas, Michael L

2012-03-01

There is growing evidence that psychiatric disorders maintain hierarchical associations where general and domain-specific factors play prominent roles (see D. Watson, 2005). Standard, unidimensional measurement models can fail to capture the meaningful nuances of such complex latent variable structures. The present study examined the ability of the multidimensional item response theory bifactor model (see R. D. Gibbons & D. R. Hedeker, 1992) to improve construct validity by serving as a bridge between measurement and clinical theories. Archival data consisting of 688 outpatients' psychiatric diagnoses and item-level responses to the Brief Symptom Inventory (BSI; L. R. Derogatis, 1993) were extracted from files at a university mental health clinic. The bifactor model demonstrated superior fit for the internal structure of the BSI and improved overall diagnostic accuracy in the sample (73%) compared with unidimensional (61%) and oblique simple structure (65%) models. Consistent with clinical theory, multiple sources of item variance were drawn from individual test items. Test developers and clinical researchers are encouraged to consider model-based measurement in the assessment of psychiatric distress.

The Adopted Adolescent. Selected Papers Number 55.

ERIC Educational Resources Information Center

Banning, Anne

This review of studies on clinical and nonclinical populations explores outcomes of adoption and developmental issues for adolescents, and in particular, developmental problems for adopted adolescents. Studies on nonclinical populations demonstrate that adoption is a highly successful form of substitute care. Prospective longitudinal studies show…

Isoforms of Vitamin E Differentially Regulate PKC α and Inflammation: A Review

PubMed Central

Cook-Mills, Joan M.

2013-01-01

Vitamin E regulation of disease has been extensively studied but most studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E with regards to animal and clinical studies. These seemingly disparate results are consistent with our recent studies demonstrating that purified natural forms of vitamin E have opposing regulatory functions during inflammation. In this review, we discuss that α-tocopherol inhibits whereas γ-tocopherol elevates allergic inflammation, airway hyperresponsiveness, leukocyte transendothelial migration, and endothelial cell adhesion molecule signaling through protein kinase Cα. Moreover, we have demonstrated that α-tocopherol is an antagonist and γ-tocopherol is an agonist of PKCα through direct binding to a regulatory domain of PKCα. In summary, we have determined mechanisms for opposing regulatory functions of α-tocopherol and γ-tocopherol on inflammation. Information from our studies will have significant impact on the design of clinical studies and on vitamin E consumption. PMID:23977443

The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders.

PubMed

Obeso, Ignacio; Cerasa, Antonio; Quattrone, Aldo

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe and painless method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment, and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols. The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson's disease (PD) with levodopa-induced dyskinesias (LIDs), essential tremor (ET) and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to "normalize" pathologically decreased or increased levels of cortical activity have given moderate progress in patient's quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.

[Development of an orphan drug to treat a genetic disease: the paradigm of agalsidase beta].

PubMed

Germain, Dominique P; Benistan, Karelle

2007-03-01

Preclinical and phase I/II studies gave the proof of principle of enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A through the demonstration of the clearance of the accumulated subtrate from plasma and tissues. In a multicenter, randomized, placebo-controlled, double-blind phase Ill study, the biological efficacy of recombinant alpha-galactosidose A (agalsidase beta 1 mg/kg/714 days) was demonstrated on the basis of complete clearance of accumulated globotriaosylceramide from the endothelia of the kidney, heart and skin. The phase III extension study data gives additional results: kidney function appears to be stabilized after 54 to 60 months of treatment with agolsidase beta in most patients. Intent-to-treat analysis of a double-blind, randomized, placebo-controlled, phase IV study, showed that, adjusted for on imbalance in baseline proteinuria, agalsidase beta significantly reduces by 53% the risk of a first clinical event (renal, cardiac and cerebrovascular), compared with placebo. Clinical benefits of ERT depend on patients' clinical status at baseline, therefore prompting for onset of ERT before irreversible damage occur and underlying the need to stratify patients' populations to better understand the outcome of ERT.

Consanguinity and family clustering of male factor infertility in Lebanon.

PubMed

Inhorn, Marcia C; Kobeissi, Loulou; Nassar, Zaher; Lakkis, Da'ad; Fakih, Michael H

2009-04-01

To investigate the influence of consanguineous marriage on male factor infertility in Lebanon, where rates of consanguineous marriage remain high (29.6% among Muslims, 16.5% among Christians). Clinic-based, case-control study, using reproductive history, risk factor interview, and laboratory-based semen analysis. Two IVF clinics in Beirut, Lebanon, during an 8-month period (January-August 2003). One hundred twenty infertile male patients and 100 fertile male controls, distinguished by semen analysis and reproductive history. None. Standard clinical semen analysis. The rates of consanguineous marriage were relatively high among the study sample. Patients (46%) were more likely than controls (37%) to report first-degree (parental) and second-degree (grandparental) consanguinity. The study demonstrated a clear pattern of family clustering of male factor infertility, with patients significantly more likely than controls to report infertility among close male relatives (odds ratio = 2.58). Men with azoospermia and severe oligospermia showed high rates of both consanguinity (50%) and family clustering (41%). Consanguineous marriage is a socially supported institution throughout the Muslim world, yet its relationship to infertility is poorly understood. This study demonstrated a significant association between consanguinity and family clustering of male factor infertility cases, suggesting a strong genetic component.

A comparative clinical study evaluating stain removal efficacy of a new sensitivity whitening dentifrice compared to commercially available whitening dentifrices.

PubMed

Hughes, Nathan; Maggio, Brenda; Sufi, Farzana; Mason, Stephen; Kleber, Carl J

2009-01-01

To assess the extrinsic stain removal efficacy of a new sensitivity dentifrice containing sodium tripolyphosphate (STP) to marketed whitening toothpastes after six weeks of product use. This was a single-center, double-blind, stratified, six-week clinical study comparing the reduction in stain area and intensity of Sensodyne Extra Whitening to Crest Maximum Strength Sensitivity Protection Whitening plus Scope and Colgate Tartar Control Plus Whitening Mint dentifrice, as measured by MacPherson's Modification of the Lobene Stain Index (MMLSI) in a forced stain model. Two-hundred and ninety-five subjects completed the study. Tooth stain MMSLI scores showed significant differences between Sensodyne and Crest dentifrices in favor of Sensodyne for all surface sites (p = 0.014), and individually for facial (p = 0.023), lingual (p = 0.027), and interproximal (p = 0.014) surfaces. No significant statistical differences between Sensodyne and Colgate dentifrices were observed for any of the surfaces. Results from this stain removal clinical study demonstrate significant extrinsic stain removal efficacy for all dentifrices relative to baseline. Significant differences between the two marketed sensitivity whitening dentifrices were demonstrated in favor of the new Sensodyne Sensitivity Whitening dentifrice.

Synergistic suppression of autoimmune arthritis through concurrent treatment with tolerogenic DC and MSC

PubMed Central

Li, Rong; Zhang, Yujuan; Zheng, Xiufen; Peng, Shanshan; Yuan, Keng; Zhang, Xusheng; Min, Weiping

2017-01-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation. The combination of MSC synergized the tolerogenic capacity of Tol-DC in inhibition of T cell responses. In murine collagen-induced arthritis (CIA) model, we demonstrated that progression of arthritis was inhibited with administration of RelB gene-silenced Tol-DC or MSC. This therapeutic effect was remarkably enhanced with concurrent treatment of combination Tol-DC and MSC as demonstrated by improved clinical symptoms, decreased clinical scores and attenuated joint damage. These therapeutic effects were associated with suppression of CII-specific T cell responses, polarization of Th and inhibition of proinflammatory cytokines, and reduced cartilage degeneration. This study for the first time demonstrates a new approach to treat autoimmune inflammatory joint disease with concurrent treatment of RelB gene-silenced Tol-DC and MSC. PMID:28230210

A Multicenter, Randomized Clinical Trial of a Cognitive Remediation Program for Childhood Survivors of a Pediatric Malignancy

ERIC Educational Resources Information Center

Butler, Robert W.; Copeland, Donna R.; Fairclough, Diane L.; Mulhern, Raymond K.; Katz, Ernest R.; Kazak, Anne E.; Noll, Robert B.; Patel, Sunita K.; Sahler, Olle Jane Z.

2008-01-01

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35%…

Granulomatous lobular mastitis.

PubMed

Miliauskas, J R; Pieterse, A S; Williams, R S

1995-02-01

Two cases of benign lobular granulomatous mastitis, both clinically felt to be carcinoma, are reported. One patient was cured by local excision of the mass while the other was cured by oral prednisolone, demonstrating the variable ways to treat this entity. The clinical and histological features were similar to those noted in previous reports. Immunological studies revealed predominantly stromal T lymphocytes and only duct intra-epithelial T lymphocytes.

Legionella pneumophila pneumonia associated with acute respiratory distress syndrome successfully treated with imipenem.

PubMed

Mofredj, A; Baraka, D

1997-01-01

Although utility of beta-lactams in the treatment of legionnaire's disease could not be demonstrated, clinical cures of human legionellosis with imipenem have been reported. We report the case of a 45-year-old man who presented clinical and radiological features of 'typical' bacterial pneumonia. He was successfully treated with imipenem. Serologic studies showed seroconversion for Legionella pneumophila.

GEMMs shine a light on resistance to androgen deprivation therapy for prostate cancer

PubMed Central

Karantanos, Theodoros; Thompson, Timothy C.

2013-01-01

Summary Androgen deprivation therapy (ADT) for advanced prostate cancer inexorably leads to resistance, and clinically useful biomarkers are lacking. The value of genetically engineered mice for co-clinical studies is clearly demonstrated in a recent publication that reveals XAF1, XIAP, and SRD5A1 as novel predictive biomarkers and therapeutic targets for ADT resistance. PMID:23845440

Electronic patient-reported data capture as a foundation of rapid learning cancer care.

PubMed

Abernethy, Amy P; Ahmad, Asif; Zafar, S Yousuf; Wheeler, Jane L; Reese, Jennifer Barsky; Lyerly, H Kim

2010-06-01

"Rapid learning healthcare" presents a new infrastructure to support comparative effectiveness research. By leveraging heterogeneous datasets (eg, clinical, administrative, genomic, registry, and research), health information technology, and sophisticated iterative analyses, rapid learning healthcare provides a real-time framework in which clinical studies can evaluate the relative impact of therapeutic approaches on a diverse array of measures. This article describes an effort, at 1 academic medical center, to demonstrate what rapid learning healthcare might look like in operation. The article describes the process of developing and testing the components of this new model of integrated clinical/research function, with the pilot site being an academic oncology clinic and with electronic patient-reported outcomes (ePROs) being the foundational dataset. Steps included: feasibility study of the ePRO system; validation study of ePRO collection across 3 cancers; linking ePRO and other datasets; implementation; stakeholder alignment and buy in, and; demonstration through use cases. Two use cases are presented; participants were metastatic breast cancer (n = 65) and gastrointestinal cancer (n = 113) patients at 2 academic medical centers. (1) Patient-reported symptom data were collected with tablet computers; patients with breast and gastrointestinal cancer indicated high levels of sexual distress, which prompted multidisciplinary response, design of an intervention, and successful application for funding to study the intervention's impact. (2) The system evaluated the longitudinal impact of a psychosocial care program provided to patients with breast cancer. Participants used tablet computers to complete PRO surveys; data indicated significant impact on psychosocial outcomes, notably distress and despair, despite advanced disease. Results return to the clinic, allowing iterative update and evaluation. An ePRO-based rapid learning cancer clinic is feasible, providing real-time research-quality data to support comparative effectiveness research.

Retail clinic visits: are resident paneled patients more likely to make multiple visits?

PubMed

Angstman, Kurt B; Garrison, Gregory M; Rohrer, James E; Dupras, Denise M; O'Grady, Jason S

2012-04-01

Primary care resident physicians generally have significantly fewer hours in outpatient clinic per week than staff physicians. With the transient nature of a primary care resident's practice, do the patients of residents utilize the health care system differently? Our hypothesis was that patients paneled with a resident physician would be more likely to utilize retail clinics with repeat week day visits than those patients paneled with a staff primary care physician. A retrospective review of 16,318 retail clinic visits made in 2009 was studied. Since the patient making a repeat retail clinic visit had experience with the services available, they were making an informed decision on the type of care desired (their primary care provider or not). The patients who made repeat retail clinical visits were divided into groups by age, those younger than 18 years and those 18 years and older. Via multiple logistic regression, patients under 18 years demonstrated that a patient paneled with a resident physician was no more likely to have repeat visits to the retail clinic than a staff physician's patient, when controlling for all other variables. Similarly, those ages 18 years and older also demonstrated no differences in resident or staff paneled patients in utilization of retail clinics during the work day. Multivariate analysis found no difference in the utilization of repeat retail clinic visits during 2009 with resident paneled patients as compared to staff physician patients.

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

PubMed

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

2011-04-01

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

Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects.

PubMed

Hahn, Margaret K; Remington, Gary; Bois, Daniel; Cohn, Tony

2010-12-01

Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.

The efficacy of routine hyperventilation for seizure activation during prolonged video-electroencephalography monitoring.

PubMed

Abubakr, Abuhuziefa; Ifeayni, Iwuchukwu; Wambacq, Ilse

2010-12-01

Hyperventilation (HV) is considered to be one of the activation procedures that provokes epileptic potentials and clinical seizures. However, the true clinical yield of HV is not well established. We retrospectively reviewed the records of all patients admitted to JFK Hospital, Edison, New Jersey, between October 2001 and December 2004 for long-term video-electroencephalography (EEG). A total of 475 patients (193 males; 282 females; age range 5-89 years) were included in the study. All patients underwent routine 3-minute HV as part of the evaluation of their clinical episodes. During the initial assessment, 165 patients did not experience a seizure event, 92 had non-epileptic events, 16 experienced psychogenic non-epileptic seizures (PNES) and six had a clinical event. During HV, of the 43 patients who had primary generalized epilepsy, nine had an abnormal EEG and two experienced seizures; however, out of the 159 patients who had partial seizures, only one patient demonstrated an abnormal EEG. Our study demonstrates that routine HV generally has a very low yield in our Epilepsy-Monitoring Unit. This finding also lends support to the idea that partial seizures are relatively resistant to HV activation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Treatment of the alcoholic organic brain syndrome: double-blind, placebo-controlled clinical, psychometric and electroencephalographic mapping studies with modafinil.

PubMed

Saletu, B; Saletu, M; Grünberger, J; Frey, R; Anderer, P; Mader, R

1993-01-01

In a double-blind study 40 abstinent hospitalized male patients with an alcoholic organic brain syndrome (OBS; ICD 9: 291.2) were treated for 6 weeks with either placebo or 200 mg modafinil b.i.d. Modafinil (CRL 40476) is a vigilance-promoting, putative central alpha 1-adrenergic agonist with a pharmacological profile quite different from that of amphetamine. Clinical investigations demonstrated that the spontaneous remission of the alcoholic OBS was augmented and accelerated by modafinil, which was found significant as compared with placebo by confirmatory statistics in the target variable, the Clinical Global Impression scale. The drug was well tolerated. Psychometric tests revealed significant improvement of the noopsyche after modafinil as compared with placebo, while the thymopsyche and psychophysiological measurements were not affected. Electroencephalographic mapping showed significant differences between the central effects of modafinil and placebo indicating an improvement of vigilance under modafinil. Typical vigilance-promoting properties were seen after acute drug administration, were less evident before the morning dose after chronic treatment but re-occurred after super-imposed daily drug administration. Thus, our clinical, psychometric and neurophysiological investigations in alcoholic OBS patients demonstrated a therapeutic effect of modafinil in the early phase of abstinence.

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.

PubMed

Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A

2017-12-01

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

Pancreatic cancer early detection: Expanding higher-risk group with clinical and metabolomics parameters

PubMed Central

Urayama, Shiro

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth and fifth leading cause of cancer death for each gender in developed countries. With lack of effective treatment and screening scheme available for the general population, the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung, breast, prostate and colorectal cancers. Endoscopic ultrasound, with its highest level of detection capacity of smaller pancreatic lesions, is the commonly employed and preferred clinical imaging-based PDAC detection method. Various molecular biomarkers have been investigated for characterization of the disease, but none are shown to be useful or validated for clinical utilization for early detection. As seen from studies of a small subset of familial or genetically high-risk PDAC groups, the higher yield and utility of imaging-based screening methods are demonstrated for these groups. Multiple recent studies on the unique cancer metabolism including PDAC, demonstrate the potential for utility of the metabolites as the discriminant markers for this disease. In order to generate an early PDAC detection screening strategy available for a wider population, we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters. PMID:25684935

CCR 20th Anniversary commentary: in search of cetuximab's first indication-combination therapy with irinotecan in colorectal cancer.

PubMed

Hicklin, Daniel J

2015-04-01

The research article by Prewett and colleagues, published in the May 1, 2002, issue of Clinical Cancer Research, provided important translational data that extended earlier preclinical and clinical studies with the human-murine chimeric anti-EGFR monoclonal antibody C225. Subsequent clinical trials with C225 led to the demonstration of its efficacy in combination with irinotecan and regulatory approval for the treatment of metastatic colorectal cancer. ©2015 American Association for Cancer Research.

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

PubMed

Ortonne, Jean-Paul; Gupta, Girish; Ortonne, Nicolas; Duteil, Luc; Queille, Catherine; Mallefet, Pascal

2010-07-01

During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub-clinical AK lesions.

Advances in the management of multiple sclerosis spasticity: recent clinical trials.

PubMed

Fernández, Oscar

2014-01-01

Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study. THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use. In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo. Moreover, after 50 weeks' treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change. Key Messages: In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray. In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms. THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term. A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use. © 2014 S. Karger AG, Basel.

Characterizing the Utility and Limitations of Repurposing an Open-Field Optical Imaging Device for Fluorescence-Guided Surgery in Head and Neck Cancer Patients.

PubMed

Moore, Lindsay S; Rosenthal, Eben L; Chung, Thomas K; de Boer, Esther; Patel, Neel; Prince, Andrew C; Korb, Melissa L; Walsh, Erika M; Young, E Scott; Stevens, Todd M; Withrow, Kirk P; Morlandt, Anthony B; Richman, Joshua S; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-02-01

The purpose of this study was to assess the potential of U.S. Food and Drug Administration-cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery. Consenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed preoperatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio characterized fluorescence contrast. In the preoperative clinic, the open-field device demonstrated potential to guide preoperative mapping of tumor borders, optimize the day of surgery, and identify occult lesions. Intraoperatively, the device demonstrated robust potential to guide surgical resections, as all peak tumor-to-background ratios were greater than 2 (range, 2.2-14.1). Postresection wound bed fluorescence was significantly less than preresection tumor fluorescence (P < 0.001). The repurposed device also successfully identified positive margins. The open-field imaging device was successfully repurposed to distinguish cancer from normal tissue in the preoperative clinic and throughout surgical resection. This study illuminated the potential for existing open-field optical imaging devices with overlapping excitation and emission spectra to be used for fluorescence-guided surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Factors influencing radiation therapy student clinical placement satisfaction

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

Bridge, Pete; Carmichael, Mary-Ann

Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanismsmore » during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning.« less

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

PubMed

Cha, Eugene K; Eastham, James A

2015-05-01

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

PubMed

Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J

2017-12-12

To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.

Clinical audit, a valuable tool to improve quality of care: General methodology and applications in nephrology.

PubMed

Esposito, Pasquale; Dal Canton, Antonio

2014-11-06

Evaluation and improvement of quality of care provided to the patients are of crucial importance in the daily clinical practice and in the health policy planning and financing. Different tools have been developed, including incident analysis, health technology assessment and clinical audit. The clinical audit consist of measuring a clinical outcome or a process, against well-defined standards set on the principles of evidence-based medicine in order to identify the changes needed to improve the quality of care. In particular, patients suffering from chronic renal diseases, present many problems that have been set as topics for clinical audit projects, such as hypertension, anaemia and mineral metabolism management. Although the results of these studies have been encouraging, demonstrating the effectiveness of audit, overall the present evidence is not clearly in favour of clinical audit. These findings call attention to the need to further studies to validate this methodology in different operating scenarios. This review examines the principle of clinical audit, focusing on experiences performed in nephrology settings.

A study on job satisfaction among clinical and non-clinical hospital staff in a teaching hospital in Lagos, Nigeria.

PubMed

Coker, O O; Coker, A O; Onuoha, B

2011-12-01

Previous studies had demonstrated that continuous and effective productivity of hospital staff are linked to job satisfaction and only those who are satisfied with their job can be maximally effective and productive. This cross-sectional descriptive survey was designed to determine the levels of job satisfaction among various groups of health care professionals working in a teaching hospital in Lagos, Nigeria. Two hundred clinical and non-clinical hospital staff were invited to take part in the study. They completed a sociodemographic questionnaire and the Job Descriptive Index (JDI). The results indicated that majority clinical and non-clinical staff were satisfied with their jobs as regards the parameters of the JDI compared with those not satisfied with their jobs. The government and health policy makers should continue to pay attention to boost job morale and satisfaction of medical health workers to continue to make them to be satisfied with their job.

Successful correction of D-lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate.

PubMed

Angell, J W; Jones, G L; Voigt, K; Grove-White, D H

2013-08-31

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically, each lamb had a metabolic acidosis characterised by D-lactic acidosis and exhibited clinical signs including: not hyperthermic, no evidence of dehydration, demonstrating an ataxic gait tending to recumbency (DLS) and possibly somnolence. These lambs received 50 mmol of sodium bicarbonate as an 8.4 per cent solution given orally, together with parenteral long-acting amoxicillin. All 18 cases made a full clinical recovery. This study demonstrates a novel effective treatment for a disease that is usually fatal, and also demonstrates a strong correlation between venous plasma bicarbonate concentrations and venous plasma D-lactate concentrations (R(2)=0.49).

Clinical Simulation: A Protocol for Evaluation of Mobile Technology.

PubMed

Mather, Carey; Jensen, Sanne; Cummings, Elizabeth

2017-01-01

For mobile technology to be accepted at point of care in healthcare environments there is a need to demonstrate benefits whilst ameliorating the risks and challenges. To provide a standardised approach to evaluation of mobile technology a simulation protocol was developed to provide guidance for its use in healthcare environments. Simulated conditions provide the opportunity to assess intended and unintended consequences and identify potential workarounds when using technology. The protocol can also be used to demonstrate the importance of the development of digital professionalism by end-users prior to students entering the clinical practice setting. The mobile technology protocol was adapted from a health information systems protocol developed and used at the ITX Lab, Denmark for use in other simulation laboratories. Use case scenarios were developed to enable evaluation of mobile technology for mobile learning of nurses, nurse supervisors, students and patients. The scenarios can be used in a range of simulated environments including hospital bedside, outpatient clinic or community settings. A case study exemplar of a nurse and patient is included to demonstrate how the mobile technology protocol can be applied.

A review of smoking cessation services in women attending colposcopy clinics in Scotland.

PubMed

Rumbles, A U; Nicholson, S C; Court, S J

2012-02-01

The most common reason for women being referred to colposcopy clinics is an abnormal smear suggesting pre-cancerous change within the cervix. It has been demonstrated that in women with low-grade lesions, smoking cessation led to a reduction in size of the cervical lesion over a 6-month period. Smoking is also recognised as an independent risk factor for treatment failure of cervical intraepithelial neoplasia. As 'stop smoking' services have become an integral part of the colposcopy clinic at St John's Hospital, Livingston, a national survey was undertaken. The aim of the survey was to establish what smoking cessation information, advice and support is available in colposcopy clinics throughout Scotland, and if staff had attended standardised training on raising the issue of smoking. The study demonstrated that 52% of colposcopy clinics in Scotland always establish smoking status but only 37% of clinics discuss the benefits of smoking cessation in relation to abnormal cervical smears. There was inaccurate and inconsistent written and verbal advice given on the benefits of cessation and whether women should cut down or stop smoking completely. The majority of staff had not attended standardised training on how to raise the issue of smoking and very few clinics have established referral pathways for smoking cessation support.

Quantitative comparison of OSEM and penalized likelihood image reconstruction using relative difference penalties for clinical PET

NASA Astrophysics Data System (ADS)

Ahn, Sangtae; Ross, Steven G.; Asma, Evren; Miao, Jun; Jin, Xiao; Cheng, Lishui; Wollenweber, Scott D.; Manjeshwar, Ravindra M.

2015-08-01

Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post-filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs.

Task-oriented evaluation of electronic medical records systems: development and validation of a questionnaire for physicians

PubMed Central

2004-01-01

Background Evaluation is a challenging but necessary part of the development cycle of clinical information systems like the electronic medical records (EMR) system. It is believed that such evaluations should include multiple perspectives, be comparative and employ both qualitative and quantitative methods. Self-administered questionnaires are frequently used as a quantitative evaluation method in medical informatics, but very few validated questionnaires address clinical use of EMR systems. Methods We have developed a task-oriented questionnaire for evaluating EMR systems from the clinician's perspective. The key feature of the questionnaire is a list of 24 general clinical tasks. It is applicable to physicians of most specialties and covers essential parts of their information-oriented work. The task list appears in two separate sections, about EMR use and task performance using the EMR, respectively. By combining these sections, the evaluator may estimate the potential impact of the EMR system on health care delivery. The results may also be compared across time, site or vendor. This paper describes the development, performance and validation of the questionnaire. Its performance is shown in two demonstration studies (n = 219 and 80). Its content is validated in an interview study (n = 10), and its reliability is investigated in a test-retest study (n = 37) and a scaling study (n = 31). Results In the interviews, the physicians found the general clinical tasks in the questionnaire relevant and comprehensible. The tasks were interpreted concordant to their definitions. However, the physicians found questions about tasks not explicitly or only partially supported by the EMR systems difficult to answer. The two demonstration studies provided unambiguous results and low percentages of missing responses. In addition, criterion validity was demonstrated for a majority of task-oriented questions. Their test-retest reliability was generally high, and the non-standard scale was found symmetric and ordinal. Conclusion This questionnaire is relevant for clinical work and EMR systems, provides reliable and interpretable results, and may be used as part of any evaluation effort involving the clinician's perspective of an EMR system. PMID:15018620

Task-oriented evaluation of electronic medical records systems: development and validation of a questionnaire for physicians.

PubMed

Laerum, Hallvard; Faxvaag, Arild

2004-02-09

Evaluation is a challenging but necessary part of the development cycle of clinical information systems like the electronic medical records (EMR) system. It is believed that such evaluations should include multiple perspectives, be comparative and employ both qualitative and quantitative methods. Self-administered questionnaires are frequently used as a quantitative evaluation method in medical informatics, but very few validated questionnaires address clinical use of EMR systems. We have developed a task-oriented questionnaire for evaluating EMR systems from the clinician's perspective. The key feature of the questionnaire is a list of 24 general clinical tasks. It is applicable to physicians of most specialties and covers essential parts of their information-oriented work. The task list appears in two separate sections, about EMR use and task performance using the EMR, respectively. By combining these sections, the evaluator may estimate the potential impact of the EMR system on health care delivery. The results may also be compared across time, site or vendor. This paper describes the development, performance and validation of the questionnaire. Its performance is shown in two demonstration studies (n = 219 and 80). Its content is validated in an interview study (n = 10), and its reliability is investigated in a test-retest study (n = 37) and a scaling study (n = 31). In the interviews, the physicians found the general clinical tasks in the questionnaire relevant and comprehensible. The tasks were interpreted concordant to their definitions. However, the physicians found questions about tasks not explicitly or only partially supported by the EMR systems difficult to answer. The two demonstration studies provided unambiguous results and low percentages of missing responses. In addition, criterion validity was demonstrated for a majority of task-oriented questions. Their test-retest reliability was generally high, and the non-standard scale was found symmetric and ordinal. This questionnaire is relevant for clinical work and EMR systems, provides reliable and interpretable results, and may be used as part of any evaluation effort involving the clinician's perspective of an EMR system.

The ascent to competence conceptual framework: an outcome of a study of belongingness.

PubMed

Levett-Jones, Tracy; Lathlean, Judith

2009-10-01

This paper presents qualitative findings from a study that explored nursing students' experience of belongingness when undertaking clinical placements. The aim is to locate the professional and practical implications of the research within an Ascent to Competence conceptual framework. The need to belong exerts a powerful influence on cognitive processes, emotional patterns, behavioural responses, health and well-being and failure to satisfy this need can have devastating consequences. The literature suggests that diminished belongingness may impede students' motivation for learning and influence the degree to which they are willing to conform rather than adopt a questioning approach to clinical practice. A mixed methods, cross national, multi-site case study approach was adopted with third-year preregistration nursing students from three universities (two in Australia and one in England) participating; 362 in the quantitative phase and 18 in the qualitative phase. Qualitative findings demonstrated that, although the primary purpose of clinical education is to facilitate students' progress towards the attainment of competence, the realisation of this goal is impacted by a wide range of individual, interpersonal, contextual and organisational factors which can be conceptualised hierarchically. By this structuring it is possible to see how belongingness is a crucial precursor to students' learning and success. The framework demonstrates that students progress to a stage where attainment of competence is possible only after their previous needs for safety and security, belongingness, healthy self-concept and learning have been met. The future of the nursing profession depends upon the development of confident, competent professionals with a healthy self-concept and a commitment to patient-centred care and self-directed learning. This paper demonstrates that the realisation of this goal is strongly influenced by the extent to which students' clinical placement experiences promote and enhance their sense of belonging.

Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array.

PubMed

Yu, Zhicong; Leng, Shuai; Jorgensen, Steven M; Li, Zhoubo; Gutjahr, Ralf; Chen, Baiyu; Halaweish, Ahmed F; Kappler, Steffen; Yu, Lifeng; Ritman, Erik L; McCollough, Cynthia H

2016-02-21

This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x-ray photon flux.

Telerehabilitation using virtual reality task can improve balance in patients with stroke.

PubMed

Cikajlo, Imre; Rudolf, Marko; Goljar, Nika; Burger, Helena; Matjačić, Zlatko

2012-01-01

The objective of the telerehabilitation is a continuation of the rehabilitation process on patients' home. The study also compares the balance training in clinical environment with the telerehabilitation approach when the physiotherapists and physicians can follow the progress remotely. In this paper, the preliminary study of the pilot project with virtual reality (VR)-based tasks for dynamic standing frame supported balance training is presented. Six patients with stroke participated in the study. The patients performed the balance training 3 weeks, 2 weeks in the clinical settings and 1 week in the home environment, five times a week, and each time for up to 20 minutes. Objective effectiveness was demonstrated by parameters as track time, number of collisions and the clinical instruments Berg Balance Scale (BBS), Timed Up & Go (TUG), 10-m walk test and standing on the unaffected and affected extremity. The outcomes were compared to the balance training group without VR and telerehabilitation support. A 2-way ANOVA was used to explore the differences between the both stroke groups. In patients who were subject to VR supported balance training, the BBS demonstrated improvement for 15%, the TUG for 29%, the 10-m walk for 26%, stance time on the affected and unaffected extremity for 200 and 67%, respectively. The follow-up demonstrated that the patients preserved the gained functional improvement. The VR task performance time and number of collisions decreased to 45 and 68%, respectively. Besides, no statistical differences were found between the telerehabilitation approach with VR supported balance training and conventional balance training in clinical settings either regarding the overall mean level or regarding the mean improvement. The telerehabilitation approach in VR supported balance training improved balance in stroke patients and had similar effect on patients' postural functional improvement as conventional balance training in clinical settings. However, when balance training is continued on patient's home instead of the hospital, it would eventually decrease the number of outpatients' visits, reduce related costs and enable treatment of larger number of patients.

Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array

NASA Astrophysics Data System (ADS)

Yu, Zhicong; Leng, Shuai; Jorgensen, Steven M.; Li, Zhoubo; Gutjahr, Ralf; Chen, Baiyu; Halaweish, Ahmed F.; Kappler, Steffen; Yu, Lifeng; Ritman, Erik L.; McCollough, Cynthia H.

2016-02-01

This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x-ray photon flux.

An optical microfluidic platform for spatiotemporal biofilm treatment monitoring

NASA Astrophysics Data System (ADS)

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

2016-01-01

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

Clinical effects of non-ablative and ablative fractional lasers on various hair disorders: a case series of 17 patients.

PubMed

Cho, Suhyun; Choi, Min Ju; Zheng, Zhenlong; Goo, Boncheol; Kim, Do-Young; Cho, Sung Bin

2013-04-01

Both ablative and non-ablative fractional lasers have been applied to various uncommon hair disorders. The purpose of this study was to demonstrate the clinical effects of fractional laser therapy on the course of primary follicular and perifollicular pathologies and subsequent hair regrowth. A retrospective review of 17 patients with uncommon hair disorders - including ophiasis, autosomal recessive woolly hair/hypotrichosis, various secondary cicatricial alopecias, pubic hypotrichosis, frontal fibrosing alopecia, and perifolliculitis abscedens et suffodiens - was conducted. All patients had been treated with non-ablative and/or ablative fractional laser therapies. The mean clinical improvement score in these 17 patients was 2.2, while the mean patient satisfaction score was 2.5. Of the 17 subjects, 12 (70.6%) demonstrated a clinical response to non-ablative and/or ablative fractional laser treatments, including individuals with ophiasis, autosomal recessive woolly hair/hypotrichosis, secondary cicatricial alopecia (scleroderma and pressure-induced alopecia), frontal fibrosing alopecia, and perifolliculitis abscedens et suffodiens. Conversely, patients with long-standing ophiasis, surgical scar-induced secondary cicatricial alopecia, and pubic hypotrichosis did not respond to fractional laser therapy. Our findings demonstrate that the use of non-ablative and/or ablative fractional lasers promoted hair growth in certain cases of uncommon hair disorders without any remarkable side effects.

Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model.

PubMed

Ghannoum, M A; Long, L; Kim, H G; Cirino, A J; Miller, A R; Mallefet, P

2010-05-01

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.

Effectiveness outcomes in attention-deficit/hyperactivity disorder.

PubMed

Weiss, Margaret D; Gadow, Kenneth; Wasdell, Michael B

2006-01-01

Attention-deficit/hyperactivity disorder (ADHD) is common, chronic, and associated with significant functional impairment. It is highly treatable. It is therefore not only a major public health problem but also one that provides a unique opportunity in medicine to make a significant difference. This article will discuss the methodology needed to demonstrate empirically the impact of treatment on actual burden of illness in practice. Where efficacy studies demonstrate whether a treatment can work, effectiveness studies tell us whether they actually do work. Clinical trials exclude incompetent, non-compliant, and seriously comorbid patients, so that the information obtained from these trials tells us the most about the patients we see the least. Small differences in effect size in pivotal trials of efficacy have become a key variable for rating treatments as first line or second line, without consideration of effectiveness variables such as comorbidity, difficulty with appetite or sleep, patient preference, capacity for compliance, timing of functional impairment, and substance use. These effectiveness variables are less well studied, but critical to clinical decision making. In reality, fewer than 10% of our patients comply with and persist with treatment. To learn more about why patients are discontinuing treatment, we need to explore measures of effectiveness empirically. Effectiveness studies are also important to provide regulatory bodies with the data they need to balance the risk of treatment with the risk of failing to treat. Practical clinical trials and naturalistic follow-up studies will allow us to evaluate the true clinical impact of short-term efficacy trials.

Predictors of Clinical Response and Remission at One year among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab

PubMed Central

Allegretti, Jessica R.; Barnes, Edward L.; Stevens, Betsey; Storm, Margaret; Ananthakrishnan, Ashwin; Yajnik, Vijay; Korzenik, Joshua

2017-01-01

Background Vedolizumab (VDZ) has demonstrated long term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Aims Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment. Results Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11 – 6.57), the addition of an immunomodulator (OR 11.49, 3.16 – 41.75) and CRP <3 (4.92, 95% CI 1.99 – 12.15) were associated with increased odds of clinical response or remission at week 54. For UC patients hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 ( OR 0.22, 95%CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Conclusions Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD. PMID:28357697

Cardiovascular photodynamic therapy: state of the art

NASA Astrophysics Data System (ADS)

Woodburn, Kathryn W.; Rockson, Stanley G.

2000-05-01

Photodynamic therapy (PDT) has been used traditionally for oncologic and ophthalmic indications. In addition, the enormous potential for the use of PDT agents in cardiovascular diseases is currently being translated into reality. Preclinical studies with various photosensitizers have demonstrated reduction in atheromatous plaque and prevention of intimal hyperplasia. With recent advances in light-based vascular devices and laser diode technology, the clinical use of cardiovascular photodynamic therapy is even more likely. Two photosensitizers, 5-aminolevulinic acid (ALA) and AntrinR (motexafin lutetium) Injection, are under clinical evaluation with many other agents in preclinical testing. Here, preclinical studies are reviewed and the clinical viability of cardiovascular photodynamic therapy is discussed.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

PubMed

Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

2016-01-01

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

The use of rasagiline in Parkinson's disease.

PubMed

Schapira, A H V

2006-01-01

Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B developed for the symptomatic treatment of Parkinson's disease. The drug has shown efficacy in improving motor features in both early and advanced Parkinson's disease patients. The drug appears to be well tolerated and its once daily fixed dose formulation should make for excellent compliance. Rasagiline has also demonstrated important neuroprotective properties in both in vitro and in vivo laboratory studies. A provisional study of neuroprotection in a delayed start clinical trial of early PD patients has also suggested that this benefit may be translated to the clinic. Additional clinical trials are underway to confirm this.

Team-Based Care with Pharmacists to Improve Blood Pressure: a Review of Recent Literature.

PubMed

Kennelty, Korey A; Polgreen, Linnea A; Carter, Barry L

2018-01-18

We review studies published since 2014 that examined team-based care strategies and involved pharmacists to improve blood pressure (BP). We then discuss opportunities and challenges to sustainment of team-based care models in primary care clinics. Multiple studies presented in this review have demonstrated that team-based care including pharmacists can improve BP management. Studies highlighted the cost-effectiveness of a team-based pharmacy intervention for BP control in primary care clinics. Little information was found on factors influencing sustainability of team-based care interventions to improve BP control. Future work is needed to determine the best populations to target with team-based BP programs and how to implement team-based approaches utilizing pharmacists in diverse clinical settings. Future studies need to not only identify unmet clinical needs but also address reimbursement issues and stakeholder engagement that may impact sustainment of team-based care interventions.

[Infective endocarditis. Systematic review of twenty years of performances in the Sociedad Argentina de Medicina].

PubMed

Marcelo, Yorio; Milian Andrés, Escudero; Luis, Camera

2008-01-01

Infective endocarditis (IE) is still a disease with high morbidity and mortality. Its diagnosis and treatment are still a major challenge in clinical practice. There have been very few studies published about IE in Argentina. We reviewed all the studies about IE published in the Argentine Medicine Society from 1980 to 2003 and we analyzed demographic, clinical and bacteriological data. 27 studies with 628 patients were included. Mean age of patients was 50.7 years old. The most frequent clinical data were fever, murmur and elevated sedimentation rate. Stafilococcus spp was the most common causative organism, followed by streptococcus spp. The echocardiographic demonstration allowed the definitive diagnosis in 2/3 of the patients. The IE data of Argentina are not different from other data published in different countries and this study shows some clinical features of IE in Argentina.

Best way to revascularize patients with main stem and three vessel lesions: patients should undergo PCI!

PubMed

Schächinger, Volker; Herdeg, Christian; Scheller, Bruno

2010-09-01

The optimal revascularization strategy for multivessel disease is under controversial discussion for long time. Until now, technical innovations have been faster than performance of clinical trials, making results of randomized studies outdated at the time of appearance. Recently, the SYNTAX trial has been published, which compared drug elutings stents (DES) implantation with Coronary artery bypass graft (CABG) patients with multivessel or left main disease in a clinically stable population. Overall, CABG was superior with respect to the clinical endpoint of death, myocardial infarction, stroke, or revascularization. However, the difference is driven by the "weakest" end point, namely repeated revascularization, whereas combined "hard" events did not demonstrate a difference. More detailed analysis demonstrates that only patients with most complex coronary anatomy gain definite benefit from CABG. In addition, SYNTAX demonstrated that left main disease is no longer a domain of CABG, since DES implantation revealed comparable results, as long as there is no concomitant multivessel disease. Regardless the results of SYNTAX, one should not forget that SYNTAX represents only a minority of daily patients in a catheterization laboratory, excluding patients with one- or two-vessel disease and those with an acute coronary syndrome. Especially in the latter, percutaneous coronary intervention has demonstrated to improve prognosis.

[Potential therapeutic usefulness of cannabis and cannabinoids].

PubMed

Lorenzo Fernández, P

2000-01-01

Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view.

Molecular virology of feline calicivirus.

PubMed

Pesavento, Patricia A; Chang, Kyeong-Ok; Parker, John S L

2008-07-01

Caliciviridae are small, nonenveloped, positive-stranded RNA viruses. Much of our understanding of the molecular biology of the caliciviruses has come from the study of the naturally occurring animal caliciviruses. In particular, many studies have focused on the molecular virology of feline calicivirus (FCV), which reflects its importance as a natural pathogen of cats. FCVs demonstrate a remarkable capacity for high genetic, antigenic, and clinical diversity; "outbreak" vaccine resistant strains occur frequently. This article updates the reader on the current status of clinical behavior and pathogenesis of FCV.

Clinical evaluation of a new pressure ulcer risk assessment instrument, the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T).

PubMed

Coleman, Susanne; Smith, Isabelle L; McGinnis, Elizabeth; Keen, Justin; Muir, Delia; Wilson, Lyn; Stubbs, Nikki; Dealey, Carol; Brown, Sarah; Nelson, E Andrea; Nixon, Jane

2018-02-01

To test the psychometric properties and clinical usability of a new Pressure Ulcer Risk Assessment Instrument including inter-rater and test-retest reliability, convergent validity and data completeness. Methodological and practical limitations associated with traditional Pressure Ulcer Risk Assessment Instruments, prompted a programme to work to develop a new instrument, as part of the National Institute for Health Research funded, Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056). Observational field test. For this clinical evaluation 230 patients were purposefully sampled across four broad levels of pressure ulcer risk with representation from four secondary care and four community NHS Trusts in England. Blinded and simultaneous paired (ward/community nurse and expert nurse) PURPOSE-T assessments were undertaken. Follow-up retest was undertaken by the expert nurse. Field notes of PURPOSE-T use were collected. Data were collected October 2012-January 2013. The clinical evaluation demonstrated "very good" (kappa) inter-rater and test-retest agreement for PURPOSE-T assessment decision overall. The percentage agreement for "problem/no problem" was over 75% for the main risk factors. Convergent validity demonstrated moderate to high associations with other measures of similar constructs. The PURPOSE-T evaluation facilitated the initial validation and clinical usability of the instrument and demonstrated that PURPOSE-T is suitable of use in clinical practice. Further study is needed to evaluate the impact of using the instrument on care processes and outcomes. © 2017 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

How I do it: a practical database management system to assist clinical research teams with data collection, organization, and reporting.

PubMed

Lee, Howard; Chapiro, Julius; Schernthaner, Rüdiger; Duran, Rafael; Wang, Zhijun; Gorodetski, Boris; Geschwind, Jean-François; Lin, MingDe

2015-04-01

The objective of this study was to demonstrate that an intra-arterial liver therapy clinical research database system is a more workflow efficient and robust tool for clinical research than a spreadsheet storage system. The database system could be used to generate clinical research study populations easily with custom search and retrieval criteria. A questionnaire was designed and distributed to 21 board-certified radiologists to assess current data storage problems and clinician reception to a database management system. Based on the questionnaire findings, a customized database and user interface system were created to perform automatic calculations of clinical scores including staging systems such as the Child-Pugh and Barcelona Clinic Liver Cancer, and facilitates data input and output. Questionnaire participants were favorable to a database system. The interface retrieved study-relevant data accurately and effectively. The database effectively produced easy-to-read study-specific patient populations with custom-defined inclusion/exclusion criteria. The database management system is workflow efficient and robust in retrieving, storing, and analyzing data. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Individual variation in botulism.

PubMed Central

Smith, G. R.

1986-01-01

Mice were treated per os with one oral LD100 of toxic filtrate from a culture of Clostridium botulinum type C. The period between dosing and the first appearance of clinical signs varied greatly (2-31 h) from one animal to another. The duration of the pre-clinical and clinical phases together ranged from 5.5 to greater than 55 h. The duration of the clinical phase alone ranged from 1.25 to greater than 24 h, except for a minority of mice in which death occurred suddenly from apparent heart failure with no premonitory signs 4.75-31 h after dosing. Toxaemia was demonstrable in all mice that had just begun to show a clinical response 3.75-6.5 h after dosing, and in some that had not. Outside these time limits toxaemia was demonstrable only rarely, and beyond 12 h after dosing never. Therefore the many (approximately 50%) mice that began to show clinical signs more than 12 h after dosing had no demonstrable toxaemia throughout the entire clinical phase of the disease. The concentrations of toxin demonstrated in the blood ranged from less than 5 to greater than or equal to 20 (but less than 40) intravenous mouse-lethal doses/ml. PMID:3741778

42 CFR 51b.405 - What information is required in the application?

Code of Federal Regulations, 2010 CFR

2010-10-01

... appropriate allied health personnel) venereal disease education, training, and clinical skills improvement...) At the option of the applicant, special studies or demonstrations to evaluate or test venereal...

The clinical learning environment and supervision by staff nurses: developing the instrument.

PubMed

Saarikoski, Mikko; Leino-Kilpi, Helena

2002-03-01

The aims of this study were (1) to describe students' perceptions of the clinical learning environment and clinical supervision and (2) to develop an evaluation scale by using the empirical results of this study. The data were collected using the Clinical Learning Environment and Supervision instrument (CLES). The instrument was based on the literature review of earlier studies. The derived instrument was tested empirically in a study involving nurse students (N=416) from four nursing colleges in Finland. The results demonstrated that the method of supervision, the number of separate supervision sessions and the psychological content of supervisory contact within a positive ward atmosphere are the most important variables in the students' clinical learning. The results also suggest that ward managers can create the conditions of a positive ward culture and a positive attitude towards students and their learning needs. The construct validity of the instrument was analysed by using exploratory factor analysis. The analysis indicated that the most important factor in the students' clinical learning is the supervisory relationship. The two most important factors constituting a 'good' clinical learning environment are the management style of the ward manager and the premises of nursing on the ward. The results of the factor analysis support the theoretical construction of the clinical learning environment modelled by earlier empirical studies.

Building a semantic web-based metadata repository for facilitating detailed clinical modeling in cancer genome studies.

PubMed

Sharma, Deepak K; Solbrig, Harold R; Tao, Cui; Weng, Chunhua; Chute, Christopher G; Jiang, Guoqian

2017-06-05

Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain "clinical pharmaceutical" in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains.

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust.

PubMed

Klein, E; Solomon, A J; Corboy, J; Bernat, J

2016-07-01

Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. Copyright © 2016 Elsevier B.V. All rights reserved.

Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) study: Methodology and baseline characteristics of a randomized controlled trial evaluating an occupation-based diabetes management intervention for young adults.

PubMed

Pyatak, Elizabeth A; Carandang, Kristine; Vigen, Cheryl; Blanchard, Jeanine; Sequeira, Paola A; Wood, Jamie R; Spruijt-Metz, Donna; Whittemore, Robin; Peters, Anne L

2017-03-01

This paper describes the study protocol used to evaluate the Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) intervention and reports on baseline characteristics of recruited participants. REAL Diabetes is an activity-based intervention designed to address the needs of young adults diagnosed with type 1 (T1D) or type 2 diabetes (T2D) from low socioeconomic status or racial/ethnic minority backgrounds. The REAL intervention incorporates tailored delivery of seven content modules addressing various dimensions of health and well-being as they relate to diabetes, delivered by a licensed occupational therapist. In this pilot randomized controlled trial, participants are assigned to the REAL Diabetes intervention or an attention control condition. The study's primary recruitment strategies included in-person recruitment at diabetes clinics, mass mailings to clinic patients, and social media advertising. Data collection includes baseline and 6-month assessments of primary outcomes, secondary outcomes, and hypothesized mediators of intervention effects, as well as ongoing process evaluation assessment to ensure study protocol adherence and intervention fidelity. At baseline, participants (n=81) were 51% female, 78% Latino, and on average 22.6years old with an average HbA1c of 10.8%. A majority of participants (61.7%) demonstrated clinically significant diabetes distress and 27.2% reported symptoms consistent with major depressive disorder. Compared to participants with T1D, participants with T2D had lower diabetes-related self-efficacy and problem-solving skills. Compared to participants recruited at clinics, participants recruited through other strategies had greater diabetes knowledge but weaker medication adherence. Participants in the REAL study demonstrate clinically significant medical and psychosocial needs. Copyright © 2017 Elsevier Inc. All rights reserved.

Pre-pregnancy BMI and body fat mass of 2 weeks old infants

USDA-ARS?s Scientific Manuscript database

Maternal programming of fetal metabolism has been previously demonstrated in animal studies. Clinical studies have also shown an association between pre-pregnancy body mass index (BMI) and anthropometric measures in infants. This study reports for the first time infant body composition at 2 weeks us...

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

PubMed

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

2015-01-01

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

Cognitive Fusion Questionnaire-Body Image: Psychometric Properties and Its Incremental Power in the Prediction of Binge Eating Severity.

PubMed

Lucena-Santos, Paola; Trindade, Inês A; Oliveira, Margareth; Pinto-Gouveia, José

2017-05-19

Given the clinical usefulness of the CFQ-BI (Cognitive Fusion Questionnaire-Body Image; the only existing measure to assess the body-image-related cognitive fusion), the present study aimed to confirm its one-factor structure, to verify its measurement invariance between clinical and non-clinical samples, to analyze its internal consistency and sensitivity to detect differences between samples, as well as to explore the incremental and convergent validities of the CFQ-BI scores in Brazilian samples.  This was a cross-sectional study, which was conducted in clinical (women with overweight or obesity in treatment for weight loss) and non-clinical samples (women from the general population). The one-factor structure was confirmed showing factorial measurement invariance across clinical and non-clinical samples. The CFQ-BI scores presented an excellent internal consistency, were able to discriminate clinical and non-clinical samples, and were positively associated with binge eating severity, general cognitive fusion, and psychological inflexibility. Furthermore, body-image-related cognitive fusion scores (CFQ-BI) presented incremental validity over a general measure of cognitive fusion in the prediction of binge eating symptoms. This study demonstrated that CFQ-BI is a short scale with reliable and robust scores in Brazilian samples, presenting incremental and convergent validities, measurement invariance, and sensitivity to detect differences between clinical and non-clinical groups of women, enabling comparative studies between them.

Development and psychometric testing of a Clinical Reasoning Evaluation Simulation Tool (CREST) for assessing nursing students' abilities to recognize and respond to clinical deterioration.

PubMed

Liaw, Sok Ying; Rashasegaran, Ahtherai; Wong, Lai Fun; Deneen, Christopher Charles; Cooper, Simon; Levett-Jones, Tracy; Goh, Hongli Sam; Ignacio, Jeanette

2018-03-01

The development of clinical reasoning skills in recognising and responding to clinical deterioration is essential in pre-registration nursing education. Simulation has been increasingly used by educators to develop this skill. To develop and evaluate the psychometric properties of a Clinical Reasoning Evaluation Simulation Tool (CREST) for measuring clinical reasoning skills in recognising and responding to clinical deterioration in a simulated environment. A scale development with psychometric testing and mixed methods study. Nursing students and academic staff were recruited at a university. A three-phase prospective study was conducted. Phase 1 involved the development and content validation of the CREST; Phase 2 included the psychometric testing of the tool with 15 second-year and 15 third-year nursing students who undertook the simulation-based assessment; Phase 3 involved the usability testing of the tool with nine academic staff through a survey questionnaire and focus group discussion. A 10-item CREST was developed based on a model of clinical reasoning. A content validity of 0.93 was obtained from the validation of 15 international experts. The construct validity was supported as the third-year students demonstrated significantly higher (p<0.001) clinical reasoning scores than the second-year students. The concurrent validity was also supported with significant positive correlations between global rating scores and almost all subscale scores, and the total scores. The predictive validity was supported with an existing tool. The internal consistency was high with a Cronbach's alpha of 0.92. A high inter-rater reliability was demonstrated with an intraclass correlation coefficient of 0.88. The usability of the tool was rated positively by the nurse educators but the need to ease the scoring process was highlighted. A valid and reliable tool was developed to measure the effectiveness of simulation in developing clinical reasoning skills for recognising and responding to clinical deterioration. Copyright © 2017. Published by Elsevier Ltd.

Pilot study demonstrating effectiveness of targeted education to improve informed consent understanding in AIDS clinical trials.

PubMed

Sengupta, Sohini; Lo, Bernard; Strauss, Ronald P; Eron, Joseph; Gifford, Allen L

2011-11-01

Assessing and improving informed consent understanding is equally important as obtaining consent from participants in clinical trial research, but developing interventions to target gaps in participants' informed consent understanding remains a challenge. We used a randomized controlled study design to pilot test an educational intervention to improve actual informed consent understanding of new enrollees in the Adult AIDS Clinical Trial Group (AACTG). Questionnaires were administered to 24 enrollees to assess their baseline understanding on eight elements of informed consent associated with AIDS clinical trials. Enrollees who scored 18/21(85%) or less were randomly assigned to in-person, targeted education (intervention), or delayed education (control). Two follow-up assessments were administered. Repeated measures ANOVA was performed to determine intervention effectiveness in improving actual informed consent understanding over time. Actual understanding improved at the immediate post-intervention time point with a significant score difference of 2.5 when comparing the intervention and delayed groups. In addition, there was a significant score difference of 3.2 when comparing baseline to three-month follow-up for the two groups, suggesting a statistically significant intervention effect to improve actual understanding of the basic elements of informed consent. The findings demonstrated that one-time targeted education can improve actual informed consent understanding one week after the intervention, but retention of these concepts may require periodic monitoring to ensure comprehension throughout the course of a clinical trial.

Does sensitivity measured from screening test-sets predict clinical performance?

NASA Astrophysics Data System (ADS)

Soh, BaoLin P.; Lee, Warwick B.; Mello-Thoms, Claudia R.; Tapia, Kriscia A.; Ryan, John; Hung, Wai Tak; Thompson, Graham J.; Heard, Rob; Brennan, Patrick C.

2014-03-01

Aim: To examine the relationship between sensitivity measured from the BREAST test-set and clinical performance. Background: Although the UK and Australia national breast screening programs have regarded PERFORMS and BREAST test-set strategies as possible methods of estimating readers' clinical efficacy, the relationship between test-set and real life performance results has never been satisfactorily understood. Methods: Forty-one radiologists from BreastScreen New South Wales participated in this study. Each reader interpreted a BREAST test-set which comprised sixty de-identified mammographic examinations sourced from the BreastScreen Digital Imaging Library. Spearman's rank correlation coefficient was used to compare the sensitivity measured from the BREAST test-set with screen readers' clinical audit data. Results: Results shown statistically significant positive moderate correlations between test-set sensitivity and each of the following metrics: rate of invasive cancer per 10 000 reads (r=0.495; p < 0.01); rate of small invasive cancer per 10 000 reads (r=0.546; p < 0.001); detection rate of all invasive cancers and DCIS per 10 000 reads (r=0.444; p < 0.01). Conclusion: Comparison between sensitivity measured from the BREAST test-set and real life detection rate demonstrated statistically significant positive moderate correlations which validated that such test-set strategies can reflect readers' clinical performance and be used as a quality assurance tool. The strength of correlation demonstrated in this study was higher than previously found by others.

Clinical presentation and outcome of dogs treated medically or surgically for thoracolumbar intervertebral disc protrusion.

PubMed

Crawford, A H; De Decker, S

2017-06-10

To date, few studies have investigated the clinical characteristics of thoracolumbar intervertebral disc protrusion (IVDP). The aim of this retrospective study was to evaluate the presentation and outcome of dogs receiving medical or surgical treatment for thoracolumbar IVDP. Eighty-four dogs were included, with a median age of 9.4 years. German shepherd dogs and Staffordshire bull terriers were the most common breeds. Significantly more surgically treated dogs (n=53) had neurological deficits and were non-ambulatory, compared with medically treated (n=31). Outcome data were available for 27 of 31 medically managed dogs; 11 initially improved, 7 remained stable and 9 deteriorated. Of 18 dogs that initially improved or stabilised, 10 (55.6 per cent) demonstrated recurrence of clinical signs within 12 months of diagnosis. Outcome data were available for 45 of 50 surgically treated dogs that survived to hospital discharge; 34 improved, 9 remained stable and 2 deteriorated following surgery. Of 43 dogs that improved or stabilised with surgical treatment, 11 (25.6 per cent) demonstrated recurrence of clinical signs within 12 months of surgery. Overall, significantly more surgically treated dogs (71.1 per cent) had a successful outcome, consisting of sustained clinical improvement of more than 12 months duration, compared with medically treated dogs (29.6 per cent). British Veterinary Association.

MRI of the hip at 7T: feasibility of bone microarchitecture, high-resolution cartilage, and clinical imaging.

PubMed

Chang, Gregory; Deniz, Cem M; Honig, Stephen; Egol, Kenneth; Regatte, Ravinder R; Zhu, Yudong; Sodickson, Daniel K; Brown, Ryan

2014-06-01

To demonstrate the feasibility of performing bone microarchitecture, high-resolution cartilage, and clinical imaging of the hip at 7T. This study had Institutional Review Board approval. Using an 8-channel coil constructed in-house, we imaged the hips of 15 subjects on a 7T magnetic resonance imaging (MRI) scanner. We applied: 1) a T1-weighted 3D fast low angle shot (3D FLASH) sequence (0.23 × 0.23 × 1-1.5 mm(3) ) for bone microarchitecture imaging; 2) T1-weighted 3D FLASH (water excitation) and volumetric interpolated breath-hold examination (VIBE) sequences (0.23 × 0.23 × 1.5 mm(3) ) with saturation or inversion recovery-based fat suppression for cartilage imaging; 3) 2D intermediate-weighted fast spin-echo (FSE) sequences without and with fat saturation (0.27 × 0.27 × 2 mm) for clinical imaging. Bone microarchitecture images allowed visualization of individual trabeculae within the proximal femur. Cartilage was well visualized and fat was well suppressed on FLASH and VIBE sequences. FSE sequences allowed visualization of cartilage, the labrum (including cartilage and labral pathology), joint capsule, and tendons. This is the first study to demonstrate the feasibility of performing a clinically comprehensive hip MRI protocol at 7T, including high-resolution imaging of bone microarchitecture and cartilage, as well as clinical imaging. Copyright © 2013 Wiley Periodicals, Inc.

A 12-month study of the hikikomori syndrome of social withdrawal: Clinical characterization and different subtypes proposal.

PubMed

Malagón-Amor, Ángeles; Martín-López, Luis Miguel; Córcoles, David; González, Anna; Bellsolà, Magda; Teo, Alan R; Pérez, Víctor; Bulbena, Antoni; Bergé, Daniel

2018-03-23

Social withdrawal is a new mental health problem increasingly common, present in different cultures, whose psychopathology and treatment is not yet established. This study aims to determine the socio-demographic and clinical features and possible clinical subtypes that predict the 12-month outcomes of cases with hikikomori syndrome, a severe form of social withdrawal. Socio-demographic and clinical data at baseline were analysed as well as data obtained for 12 months after at-home treatment in 190 cases. The inclusion criteria were: spending all time at home, avoiding social situations and relationships, significant deterioration due to social isolation, with a minimum duration of 6 months. Six major diagnostic groups were identified: affective, anxiety, psychotic, drug use, personality and other Axis I disorders. The anxiety-affective subgroup demonstrated lower clinical severity, but worse evolution. Less than half of the cases were available for medical follow-up at 12-months. Subjects undergoing intensive treatment had a higher medical follow-up rate and better social networks at 12-months. Therefore, our findings provide data to reach consensus on the specific characteristics of social isolation hikikomori syndrome. The analysis demonstrated the fragility and tendency to relapse and have disengagement, particularly relevant in the anxiety-affective subgroup, suggesting that intensive treatments are more effective. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost of Treatment Procedures in the National Preventive Dentistry Demonstration Program.

ERIC Educational Resources Information Center

Foch, Craig B.; And Others

The National Preventive Dentistry Demonstration Program (NPDDP) delivered five different regimens of school based preventive dental care to groups of children in 10 American cities between 1977 and 1981. All clinical techniques employed had previously been demonstrated to be both safe and effective in clinical trials. The purpose of the NPDDP was…

Using electronic mail to improve MMR uptake amongst third level students.

PubMed

Cooney, F; Ryan, A; Schinaia, N; Breslin, A

2010-03-01

This study assessed the usefulness of email in informing third level students about special MMR clinics being provided on campus during a mumps outbreak in the North West of Ireland. Email messages were sent directly to students, informing them of the clinics, inviting them to make a clinic appointment by email and providing details of walk-in clinics. At the clinics, all 177 attendees were asked to fill out a questionnaire and the response rate was 89% (n=158). Regarding the main sources of information about the vaccination clinics, email was selected by 117 (74%) students, word-of-mouth by 27 (17%), posters/leaflets by 8 (5%), and other sources by 6 (4%). Use of email as a source of information was rated as very good/excellent by 115 (73%), as good by 35 (22%) and poor/fair by 8 (5%). This study demonstrates that email is a useful and acceptable way of informing third level students about immunisation clinics in an outbreak situation.

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

Minocycline attenuates noise-induced hearing loss in rats.

PubMed

Zhang, Jing; Song, Yong-Li; Tian, Ke-Yong; Qiu, Jian-Hua

2017-02-03

Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days. In conclusion, the present study demonstrated that minocycline, a clinically approved drug with a good safety profile, can attenuate NIHL in rats and may potentially be used for treatment of hearing loss in clinic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Infant Brain Development and Vulnerability to Later Internalizing Difficulties: The Generation R Study

ERIC Educational Resources Information Center

Herba, Catherine M.; Roza, Sabine J.; Govaert, Paul; van Rossum, Joram; Hofman, Albert; Jaddoe, Vincent; Verhulst, Frank C.; Tiemeier, Henning

2010-01-01

Objective: Although clinical studies have demonstrated smaller subcortical volumes in structures such as the amygdala, hippocampus, caudate nucleus, and thalamus in adults and adolescents with depressive disorders and anxiety, no study has assessed such structures in babies, long before the development of the disorders. This study examined whether…

Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.

PubMed

You, Yanqin; Sun, Yan; Li, Xuchao; Li, Yali; Wei, Xiaoming; Chen, Fang; Ge, Huijuan; Lan, Zhangzhang; Zhu, Qian; Tang, Ying; Wang, Shujuan; Gao, Ya; Jiang, Fuman; Song, Jiaping; Shi, Quan; Zhu, Xuan; Mu, Feng; Dong, Wei; Gao, Vince; Jiang, Hui; Yi, Xin; Wang, Wei; Gao, Zhiying

2014-08-01

This article demonstrates a prominent noninvasive prenatal approach to assist the clinical diagnosis of a single-gene disorder disease, maple syrup urine disease, using targeted sequencing knowledge from the affected family. The method reported here combines novel mutant discovery in known genes by targeted massively parallel sequencing with noninvasive prenatal testing. By applying this new strategy, we successfully revealed novel mutations in the gene BCKDHA (Ex2_4dup and c.392A>G) in this Chinese family and developed a prenatal haplotype-assisted approach to noninvasively detect the genotype of the fetus (transmitted from both parents). This is the first report of integration of targeted sequencing and noninvasive prenatal testing into clinical practice. Our study has demonstrated that this massively parallel sequencing-based strategy can potentially be used for single-gene disorder diagnosis in the future.

Enabling Genomic-Phenomic Association Discovery without Sacrificing Anonymity

PubMed Central

Heatherly, Raymond D.; Loukides, Grigorios; Denny, Joshua C.; Haines, Jonathan L.; Roden, Dan M.; Malin, Bradley A.

2013-01-01

Health information technologies facilitate the collection of massive quantities of patient-level data. A growing body of research demonstrates that such information can support novel, large-scale biomedical investigations at a fraction of the cost of traditional prospective studies. While healthcare organizations are being encouraged to share these data in a de-identified form, there is hesitation over concerns that it will allow corresponding patients to be re-identified. Currently proposed technologies to anonymize clinical data may make unrealistic assumptions with respect to the capabilities of a recipient to ascertain a patients identity. We show that more pragmatic assumptions enable the design of anonymization algorithms that permit the dissemination of detailed clinical profiles with provable guarantees of protection. We demonstrate this strategy with a dataset of over one million medical records and show that 192 genotype-phenotype associations can be discovered with fidelity equivalent to non-anonymized clinical data. PMID:23405076

Diagnostic accuracy of clinical tests for assessment of hamstring injury: a systematic review.

PubMed

Reiman, Michael P; Loudon, Janice K; Goode, Adam P

2013-04-01

Systematic literature review. The diagnosis of a hamstring injury has traditionally relied on various clinical measures (eg, palpation, swelling, manual resistance), as well as the use of diagnostic imaging. But a few studies have suggested the use of specific clinical tests that may be helpful for the diagnostic process. To summarize the current literature on the diagnostic accuracy of orthopaedic special tests for hamstring injuries and to determine their clinical utility. A computer-assisted literature search of the MEDLINE, CINAHL, and Embase databases (along with a manual search of grey literature) was conducted using key words related to diagnostic accuracy of hamstring injuries. To be considered for inclusion in the review, the study required (1) patients with hamstring or posterior thigh pain; (2) a cohort, case-control, or cross-sectional design; (3) inclusion of at least 1 clinical examination test used to evaluate hamstring pathology; (4) comparison against an acceptable reference standard; (5) reporting of diagnostic accuracy of the measures (sensitivity [SN], specificity [SP], or likelihood ratios); and (6) publication in English. SN, SP, and positive and negative likelihood ratios were calculated for each diagnostic test. The search strategy identified 602 potential articles, of which only 3 articles met the inclusion criteria, with only 1 of these 3 articles being of high quality. Two of the studies investigated a single special test, whereas the third article examined a composite clinical assessment employing various special tests. The SN values ranged from 0.55 (95% confidence interval [CI]: 0.46, 0.69) for the active range-of-motion test to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test. The SP values ranged from 0.03 (95% CI: 0.00, 0.22) for the composite clinical assessment to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test, active range-of-motion test, passive range-of-motion test, and resisted range-of-motion test. The use of a single special test demonstrated stronger SP than SN properties, whereas the composite clinical assessment demonstrated stronger SN than SP properties. Very few studies have investigated the utilization of clinical special tests for the diagnosis of hamstring injuries. Further studies of higher quality design are suggested prior to advocating independent clinical utilization of these special tests. Diagnosis, level 3b.

Deep molecular responses for treatment-free remission in chronic myeloid leukemia.

PubMed

Dulucq, Stéphanie; Mahon, Francois-Xavier

2016-09-01

Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Validated Measures of Insomnia, Function, Sleepiness, and Nasal Obstruction in a CPAP Alternatives Clinic Population.

PubMed

Lam, Austin S; Collop, Nancy A; Bliwise, Donald L; Dedhia, Raj C

2017-08-15

Although efficacious in the treatment of obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) can be difficult to tolerate, with long-term adherence rates approaching 50%. CPAP alternatives clinics specialize in the evaluation and treatment of CPAP-intolerant patients; yet this population has not been studied in the literature. To better understand these patients, we sought to assess insomnia, sleep-related functional status, sleepiness, and nasal obstruction, utilizing data from validated instruments. After approval from the Emory University Institutional Review Board, a retrospective chart review was performed from September 2015 to September 2016 of new patient visits at the Emory CPAP alternatives clinic. Patient demographics and responses were recorded from the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), Epworth Sleepiness Scale, and Nasal Obstruction Symptom Evaluation questionnaires. A total of 172 patients were included, with 81% having moderate-severe OSA. Most of the patients demonstrated moderate-severe clinical insomnia and at least moderate nasal obstruction. FOSQ-10 scores indicated sleep-related functional impairment in 88%. However, most patients did not demonstrate excessive daytime sleepiness. This patient population demonstrates significant symptomatology and functional impairment. Because of the severity of their OSA, they are at increased risk of complications. In order to mitigate the detrimental effects of OSA, these significantly impacted patients should be identified and encouraged to seek CPAP alternatives clinics that specialize in the treatment of this population. © 2017 American Academy of Sleep Medicine

Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis.

PubMed

Kim, Jimin P; Xie, Zhiwei; Creer, Michael; Liu, Zhiwen; Yang, Jian

2017-01-01

Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.

Fuzzy control for closed-loop, patient-specific hypnosis in intraoperative patients: a simulation study.

PubMed

Moore, Brett L; Pyeatt, Larry D; Doufas, Anthony G

2009-01-01

Research has demonstrated the efficacy of closed-loop control of anesthesia using bispectral index (BIS) as the controlled variable, and the recent development of model-based, patient-adaptive systems has considerably improved anesthetic control. To further explore the use of model-based control in anesthesia, we investigated the application of fuzzy control in the delivery of patient-specific propofol-induced hypnosis. In simulated intraoperative patients, the fuzzy controller demonstrated clinically acceptable performance, suggesting that further study is warranted.

Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis.

PubMed

Anzueto, A; Fisher, C L; Busman, T; Olson, C A

2001-01-01

Clarithromycin has established efficacy and safety in the treatment of respiratory infections. This study examined the efficacy and safety of a new extended-release formulation of clarithromycin compared with amoxicillin/clavulanate in the treatment of acute exacerbation of chronic bronchitis (AECB). This phase IIIB, multicenter, randomized, parallel-group, investigator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500-mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tablet twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinuation), and between study days 17 and 21 (test of cure). Of 287 patients randomized and treated, 270 were clinically evaluable (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups were well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 87% of clarithromycin- and amoxicillin/clavulanate-treated patients, respectively, demonstrated clinical cure (as defined in 1998 draft US Food and Drug Administration guidelines); among clinically and bacteriologically evaluable patients, 92% versus 89%, respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were similar in the 2 groups (88% clarithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuation of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulanate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse events. Adverse events generally occurred with a similar frequency in the 2 groups; however, taste alteration was more common with clarithromycin (9/142 [6%]) than with amoxicillin/clavulanate (1/145 [1%]; P = 0.01). Mean severity scores for gastrointestinal adverse events showed a significant difference between groups (1.16 for clarithromycin-treated patients and 1.58 for amoxicillin/clavulanate-treated patients: P = 0.016). The results of this study demonstrate the clinical and bacteriologic equivalence and improved gastrointestinal tolerability of a 7-day course of once-daily extended-release clarithromycin relative to a 10-day course of twice-daily amoxicillin/clavulanate in the treatment of AECB.

Hepatic Histological Findings in Suspected Drug-Induced Liver Injury: Systematic Evaluation and Clinical Associations

PubMed Central

Kleiner, David E; Chalasani, Naga P; Lee, William M; Fontana, Robert J; Bonkovsky, Herbert L; Watkins, Paul B; Hayashi, Paul H; Davern, Timothy J; Navarro, Victor; Reddy, Rajender; Talwalkar, Jayant A; Stolz, Andrew; Gu, Jiezhun; Barnhart, Huiman; Hoofnagle, Jay H

2014-01-01

Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome. (Hepatology 2014;59:661–670) PMID:24037963

Enhancing State Medical Home Capacity through a Care Coordination Technical Assistance Model.

PubMed

Berry, Susan; Barovechio, Patti; Mabile, Emily; Tran, Tri

2017-10-01

Introduction A practice-based care coordination (CC) model was developed by Louisiana's Title V Children's Special Health Services (CSHS) program to meet the overwhelming needs of the New Orleans post-Katrina population. The pilot clinic demonstrated an improvement in medical home (MH) capacity over the course of 3 months. The purpose of the current study is to evaluate the replicability of the model and sustainability of MH improvement over at least 2 years, while identifying factors that may modify the effect of the intervention. Methods The CSHS CC model utilizing a practice based care coordinator was implemented in 15 academic primary care pediatric clinics. Increase in MH capacity was determined using the MH Index-Short Version (MHI-SV) tool. Results The analysis of the MHI-SV scores for the ten clinics with >2 years of data demonstrated a significant improvement with each of the ten MHI-SV indicators. The mean clinic MHI-SV score improved from 19.70 to 34.15 on a scale of 10-50. Characteristics associated with the greatest MHI score improvement were rural geographic location, having an electronic health record, and using social workers or nurses as care coordinators. Characteristics associated with lower MHI scores were physician or care coordinator turnover and using stand-alone databases rather than tracking CC activities within the central patient record. Conclusion This study provides a flexible framework for implementing CC services in pediatric, family medicine, and medicine-pediatric practices, and demonstrates the value of CC as a driver for improvement in medical home capacity.

Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells in Vitro

PubMed Central

Schenk, Erin L.; Koh, Brian D.; Flatten, Karen S.; Peterson, Kevin L.; Parry, David; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Karnitz, Larry M.; Kaufmann, Scott H.

2012-01-01

Purpose Previous studies have demonstrated that the replication checkpoint, which involves the kinases ATR and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical AML during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro. Experimental design AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays. Results Immunoblotting demonstrated increased Chk1 phosphorylation, a marker of checkpoint activation, in over half of Chk1-containing AMLs after 48 h of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S phase arrest, but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the anti-proliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors. Conclusions These results not only provide evidence for cytarabine-induced S phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted. PMID:22869869

Effectiveness of implementation strategies for clinical guidelines to community pharmacy: a systematic review.

PubMed

Watkins, Kim; Wood, Helen; Schneider, Carl R; Clifford, Rhonda

2015-10-29

The clinical role of community pharmacists is expanding, as is the use of clinical guidelines in this setting. However, it is unclear which strategies are successful in implementing clinical guidelines and what outcomes can be achieved. The aim of this systematic review is to synthesise the literature on the implementation of clinical guidelines to community pharmacy. The objectives are to describe the implementation strategies used, describe the resulting outcomes and to assess the effectiveness of the strategies. A systematic search was performed in six electronic databases (Medline, EMBASE, CINAHL, Web of Science, Informit, Cochrane Library) for relevant articles. Studies were included if they reported on clinical guidelines implementation strategies in the community pharmacy setting. Two researchers completed the full-search strategy, data abstraction and quality assessments, independently. A third researcher acted as a moderator. Quality assessments were completed with three validated tools. A narrative synthesis was performed to analyse results. A total of 1937 articles were retrieved and the titles and abstracts were screened. Full-text screening was completed for 36 articles resulting in 19 articles (reporting on 22 studies) included for review. Implementation strategies were categorised according to a modified version of the EPOC taxonomy. Educational interventions were the most commonly utilised strategy (n = 20), and computerised decision support systems demonstrated the greatest effect (n = 4). Most studies were multifaceted and used more than one implementation strategy (n = 18). Overall outcomes were moderately positive (n = 17) but focused on process (n = 22) rather than patient (n = 3) or economic outcomes (n = 3). Most studies (n = 20) were rated as being of low methodological quality and having low or very low quality of evidence for outcomes. Studies in this review did not generally have a well thought-out rationale for the choice of implementation strategy. Most utilised educational strategies, but the greatest effect on outcomes was demonstrated using computerised clinical decision support systems. Poor methodology, in the majority of the research, provided insufficient evidence to be conclusive about the best implementation strategies or the benefit of clinical guidelines in this setting. However, the generally positive outcomes across studies and strategies indicate that implementing clinical guidelines to community pharmacy might be beneficial. Improved methodological rigour in future research is required to strengthen the evidence for this hypothesis. PROSPERO 2012: CRD42012003019 .

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders

PubMed Central

Conelea, Christine A.; Wellen, Brianna; Woods, Douglas W.; Greene, Deanna J.; Black, Kevin J.; Specht, Matthew; Himle, Michael B.; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression. PMID:29875706

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders.

PubMed

Conelea, Christine A; Wellen, Brianna; Woods, Douglas W; Greene, Deanna J; Black, Kevin J; Specht, Matthew; Himle, Michael B; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

Evidence of improved knowledge and skills after an elective rotation in a hospice and palliative care program for internal medicine residents.

PubMed

von Gunten, Charles F; Twaddle, Martha; Preodor, Michael; Neely, Kathy Johnson; Martinez, Jeanne; Lyons, John

2005-01-01

There is compelling evidence that residents training in primary care need education in palliative care. Evidence for effective curricula is needed. The objective of this study was to test whether a clinical elective improves measures of knowledge and skill. Residents from three categorical training programs in internal medicine were recruited to an elective including clinical experiences in an acute hospital palliative care consultation service, on an acute hospice and palliative care unit, and in-home hospice care. A 25-question pre- and post-test and a videotaped interview with a standardized patient were used to assess communication skills and measure outcomes. Residents demonstrated a 10 percent improvement in knowledge after the four-week elective (p < 0.05). All residents demonstrated basic competency in communication skills at the end of the rotation. These results indicate that clinical rotation shows promise as an educational intervention to improve palliative care knowledge and skills in primary care residents. An important limitation of the study is that it is an elective; further studies with a required rotation and/or a control group are needed to confirm the findings.

Evidence-based dentistry: a model for clinical practice.

PubMed

Faggion, Clóvis M; Tu, Yu-Kang

2007-06-01

Making decisions in dentistry should be based on the best evidence available. The objective of this study was to demonstrate a practical procedure and model that clinicians can use to apply the results of well-conducted studies to patient care by critically appraising the evidence with checklists and letter grade scales. To demonstrate application of this model for critically appraising the quality of research evidence, a hypothetical case involving an adult male with chronic periodontitis is used as an example. To determine the best clinical approach for this patient, a four-step, evidence-based model is demonstrated, consisting of the following: definition of a research question using the PICO format, search and selection of relevant literature, critical appraisal of identified research reports using checklists, and the application of evidence. In this model, the quality of research evidence was assessed quantitatively based on different levels of quality that are assigned letter grades of A, B, and C by evaluating the studies against the QUOROM (Quality of Reporting Meta-Analyses) and CONSORT (Consolidated Standards of Reporting Trials) checklists in a tabular format. For this hypothetical periodontics case, application of the model identified the best available evidence for clinical decision making, i.e., one randomized controlled trial and one systematic review of randomized controlled trials. Both studies showed similar answers for the research question. The use of a letter grade scale allowed an objective analysis of the quality of evidence. A checklist-driven model that assesses and applies evidence to dental practice may substantially improve dentists' decision making skill.

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

PubMed

Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

2017-07-01

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.

PubMed

Konno, Sensuke

2009-07-30

Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.

The clinical features of the overlap between COPD and asthma

PubMed Central

2011-01-01

Background The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. Methods We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. Results 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. Conclusion Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. Trial registration ClinicalTrials.gov: NCT00608764 PMID:21951550

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

PubMed Central

Oliver, Georgina; Dean, Olivia; Camfield, David; Blair-West, Scott; Ng, Chee; Berk, Michael; Sarris, Jerome

2015-01-01

Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. Methods PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. Results Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400–3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research. PMID:25912534

Integrated care in rural health: Seeking sustainability.

PubMed

Peterson, Mary; Turgesen, Jeri; Fisk, Laura; McCarthy, Seamus

2017-06-01

The increased awareness of the financial impact associated with social determinants of health coincides with expectations of the Affordable Care Act (HR 3590) to improve care while reducing costs. The integration of behavioral health providers (BHPs) into primary care has demonstrated improved clinical outcomes. This study was designed with 2 aims, including the evaluation of the financial viability of an integrated care model in a rural setting and the demonstration of incorporating practice-based research into clinical work. A rural health plan caring for 22,000 members funded a pilot project placing BHPs in 3 clinics to provide integrated care. Patient utilization of medical services for 6 months following BHP services was compared with baseline utilization. The BHPs treated 256 unique patients, with a total of 459 consultations. The percentage of patients receiving BHP services varied between clinics (Clinic A = 1.4%, Clinic B = 2.7%, and Clinic C = 3.9%). A between-clinic analysis showed differences in medical claims data between baseline and post-BH services. The overall effect sizes for reduced medical utilization for patients at clinics B and C were very large, Hedge's g = -2.31 and -4.79, respectively. Utilization of 4 of the services (emergency, lab, outpatient, and primary care) showed the large reductions in their costs. In contrast, the data for Clinic A showed no change. Patients receiving behavioral health services within the integrated care model may decrease utilization of medical services following treatment, resulting in cost offset. Potential reasons for variability between clinics are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia.

PubMed

Todd, Richard W; Etherington, Ian J; Luesley, David M

2002-04-01

The aim of this study was to investigate the effects of topical 5% Imiquimod (3M Pharmaceuticals, St. Paul, Minnessota) on high-grade vulval intraepithelial neoplasia (VIN). A prospective uncontrolled observational study was performed. Fifteen patients with histologically confirmed VIN 3 were asked to self-administer 5% Imiquimod cream to their vulval lesions up to three times weekly for 16 weeks. Review was conducted at 1, 2, 3, 4, 6, and 9 months postrecruitment. Lesions were photodocumented and at 4 months any areas demonstrating a clinical response were biopsied. Of 15 patients recruited, 4 demonstrated a clinical improvement in their disease, 3 of whom had negative biopsies posttreatment. Local side effects limited the frequency of application such that 7 patients applied the cream once weekly, 6 twice weekly, and 2 three times weekly. 5% Imiquimod cream appears to have an effect when used on high-grade VIN. The frequency of application was limited by local side effects which may have reduced the clinical responses seen. Measures to alleviate local side effects may allow more aggressive use of Imiquimod and lead to improved responses.

Development of a multiplexed urine assay for prostate cancer diagnosis.

PubMed

Vener, Tatiana; Derecho, Carlo; Baden, Jonathan; Wang, Haiying; Rajpurohit, Yashoda; Skelton, Joanne; Mehrotra, Jyoti; Varde, Shobha; Chowdary, Dondapati; Stallings, Walt; Leibovich, Bradley; Robin, Howard; Pelzer, Alexandre; Schäfer, Georg; Auprich, Marco; Mannweiler, Sebastian; Amersdorfer, Peter; Mazumder, Abhijit

2008-05-01

Several studies have demonstrated the value of DNA methylation in urine-based assays for prostate cancer diagnosis. However, a multicenter validation with a clinical prototype has not been published. We developed a multiplexed, quantitative methylation-specific polymerase chain reaction (MSP) assay consisting of 3 methylation markers, GSTP1, RARB, and APC, and an endogenous control, ACTB, in a closed-tube, homogeneous assay format. We tested this format with urine samples collected after digital rectal examination from 234 patients with prostate-specific antigen (PSA) concentrations > or =2.5 microg/L in 2 independent patient cohorts from 9 clinical sites. In the first cohort of 121 patients, we demonstrated 55% sensitivity and 80% specificity, with area under the curve (AUC) 0.69. In the second independent cohort of 113 patients, we found a comparable sensitivity of 53% and specificity of 76% (AUC 0.65). In the first cohort, as well as in a combined cohort, the MSP assay in conjunction with total PSA, digital rectal examination status, and age improved the AUC without MSP, although the difference was not statistically significant. Importantly, the GSTP1 cycle threshold value demonstrated a good correlation (R = 0.84) with the number of cores found to contain prostate cancer or premalignant lesions on biopsy. Moreover, samples that exhibited methylation for either GSTP1 or RARB typically contained higher tumor volumes at prostatectomy than those samples that did not exhibit methylation. These data confirm and extend previously reported studies and demonstrate the performance of a clinical prototype assay that should aid urologists in identifying men who should undergo biopsy.

Factors influencing radiation therapy student clinical placement satisfaction

PubMed Central

Bridge, Pete; Carmichael, Mary-Ann

2014-01-01

Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning. PMID:26229635

Natural and Artificial Intelligence in Neurosurgery: A Systematic Review.

PubMed

Senders, Joeky T; Arnaout, Omar; Karhade, Aditya V; Dasenbrock, Hormuzdiyar H; Gormley, William B; Broekman, Marike L; Smith, Timothy R

2017-09-07

Machine learning (ML) is a domain of artificial intelligence that allows computer algorithms to learn from experience without being explicitly programmed. To summarize neurosurgical applications of ML where it has been compared to clinical expertise, here referred to as "natural intelligence." A systematic search was performed in the PubMed and Embase databases as of August 2016 to review all studies comparing the performance of various ML approaches with that of clinical experts in neurosurgical literature. Twenty-three studies were identified that used ML algorithms for diagnosis, presurgical planning, or outcome prediction in neurosurgical patients. Compared to clinical experts, ML models demonstrated a median absolute improvement in accuracy and area under the receiver operating curve of 13% (interquartile range 4-21%) and 0.14 (interquartile range 0.07-0.21), respectively. In 29 (58%) of the 50 outcome measures for which a P -value was provided or calculated, ML models outperformed clinical experts ( P < .05). In 18 of 50 (36%), no difference was seen between ML and expert performance ( P > .05), while in 3 of 50 (6%) clinical experts outperformed ML models ( P < .05). All 4 studies that compared clinicians assisted by ML models vs clinicians alone demonstrated a better performance in the first group. We conclude that ML models have the potential to augment the decision-making capacity of clinicians in neurosurgical applications; however, significant hurdles remain associated with creating, validating, and deploying ML models in the clinical setting. Shifting from the preconceptions of a human-vs-machine to a human-and-machine paradigm could be essential to overcome these hurdles. Published by Oxford University Press on behalf of Congress of Neurological Surgeons 2017.

The utility of observational studies in clinical decision making: lessons learned from statin trials.

PubMed

Foody, JoAnne M; Mendys, Phillip M; Liu, Larry Z; Simpson, Ross J

2010-05-01

Contemporary clinical decision making is well supported by a wide variety of information sources, including clinical practice guidelines, position papers, and insights from randomized controlled trials (RCTs). Much of our fundamental understanding of cardiovascular risk factors is based on multiple observations from major epidemiologic studies, such as The Seven Country Studies and the US-based Framingham Heart Study. These studies provided the framework for the development of clinical practice guidelines, including the National Cholesterol Education Program Adult Treatment Panel series. The objective of this article is to highlight the value of observational studies as a complement to clinical trial data for clinical decision making in real-world practice. Although RCTs are still the benchmark for assessing clinical efficacy and safety of a specific therapeutic approach, they may be of limited utility to practitioners who must then adapt the lessons learned from the trial into the patient care environment. The use of well-structured observational studies can improve our understanding of the translation of clinical trials into clinical practice, as demonstrated here with the example of statins. Although such studies have their own limitations, improved techniques for design and analysis have reduced the impact of bias and confounders. The introduction of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines has provided more uniformity for such studies. When used together with RCTs, observational studies can enhance our understanding of effectiveness and utility in real-world clinical practice. In the examples of statin observational studies, the results suggest that relative effectiveness of different statins and potential impact of switching statins should be carefully considered in treating individual patients by practicing physicians.

Brain-controlled functional electrical stimulation therapy for gait rehabilitation after stroke: a safety study.

PubMed

McCrimmon, Colin M; King, Christine E; Wang, Po T; Cramer, Steven C; Nenadic, Zoran; Do, An H

2015-07-11

Many stroke survivors have significant long-term gait impairment, often involving foot drop. Current physiotherapies provide limited recovery. Orthoses substitute for ankle strength, but they provide no lasting therapeutic effect. Brain-computer interface (BCI)-controlled functional electrical stimulation (FES) is a novel rehabilitative approach that may generate permanent neurological improvements. This study explores the safety and feasibility of a foot-drop-targeted BCI-FES physiotherapy in chronic stroke survivors. Subjects (n = 9) operated an electroencephalogram-based BCI-FES system for foot dorsiflexion in 12 one-hour sessions over four weeks. Gait speed, dorsiflexion active range of motion (AROM), six-minute walk distance (6MWD), and Fugl-Meyer leg motor (FM-LM) scores were assessed before, during, and after therapy. The primary safety outcome measure was the proportion of subjects that deteriorated in gait speed by ≥0.16 m/s at one week or four weeks post-therapy. The secondary outcome measures were the proportion of subjects that experienced a clinically relevant decrease in dorsiflexion AROM (≥2.5°), 6MWD (≥20 %), and FM-LM score (≥10 %) at either post-therapy assessment. No subjects (0/9) experienced a clinically significant deterioration in gait speed, dorsiflexion AROM, 6MWT distance, or FM-LM score at either post-therapy assessment. Five subjects demonstrated a detectable increase (≥0.06 m/s) in gait speed, three subjects demonstrated a detectable increase (≥2.5°) in dorsiflexion AROM, five subjects demonstrated a detectable increase (≥10 %) in 6MWD, and three subjects demonstrated a detectable increase (≥10 %) in FM-LM. Five of the six subjects that exhibited a detectable increase in either post-therapy gait speed or 6MWD also exhibited significant (p < 0.01 using a Mann-Whitney U test) increases in electroencephalogram event-related synchronization/desynchronization. Additionally, two subjects experienced a clinically important increase (≥0.16 m/s) in gait speed, and four subjects experienced a clinically important increase (≥20 %) in 6MWD. Linear mixed models of gait speed, dorsiflexion AROM, 6MWD, and FM-LM scores suggest that BCI-FES therapy is associated with an increase in lower motor performance at a statistically, yet not clinically, significant level. BCI-FES therapy is safe. If it is shown to improve post-stroke gait function in future studies, it could provide a new gait rehabilitation option for severely impaired patients. Formal clinical trials are warranted.

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials

PubMed Central

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality, VR therapy, treatment, and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78–0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness. PMID:28386517

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials.

PubMed

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley; Danovitch, Itai

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality , VR therapy , treatment , and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78-0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness.

Leveraging Digital Health Technologies and Outpatient Sampling in Clinical Drug Development: A Phase 1 Exploratory Study.

PubMed

Dockendorf, Marissa F; Murthy, Gowri; Bateman, Kevin P; Kothare, Prajakti A; Anderson, Melanie; Xie, Iris; Sachs, Jeff R; Burlage, Rubi; Goldman, Andra; Moyer, Matthew; Shah, Jyoti; Ruba, Rachel; Shipley, Lisa; Harrelson, Jane

2018-06-09

Merck & Co., Inc. (Kenilworth, New Jersey) is investing in approaches to enrich clinical trial data and augment decision-making through utilization of digital health technologies, outpatient sampling, and real-time data access. As part of this strategy, a Phase 1 study was conducted to explore a few technologies of interest. In this fixed-sequence, two-period trial, 16 healthy subjects were administered 50-mg once-daily sitagliptin packaged in a bottle that electronically captured the date and time study medication was dispensed (Period 1) and in a traditional pharmacy bottle (Period 2). Dried blood spot (DBS) samples were collected for sitagliptin concentration analysis on select study days, both in-clinic and at-home, with collection time recorded using an electronic diary in Period 1 and by clinic staff in Period 2. Study results demonstrated the feasibility and subject acceptance of collecting digital adherence data and outpatient DBS samples in clinical trials and highlighted areas for future improvements. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The impact of rheologically controlled materials on the identification of airway compromise on the clinical and videofluoroscopic swallowing examinations.

PubMed

Groher, Michael E; Crary, Michael A; Carnaby Mann, Giselle; Vickers, Zata; Aguilar, Carlos

2006-10-01

Numerous studies have suggested that the clinical evaluation of swallowing fails to adequately identify those patients who aspirate or do not aspirate on a videofluoroscopic swallowing examination. These conclusions, however, are based on comparisons between swallowed materials that were not rheologically matched. The present study used a battery of rheologically matched test materials, involving thin and thick liquids and cohesive and adhesive semisolids. Using these test items, results from a clinical swallow evaluation were compared to the results of a videofluorographic evaluation using identical test materials. Results suggest that the use of three test materials, including thin and thick liquids given in volumes of 5 and 10 ml, demonstrated the strongest associations between cough on the clinical examination and aspiration on the videofluoroscopic examination.

Launching Effectiveness Research to Guide Practice in Neurosurgery: A National Institute Neurological Disorders and Stroke Workshop Report

PubMed Central

Walicke, Patricia; Abosch, Aviva; Asher, Anthony; Barker, Fred G.; Ghogawala, Zoher; Harbaugh, Robert; Jehi, Lara; Kestle, John; Koroshetz, Walter; Little, Roderick; Rubin, Donald; Valadka, Alex; Wisniewski, Stephen

2017-01-01

Abstract This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lack sufficient rigor. The workshop considered possible solutions, such as (1) statistical methods for demonstrating causality using observational data; (2) characteristics required of a registry supporting effectiveness research; (3) trial designs combining advantages of observational studies and RCTs; and (4) equipoise, an identified challenge for RCTs. In the future, advances in information technology potentially could lead to creation of a massive database where clinical data from all neurosurgeons are integrated and analyzed, ending the separation of clinical research and practice and leading to a new “science of practice.” PMID:28362926

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

PubMed

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

The IDEA Assessment Tool: Assessing the Reporting, Diagnostic Reasoning, and Decision-Making Skills Demonstrated in Medical Students' Hospital Admission Notes.

PubMed

Baker, Elizabeth A; Ledford, Cynthia H; Fogg, Louis; Way, David P; Park, Yoon Soo

2015-01-01

Construct: Clinical skills are used in the care of patients, including reporting, diagnostic reasoning, and decision-making skills. Written comprehensive new patient admission notes (H&Ps) are a ubiquitous part of student education but are underutilized in the assessment of clinical skills. The interpretive summary, differential diagnosis, explanation of reasoning, and alternatives (IDEA) assessment tool was developed to assess students' clinical skills using written comprehensive new patient admission notes. The validity evidence for assessment of clinical skills using clinical documentation following authentic patient encounters has not been well documented. Diagnostic justification tools and postencounter notes are described in the literature (1,2) but are based on standardized patient encounters. To our knowledge, the IDEA assessment tool is the first published tool that uses medical students' H&Ps to rate students' clinical skills. The IDEA assessment tool is a 15-item instrument that asks evaluators to rate students' reporting, diagnostic reasoning, and decision-making skills based on medical students' new patient admission notes. This study presents validity evidence in support of the IDEA assessment tool using Messick's unified framework, including content (theoretical framework), response process (interrater reliability), internal structure (factor analysis and internal-consistency reliability), and relationship to other variables. Validity evidence is based on results from four studies conducted between 2010 and 2013. First, the factor analysis (2010, n = 216) yielded a three-factor solution, measuring patient story, IDEA, and completeness, with reliabilities of .79, .88, and .79, respectively. Second, an initial interrater reliability study (2010) involving two raters demonstrated fair to moderate consensus (κ = .21-.56, ρ =.42-.79). Third, a second interrater reliability study (2011) with 22 trained raters also demonstrated fair to moderate agreement (intraclass correlations [ICCs] = .29-.67). There was moderate reliability for all three skill domains, including reporting skills (ICC = .53), diagnostic reasoning skills (ICC = .64), and decision-making skills (ICC = .63). Fourth, there was a significant correlation between IDEA rating scores (2010-2013) and final Internal Medicine clerkship grades (r = .24), 95% confidence interval (CI) [.15, .33]. The IDEA assessment tool is a novel tool with validity evidence to support its use in the assessment of students' reporting, diagnostic reasoning, and decision-making skills. The moderate reliability achieved supports formative or lower stakes summative uses rather than high-stakes summative judgments.

The Hampstead Clinic at work. Discussions in the Diagnostic Profile Research Group.

PubMed

Koch, Ehud

2012-01-01

Minutes of the Hampstead Clinic's Diagnostic Profile Research Group during a fifteen-month period (1964-1965) are reviewed and discussed. A wide range of topics were considered and discussed, with a special focus on the affective life, object relations, and ego function of atypical children in comparison to the early ego functions and differentiation of normal and neurotic children. These lively clinical and theoretical discussions and their implications for therapeutic work with a wide range of children, demonstrate the multifaceted leadership and contributions of Anna Freud as teacher, clinician, and thinker, and of the Hampstead Clinic as a major center for psychoanalytic studies.

T-cell receptor gene therapy: critical parameters for clinical success.

PubMed

Linnemann, Carsten; Schumacher, Ton N M; Bendle, Gavin M

2011-09-01

T-cell receptor (TCR) gene therapy aims to induce immune reactivity against tumors by introducing genes encoding a tumor-reactive TCR into patient T cells. This approach has been extensively tested in preclinical mouse models, and initial clinical trials have demonstrated the feasibility and potential of TCR gene therapy as a cancer treatment. However, data obtained from preclinical and clinical studies suggest that both the therapeutic efficacy and the safety of TCR gene therapy can be and needs to be further enhanced. This review highlights those strategies that can be followed to develop TCR gene therapy into a clinically relevant treatment option for cancer patients.

Combination of photodynamic therapy and immunomodulation — current status and future trends

PubMed Central

Qiang, Yong-Gang; Yow, Christine M.N.; Huang, Zheng

2008-01-01

Photodynamic therapy (PDT) has been used for the treatment of non-malignant and malignant diseases from head to toe. Over the last decade its clinical application has gained increasing acceptance around the world. Pre-clinical studies demonstrate that, in addition to the direct local cytotoxicity and vascular effects, PDT can induce various host immune responses. Recent clinical data also show that improved clinical outcomes are obtained through the combination of PDT and immunomodulation. This review will summarize and discuss recent progress in developing innovative regimen of PDT combined with immunomodulation for the treatment of both non-malignant and malignant diseases. PMID:18161883

Annexin A2 is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer

PubMed Central

Luo, Shi; Xie, Chubo; Wu, Ping; He, Jian; Tang, Yaoyun; Xu, Jing; Zhao, Suping

2017-01-01

Due to the lack of a definite diagnosis, a frequent recurrence rate and resistance to chemotherapy or radiotherapy, the clinical outcome for patients with advanced laryngeal cancer has not improved over the last decade. Annexin A2 is associated with the invasion and metastasis of cancer cells. In the present study, it was demonstrated using differential proteomics analysis that Annexin A2 is highly expressed in laryngeal carcinoma tissues and this was confirmed using immunohistochemistry, which demonstrated that the expression of Annexin A2 in laryngeal carcinoma tissues was significantly higher than in healthy adjacent tissue. In addition, its potential predictive value in the prognosis of patients with laryngeal carcinoma was evaluated. The results demonstrated that Annexin A2 expression was significantly associated with tumor size, lymph node metastasis, distant metastasis and clinical stage. In addition, higher Annexin A2 expression was associated with a poor prognosis of patients with laryngeal cancer. Thus, the results of the present study indicate that Annexin A2 expression is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer. PMID:29285166

Metabolite-cycled density-weighted concentric rings k-space trajectory (DW-CRT) enables high-resolution 1 H magnetic resonance spectroscopic imaging at 3-Tesla.

PubMed

Steel, Adam; Chiew, Mark; Jezzard, Peter; Voets, Natalie L; Plaha, Puneet; Thomas, Michael Albert; Stagg, Charlotte J; Emir, Uzay E

2018-05-17

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla. Single-slice full-intensity MRSI data (short echo time (TE) semi-LASER TE = 32 ms) were acquired from 6 healthy volunteers with an in-plane resolution of 5 × 5 mm in 13 min 30 sec using this approach. Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate (median Cramer-Rao Lower Bound [CRLB] = 3%), glutamate+glutamine (8%), and glutathione (13%). In addition, we demonstrate potential clinical utility of this technique by optimizing the TE to detect 2-hydroxyglutarate (long TE semi-LASER, TE = 110 ms), to produce relevant high-resolution metabolite maps of grade III IDH-mutant oligodendroglioma in a single patient. This study demonstrates the potential utility of MRSI in the clinical setting at 3 Tesla.

Arthroscopic and magnetic resonance image appearance and reconstruction of the anterior talofibular ligament in cases of apparent functional ankle instability.

PubMed

Takao, Masato; Innami, Ken; Matsushita, Takashi; Uchio, Yuji; Ochi, Mitsuo

2008-08-01

Many patients report feeling functional ankle instability, despite having no clinically demonstrable lateral instability. Some patients who experience functional instability of the ankle have substantial abnormalities of the anterior talofibular ligament despite having apparently normal lateral laxity in clinical examination. Case series; Level of evidence, 4. Fourteen patients who had functional ankle instability after sprain, despite having no clinically demonstrable lateral instability, were included in this study. All subjects underwent standard stress radiography, magnetic resonance imaging, and ankle arthroscopy. These patients were treated with anatomical reconstruction of the anterior talofibular ligament. Arthroscopic assessment revealed 3 cases with no ligamentous structure with scar tissue, 9 cases with partial ligament tears and scar tissue on the disrupted anterior talofibular ligament fiber, and 2 cases of abnormal course of the ligament at the fibular or talar attachment. Magnetic resonance imaging revealed the following: 5 cases of discontinuity of the anterior talofibular ligament, 2 cases of narrowing of the anterior talofibular ligament, 4 cases of high-intensity lesion in the anterior talofibular ligament, and 3 normal cases. The mean American Orthopaedic Foot and Ankle Society Ankle Hindfoot scale score was 66.2 +/- 3.2 points at preoperation and 92.3 +/- 4.4 points 2 years after surgery. All patients in this study with functional ankle instability, despite their having no demonstrable abnormal lateral laxity, had morphologic ligamentous abnormality on arthroscopic assessment.

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

PubMed

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?

PubMed

Russo, Ethan B

2008-04-01

This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.

Combination of 595-nm pulsed dye laser, long-pulsed 755-nm alexandrite laser, and microdermabrasion treatment for keratosis pilaris: retrospective analysis of 26 Korean patients.

PubMed

Lee, Sang Ju; Choi, Min Ju; Zheng, Zhenlong; Chung, Won Soon; Kim, Young Koo; Cho, Sung Bin

2013-06-01

Keratosis pilaris (KP) has beenpresented as small keratotic follicular papules with or without surrounding erythema. Various treatments with laser or light therapy have been used for the management of KP with various clinical outcomes. In the present study, we investigated the efficacy and safety of a combination therapy for KP. A total of 29 anatomical sites with KP in 26 patients were treated using a 595-nm pulsed dye laser (PDL) with nonpurpuragenic fluences, a long-pulsed 755-nm alexandrite laser, and microdermabrasion. Clinical improvement was assessed by comparing preand posttreatment clinical photographs and patient satisfaction rates. Evaluation of the clinical results three months after the treatments showed that 12 of the 29 anatomical sites (41.4%) demonstrated Grade 3 clinical improvement, ten (34.5%) had Grade 2 clinical improvement, four (13.8%) showed Grade 1 improvement, and three (10.3%) showed Grade 4 improvement. We observed that KP lesions improved not only in erythema and skin texture, but also in brownish dyschromias. Potential adverse events were not observed, except prolonged posttherapy scaling. Our observations demonstrate that combination therapy using a 595-nm PDL, a long-pulsed 755-nm alexandrite laser, and microdermabrasion can have a positive therapeutic effect on KP.

A Comprehensive, Simulation-Based Approach to Teaching Clinical Skills: The Medical Students’ Perspective

PubMed Central

Evans, Leigh V.; Crimmins, Ashley C.; Bonz, James W.; Gusberg, Richard J.; Tsyrulnik, Alina; Dziura, James D.; Dodge, Kelly L.

2014-01-01

The purpose of this study was to determine if third-year medical students participating in a mandatory 12-week simulation course perceived improvement in decision-making, communication, and teamwork skills. Students participated in or observed 24 acute emergency scenarios. At 4-week intervals, students completed 0-10 point Likert scale questionnaires evaluating the curriculum and role of team leader. Linear contrasts were used to examine changes in outcomes. P-values were Bonferroni-corrected for multiple pairwise comparisons. Student evaluations (n = 96) demonstrated increases from week 4 to 12 in educational value (p = 0.006), decision-making (p < 0.001), communication (p = 0.02), teamwork (p = 0.01), confidence in management (p < 0.001), and translation to clinical experience (p < 0.001). Regarding the team leader role, students reported a decrease in stress (p = 0.001) and increase in ability to facilitate team function (p < 0.001) and awareness of team building (p = <0.001). Ratings demonstrate a positive impact of simulation on both clinical management skills and team leadership skills. A simulation curriculum can enhance the ability to manage acute clinical problems and translates well to the clinical experience. These positive perceptions increase as the exposure to simulation increases. PMID:25506290

Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.

PubMed

Dworkin, Robert H; Turk, Dennis C; Peirce-Sandner, Sarah; Baron, Ralf; Bellamy, Nicholas; Burke, Laurie B; Chappell, Amy; Chartier, Kevin; Cleeland, Charles S; Costello, Ann; Cowan, Penney; Dimitrova, Rozalina; Ellenberg, Susan; Farrar, John T; French, Jacqueline A; Gilron, Ian; Hertz, Sharon; Jadad, Alejandro R; Jay, Gary W; Kalliomäki, Jarkko; Katz, Nathaniel P; Kerns, Robert D; Manning, Donald C; McDermott, Michael P; McGrath, Patrick J; Narayana, Arvind; Porter, Linda; Quessy, Steve; Rappaport, Bob A; Rauschkolb, Christine; Reeve, Bryce B; Rhodes, Thomas; Sampaio, Cristina; Simpson, David M; Stauffer, Joseph W; Stucki, Gerold; Tobias, Jeffrey; White, Richard E; Witter, James

2010-05-01

There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain. Copyright 2010 International Association for the Study of Pain. All rights reserved.

Nurse-led clinics reduce severity of childhood atopic eczema: a review of the literature.

PubMed

Moore, E; Williams, A; Manias, E; Varigos, G

2006-12-01

The increasing prevalence and impact of atopic eczema in children in Western countries such as Australia substantiate the need to evaluate the current management of this illness. It has been well documented that the most important aspects in the management of atopic eczema are to allow adequate time for education and demonstration of treatments. However, current models of healthcare funding restrict the opportunity for patient education during medical consultation times. The contribution of nursing to patient care through nurse-led clinics has significant potential in the management of many common chronic illnesses, although atopic eczema has received minimal attention by researchers to date. To discuss the current clinical management of atopic eczema, and to identify the evidence surrounding the benefits of nurse-led clinics in managing patients with chronic illnesses. Systematic searches were undertaken using the Cochrane Library, MedLine, PUBMed and CINAHL from 1995 to 2005. Manual searches of references of retrieved articles identified two additional key studies from 1990 and 1993 which were also included in the review. In total, 22 relevant publications were identified. These included both primary research and descriptive studies that covered the medical management of eczema, patient education and improved patient outcomes. The evidence emerging from the literature indicates that the current management of eczema through doctor-led clinics could be improved, with doctors often lacking the time to offer sufficient patient education to manage chronic illnesses effectively. The literature supports the efficacy of nurse-led clinics in the management of chronic illnesses. The benefits of nurse-led clinics include increased patient satisfaction, longer consultations resulting in improved patient education and similar health outcomes when compared with care from a doctor. No studies were identified comparing nurse-led and doctor-led clinics in the management of eczema. The most effective way to manage atopic eczema is to provide adequate time for education and demonstration of treatments, which the literature suggests can be achieved through nurse-led clinics. The literature review supports an investigation researching the outcomes of a nurse-led clinic on reducing the severity of eczema in children.

Clinical utility and impact of autopsies on clinical practice among doctors in a large teaching hospital in Ghana

PubMed Central

Tette, Edem; Yawson, Alfred E.; Tettey, Yao

2014-01-01

Background Autopsies can provide a good indication of the quality of patient care, in terms of the accuracy of clinical diagnosis and the quality of treatment given. Designs This was a cross-sectional study among clinicians at the Korle-Bu Teaching Hospital (KBTH) in 2012. Data were collected with a 69-item, self-administered, structured questionnaire. A total of 215 questionnaires were sent out and 119 clinicians responded. Data were collected on the benefits and utility of autopsies for medical practice, care of patients, and management of clinical wards. Survey data were analyzed by simple descriptive statistics (i.e. proportions, ratios, and percentages). Data were analyzed using SPSS version 21. Objective This study examined the views of clinicians regarding the utility of autopsies and their influence on clinical practice in a large teaching hospital in Ghana. Results Overall, clinicians in KBTH agreed that autopsy reports are useful in answering clinical questions (55/119; 46.2%), confirming or verifying clinical diagnoses (54/119; 45.4%), providing information on unsuspected diagnoses (40/119; 33.6%), and for medical education (90/119; 75.6%). Overall, 70/119 (58.8%) of clinicians agreed that autopsy findings improve completeness and reliability of death certification and provide information on clinical effectiveness of treatment and patient management. However, only 23/119 (19.3%) of sampled clinicians had personal interactions with a pathologist during autopsy processes and 93/119 (78.2%) had not attended any autopsy demonstrations in the past 6 months. Attendance of pathologists at clinicopathological meetings of clinical departments of KBTH was minimal. Unfortunately, the use of autopsy reports for auditing clinical diagnostic performance was not seen as essential. Conclusion Strengthening the interaction between doctors and pathologists is essential in improving the autopsy process and utilization in the hospital. KBTH should create opportunities for doctors to attend autopsy demonstrations and for pathologists to attend clinicopathological meetings in the hospital. PMID:24499743

Community-based primary care: improving and assessing diabetes management.

PubMed

Gannon, Meghan; Qaseem, Amir; Snow, Vincenza

2010-01-01

Morbidity and mortality associated with diabetes make it a prime target for quality improvement research. Quality gaps and racial/gender disparities persist throughout this population of patients necessitating a sustainable improvement in the clinical management of diabetes. The authors of this study sought (1) to provide a population perspective on diabetes management, and (2) to reinforce evidence-based clinical guidelines through a Web-based educational module.The project also aimed to gain insight into working remotely with a community of rural physicians. This longitudinal pre-post intervention study involved 18 internal medicine physicians and included 3 points of medical record data abstraction over 24 months. A Web-based educational module was introduced after the baseline data abstraction. This module contained chapters on clinical education, practice tools, and self-assessment. The results showed a sustained improvement in most clinical outcomes and demonstrated the effectiveness of using Web-based mediums to reinforce clinical guidelines and change physician behavior.

The Role of Platelet Rich Plasma (PRP) and Other Biologics for Rotator Cuff Repair.

PubMed

Greenspoon, Joshua A; Moulton, Samuel G; Millett, Peter J; Petri, Maximilian

2016-01-01

Surgical treatment of rotator cuff tears has consistently demonstrated good clinical and functional outcomes. However, in some cases, the rotator cuff fails to heal. While improvements in rotator cuff constructs and biomechanics have been made, the role of biologics to aid healing is currently being investigated. A selective literature search was performed and personal surgical experiences are reported. Biologic augmentation of rotator cuff repairs can for example be performed wtableith platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Clinical results on PRP application have been controversial. Application of MSCs has shown promise in animal studies, but clinical data on its effectiveness is presently lacking. The role of Matrix Metalloproteinase (MMP) inhibitors is another interesting field for potential targeted drug therapy after rotator cuff repair. Large randomized clinical studies need to confirm the benefit of these approaches, in order to eventually lower retear rates and improve clinical outcomes after rotator cuff repair.

Efficacy and Tolerability of an Acne Treatment Regimen with Antiaging Benefits in Adult Women

PubMed Central

Jiang, Lily I.; Hino, Peter D.; Parker, Lydia; Stephens, Thomas J.; Mccook, John

2018-01-01

Objective: The objective of this study was to assess clinical safety and efficacy of a novel acne treatment regimen in adult women. Methods: Participants in the study included an ethnically diverse group of adult women (n=24) with mild-to-moderate acne who were treated twice daily with a topical regimen (cleanser, acne cream, and rebalancing gel) for eight weeks. Following baseline assessments, subjects returned to clinic at Weeks 2, 4, and 8 for clinical assessments and self-assessment questionnaires. Results: Twenty-one of the 24 enrolled women completed the eight-week clinical trial. Statistically significant clinical improvements were seen in both acne and aging parameters over time. The product regimen was well tolerated without adverse reactions commonly seen with topical acne products. Conclusion: The regimen demonstrated efficacy and tolerability in adult women with acne and signs of skin aging. PMID:29942425

Open Tibial Inlay PCL Reconstruction: Surgical Technique and Clinical Outcomes.

PubMed

Vellios, Evan E; Jones, Kristofer J; McAllister, David R

2018-06-01

To review the current literature on clinical outcomes following open tibial inlay posterior cruciate ligament (PCL) reconstruction and provide the reader with a detailed description of the author's preferred surgical technique. Despite earlier biomechanical studies which demonstrated superiority of the PCL inlay technique when compared to transtibial techniques, recent longitudinal cohort studies have shown no significant differences in clinical or functional outcomes at 10-year follow-up. Furthermore, no significant clinical differences have been shown between graft types used and/or single- versus double-bundle reconstruction methods. The optimal treatment for the PCL-deficient knee remains unclear. Open tibial inlay PCL reconstruction is safe, reproducible, and avoids the "killer turn" that may potentially lead to graft weakening and failure seen in transtibial reconstruction methods. No significant differences in subjective outcomes or clinical laxity have been shown between single-bundle versus double-bundle reconstruction methods.

A Systematic Review of the Impact of Physician Implicit Racial Bias on Clinical Decision Making.

PubMed

Dehon, Erin; Weiss, Nicole; Jones, Jonathan; Faulconer, Whitney; Hinton, Elizabeth; Sterling, Sarah

2017-08-01

Disparities in diagnosis and treatment of racial minorities exist in the emergency department (ED). A better understanding of how physician implicit (unconscious) bias contributes to these disparities may help identify ways to eliminate such racial disparities. The objective of this systematic review was to examine and summarize the evidence on the association between physician implicit racial bias and clinical decision making. Based on PRISMA guidelines, a structured electronic literature search of PubMed, CINAHL, Scopus, and PsycINFO databases was conducted. Eligible studies were those that: 1) included physicians, 2) included the Implicit Association Test as a measure of implicit bias, 3) included an assessment of physician clinical decision making, and 4) were published in peer-reviewed journals between 1998 and 2016. Articles were reviewed for inclusion by two independent investigators. Data extraction was performed by one investigator and checked for accuracy by a second investigator. Two investigators independently scored the quality of articles using a modified version of the Downs and Black checklist. Of the 1,154 unique articles identified in the initial search, nine studies (n = 1,910) met inclusion criteria. Three of the nine studies involved emergency providers including residents, attending physicians, and advanced practice providers. The majority of studies used clinical vignettes to examine clinical decision making. Studies that included emergency medicine (EM) providers had vignettes relating to treatment of acute myocardial infarction, pain, and pediatric asthma. An implicit preference favoring white people was common across providers, regardless of specialty. Two of the nine studies found evidence of a relationship between implicit bias and clinical decision making; one of these studies included EM providers. This one study found that EM and internal medicine residents who demonstrated an implicit preference for white individuals were more likely to treat white patients and not black patients with thrombolysis for myocardial infarction. Evidence from the two studies reporting a relationship between physician implicit racial bias and decision making was low in quality. The current literature indicates that although many physicians, regardless of specialty, demonstrate an implicit preference for white people, this bias does not appear to impact their clinical decision making. Further studies on the impact of implicit racial bias on racial disparities in ED treatment are needed. © 2017 by the Society for Academic Emergency Medicine.

Neuropathic pain screening questionnaires have limited measurement properties. A systematic review.

PubMed

Mathieson, Stephanie; Maher, Christopher G; Terwee, Caroline B; Folly de Campos, Tarcisio; Lin, Chung-Wei Christine

2015-08-01

The Douleur Neuropathique 4 (DN4), ID Pain, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), PainDETECT, and Neuropathic Pain Questionnaire have been recommended as screening questionnaires for neuropathic pain. This systematic review aimed to evaluate the measurement properties (eg, criterion validity and reliability) of these questionnaires. Online database searches were conducted and two independent reviewers screened studies and extracted data. Methodological quality of included studies and the measurement properties were assessed against established criteria. A modified Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the level of evidence. Thirty-seven studies were included. Most studies recruited participants from pain clinics. The original version of the DN4 (French) and Neuropathic Pain Questionnaire (English) had the most number of satisfactory measurement properties. The ID Pain (English) demonstrated satisfactory hypothesis testing and reliability, but all other properties tested were unsatisfactory. The LANSS (English) was unsatisfactory for all properties, except specificity. The PainDETECT (English) demonstrated satisfactory hypothesis testing and criterion validity. In general, the cross-cultural adaptations had less evidence than the original versions. Overall, the DN4 and Neuropathic Pain Questionnaire were most suitable for clinical use. These screening questionnaires should not replace a thorough clinical assessment. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Use of dynamic images in radiology education: Movies of CT and MRI in the anatomy classroom.

PubMed

Jang, Hye Won; Oh, Chang-Seok; Choe, Yeon Hyeon; Jang, Dong Su

2018-04-19

Radiology education is a key component in many preclinical anatomy courses. However, the reported effectiveness of radiology education within such anatomy classrooms has varied. This study was conducted to determine if a novel educational method using dynamic images of movies of computed tomography (CT) and magnetic resonance imaging (MRI) was effective in radiology education during a preclinical anatomy course, aided by clay modeling, specific hand gestures (digit anatomy), and reports from dissection findings uploaded to the anatomy course website (digital reports). Feedback surveys using a five-point Likert scale were administered to better clarify students' opinions regarding their understanding of CT and MRI of anatomical structures, as well as to determine if such preclinical radiology education was helpful in their clinical studies. After completion of the anatomy course taught with dynamic images of CT and MRI, most students demonstrated an adequate understanding of basic CT and MR images. Additionally, students in later clinical years generally believed that their study of radiologic images during the preclinical anatomy course was helpful for their clinical studies and clerkship rotations. Moreover, student scores on imaging anatomy examinations demonstrated meaningful improvements in performance after using dynamic images from movies of CT and MRI. Anat Sci Educ. © 2018 American Association of Anatomists. © 2018 American Association of Anatomists.

Calcitriol in Combination Therapy for Prostate Cancer: Pharmacokinetic and Pharmacodynamic Interactions

PubMed Central

Ben-Eltriki, Mohamed; Deb, Subrata; Guns, Emma S. Tomlinson

2016-01-01

Epidemiological studies indicate that vitamin D insufficiency could have an etiological role in prostate cancer. In addition, calcitriol, used in combination with currently available drugs, has the potential to potentiate their anticancer effects or act synergistically by inhibiting distinct mechanisms involved in prostate cancer growth. Clinical data have not yet provided sufficient evidence to demonstrate benefit of vitamin D due to the limited and underpowered studies that have been published to date. Here, we review the preclinical and clinical studies that describe the activity of calcitriol, applied either alone or in combination and assessed the mechanistic basis of pharmacodynamic and pharmacokinetic interactions with calcitriol. Important considerations for calcitriol use in combination therapy with respect to safety and clinical outcomes have been discussed. Many of these combinations have therapeutic potential for the treatment of several cancer types and it is anticipated that future clinical research will put emphasis on well‑designed clinical trials to establish efficacy. PMID:26918053

Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus.

PubMed

Chamberlain, Daniel B; Chamberlain, James M

2017-01-01

We demonstrate the application of a Bayesian approach to a recent negative clinical trial result. A Bayesian analysis of such a trial can provide a more useful interpretation of results and can incorporate previous evidence. This was a secondary analysis of the efficacy and safety results of the Pediatric Seizure Study, a randomized clinical trial of lorazepam versus diazepam for pediatric status epilepticus. We included the published results from the only prospective pediatric study of status in a Bayesian hierarchic model, and we performed sensitivity analyses on the amount of pooling between studies. We evaluated 3 summary analyses for the results: superiority, noninferiority (margin <-10%), and practical equivalence (within ±10%). Consistent with the original study's classic analysis of study results, we did not demonstrate superiority of lorazepam over diazepam. There is a 95% probability that the true efficacy of lorazepam is in the range of 66% to 80%. For both the efficacy and safety outcomes, there was greater than 95% probability that lorazepam is noninferior to diazepam, and there was greater than 90% probability that the 2 medications are practically equivalent. The results were largely driven by the current study because of the sample sizes of our study (n=273) and the previous pediatric study (n=61). Because Bayesian analysis estimates the probability of one or more hypotheses, such an approach can provide more useful information about the meaning of the results of a negative trial outcome. In the case of pediatric status epilepticus, it is highly likely that lorazepam is noninferior and practically equivalent to diazepam. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis.

PubMed

Prijic, Sergej; Buchhorn, Reiner; Kosutic, Jovan; Vukomanovic, Vladislav; Prijic, Andreja; Bjelakovic, Bojko; Zdravkovic, Marija

2014-01-01

Numerous prospective randomized clinical trials demonstrated favorable effect of beta-blockers in adults with chronic heart failure. However, effectiveness of beta blockers in pediatric patients with systemic ventricle systolic dysfunction was not recognized sufficiently. Limited number of pediatric patients might be the course of unrecognized carvediolol treatment benefit. Currently, no meta-analysis has examined the impact of carvedilol and conventional therapy on the clinical outcome in children with chronic heart failure due to impaired systemic ventricle systolic function. We have systematically searched the Medline/PubMed and Cochrane Library for the controlled clinical trials that examine carvedilol and standard treatment efficacy in pediatric patients with systemic ventricle systolic dysfunction. Mean differences for continuous variables, odds ratios for dichotomous outcomes, heterogeneity between studies and publication bias were calculated using Cochrane Review Manager (Rev Man 5.2). Total of 8 prospective/observational studies met established criteria. Odds ratio for chronic heart failure related mortality/heart transplantation secondary to carvedilol was 0.52 (95% CI: 0.28-0.97, I(2) = 0%). Our analysis showed that carvedilol could prevent 1 death/ heart transplantation by treating 14 pediatric patients with impaired systemic ventricle systolic function. Meta-analysis demonstrated clinical outcome benefit of carvedilol in children with chronic heart failure.

[Clinical manifestations of 20 cases of the superior semicircular canal dehiscence syndrome and the intervention strategies].

PubMed

Zhang, X A; Li, Y; Dai, C F

2016-02-01

The objective of this study is to investigate the clinical manifestations of the superior semicircular canal dehiscence syndrome(SSCDS) and the treatment strategies. Data from 20 cases diagnosed with SSCDS from September 2004 to December 2014 were retrospectively analyzed in this study. The clinical presentations including symptoms, signs, audiological and vestibular function examination, and their imaging characteristics and treatment strategies were reviewed. All of the patients demonstrated variable degree of vertigo. Four patients could not tolerate the environmental noise. Autophony was noted in nine cases, among whom, two patients could feel their eye movements and heart beat, one patient could feel his footstep, one patient couldn't endure the singing by himself. Slow component vertical tortional eye movement away from the effected eye were observed in twelve patients when loud noise was given or middle ear or intracranial pressure increased. Head movement was induced by loud noise in one case. Ten patients presented with low frequency hearing loss. One case was concomitance with chronic otitis media and demonstrated severe sensorineural hearing loss. Nine patients demonstrated normal hearing. Decreased thresholds were showed by VEMP examination in six cases. Variable bone defect overlying in the SSCDS was confirmed by CT scans in all of the cases. The surgical repair of the superior semicircular canal dehiscence was performed through the middle cranial fossa approach in three cases and mastoid approach in two cases. The dizziness and the autophony were significantly alleviated after surgery. The clinical manifestations of SSCDS mainly demonstrate dizziness, autophony and loss of low frequency hearing. Treatment strategies are mainly composed of avoidance of environmental noise and shouting voice of the patients themselves. Surgical repair of the superior semicircular canal dehiscence was proposed to conduct, either through the middle cranial fossa approach or mastoid approach, when the patient couldn't tolerate the sypmtoms.

Diagnostic colonoscopy: performance measurement study.

PubMed

Kuznets, Naomi

2002-07-01

This is the fifth of a series of best practices studies undertaken by the Performance Measurement Initiative (PMI), the centerpiece of the Institute for Quality Improvement (IQI), a not-for-profit quality improvement subsidiary of the Accreditation Association for Ambulatory Health Care (AAAHC) (Performance Measurement Initiative, 1999a, 1999b, 2000a, 2000b). The IQI was created to offer clinical performance measurement and improvement opportunities to ambulatory health care organizations and others interested in quality patient care. The purpose of the study was to provide opportunities to initiate clinical performance measurement on key processes and outcomes for this procedure and use this information for clinical quality improvement. This article provides performance measurement information on how organizations that have demonstrated and validated differences in clinical practice can have similar outcomes, but at a dramatically lower cost. The intent of the article is to provide organizations with alternatives in practice to provide a better value to their patients.

Impact of Ischemic Preconditioning on Outcome in Clinical Liver Surgery: A Systematic Review

PubMed Central

Chu, Michael J. J.; Vather, Ryash; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.

2015-01-01

Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery. Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies. Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection. Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC. PMID:25756045

Incidence of postoperative hypothermia and the relationship to clinical variables.

PubMed

Burns, Shari M; Piotrowski, Kathy; Caraffa, Guy; Wojnakowski, Mary

2010-10-01

A prospective, quantitative, correlational study was conducted to determine the incidence of postoperative hypothermia and the relationship of hypothermia to numerous clinical variables previously studied. The study reflects the researchers' interest in updating previous data regarding the incidence of hypothermia. Although hypothermia remains a significant clinical concern, interventions aimed at minimizing hypothermia have evolved over the past 20 years, thus prompting new interest in determining the extent to which hypothermia exists in today's PACU patients. A convenience sample of 287 adult, nonemergency patients scheduled for surgery were included in the study. Hypothermia (temperature <36°C) was demonstrated in only 4% of the sample (N = 287). Because of the low incidence of hypothermia, correlation statistics were not performed. The study provides a foundation for future research regarding this important clinical phenomenon while offering evidence supporting efforts to avoid hypothermia in today's surgical patients. Copyright © 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Shiny FHIR: An Integrated Framework Leveraging Shiny R and HL7 FHIR to Empower Standards-Based Clinical Data Applications.

PubMed

Hong, Na; Prodduturi, Naresh; Wang, Chen; Jiang, Guoqian

2017-01-01

In this study, we describe our efforts in building a clinical statistics and analysis application platform using an emerging clinical data standard, HL7 FHIR, and an open source web application framework, Shiny. We designed two primary workflows that integrate a series of R packages to enable both patient-centered and cohort-based interactive analyses. We leveraged Shiny with R to develop interactive interfaces on FHIR-based data and used ovarian cancer study datasets as a use case to implement a prototype. Specifically, we implemented patient index, patient-centered data report and analysis, and cohort analysis. The evaluation of our study was performed by testing the adaptability of the framework on two public FHIR servers. We identify common research requirements and current outstanding issues, and discuss future enhancement work of the current studies. Overall, our study demonstrated that it is feasible to use Shiny for implementing interactive analysis on FHIR-based standardized clinical data.

eHealth and the use of individually tailored information: A systematic review.

PubMed

Conway, Nicholas; Webster, Clare; Smith, Blair; Wake, Deborah

2017-09-01

Tailored messages are those that specifically target individuals following an assessment of their unique characteristics. This systematic review assesses the evidence regarding the effectiveness of tailoring within eHealth interventions aimed at chronic disease management. OVID Medline/Embase databases were searched for randomised control trials, controlled clinical, trials, before -after studies, and time series analyses from inception - May 2014. Objectively measured clinical processes/outcomes were considered. Twenty-two papers were eligible for inclusion: 6/22 used fully tailored messaging and 16/22 used partially tailored messages. Two studies isolated tailoring as the active component. The remainder compared intervention with standard care. In all, 12/16 studies measuring clinical processes and 2/6 studies reporting clinical outcomes showed improvements, regardless of target group. Study quality was low and design did not allow for identification of interventions' active component. Heterogeneity precluded meta-analysis. This review has demonstrated that there is a lack of evidence to suggest that tailoring within an eHealth context confers benefit over non-tailored eHealth interventions.

Accrued Cost Savings of a Free Clinic Using Quality-Adjusted Life Years Saved and Return on Investment.

PubMed

Sanders, Jim; Lacey, Marcus; Guse, Clare E

2017-01-01

Savings garnered through the provision of preventive services is a form of profit for health systems. Free clinics have been using this logic to demonstrate their cost-savings. The Community-Based Chronic Disease Management (CCDM) clinic treats hypertension using nurse-led teams, clinical protocols, and community-based settings. We calculated CCDM's cost-effectiveness from 2007 to 2013 using 2 metrics: Quality-adjusted life years (QALYs) saved and return on investment (ROI). QALYs were calculated using the Clinical Preventive Burden (CPB) score for hypertension care. ROI was calculated by tallying the savings from prevented heart attacks, strokes, and emergency department visits against the total operating costs. Using conservative assumptions for cost estimates, hypertension care resulted in a value of QALYs saved of $711,000 to $2,133,000 and an ROI ratio range of 0.35 to 1.20. Our study shows that when using conservative assumptions to calculate cost-savings, our free clinic did not save money. Cost-savings did occur, but the amount was modest, was less than that of cost-inputs, and was not likely captured by any single health entity. Although free clinics remain a vital health care access point for many Americans, it has yet to be demonstrated that they generate a net savings. © Copyright 2017 by the American Board of Family Medicine.

Evaluating clinical librarian services: a systematic review.

PubMed

Brettle, Alison; Maden-Jenkins, Michelle; Anderson, Lucy; McNally, Rosalind; Pratchett, Tracey; Tancock, Jenny; Thornton, Debra; Webb, Anne

2011-03-01

  Previous systematic reviews have indicated limited evidence and poor quality evaluations of clinical librarian (CL) services. Rigorous evaluations should demonstrate the value of CL services, but guidance is needed before this can be achieved.   To undertake a systematic review which examines models of CL services, quality, methods and perspectives of clinical librarian service evaluations.   Systematic review methodology and synthesis of evidence, undertaken collaboratively by a group of 8 librarians to develop research and critical appraisal skills.   There are four clear models of clinical library service provision. Clinical librarians are effective in saving health professionals time, providing relevant, useful information and high quality services. Clinical librarians have a positive effect on clinical decision making by contributing to better informed decisions, diagnosis and choice of drug or therapy. The quality of CL studies is improving, but more work is needed on reducing bias and providing evidence of specific impacts on patient care. The Critical Incident Technique as part of a mixed method approach appears to offer a useful approach to demonstrating impact.   This systematic review provides practical guidance regarding the evaluation of CL services. It also provides updated evidence regarding the effectiveness and impact of CL services. The approach used was successful in developing research and critical appraisal skills in a group of librarians. © 2010 The authors. Health Information and Libraries Journal © 2010 Health Libraries Group.

Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) Study: Methodology and Baseline Characteristics of a Randomized Controlled Trial Evaluating an Occupation-Based Diabetes Management Intervention for Young Adults

PubMed Central

Pyatak, Elizabeth A.; Carandang, Kristine; Vigen, Cheryl; Blanchard, Jeanine; Sequeira, Paola A.; Wood, Jamie R.; Spruijt-Metz, Donna; Whittemore, Robin; Peters, Anne L.

2017-01-01

Overview This paper describes the study protocol used to evaluate the Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) intervention and reports on baseline characteristics of recruited participants. REAL Diabetes is an activity-based intervention designed to address the needs of young adults diagnosed with type 1 (T1D) or type 2 diabetes (T2D) from low socioeconomic status or racial/ethnic minority backgrounds. The REAL intervention incorporates tailored delivery of seven content modules addressing various dimensions of health and well-being as they relate to diabetes, delivered by a licensed occupational therapist. Methods In this pilot randomized controlled trial, participants are assigned to the REAL Diabetes intervention or an attention control condition. The study’s primary recruitment strategies included in-person recruitment at diabetes clinics, mass mailings to clinic patients, and social media advertising. Data collection includes baseline and 6-month assessments of primary outcomes, secondary outcomes, and hypothesized mediators of intervention effects, as well as ongoing process evaluation assessment to ensure study protocol adherence and intervention fidelity. Results At baseline, participants (n=81) were 51% female, 78% Latino, and on average 22.6 years old with an average HbA1c of 10.8%. A majority of participants (61.7%) demonstrate clinically significant diabetes distress and 27.2% report symptoms consistent with major depressive disorder. Compared to participants with T1D, participants with T2D had lower diabetes-related self-efficacy and problem-solving skills. Compared to participants recruited at clinics, participants recruited through other strategies had greater diabetes knowledge but weaker medication adherence. Discussion Participants in the REAL study demonstrate clinically significant medical and psychosocial needs. PMID:28064028

Nutritional Management of Metabolic Endotoxemia: A Clinical Review.

PubMed

Brown, Benjamin I

2017-07-01

Context • Diet-induced, metabolic endotoxemia is emerging as an important contributory factor to the development of a wide range of chronic diseases, including cardiometabolic, autoimmune, psychiatric, and neurodegenerative illnesses. Emerging human clinical studies have demonstrated that diet and dietary components are potent modifiers of circulating endotoxins and can be used to reduce plasma levels significantly and improve metabolic health. Objective • The aim of the current study was to explore briefly the concept of metabolic endotoxemia and its relationship to disease development, to examine the influence of diet and dietary components on circulating endotoxins, and, finally, discuss the clinical relevance of nutritional interventions for management of metabolic endotoxemia. Design • The researcher performed a literature review of dietary and nutritional interactions with metabolic endotoxemia with a focus on studies relevant to clinical practice. Setting • The study took place at the UK College of Nutrition and Health (London, England). Results • Improving dietary quality, optimizing the intake of phytonutrient-rich foods, improving micronutrient status, consuming fermented foods, manipulating the gut microflora with prebiotics and probiotics, and using specific nutritional supplements, such as glutamine, lactoferrin, resveratrol, and berberine, have been shown to be effective in targeting metabolic endotoxemia. Conclusions • Diet, dietary components, and nutritional supplements, including prebiotics and probiotics, have demonstrated the ability to provide clinically important reductions in circulating endotoxins and improve related sequels, such as inflammation and other negative health markers. The development of personalized nutritional interventions for the management of metabolic endotoxemia is a promising area for future research due to the potential of such interventions to improve multiple aspects of human health and mitigate a wide range of chronic diseases.

Testing the effects of educational toilet posters: a novel way of reducing haemolysis of blood samples within ED.

PubMed

Corkill, David

2012-02-01

Haemolysed blood samples are an unnecessary burden on Emergency Departments (ED) as they increase workloads and drive down efficiencies. Little empirical data exists that demonstrates the effectiveness of educational posters displayed in staff toilet cubicles. This study explored the impact educational toilet posters have on reducing haemolysis rates within the ED. A time series study of the clinical effect of educational toilet posters on reducing haemolysis rates throughout a 12 month period at the Gold Coast Hospital ED was undertaken. The GCH ED is a tertiary emergency service that has approximately 66,000 patient presentations per year. Data was collected prospectively. Analysis was undertaken to investigate the effects on total number of haemolysed samples and those clinically significant samples with a haemolytic index >3. Further investigation explored the specific effects on medical and nursing staff. Analysis undertaken using an independent t-test found that the pre-intervention data demonstrates a medium haemolysis rate of 4.92% (SD=1.04). This is a statistically significantly different (t=3.56, df=50, p=0.001) from the median post intervention data of 3.95% (SD=0.84). The difference of 0.97% (95%CI=0.42, 1.52) represents a 19.72% reduction in clinically significant haemolysed samples over the study period. This study reveals that the use of educational toilet posters had a positive impact on reducing the rates of haemolysed samples collected within the ED. This simple and cost effective educational initiative changed the behaviour of clinical staff. Further investigation is warranted to examine the impact of educational toilet posters on additional clinical scenarios. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease.

PubMed

Galiè, Nazzareno; Denton, Christopher P; Dardi, Fabio; Manes, Alessandra; Mazzanti, Gaia; Li, Baohui; Varanese, Lucio; Esler, Anne; Harmon, Cathi; Palazzini, Massimiliano

2017-05-15

The primary objective of this post hoc analysis was to evaluate clinical outcomes of tadalafil in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD-PAH) compared with patients with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy endpoints, and safety. This analysis included adult patients with CTD-PAH or I/H-PAH who participated in the PHIRST and PHIRST-2 studies. Patients were randomized 1:1:1:1:1 to tadalafil (2.5, 10, 20, or 40mg) or placebo in the PHIRST study and the majority of these patients were subsequently assigned 40mg in PHIRST-2. Patients taking 20mg in PHIRST without demonstrating clinical worsening continued on 20mg in PHIRST-2. Outcomes analyzed included 6MWD, WHO-FC, and incidence and time to first occurrence of clinical worsening. Safety was assessed through evaluation of adverse events (AEs), clinical laboratory data, electrocardiograms, and physical examinations. Increased 6MWD in PHIRST was maintained in both CTD-PAH and I/H-PAH subgroups for 52weeks. Patients with CTD-PAH tended to be older, were more likely female, had lower exercise capacity, were more likely to have clinical worsening, and experienced AEs more frequently than patients with I/H-PAH. The effect of tadalafil treatment in patients enrolled in both PHIRST studies was detectable for both I/H-PAH and CTD-PAH subgroups. In general, subgroup differences were modest. Patients with CTD-PAH may perform less well than patients with I/H-PAH in safety and efficacy measures in all treatment groups, which is similar to other studies demonstrating a worse prognosis for patients with CTD-PAH. Copyright © 2017. Published by Elsevier B.V.

Evaluation of nursing students' communication abilities in clinical courses in hospitals.

PubMed

Shafakhah, Mahnaz; Zarshenas, Ladan; Sharif, Farkhondeh; Sabet Sarvestani, Raheleh

2015-01-26

Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has established, improving communication as a priority for improving patient safety since 2006. Therefore, the present study aimed to evaluate nursing students' communication abilities to recognize their strengths and weaknesses in communication skills. This cross-sectional study was carried out in 2014. The study participants included all the nursing students who passed two semesters in Fatemeh School of Nursing and Midwifery in Shiraz, Iran. The students' communication skills were assessed using a self-administered questionnaire. Then, the data were entered into the SPSS statistical software (v. 16) and analyzed using both descriptive (mean and percentage) and inferential statistics (Pearson correlation and ANOVA). Among the 200 students who completed the questionnaires, 58% were female and 42% were male with the mean age of 21.79 years (SD=2.14). The results of Pearson correlation analysis demonstrated a significant correlation between the nursing students' clinical communication behavior scores and treatment communication ability scores (P<0.001). The findings demonstrated that most nursing students required improvement in their communication skills in both clinical communication behavior and treatment communication ability. Besides, a significant difference was observed among the students of different terms regarding clinical communication behaviors (P?0.05), but not concerning communication abilities. Nursing students in higher semesters had better communication skills. The results showed that nursing students in this university had a moderate ability in clinical and treatment communication. Thus, paying attention to standard education, curriculum revision, and adding some specific theoretical lessons for improving communication skills are mandatory during the bachelor's degree.

The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

PubMed

Staudacher, Heidi M; Whelan, Kevin

2017-08-01

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mechanical Stimulation (Pulsed Electromagnetic Fields “PEMF” and Extracorporeal Shock Wave Therapy “ESWT”) and Tendon Regeneration: A Possible Alternative

PubMed Central

Rosso, Federica; Bonasia, Davide E.; Marmotti, Antonio; Cottino, Umberto; Rossi, Roberto

2015-01-01

The pathogenesis of tendon degeneration and tendinopathy is still partially unclear. However, an active role of metalloproteinases (MMP), growth factors, such as vascular endothelial growth factor (VEGF) and a crucial role of inflammatory elements and cytokines was demonstrated. Mechanical stimulation may play a role in regulation of inflammation. In vitro studies demonstrated that both pulsed electromagnetic fields (PEMF) and extracorporeal shock wave therapy (ESWT) increased the expression of pro-inflammatory cytokine such as interleukin (IL-6 and IL-10). Moreover, ESWT increases the expression of growth factors, such as transforming growth factor β(TGF-β), (VEGF), and insulin-like growth factor 1 (IGF1), as well as the synthesis of collagen I fibers. These pre-clinical results, in association with several clinical studies, suggest a potential effectiveness of ESWT for tendinopathy treatment. Recently PEMF gained popularity as adjuvant for fracture healing and bone regeneration. Similarly to ESWT, the mechanical stimulation obtained using PEMFs may play a role for treatment of tendinopathy and for tendon regeneration, increasing in vitro TGF-β production, as well as scleraxis and collagen I gene expression. In this manuscript the rational of mechanical stimulations and the clinical studies on the efficacy of extracorporeal shock wave (ESW) and PEMF will be discussed. However, no clear evidence of a clinical value of ESW and PEMF has been found in literature with regards to the treatment of tendinopathy in human, so further clinical trials are needed to confirm the promising hypotheses concerning the effectiveness of ESWT and PEMF mechanical stimulation. PMID:26617513

Preliminary results of miniaturized and robust ultrasound guided diffuse optical tomography system for breast cancer detection

NASA Astrophysics Data System (ADS)

Vavadi, Hamed; Mostafa, Atahar; Li, Jinglong; Zhou, Feifei; Uddin, Shihab; Xu, Chen; Zhu, Quing

2017-02-01

According to the World Health Organization, breast cancer is the most common cancer among women worldwide, claiming the lives of hundreds of thousands of women each year. Near infrared diffuse optical tomography (DOT) has demonstrated a great potential as an adjunct modality for differentiation of malignant and benign breast lesions and for monitoring treatment response of patients with locally advanced breast cancers. The path toward commercialization of DOT techniques depends upon the improvement of robustness and user-friendliness of this technique in hardware and software. In the past, our group have developed three frequency domain prototype systems which were used in several clinical studies. In this study, we introduce our newly under development US-guided DOT system which is being improved in terms of size, robustness and user friendliness by several custom electronic and mechanical design. A new and robust probe designed to reduce preparation time in clinical process. The processing procedure, data selection and user interface software also updated. With all these improvements, our new system is more robust and accurate which is one step closer to commercialization and wide use of this technology in clinical settings. This system is aimed to be used by minimally trained user in the clinical settings with robust performance. The system performance has been tested in the phantom experiment and initial results are demonstrated in this study. We are currently working on finalizing this system and do further testing to validate the performance of this system. We are aiming toward use of this system in clinical setting for patients with breast cancer.

77 FR 37059 - Draft Guidance for Industry on Active Controls in Studies To Demonstrate Effectiveness of a New...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0419... who conduct studies using active controls and have a basic understanding of statistical principles... clinical investigators who conduct studies using active controls and have a basic understanding of...

Clinical audit, a valuable tool to improve quality of care: General methodology and applications in nephrology

PubMed Central

Esposito, Pasquale; Dal Canton, Antonio

2014-01-01

Evaluation and improvement of quality of care provided to the patients are of crucial importance in the daily clinical practice and in the health policy planning and financing. Different tools have been developed, including incident analysis, health technology assessment and clinical audit. The clinical audit consist of measuring a clinical outcome or a process, against well-defined standards set on the principles of evidence-based medicine in order to identify the changes needed to improve the quality of care. In particular, patients suffering from chronic renal diseases, present many problems that have been set as topics for clinical audit projects, such as hypertension, anaemia and mineral metabolism management. Although the results of these studies have been encouraging, demonstrating the effectiveness of audit, overall the present evidence is not clearly in favour of clinical audit. These findings call attention to the need to further studies to validate this methodology in different operating scenarios. This review examines the principle of clinical audit, focusing on experiences performed in nephrology settings. PMID:25374819

Hyperbaric oxygen therapy and preconditioning for ischemic and hemorrhagic stroke.

PubMed

Hu, Sheng-Li; Feng, Hua; Xi, Guo-Hua

2016-01-01

To date, the therapeutic methods for ischemic and hemorrhagic stroke are still limited. The lack of oxygen supply is critical for brain injury following stroke. Hyperbaric oxygen (HBO), an approach through a process in which patients breathe in 100% pure oxygen at over 101 kPa, has been shown to facilitate oxygen delivery and increase oxygen supply. Hence, HBO possesses the potentials to produce beneficial effects on stroke. Actually, accumulated basic and clinical evidences have demonstrated that HBO therapy and preconditioning could induce neuroprotective functions via different mechanisms. Nevertheless, the lack of clinical translational study limits the application of HBO. More translational studies and clinical trials are needed in the future to develop effective HBO protocols.

Could home sexually transmitted infection specimen collection with e-prescription be a cost-effective strategy for clinical trials and clinical care?

PubMed

Blake, Diane R; Spielberg, Freya; Levy, Vivian; Lensing, Shelly; Wolff, Peter A; Venkatasubramanian, Lalitha; Acevedo, Nincoshka; Padian, Nancy; Chattopadhyay, Ishita; Gaydos, Charlotte A

2015-01-01

Results of a recent demonstration project evaluating feasibility, acceptability, and cost of a Web-based sexually transmitted infection (STI) testing and e-prescription treatment program (eSTI) suggest that this approach could be a feasible alternative to clinic-based testing and treatment, but the results need to be confirmed by a randomized comparative effectiveness trial. We modeled a decision tree comparing (1) cost of eSTI screening using a home collection kit and an e-prescription for uncomplicated treatment versus (2) hypothetical costs derived from the literature for referral to standard clinic-based STI screening and treatment. Primary outcome was number of STIs detected. Analyses were conducted from the clinical trial perspective and the health care system perspective. The eSTI strategy detected 75 infections, and the clinic referral strategy detected 45 infections. Total cost of eSTI was $94,938 ($1266/STI detected) from the clinical trial perspective and $96,088 ($1281/STI detected) from the health care system perspective. Total cost of clinic referral was $87,367 ($1941/STI detected) from the clinical trial perspective and $71,668 ($1593/STI detected) from the health care system perspective. Results indicate that eSTI will likely be more cost-effective (lower cost/STI detected) than clinic-based STI screening, both in the context of clinical trials and in routine clinical care. Although our results are promising, they are based on a demonstration project and estimates from other small studies. A comparative effectiveness research trial is needed to determine actual cost and impact of the eSTI system on identification and treatment of new infections and prevention of their sequelae.

Location of residence associated with the likelihood of patient visit to the preoperative assessment clinic

PubMed Central

Seidel, Judy E; Beck, Cynthia A; Pocobelli, Gaia; Lemaire, Jane B; Bugar, Jennifer M; Quan, Hude; Ghali, William A

2006-01-01

Background Outpatient preoperative assessment clinics were developed to provide an efficient assessment of surgical patients prior to surgery, and have demonstrated benefits to patients and the health care system. However, the centralization of preoperative assessment clinics may introduce geographical barriers to utilization that are dependent on where a patient lives with respect to the location of the preoperative assessment clinic. Methods The association between geographical distance from a patient's place of residence to the preoperative assessment clinic, and the likelihood of a patient visit to the clinic prior to surgery, was assessed for all patients undergoing surgery at a tertiary health care centre in a major Canadian city. The odds of attending the preoperative clinic were adjusted for patient characteristics and clinical factors. Results Patients were less likely to visit the preoperative assessment clinic prior to surgery as distance from the patient's place of residence to the clinic increased (adjusted OR = 0.52, 95% CI 0.44–0.63 for distances between 50–100 km, and OR = 0.26, 95% CI 0.21–0.31 for distances greater than 250 km). This 'distance decay' effect was remarkable for all surgical specialties. Conclusion The present study demonstrates that the likelihood of a patient visiting the preoperative assessment clinic appears to depend on the geographical location of patients' residences. Patients who live closest to the clinic tend to be seen more often than patients who live in rural and remote areas. This observation may have implications for achieving the goals of equitable access, and optimal patient care and resource utilization in a single universal insurer health care system. PMID:16504058

Emotional intelligence, performance, and retention in clinical staff nurses.

PubMed

Codier, Estelle; Kamikawa, Cindy; Kooker, Barbara M; Shoultz, Jan

2009-01-01

Emotional intelligence has been correlated with performance, retention, and organizational commitment in professions other than nursing. A 2006 pilot study provided the first evidence of a correlation between emotional intelligence and performance in clinical staff nurses. A follow-up study was completed, the purpose of which was to explore emotional intelligence, performance level, organizational commitment, and retention. A convenience sample of 350 nurses in a large medical center in urban Hawaii participated in this study. This article reports the findings pertaining to the subset of 193 clinical staff nurses who responded. The Mayer-Salovey-Caruso Emotional Intelligence Test instrument was used to measure emotional intelligence abilities. Performance was defined as ranking on a clinical ladder. Commitment was scored on a Likert scale. The following variables measured retention: total years in nursing, years in current job, total years anticipated in current job, and total anticipated career length. Emotional intelligence scores in clinical staff nurses correlated positively with both performance level and retention variables. Clinical staff nurses with higher emotional intelligence scores demonstrated higher performance, had longer careers, and greater job retention.

The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

PubMed Central

2013-01-01

Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral responses. Serial FMAERs may be useful for tracking language change in LKS. Cortical FMAERs may augment invasive cortical language testing in epilepsy surgical patients. The FMAER may be normal in ASD and other language disorders when pathology spares the superior temporal gyrus and surround but presumably involves other brain regions. Ear/mastoid reference electrodes should be avoided and multichannel, reference free recordings utilized. Source analysis may assist in better understanding of complex FMAER findings. PMID:23351174

Convergent validity of actigraphy with polysomnography and parent reports when measuring sleep in children with Down syndrome.

PubMed

Esbensen, A J; Hoffman, E K; Stansberry, E; Shaffer, R

2018-04-01

There is a need for rigorous measures of sleep in children with Down syndrome as sleep is a substantial problem in this population and there are barriers to obtaining the gold standard polysomnography (PSG). PSG is cost-prohibitive when measuring treatment effects in some clinical trials, and children with Down syndrome may not cooperate with undergoing a PSG. Minimal information is available on the validity of alternative methods of assessing sleep in children with Down syndrome, such as actigraphy and parent ratings. Our study examined the concurrent and convergent validity of different measures of sleep, including PSG, actigraphy and parent reports of sleep among children with Down syndrome. A clinic (n = 27) and a community (n = 47) sample of children with Down syndrome were examined. In clinic, children with Down syndrome wore an actigraph watch during a routine PSG. In the community, children with Down syndrome wore an actigraph watch for a week at home at night as part of a larger study on sleep and behaviour. Their parent completed ratings of the child's sleep during that same week. Actigraph watches demonstrated convergent validity with PSG when measuring a child with Down syndrome's total amount of sleep time, total wake time after sleep onset and sleep period efficiency. In contrast, actigraph watches demonstrated poor correlations with parent reports of sleep, and with PSG when measuring the total time in bed and total wake episodes. Actigraphy, PSG and parent ratings of sleep demonstrated poor concurrent validity with clinical diagnosis of obstructive sleep apnoea. Our current data suggest that actigraph watches demonstrate convergent validity and are sensitive to measuring certain sleep constructs (duration, efficiency) in children with Down syndrome. However, parent reports, such as the Children's Sleep Habits Questionnaire, may be measuring other sleep constructs. These findings highlight the importance of selecting measures of sleep related to target concerns. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Use of Flowchart for Automation of Clinical Protocols in mHealth.

PubMed

Dias, Karine Nóra; Welfer, Daniel; Cordeiro d'Ornellas, Marcos; Pereira Haygert, Carlos Jesus; Dotto, Gustavo Nogara

2017-01-01

For healthcare professionals to use mobile applications we need someone who knows software development, provide them. In healthcare institutions, health professionals use clinical protocols to govern care, and sometimes these documents are computerized through mobile applications to assist them. This work aims to present a proposal of an application of flow as a way of describing clinical protocols for automatic generation of mobile applications to assist health professionals. The purpose of this research is to enable health professionals to develop applications from the description of their own clinical protocols. As a result, we developed a web system that automates clinical protocols for an Android platform, and we validated with two clinical protocols used in a Brazilian hospital. Preliminary results of the developed architecture demonstrate the feasibility of this study.

Effect of magnesium supplementation on insulin resistance in humans: A systematic review.

PubMed

Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; de Alencar, Geórgia Rosa Reis; de Oliveira, Ana Raquel Soares; Cruz, Kyria Jayanne Clímaco; Marreiro, Dilina do Nascimento; Freitas, Betânia de Jesus E Silva de Almendra; de Carvalho, Cecília Maria Resende; Martins, Maria do Carmo de Carvalho E; Frota, Karoline de Macedo Gonçalves

2017-06-01

Recent studies have demonstrated that minerals play a role in glucose metabolism disorders in humans. Magnesium, in particular, is an extensively studied mineral that has been shown to function in the management of hyperglycemia, hyperinsulinemia, and insulin resistance (IR) action. The aim of this study was to investigate the effect of magnesium supplementation on IR in humans via systematic review of the available clinical trials. This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. A survey was conducted to select clinical trials related to the effects of this mineral in insulin sensitivity using the following databases: PubMed, SciVerse Scopus, ScienceDirect, and SciVerse Cochrane. After the selection process, 12 articles were identified as eligible, representing different clinical conditions and being free of restriction with regard to sex, age, ethnicity, and differential dosing/shape of magnesium. The results of eight clinical trials showed that supplementation with magnesium influences serum fasting glucose concentrations, and five trials determined an effect on fasting insulin levels. The results of seven studies demonstrated that mineral supplementation reduced homeostasis model assessment for IR values. The data of this systematic review provide evidence as to the benefits of magnesium supplementation in reducing IR in patients with hypomagnesemia presenting IR. However, new intervention studies are needed to elucidate the role of the nutrient in protection against this metabolic disorder, as well as the standardization of the type, dose, and time of magnesium supplementation. Copyright © 2017 Elsevier Inc. All rights reserved.

Brillouin microscopy: assessing ocular tissue biomechanics.

PubMed

Yun, Seok Hyun; Chernyak, Dimitri

2018-07-01

Assessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. Many researchers and clinicians have identified corneal biomechanics as source of variability in refractive procedures and one of the main factors in keratoconus. However, it has been difficult to accurately characterize corneal biomechanics in patients. The recent development of Brillouin light scattering microscopy heightens the promise of bringing biomechanics into the clinic. The aim of this review is to overview the progress and discuss prospective applications of this new technology. Brillouin microscopy uses a low-power near-infrared laser beam to determine longitudinal modulus or mechanical compressibility of tissue by analyzing the return signal spectrum. Human clinical studies have demonstrated significant difference in the elastic properties of normal corneas versus corneas diagnosed with mild and severe keratoconus. Clinical data have also shown biomechanical changes after corneal cross-linking treatment of keratoconus patients. Brillouin measurements of the crystalline lens and sclera have also been demonstrated. Brillouin microscopy is a promising technology under commercial development at present. The technique enables physicians to characterize the biomechanical properties of ocular tissues.

Accuracy of computer-guided surgery for dental implant placement in fully edentulous patients: A systematic review

PubMed Central

Marlière, Daniel Amaral Alves; Demétrio, Maurício Silva; Picinini, Leonardo Santos; De Oliveira, Rodrigo Guerra; Chaves Netto, Henrique Duque De Miranda

2018-01-01

Assess clinical studies regarding accuracy between virtual planning of computer-guided surgery and actual outcomes of dental implant placements in total edentulous alveolar ridges. A PubMed search was performed to identify only clinical studies published between 2011 and 2016, searching the following combinations of keywords: “Accuracy AND Computer-Assisted Surgery AND Dental Implants.” Study designs were identified using the terms: Case Reports, Clinical study, Randomized Controlled Trial, Systematic Reviews, Meta-Analysis, humans. Level of agreement between the authors in the study selection process was substantial (k = 0.767), and the study eligibility was considered excellent (k = 0.863). Seven articles were included in this review. They describe the use of bone and muco-supported guides, demonstrating angular deviations cervically and apically ranging from (minimum and maximum means), respectively, 1.85–8.4 (°), 0.17–2.17 (mm), and 0.77–2.86 (mm). Angular deviations obtained most inaccuracy in maxila. For cervical and apical deviations, accuracy was preponderantly lower in maxilla. Despite the similar deviations measurement approaches described, clinical relevance of this study may be useful to warn the surgeon that safety margins in clinical situations. PMID:29657542

Clinical comparison and performance perspective of three aligning arch wires.

PubMed

Evans, T J; Jones, M L; Newcombe, R G

1998-07-01

To clinically evaluate three commonly used orthodontic tooth aligning arch wires: 016 x 022 inch active martensitic medium force nickel titanium, 016 x 022 inch graded force active martensitic nickel titanium, and 0.0155 inch multistrand stainless steel. A prospective randomized clinical trial. Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients. Analysis based on completed records for 98 arch wires and 51 patients. A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were randomly allocated two different arch wires from a possible three under trial. Good quality impressions were taken of the dental arches at the designated serial stages of alignment (start, T0; 4 weeks, T4; 8 weeks, T8). The resultant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions (horizontal plane only). The measurement error was within acceptable limits (range, 0.05 to 0.09 mm) and showed no significant bias. ANOVA statistical models were fitted to the data to adjust for a number of variables. No significant difference in aligning capability (p > 0.05), in either two or three dimensions, was demonstrated between the three arch wires in the trial. Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistrand stainless steel wires in this randomized clinical trial. The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response. Alternatively, it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment.

Translational Immuno- and Neuro-imaging Demonstrate Corneal Neuro-immune Crosstalk

PubMed Central

Hamrah, Pedram; Seyed-Razavi, Yashar; Yamaguchi, Takefumi

2017-01-01

Corneal immuno- and neuro-imaging approaches facilitate in vivo analyses of the cornea, including high-resolution imaging of corneal immune cells and nerves. This approach facilitates the analyses of underlying immune and nerve alterations not detected by clinical slit-lamp examination alone. In this review, we describe recent work performed in our translational ocular immunology center with a focus on ‘bench-to-bedside’ and ‘bedside-to-bench’ research. The ability to visualize dendritiform immune cells (DCs) in patients with laser in vivo confocal microscopy (IVCM), recently discovered in the central murine cornea, has allowed us to demonstrated their utility as a potential surrogate biomarker for inflammatory ocular surface diseases. This biomarker for inflammation allows the measurement of therapeutic efficacy of anti-inflammatory drugs and its utility as an endpoint in clinical trials with high inter-observer agreement. IVCM image analyses from our studies demonstrated a significant increase in DC density and size in ocular disease, a positive correlation between DC density and clinical signs and symptoms of disease and pro-inflammatory tear cytokines, and a strong negative correlation between DC density and subbasal nerve density. In conjunction with pre-clinical research investigating the inflammatory state in a partial or fully denervated cornea, our results indicated that corneal nerves are directly involved in the regulation of homeostasis and immune privilege in the cornea. PMID:27631352

Rasagiline: A second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease.

PubMed

Chen, Jack J; Ly, Anh-Vuong

2006-05-15

The pharmacology, pharmacokinetics, clinical efficacy, and safety of rasagiline are reviewed. Rasagiline is a novel, investigational propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). Rasagiline demonstrates complete and selective inhibition of MAO-B and is at least five times more potent than selegiline. Unlike selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to the nonamphetamine compound aminoindan. Clinical studies have revealed that rasagiline is associated with improved outcomes in patients with early Parkinson's disease (PD) and also reduces "off" time in patients with moderate to advanced PD with motor fluctuations. Rasagiline is rapidly absorbed by the gastrointestinal tract and readily crosses the blood-brain barrier. The optimal therapeutic dosage is 0.5-1 mg administered orally once daily. Rasagiline appears to be well tolerated, although elderly patients may be more prone to treatment-emergent adverse cardiovascular and psychiatric effects. At the recommended therapeutic dosage of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, rasagiline has demonstrated neuroprotective properties in experimental laboratory models. The mechanisms whereby rasagiline exerts neuroprotective effects are multifactorial and include upregulation of cellular antioxidant activity and antiapoptotic factors. Rasagiline is an investigational selective and irreversible inhibitor of MAO-B that has demonstrated efficacy and safety for the treatment of PD. Whether rasagiline is associated with clinically significant neuroprotection is the subject of ongoing clinical trials.

Integration in primary community care networks (PCCNs): examination of governance, clinical, marketing, financial, and information infrastructures in a national demonstration project in Taiwan

PubMed Central

Lin, Blossom Yen-Ju

2007-01-01

Background Taiwan's primary community care network (PCCN) demonstration project, funded by the Bureau of National Health Insurance on March 2003, was established to discourage hospital shopping behavior of people and drive the traditional fragmented health care providers into cooperate care models. Between 2003 and 2005, 268 PCCNs were established. This study profiled the individual members in the PCCNs to study the nature and extent to which their network infrastructures have been integrated among the members (clinics and hospitals) within individual PCCNs. Methods The thorough questionnaire items, covering the network working infrastructures – governance, clinical, marketing, financial, and information integration in PCCNs, were developed with validity and reliability confirmed. One thousand five hundred and fifty-seven clinics that had belonged to PCCNs for more than one year, based on the 2003–2005 Taiwan Primary Community Care Network List, were surveyed by mail. Nine hundred and twenty-eight clinic members responded to the surveys giving a 59.6 % response rate. Results Overall, the PCCNs' members had higher involvement in the governance infrastructure, which was usually viewed as the most important for establishment of core values in PCCNs' organization design and management at the early integration stage. In addition, it found that there existed a higher extent of integration of clinical, marketing, and information infrastructures among the hospital-clinic member relationship than those among clinic members within individual PCCNs. The financial infrastructure was shown the least integrated relative to other functional infrastructures at the early stage of PCCN formation. Conclusion There was still room for better integrated partnerships, as evidenced by the great variety of relationships and differences in extent of integration in this study. In addition to provide how the network members have done for their initial work at the early stage of network forming in this study, the detailed surveyed items, the concepts proposed by the managerial and theoretical professionals, could be a guide for those health care providers who have willingness to turn their business into multi-organizations. PMID:17577422

Integration in primary community care networks (PCCNs): examination of governance, clinical, marketing, financial, and information infrastructures in a national demonstration project in Taiwan.

PubMed

Lin, Blossom Yen-Ju

2007-06-19

Taiwan's primary community care network (PCCN) demonstration project, funded by the Bureau of National Health Insurance on March 2003, was established to discourage hospital shopping behavior of people and drive the traditional fragmented health care providers into cooperate care models. Between 2003 and 2005, 268 PCCNs were established. This study profiled the individual members in the PCCNs to study the nature and extent to which their network infrastructures have been integrated among the members (clinics and hospitals) within individual PCCNs. The thorough questionnaire items, covering the network working infrastructures--governance, clinical, marketing, financial, and information integration in PCCNs, were developed with validity and reliability confirmed. One thousand five hundred and fifty-seven clinics that had belonged to PCCNs for more than one year, based on the 2003-2005 Taiwan Primary Community Care Network List, were surveyed by mail. Nine hundred and twenty-eight clinic members responded to the surveys giving a 59.6 % response rate. Overall, the PCCNs' members had higher involvement in the governance infrastructure, which was usually viewed as the most important for establishment of core values in PCCNs' organization design and management at the early integration stage. In addition, it found that there existed a higher extent of integration of clinical, marketing, and information infrastructures among the hospital-clinic member relationship than those among clinic members within individual PCCNs. The financial infrastructure was shown the least integrated relative to other functional infrastructures at the early stage of PCCN formation. There was still room for better integrated partnerships, as evidenced by the great variety of relationships and differences in extent of integration in this study. In addition to provide how the network members have done for their initial work at the early stage of network forming in this study, the detailed surveyed items, the concepts proposed by the managerial and theoretical professionals, could be a guide for those health care providers who have willingness to turn their business into multi-organizations.

A metadata approach for clinical data management in translational genomics studies in breast cancer.

PubMed

Papatheodorou, Irene; Crichton, Charles; Morris, Lorna; Maccallum, Peter; Davies, Jim; Brenton, James D; Caldas, Carlos

2009-11-30

In molecular profiling studies of cancer patients, experimental and clinical data are combined in order to understand the clinical heterogeneity of the disease: clinical information for each subject needs to be linked to tumour samples, macromolecules extracted, and experimental results. This may involve the integration of clinical data sets from several different sources: these data sets may employ different data definitions and some may be incomplete. In this work we employ semantic web techniques developed within the CancerGrid project, in particular the use of metadata elements and logic-based inference to annotate heterogeneous clinical information, integrate and query it. We show how this integration can be achieved automatically, following the declaration of appropriate metadata elements for each clinical data set; we demonstrate the practicality of this approach through application to experimental results and clinical data from five hospitals in the UK and Canada, undertaken as part of the METABRIC project (Molecular Taxonomy of Breast Cancer International Consortium). We describe a metadata approach for managing similarities and differences in clinical datasets in a standardized way that uses Common Data Elements (CDEs). We apply and evaluate the approach by integrating the five different clinical datasets of METABRIC.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

PubMed

van der Valk, Johanna P M; Gerth van Wijk, Roy; Dubois, Anthony E J; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F J; Wichers, Harry J; de Jong, Nicolette W

2016-01-01

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. www.ncbi.nlm.nih.gov/pubmed NTR3572.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

PubMed Central

van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

2016-01-01

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572 PMID:26967158

High performance communication by people with paralysis using an intracortical brain-computer interface.

PubMed

Pandarinath, Chethan; Nuyujukian, Paul; Blabe, Christine H; Sorice, Brittany L; Saab, Jad; Willett, Francis R; Hochberg, Leigh R; Shenoy, Krishna V; Henderson, Jaimie M

2017-02-21

Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O'Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4-4.2) and information throughput (by a factor of 2.2-4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function.Clinical Trial No: NCT00912041.

The periodontal abscess (II). Short-term clinical and microbiological efficacy of 2 systemic antibiotic regimes.

PubMed

Herrera, D; Roldán, S; O'Connor, A; Sanz, M

2000-06-01

The aim of this short-term open parallel longitudinal clinical study was to compare the clinical and microbiological efficacy of 2 different antibiotic regimes in the treatment of acute periodontal abscesses. After patient selection, a clinical examination was carried out recording the following variables: pain, edema, redness, swelling, bleeding on probing, suppuration, tooth mobility, lymphadenopathy, and probing pocket depth. Microbiological samples were taken from the lesion and the patient was randomly assigned to one of two antibiotic regimes: azithromycin or amoxicillin/clavulanate. Clinical variables were recorded, and microbiological samples were taken, at 3-5 days, 10-12 days and 30 days. Additional mechanical treatment (debridement and scaling) was performed in the third visit (10-12 days). Blood and urine samples were collected at baseline and after 10-12 days. Microbiological samples were processed by anaerobic culturing, and isolated periodontal pathogens were tested for antibiotic susceptibility by means of the spiral gradient endpoint methodology. 15 patients took azithromycin, and 14 amoxicillin/clavulanate. Subjective clinical variables demonstrated statistically significant improvements with both antibiotic regimes, which lasted for at least 1 month (p<0.01). Objective clinical variables also showed clear improvements, being statistically significant after 30 days with probing pocket depth in the azithromycin group (p<0.01). Microbiologically, short-term reductions were detected with both antibiotics, however fast recolonization occurred after the third visit. No significant differences were found between both treatment regimes. Antibiotic susceptibilities demonstrated no resistances for amoxicillin/clavulanate, while 2-3 strains of each studied pathogen were resistant to azithromycin. However, both antibiotic regimes were effective in the short-term treatment of periodontal abscesses in periodontitis patients.

Topically delivered dissolved oxygen reduces inflammation and positively influences structural proteins in healthy intact human skin.

PubMed

Kellar, Robert S; Audet, Robert G; Roe, David F; Rheins, Lawrence A; Draelos, Zoe Diana

2013-06-01

As oxygen is essential for wound healing and there is limited diffusion across the stratum corneum into the epidermis, we wanted to evaluate whether the topical delivery of a total dissolved oxygen in dressing form on intact human subject skin would improve clinical and histologic skin functioning. Fifty normal, healthy subjects completed a pilot clinical evaluation to assess the efficacy and tolerability of a dissolved oxygen dressing (OxygeneSys™-Continuous) to improve the health and appearance of intact skin. Clinical analysis was performed on 50 subjects; histological and gene expression analysis was performed on 12 of the 50 subjects to assess the effect of the dissolved oxygen dressing. Clinical data demonstrate that the dressing is well tolerated, and several measures of skin health and integrity showed improvements compared with a control dressing site. Skin hydration measurements showed a statistically significant increase in skin hydration at 0-4, 4-8, and 0-8 weeks (P < 0.05 at each time point). The blinded clinical investigator's grading of desquamation, roughness, and skin texture show significant decreases from baseline to the 8-week time point (P < 0.05). The dressings were removed prior to the blinded clinical investigator's grading. These data were supported by the histological and gene expression studies, which showed a general reduction in inflammatory response markers and transcription products (IL-6, IL-8, TNF-alpha, MMP-1, and MMP-12), while facilitating a general increase in structural skin proteins (collagen I, elastin, and filaggrin). Additionally, p53 signals from biopsy samples support the clinical investigator's observations of no safety concerns. The data from this study demonstrate that the dressing has no deleterious effects and stimulates beneficial effects on intact, nonwounded skin. © 2013 Wiley Periodicals, Inc.

Evaluation of the impact of urban pollution on the quality of skin: a multicentre study in Mexico.

PubMed

Lefebvre, M-A; Pham, D-M; Boussouira, B; Bernard, D; Camus, C; Nguyen, Q-L

2015-06-01

After pilot and preliminary studies aimed at identifying pertinent biochemical parameters, a multicenter clinical study was performed to evaluate the effect of pollution on human skin. The clinical study was performed in collaboration with the 'Centre Régional de lutte contre le cancer de Montpellier' and the 'National Institute of Public Health of Mexico' on 96 subjects in Mexico City (exposed to pollution) and 93 subjects in Cuernavaca (less exposed to pollution). Both biochemical and clinical skin parameters were studied. The study demonstrated significant quantitative and qualitative modifications of parameters related to sebum excretion in Mexico City compared to Cuernavaca one: An increased level of sebum excretion rate, a lower level of vitamin E and squalene in sebum, an increase of lactic acid and a higher erythematous index on the face of the subjects. In the stratum corneum, a significant higher level of carbonylated proteins and a lower level of IL 1α were noticed, as well as a decrease of ATP concentration with a decrease of chymotrysin like activity, without modifications of corneodesmosin content and trypsin like activity. From a clinical point of view, a higher frequency of atopic and urticarial skins, a higher frequency of red dermographism, an important seborrheic status at the forehead level and a lower level of dandruffs were noted in Mexico City population. The analysis taking into account the sex does not modify the observed results. The study demonstrated an important impact of polluted environmental conditions on skin quality, evidencing important modifications of superficial biochemical parameters. The cause/effects relationships of these modifications remain, however, to be further assessed by a complementary in vitro/in vivo approaches. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Use of antipsychotic blood levels in clinician decision making: A cross-over study using clinical vignettes of patients with schizophrenia.

PubMed

Savitz, Adam; Melkote, Rama; Riley, Ralph; Pobre, Maria A; McQuarrie, Kelly; Williamson, David; Banderas, Benjamin

2018-05-19

The cause of treatment failure of antipsychotic medications is often difficult to determine in patients with schizophrenia. Evaluation of antipsychotic blood levels (ABLs) may aid clinicians in determining the cause of antipsychotic failure. The Clinical Assessment of the Schizophrenia Patient (CASP) was developed to evaluate clinical decision making during outpatient visits. The CASP assesses changes in medications, psychosocial treatments, and acute interventions along with factors influencing clinical decision making. Nine vignettes representative of clinical situations in patients with schizophrenia were created in two versions (one with ABLs, one without ABLs). The CASP was used to evaluate clinical decisions using the vignettes. Thirty-four clinicians participated in the study. In 8 out of 9 vignettes, most clinicians (at least 89.7%) made a different clinical decision with ABLs compared to without ABLs. In assessing the usefulness of ABLs, a majority (60.7%-85.7%, depending on the vignette) of clinicians responded that ABLs changed their clinical decision for 8 vignettes. Most clinicians (79%-93%) responded that they were more confident in their decisions with ABL information. This study demonstrated that ABLs have the potential to influence clinical decision making in the treatment of patients with schizophrenia. Copyright © 2018. Published by Elsevier B.V.

Impact of electronic health record clinical decision support on the management of pediatric obesity.

PubMed

Shaikh, Ulfat; Berrong, Jeanette; Nettiksimmons, Jasmine; Byrd, Robert S

2015-01-01

Clinicians vary significantly in their adherence to clinical guidelines for overweight/obesity. This study assessed the impact of electronic health record-based clinical decision support in improving the diagnosis and management of pediatric obesity. The study team programmed a point-of-care alert linked to a checklist and standardized documentation templates to appear during health maintenance visits for overweight/obese children in an outpatient teaching clinic and compared outcomes through medical record reviews of 574 (287 control and 287 intervention) visits. The results demonstrated a statistically significant increase in the diagnosis of overweight/obesity, scheduling of follow-up appointments, frequency of ordering recommended laboratory investigations, and assessment and counseling for nutrition and physical activity. Although clinical guideline adherence increased significantly, it was far from universal. It is unknown if modest improvements in adherence to clinical guidelines translate to improvements in children's health. However, this intervention was relatively easy to implement and produced measurable improvements in health care delivery. © 2014 by the American College of Medical Quality.

Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction.

PubMed

Dautremont, Jonathan F; Rudmik, Luke R; Yeung, Justin; Asante, Tiffany; Nakoneshny, Steve C; Hoy, Monica; Lui, Amanda; Chandarana, Shamir P; Matthews, Thomas W; Schrag, Christiaan; Dort, Joseph C

2013-12-19

The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction. This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer. 118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are $22,733 and $16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was $6,169 per patient. Implementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

Transforming the practice of medicine using genomics

PubMed Central

Ginsburg, Geoffrey S.; Ginsburg, Geoffrey S.; J. McCarthy, Jeanette

2009-01-01

Recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in complex diseases. Such studies herald the future for genomic medicine and the opportunity for personalized prognosis in a variety of clinical contexts that utilize genomescale molecular information. Several key areas represent logical and critical next steps in the use of complex genomic profiling data towards the goal of personalized medicine. First, analyses should be geared toward the development of molecular profiles that predict future events – such as major clinical events or the response, resistance, or adverse reaction to therapy. Secondly, these must move into actual clinical practice by forming the basis for the next generation of clinical trials that will employ these methodologies to stratify patients. Lastly, there remain formidable challenges is in the translation of genomic technologies into clinical medicine that will need to be addressed: professional and public education, health outcomes research, reimbursement, regulatory oversight and privacy protection. PMID:22461094

Lost in translation: neuropsychiatric drug development.

PubMed

Becker, Robert E; Greig, Nigel H

2010-12-08

Recent studies have identified troubling method and practice lapses in neuropsychiatric drug developments. These problems have resulted in errors that are of sufficient magnitude to invalidate clinical trial data and interpretations. We identify two potential sources for these difficulties: investigators selectively choosing scientific practices for demonstrations of efficacy in human-testing phases of drug development and investigators failing to anticipate the needs of practitioners who must optimize treatment for the individual patient. When clinical investigators neglect to use clinical trials as opportunities to test hypotheses of disease mechanisms in humans, the neuropsychiatric knowledge base loses both credibility and scope. When clinical investigators do not anticipate the need to translate discoveries into applications, the practitioner cannot provide optimal care for the patient. We conclude from this evidence that clinical trials, and other aspects of neuropsychiatric drug development, must adopt more practices from basic science and show greater responsiveness to conditions of clinical practice. We feel that these changes are necessary to overcome current threats to the validity and utility of studies of neurological and psychiatric drugs.

Bone Marrow Aspirate Concentrate for Cartilage Defects of the Knee: From Bench to Bedside Evidence.

PubMed

Cotter, Eric J; Wang, Kevin C; Yanke, Adam B; Chubinskaya, Susan

2018-04-01

Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including ["bone marrow aspirate" and "cartilage"], ["mesenchymal stem cells" and "cartilage"], and ["bone marrow aspirate" and "mesenchymal stem cells" and "orthopedics"]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived-mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study

PubMed Central

2013-01-01

Purpose Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus. Methods Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium-based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments. Results No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results. Conclusion The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities. PMID:23819489

The selective estrogen receptor modulators in breast cancer prevention.

PubMed

Li, Fangxuan; Dou, Jinli; Wei, Lijuan; Li, Shixia; Liu, Juntian

2016-05-01

Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

A Review of the Use of Topical Calendula in the Prevention and Treatment of Radiotherapy-Induced Skin Reactions.

PubMed

Kodiyan, Joyson; Amber, Kyle T

2015-04-23

Calendula is a topical agent derived from a plant of the marigold family Calendula Officinalis. Containing numerous polyphenolic antioxidants, calendula has been studied in both the laboratory and clinical setting for the use in treating and preventing radiation induced skin toxicity. Despite strong evidence in the laboratory supporting calendula's mechanism of action in preventing radiation induced skin toxicity, clinical studies have demonstrated mixed results. In light of the controversy surrounding the efficacy of calendula in treating and preventing radiodermatitis, the topic warrants further discussion.

Developing Medicare Competitive Bidding: A Study of Clinical Laboratories

PubMed Central

Hoerger, Thomas J.; Meadow, Ann

1997-01-01

Competitive bidding to derive Medicare fees promises several advantages over administered fee systems. The authors show how incentives for cost savings, quality, and access can be incorporated into bidding schemes, and they report on a study of the clinical laboratory industry conducted in preparation for a bidding demonstration. The laboratory industry is marked by variable concentration across geographic markets and, among firms themselves, by social and economic heterogeneity. The authors conclude that these conditions can be accommodated by available bidding design options and by careful selection of bidding markets. PMID:10180003

Once-daily luliconazole cream 1% for the treatment of interdigital tinea pedis.

PubMed

Gold, Michael H; Olin, Jason T

2015-01-01

Luliconazole is an imidazole antifungal agent with a unique chemical structure. In this article, we summarize the in vitro data, animal studies and clinical trial data relating to the use of topical luliconazole cream 1% in the treatment of tinea pedis. Preclinical studies have demonstrated potent activity against dermatophytes. Luliconazole has strong fungicidal activity against Trichophyton spp., similar to that seen with terbinafine. Evidence from clinical trials in tinea pedis have shown once-daily application of luliconazole cream 1% for 14 days to be effective and well tolerated.

Current Directions in Videoconferencing Tele-Mental Health Research

PubMed Central

Richardson, Lisa K.; Frueh, B. Christopher; Grubaugh, Anouk L.; Egede, Leonard; Elhai, Jon D.

2009-01-01

The provision of mental health services via videoconferencing tele-mental health has become an increasingly routine component of mental health service delivery throughout the world. Emphasizing the research literature since 2003, we examine: 1) the extent to which the field of tele-mental health has advanced the research agenda previously suggested; and 2) implications for tele-mental health care delivery for special clinical populations. Previous findings have demonstrated that tele-mental health services are satisfactory to patients, improve outcomes, and are probably cost effective. In the very small number of randomized controlled studies that have been conducted to date, tele-mental health has demonstrated equivalent efficacy compared to face-to-face care in a variety of clinical settings and with specific patient populations. However, methodologically flawed or limited research studies are the norm, and thus the research agenda for tele-mental health has not been fully maximized. Implications for future research and practice are discussed. PMID:20161010

In Vitro Antimicrobial and Modulatory Activity of the Natural Products Silymarin and Silibinin

PubMed Central

Rakelly de Oliveira, Dayanne; Relison Tintino, Saulo; Morais Braga, Maria Flaviana Bezerra; Boligon, Aline Augusti; Linde Athayde, Margareth; Douglas Melo Coutinho, Henrique; de Menezes, Irwin Rose Alencar; Fachinetto, Roselei

2015-01-01

Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line. PMID:25866771

Implementation of clinical decision rules in the emergency department.

PubMed

Stiell, Ian G; Bennett, Carol

2007-11-01

Clinical decision rules (CDRs) are tools designed to help clinicians make bedside diagnostic and therapeutic decisions. The development of a CDR involves three stages: derivation, validation, and implementation. Several criteria need to be considered when designing and evaluating the results of an implementation trial. In this article, the authors review the results of implementation studies evaluating the effect of four CDRs: the Ottawa Ankle Rules, the Ottawa Knee Rule, the Canadian C-Spine Rule, and the Canadian CT Head Rule. Four implementation studies demonstrated that the implementation of CDRs in the emergency department (ED) safely reduced the use of radiography for ankle, knee, and cervical spine injuries. However, a recent trial failed to demonstrate an impact on computed tomography imaging rates. Well-developed and validated CDRs can be successfully implemented into practice, efficiently standardizing ED care. However, further research is needed to identify barriers to implementation in order to achieve improved uptake in the ED.

Enhanced MRI relaxivity of aquated Gd3+ ions by carboxyphenylated water-dispersed graphene nanoribbons

NASA Astrophysics Data System (ADS)

Gizzatov, Ayrat; Keshishian, Vazrik; Guven, Adem; Dimiev, Ayrat M.; Qu, Feifei; Muthupillai, Raja; Decuzzi, Paolo; Bryant, Robert G.; Tour, James M.; Wilson, Lon J.

2014-02-01

The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ ions can serve as a high-performance contrast agent (CA) for applications in T1- and T2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times for r1 and 21 times for r2.The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ ions can serve as a high-performance contrast agent (CA) for applications in T1- and T2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times for r1 and 21 times for r2. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06026h

Tuberculous otitis media: a clinical and radiologic analysis of 52 patients.

PubMed

Cho, Yang-Sun; Lee, Hyun-Seok; Kim, Sang-Woo; Chung, Kyu-Hwan; Lee, Dong-Kyung; Koh, Won-Jung; Kim, Myung-Gu

2006-06-01

This retrospective study reports on the clinical and radiologic features and the treatment outcomes of patients with tuberculous otitis media (TOM). We reviewed the medical records of 52 patients (53 ears) with TOM between 1993 and 2005 and analyzed temporal bone computed tomography scans of 23 patients. The diagnosis of TOM was made if a specimen of the middle ear revealed the presence of acid fast bacilli (AFB), grew Mycobacterium tuberculosis (M. Tb) on a culture, revealed characteristic histology, and/or was positive for polymerase chain reaction (PCR) for M. Tb. The highest incidence of the disease was observed among patients in their 30s. The main symptom was otorrhea, and the duration of symptoms was shorter than with nonspecific chronic otitis media. Most patients demonstrated a moderate to severe hearing loss. Five patients (9.6%) demonstrated a peripheral-type facial palsy. Temporal bone CT scans demonstrated relatively well-pneumatized mastoids and occupation by soft tissue of the entire tympanum and mastoid air cells. Six patients demonstrated bone destruction that involved the cortex of the mastoid bone. In most patients, antituberculous medication was effective treatment. The patients who underwent chemotherapy after surgery achieved more rapid healing of the ear and more frequent closure of the tympanic membrane than those who did not receive surgery. Clinicians should have a high index of suspicion and be aware of the clinical and radiologic characteristics of TOM.

Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.

PubMed

Timms, John F; Hale, Oliver J; Cramer, Rainer

2016-06-01

The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.

Electromyography findings of the cricopharyngeus in association with ipsilateral pharyngeal and laryngeal muscles.

PubMed

Halum, Stacey L; Shemirani, Nima L; Merati, Albert L; Jaradeh, Safwan; Toohill, Robert J

2006-04-01

We reviewed a large series of cricopharyngeal (CP) muscle electromyography (EMG) results and compared them with the EMG results from the inferior constrictor (IC), thyroarytenoid, (TA), cricothyroid (CT), and posterior cricoarytenoid (PCA) muscles. We performed a retrospective review of all CP muscle EMG reports from studies performed between January 1996 and June 2003. All of the tested elements from the CP muscle EMG reports were recorded. The EMG results were recorded for the ipsilateral IC, TA, CT, and PCA muscles if they were simultaneously tested. Each muscle result was classified as normal, neurogenic inactive axonal injury (IAI), or neurogenic active axonal injury (AAI), and the muscle findings were compared. A patient chart review was performed to determine a clinical correlation. Fifty-nine patients underwent CP muscle EMG. Eighteen patients had bilateral EMG studies, making a total of 77 CP muscle studies. Nineteen sets of CP muscle results were normal, 43 demonstrated neurogenic IAI, and 15 demonstrated neurogenic AAI. The ipsilateral IC and CP muscles had the same innervation status in 27 of 28 studies (p < .0001). When the ipsilateral TA muscle was studied simultaneously with the CP muscle, 31 of 50 studies had the same innervation status (p = .005). The ipsilateral CT and CP muscles demonstrated the same innervation status in 40 of 50 studies (p < .0001). The correlations between the CP and IC muscle findings and between the CP and CT muscle findings were both stronger than the correlation between the CP and TA muscle findings (p < .0001 and p = .024, respectively). The chart review demonstrated the clinical findings to be consistent with the EMG results. The EMG studies demonstrated that CP muscle findings have the strongest correlation with IC muscle findings, followed by the CT and TA muscles. This outcome does not support theories indicating that the recurrent laryngeal nerve innervates the CP muscle in all cases.

Development and Validation of a Clinic-Based Prediction Tool to Identify Female Athletes at High Risk for Anterior Cruciate Ligament Injury

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Khoury, Jane; Succop, Paul; Hewett, Timothy E.

2012-01-01

Background Prospective measures of high knee abduction moment (KAM) during landing identify female athletes at high risk for anterior cruciate ligament injury. Laboratory-based measurements demonstrate 90% accuracy in prediction of high KAM. Clinic-based prediction algorithms that employ correlates derived from laboratory-based measurements also demonstrate high accuracy for prediction of high KAM mechanics during landing. Hypotheses Clinic-based measures derived from highly predictive laboratory-based models are valid for the accurate prediction of high KAM status, and simultaneous measurements using laboratory-based and clinic-based techniques highly correlate. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods One hundred female athletes (basketball, soccer, volleyball players) were tested using laboratory-based measures to confirm the validity of identified laboratory-based correlate variables to clinic-based measures included in a prediction algorithm to determine high KAM status. To analyze selected clinic-based surrogate predictors, another cohort of 20 female athletes was simultaneously tested with both clinic-based and laboratory-based measures. Results The prediction model (odds ratio: 95% confidence interval), derived from laboratory-based surrogates including (1) knee valgus motion (1.59: 1.17-2.16 cm), (2) knee flexion range of motion (0.94: 0.89°-1.00°), (3) body mass (0.98: 0.94-1.03 kg), (4) tibia length (1.55: 1.20-2.07 cm), and (5) quadriceps-to-hamstrings ratio (1.70: 0.48%-6.0%), predicted high KAM status with 84% sensitivity and 67% specificity (P < .001). Clinic-based techniques that used a calibrated physician’s scale, a standard measuring tape, standard camcorder, ImageJ software, and an isokinetic dynamometer showed high correlation (knee valgus motion, r = .87; knee flexion range of motion, r = .95; and tibia length, r = .98) to simultaneous laboratory-based measurements. Body mass and quadriceps-to-hamstrings ratio were included in both methodologies and therefore had r values of 1.0. Conclusion Clinically obtainable measures of increased knee valgus, knee flexion range of motion, body mass, tibia length, and quadriceps-to-hamstrings ratio predict high KAM status in female athletes with high sensitivity and specificity. Female athletes who demonstrate high KAM landing mechanics are at increased risk for anterior cruciate ligament injury and are more likely to benefit from neuromuscular training targeted to this risk factor. Use of the developed clinic-based assessment tool may facilitate high-risk athletes’ entry into appropriate interventions that will have greater potential to reduce their injury risk. PMID:20595554

Clinical Use of Deferoxamine in Distraction Osteogenesis of Irradiated Bone

PubMed Central

Momeni, Arash; Rapp, Scott; Donneys, Alexis; Buchman, Steven R.; Wan, Derrick C.

2016-01-01

The deleterious effects of radiotherapy, including hypovascularity and hypocellularity, have made distraction of irradiated bones challenging. Animal studies, however, have demonstrated adjunctive measures such as the administration of deferoxamine to significantly improve bone regeneration across irradiated distraction gaps. In this report, we demonstrate, for the first time, enhanced bone formation following deferoxamine application in a patient following distraction of a previously irradiated maxilla. CT imaging of the pterygomaxillary buttress on the side of administration revealed significantly increased bone area and density relative to the contralateral buttress. This is the first presentation of clinical deferoxamine use to promote bone formation following irradiated bone distraction and highlights the promise for this adjunctive measure to make outcomes after distraction of irradiated bone more reliable. PMID:27171947

The Translational Role of Diffusion Tensor Image Analysis in Animal Models of Developmental Pathologies

PubMed Central

Oguz, Ipek; McMurray, Matthew S.; Styner, Martin; Johns, Josephine M.

2013-01-01

Diffusion Tensor Magnetic Resonance Imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers. PMID:22627095

Collaborative Approach in the Development of High‐Performance Brain–Computer Interfaces for a Neuroprosthetic Arm: Translation from Animal Models to Human Control

PubMed Central

Collinger, Jennifer L.; Kryger, Michael A.; Barbara, Richard; Betler, Timothy; Bowsher, Kristen; Brown, Elke H. P.; Clanton, Samuel T.; Degenhart, Alan D.; Foldes, Stephen T.; Gaunt, Robert A.; Gyulai, Ferenc E.; Harchick, Elizabeth A.; Harrington, Deborah; Helder, John B.; Hemmes, Timothy; Johannes, Matthew S.; Katyal, Kapil D.; Ling, Geoffrey S. F.; McMorland, Angus J. C.; Palko, Karina; Para, Matthew P.; Scheuermann, Janet; Schwartz, Andrew B.; Skidmore, Elizabeth R.; Solzbacher, Florian; Srikameswaran, Anita V.; Swanson, Dennis P.; Swetz, Scott; Tyler‐Kabara, Elizabeth C.; Velliste, Meel; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian

2013-01-01

Abstract Our research group recently demonstrated that a person with tetraplegia could use a brain–computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able‐bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short‐term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real‐world clinical situations. PMID:24528900

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

PubMed

Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

2010-04-16

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.

Surrogate and clinical endpoints in interventional cardiology: are statistics the brakes?

PubMed

Waliszewski, Matthias; Rittger, Harald

2016-10-01

Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-generation drug-eluting stents having enhanced technical attributes and long-term clinical benefits, the proof of incremental angiographic or long-term clinical efficacy becomes more challenging. The purpose of this review is to provide an overview of the most common and alternative study endpoints in interventional cardiology and their potential reimbursement value. Moreover, we intend to describe the statistical limitations in order to demonstrate differences between potential treatment groups. Furthermore, careful endpoint recommendations for a given patient number are offered for future study designs. The number of patients per treatment group was estimated for various study designs such as noninferiority test hypotheses with hard clinical endpoints and various surrogate endpoints. To test for differences in various surrogate endpoint scenarios, the corresponding patient group sizes were explored. To evaluate these endpoints in terms of their reimbursement impact, preferred endpoints for technical appraisals in interventional cardiology at the National Institute of Health and Care Excellence (NICE) were used. Even with the most stringent experimental control to reduce bias-introducing factors, studies with hard primary clinical endpoints such as the occurrence of major adverse cardiac events (MACE) or target-lesion revascularization (TLR) rates remain the gold standard, with numbers reaching into the 300-700 patient range per group. Study designs using loss in fractional-flow reserve (FFR) or stent-strut-coverage rates can be statistically formulated; however, the clinical ramifications for the patient remain to be discussed. Nonrandomized study designs with intrapatient angiographic controls in nontarget vessels may merit further thoughts and explorations. From a reimbursement impact, the primary endpoints MACE and TLR are the best choices for a moderately sized study population of 500 patients per group. Angiographic endpoints, in particular minimal lumen diameter (MLD), are not useful in this context. The emerging endpoints such as loss in FFR or stent coverage require smaller patient populations. However, their impact on reimbursement-related decisions is limited. © The Author(s), 2016.

Surrogate and clinical endpoints in interventional cardiology: are statistics the brakes?

PubMed Central

Waliszewski, Matthias; Rittger, Harald

2016-01-01

Background: Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-generation drug-eluting stents having enhanced technical attributes and long-term clinical benefits, the proof of incremental angiographic or long-term clinical efficacy becomes more challenging. The purpose of this review is to provide an overview of the most common and alternative study endpoints in interventional cardiology and their potential reimbursement value. Moreover, we intend to describe the statistical limitations in order to demonstrate differences between potential treatment groups. Furthermore, careful endpoint recommendations for a given patient number are offered for future study designs. Methods: The number of patients per treatment group was estimated for various study designs such as noninferiority test hypotheses with hard clinical endpoints and various surrogate endpoints. To test for differences in various surrogate endpoint scenarios, the corresponding patient group sizes were explored. To evaluate these endpoints in terms of their reimbursement impact, preferred endpoints for technical appraisals in interventional cardiology at the National Institute of Health and Care Excellence (NICE) were used. Results: Even with the most stringent experimental control to reduce bias-introducing factors, studies with hard primary clinical endpoints such as the occurrence of major adverse cardiac events (MACE) or target-lesion revascularization (TLR) rates remain the gold standard, with numbers reaching into the 300–700 patient range per group. Study designs using loss in fractional-flow reserve (FFR) or stent-strut-coverage rates can be statistically formulated; however, the clinical ramifications for the patient remain to be discussed. Nonrandomized study designs with intrapatient angiographic controls in nontarget vessels may merit further thoughts and explorations. Conclusions: From a reimbursement impact, the primary endpoints MACE and TLR are the best choices for a moderately sized study population of 500 patients per group. Angiographic endpoints, in particular minimal lumen diameter (MLD), are not useful in this context. The emerging endpoints such as loss in FFR or stent coverage require smaller patient populations. However, their impact on reimbursement-related decisions is limited. PMID:27378486

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed

Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Developmental trajectories of infants and toddlers with good initial presentation following moderate or severe traumatic brain injury: a pilot clinical assessment project.

PubMed

Pomerleau, Geneviève; Hurteau, Anne-Marie; Parent, Line; Doucet, Katrine; Corbin-Berrigan, Laurie-Ann; Gagnon, Isabelle

2012-01-01

The purpose of this study was to review the feasibility and usefulness of instituting a clinical protocol of scheduled assessments for children after a moderate or severe traumatic brain injury (TBI) sustained before the age of 2 years and showing no immediate deficits at hospital discharge, as well as to explore the early developmental trajectories of these children. Exploratory analytical cohort study. Pediatric Trauma Center Out-patient services. 31 children were followed within the clinical protocol of scheduled assessments. The protocol included an immediate post-injury clinical assessment of infants who sustained a TBI and follow-up assessments at the ages of 9 months, 18 months (if injured prior to that age), 30 months, and 42 months. Domains assessed at each scheduled visit included hearing, speech and language, motor performance, personal social abilities, and adaptive behaviors. Clinicians reported few difficulties with scheduling or administering the assessments, maintaining a 67% participation rate at the end of the follow-up period, thus demonstrating the feasibility of the protocol in this population. Scores on the majority of formal tests showed high variability and 15-20% of children presented with clinically significant motor and/or language delays. By 42 months of age, difficulties with adaptive behavior and personal social abilities were identified in our sample of children when compared to published norms. Qualitative clinical findings from professionals identified between 25-50% of children with potential attentional difficulties throughout the follow-up period. Findings from this study demonstrate the feasibility of implementing a clinical protocol of assessment for infants and toddlers who sustain a TBI before the age of 2 years and present with no impairments at the time of discharge from hospital. Developmental problems in this population appear to be easier to identify later in the toddler years as opposed to immediately following the TBI, emphasizing the importance of providing screening for developmental issues in this population prior to school entry.

Contrast enhanced Gd-DTPA magnetic resonance imaging in the evaluation of rheumatoid arthritis during a clinical trial with DMARDs. A prospective two-year follow-up study on hand joints in 31 patients.

PubMed

Jevtic, V; Watt, I; Rozman, B; Kos-Golja, M; Praprotnik, S; Logar, D; Presetnik, M; Demsar, F; Jarh, O; Campion, G; Musikic, P

1997-01-01

The aim of this prospective 24-month follow-up study was to compare clinical features with radiological and magnetic resonance imaging (MRI) findings in evaluating synovial proliferation in the hand joints of 31 patients with rheumatoid arthritis (RA). A single joint was used for the follow-up of each patient. Thirty-one small hand joints were examined by conventional radiography and MRI before and after 24 months of treatment. MRI assessment of disease progression (volume and/or signal intensity of the synovial proliferation on T1 weighted precontrast, T1 weighted postcontrast and T2 weighted images) was compared with a clinical assessment of the chosen joints, and with a plain x-ray film evaluation (Larsen's score). Of 26 joints which clinically improved (14 markedly and 14 slightly) during the study, on MRI 16 showed improvement, 8 showed no change, and 2 showed deterioration. Four clinically unchanged joints appeared improved on MRI. One joint deteriorated clinically and on MRI. Overall, there was a 58% congruence between clinical and MRI findings. On x-ray 23 joints showed no change; nine of these were also unchanged on MRI, while 13 showed improvement and one deterioration. Only in 2 out of 8 joints showing deterioration on x-ray were the MRI findings in accordance. In the remaining six joints MRI showed improvement. The congruence between x-ray and MRI was therefore 36%. The long-term follow-up of rheumatoid synovial proliferation of the small joints in the hand using contrast enhanced MRI is feasible and may provide additional information regarding disease activity. Important advantages over conventional radiography methods are its ability to demonstrate qualitative differences of synovial proliferation within bone erosions, and demonstrate not only deterioration, but also the improvement of inflammatory disease.

The Validity of the Montgomery-Asberg Depression Rating Scale in an Inpatient Sample with Alcohol Dependence

PubMed Central

Hobden, Breanne; Schwandt, Melanie L.; Carey, Mariko; Lee, Mary R.; Farokhnia, Mehdi; Bouhlal, Sofia; Oldmeadow, Christopher; Leggio, Lorenzo

2017-01-01

Background The Montgomery-Asberg Depression Rating Scale (MADRS) is commonly used to examine depressive symptoms in clinical settings, including facilities treating patients for alcohol addiction. No studies have examined the validity of the MADRS compared to an established clinical diagnostic tool of depression in this population. This study aimed to examine: 1) the validity of the MADRS compared to a clinical diagnosis of a depressive disorder (using the Structured Clinical Interview for DSM-IV (SCID)) in patients seeking treatment for alcohol dependence (AD); 2) whether the validity of the MADRS differs by type of SCID-based diagnosis of depression; and 3) which items contribute to the optimal predictive model of the MADRS compared to a SCID diagnosis of a depressive disorder. Methods Individuals seeking treatment for AD and admitted to an inpatient unit were administered the MADRS at day 2 of their detoxification program. Clinical diagnoses of AD and depression were made via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV at the beginning of treatment. Results In total, 803 participants were included in the study. The MADRS demonstrated low overall accuracy relative to the clinical diagnosis of depression with an area under the curve of 0.68. The optimal threshold for balancing sensitivity and specificity identified by the Euclidean distance was >14. This cut-point demonstrated a sensitivity of 66%, a specificity of 60%, a positive predictive value of 50% and a negative predictive value of 75%. The MADRS performed slightly better for major depressive disorders compared to alcohol-induced depression. Items related to lassitude, concentration and appetite slightly decreased the accuracy of the MADRS. Conclusion The MADRS does not appear to be an appropriate substitute for a diagnostic tool among alcohol-dependent patients. The MADRS may, however, still be a useful screening tool assuming careful consideration of cut-off scores. PMID:28421616

Applying semantic web technologies for phenome-wide scan using an electronic health record linked Biobank

PubMed Central

2012-01-01

Background The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form “biobanks” where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on a large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypotheses generation. Results In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped for Type 2 Diabetes and Hypothyroidism to discover gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries. Conclusions This study demonstrates how Semantic Web technologies can be applied in conjunction with clinical data stored in EHRs to accurately identify subjects with specific diseases and phenotypes, and identify genotype-phenotype associations. PMID:23244446

Bilastine for the relief of allergy symptoms.

PubMed

Sádaba Díaz de Rada, B; Azanza Perea, J R; Gomez-Guiu Hormigos, A

2011-04-01

Bilastine is a potent inhibitor of the histamine H1 receptor. It was recently approved in 28 countries of the European Union for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. Data from preclinical studies confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic and antiallergic properties in vivo. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. Bilastine has demonstrated a good safety profile, without serious adverse effects or antimuscarinic effects in clinical trials. There were no significant changes in laboratory tests, electrocardiograms or vital signs. In clinical studies, oral treatment with bilastine 20 mg once daily improved allergic rhinitis with greater efficacy than placebo and comparable to cetirizine and desloratadine. Bilastine 20 mg was more effective than placebo and equivalent to levocetirizine in chronic urticaria, relieving symptoms, improving quality of life and controlling sleep disorders. 2011 Prous Science, S.A.U. or its licensors. All rights reserved.

Correlation between bullying and clinical depression in adolescent patients

PubMed Central

Kaltiala-Heino, Riittakerttu; Fröjd, Sari

2011-01-01

A literature review of the associations between involvement in bullying and depression is presented. Many studies have demonstrated a concurrent association between involvement in bullying and depression in adolescent population samples. Not only victims but also bullies display increased risk of depression, although not all studies have confirmed this for the bullies. Retrospective studies among adults support the notion that victimization is followed by depression. Prospective follow-up studies have suggested both that victimization from bullying may be a risk factor for depression and that depression may predispose adolescents to bullying. Research among clinically referred adolescents is scarce but suggests that correlations between victimization from bullying and depression are likely to be similar in clinical and population samples. Adolescents who bully present with elevated numbers of psychiatric symptoms and psychiatric and social welfare treatment contacts. PMID:24600274

Exploring the measurement properties of the osteopathy clinical teaching questionnaire using Rasch analysis.

PubMed

Vaughan, Brett

2018-01-01

Clinical teaching evaluations are common in health profession education programs to ensure students are receiving a quality clinical education experience. Questionnaires students use to evaluate their clinical teachers have been developed in professions such as medicine and nursing. The development of a questionnaire that is specifically for the osteopathy on-campus, student-led clinic environment is warranted. Previous work developed the 30-item Osteopathy Clinical Teaching Questionnaire. The current study utilised Rasch analysis to investigate the construct validity of the Osteopathy Clinical Teaching Questionnaire and provide evidence for the validity argument through fit to the Rasch model. Senior osteopathy students at four institutions in Australia, New Zealand and the United Kingdom rated their clinical teachers using the Osteopathy Clinical Teaching Questionnaire. Three hundred and ninety-nine valid responses were received and the data were evaluated for fit to the Rasch model. Reliability estimations (Cronbach's alpha and McDonald's omega) were also evaluated for the final model. The initial analysis demonstrated the data did not fit the Rasch model. Accordingly, modifications to the questionnaire were made including removing items, removing person responses, and rescoring one item. The final model contained 12 items and fit to the Rasch model was adequate. Support for unidimensionality was demonstrated through both the Principal Components Analysis/t-test, and the Cronbach's alpha and McDonald's omega reliability estimates. Analysis of the questionnaire using McDonald's omega hierarchical supported a general factor (quality of clinical teaching in osteopathy). The evidence for unidimensionality and the presence of a general factor support the calculation of a total score for the questionnaire as a sufficient statistic. Further work is now required to investigate the reliability of the 12-item Osteopathy Clinical Teaching Questionnaire to provide evidence for the validity argument.

Management of atrial fibrillation: focus on the role of dronedarone.

PubMed

Cheng, Judy Wm

2011-01-01

Dronedarone is an amiodarone derivative that was approved in the US in July 2009 to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF), who are in sinus rhythm (SR), or who will be cardioverted. This article reviews the pharmacology, adverse effects, and clinical evidence available to date on the use of dronedarone in the management of AF and its potential role in the emergency department setting. In the EURIDIS and ADONIS studies evaluating the efficacy of dronedarone in maintaining SR, dronedarone significantly reduced the risk of recurrence of AF compared to placebo, by 22% and 27%, respectively. The ERATO study examined the ability of dronedarone to control ventricular rate in permanent AF. The DIONYSOS study demonstrated that recurrences of AF were more frequent with dronedarone. However, discontinuation of therapy due to intolerance was more frequent with amiodarone. Furthermore, the ATHENA study demonstrated that dronedarone reduced mortality and cardiovascular hospitalization by 24% (P < 0.05) in patients in SR but with other associated risks and a history of AF. However, the ANDROMEDA study, evaluating the use of dronedarone in patients with recent decompensated heart failure, and the PALLAS study, evaluating the use of dronedarone in patients with chronic AF, were both terminated prematurely due to a trend toward an increased risk of cardiovascular events. Dronedarone has been demonstrated to be effective in reducing the incidence of AF recurrence. It appears to be less effective but better tolerated than amiodarone. Dronedarone appears to have a low proarrhythmic risk and is the first anti-arrhythmic that has been demonstrated to reduce cardiovascular mortality and cardiovascular hospitalization in clinically stable patients with other risk factors for recurrent AF. Therefore, dronedarone can be recommended as an anti-arrhythmic of choice in clinically stable patients for maintaining SR. If dronedarone is to be used in a patient with chronic stable heart failure, the patient must be monitored closely for any worsening of heart failure symptoms. The drug must be discontinued should the heart failure symptoms worsen.

Knowledge of carbohydrate counting and insulin dose calculations in paediatric patients with type 1 diabetes mellitus.

PubMed

Finner, Natalie; Quinn, Anne; Donovan, Anna; O'Leary, Orla; O'Gorman, Clodagh S

2015-12-01

Patients with type 1 diabetes mellitus (T1DM) who are able to adjust their insulin doses according to the carbohydrate content of a meal, as well as their blood glucose, are likely to have improved glycaemic control (Silverstein et al., 2005). With improved glycaemic control, patients have a lower risk of developing long-term microvascular complications associated with T1DM (Diabetes Control and Complications Trial Research Group, 1993). To assess the carbohydrate and insulin knowledge of patients attending our paediatric diabetes clinic at the University Hospital Limerick (UHL), the validated PedCarbQuiz (PCQ) was applied to our clinic population. This study was completed by applying a questionnaire called the PedCarbQuiz (PCQ) to children exclusively attending our paediatric diabetes clinic at UHL. Of the clinic's 220 patients, 81 participated in the study. The average total PCQ score (%) was higher in the continuous subcutaneous insulin infusion (CSII) group compared with the multiple daily insulin (MDI) injection user group (79.1 ± 12.1 versus 65.9 ± 6.6 p = 0.005). The CSII group also had a higher average carbohydrate score (%) compared with the MDI group (79.4 ± 12.4 versus 66.3 ± 16.2, p = 0.004). This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is better among patients treated with CSII compared with MDI. However, knowledge in both groups is poorer than in the original US sample. This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is poorer than in a US based sample, although this knowledge is better among patients treated with CSII compared with MDI. This highlights the need for improved resources for diabetes and carbohydrate counting education for patients with T1DM.

Computed tomography of adult colonic intussusception: clinical and experimental studies

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

Iko, B.O.; Teal, J.S.; Siram, S.M.

1984-10-01

The CT features of a case of adult ileocolic intussusception and of experimentally induced ileocolic, cecocolic, and colocolic intussusceptions are presented. Both the clinical and experimental cases demonstrated (1) target masses with enveloped, eccentrically located areas of low density and (2) interspersed low- and high-density stripes within the intussusception producing a layered or stratified pattern. This layered pattern of abdominal masses may be characteristic of intussusceptions regardless of location.

Introducing a partnership doctor-patient communication guide for teachers in the culturally hierarchical context of Indonesia.

PubMed

Claramita, Mora; Susilo, Astrid Pratidina; Kharismayekti, Manik; van Dalen, Jan; van der Vleuten, Cees

2013-01-01

A guide for a partnership style of doctor-patient communication tailored to a Southeast Asian culture was previously developed and validated. We introduced the guide to clinical teachers in Indonesia through a participatory approach. Evaluation was based on teachers' demonstrated comprehension and ability to teach the guide. Three junior researchers invited twelve senior clinical teachers to learn about the guide by writing a chapter on doctor-patient communication using their clinical expertise, reflections on the guide, and the international literature. A participatory study comprised of two cycles (producing first and second drafts of the chapters) was conducted over 18 months with guidance from researchers and written feedback from an expert in communication skills. Qualitative content-analysis was used to assess the content of the submitted chapters. The clinical teachers understood the concept of partnership style doctor-patient communication but demonstrated limited reflection on the Southeast Asian culture. Teachers had difficulty translating the guide into a written learning guide. However, teachers proposed an adapted guide with a simpler structure, tailored to their clinical environment characterized by high patient load and limited time for doctor-patient communications. The adapted guide was proof of the teachers' willingness to learn about a partnership style of doctor-patient communications. However, the process of introducing the guide was hindered by the wide power distance between participants throughout all aspects of the study, including communication between senior teachers and more junior researchers.

In vivo detection of oral epithelial cancer using endogenous fluorescence lifetime imaging: a pilot human study (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jo, Javier A.; Hwang, Dae Yon; Palma, Jorge; Cheng, Shuna; Cuenca, Rodrigo; Malik, Bilal; Jabbour, Joey; Cheng, Lisa; Wright, John; Maitland, Kristen

2016-03-01

Endogenous fluorescence lifetime imaging (FLIM) provides direct access to the concomitant functional and biochemical changes accompanying tissue transition from benign to precancerous and cancerous. Since FLIM can noninvasively measure different and complementary biomarkers of precancer and cancer, we hypothesize that it will aid in clinically detecting early oral epithelial cancer. Our group has recently demonstrated the detection of benign from premalignant and malignant lesions based on endogenous multispectral FLIM in the hamster cheek-pouch model. Encouraged by these positive preliminary results, we have developed a handheld endoscope capable of acquiring multispectral FLIM images in real time from the oral mucosa. This novel FLIM endoscope is being used for imaging clinically suspicious pre-malignant and malignant lesions from patients before undergoing tissue biopsy for histopathological diagnosis of oral epithelial cancer. Our preliminary results thus far are already suggesting the potential of endogenous FLIM for distinguishing a variety of benign lesions from advanced dysplasia and squamous cell carcinoma (SCC). To the best of out knowledge, this is the first in vivo human study aiming to demonstrate the ability to predict the true malignancy of clinically suspicious lesions using endogenous FLIM. If successful, the resulting clinical tool will allow noninvasive real-time detection of epithelial precancerous and cancerous lesions in the oral mucosa and could potentially be used to assist at every step involved on the clinical management of oral cancer patients, from early screening and diagnosis, to treatment and monitoring of recurrence.

From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners.

PubMed

Wenrich, Marjorie D; Jackson, Molly Blackley; Maestas, Ramoncita R; Wolfhagen, Ineke H A P; Scherpbier, Albert J J

2015-11-01

Medical students learn clinical skills at the bedside from teaching clinicians, who often learn to teach by teaching. Little is known about the process of becoming an effective clinical teacher. Understanding how teaching skills and approaches change with experience may help tailor faculty development for new teachers. Focusing on giving feedback to early learners, the authors asked: What is the developmental progression of clinician-teachers as they learn to give clinical skills feedback to medical students? This qualitative study included longitudinal interviews with clinician-teachers over five years in a new clinical skills teaching program for preclinical medical students. Techniques derived from grounded theory were used for initial analyses. The current study focused on one theme identified in initial analyses: giving feedback to students. Transcript passages were organized by interview year, coded, and discussed in year clusters; thematic codes were compared and emergent codes developed. Themes related to giving feedback demonstrated a dyadic structure: characteristic of less experienced teachers versus characteristic of experienced teachers. Seven dominant dyadic themes emerged, including teacher as cheerleader versus coach, concern about student fragility versus understanding resilience, and focus on creating a safe environment versus challenging students within a safe environment. With consistent teaching, clinical teachers demonstrated progress in giving feedback to students in multiple areas, including understanding students' developmental trajectory and needs, developing tools and strategies, and adopting a dynamic, challenging, inclusive team approach. Ongoing teaching opportunities with targeted faculty development may help improve clinician-teachers' feedback skills and approaches.

The implementation of computerized cognitive behavioural therapies in a service user-led, third sector self help clinic.

PubMed

Cavanagh, Kate; Seccombe, Nick; Lidbetter, Nicky

2011-07-01

The efficacy and effectiveness of a computerized cognitive behavioural therapy (CCBT) package, Beating the Blues, has been demonstrated in a large randomized controlled trial and several pragmatic studies in the National Health Service (NHS). The current study tests the generalizability of this finding to the implementation of CCBT in a service user-led, third sector Self Help Clinic. 510 referrals for the Beating the Blues program were received over a 16 month period in routine care. The Patient Health Questionnaire Depression (PHQ-9) and Anxiety (GAD-7) Scales were administered pre-treatment and during each treatment session. The 10-item Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), Work and Social Adjustment Scale and Patient Experience Questionnaire were also administered pre-treatment and immediately on completing treatment. More than two-thirds of referrals were suitable for treatment and completed a baseline assessment; 84% of these started the Beating the Blues program. Two-hundred and twenty-six people meeting caseness criteria at baseline completed at least two sessions of CCBT. Of these, 50% met recovery criteria at their final point of measurement. Completer and intention-to-treat analysis also demonstrated statistically and clinically significant improvements on key outcome measures. CCBT can be effectively implemented in a service user-led, third sector Self Help Clinic, increasing access to psychological therapies to meet local needs for tier two interventions for depression and anxiety.

Correlation between clinical fetal head station and sonographic angle of progression during the second stage of labor.

PubMed

Perlman, Sharon; Kivilevitch, Zvi; Moran, Orit; Katorza, Eldad; Kees, Salim; Achiron, Reuven; Gilboa, Yinon

2017-08-04

To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range. A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed. Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001). This correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r 2  = 0.423, p < .001). After aggregation of the mean AOP per FHS, the relative predicted centiles values and standard deviation were calculated. The mean Z score between measured and predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006). Our results demonstrate a significant correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor.

Applying Advanced Analytical Approaches to Characterize the Impact of Specific Clinical Gaps and Profiles on the Management of Rheumatoid Arthritis.

PubMed

Ruiz-Cordell, Karyn D; Joubin, Kathy; Haimowitz, Steven

2016-01-01

The goal of this study was to add a predictive modeling approach to the meta-analysis of continuing medical education curricula to determine whether this technique can be used to better understand clinical decision making. Using the education of rheumatologists on rheumatoid arthritis management as a model, this study demonstrates how the combined methodology has the ability to not only characterize learning gaps but also identify those proficiency areas that have the greatest impact on clinical behavior. The meta-analysis included seven curricula with 25 activities. Learners who identified as rheumatologists were evaluated across multiple learning domains, using a uniform methodology to characterize learning gains and gaps. A performance composite variable (called the treatment individualization and optimization score) was then established as a target upon which predictive analytics were conducted. Significant predictors of the target included items related to the knowledge of rheumatologists and confidence concerning 1) treatment guidelines and 2) tests that measure disease activity. In addition, a striking demographic predictor related to geographic practice setting was also identified. The results demonstrate the power of advanced analytics to identify key predictors that influence clinical behaviors. Furthermore, the ability to provide an expected magnitude of change if these predictors are addressed has the potential to substantially refine educational priorities to those drivers that, if targeted, will most effectively overcome clinical barriers and lead to the greatest success in achieving treatment goals.

Potential Role of N-Acetylcysteine in the Management of Substance Use Disorders

PubMed Central

Gipson, Cassandra D.; Malcolm, Robert J.; Kalivas, Peter W.; Gray, Kevin M.

2014-01-01

There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will focus specifically on N-acetylcysteine (NAC), a safe and well-tolerated glutamatergic agent, as a promising potential pharmacotherapy for the treatment of SUDs across several substances of abuse. Building on recently published reviews of the clinical efficacy of NAC across a broad range of conditions, this review will more specifically discuss NAC as a pharmacotherapy for SUDs, devoting particular attention to the safety and tolerability profile of NAC, the wealth of preclinical evidence that has demonstrated the role of glutamate dysregulation in addiction, and the limited but growing clinical literature that has assessed the efficacy of NAC across multiple substances of abuse. Preliminary clinical studies show the promise of NAC in terms of safety, tolerability, and potential efficacy for promoting abstinence from cocaine, nicotine, and cannabis. Results from randomized clinical trials have been mixed, but several mechanistic and methodological factors are discussed to refine the use of NAC in promoting abstinence and relapse prevention across several substances of abuse. Further preclinical and clinical investigation into the use of NAC for SUDs will be vital in addressing current deficits in the treatment of SUDs. PMID:24442756

Expert System Shells for Rapid Clinical Decision Support Module Development: An ESTA Demonstration of a Simple Rule-Based System for the Diagnosis of Vaginal Discharge

PubMed Central

2012-01-01

Objectives This study demonstrates the feasibility of using expert system shells for rapid clinical decision support module development. Methods A readily available expert system shell was used to build a simple rule-based system for the crude diagnosis of vaginal discharge. Pictures and 'canned text explanations' are extensively used throughout the program to enhance its intuitiveness and educational dimension. All the steps involved in developing the system are documented. Results The system runs under Microsoft Windows and is available as a free download at http://healthcybermap.org/vagdisch.zip (the distribution archive includes both the program's executable and the commented knowledge base source as a text document). The limitations of the demonstration system, such as the lack of provisions for assessing uncertainty or various degrees of severity of a sign or symptom, are discussed in detail. Ways of improving the system, such as porting it to the Web and packaging it as an app for smartphones and tablets, are also presented. Conclusions An easy-to-use expert system shell enables clinicians to rapidly become their own 'knowledge engineers' and develop concise evidence-based decision support modules of simple to moderate complexity, targeting clinical practitioners, medical and nursing students, as well as patients, their lay carers and the general public (where appropriate). In the spirit of the social Web, it is hoped that an online repository can be created to peer review, share and re-use knowledge base modules covering various clinical problems and algorithms, as a service to the clinical community. PMID:23346475

Flipped clinical training: a structured training method for undergraduates in complete denture prosthesis.

PubMed

K, Anbarasi; K, Kasim Mohamed; Vijayaraghavan, Phagalvarthy; Kandaswamy, Deivanayagam

2016-12-01

To design and implement flipped clinical training for undergraduate dental students in removable complete denture treatment and predict its effectiveness by comparing the assessment results of students trained by flipped and traditional methods. Flipped training was designed by shifting the learning from clinics to learning center (phase I) and by preserving the practice in clinics (phase II). In phase I, student-faculty interactive session was arranged to recap prior knowledge. This is followed by a display of audio synchronized video demonstration of the procedure in a repeatable way and subsequent display of possible errors that may occur in treatment with guidelines to overcome such errors. In phase II, live demonstration of the procedure was given. Students were asked to treat three patients under instructor's supervision. The summative assessment was conducted by applying the same checklist criterion and rubric scoring used for the traditional method. Assessment results of three batches of students trained by flipped method (study group) and three traditionally trained previous batches (control group) were taken for comparison by chi-square test. The sum of traditionally trained three batch students who prepared acceptable dentures (score: 2 and 3) and unacceptable dentures (score: 1) was compared with the same of flipped trained three batch students revealed that the number of students who demonstrated competency by preparing acceptable dentures was higher for flipped training (χ 2 =30.996 with p<0.001). The results reveal the supremacy of flipped training in enhancing students competency and hence recommended for training various clinical procedures.

PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

PubMed

Gewirtz, Henry

2017-12-01

This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata.

PubMed

Pinto, Ana Cecília Versiani Duarte; Andrade, Tatiana Cristina Pedro Cordeiro de; Brito, Fernanda Freitas de; Silva, Gardênia Viana da; Cavalcante, Maria Lopes Lamenha Lins; Martelli, Antonio Carlos Ceribelli

2017-01-01

Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm.

[Pharmacological action and clinical aspects of salmeterol].

PubMed

Oguri, Kojiro

2003-09-01

Previous systemic beta(2) agonists such as procatrol tablets and tulobuterol patch were developed in Japan to address nocturnal symptoms and maintenance of lung function in asthmatic patients. Salmeterol, a potent and highly selective in beta(2) adrenocepter agonist with a duration of action greater than 12 h, was developed to provide long duration of bronchodilation with binding to a non-active site in the beta(2)-adrenocepter. Salmeterol is administrated via dry power inhalation and clinical studies have showed it has a good efficacy and a good safety profile, similar to inhaled steroids. Indeed, many clinical studies showed that salmeterol demonstrated better efficacy than long-acting beta(2)-agonist oral bronchodilators, theophyllines, and leukotriene-receptor antagonists in asthmatic patients and anticholinergic agents and theophyllines in COPD patients. Salmeterol will provide clinical benefits for Japanese asthma and COPD patients.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata*

PubMed Central

Pinto, Ana Cecília Versiani Duarte; de Andrade, Tatiana Cristina Pedro Cordeiro; de Brito, Fernanda Freitas; da Silva, Gardênia Viana; Cavalcante, Maria Lopes Lamenha Lins; Martelli, Antonio Carlos Ceribelli

2017-01-01

Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm. PMID:28225970

Conceptualization and Assessment of Disengagement in Romantic Relationships

PubMed Central

Barry, Robin A.; Lawrence, Erika; Langer, Amie

2008-01-01

Research examining relationship distress and dissolution highlights the importance of romantic disengagement. However, prior conceptualizations and measures of romantic disengagement have tended to combine disengagement with related but distinct constructs hindering the study of romantic disengagement. In the present study we conducted exploratory factor analyses to demonstrate that disengagement is a relatively distinct construct and to clarify the conceptualization of romantic disengagement. More importantly, we developed a novel measure– the Romantic Disengagement Scale (RDS). The RDS demonstrated adequate fit across samples of dating individuals, married couples and women in physically aggressive relationships. The RDS also demonstrated strong divergent and incremental validity. Implications for enhancing conceptual models, research methodology, and clinical interventions are discussed. PMID:19727315

Effectiveness of ultraviolet devices and hydrogen peroxide systems for terminal room decontamination: Focus on clinical trials.

PubMed

Weber, David J; Rutala, William A; Anderson, Deverick J; Chen, Luke F; Sickbert-Bennett, Emily E; Boyce, John M

2016-05-02

Over the last decade, substantial scientific evidence has accumulated that indicates contamination of environmental surfaces in hospital rooms plays an important role in the transmission of key health care-associated pathogens (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, Acinetobacter spp). For example, a patient admitted to a room previously occupied by a patient colonized or infected with one of these pathogens has a higher risk for acquiring one of these pathogens than a patient admitted to a room whose previous occupant was not colonized or infected. This risk is not surprising because multiple studies have demonstrated that surfaces in hospital rooms are poorly cleaned during terminal cleaning. To reduce surface contamination after terminal cleaning, no touch methods of room disinfection have been developed. This article will review the no touch methods, ultraviolet light devices, and hydrogen peroxide systems, with a focus on clinical trials which have used patient colonization or infection as an outcome. Multiple studies have demonstrated that ultraviolet light devices and hydrogen peroxide systems have been shown to inactivate microbes experimentally plated on carrier materials and placed in hospital rooms and to decontaminate surfaces in hospital rooms naturally contaminated with multidrug-resistant pathogens. A growing number of clinical studies have demonstrated that ultraviolet devices and hydrogen peroxide systems when used for terminal disinfection can reduce colonization or health care-associated infections in patients admitted to these hospital rooms. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Non-invasive measurement of brain temperature with microwave radiometry: demonstration in a head phantom and clinical case.

PubMed

Stauffer, Paul R; Snow, Brent W; Rodrigues, Dario B; Salahi, Sara; Oliveira, Tiago R; Reudink, Doug; Maccarini, Paolo F

2014-02-01

This study characterizes the sensitivity and accuracy of a non-invasive microwave radiometric thermometer intended for monitoring body core temperature directly in brain to assist rapid recovery from hypothermia such as occurs during surgical procedures. To study this approach, a human head model was constructed with separate brain and scalp regions consisting of tissue equivalent liquids circulating at independent temperatures on either side of intact skull. This test setup provided differential surface/deep tissue temperatures for quantifying sensitivity to change in brain temperature independent of scalp and surrounding environment. A single band radiometer was calibrated and tested in a multilayer model of the human head with differential scalp and brain temperature. Following calibration of a 500MHz bandwidth microwave radiometer in the head model, feasibility of clinical monitoring was assessed in a pediatric patient during a 2-hour surgery. The results of phantom testing showed that calculated radiometric equivalent brain temperature agreed within 0.4°C of measured temperature when the brain phantom was lowered 10°C and returned to original temperature (37°C), while scalp was maintained constant over a 4.6-hour experiment. The intended clinical use of this system was demonstrated by monitoring brain temperature during surgery of a pediatric patient. Over the 2-hour surgery, the radiometrically measured brain temperature tracked within 1-2°C of rectal and nasopharynx temperatures, except during rapid cooldown and heatup periods when brain temperature deviated 2-4°C from slower responding core temperature surrogates. In summary, the radiometer demonstrated long term stability, accuracy and sensitivity sufficient for clinical monitoring of deep brain temperature during surgery.

Characterization and Peripheral Blood Biomarker Assessment of Jo-1 Antibody-Positive Interstitial Lung Disease

PubMed Central

Richards, Thomas J.; Eggebeen, Aaron; Gibson, Kevin; Yousem, Samuel; Fuhrman, Carl; Gochuico, Bernadette R.; Fertig, Noreen; Oddis, Chester V.; Kaminski, Naftali; Rosas, Ivan O.; Ascherman, Dana P.

2009-01-01

Objectives Combining clinical, radiographic, functional, and serum protein biomarker assessment, this study defines the prevalence and clinical characteristics of ILD in a large cohort of patients possessing anti-Jo-1 antibodies. Methods Clinical records, pulmonary function testing, and imaging studies determined the existence of ILD in anti-Jo-1 antibody positive (anti-Jo-1 Ab+) individuals accumulated in the University of Pittsburgh Myositis Database from 1982–2007. Multiplex ELISA of serum inflammatory markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups then permitted assessment of serum proteins associated with anti-Jo-1 Ab+ ILD. Results Among 90 anti-Jo-1 Ab+ individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met criteria for ILD. While computerized tomography scans revealed a variety of patterns suggestive of underlying UIP or NSIP, review of histopathologic abnormalities in a subset (n=22) of individuals undergoing open lung biopsy demonstrated a preponderance of UIP and DAD. Multiplex ELISA yielded statistically significant associations between Jo-1 Ab+ ILD and elevated serum levels of CRP, CXCL9, and CXCL10 that distinguished this subgroup from IPF and anti-SRP Ab+ myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these subgroups with high sensitivity and specificity. Conclusion In this large cohort of anti-Jo-1 Ab+ individuals, the incidence of ILD approaches 90%. Multiplex ELISA demonstrates disease-specific associations between Jo-1 Ab+ ILD and serum levels of CRP as well as the IFN-γ-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD. PMID:19565490

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

Concussion Attitudes and Beliefs, Knowledge, and Clinical Practice: Survey of Physical Therapists.

PubMed

Yorke, Amy M; Littleton, Sheila; Alsalaheen, Bara A

2016-07-01

A concussion is considered a mild traumatic brain injury that may cause physical, cognitive, affective, and sleep dysfunction. Physical therapists have been identified as health care providers involved in the multidisciplinary care of a patient with concussion. The purpose of this study was to describe the current attitudes and beliefs, knowledge, and practice of physical therapists in the treatment of patients with concussion. A 55-question electronic survey divided into 6 sections-(1) demographics, (2) current practice in concussion, (3) youth concussion legislation, (4) attitudes and beliefs toward concussion management, (5) concussion knowledge, and (6) clinical decision making-was developed and distributed online through selected American Physical Therapy Association sections. A total of 1,272 physical therapists completed the survey. Seventy percent of the respondents (n=894) reported having concussion training. Although supportive of the role of the physical therapist in the treatment of a person with concussion, the respondents demonstrated less confidence when making return-to-play decisions. Respondents correctly answered, on average, 13 (out of 15) concussion knowledge questions, with gaps exhibited in understanding the clinical utilization of concussion severity scales, the conservative treatment of youth who sustain a concussion, and anticipated normal computed tomography and magnetic resonance imaging after a concussion. When provided with clinical scenarios, respondents were able to recognize when a referral to a physician was indicated; however, they demonstrated variability in identifying a need for vestibular or manual physical therapy. Convenience sampling was utilized, limiting generalizability of the results of the study to the physical therapy profession as a whole. Physical therapists demonstrated a solid foundation of concussion knowledge, but gaps still existed. Future professional development opportunities should be developed to target identified gaps in knowledge and current practice patterns. © 2016 American Physical Therapy Association.

Periodontal regeneration around natural teeth.

PubMed

Garrett, S

1996-11-01

1. Evidence is conclusive (Table 2) that periodontal regeneration in humans is possible following the use of bone grafts, guided tissue regeneration procedures, both without and in combination with bone grafts, and root demineralization procedures. 2. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change beyond that achieved with debridement alone in treating mandibular and maxillary (buccal only) Class II furcations. Similar data exist for intraosseous defects. Evidence suggests that the use of bone grafts or GTR procedures produce equal clinical benefit in treating intraosseous defects. Further research is necessary to evaluate GTR procedures compared to, or combined with, bone grafts in treating intraosseous defects. 3. Although there are some data suggesting hopeful results in Class II furcations, the clinical advantage of procedures combining present regenerative techniques remains to be demonstrated. Additional randomized controlled trials with sufficient power are needed to demonstrate the potential usefulness of these techniques. 4. Outcomes following regenerative attempts remain somewhat variable with differences in results between studies and individual subjects. Some of this variability is likely patient related in terms of compliance with plaque control and maintenance procedures, as well as personal habits; e.g., smoking. Variations in the defects selected for study may also affect predictability of outcomes along with other factors. 5. There is evidence to suggest that present regenerative techniques lead to significant amounts of regeneration at localized sites on specific teeth. However, if complete regeneration is to become a reality, additional stimuli to enhance the regenerative process are likely needed. Perhaps this will be accomplished in the future, with combined procedures that include appropriate polypeptide growth factors or tissue factors to provide additional stimulus.

Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): results from the CanACT study.

PubMed

Haraoui, Boulos; Cividino, Alfred; Stewart, Jacqueline; Guérette, Benoît; Keystone, Edward C

2011-11-17

This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA). Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events. A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated. This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA. NCT00649545.

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

PubMed

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

2017-07-01

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

Bioactive properties and clinical safety of a novel milk protein peptide

PubMed Central

2011-01-01

Background Milk protein fractions and peptides have been shown to have bioactive properties. This preliminary study examined the potential mechanisms of action and clinical safety of novel milk protein peptide (MP). Findings A novel MP mixture inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and insulin receptor (IR) with IC50 of 9.85 μM, 7.7 μM, and 6.18 μM respectively. In vitro, this multi-kinase inhibitor causes apoptosis in HT-29 colon cancer cells, and in a C. elegans worm study, showed a weak but significant increase in lifespan. A six week double-blind, placebo-controlled study involving 73 healthy volunteers demonstrated that the MP mixture is safe to consume orally. All clinical blood markers remained within normal levels and no clinically significant side effects were reported. There was some evidence of improved insulin sensitivity, neutrophil-to-lymphocyte ratio (NLR), and quality of life assessment of role of physical function. Conclusions These data in combination with the observed in vitro anti-cancer properties warrant further clinical studies to investigate this MP mixture as a potential clinical nutrition intervention for improving the quality of life and clinical outcomes in cancer patients. Trial Registration NCT01412658 PMID:21943352

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review

PubMed Central

Huang, Eileen; Pillai, Satish K.; Bower, William A.; Hendricks, Katherine A.; Guarnizo, Julie T.; Hoyle, Jamechia D.; Gorman, Susan E.; Boyer, Anne E.; Quinn, Conrad P.; Meaney-Delman, Dana

2016-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident. PMID:26690378

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

PubMed

Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana

2015-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.

Clinical Education in Athletic Training

ERIC Educational Resources Information Center

Edler, Jessica R.; Eberman, Lindsey E.; Walker, Stacy

2017-01-01

Context: Clinical education is a foundational component of healthcare education by which students acquire, practice, and demonstrate competency in clinical proficiencies through classroom, laboratory, and clinical experiences. Currently, the most common practice of clinical education in athletic training is clinical integration. Objective: The…

Manipulation method for the treatment of ankle equinus.

PubMed

Dananberg, H J; Shearstone, J; Guillano, M

2000-09-01

Ankle equinus is a well-known clinical entity that has previously been shown to compound a variety of foot and ankle conditions. Treatments for this disorder have included surgery to lengthen the Achilles tendon and daily stretching. This article describes a method of manual manipulation that can immediately and substantially increase ankle joint dorsiflexion. Patients treated with manipulation in the current study demonstrated nearly twice as much dorsiflexion motion as that demonstrated by patients in a prior study who were treated with a 5-minute daily stretching program for 6 months.

Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications12

PubMed Central

Davis-Yadley, Ashley H; Malafa, Mokenge P

2015-01-01

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. PMID:26567201

Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.

PubMed

Davis-Yadley, Ashley H; Malafa, Mokenge P

2015-11-01

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. © 2015 American Society for Nutrition.

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

PubMed

Silva, Paula Simplício da; Mediano, Mauro Felippe Felix; Silva, Gilberto Marcelo Sperandio da; Brito, Patricia Dias de; Cardoso, Claudia Santos de Aguiar; Almeida, Cristiane Fonseca de; Sangenis, Luiz Henrique Conde; Pinheiro, Roberta Olmo; Hasslocher-Moreno, Alejandro Marcel; Brasil, Pedro Emmanuel Alvarenga Americano do; Sousa, Andrea Silvestre de

2017-06-09

Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. NCT01863576.

Ensuring respect for persons in COMPASS: a cluster randomised pragmatic clinical trial.

PubMed

Andrews, Joseph E; Moore, J Brian; Weinberg, Richard B; Sissine, Mysha; Gesell, Sabina; Halladay, Jacquie; Rosamond, Wayne; Bushnell, Cheryl; Jones, Sara; Means, Paula; King, Nancy M P; Omoyeni, Diana; Duncan, Pamela W

2018-05-02

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

What is the definition of sports-related concussion: a systematic review.

PubMed

McCrory, Paul; Feddermann-Demont, Nina; Dvořák, Jiří; Cassidy, J David; McIntosh, Andrew; Vos, Pieter E; Echemendia, Ruben J; Meeuwisse, Willem; Tarnutzer, Alexander A

2017-06-01

Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC. This is a systematic literature review. Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016). Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data. Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation. SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effectiveness, safety, and economic evaluation of Korean medicine for unexplained infertile women: A multi-center, prospective, observational study protocol.

PubMed

Kim, Su-Hyun; Jo, Junyoung; Kim, Dong-Il

2017-12-01

Infertility is a condition in which a woman has not been pregnant despite having had normal intercourse for 1 year. The number of unexplained infertile females is increasing because of late marriage customs, as well as environmental and lifestyle habits. In Korea, infertile females have been treated with Korean medicine (KM). However, these effects have not been objectively confirmed through clinical trials. Therefore, this study was conducted to demonstrate the effectiveness of herbal medicine treatment in infertile patients and to demonstrate the economic feasibility through economical evaluation with assisted reproductive technology.This study is designed as a multicenter, single-arm clinical trial. All participants included will be from 3 Korean Medicine hospitals in Korea and will voluntarily sign an informed consent agreement. All recruited patients will conduct related surveys and tests, and be provided with treatment according to their menstrual cycle. Patients will take herbal medicines for 4 menstruation cycles and receive acupuncture and moxibustion treatment at 3 times (menstrual cycle day 3, 8, 14) during 4 menstruation cycles. They will also undergo an approximately 4 menstrual cycle treatment period, and 3 menstrual cycle observation period. If pregnant during the study, participants will take the herbal medicine for implantation for about 15 days. In this study, the primary outcome will be the clinical pregnancy rate, whereas the secondary outcome will include the implantation rate, ongoing pregnancy rate, and live birth rate.Ultimately, this study will provide clinical data regarding the effectiveness and safety of KM treatment for females with unexplained infertility and important evidence for establishing standard KM treatments for unexplained infertility. Moreover, we will identify the most cost-effective way to treat unexplained infertility. Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002235. Date: February 21, 2017 (retrospectively registered). Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Text messaging to support off-campus clinical nursing facilitators: a descriptive survey.

PubMed

Howard, Christine; Fox, Amanda R; Coyer, Fiona

2014-06-01

Managing large student cohorts can be a challenge for university academics, coordinating these units. Bachelor of Nursing programmes have the added challenge of managing multiple groups of students and clinical facilitators whilst completing clinical placement. Clear, time efficient and effective communication between coordinating academics and clinical facilitators is needed to ensure consistency between student and teaching groups and prompt management of emerging issues. This study used a descriptive survey to explore the use of text messaging via a mobile phone, sent from coordinating academics to off-campus clinical facilitators, as an approach to providing direction and support. The response rate was 47.8% (n=22). Correlations were found between the approachability of the coordinating academic and clinical facilitator perception that, a) the coordinating academic understood issues on clinical placement (r=0.785, p<0.001), and b) being part of the teaching team (r=0.768, p<0.001). Analysis of responses to qualitative questions revealed three themes: connection, approachability and collaboration. This study demonstrates that use of regular text messages improves communication between coordinating academics and clinical facilitators. Findings suggest improved connection, approachability and collaboration between the coordinating academic and clinical facilitation staff. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of futility monitoring guidelines using completed phase III oncology trials.

PubMed

Zhang, Qiang; Freidlin, Boris; Korn, Edward L; Halabi, Susan; Mandrekar, Sumithra; Dignam, James J

2017-02-01

Futility (inefficacy) interim monitoring is an important component in the conduct of phase III clinical trials, especially in life-threatening diseases. Desirable futility monitoring guidelines allow timely stopping if the new therapy is harmful or if it is unlikely to demonstrate to be sufficiently effective if the trial were to continue to its final analysis. There are a number of analytical approaches that are used to construct futility monitoring boundaries. The most common approaches are based on conditional power, sequential testing of the alternative hypothesis, or sequential confidence intervals. The resulting futility boundaries vary considerably with respect to the level of evidence required for recommending stopping the study. We evaluate the performance of commonly used methods using event histories from completed phase III clinical trials of the Radiation Therapy Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group. We considered published superiority phase III trials with survival endpoints initiated after 1990. There are 52 studies available for this analysis from different disease sites. Total sample size and maximum number of events (statistical information) for each study were calculated using protocol-specified effect size, type I and type II error rates. In addition to the common futility approaches, we considered a recently proposed linear inefficacy boundary approach with an early harm look followed by several lack-of-efficacy analyses. For each futility approach, interim test statistics were generated for three schedules with different analysis frequency, and early stopping was recommended if the interim result crossed a futility stopping boundary. For trials not demonstrating superiority, the impact of each rule is summarized as savings on sample size, study duration, and information time scales. For negative studies, our results show that the futility approaches based on testing the alternative hypothesis and repeated confidence interval rules yielded less savings (compared to the other two rules). These boundaries are too conservative, especially during the first half of the study (<50% of information). The conditional power rules are too aggressive during the second half of the study (>50% of information) and may stop a trial even when there is a clinically meaningful treatment effect. The linear inefficacy boundary with three or more interim analyses provided the best results. For positive studies, we demonstrated that none of the futility rules would have stopped the trials. The linear inefficacy boundary futility approach is attractive from statistical, clinical, and logistical standpoints in clinical trials evaluating new anti-cancer agents.

A call for change: clinical evaluation of student registered nurse anesthetists.

PubMed

Collins, Shawn; Callahan, Margaret Faut

2014-02-01

The ability to integrate theory with practice is integral to a student's success. A common reason for attrition from a nurse anesthesia program is clinical issues. To document clinical competence, students are evaluated using various tools. For use of a clinical evaluation tool as possible evidence for a student's dismissal, an important psychometric property to ensure is instrument validity. Clinical evaluation instruments of nurse anesthesia programs are not standardized among programs, which suggests a lack of instrument validity. The lack of established validity of the instruments used to evaluate students' clinical progress brings into question their ability to detect a student who is truly in jeopardy of attrition. Given this possibility, clinical instrument validity warrants research to be fair to students and improve attrition rates based on valid data. This ex post facto study evaluated a 17-item clinical instrument tool to demonstrate the need for validity of clinical evaluation tools. It also compared clinical scores with scores on the National Certification Examination.

Outcomes of Integrated Behavioral Health with Primary Care.

PubMed

Balasubramanian, Bijal A; Cohen, Deborah J; Jetelina, Katelyn K; Dickinson, L Miriam; Davis, Melinda; Gunn, Rose; Gowen, Kris; deGruy, Frank V; Miller, Benjamin F; Green, Larry A

2017-01-01

Integrating behavioral health and primary care is beneficial to patients and health systems. However, for integration to be widely adopted, studies demonstrating its benefits in community practices are needed. The objective of this study was to evaluate effect of integrated care, adapted to local contexts, on depression severity and patients' experience of care. This study used a convergent mixed-methods design, merging findings from a quasi-experimental study with patient interviews conducted as part of Advancing Care Together, a community demonstration project that created an innovation incubator for practices implementing evidence-based integration strategies. The study included 475 patients with a 9-item Patient Health Questionnaire (PHQ-9) score ≥10 at baseline, from 5 practices. Statistically significant reductions in mean PHQ-9 scores were observed in all practices, ranging from 2.72 to 6.46 points. Clinically, 50% of patients had a ≥5-point reduction in PHQ-9 score and 32% had a ≥50% reduction. This finding was corroborated by patient interviews that demonstrated positive experiences with behavioral health clinicians and acquiring new skills to cope with adverse situations at work and home. Integrating behavioral health and primary care, when adapted to fit into community practices, reduced depression severity and enhanced patients' experience of care. Integration is a worthwhile investment; clinical leaders, policymakers, and payers should support integration in their communities. © Copyright 2017 by the American Board of Family Medicine.

Sinuplasty (Balloon Catheter Dilation)

MedlinePlus

... be done without actual tissue removal. Although this technology initially was met with criticism, clinical studies have demonstrated that it is a safe tool in the management of chronic sinusitis. The American Rhinologic Society as well as the American Academy of Otolaryngology- ...

Mild clinical involvement in two males with a large FMR1 premutation

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

Hagerman, R.; O`Connor, R.; Staley, L.

1994-09-01

Both male and female individuals who carry the FMR1 premutation are considered to be clinically unaffected and have been reported to have normal transcription of their FMR1 gene and normal FMR1 protein (FMRP) production. We have evaluated two males who are mildly affected clinically with features of fragile X syndrome and demonstrate a large premutation on DNA studies. The first patient is a 2 year 8 month old boy who demonstrated the fragile X chromosome in 3% of his lymphocytes on cytogenetic testing. His physical features include mildly prominent ears and hyperextensible finger joints. He has language delays along withmore » behavioral problems including tantrums and attention deficit. Developmental testing revealed a mental scale of 116 on the Bayley Scales of Infant Development, which is in the normal range. DNA testing demonstrated a premutation with 161 CGG repeats. This premutation was methylated in a small percent of his cells (<2%). These findings were observed in both blood leukocytes and buccal cells. Protein studies of transformed lymphocytes from this boy showed approximately 50 to 70% of the normal level of FMRP. The second patient is a 14 year old male who was cytogenetically negative for fragile X expression. His physical exam demonstrates a long face, a high palate and macroorchidism, (testicular volume of approximately 35 ml). His overall full scale IQ on the WISC-III is 73. He has language deficits and visual spatial perceptual deficits which have caused significant learning problems in school. Behaviorally he has problems with shyness and social anxiety, although he does not have attention deficit hyperactivity disorder. DNA testing revealed an FMR1 mutation of approximately 210 CGG repeats that is methylated in 4.7% of his cells.« less

Hsp-27 levels and thrombus burden relate to clinical outcomes in patients with ST-segment elevation myocardial infarction

PubMed Central

Tian, Maozhou; Zhu, Lingmin; Lin, Hongyang; Lin, Qiaoyan; Huang, Peng; Yu, Xiao; Jing, Yanyan

2017-01-01

High thrombus burden, subsequent distal embolization, and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the biological function and clinical association of Hsp-27 with thrombus burden and clinical outcomes in patients with STEMI is not clear. Consecutive patients (n = 146) having STEMI undergoing primary percutaneous coronary intervention (pPCI) within 12 hours from the onset of symptoms were enrolled in this prospective study in the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, P.R. China. Patients were divided into low thrombus burden and high thrombus burden groups. The present study demonstrated that patients with high-thrombus burden had higher plasma Hsp-27 levels ([32.0 ± 8.6 vs. 58.0 ± 12.3] ng/mL, P < 0.001). The median value of Hsp-27 levels in all patients with STEMI was 45 ng/mL. Using the receiver operating characteristic (ROC) curve analysis, plasma Hsp-27 levels were of significant diagnostic value for high thrombus burden (AUC, 0.847; 95% CI, 0.775–0.918; P < 0.01). The multivariate cox regression analysis demonstrated that Hsp-27 > 45 ng/mL (HR 2.801, 95% CI 1.296–4.789, P = 0.001), were positively correlated with the incidence of major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis demonstrated that MACE-free survival at 180-day follow-up was significantly lower in patients with Hsp-27 > 45 ng/mL (log rank = 10.28, P < 0.001). Our data demonstrate that plasma Hsp-27 was positively correlated with high thrombus burden and the incidence of MACE in patients with STEMI who underwent pPCI. PMID:29088740

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

PubMed Central

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

2013-01-01

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

From bench to bedside: An overview of rotigotine for the treatment of restless legs syndrome.

PubMed

Bogan, Richard K

2014-03-01

Restless legs syndrome (RLS) is a common chronic neurologic disorder. Symptoms are most prevalent during the evening and at night, although daytime symptoms may emerge as the disease progresses. Dopamine agonists are currently considered first-line therapy for moderate to severe idiopathic RLS. Most dopamine agonists have short half-lives and are administered in the evening, shortly before the onset of RLS symptoms. Rotigotine is a non-ergot dopamine receptor agonist that has been specifically developed as a transdermal patch to provide continuous drug delivery over a 24-hour period. This review details the development of rotigotine, from the preclinical studies that established its pharmacokinetic profile to large-scale clinical trials in patients with RLS. Placebo-controlled trials that demonstrated the efficacy and tolerability of rotigotine are discussed, in addition to open-label studies that investigated long-term therapy. Studies were identified by a PubMed search using the key word rotigotine in conjunction with restless legs syndrome and by reviewing reference lists of retrieved publications. All clinical trials of rotigotine in RLS published before September 2013 were included. Preclinical studies have established activity of rotigotine as a dopamine receptor agonist, and pharmacokinetic data have shown that transdermal delivery maintains stable plasma levels over 24 hours. Rotigotine has demonstrated efficacy in improving moderate to severe RLS symptoms in randomized, placebo-controlled trials, based on scores on the International RLS Study Group rating scale, the RLS-6 scale, and the Clinical Global Impression-Severity subscale. Results of an open-label extension study suggest that efficacy may be maintained for up to 5 years. A polysomnographic study demonstrated an improvement in periodic limb movement index with rotigotine, and subjective assessments have suggested beneficial effects in terms of amelioration of sleep disturbances. Premature discontinuations from rotigotine treatment have ranged from 8% to 38% in studies of 6 weeks to 12 months in duration; 57% of patients discontinued prematurely during a 5-year study. In each trial, adverse events were typical of dopaminergic stimulation and use of a transdermal patch. The most common adverse events were application-site reactions, with a reported prevalence ranging from 17% (1-month sleep laboratory trial) to 58% (5-year open-label extension study). Clinically significant augmentation was recorded in 39 of 295 patients (13%) receiving rotigotine during the 5-year study, of whom 15 (5%) were receiving a dose within the US Food and Drug Administration-approved range of 1 to 3 mg/24 h. Findings from clinical studies have suggested that rotigotine is efficacious in improving RLS symptoms and is generally well-tolerated. The risk of developing clinically significant augmentation appears to be low. As such, rotigotine represents an important addition for RLS treatment. Copyright © 2014 The Authors. Published by EM Inc USA.. All rights reserved.

Development and Validation of the Body-Focused Shame and Guilt Scale

PubMed Central

Weingarden, Hilary; Renshaw, Keith D.; Tangney, June P.; Wilhelm, Sabine

2015-01-01

Body shame is described as central in clinical literature on body dysmorphic disorder (BDD). However, empirical investigations of body shame within BDD are rare. One potential reason for the scarcity of such research may be that existing measures of body shame focus on eating and weight-based content. Within BDD, however, body shame likely focuses more broadly on shame felt in response to perceived appearance flaws in one’s body parts. We describe the development and validation of the Body-Focused Shame and Guilt Scale (BF-SGS), a measure of BDD-relevant body shame, across two studies: a two time-point study of undergraduates, and a follow-up study in two Internet-recruited clinical samples (BDD, obsessive compulsive disorder) and healthy controls. Across both studies, the BF-SGS shame subscale demonstrated strong reliability and construct validity, with Study 2 providing initial clinical norms. PMID:26640760

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

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

Management of Noncompressible Hemorrhage Using Vena Cava Ultrasound

DTIC Science & Technology

2016-10-01

with this study, Dr. Doucet has produced “Protocol Video USA-IVC Study (Version 5)” that is posted on youtube : https://youtu.be/54-Z6fiJpPY This video... youtube : https://youtu.be/54-Z6fiJpPY This video contains study design, procedures, inclusion/exclusion criteria and a demonstration to train clinical

Clinical compliance of viewing conditions in radiology reporting environments against current guidelines and standards

NASA Astrophysics Data System (ADS)

Daly, S.; Rainford, L.; Butler, M. L.

2014-03-01

Several studies have demonstrated the importance of environmental conditions in the radiology reporting environment, with many indicating that incorrect parameters could lead to error and misinterpretation. Literature is available with recommendations as to the levels that should be achieved in clinical practice, but evidence of adherence to these guidelines in radiology reporting environments is absent. This study audited the reporting environments of four teleradiologist and eight hospital based radiology reporting areas. This audit aimed to quantify adherence to guidelines and identify differences in the locations with respect to layout and design, monitor distance and angle as well as the ambient factors of the reporting environments. In line with international recommendations, an audit tool was designed to enquire in relation to the layout and design of reporting environments, monitor angle and distances used by radiologists when reporting, as well as the ambient factors such as noise, light and temperature. The review of conditions were carried out by the same independent auditor for consistency. The results obtained were compared against international standards and current research. Each radiology environment was given an overall compliance score to establish whether or not their environments were in line with recommended guidelines. Poor compliance to international recommendations and standards among radiology reporting environments was identified. Teleradiology reporting environments demonstrated greater compliance than hospital environments. The findings of this study identified a need for greater awareness of environmental and perceptual issues in the clinical setting. Further work involving a larger number of clinical centres is recommended.

The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.

PubMed

Wolff, M S; Schenkel, A B

2018-02-01

Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.

Biomechanical Comparison of Single- Versus Double-Row Capsulolabral Repair for Shoulder Instability: A Review.

PubMed

Yousif, Matthew John; Bicos, James

2017-12-01

The glenohumeral joint is the most commonly dislocated joint in the body. Failure rates of capsulolabral repair have been reported to be approximately 8%. Recent focus has been on restoration of the capsulolabral complex by a double-row capsulolabral repair technique in an effort to decrease redislocation rates after arthroscopic capsulolabral repair. To present a review of the biomechanical literature comparing single- versus double-row capsulolabral repairs and discuss the previous case series of double-row fixation. Narrative review. A simple review of the literature was performed by PubMed search. Only biomechanical studies comparing single- versus double-row capsulolabral repair were included for review. Only those case series and descriptive techniques with clinical results for double-row repair were included in the discussion. Biomechanical comparisons evaluating the native footprint of the labrum demonstrated significantly superior restoration of the footprint through double-row capsulolabral repair compared with single-row repair. Biomechanical comparisons of contact pressure at the repair interface, fracture displacement in bony Bankart lesion, load to failure, and decreased external rotation (suggestive of increased load to failure) were also significantly in favor of double- versus single-row repair. Recent descriptive techniques and case series of double-row fixation have demonstrated good clinical outcomes; however, no comparative clinical studies between single- and double-row repair have assessed functional outcomes. The superiority of double-row capsulolabral repair versus single-row repair remains uncertain because comparative studies assessing clinical outcomes have yet to be performed.

Surveillance imaging for lymphoma: pros and cons.

PubMed

Lynch, Ryan C; Zelenetz, Andrew D; Armitage, James O; Carson, Kenneth R

2014-01-01

There is no international consensus on the optimal frequency or duration of computed tomography or positron emission tomography scanning for surveillance in patients who achieve complete remission after initial therapy for lymphoma. Although some clinical practice guidelines suggest periodic imaging is reasonable, others suggest little or no benefit to this practice. From a theoretical perspective, the frequency and duration of surveillance imaging is largely dependent upon the lymphoma subtype. Aggressive lymphomas with a fast growth rate will require surveillance more frequently and for a shorter duration compared to the indolent lymphomas. Historically, relapse has been detected in a majority of patients based upon clinically evident signs and symptoms. Currently, no study has demonstrated an overall survival difference for patients with relapse detected by imaging as opposed to clinical evaluation, although one study did demonstrate a lower second-line International Prognostic Index in patients with relapse detected by surveillance imaging. Enthusiasm for this finding has been tempered by recent studies highlighting the potential long-term risk of secondary malignancies because of ionizing radiation exposure from diagnostic imaging. These factors along with the significant costs associated with diagnostic imaging have contributed to an ongoing debate regarding the relative costs, risks, and benefits of radiographic surveillance. Herein we present perspectives for and against routine surveillance imaging in an effort to facilitate a better understanding of the issues relevant to what is ultimately a clinical decision made by an oncologist and his or her patient.

Role of Google Glass in improving patient satisfaction for otolaryngology residents: a pilot study.

PubMed

Son, E; Halbert, A; Abreu, S; Hester, R; Jefferson, G; Jennings, K; Pine, H; Watts, T

2017-04-01

To demonstrate the feasibility and efficacy of the Google Glass as a tool to improve patient satisfaction and patient-physician communication for otolaryngology residents in the outpatient clinic setting. The primary outcome of the study was to improve patient satisfaction scores based on physician communication-related questions from Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. Prospective randomised trial. Tertiary care hospital. To evaluate the effect on patient satisfaction, five residents were recorded using the Google Glass in an outpatient clinic setting by 50 randomised patients. Modified surveys based on the CG-CAHPS survey were completed by patients at the conclusion of each clinic encounter. The recorded videos were evaluated by two independent faculties. Summarised data and video were distributed to each resident for review as the intervention. The residents were recorded again by 45 additional patients with evaluation by patients and faculties. After intervention, the scores from faculty surveys regarding patient satisfaction including the subject of better explanations (P > 0.001), listening carefully (P > 0.001), addressing patient questions (P > 0.001), displaying respect (P > 0.001) and spending adequate time (P = 0.0005) all significantly improved, as well as overall performance (P = 0.014). The scores from patient surveys did significantly improve. This study demonstrates the improvements in patient satisfaction and patient-physician communication can be achieved with the use of Google Glass as a first-person recording device in the outpatient otolaryngology clinic setting. © 2016 John Wiley & Sons Ltd.

Gaze perception in social anxiety and social anxiety disorder

PubMed Central

Schulze, Lars; Renneberg, Babette; Lobmaier, Janek S.

2013-01-01

Clinical observations suggest abnormal gaze perception to be an important indicator of social anxiety disorder (SAD). Experimental research has yet paid relatively little attention to the study of gaze perception in SAD. In this article we first discuss gaze perception in healthy human beings before reviewing self-referential and threat-related biases of gaze perception in clinical and non-clinical socially anxious samples. Relative to controls, socially anxious individuals exhibit an enhanced self-directed perception of gaze directions and demonstrate a pronounced fear of direct eye contact, though findings are less consistent regarding the avoidance of mutual gaze in SAD. Prospects for future research and clinical implications are discussed. PMID:24379776

Correlates of immune protection: Standardized and automated assays to interrogate correlates of immunity--Phacilitate Vaccine Forum Washington 2011. The Grand Hyatt, Washington, DC January 24–26, 2011.

PubMed

Bolton, Wade

2011-06-01

The utility of functional cell mediated immune assays in the assessment of immune response or immunogenicity is increasing significantly as we search for surrogates to determine vaccine efficacy or therapeutic response. No definitive reports to date have demonstrated that CMI assays in human clinical trials correlate with clinical outcome, although animal and non human primate studies have reported surrogacy in varying degrees. This report discusses the approaches identified, their advantages and disadvantages, and their justification for inclusion in the clinical trial setting.

Gene therapy for inherited retinal degenerations: initial successes and future challenges

NASA Astrophysics Data System (ADS)

Gupta, Priya R.; Huckfeldt, Rachel M.

2017-10-01

Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.

Leucoreduction of blood components: an effective way to increase blood safety?

PubMed Central

Bianchi, Maria; Vaglio, Stefania; Pupella, Simonetta; Marano, Giuseppe; Facco, Giuseppina; Liumbruno, Giancarlo M.; Grazzini, Giuliano

2016-01-01

Over the past 30 years, it has been demonstrated that removal of white blood cells from blood components is effective in preventing some adverse reactions such as febrile non-haemolytic transfusion reactions, immunisation against human leucocyte antigens and human platelet antigens, and transmission of cytomegalovirus. In this review we discuss indications for leucoreduction and classify them into three categories: evidence-based indications for which the clinical efficacy is proven, indications based on the analysis of observational clinical studies with very consistent results and indications for which the clinical efficacy is partial or unproven. PMID:26710353

The effectiveness of humane teaching methods in veterinary education.

PubMed

Knight, Andrew

2007-01-01

Animal use resulting in harm or death has historically played an integral role in veterinary education, in disciplines such as surgery, physiology, biochemistry, anatomy, pharmacology, and parasitology. However, many non-harmful alternatives now exist, including computer simulations, high quality videos, ''ethically-sourced cadavers'' such as from animals euthanased for medical reasons, preserved specimens, models and surgical simulators, non-invasive self-experimentation, and supervised clinical experiences. Veterinary students seeking to use such methods often face strong opposition from faculty members, who usually cite concerns about their teaching efficacy. Consequently, studies of veterinary students were reviewed comparing learning outcomes generated by non-harmful teaching methods with those achieved by harmful animal use. Of eleven published from 1989 to 2006, nine assessed surgical training--historically the discipline involving greatest harmful animal use. 45.5% (5/11) demonstrated superior learning outcomes using more humane alternatives. Another 45.5% (5/11) demonstrated equivalent learning outcomes, and 9.1% (1/11) demonstrated inferior learning outcomes. Twenty one studies of non-veterinary students in related academic disciplines were also published from 1968 to 2004. 38.1% (8/21) demonstrated superior, 52.4% (11/21) demonstrated equivalent, and 9.5% (2/21) demonstrated inferior learning outcomes using humane alternatives. Twenty nine papers in which comparison with harmful animal use did not occur illustrated additional benefits of humane teaching methods in veterinary education, including: time and cost savings, enhanced potential for customisation and repeatability of the learning exercise, increased student confidence and satisfaction, increased compliance with animal use legislation, elimination of objections to the use of purpose-killed animals, and integration of clinical perspectives and ethics early in the curriculum. The evidence demonstrates that veterinary educators can best serve their students and animals, while minimising financial and time burdens, by introducing well-designed teaching methods not reliant on harmful animal use.

An integrative review on coping skills in nursing students: implications for policymaking.

PubMed

Labrague, L J; McEnroe-Petitte, D M; Al Amri, M; Fronda, D C; Obeidat, A A

2018-06-01

This study critically appraised both quantitative and qualitative studies describing coping strategies utilized by nursing students when faced with stress. Stress in nursing students during clinical training is well documented in the nursing literature. The need to utilize positive-coping strategies is necessary to effectively deal with stress and its accompanying stressors. An integrative review method was used in this review. PsycINFO, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE and Scopus were the databases used in searching for relevant literature using the following search terms; 'coping', 'nursing students', clinical training', 'ways of coping' and 'clinical practice'. A total of 27 studies published from 2001 to 2016 were included in this review. Findings demonstrated that nursing students utilized problem-focused coping strategies rather than emotion-focused coping strategies. Specific coping behaviours utilized included problem-solving behaviours, self-confident approaches and seeking of support from family and friends. The review contributes to the growing literature on coping strategies in nursing students and may have implications on nursing education and nursing policy. This review also demonstrated a scarcity of studies that links specific coping strategies to nursing school stressors and examines predictors of coping skills in nursing students. Institutionalization of structured student orientation programme, implementation of well-planned mentoring programmes and establishment of support unit/centres may be helpful in supporting nursing students during their clinical placement. By developing empirically based interventions, nursing faculty can assist nursing students in strengthening their positive-coping skills to effectively deal with various stressors encountered. © 2017 International Council of Nurses.